Comparing levonorgestrel intrauterine system with hysteroscopic niche resection in women with postmenstrual spotting related to a niche in the uterine cesarean scar: a randomized, open-label, controlled trial.
Postmenstrual spotting and chronic pelvic pain after cesarean delivery are associated with the presence of niches. Levonorgestrel intrauterine system (52 mg) and hysteroscopic niche resection have been shown to relieve niche-related symptoms at 6 months after the intervention. This trial aimed to compare the effectiveness of 52-mg levonorgestrel intrauterine system with that of hysteroscopic niche resection in reducing niche-related postmenstrual spotting. This randomized, open-label, controlled trial was conducted at a medical center in Shanghai, China. Women with symptoms of postmenstrual spotting after cesarean delivery, with a niche depth of at least 2 mm and residual myometrium of at least 2.2 mm on magnetic resonance imaging, and no intention to conceive within the next year were randomly assigned to receive treatment with 52-mg levonorgestrel intrauterine system or hysteroscopic niche resection. The primary outcome was the reduction in postmenstrual spotting at 6 months after randomization, defined as the percentage of women with a reduction of at least 50% in spotting days relative to baseline. Efficacy and safety were assessed using intention-to-treat analysis. Between September 2019 and January 2022, 208 women were randomized into the levonorgestrel intrauterine system group (N=104) or the hysteroscopic niche resection group (N=104). At the 6-month follow-up, a 50% reduction in spotting had occurred in 78.4% (80/102) of women in the levonorgestrel intrauterine system group and in 73.1% (76/104) of women in the hysteroscopic niche resection group (relative risk, 1.07 [95% confidence interval, 0.92-1.25]; P=.370). Spotting decreased over time (Ptrend=.001), with a stronger reduction observed in the levonorgestrel intrauterine system group (P=.001). There was also a significant interaction between time and treatment (P=.007). From 9 months onward, a more significant reduction in spotting was observed in the levonorgestrel intrauterine system group than in the hysteroscopic niche resection group (9 months, 89.2% vs 72.1%; relative risk, 1.24 [95% confidence interval, 1.08-1.42]; 12 months, 90.2% vs 70.2%; relative risk, 1.29 [95% confidence interval, 1.12-1.48]). Moreover, compared with the hysteroscopic niche resection group, the levonorgestrel intrauterine system group had significantly fewer postmenstrual spotting days and total bleeding days from 6 months onward (all P<.001), and less pelvic pain from 3 months onward (all P<.010). No intervention-related complications were reported in any group. During follow-up, 11 (10.8%) women reported hormone-related side effects, and 2 women (2.0%) in the levonorgestrel intrauterine system group had spontaneous partial expulsion. Meanwhile, 3 unintended pregnancies were reported in the hysteroscopic niche resection group. In women with niche-related postmenstrual spotting, the levonorgestrel intrauterine system was not more effective than hysteroscopic niche resection in reducing the number of spotting days by at least 50% at 6 months. However, the levonorgestrel intrauterine system was superior in reducing spotting from 9 months onward, and it reduced the absolute number of spotting days from 6 months onward and pelvic pain from 3 months onward.


Flexible aqueous supercapacitors with excellent cycling performance and high-energy density based on mesocrystalline NiCo-LDHs.
Flexible aqueous supercapacitors are promising candidates as safe power sources for wearable electronic devices (WEDs). However, the absence of advanced electrode materials with high structural stability has become the most critical factor hindering the development, which is closely related to the poor interface combination between the active substances and flexible collectors. Herein, a unique rigid layered double hydroxide (LDH) nanorod array with the mesocrystalline feature is created using the NiO-Ni layer as the inducer by the electrodeposition strategy. Differing from the traditional NiCo-LDH nanosheets directly grown on a carbon cloth, an elaborately designed NiO-Ni buffer can simultaneously and effectively improve the bidirectional combination with active substances and collectors, also the mesocrystalline LDH showed enhanced intrinsic stability through the reinforcing effect of grain boundaries. Benefiting from these, the assembled supercapacitor exhibited pre-eminent cycle stability (increased from 64% of the initial capacity after 10 000 cycles to no significant attenuation after 50 000 cycles) and ultrahigh energy density. When it was used as a flexible device, a remarkable energy density of 70.4 W h kg-1 could be harvested and processed with high flexibility in the bending state and good temperature adaptability. This study provides an excellent design strategy for the development of next-generation flexible supercapacitors with the goal of better comprehensive performances.


ESTROGEN LEVELS DO NOT RISE WITH TESTOSTERONE TREATMENT FOR TRANSGENDER MEN.
Existing transgender treatment guidelines suggest that for transmasculine treatment, there is a possible need for estrogen-lowering strategies adjunct to testosterone therapy. Further, guidelines advocate consideration of prophylactic female reproductive tissue surgeries for transgender men to avoid the possibility of estrogen-related health risks. Despite the paucity of objective data, some transgender men seek conversion inhibitors. We sought to determine estradiol levels in transgender men treated with testosterone therapy and the change in those levels with treatment, if any. Estradiol levels were extracted from the electronic medical records of 34 anonymized transgender men treated with testosterone therapy at the Endocrinology Clinic at Boston Medical Center. Data were sufficient to observe 6 years of follow-up. With increased testosterone levels in trans-gender men, a significant decrease in estradiol levels was noted. There was a significant negative correlation between testosterone levels and body mass index, which may serve to explain part of the mechanism for the fall in estradiol levels. Even though the fall in estradiol levels was significant statistically, the actual levels remained within the normal male range, even with 6 years of follow-up. These data suggest that when exogenous testosterone is used to achieve normal serum male testosterone levels for transgender men, it is converted to normal male levels of estradiol, with some decline in those estradiol levels that might be attributable to a fall in fat mass. There appears to be no role for aromatase conversion inhibitors or other estrogen-reducing strategies in trans-gender men. Abbreviation: BMI = body mass index.


Rational Design of Cell-Active Inhibitors of PARP10.
Poly-ADP-ribose polymerases (PARPs 1-16) have emerged as major regulators of diverse cellular processes. PARPs can be subclassified based on their ability to catalyze poly-ADP-ribosylation (PARylation) or mono-ADP-ribosylation (MARylation). While much is known about the cellular roles of PARPs that catalyze PARylation (e.g., PARP1), the function of PARPs that catalyze MARylation (e.g., PARP10) is substantially less understood. This is due in large part to the lack of small-molecule inhibitors that are selective for individual PARP family members that catalyze MARylation. Herein, we describe the rational design and synthesis of selective inhibitors of PARP10. Using structure-based design, we targeted a hydrophobic subpocket within the nicotinamide-binding site of PARP10. We synthesized a series of small molecules based on a 3,4-dihydroisoquinolin-1(2H)-one (dq, 1) scaffold that contain various substituents at the C-5 and C-6 positions designed to exploit this hydrophobic subpocket. We found a dq analogue (22) that contains a methyl group at the C-5 position and a substituted pyridine at the C-6 position that exhibits >10-fold selectivity for PARP10 over a large subset of other PARP family members. The results of this study will serve as a platform for future small-molecule probe development for PARP10 and other PARP family members that catalyze MARylation.


Conformation orientation of syndiotactic polypropylene induced by deformation at different temperatures.
Two syndiotactic polypropylene (sPP) sample films (S0 and S90) with different initial structures were prepared in this paper by isothermal crystallization from the melt at 0 and 90 degrees C, respectively. The polymorphic transitions of the two samples induced by deformation at different temperatures (20, 40, and 60 degrees C) were investigated by rheo-optical FTIR spectroscopy. The results indicated that stretching leads to the transition from the helical to trans-planar conformation and improves the orientation of both helical and trans-planar conformations for the sPP films. With increasing stretching temperature, the conformational transitions for the two sPP samples are all suppressed, and the orientation behavior of the two samples appears completely different. The orientation degree of S0 decreases with increasing stretching temperature, while that of S90 increases. These results suggest that the stretching temperature and initial structure have great influence on the conformation transition and orientation behavior of the sPP sample. On the basis of the experimental results, the schematic illustration of the conformation transition and orientation behavior of sPP during stretching has been proposed.


Renal cell carcinoma metastasizing to adenocarcinoma of esophagogastric junction: a rare case of tumor-to-tumor metastasis.
The simultaneous occurrence of two primary tumors in one patient is not uncommon, but one tumor metastasizing to another malignancy is a rare phenomenon. Tumor-to-tumor metastasis was first described by Berent in 1902. Since then fewer than 200 cases have been reported in the literature. In most of these cases renal cell carcinoma acted as a recipient tumor. In tumor-to-tumor metastasis renal cell carcinoma acting as a donor is exceedingly rare and there are no reported cases of adenocarcinoma of the esophagogastric junction acting as a recipient. We present a case of renal cell carcinoma metastasizing to an adenocarcinoma of esophagogastric junction. To our knowledge, this is the first reported case of such a combination.


Immunological Mechanisms in Inflammation-Associated Colon Carcinogenesis.
Patients with chronic inflammatory bowel diseases are at an increased risk of developing colitis-associated cancer (CAC). Chronic inflammation positively correlates with tumorigenesis. Similarly, the cumulative rate of incidence of developing CAC increases with prolonged colon inflammation. Immune signaling pathways, such as nuclear factor (NF)-κB, prostaglandin E2 (PGE2)/cyclooxygenase-2 (COX-2), interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3), and IL-23/T helper 17 cell (Th17), have been shown to promote CAC tumorigenesis. In addition, gut microbiota contributes to the development and progression of CAC. This review summarizes the signaling pathways involved in the pathogenesis following colon inflammation to understand the underlying molecular mechanisms in CAC tumorigenesis.


Pedal-cycle injuries among children aged <6 years--Wisconsin, 2002-2004.
Measures to improve pedal-cycle safety and increase helmet use often target school-age children rather than younger children, even though preschool children wearing helmets have fewer injuries and are more likely to wear helmets in the future, compared with children who do not wear helmets. Children aged <6 years also use pedal cycles; whether they are passengers on a parent's bicycle, riding a tricycle or pedal car, or learning to ride a bicycle, these young cyclists often sustain injuries. To provide guidance for intervention strategies targeted to young children in Wisconsin, CDC and the Wisconsin Division of Public Health analyzed data collected from January 1, 2002 through December 31, 2004, from all nonfederal emergency departments (EDs) and hospitals in Wisconsin regarding pedal-cycle injuries among children aged <6 years. This report describes the results of that analysis, which indicated that, during 2002--2004, a total of 2,046 ED visits by Wisconsin residents aged <6 years for pedal-cycle injuries occurred; for 1,305 (63.8%) of these visits, the primary diagnosis was a head or neck injury. These findings underscore the need for interventions designed to reduce head and neck injuries in the youngest users of pedal cycles.


