Effect of evolocumab on fasting and post fat load lipids and lipoproteins in familial dysbetalipoproteinemia.
Familial dysbetalipoproteinemia (FD) is the second most common monogenic lipid disorder (prevalence 1 in 850-3500), characterized by postprandial remnant accumulation and associated with increased cardiovascular disease (CVD) risk. Many FD patients do not achieve non-HDL-C treatment goals, indicating the need for additional lipid-lowering treatment options. To evaluate the effect of the PCSK9 monoclonal antibody evolocumab added to standard lipid-lowering therapy on fasting and post fat load lipids and lipoproteins in patients with FD. A randomized placebo-controlled double-blind crossover trial comparing evolocumab (140 mg subcutaneous every 2 weeks) with placebo during two 12-week treatment periods. At the start and end of each treatment period patients received an oral fat load. The primary endpoint was the 8-hour post fat load non-HDL-C area under the curve (AUC). Secondary endpoints included fasting and post fat load lipids and lipoproteins. In total, 28 patients completed the study. Mean age was 62±9 years and 93% had an Ɛ2Ɛ2 genotype. Evolocumab reduced the 8-hour post fat load non-HDL-C AUC with 49% (95%CI 42-55) and apolipoprotein B (apoB) AUC with 47% (95%CI 41-53). Other fasting and absolute post fat load lipids and lipoproteins including triglycerides and remnant-cholesterol were also significantly reduced by evolocumab. However, evolocumab did not have significant effects on the rise above fasting levels that occurred after consumption of the oral fat load. Evolocumab added to standard lipid-lowering therapy significantly reduced fasting and absolute post fat load concentrations of non-HDL-C, apoB and other atherogenic lipids and lipoproteins in FD patients. The clinically significant decrease in lipids and lipoproteins can be expected to translate into a reduction in CVD risk in these high-risk patients.


Filament organization of the bacterial actin MreB is dependent on the nucleotide state.
MreB, the bacterial ancestor of eukaryotic actin, is responsible for shape in most rod-shaped bacteria. Despite belonging to the actin family, the relevance of nucleotide-driven polymerization dynamics for MreB function is unclear. Here, we provide insights into the effect of nucleotide state on membrane binding of Spiroplasma citri MreB5 (ScMreB5). Filaments of ScMreB5WT and an ATPase-deficient mutant, ScMreB5E134A, assemble independently of the nucleotide state. However, capture of the filament dynamics revealed that efficient filament formation and organization through lateral interactions are affected in ScMreB5E134A. Hence, the catalytic glutamate functions as a switch, (a) by sensing the ATP-bound state for filament assembly and (b) by assisting hydrolysis, thereby potentially triggering disassembly, as observed in other actins. Glu134 mutation and the bound nucleotide exhibit an allosteric effect on membrane binding, as observed from the differential liposome binding. We suggest that the conserved ATP-dependent polymerization and disassembly upon ATP hydrolysis among actins has been repurposed in MreBs for modulating filament organization on the membrane.


What speech-language pathologists need to know about auditory processing disorder.
To consider whether auditory processing disorder (APD) is truly a distinct clinical entity or whether auditory problems are more appropriately viewed as a processing deficit that may occur with various developmental disorders. Theoretical and clinical factors associated with APD are critically evaluated. There are compelling theoretical and clinical reasons to question whether APD is in fact a distinct clinical entity. Not only is there little evidence that auditory perceptual impairments are a significant risk factor for language and academic performance (e.g., Hazan, Messaoud-Galusi, Rosan, Nouwens, & Shakespeare, 2009; Watson & Kidd, 2009), there is also no evidence that auditory interventions provide any unique benefit to auditory, language, or academic outcomes (Fey et al., 2011). Because there is no evidence that auditory interventions provide any unique therapeutic benefit (Fey et al., 2011), clinicians should treat children who have been diagnosed with APD the same way they treat children who have been diagnosed with language and learning disabilities. The theoretical and clinical problems associated with APD should encourage clinicians to consider viewing auditory deficits as a processing deficit that may occur with common developmental language and reading disabilities rather than as a distinct clinical entity.


PIV and CFD investigation of paddle flocculation hydrodynamics at low rotational speeds.
In this study, flocculation hydrodynamics were evaluated by investigating the velocity field of turbulent flow experimentally and numerically, in a laboratory scale paddle flocculator. Turbulence that either promotes the particle aggregation or the breakage of flocs is complicated and has been considered and compared in this work using two turbulence models; namely, the SST k-ω and the IDDES. Results showed that IDDES provided very slight improvement as compared to SST k-ω, yielding the latter sufficient in accurately simulating the flow inside the paddle flocculator. A Goodness-of-Fit evaluation was adopted to study the convergence between PIV and CFD results, and to compare the results of the used CFD turbulence models. The study focused, as well, on the quantification of the slippage factor k, as 0.18 at low rotational speeds of 3 rpm and 4 rpm, and compared to conventional typical value of 0.25. This reduction of k from 0.25 to 0.18 yields around 27-30% increase in the power imparted to the fluid, and about 14% increase in velocity gradient (G). This implies that more mixing is provided than expected, and therefore, less energy is input and thus the electric consumption for the flocculation unit at a drinking water treatment plant could be potentially decreased.


Postsurgical high flow priapism treated by transarterial embolizaton: a case report.
The authors report a case of painful priapism, caused by iatrogenic arterial injury from endoscopic internal urethrotomy procedure for stricture urethra, which increased blood circulation in the penis. On physical examination, there was sustained erection, turgid corpora, swelling of penis and prepuce and tenderness at the perineal area. Bilateral selective internal iliac angiograms showed a prominent right internal pudendal artery and deep penile artery terminating in an arterio-sinusoidal fistula. This case was treated by superselective arterial embolization with Gelfoam pledgets and the treatment was successfully carried out in one session. However the patient sill had erectile dysfunction for six months. After that, the erectile dysfunction gradually improved. Finally, the patient had normal erectile function one year after embolization.


AIDS--a global concern.
HIV and AIDS are diseases which have rocked the health care agencies throughout the world in the 1980's. The editor of Midwifery has tried to secure a paper on the impact of AIDS on midwifery in some parts of the world. As much research has still to be done this paper is not available at the moment. The following paper was offered for publication and although written for nurses (it was presented at the 3rd International Intensive Care conference, Montreal Canada in August 1988) its message is for all health care workers.


Genome-wide association study across pediatric central nervous system tumors implicates shared predisposition and points to 1q25.2 (PAPPA2) and 11p12 (LRRC4C) as novel candidate susceptibility loci.
Central nervous system (CNS) tumors constitute the most common form of solid neoplasms in children, but knowledge on genetic predisposition is sparse. In particular, whether susceptibility attributable to common variants is shared across CNS tumor types in children has not been investigated. The purpose of this study was to explore potential common genetic risk variants exhibiting pleiotropic effects across pediatric CNS tumors. We also investigated whether such susceptibility differs between early and late onset of disease. A Danish nationwide genome-wide association study (GWAS) of 1,097 consecutive patients (< 15 years of age) with CNS tumors and a cohort of 4,745 population-based controls. For both the overall cohort and patients diagnosed after the age of four, the strongest association was rs12064625 which maps to PAPPA2 at 1q25.2 (p = 3.400 × 10-7 and 9.668 × 10-8, respectively). PAPPA2 regulates local bioavailability of insulin-like growth factor I (IGF-I). IGF-I is fundamental to CNS development and is involved in tumorigenesis across a wide range of different cancers. For the younger children, the strongest association was provided by rs11036373 mapping to LRRC4C at 11p12 (p = 7.620 × 10-7), which encoded protein acts as an axon guidance molecule during CNS development and has not formerly been associated with brain tumors. This GWAS indicates shared susceptibility attributable to common variants across pediatric CNS tumor types. Variations in genetic loci with roles in CNS development appear to be involved, possibly via altered IGF-I related pathways.