Ca2+ metabolism in arteries of spontaneously hypertensive rats: assessment by proton-induced X-ray emission.
Changes of intracellular Ca2+-metabolism have been considered to be of importance for the pathogenesis of essential hypertension. In the present study particle-induced X-ray emission (PIXE) was used to get information on the spatial distribution of Ca2+ in aortas and renal arteries of spontaneously hypertensive (SHR) and normotensive rats. Our findings demonstrate a significant Ca2+ elevation in the aorta and renal artery of SHR versus normotensive Wistar-Kyoto (WKY) rats (3317 +/- 734 micrograms Ca2+/g tissue versus 1623 +/- 569 micrograms Ca2+/g tissue and 3432 +/- 1867 micrograms Ca2+/g tissue versus 1050 +/- 554 micrograms Ca2+/g tissue).


Criminal justice system contact and mortality among offenders with mental illness in British Columbia: an assessment of mediation.
Persons with mental illness are over-represented in prison populations around the world. They are more vulnerable to arrest and more likely to experience repeated encounters with the criminal justice system. Whether criminal justice involvement, in and of itself, is associated with higher mortality, particularly among offenders with mental illness, is unknown. The authors conducted a mediation analysis of mortality rates in a cohort of 79,088 offenders from British Columbia using administrative records spanning 2001-2010, where the mediating variable was the individual-level rate of criminal sentencing. During 339,506 person-years of follow-up, there were 1841 deaths. The diagnosis of mental illness had no direct association with higher mortality after adjustment for confounders (HR=0.98, 95% CI 0.86 to 1.06). However, mental illness had an indirect association with mortality that was mediated through more frequent criminal justice involvement (HR=1.02, 95% CI 1.01 to 1.04). These findings support the hypothesis that offenders with mental illness experience higher mortality that is mediated by higher rates of criminal justice contact. The results of our study indicate that criminal justice diversion programmes are further warranted because they may contribute to the prevention of mortality among offenders with mental illness.


Measure post-bloodmeal dispersal of mosquitoes and duration of radioactivity by using the isotope ³²P.
The radioactive isotope (32)P-labeled disodium phosphate (Na₂H(32)PO₄) was injected via the jugular vein into a cow kept in a shed in Maozhuang Village, Cao Township of Shanxian County, China. Over the following 5 d, mosquitoes feeding on the cow were captured at distances up to 400 m to determine dispersal distance. The duration of radioactivity in the cow and marked mosquitoes was 10 d. The results showed that after blood feeding, Anopheles sinensis and Culex tritaeniorhynchus temporarily rested in the cattle shed and then flew outdoors. In contrast, Culex pipiens pallens remained in the cattle shed after feeding. These findings confirmed that local An. sinensis and Cx. tritaeniorhynchus were partially endophilic and tended to rest out of doors, whereas Cx. pipiens pallens was endophilic. For marked An. sinensis and Cx. tritaeniorhynchus, there was a significant tendency for dispersal to be in a northeast and east direction, probably because of the presence of heavy shading by an agricultural field, a small river for mosquito oviposition sites, and locations downwind from the blood source. The furthest flight distances for An. sinensis and Cx. tritaeniorhynchus were 210 and 240 m; therefore, control of these mosquitoes should include resting places indoors and outdoors within a radius of 250 m from confirmed cases.


Social integration after moving to a new city predicts lower systolic blood pressure.
Residential mobility is linked to higher incidence of cardiovascular disease (CVD) and mortality. A mechanism by which residential relocation may impact health is through the disruption of social networks. To examine whether moving to a new city is associated with increased CVD risk and whether the extent to which movers rebuild their social network after relocating predicts improved CVD risk and psychosocial well-being, recent movers (n = 26), and age- and sex-matched nonmovers (n = 20) were followed over 3 months. Blood pressure, C-reactive protein/albumin ratio (CRP/ALB), social network size, and psychosocial well-being were measured at intake (within 6 weeks of residential relocation for movers) and 3 months later. Multiple regression indicated higher systolic blood pressure (SBP) for movers (M = 107.42, SD = 11.39), compared with nonmovers (M = 102.37, SD = 10.03) at intake, though this trend was not statistically significant. As predicted, increases in movers' social network size over 3 months predicted decreases in SBP, even after controlling for age, sex, and waist-to-hip ratio, b = -2.04 mmHg, 95% CI [-3.35, -.73]. Associations between increases in movers' social ties and decreases in depressive symptoms and stress were in the predicted direction but did not meet the traditional cutoff for statistical significance. Residential relocation and movers' social network size were not associated with CRP/ALB in this healthy sample. This study provides preliminary evidence for increased SBP among recent movers; furthermore, it suggests that this elevation in CVD risk may decrease as individuals successfully rebuild their social network.


Size distribution characteristics of elemental carbon emitted from Chinese vehicles: results of a tunnel study and atmospheric implications.
The size distribution characteristics of elemental carbon (EC) emissions from Chinese vehicles have not been previously described. In this study, we collected size-segregated aerosol samples using a 10-stage MOUDI sampler (0.056-18 microm) in the Zhujiang tunnel, a roadway tunnel in the urban area of Guangzhou, China. The samples were analyzed for EC, organic carbon (OC), and inorganic ions. Fine particles had an OC/EC ratio of 0.57, indicating a dominant contribution of EC from diesel vehicles. Both EC and OC showed a dominant accumulation mode with a mass median aerodynamic diameter (MMAD) of 0.42 microm. In comparison, studies available in the literature typically reported a much lower MMAD for EC (approximately 0.1 microm) in vehicular emissions in North America. A theoretical analysis indicated that the larger EC particles observed in this study could not have resulted from after-emission growth processes (i.e., water accretion, coagulation, and vapor condensation). This leaves operating conditions such as high engine loads and low combustion efficiencies, which are more prevalent in diesel-fueled Chinese vehicles, as a more plausible inherent reason for producing the larger EC agglomerates. While fresh 0.1 microm EC particles are unlikely to act as cloud condensation nuclei (CCN), calculations showed that EC particles as large as 0.42 microm are effective CCN at atmospherically relevant critical supersaturation values of less than 1%. As a result, fresh EC particles from Chinese vehicle emissions could readily undergo cloud processing and form internal mixtures with sulfate in the residue droplet mode particles. This prediction is consistent with observations that EC frequently showed a dominant droplet mode in urban atmospheres in this region. The internal mixing of EC with highly hygroscopic sulfate would facilitate its removal by wet deposition and shorten its lifetime in the atmosphere. In addition, the light-absorbing capabilities of EC particles could also be enhanced due to their internal mixing with sulfate. Numerical aerosol models need to take these factors into consideration for better predictions of the behaviors and effects of urban aerosols in China.


Optimum dosage regimen of palivizumab?
Palivizumab is a humanized, monoclonal antibody used to protect at-risk infants against respiratory syncytial virus (RSV) infection. The regular dosage scheme causes a low initial trough level and accumulation of the antibody after subsequent injections. Using a simple pharmacokinetic model, the authors devised an alternative dosage regimen that might correct these problems while cutting costs by 35%. To spare health care budgets, dosage schemes for future monoclonal antibodies must be chosen carefully.


Synthesis, antiviral activity, preliminary pharmacokinetics and structural parameters of thiazolide amine salts.
Background: The thiazolides, typified by nitazoxanide, are an important class of anti-infective agents. A significant problem with nitazoxanide and its active circulating metabolite tizoxanide is their poor solubility. Results: We report the preparation and evaluation of a series of amine salts of tizoxanide and the corresponding 5-Cl thiazolide. These salts demonstrated improved aqueous solubility and absorption, as shown by physicochemical and in vivo measurements. They combine antiviral activity against influenza A virus with excellent cell safety indices. We also report the x-ray crystal structural data of the ethanolamine salt. Conclusion: The ethanol salt of thiazolide retains the activity of the parent together with an improved cell safety index, making it a good candidate for further evaluation.


Intestinal expression patterns of transcription factors and markers for interstitial cells in the larval zebrafish.
For the digestion of food, it is important for the gut to be differentiated regionally and to have proper motor control. However, the number of transcription factors that regulate its development is still limited. Meanwhile, the interstitial cells of the gastrointestinal (GI) tract are necessary for intestinal motility in addition to the enteric nervous system. There are anoctamine1 (Ano1)-positive and platelet-derived growth factor receptor α (Pdgfra)-positive interstitial cells in mammal, but Pdgfra-positive cells have not been reported in the zebrafish. To identify new transcription factors involved in GI tract development, we used RNA sequencing comparing between larval and adult gut. We isolated 40 transcription factors that were more highly expressed in the larval gut. We demonstrated expression patterns of the 13 genes, 7 of which were newly found to be expressed in the zebrafish larval gut. Six of the 13 genes encode nuclear receptors. The osr2 is expressed in the anterior part, while foxP4 in its distal part. Also, we reported the expression pattern of pdgfra for the first time in the larval zebrafish gut. Our data provide fundamental knowledge for studying vertebrate gut regionalization and motility by live imaging using zebrafish.


Validity and reliability of the DDS for severity of delirium in the ICU.
Until now, there has been no gold standard for monitoring delirium in intensive care unit (ICU) patients. In this prospective cohort study, a new score, the Delirium Detection Score (DDS), for severity of delirium in the ICU was evaluated. After ethical approval and written informed consent, intensive care doctors and nurses assessed 1073 consecutive patients in surgical ICUs using the DDS together with the Ramsay Sedation Scale (RSS). The DDS is composed of eight criteria (orientation, hallucination, agitation, anxiety, seizures, tremor, paroxysmal sweating, and altered sleep- wake rhythm). Additionally, intensive care doctors had to document the Sedation-Agitation Scale (SAS) combined with a defined clinical assessment. For interrater reliability, pair of evaluators assessed patients in a blinded fashion at the same time. RSS1 (9%) was associated with a significantly (p < 0.001) higher DDS than RSS levels 2-6. The DDS increased with the severity of delirium (p < 0.001). The receiver operating characteristics (ROC) for the differentiation between no delirium (SAS < 4) and symptoms of delirium at all (SAS 5-7) showed an area under the curve (AUC) of 0.802 (95% confidential interval (CI): 0.719-0.898; p < 0.001) and 69% sensitivity and 75% specificity was determined. For reliability, a Cronbach's alpha of 0.667 was calculated. The paired comparisons revealed an intraclass correlation between 0.642 and 0.758. The DDS demonstrated good validity with excellent sensitivity and specificity for delirium. The severity of delirium can be more accurately estimated by the DDS. By its composition of several items, the DDS might help to start a symptom-guided therapy immediately.


Pemetrexed conjugated with gold nanoparticles - Synthesis, characterization and a study of noncovalent interactions.
Gold nanoparticles (AuNPs) have been widely used as nanocarriers in drug delivery application. However, the binding mechanism between AuNPs and drug bases still remains a puzzle. Our study included: (i) optimization of three synthesis of the AuNPs-pemetrexed (PE) nanocomposites formation which was monitored by UV-Vis spectroscopy, (ii) identification of PE in gold nanocomposites and mechanism of PE interaction with gold nanoparticles by electrochemistry, NMR and Raman measurements, (iii) characterization of the three nanocomposites by TEM, DSL, ESL, zeta potential, XRPD and TGA analysis. The obtained nanocomposites are homogeneously shaped and have a maximum diameter of around 14nm and 88nm, as measured by the TEM and DSL techniques, respectively. The zeta potential of the nanocomposites is -43mV and suggests a high stability of the nanoparticles and lower toxicity for the normal cells. Quantum chemical calculations were also performed on model systems to estimate the strength of the AuNPs-PE interaction. Taking into account the experimental and theoretical data a mechanism of the nanocomposites' formation has been proposed in which PE interacts with the gold surface by the COOH/COO- group.


Indoor salt water baths followed by artificial ultraviolet B light for chronic plaque psoriasis.
Chronic plaque psoriasis is an immune-mediated, chronic, inflammatory skin disease, which can impair quality of life and social interaction. Disease severity can be classified by the psoriasis area and severity index (PASI) score ranging from 0 to 72 points. Indoor artificial salt bath with or without artificial ultraviolet B (UVB) light is used to treat psoriasis, simulating sea bathing and sunlight exposure; however, the evidence base needs clear evaluation. To assess the effects of indoor (artificial) salt water baths followed by exposure to artificial UVB for treating chronic plaque psoriasis in adults. We searched the following databases up to June 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trial registers, and checked the reference lists of included studies, recent reviews, and relevant papers for further references to relevant trials. Randomised controlled trials (RCTs) of salt bath indoors followed by exposure to artificial UVB in adults who have been diagnosed with chronic plaque type psoriasis. We included studies reporting between-participant data and within-participant data. We evaluated two different comparisons: 1) salt bath + UVB versus other treatment without UVB; eligible comparators were exposure to psoralen bath, psoralen bath + artificial ultraviolet A UVA) light, topical treatment, systemic treatment, or placebo, and 2) salt bath + UVB versus other treatment + UVB or UVB only; eligible comparators were exposure to bath containing other compositions or concentrations + UVB or UVB only. We used standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence. The primary efficacy outcome was PASI-75, to detect people with a 75% or more reduction in PASI score from baseline. The primary adverse outcome was treatment-related adverse events requiring withdrawal. For the dichotomous variables PASI-75 and treatment-related adverse events requiring withdrawal, we estimated the proportion of events among the assessed participants. The secondary outcomes were health-related quality of life using the Dermatology Life Quality Index, (DLQI) pruritus severity measured using a visual analogue scale, time to relapse, and secondary malignancies. We included eight RCTs: six reported between-participant data (2035 participants; 1908 analysed), and two reported within-participant data (70 participants, 68 analysed; 140 limbs; 136 analysed). One study reported data for the comparison salt bath with UVB versus other treatment without UVB; and eight studies reported data for salt bath with UVB versus other treatment with UVB or UVB only. Of these eight studies, only five reported any of our pre-specified outcomes and assessed the comparison of salt bath with UVB versus UVB only. The one included trial that assessed salt bath plus UVB versus other treatment without UVB (psoralen bath + UVA) did not report any of our primary outcomes. The mean age of the participants ranged from 41 to 50 years of age in 75% of the studies. None of the included studies reported on the predefined secondary outcomes of this review. We judged seven of the eight studies as at high risk of bias in at least one domain, most commonly performance bias. Total trial duration ranged between at least two months and up to 13 months. In five studies, the median participant PASI score at baseline ranged from 15 to 18 and was balanced between treatment arms. Three studies did not report PASI score. Most studies were conducted in Germany; all were set in Europe. Half of the studies were multi-centred (set in spa centres or outpatient clinics); half were set in a single centre in either an unspecified settings, a psoriasis daycare centre, or a spa centre. Commercial spa or salt companies sponsored three of eight studies, health insurance companies funded another, the association of dermatologists funded another, and three did not report on funding. When comparing salt bath plus UVB versus UVB only, two between-participant studies found that salt bath plus UVB may improve psoriasis when measured using PASI 75 (achieving a 75% or more reduction in PASI score from baseline) (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.24 to 2.35; 278 participants; low-certainty evidence). Assessment was conducted at the end of treatment, which was equivalent to six to eight weeks after start of treatment. The two trials which contributed data for the primary efficacy outcome were conducted by the same group, and did not blind outcome assessors. The German Spas Association funded one of the trials and the funding source was not stated for the other trial. Two other between-participant studies found salt bath plus UVB may make little to no difference to outcome treatment-related adverse events requiring withdrawal compared with UVB only (RR 0.96, 95% CI 0.35 to 2.64; 404 participants; low-certainty evidence). One of the studies reported adverse events, but did not specify the type of events; the other study reported skin irritation. One within-participant study found similar results, with one participant reporting severe itch immediately after Dead Sea salt soak in the salt bath and UVB group and two instances of inadequate response to phototherapy and conversion to psoralen bath + UVA reported in the UVB only group (low-certainty evidence). Salt bath with artificial ultraviolet B (UVB) light may improve psoriasis in people with chronic plaque psoriasis compared with UVB light treatment alone, and there may be no difference in the occurrence of treatment-related adverse events requiring withdrawal. Both results are based on data from a limited number of studies, which provided low-certainty evidence, so we cannot draw any clear conclusions. The reporting of our pre-specified outcomes was either non-existent or limited, with a maximum of two studies reporting a given outcome. The same group conducted the two trials which contributed data for the primary efficacy outcome, and the German Spas Association funded one of these trials. We recommend further RCTs that assess PASI-75, with detailed reporting of the outcome and time point, as well as treatment-related adverse events. Risk of bias was an issue; future studies should ensure blinding of outcome assessors and full reporting.


Programs take the edge off pharmacy cost increases.
With prescription drug spending going up more than 17% last year and showing no signs of easing, health plans and at-risk providers continue to search for ways to staunch the bleeding. Here are two proven programs that take the edge off pharmacy cost increases.


Association of TNF-α promoter polymorphisms with the outcome of persistent HBV infection in a northeast Chinese Han population.
Tumor necrosis factor-α (TNF-α) plays an important role in the pathogenesis and clinical outcome of chronic hepatitis B virus (HBV) infection. The objective of this study was to evaluate the relationship between functional polymorphisms of TNF-α and different outcomes of persistent HBV infection in a northeast Chinese Han population. Here 189 HBV spontaneously recovered subjects (SR), 571 HBV-infected patients including 180 chronic hepatitis B (CHB), 196 liver cirrhosis (LC), and 195 hepatocellular carcinoma (HCC) individuals were enrolled in this study. All the samples were genotyped for TNF-α -857C/T and -863C/A using the polymerase chain reaction-restriction fragment length polymorphism method. The frequency of -857CC genotype was significantly higher in CHB and LC individuals compared with that of SR subjects (P= 0.03, OR = 1.57, 95% CI 1.04-2.39 and P= 0.03, OR = 1.57, 95% CI 1.04-2.35, respectively). A significant difference in the distribution of the allele -857C was observed for both CHB vs. SR (P= 0.01, OR = 1.52, 95% CI 1.08-2.13) and LC vs. SR (P= 0.02, OR = 1.47, 95% CI 1.06-2.04) cohorts. In addition, the frequency of -863AA genotype was significantly higher in CHB and LC patients than that of SR subjects (P= 0.01, OR = 3.90, 95% CI 1.35-11.23 and P= 0.01, OR = 3.83, 95% CI 1.34-10.96, respectively), and allele -863A frequency was significantly more common in CHB, LC, and HCC cohorts than that of SR controls (P= 0.004, OR = 1.72, 95% CI 1.19-2.50; P= 0.001, OR = 1.81, 95% CI 1.26-2.61 and P= 0.001, OR = 1.90, 95% CI 1.33-2.73, respectively). Our data also revealed that haplotype CA was strongly associated with persistent HBV infection. These results suggest an association between the TNF-α promoter variants and different outcomes of persistent HBV infection in the studied population.


Ultrafast scene detection and recognition with limited visual information.
Humans can detect target color pictures of scenes depicting concepts like picnic or harbor in sequences of six or twelve pictures presented as briefly as 13 ms, even when the target is named after the sequence (Potter, Wyble, Hagmann, & McCourt, 2014). Such rapid detection suggests that feedforward processing alone enabled detection without recurrent cortical feedback. There is debate about whether coarse, global, low spatial frequencies (LSFs) provide predictive information to high cortical levels through the rapid magnocellular (M) projection of the visual path, enabling top-down prediction of possible object identities. To test the "Fast M" hypothesis, we compared detection of a named target across five stimulus conditions: unaltered color, blurred color, grayscale, thresholded monochrome, and LSF pictures. The pictures were presented for 13-80 ms in six-picture rapid serial visual presentation (RSVP) sequences. Blurred, monochrome, and LSF pictures were detected less accurately than normal color or grayscale pictures. When the target was named before the sequence, all picture types except LSF resulted in above-chance detection at all durations. Crucially, when the name was given only after the sequence, performance dropped and the monochrome and LSF pictures (but not the blurred pictures) were at or near chance. Thus, without advance information, monochrome and LSF pictures were rarely understood. The results offer only limited support for the Fast M hypothesis, suggesting instead that feedforward processing is able to activate conceptual representations without complementary reentrant processing.