Histoenzymological Characteristics of Smooth Muscle Cells in Myocardial Vessels: A Comparative Study under Conditions of Increased Left or Right Ventricular Afterload.
Histoenzymological methods were used to study metabolism of smooth muscle cells of intramural myocardial arteries during experimental aortic or pulmonary artery stenosis. Aortic stenosis was accompanied by changes in smooth muscles of the left ventricle manifested by deceleration of tricarboxylic acid cycle, inhibition of oxidation of free fatty acids and their metabolites, flux redistribution in the glycolytic cascade, and inhibition of shuttle systems and biosynthetic processes. Similar metabolic alterations were observed in vessels of the ventricular septum, but they were not revealed in vessels of the right ventricle (except glycolysis stimulation). Under conditions of pulmonary artery stenosis, histoenzymological alterations in vascular smooth muscle of both ventricles and ventricular septum were similar, which attested to acceleration of tricarboxylic acid cycle, stimulation of oxidation of the free fatty acids with their metabolites, acceleration of glycolysis, and activation of the shuttle systems and biosynthetic processes. Comparative analysis of histoenzymological alterations revealed substantial differences in the character of metabolic changes under conditions of increased left and right ventricular afterload, which can be caused by peculiarities in myocardial blood flow, severity of circulatory disorders, severity of hypoxia, and intensity of processes maintaining ionic homeostasis in vascular smooth muscles and transport across the histohematic barriers. The data attest to important metabolic role of glycolysis in vascular smooth muscles of the myocardium, especially under conditions of enhanced afterload of the right ventricle.


Human cold agglutinins against "cryptic" erythrocyte antigens.
Two examples of human IgM cold agglutinins agglutinated human RBC only after enzyme treatment in vitro. Proteases were optimally effective, neuraminidase was also effective. The cold agglutinins did not coat native RBC but were directed against "cryptic" RBC determinants. The cold agglutinins belonged to the anti -I/-i complex indicating a "new" type of I/i determinants. They were strongly accessible to cold agglutinin interaction on native RBC of a patient with congenital dyserythropoietic anaemia. Enzyme treatment of RBC was shown to be not only suited for defining cold agglutinin specificities but also essential for detecting the "new" type of cold agglutinins, obviously causing autoimmune haemolytic anaemia in vivo.


Poisoning due to pyrethrins.
The pyrethrins have a long and fascinating history. They were derived from dried chrysanthemum flower heads that were found to have pesticidal activity centuries ago. They comprise a complex mixture of six main chemicals. Commercial formulations usually contain piperonyl butoxide, which inhibits metabolic degradation of the active ingredients. Pyrethrins are readily absorbed from the gut and respiratory tract but poorly absorbed through skin. The active components are rapidly and extensively metabolised in the liver. Pyrethrins probably act on sodium channels resulting in nervous system overactivity. The possibility that they also induce hypersensitivity, which may be fatal when the respiratory tract is involved, has been debated for many years. A few clinical reports support this suggestion but the limited epidemiological evidence available is against it. The number of reports of toxicity caused by pyrethrins has greatly decreased over recent years. The pyrethrins are generally of low acute toxicity but convulsions may occur if substantial amounts are ingested. Two deaths from acute asthma have been attributed to pyrethrins and clinical reports suggest that they may also cause a variety of forms of dermatitis. Ocular exposure has resulted in corneal erosions. Management of pyrethrin toxicity is supportive and symptomatic.


Operational strategy of high rate anaerobic digester with mixed organic wastes: effect of co-digestion on biogas yield at full scale.
The present research work is aimed at providing an economically feasible solution for the farmers to exploit the mixed organic wastes (MOW) as resources for the generation of biogas based electrical power and utilize the same for irrigation purpose to reduce the dependence on electricity board. A full scale biomethanation plant has been installed based on anaerobic gas lift reactor (AGR) technology to analyse, understand the operational parameters of anaerobic digestion and assess the performance of a high rate biomethanation plant by co-digesting the MOW such as poultry litter (PL), cattle manure (CM) and napier grass (NG) at ambient temperature. The biomethanation plant was incorporated with inline pre and post-processing unit assembly. The plant was fed with 1000 kg of MOW per day having 250 kg of total solids, about 178-200 kg of volatile solids and operated continuously for 52 weeks under ambient temperature. Electrical power generated (84.5-104 kWh/day) from biogas (65-80 m3/day) containing methane (40-48 m3/day) was used for operating the water pumps for agricultural purpose and the digestate (115-130 kg/day) was exploited as organic manure for growing crops in the same field. Napier grass was grown in the same land and other feedstocks were procured from the nearby area at the cost of $10-$15 per ton. Around 6 acres of land was being cultivated using the biogas based power generated from the MOW that was being used for growing vegetables and maize.