An analysis of effects of heterozygosity in dairy cattle for bovine tuberculosis resistance.
Genetic selection of cattle more resistant to bovine tuberculosis (bTB) may offer a complementary control strategy. Hypothesising underlying non-additive genetic variation, we present an approach using genome-wide high density markers to identify genomic loci with dominance effects on bTB resistance and to test previously published regions with heterozygote advantage in bTB. Our data comprised 1151 Holstein-Friesian cows from Northern Ireland, confirmed bTB cases and controls, genotyped with the 700K Illumina BeadChip. Genome-wide markers were tested for associations between heterozygosity and bTB status using marker-based relationships. Results were tested for robustness against genetic structure, and the genotypic frequencies of a significant locus were tested for departures from Hardy-Weinberg equilibrium. Genomic regions identified in our study and in previous publications were tested for dominance effects. Genotypic effects were estimated through ASReml mixed models. A SNP (rs43032684) on chromosome 6 was significant at the chromosome-wide level, explaining 1.7% of the phenotypic variance. In the controls, there were fewer heterozygotes for rs43032684 (P < 0.01) with the genotypic values suggesting that heterozygosity confers a heterozygote disadvantage. The region surrounding rs43032684 had a significant dominance effect (P < 0.01). SNP rs43032684 resides within a pseudogene with a parental gene involved in macrophage response to infection and within a copy-number-variation region previously associated with nematode resistance. No dominance effect was found for the region on chromosome 11, as indicated by a previous candidate region bTB study. These findings require further validation with large-scale data.


High WNT6 expression indicates unfavorable survival outcome for patients with colorectal liver metastasis after liver resection.
Objective: As a member of the Wnt family, WNT6 contributes to tumorigenesis and the development of various types of cancer. However, the expression status of WNT6 in colorectal liver metastasis (CRLM) and its prognostic value remain to be elucidated. In this study, we evaluated the association of WNT6 expression with survival outcomes in CRLM patients undergoing liver resection. Methods: The medical records of 106 consecutive CRLM patients undergoing curative tumor resection between October 1996 and December 2011 were retrospectively selected. WNT6 expression was detected using immunohistochemistry (IHC) analyses on paraffin-embedded specimens. The IHC score was determined according to the percentage and intensity of positively stained cells. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and the log-rank test, and independent prognostic factors were determined by Cox regression modeling. Results: We found that WNT6 was commonly expressed in 93.4% (99/106) of colorectal cancer tissues. The median IHC score of WNT6 expression was significantly lower in patients receiving preoperative chemotherapy than those without preoperative chemotherapy (1.33 vs. 2.33, P = 0.033). Survival analysis indicated that patients with high WNT6 expression had poorer 5-year OS than those with low WNT6 expression (31.0% vs. 62.2%, P = 0.012). The 5-year OS rate was significantly lower in the high WNT6 group than in the low WNT6 group (36.8% vs. 79.9%, P = 0.013) in low-risk patients but was comparable among the high-risk patients (22.7% vs. 34.7%, P = 0.433). Multivariate analysis indicated that high WNT6 expression was independently associated with poor OS (hazard ratio [HR]: 2.089; 95% confidence interval [CI]: 1.231-3.545; P = 0.006). Conclusions: High expression of WNT6 was associated with unfavorable oncologic prognosis in patients with CRLM undergoing liver resection. Detection of WNT6 expression may be valuable for guiding postoperative treatment.


Genetic variability and history of a native Finnish horse breed.
The Finnhorse was established as a breed more than 110 years ago by combining local Finnish landraces. Since its foundation, the breed has experienced both strong directional selection, especially for size and colour, and severe population bottlenecks that are connected with its initial foundation and subsequent changes in agricultural and forestry practices. Here, we used sequences of the mitochondrial control region and genomic single nucleotide polymorphisms (SNPs) to estimate the genetic diversity and differentiation of the four Finnhorse breeding sections: trotters, pony-sized horses, draught horses and riding horses. Furthermore, we estimated inbreeding and effective population sizes over time to infer the history of this breed. We found a high level of mitochondrial genetic variation and identified 16 of the 18 haplogroups described in present-day horses. Interestingly, one of these detected haplogroups was previously reported only in the Przewalski's horse. Female effective population sizes were in the thousands, but declines were evident at the times when the breed and its breeding sections were founded. By contrast, nuclear variation and effective population sizes were small (approximately 50). Nevertheless, inbreeding in Finnhorses was lower than in many other horse breeds. Based on nuclear SNP data, genetic differentiation among the four breeding sections was strongest between the draught horses and the three other sections (FST = 0.007-0.018), whereas based on mitochondrial DNA data, it was strongest between the trotters and the pony-sized and riding horses (ΦST = 0.054-0.068). The existence of a Przewalski's horse haplogroup in the Finnhorse provides new insights into the domestication of the horse, and this finding supports previous suggestions of a close relationship between the Finnhorse and eastern primitive breeds. The high level of mitochondrial DNA variation in the Finnhorse supports its domestication from a large number of mares but also reflects that its founding depended on many local landraces. Although inbreeding in Finnhorses was lower than in many other horse breeds, the small nuclear effective population sizes of each of its breeding sections can be considered as a warning sign, which warrants changes in breeding practices.


Nongenomic actions of adrenal steroids in the central nervous system.
Mineralocorticoids and glucocorticoids are steroid hormones that are released by the adrenal cortex in response to stress and hydromineral imbalance. Historically, adrenocorticosteroid actions are attributed to effects on gene transcription. More recently, however, it has become clear that genome-independent pathways represent an important facet of adrenal steroid actions. These hormones exert nongenomic effects throughout the body, although a significant portion of their actions are specific to the central nervous system. These actions are mediated by a variety of signalling pathways, and lead to physiologically meaningful events in vitro and in vivo. We review the nongenomic effects of adrenal steroids in the central nervous system at the levels of behaviour, neural system activity, individual neurone activity and subcellular signalling activity. A clearer understanding of adrenal steroid activity in the central nervous system will lead to a better ability to treat human disease as well as reduce the side-effects of the steroid treatments already in use.


Rational design of interfacial properties of ferric (hydr)oxide nanoparticles by adsorption of fatty acids from aqueous solutions.
Notwithstanding the great practical importance, still open are the questions how, why, and to what extent the size, morphology, and surface charge of metal (hydr)oxide nanoparticles (NPs) affect the adsorption form, adsorption strength, surface density, and packing order of organic (bio)molecules containing carboxylic groups. In this article, we conclusively answer these questions for a model system of ferric (hydr)oxide NPs and demonstrate applicability of the established relationships to manipulating their hydrophobicity and dispersibility. Employing in situ Fourier transform infrared (FTIR) spectroscopy and adsorption isotherm measurements, we study the interaction of 150, 38, and 9 nm hematite (α-Fe(2)O(3)) and ∼4 nm 2-line ferrihydrite with sodium laurate (dodecanoate) in water. We discover that, independent of morphology, an increase in size of the ferric (hydr)oxide NPs significantly improves their adsorption capacity and affinity toward fatty acids. This effect favors the formation of bilayers, which in turn promotes dispersibility of the larger NPs in water. At the same time, the local order in self-assembled monolayer (SAM) strongly depends on the morphological compatibility of the NP facets with the geometry-driven well-packed arrangements of the hydrocarbon chains as well as on the ratio of the chemisorbed to the physically adsorbed carboxylate groups. Surprisingly, the geometrical constraints can be removed, and adsorption capacity can be increased by negatively polarizing the NPs due to promotion of the outer-sphere complexes of the fatty acid. We interpret these findings and discuss their implications for the nanotechnological applications of surface-functionalized metal (hydr)oxide NPs.


Influence of seasonal variability on orthopedic surgical outcomes in pediatric patients: a review of surgical site infections.
Surgical site infections (SSIs) are challenging, with highly variable reported rates for children undergoing orthopedic surgery. It has been shown in adults that there is seasonal variability in SSI rates, with peak incidences in the summer months. We reviewed 8766 pediatric orthopedic procedures completed at a quaternary children's hospital over a 43-month period. Data collected included: age, sex, BMI, season of procedure, cultures, and other variables related to risks and treatment of SSIs. Of 4875 male and 3891 female pediatric patients undergoing orthopedic procedures, 47 patients (0.54%) with an average age of 11.3 years (range: 2.0-18.6) developed an SSI. Average time between surgery and diagnosis was 27.7 ± 19.8 days. Sixty percent of SSI patients had a BMI in the 85th percentile or above, and 49% of SSI patients had a BMI above the 95th percentile. Thirty-eight patients had positive cultures, with most common infections being due to methicillin-sensitive Staphylococcus aureus in 11 (29%) cases, polymicrobial in 9 (24%), pseudomonas in 5 (13%), and coagulase-negative Staphylococcus in 5 (13%). SSI rate in winter (0.18%) was significantly lower than in autumn (0.77%, P = 0.006) and summer (0.69%, P = 0.02). The difference did not reach statistical significance from the infection rate in spring (0.53%, P = 0.06). Twenty-nine (62%) SSI cases were considered elective in nature, and the other 18 (38%) cases were for acute traumatic injuries. There is a significantly higher SSI rate in summer and autumn than winter for pediatric patients undergoing orthopedic surgeries. Most patients with SSIs were overweight or obese.


Cardiac anesthesia and surgery in geriatric patients: epidemiology, current surgical outcomes, and future directions.
The mean life expectancy of the population of the United States is projected to increase from 78.3 years at present to over 81 years in 2025, with a concomitant increase in the percentage of the population over the age of 75 years. Elderly patients are more likely to present with valvular and coronary artery disease than younger patients, and as better perioperative management contributes to improving post-operative outcomes and lower referral thresholds, very elderly patients form an increasingly large proportion of the cardiac surgical population. This article summarizes the impact of age-related pathophysiologic changes on patients' response to cardiac surgery and anesthesia, outlines useful perioperative strategies in this age group, and reviews the literature on outcomes after valvular and coronary in elderly patients.