Bovine seminal ribonuclease precursor synthesized in vitro.
Native bovine seminal ribonuclease is a dimeric protein, whose identical subunits (Mr 14500), linked through two disulfide bridges, can be dissociated by a selective reduction procedure. Evidence is presented that the synthesis in vitro, under reducing conditions, of bovine seminal RNAase, directed by polyadenylated RNA isolated from bull seminal vesicles (where the enzyme is synthesized in vivo), occurs in the form of a precursor, 18000-Da polypeptide. The precursor nature of this translation product was deduced by two criteria: (1) its specific immunoprecipitation with anti-bovine seminal RNAase antibodies; (2) its processing by dog pancreas microsomal membranes to produce a protein with a molecular weight similar to that of the subunit(s) of bovine seminal RNAase. Moreover, evidence is offered that the precursor polypeptide is able to form in vitro a dimeric molecule under conditions where no exogenous reducing agents were added.


Challenges to superfund community nutrition programs in kentucky.
Since 2000, the University of Kentucky's (UK's) Superfund Basic Research Program (SBRP) Community Outreach Core has provided support and guidance through Superfund Community Action through Nutrition (SCAN) programs, which meet the needs of individuals and communities affected by environmental contaminants. It has been shown that nutrition may modulate the toxicity of Superfund chemicals. SCAN programs integrate nutrition education, nutrition science research, and health communication to increase understanding of health risks associated with residing near Superfund sites. Two critical tasks must be accomplished. SCAN personnel must identify and recruit affected community members, and then, offer meaningful programs. Certain quantitative outcome measures and legal issues presented both challenges and opportunities. Community members preferred qualitative evaluation discussions, which showed increased knowledge and improved attitudes following SCAN programs. SCAN, in full partnership with affected communities, translates safe, effective nutrition information to reduce health risks associated with exposure to Superfund pollutants.


Cognitive, social, and other correlates of specific reading retardation.
Children with specific reading retardation were matched with controls on the basis of age, sex, intelligence, and (less successfully) parental education. All subjects were tested on a variety of automated performance tests including the Matching Familiar Figures (MFF) Task, Auditory-Visual Integration, Short-Term Memory, the Continuous Performance Task (CPT), and Motor Performance. All children were assessed socially using the Conners Teacher Questionnaire, and reading-retarded children were rated on the Behavior Problem Checklist. Finally, all children were screened with the Finger Twitch Test and were assessed for left-right awareness. Statistical analysis suggested that the following performance tests discriminated between the groups in this respective order of importance: MFF (Accuracy), Auditory-Visual Integration, and the CPT. The Short-Term Memory Task, MFF Decision Time, and Motor Performance did not distinguish between the groups. Multiple regression equations suggested that scores on the performance tests could account for about 40% of the variance in reading attainment. Several factors from the rating scales (notably those pertaining to attention and anxiety) and left-right awareness also discriminated between the groups.


New approach to the treatment of adolescent hip dysplasia.
Hip dysplasia refers to the acetabular or femoral head shape and size and the relationships among their unusual growth; the most common types are acetabular hypogenesis and head mortar containing extraordinarily. The cause of disease is still not clear. There is a lack of unified classification standards and clinical diagnosis criteria. The main pathological change is the performance of the above of acetabular and the frontal defects. The acetabular bone is transferred to the hip center, which reduces femoral head acetabular tolerance and causes insufficient coverage. DDH (Developmental Dysplasia of Hip) may be associated with different degrees of hip subluxation, the acetabular bone becomes lighter and the hip joint capsule around the relaxation is the main cause of dislocation [1]. The patients with DDH and relationship have an involuted femoral articular surface, with abnormal relations. This can lead to articular cartilage degeneration, and cause osteoarthritis, which has a serious influence on patients' mental health and quality of life [2]. Therefore, the acetabular malformation must be corrected. This is performed by renewing the stability of articulation and decreasing the abnormal joint stress by the research and application. Nowadays, there is a simple operation based on the acetabular technique, the description of the three places: steel ilium osteotomies acetabular, joint capsule osteotomies around, Pemberton's description of the joint capsule around ilium osteotomies, etc. In particular, each has their respective advantages with regard to the operation method. However, complex, surgical trauma surgery methods also exist; nevertheless, pelvic change is heavy, the graft will not last as long, and may also be absorbed, among other shortcomings. In this report we use the lateral femoral screw with belt/vascular pedicle flap transfer of the ilium acetabular in the treatment of adolescent hip dysplasia, using a method that is different from other current operation methods. We use the false mortar joint capsule on the cut mortar in the upper part, which forms the false mortar bone cortex. The attachment connected the joint capsule together and turned down the mortar, forming concentric circles; arc grooves were cut high above the acetabular joint, which will turn down the vascular pedicle flap around the bone implant slots with screws, remove bone in the high bone disc and turn over the high board between the full bone. The mortar tolerates the increasing pressure and provides stability of the hip with a vascular pedicle flap and can provide good blood supply to the bone, avoiding the traditional acetabular osteotomy and the absorption of bone caused by a hip subluxation.