Dynamic regulation of hepatic lipid droplet properties by diet.
Cytoplasmic lipid droplets (CLD) are organelle-like structures that function in neutral lipid storage, transport and metabolism through the actions of specific surface-associated proteins. Although diet and metabolism influence hepatic CLD levels, how they affect CLD protein composition is largely unknown. We used non-biased, shotgun, proteomics in combination with metabolic analysis, quantitative immunoblotting, electron microscopy and confocal imaging to define the effects of low- and high-fat diets on CLD properties in fasted-refed mice. We found that the hepatic CLD proteome is distinct from that of CLD from other mammalian tissues, containing enzymes from multiple metabolic pathways. The hepatic CLD proteome is also differentially affected by dietary fat content and hepatic metabolic status. High fat feeding markedly increased the CLD surface density of perilipin-2, a critical regulator of hepatic neutral lipid storage, whereas it reduced CLD levels of betaine-homocysteine S-methyltransferase, an enzyme regulator of homocysteine levels linked to fatty liver disease and hepatocellular carcinoma. Collectively our data demonstrate that the hepatic CLD proteome is enriched in metabolic enzymes, and that it is qualitatively and quantitatively regulated by diet and metabolism. These findings implicate CLD in the regulation of hepatic metabolic processes, and suggest that their properties undergo reorganization in response to hepatic metabolic demands.


[Emotional and psychosomatic disorders].
The authors made the review of literature in the field of the emotional processes. Both the increase and the decrease in emotional tension can cause disturbances in the neuro-vegetative system. Neurophisiologial examinations show that the emotions lead to the hypothalamus activation which can cause the defensive visceral, motoric and neurohormonal reactions. The long-lasting emotions lead to disturbance in homeostasis processes which can cause the functional disorders in systems and organs or psychosomatic diseases. The explanation of these processes needs to be related to the functioning of the neurvous emotional mechanisms.


Selective in vivo inhibition by quinidine of methoxyphenamine oxidation in rat models of human debrisoquine polymorphism.
1. Lewis and Dark Agouti (DA) rat strains (n = 4), models of human extensive and poor metabolizer phenotypes of debrisoquine/sparteine, respectively, were dosed with methoxyphenamine with and without prior administration of quinidine. Methoxyphenamine and its three metabolites, namely N-desmethylmethoxyphenamine, O-desmethylmethoxyphenamine and 5-hydroxymethoxyphenamine were quantified in 0-24 h urine. 2. The oxidative metabolic routes of methoxyphenamine which had been previously shown to involve the debrisoquine/sparteine isozyme, namely O-demethylation and aromatic 5-hydroxylation, were both significantly inhibited by quinidine in the two rat strains. 3. The oxidative metabolic route of methoxyphenamine which had been previously shown to not involve the debrisoquine/sparteine isozyme, namely N-demethylation, was not significantly inhibited by quinidine in either rat strain. 4. The Lewis strain pretreated with quinidine resembled the DA strain without such pretreatment in terms of O-desmethylmethoxyphenamine and 5-hydroxymethoxyphenamine in that the mean percentages of the dose excreted as these two metabolites and the mean O-desmethylmethoxyphenamine/methoxyphenamine and 5-hydroxymethoxyphenamine/methoxyphenamine ratios were similar to one another. 5. Ten days after quinidine administration to the Lewis strain of rat, all parameters of methoxyphenamine and its metabolites returned to normal. 6. A protocol involving substrate administration to Lewis strain rats with and without prior administration of quinidine could be developed as an attractive approach to screen substrates for metabolism in vivo by the debrisoquine/sparteine isozyme. Such an approach obviates interstrain differences.


Lipofibromatous hamartoma of the median nerve: 3T MRI evaluation by constrained spherical deconvolution analysis.
In this study we described a case of lipofibromatous hamartoma involving the median nerve. We adopted diffusion tensor imaging and constrained spherical deconvolution-based tractography to reconstruct the affected median nerve. Moreover, we extracted diffusion-based parameters reflecting axonal integrity loss of median nerve fibres. Our data showed that constrained spherical deconvolution-based tractography outperformed the diffusion tensor imaging-based method, allowing the detection of the entire median nerve, including its branches, thus offering a robust method to investigate the involvement of the median nerve in pathological conditions. All clinical and technical implications are extensively described.


Understanding leisure-time physical activity: Voices of people with MS who have moderate-to-severe disability and their family caregivers.
Physical activity (PA) is beneficial for all people, yet people affected by multiple sclerosis (MS) find regular PA challenging. These people may include individuals with the disease who have moderate-to-severe disability and their family caregivers. For researchers and clinicians to effectively promote PA among caregiver/care-recipient dyads with moderate-to-severe MS, a comprehensive understanding of the shared PA experiences of these dyads would be beneficial. We explored shared experiences of caregiver/care-recipient dyads affected by moderate-to-severe MS about PA and directions for intervention. Six focus groups with 23 people with moderate-to-severe MS and 12 family caregivers were conducted. Data were analysed using a constant comparative approach. Three major themes emerged as follows: (i) PA is a continuum, (ii) cycle of disengagement and (iii) cycle of adjustment. The first theme captured the dyads understanding that PA falls along a continuum ranging from highly structured to unstructured activities. Cycle of disengagement captured the experiences of dyads engaging in little or no PA. These dyads perceived internal and external issues as drivers of the cycle of disengagement, while availability of supportive programmes and services or people helped the dyads to break out of the cycle. When the cycle of disengagement was broken, the dyads described moving towards the cycle of adjustment, where they were able to learn skills and take action to incorporate PA into daily routines. This research highlights the need to adopt an integrative approach that acknowledges the caregiver/care-recipient dyad with moderate-to-severe MS as a focus for PA intervention.


[The alcohol effect on natural chronobiological rhythms of suicidal activity in patients supervised by addiction treatment specialists and psychiatrists].
To study the alcohol effect on chronological rhythms of suicidal activity in patients supervised by addiction treatment specialists and psychiatrists. We have analyzed 1094 cases of suicides committed by men who lived in Cheboksary and Novocheboksarsk. The suicide committers were divided into two groups by presence or absence of blood and/or urine alcohol; each group was subdivided into three subgroups: a) mentally healthy suicide committers (MHSC), b) those who were under the supervision of the psychiatrist (PS), c) those who were supervised by addiction treatment specialists (ATS). Chronobiological rhythms were assessed using z-scores, frequency biological rhythms were evaluated with Kolmogorov-Smirnov's test with the Lilliefors correction and rank correlation. The trends of each chronobiological number were computed, the differences of obliquing angle of the trend were evaluated using 2×2 contingency tables (c2 with Mac-Namara's amendment). All suicide committers of the 1st group showed daily rising suicide trend, which had highs in the active wakefulness period. In the 2nd group, the trend did not change in MHSC and ATS, but in PS it significantly changed to descending with two peaks at 6-8:59 and 18-20:59. Upward weekly trend in PS in both groups was almost the same (in the 1st group the obliquing angle of the trend was 19° and in the 2nd group - 21°), the maximum was observed on Saturday and Sunday. In MHSC of the 1st group, the trend was moving downward, and in the 2nd group it was low. Both MHSC and ATS had the maximum on Monday. Annual trend in the 1st group in all samples was low. In the 2nd group, the trend remained low at MHSC and ATS and changed up in PS (16°) with the maximum in November-December. Chronobiological characteristics of deaths confirmed by peaks exceeding the average proportion of suicides from 1.5 to 2.5 times were noted in all groups of suicide committers. Alcohol intake significantly changed the suicidal chronobiological rhythm in PS.


New xanthate-based radical cyclization onto alkynes.
To bypass the failure of radical cyclization involving a xanthate transfer on alkynes, a new reductive cyclization strategy has been completed with the use of a stoichiometric amount of dilauroyl peroxide in isopropanol. When the starting xanthates are prepared via a Ugi 4-component reaction with propargylamine, exomethylene lactams are formed in good yields.


Bioinspired, Shape-Morphing Scale Battery for Untethered Soft Robots.
Geometrically multifunctional structures inspired by nature can address the challenges in the development of soft robotics. A bioinspired structure based on origami and kirigami can significantly enhance the stretchability and reliability of soft robots. This study proposes a novel structure with individual, overlapping units, similar to snake scales that can be used to construct shape-morphing batteries for untethered soft robots. The structure is created by folding well-defined, two-dimensional patterns with cutouts. The folding lines mimic the hinge structure of snakeskin, enabling stable deformations without mechanical damage to rigid cells. The structure realizes multi-axial deformability and a zero Poisson's ratio without off-axis distortion to the loading axis. Moreover, to maximize areal density, the optimal cell shape is designed as a hexagon. The structure is applied to a stretchable Li-ion battery, constructed to form an arrangement of electrically interconnected, hexagonal pouch cells. In situ electrochemical characterization and numerical simulation confirm that the shape-morphing scale battery maintains its performance under dynamic deformation with a 90% stretching ratio and 10-mm-radius bending curve, guaranteeing a long-lasting charging/discharging cycle life during cyclic bending and stretching (exceeding 36,000 cycles). Finally, the shape-morphing energy storage device is applied to movable robots, mimicking crawling and slithering, to demonstrate excellent conformability and deformability.


Chemotactic responses of normal human basophils to C5a and to lymphocyte-derived chemotactic factor.
Peripheral blood basophils from normal human subjects responded chemotactically to the complement component C5a and also to the supernatant fluid from cultured human lymphocytes stimulated by mitogens or specific antigen. Basophil chemotactic factor (BCF) was detected in stimulated lymphocyte cultures within 24 hr and increased for the first 3 days. BCF was found after stimulation of lymphocytes by B or T cell mitogens as well as by specific antigen. The amount of BCF in culture fluids was independent of cell proliferation. Monocyte chemotactic factor (MCF) and BCF could not be separated from one another by Sephadex or DEAE chromatography. Both activities were eluted from Sephadex G-100 columns in a m.w. region of about 15,000 daltons and were found after ion exchange chromatography on DEAE in a peak eluted by 0.1 M NaCl. These findings suggest that mitogen or antigen-stimulated lymphocytes secrete a molecule that is chemotactic for both monocytes and basophils. Thus, in the absence of a basophil-specific chemotactic molecule, the preferential accumulation of basophils in certain types of delayed hypersensitivity skin reactions must be due to additional factors such as basophil chemotaxis augmentation factor.