Resolution of aortic regurgitation due to Venturi effect after device closure of ruptured sinus of Valsalva aneurysm.
We describe a case of a ruptured sinus of Valsalva with severe aortic regurgitation treated by transcatheter device closure. The regurgitation was purely due to leaflet entrapment because of the hemodynamic Venturi effect which was effectively treated.


Laparoscopic liver resection: lessons learnt after 100 cases.
To share our institutional experience in laparoscopic liver resection and our learning curve after the first 100 cases of laparoscopic liver resection. Case series with internal comparison. A regional hospital in Hong Kong. Our institution started performing laparoscopic liver resection since 2006. All patients who underwent laparoscopic liver resections from March 2006 to October 2012 were identified in a prospectively collected database. The demographic data and operative outcomes of these patients were extracted, and results of the early (from March 2006 to May 2010) and late (from June 2010 to October 2012) study periods were compared. Between March 2006 and October 2012, 100 laparoscopic liver resections were performed for 98 patients in the Department of Surgery, Kwong Wah Hospital, Hong Kong. They were 69 (70%) males and 29 (30%) females, and the median age was 65 years. The final histological diagnoses were as follows: hepatocellular carcinoma (n=72), colorectal liver metastases (n=14), intrahepatic cholangiocarcinoma (n=4), and benign disease (n=10). There were more anatomical resections, major hepatectomies as well as resections of more anatomically challenging right-sided and posterosuperior lesions in the late versus the early period; however, operative outcomes remained comparable in both periods. Laparoscopic hepatectomies are feasible with growing experience. Bearing in mind the diversity in the level of operative techniques with various types of laparoscopic liver resections, more experience is needed to overcome the learning curve.


Forensic medicine: a forgotten world of opportunities and challenges for research.
Forensic medicine deals with a wide variety of cases. To accomplish the main objectives, this professional field needs to adopt and apply findings from other sciences, namely, different medical specialties and other forensic sciences. The opposite is not yet entirely true due to the fact that forensic medicine deals with cases that are very far away from other medical and scientific interests. It is obvious that this forgotten world of forensic medicine … is also a new world of opportunities and challenges to research in all scientific areas.


Efficacy of inferior vena cava filters in anticoagulated patients.
The benefit of an inferior vena cava (IVC) filter in addition to standard anticoagulation regimens is unknown. We examined data for patients who received IVC filters with anticoagulation (AC-Filter) after an episode of venous thromboembolism (VTE) and compared them with data for those who received anticoagulation only (AC-Only). Outcome measures were new pulmonary embolism (PE), recurrent deep vein thrombosis (DVT), and mortality at 90 days and at 5 years. Demographic data included age, gender, and ethnicity/race, prior thromboembolic history, cancer, serum albumin, and time in therapeutic range. In addition, subsets matched for age, gender and race/ethnicity were examined in detail. AC-Filter patients (n = 251), when compared to AC-Only patients (n = 1377), did not differ significantly with regard to gender or cancer status, but white males in general had better outcomes. AC-Filter patients were more likely to have had a previous history of PE or VTE (P < 0.001). In comparison to AC-Only patients, AC-Filter patients had lower mean serum albumin levels (3.1 +/- 0.8 vs. 3.6 +/-0.8 mg dL(-1), P < 0.001) and were older (65 +/- 16.1 years vs. 60 +/- 17.5 years, P < 0.001). After stratification according to previous history of PE or VTE prior to the index VTE event, no differences in the outcome measures of new PE, recurrent DVT or mortality were identified between groups, but patients with a prior history of PE from either group were more likely to have a new PE (hazard ratio 1.9, P < 0.001). These data suggest that IVC filters may not provide any substantial additional benefit for patients who can tolerate anticoagulant therapy.