Nosocomial bloodstream infections in children: an 8-year experience at a tertiary-care hospital in Finland.
Laboratory-based surveillance at a Finnish paediatric tertiary-care centre during the period 1999-2006 identified 739 nosocomial bloodstream infections (BSIs) (1.6 BSIs/1000 patient-days). High rates were detected among haematology patients (4.9 BSIs/1000 patient-days) and neonatology patients (3.2 BSIs/1000 patient-days). Most BSIs (95%) were primary infections, and 75% of those were associated with a central line. The most common pathogens were coagulase-negative staphylococci (52%), Staphylococcus aureus (7%) and Candida species (6%). The overall mortality rate within 7 days after the first positive blood culture was 3%. Those who died were more likely to have been admitted to an intensive-care unit or to have undergone surgery.


Transcatheter alcohol ablation of the septum in a patient of hypertrophic obstructive cardiomyopathy.
We performed transcatheter alcohol ablation of the septum in a case of hypertrophic obstructive cardiomyopathy. The patient showed marked reduction in LVOT gradient; however, he developed complete atrioventricular (AV) dissociation following the procedure, requiring AV sequential pacing. This important complication of this novel technique is highlighted.


Placental pathology associated with small for gestational age infants.
Infants with intrauterine growth restriction (IUGR) are at an increased risk of perinatal disease, including death. Many, but not all small for gestational age infants (SGA) have IUGR. Placental disease is an important cause of IUGR, and gross and microscopic examination is critical in explaining such cases. Reports of placentas from infants with a birth weight < 2SD from the mean (approx 3rd centile) born between Jan 2004-Dec 2011 were evaluated. The principal pathology was determined in each case. Where two or more pathologic findings were present, they were ranked as principal and co-existing in terms of severity. There were 69,493 deliveries over the study period. 461 SGA cases were identified. No placenta was available in 44 cases, and 21 cases of known anomalies were excluded, leaving a study group of 396 cases. Pathology potentially causing or contributing to SGA and/or IUGR was identified in 84.1% of cases. Significant co-existing pathology was seen in 88 cases (22%). Placental examination provides key information in understanding abnormal fetal growth.


Ephedrae herba, a component of Japanese herbal medicine Mao-to, efficiently activates the replication of latent human immunodeficiency virus type 1 (HIV-1) in a monocytic cell line.
The persistence of latent human immunodeficiency virus type 1 (HIV-1)-infected cellular reservoirs, despite prolonged treatment with highly active antiretroviral therapy (HAART), represents a major hurdle to virus eradication. In this study, we evaluated the effect of Japanese herbal medicine on the induction of HIV-1 replication in latently infected monocytic cell line, U1, in order to eradicate virus efficiently. We found that Mao-to was able to induce HIV-1 replication either alone or in combination with tumor necrosis factor-alpha (TNF-alpha). Among the four components of Mao-to, only Ephedrae herba had strong effects in inducing HIV-1 replication. Analysis by Western blotting revealed that Ephedrae herba induced the nuclear translocation of nuclear factor-kappa B (NF-kappaB). Reporter assay data also showed that Ephedrae herba and, slightly, Mao-to activated the NF-kappaB promoter, indicating that these herbal agents may induce HIV-1 replication through NF-kappaB activation. These findings suggest that Mao-to and its component, Ephedrea herba, may be good candidates to augment HAART by inducing the expression of latent HIV-1 with the ultimate goal of eliminating persistent viral reservoirs in individuals infected with HIV-1.


A surprising abundance of human disease genes in a simple "basal" animal, the starlet sea anemone (Nematostella vectensis).
Invertebrate animals have provided important insights into the mechanisms of, and treatment for, numerous human diseases. A surprisingly high proportion of genes underlying human disease are present in the genome of a simple, evolutionarily basal invertebrate animal, Nematostella vectensis, including some genes that are absent in established invertebrate model organisms. This, together with the laboratory tractability and regenerative capability of N. vectensis, recommends the species as an important new experimental model for the study of genes underlying human disease.


High-level expression of tamavidin 2 in human cells by codon-usage optimization.
Tamavidin 2 is a fungal protein that binds to biotin with an extremely high affinity. Tamavidin 2 is superior to avidin or streptavidin in terms of its low-level non-specific binding and high-level thermal stability. However, the gene for tamavidin 2 is highly expressed in Escherichia coli but not in mammalian cells, restricting its application as an affinity tag in mammalian cells. Here, we optimized the codon usage of tamavidin 2 for human cells and found that the resultant mutant expressed tamavidin 2 at approximately 30-fold higher level compared with the native gene. The protein thus produced in human cells could be purified by iminobiotin affinity chromatography, bound tightly to biotin, and was stable at high temperature (82 °C). This powerful technology for high-level expression of tamavidin 2 in mammalian cells will be of value in evaluating various fusion proteins produced in mammalian cells for numerous applications.


Relationship of locomotive syndrome with health-related quality of life among patients with obstructive sleep apnea syndrome.
[Purpose] This study aimed to examine the prevalence of locomotive syndrome among patients with obstructive sleep apnea syndrome (OSAS) using the "loco-check" recently developed by the Japanese Orthopedic Association, and to compare health-related quality of life (HRQOL) among patients with and without locomotive syndrome. [Subjects and Methods] This cross-sectional study evaluated 1,195 outpatients with OSAS (1,030 males and 165 females). Locomotive syndrome was evaluated using the Japanese Orthopedic Association's "loco-check". HRQOL and psychological distress were evaluated using the EuroQol 5-dimensional (EQ-5D) and 6-item Kessler questionnaires. [Results] Locomotive syndrome was detected in 578 patients (48.4%), including 398 males (38.6% of males) and 119 females (70.3% of females). Patients with OSAS and locomotive syndrome had significantly lower EQ-5D scores, compared to patients without locomotive syndrome. Multiple regression analysis revealed that HRQOL among patients with OSAS was independently associated with locomotive syndrome, age, gender, body mass index, apnea hypopnea index, the Japanese version of the Epworth Sleepiness Scale score, and exercise habits. [Conclusion] The prevalence of locomotive syndrome was thought to be comparatively high in patients with OSAS, and locomotive syndrome was associated with lower HRQOL, even after adjusting for confounding factors. Prevention or management of locomotive syndrome may be beneficial for improving HRQOL among patients with OSAS.


Defining specific allergens for improved component-resolved diagnosis of shrimp allergy in adults.
Shrimp is one of the predominant causes of food allergy among adults, often presenting with severe reactions. Current in vitro diagnostics are based on quantification of patient specific-IgE (sIgE) to shrimp extract. Tropomyosin is the known major shrimp allergen, but IgE sensitisation to other allergens is poorly characterised. In this study, the binding of IgE to various shrimp allergens, additional to tropomyosin, was investigated using sera from 21 subjects who had clinical reactions to one or more shellfish species. Total shrimp-sIgE was quantified using ImmunoCAP, while allergen-sIgEs were quantified using immunoblotting and mass spectrometry, and immuno-PCR to recombinant shrimp tropomyosin. Sixty-two percent of subjects (13/21) were positive to shrimp by ImmunoCAP. IgE from 43% of subjects (9/21) bound tropomyosin, while an additional 29% of subjects (6/21) demonstrated IgE-binding solely to other shrimp allergens, including sarcoplasmic calcium-binding protein, arginine kinase and hemocyanin. Furthermore, IgE sensitisation to other shrimp allergens was demonstrated in 50% of subjects (4/8) who were ImmunoCAP negative. The lack of standardised shrimp allergens and inadequacy of current extracts for shrimp allergy diagnosis is highlighted by this study. Comprehensive knowledge of less studied allergens and their inclusion in component-resolved diagnostics will improve diagnostic accuracy, benefitting the wider population suffering from shellfish allergy.


New genome sequences of gamboa viruses (family bunyaviridae, genus orthobunyavirus) isolated in panama and Argentina.
We describe here the nearly complete open reading frame (ORF) of five Gamboa virus strains isolated in Panama and Argentina. The viruses with complete ORF showed the regular genome organization observed in other orthobunyaviruses with exception to the presence of NSs protein. All predicted proteins showed homology with viruses belonging to members of the family Bunyaviridae.


[Acute nonspecific inflammatory reaction and modification of resistance to Toxoplasma gondii].
Two series of mice have been injected by peritoneal route with a suspension of Toxoplasma diluted by logarithmic progression of ratio of ten. Only one of two series had been inoculated by pleural route with inflammatory inoculum (calcium pyrophosphate microcrystals). The mice with inflammatory-treatment developed a slightly higher resistance to toxoplasmosis infection: in this group, throughout the entire experiment, mortalities have been delayed, the evolution of LD 50 showed lower titer, death rates have been lower than in the untreated group.


When Should a Positive Surgical Margin Ring a Bell? An Analysis of a Multi-Institutional Robot-Assisted Laparoscopic Radical Prostatectomy Database.
The impact of positive surgical margin (SM) on cancer control outcomes in prostate cancer patients is a subject of continuous debate. We test the hypothesis that the impact of SM on clinical recurrence (CR) rate may vary based on the other clinical/pathologic characteristics of the tumor. We focused on 5290 patients treated with robot-assisted radical prostatectomy and pelvic node dissection, between 2002 and 2013, at three tertiary care centers. Regression tree analysis stratified patients into risk groups based on their tumor characteristics and the corresponding CR rate. Kaplan-Meier log-rank and multivariable Cox regression models tested the relationship between SM status and CR rate in each tree-generated risk group. Mean (median) follow-up time was 47.7 (39.0) months. Regression tree analysis that considered all available covariates, except SM status, divided patients based on their CR risk into the following risk groups: (1) high risk (any pT3b/pT4 disease); (2) intermediate risk (≤pT3a disease and pGS 8-10); (3) low risk (≤pT3a, pGS ≤7, and prostate-specific antigen [PSA] >9 ng/mL); and (4) very low risk (≤pT3a, pGS ≤7, and PSA ≤9 ng/mL). Positive SM had a significant detrimental impact on CR risk only in two groups: intermediate risk (p < 0.001) and high risk (p = 0.01). These observations were confirmed by multivariable analyses. Our findings show that positive SM had a detrimental impact on CR only in a minority of patients (15%), specifically in those with advanced pathologic stage and/or pathologically poorly differentiated tumor. For all the remaining patients (85%), positive SM by itself did not increase the risk of CR.