The African-387 C>T TGFB1 variant is functional and associates with the ophthalmoplegic complication in juvenile myasthenia gravis.
Although extraocular muscles are commonly affected by myasthenia gravis (MG) at presentation, a treatment-resistant ophthalmoplegic complication of MG (OP-MG) occurs in younger patients with African-genetic ancestry. In MG, pathogenic antibodies activate complement-mediated muscle damage and this may be potentiated in some OP-MG cases because of relative deficiency of decay-accelerating factor/CD55. Extending this argument, we hypothesized that OP-MG individuals may harbor African-specific polymorphisms in key genes influencing extraocular muscle remodeling. We screened the regulatory region of the transforming growth factor beta-1 (TGFB1) gene encoding the cytokine pivotal in muscle healing responses. We show the frequency of an African-specific polymorphism TGFB1 c.-387 T (rs11466316) among South Africans with African-genetic ancestry is higher than 1000 Genomes African controls (17.2% vs 4.8%; P<1 × 10(-7)), and associates with juvenile OP-MG (28%; P=0.043). Further, TGFB1 -387 C>T is functional because it represses the TGFB1 promoter construct basal activity by fivefold, and OP-MG fibroblasts (-387 C/T or T/T) have lower basal TGFB1 mRNA transcripts compared with controls (-387 C/C)(P=0.001). Co-transfections with Sp1 show less responsiveness of the -387 T promoter compared with wild-type -387 C (P=0.015). Our findings suggest that population-specific alleles may lower TGFB1 expression, thereby influencing OP-MG susceptibility by inhibiting extraocular muscle CD55 upregulation and/or altered endplate remodeling.


Tunable Valley Polarization and Valley Orbital Magnetic Moment Hall Effect in Honeycomb Systems with Broken Inversion Symmetry.
In this Letter, a tunable valley polarization is investigated for honeycomb systems with broken inversion symmetry such as transition-metal dichalcogenide MX2 (M = Mo, W; X = S, Se) monolayers through elliptical pumping. Compared to circular pumping, elliptical pumping is a more universal and effective method to create coherent valley polarization. When two valleys of MX2 monolayers are doped or polarized, a novel anomalous Hall effect (called valley orbital magnetic moment Hall effect) is predicted. Valley orbital magnetic moment Hall effect can generate an orbital magnetic moment current without the accompaniment of a charge current, which opens a new avenue for exploration of valleytronics and orbitronics. Valley orbital magnetic moment Hall effect is expected to overshadow spin Hall effect and is tunable under elliptical pumping.


Early aspirin initiation following heart transplantation is associated with reduced risk of allograft vasculopathy during long-term follow-up.
Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality after heart transplantation (HT). Enhanced platelet reactivity is a contributing factor. We aimed to investigate the association between early initiation of aspirin therapy post-HT and the 15-year risk of the development of CAV. We studied 206 patients who underwent HT between 1991 and 2016. Multivariate Cox proportional hazards regression modeling was employed to evaluate the association between early aspirin initiation and the long-term risk of CAV. Ninety-seven patients (47%) received aspirin therapy. At 15 years of follow-up, the rate of CAV was lowered by sixfold in patients treated with aspirin compared with the non-treated patients: 7% vs 37% (log-rank P-value<.001). The corresponding rates of the combined end-point of CAV or death were also lower in patients treated with aspirin, compared with the non-treated patients: 42% vs 78% (log-rank P < .001). Consistently, multivariate analysis showed that early aspirin therapy was associated with a significant 84% (P < .001) reduction in CAV risk, and with a corresponding 68% (P < .0001) reduction in the risk of the combined end-point of CAV or death. We further validated these results using a propensity score-adjusted Cox model. Early aspirin initiation is independently associated with a significant reduction in the risk of CAV.