The role of CAPG in molecular communication between the embryo and the uterine endometrium: Is its function conserved in species with different implantation strategies?
During the preimplantation period of pregnancy in eutherian mammals, transcriptional and proteomic changes in the uterine endometrium are required to facilitate receptivity to an implanting blastocyst. These changes are mediated, in part, by proteins produced by the developing conceptus (inner cell mass and extraembryonic membranes). We hypothesized that this common process in early pregnancy in eutheria may be facilitated by highly conserved conceptus-derived proteins such as macrophage capping protein (CAPG). We propose that CAPG may share functionality in modifying the transcriptome of the endometrial epithelial cells to facilitate receptivity to implantation in species with different implantation strategies. A recombinant bovine form of CAPG (91% sequence identity between bovine and human) was produced and bovine endometrial epithelial (bEECs) and stromal (bESCs) and human endometrial epithelial cells (hEECs) were cultured for 24 hours with and without recombinant bovine CAPG (rbCAPG). RNA sequencing and quantitative real-time PCR analysis were used to assess the transcriptional response to rbCAPG (Control, vehicle, CAPG 10, 100, 1000 ng/mL: n = 3 biological replicates per treatment per species). Treatment of bEECs with CAPG resulted in alterations in the abundance of 1052 transcripts (629 increased and 423 decreased) compared to vehicle controls. Treatment of hEECs with bovine CAPG increased expression of transcripts previously known to interact with CAPG in different systems (CAPZB, CAPZA2, ADD1, and ADK) compared with vehicle controls (P < .05). In conclusion, we have demonstrated that CAPG, a highly conserved protein in eutherian mammals, elicits a transcriptional response in the endometrial epithelium in species with different implantation strategies that may contribute to pregnancy success.


[A method for combined scatter and attenuation correction without transmission measurement for myocardial SPECT with 99m-Tc binding].
A new strategy is introduced for a double-head gamma-camera to calculate and to correct for attenuation distribution from count rates of backscattered radiation of 99mTc in the human thorax/myocardium setting. The intention was to gain segmented and calibrated images of distribution employing the structures of lungs and other tissues, so that attenuation may be subsequently corrected by the method of Chang Acquisition was done simultaneously in three energy window for 99mTc to receive both emitted and scattered radiation. The acquire projections were used to calculate the attenuation distribution and to execute a scatter correction by the method of Ogawa et. al. By measuring phantoms and evaluating a set of patient studies, quality for both of the approaches towards attenuated distribution and the quality of attenuation correction was tested and an optimal setting for parameters involved was selected. The procedure adequately approaches the correction for both emitted and scattered radiation in SPECT, as experienced in phantom and patient studies. Clinical usefulness was preliminary documented in selected cases. In normal perfusion, distribution was more homogeneous. Perfusion defects appeared more definitive. Problems occurred in high adjacent non-target activity (e.g., in the gallbladder) and with low count rate statistics. Myocardial 99mTc MIBI SPECT may be effectively corrected for both attenuation a scatter without an additional transmission device.


Development and validation of a patient-centered health-related quality-of-life measure: the chronic heart failure assessment tool.
Despite the importance of health-related quality of life (HRQL) as an outcome measure in chronic heart failure (CHF), instruments currently available have been developed by clinicians or researchers; none have been derived from the patient's perspective. The purpose of this study was to develop and validate a patient-derived, disease-specific HRQL measure. The psychometric testing of the Chronic Heart Failure Assessment Tool (CHAT) followed 2 phases: testing the psychometric properties (n = 223) of the 51-item version of the CHAT in a postal survey and validation of the CHAT (n = 68) using the Medical Outcomes Study 36-Item Short-Form Health Survey and the Minnesota Living With Heart Failure questionnaire. The CHAT contains questions measuring 7 themes of HRQL: physical ability, emotional state, self-perception, relationships, coping with symptoms, maintaining social/lifestyle status, and cognitive aspects in respect to CHF. Factor analysis was used to analyze these themes. Four domains emerged: symptoms, activity levels, psychosocial aspects, and emotions. The CHAT comprises dimensions of HRQL identified by patients in the study population that may more appropriately reflect the concerns of patients. Further work is recommended to develop this tool for use as an HRQL measure in a CHF population.


Structural analysis of 2,6-[bis(alkyloxy)methyl]-phenyltin derivatives using electrospray ionization mass spectrometry.
Electrospray ionization (ESI) mass spectrometry was applied to the structural analysis of 23 2,6-[bis(alkyloxy)methyl]phenyltin(IV) derivatives. The mass spectra were measured in both polarity modes and multistage tandem mass spectrometric (MS(n)) measurements were performed on the ion trap analyser for positively charged tin-containing ions. The sum of complementary ions observed in the positive-ion mode (i.e. [M-R(3)](+) ion) and in the negative-ion mode (i.e. [R(3)](-) ion) permits molecular mass determination in spite of the fact that the molecular adducts were often missing even in the first-order mass spectra. The subsequent fragmentation of [M-R(3)](+) ions studied by MS(n) and the correlation of observed fragment ions with the expected structures of synthesized organotin(IV) compounds allowed us to understand the fragmentation behaviour and the mechanism of the ion formation for studied compounds. The typical neutral losses are alkenes, alcohols and aldehydes. The fragmentation pattern of one selected compound was supported by MS(n) measurements of an isotopically labelled analogue to confirm unusual ion-molecule reactions of some fragment ions with water in the ion trap.


A molecular understanding of complementary chromatic adaptation.
Photosynthetic activity and the composition of the photosynthetic apparatus are strongly regulated by environmental conditions. Some visually dramatic changes in pigmentation of cyanobacterial cells that occur during changing nutrient and light conditions reflect marked alterations in components of the major light-harvesting complex in these organisms, the phycobilisome. As noted well over 100 years ago, the pigment composition of some cyanobacteria is very sensitive to ambient wavelengths of light; this sensitivity reflects molecular changes in polypeptide constituents of the phycobilisome. The levels of different pigmented polypeptides or phycobiliproteins that become associated with the phycobilisome are adjusted to optimize absorption of excitation energy present in the environment. This process, called complementary chromatic adaptation, is controlled by a bilin-binding photoreceptor related to phytochrome of vascular plants; however, many other regulatory elements also play a role in chromatic adaptation. My perspectives and biases on the history and significance of this process are presented in this essay.


Minimally invasive cardiac surgery using a flexible aortic clamp.
Minimally invasive surgery for mitral valve disease has been performed using a variety of technologies, some of which are complex, have a steep learning curve, and are expensive. We have adopted a simple cost-effective approach over the last 7 years to perform a variety of minimally invasive procedures with excellent outcomes. There have been no strokes, no mortalities, and no episodes of limb ischemia in our series. No patient has required reoperation.


Proteolytic action of GlpG, a rhomboid protease in the Escherichia coli cytoplasmic membrane.
We characterized Escherichia coli GlpG as a membrane-embedded protease and a possible player in the regulated intramembrane proteolysis in this organism. From the sequence features, it belongs to the widely conserved rhomboid family of membrane proteases. We verified the expected topology of GlpG, and it traverses the membrane six times. A model protein having an N-terminal and periplasmically localized beta-lactamase (Bla) domain, a LacY-derived transmembrane region, and a cytosolic maltose binding protein (MBP) mature domain was found to be GlpG-dependently cleaved in vivo. This proteolytic reaction was reproduced in vitro using purified GlpG and purified model substrate protein, and the cleavage was shown to occur between Ser and Asp in a region of high local hydrophilicity, which might be located in a juxtamembrane rather than an intramembrane position. The conserved Ser and His residues of GlpG were essential for the proteolytic activities. Our results using several variant forms of the model protein suggest that GlpG recognizes features of the transmembrane regions of substrates. These results point to a detailed molecular mechanism and cellular analysis of this interesting class of membrane-embedded proteases.


Contrasting effects of acute and chronic treatment with imipramine and fluoxetine on inhibitory avoidance and escape responses in mice exposed to the elevated T-maze.
The elevated T-maze (ETM) is an animal model of anxiety-like behavior that assesses two different defensive behavioral tasks in the same animal-acquisition of inhibitory avoidance and latency to escape from an open and elevated arm. In rats, cute and chronic treatments with anxiolytic-like drugs impair avoidance acquisition while only chronic administration of panicolytic-like drugs impairs open arm withdrawal. To date, only the acute effects of anxiolytic/anxiogenic or panicolytic/panicogenic drugs have been tested in the mouse ETM and the results have partially corroborated those found in the rat ETM. This study investigated the effects of acute (a single intraperitoneal injection 30 min before testing) and chronic (daily i.p. injections for 15 consecutive days) treatment with imipramine or fluoxetine, non-selective and selective serotonin reuptake inhibitors, respectively, on inhibitory avoidance and escape tasks in the mouse ETM. Neither acute nor chronic treatment with imipramine (0, 1, 5 or 10 mg/kg, i.p.) significantly changed the behavioral profile of mice in the two ETM tasks. Interestingly, while acute fluoxetine (0, 5, 10, 20 or 40 mg/kg, i.p.) facilitated inhibitory avoidance and impaired escape latency, chronic treatment (0, 5, 20 or 40 mg/kg, i.p.) with this selective serotonin reuptake inhibitor (SSRI) produced an opposite effect, i.e., it impaired inhibitory avoidance acquisition and facilitated open arm withdrawal. Importantly, acute or chronic treatment with imipramine (except at the highest dose that increased locomotion when given acutely) or fluoxetine failed to alter general locomotor activity in mice as assessed in an ETM in which all arms were enclosed by lateral walls (eETM). These results suggest that inhibitory avoidance acquisition is a useful task for the evaluation of acute and chronic effects of SSRI treatment on anxiety in mice. However, as open arm latency was actually increased and reduced by acute and chronic fluoxetine, respectively, this does not seem to be a useful measure of escape from a proximal threat in this species.


Positive nitrogen balance in burn patients.
Two case-histories of patients with full thickness burns covering 60 and 70% of their bodies are presented. In spite of the obligatory increase in the metabolic rate, both patients had a positive nitrogen balance from the very beginning, maintained exclusively by peroral nutrition.


Behaviour consistency is a sensitive tool for distinguishing the effects of aging on physical activity.
We attempted to establish a novel parameter of behaviour consistency to help determine the effect of age on physical activity. Using the speed of movement to quantify behaviour might not be sufficient to determine this effect. The slowing of motor activities that occurs with aging is related to the decline of the aging brain. Previous studies have found different running-related hippocampal theta rhythm responses in the aging and exercise model. Therefore, we hypothesized that a familiarity with the environment and physical strength affect behavioural consistency in rats during running exercises. For this study, we used a treadmill and 30-minute running test at constant speeds and compared changes in the triaxial accelerometer and hippocampal theta rhythm between adult and middle-aged rats. No significant differences in RR intervals, mean cross-correlations (MCCs), or the proportion of good correlation coefficient (PGCC) were observed between adult and middle-aged rats in awake states before running on the treadmill. The root mean square (RMS) of the triaxial acceleration vectors in middle-aged rats was higher than that in adult rats. In the treadmill running tests, the RMS observed in middle-aged rats was significantly lower than that observed in adult rats. MCC and PGCC, which indicate movement consistencies, were significantly higher in middle-aged rats than they were in adult rats during the entire running test. However, only the RMS of the adult rats showed a negative correlation with exercise duration. Both MCC and PGCC were positively correlated with exercise duration. By contrast, a similar phenomenon was not found in the changes or differences in hippocampal theta rhythms between these two groups. Therefore, we consider that the MCC and PGCC could distinguish age-related movement differences and indicate coordination/adaptation during exercise. Changes in physical activity and alterations in the hippocampal theta rhythm were not different between the groups.


Evaluation of temperature gradient capillary electrophoresis for detection of the Factor V Leiden mutation: coincident identification of a novel polymorphism in Factor V.
The Factor V Leiden mutation (G1691A) is a clinically important polymorphism that results in an increased risk of thrombosis. The goal of this study was to compare a temperature gradient capillary electrophoresis (TGCE) platform for the detection of Factor V gene mutations to a conventional restriction fragment length polymorphism (RFLP) assay. Three hundred and four samples were analyzed by both TGCE and a common clinical Mnl I/RFLP assay. Concordance of results between the two assays was observed for 302/304 (99.3%) of the samples. All of the Leiden mutants (23/23, 100%) were identified by TGCE. Of the two discrepant results, one was caused by low peak heights in the TGCE output data and was easily rectified by the addition of a minimum peak height threshold. The second discrepancy resulted from the presence of a G-->A transition 95 bp downstream of the Leiden mutation site. This polymorphism represents a previously unreported alteration of the Factor V gene. The TGCE assay is less labor-intensive and has a higher throughput capacity than the Mnl I/RFLP assay. TGCE is a less specific assay than the Mnl I/RFLP assay that allows for the detection of novel polymorphisms, but also creates the need for all positive TGCE results to be confirmed by an alternate method such as sequencing. Our results demonstrate that TGCE is a highly sensitive method for mutation detection and has utility for mutation discovery analysis.


Six new C-21 steroidal glycosides from Dregea sinensis Hemsl.
Six new C-21 steroidal glycosides (1-6) were separated from the root of Dregea sinensis Hemsl. and their structures were elucidated using extensive nuclear magnetic resonance, mass spectrometry, and infrared spectral analyses. Isolated compounds were evaluated for antitumor activity, which showed that compound 3 had moderate activity in Jurkat cells (IC50 19.54 ± 0.91 μM), and compounds 1-4 had significant effects against IL-2R and TNFR2 (IC50 1.518 ± 0.06 μM to 5.9 ± 0.07 μM).


[Renal microscopic hematuria in rheumatoid polyarthritis].
In a retrospective study of 162 cases of rheumatoid arthritis we found that 24 patients (14.8%) had presented with microscopic haematuria with or without proteinuria. Renal biopsy had been performed in 15 of these 24 patients. Apart from the classical lesions of extramembranous glomerulonephritis, amyloidosis and interstitial nephritis, 60% of histological results showed lesions of mesangial glomerulonephritis. These lesions seemed to be independent of maintenance treatments, but they might have been facilitated by the chronic inflammation kept going by the rheumatoid disease itself.


Gudmundur Finnbogason, "sympathetic understanding," and early Icelandic psychology.
Gudmundur Finnbogason (1873-1944) was a pioneer of Icelandic psychology. He was educated at the University of Copenhagen where he finished his M.A. in 1901 in philosophy, specializing in psychology. During the years 1901-1905, Finnbogason played a major role in establishing and shaping the future of primary education in Iceland. He defended his doctoral thesis on "sympathetic understanding" at the University of Copenhagen in 1911. This work deals with the psychology of imitation. In it Finnbogason defends the view that imitation is basically perception so that there is a direct link from perception to motor behavior. Through imitation people tend to assume the countenance and demeanor of other people, thus showing, in Finnbogason's terminology, "sympathetic understanding." Finnbogason's theory of imitation in many respects anticipates contemporary approaches to the psychology of imitation. In 1918 Finnbogason became professor of applied psychology at the recently founded University of Iceland. Here he attempted to establish psychology as an independent discipline. In this he was unsuccessful; his chair was abolished in 1924.


A newly identified single nucleotide polymorphism in the promoter of the matrix metalloproteinase-1 gene.
Matrix metalloproteinase-1 (MMP-1) is a member of the matrix metalloproteinase enzyme family that degrades components of the extracellular matrix. Recent studies have demonstrated several polymorphic sites in the promoter of the MMP-1 gene. A newly identified single nucleotide polymorphism (SNP) at position -519 in the promoter region of the MMP-1 gene is reported. This polymorphism consists in a guanine to adenine substitution. A linkage between polymorphisms -519A/G and -1607 1G/2G was also studied.


Synthesis of the Escherichia coli K-12 nucleoid-associated DNA-binding protein H-NS is subjected to growth-phase control and autoregulation.
Mutations in the structural gene (hns) for the Escherichia coli nucleoid-associated DNA-binding protein H-NS cause highly pleiotropic effects on gene expression, site-specific recombination, transposition of phage Mu, the stability of the genetic material and the topological state of the DNA. We have investigated the regulation of hns expression and found that hns transcription is subjected to stationary phase induction and negative autoregulation. A set of hns-lacZ protein and operon fusions was constructed in vitro and integrated in single copy into the attB site of the bacterial genome. Quantification of beta-galactosidase activity along the bacterial growth curve showed that hns expression increases approximately 10-fold in stationary phase compared with exponentially growing cells. Immunological detection of the H-NS protein in growing and stationary phase cells supported the genetic data and showed that H-NS synthesis varies with growth phase. In addition, primer extension experiments demonstrated that the amount of hns mRNA is elevated in stationary phase cultures and that hns transcription is directed by a unique promoter functioning in both log and stationary phase. Disruption of the hns gene by an insertion mutation led to the derepression (approximately fourfold) of the expression of an hns-lacZ operon fusion integrated at the attB site, showing that hns transcription is subjected to negative regulation by its own gene product. Autoregulation of hns expression is particularly pronounced in log phase. Both stationary phase control and autoregulation of hns transcription are associated with a 130 bp fragment that contains the hns promoter. In order to study the interaction of H-NS with its own regulatory region, we developed an efficient overproduction procedure and a simple purification scheme for H-NS. DNA gel retardation assays showed that the H-NS protein can preferentially interact with a restriction fragment carrying the hns promoter. This restriction fragment showed features of curved DNA as judged by two-dimensional polyacrylamide gel electrophoresis performed at 4 degrees C and 60 degrees C.


[Segmental reversal of the small bowel as treatment of short bowel syndrome in adults].
Short bowel syndrome is the result of extensive surgical resection, inherited defects or loss of functional absorbing intestine. Parenteral nutrition is associated with high economical expenses, increased morbidity and decreased quality of life. Intestinal transplantation is associated with high morbidity and mortality rates. Segmental reversal of the small bowel can prolong the transit time in the small bowel and in many cases permanently end parenteral nutrition dependency. Segmental reversal of the small bowel should be integrated in the surgical treatment of adults with short bowel syndrome.


Development and Validation of an Inflammatory-Frailty Index for Kidney Transplantation.
Physical frailty phenotype is characterized by decreased physiologic reserve to stressors and associated with poor outcomes, such as delirium and mortality, that may result from post-kidney transplant (KT) inflammation. Despite a hypothesized underlying pro-inflammatory state, conventional measures of frailty typically do not incorporate inflammatory biomarkers directly. Among KT candidates and recipients, we evaluated the inclusion of inflammatory biomarkers with traditional physical frailty phenotype components. Among 1154 KT candidates and recipients with measures of physical frailty phenotype and inflammation (interleukin 6 [IL6], tumor necrosis factor alpha [TNFα], C-reactive protein [CRP]) at 2 transplant centers (2009-2017), we evaluated construct validity of inflammatory-frailty using latent class analysis. Inflammatory-frailty measures combined 5 physical frailty phenotype components plus the addition of an individual inflammatory biomarkers, separately (highest tertiles) as a sixth component. We then used Kaplan-Meier methods and adjusted Cox proportional hazards to assess post-KT mortality risk by inflammatory-frailty (n = 378); Harrell's C-statistics assessed risk prediction (discrimination). Based on fit criteria, a 2-class solution (frail vs nonfrail) for inflammatory-frailty was the best-fitting model. Five-year survival (frail vs nonfrail) was: 81% versus 93% (IL6-frailty), 87% versus 89% (CRP-frailty), and 83% versus 91% (TNFα-frailty). Mortality was 2.07-fold higher for IL6-frail recipients (95% CI: 1.03-4.19, p = .04); there were no associations between the mortality and the other inflammatory-frailty indices (TNFα-frail: 1.88, 95% CI: 0.95-3.74, p = .07; CRP-frail: 1.02, 95% CI: 0.52-2.03, p = .95). However, none of the frailty-inflammatory indices (all C-statistics = 0.71) improved post-KT mortality risk prediction over the physical frailty phenotype (C-statistics = 0.70). Measurement of IL6-frailty at transplantation can inform which patients should be targeted for pre-KT interventions. However, the traditional physical frailty phenotype is sufficient for post-KT mortality risk prediction.