Risk factors for postcesarean endomyometritis.
Postcesarean endomyometritis is the most common nosocomial infection treated by obstetrician-gynecologists. One important prevention strategy is the use of perioperative antibiotic prophylaxis initiated after occlusion of the umbilical cord for parturient patients with a high risk of this infection. However, the identification of these high risk patients remains problematic. Numerous clinical risk factors have been identified in the literature. Important intrinsic risk factors include indigent socioeconomic status, anemia, and preterm gestational age at the time of cesarean section. The three most consistently identified extrinsic risk factors include labor prior to cesarean section, the duration of ruptured chorioamniotic membranes, and the number of preoperative vaginal examinations. Alternatively, many investigators have attempted to define high-risk patients utilizing various laboratory tests, such as Gram staining or bacterial culture of amniotic fluid, chorioamniotic membranes, or endometrial biopsy specimens; although specific, these tests have not been sufficiently sensitive predictors of infection. Currently, assessment of the duration of ruptured membranes and length of labor remain the most sensitive, readily available, and therefore clinically useful predictors of postcesarean endomyometritis.


[Transient hyperphosphatasemia in childhood].
During hospitalisation four infants were found to have a marked increase in serum alkaline phosphatase, which could be attributed neither to clinical nor paraclinical diseases and is considered transitory hyperphosphatasaemia. This phenomenon is briefly discussed on the basis of the literature. The children should be protected from extensive diagnostical measures.


Detection of Low-Abundance DNA Modifications Using Signal Amplification-Based Immunocytochemistry.
Immunocytochemistry can be instrumental in assessing the spatial distribution and relative levels of epigenetic modifications. Although conventional immunostaining has been utilized for the detection of 5-methylcytosine (5mC) in animal cells and tissues for several decades, the sensitivity of techniques based on the use of fluorophore-conjugated secondary antibodies is not always sufficient for studying DNA modifications that are less abundant in DNA compared with 5mC. Here we describe a protocol for sensitive immunocytochemistry that utilizes peroxidase-conjugated secondary antibodies coupled with catalyzed reporter deposition and allows for detection of low-abundance noncanonical bases (e.g., 5-carboxylcytosine, 5caC, 5-formylcytosine, 5fC, 5-hydroxymethyluracil, 5hmU) in mammalian DNA. This method can be employed for evaluation of the levels and nuclear distribution of DNA modifications and permits their colocalization with protein markers in animal cells.


Heterophile antibody positive infectious mononucleosis.
The present study has been carried out to analyse the trend of heterophile antibody positive infectious mononucleosis cases. A total of 1741 cases of clinically suspected infectious mononucleosis from various age groups were investigated during the period January, 1986 to December, 2000 and were analysed for infectious mononucleosis (IM) specific heterophile antibody by Paul-Bunnel-Davidsohn (PBD) test. Forty seven heterophile antibody negative samples were also tested simultaneously for the presence of the IgG antibody to viral capsid antigen (VCA) and Epstein Barr nuclear antigen (EBNA) to detect the exposure to Epstein Barr Virus (EBV) infection. The overall percentage of EBV specific heterophile (Paul-Bunnel) antibody positivity was found to be 11.1% (194/1741). The average Paul-Bunnel antibody positivity between 1986 to 1990 was 20.5% which declined drastically to 5.7% during 1991-2000. Males comprised of 55.2% of the serologically proven IM cases. Of the 47 heterophile antibody negative cases, 38 (80.9%) and 33 (70.2%) were found to be positive for anti-VCA IgG and anti-EBNA IgG antibodies respectively. Paul Bunnel antibody positivity was found to be higher in >14 year age group patients than those below 14 years. These findings suggest that the EBV infection still continues to be endemic in this part of the country, however, a declining trend in IM cases was observed during the last decade.


A simple, rapid assay for plasma oxalate in uraemic patients using oxalate oxidase, which is free from vitamin C interference.
An enzymatic assay for the determination of oxalate in plasma was developed which is specific, simple, rapid and requires no specialised equipment; interference from vitamin C was removed by incubation of acidified plasma ultrafiltrate with ascorbate oxidase prior to oxalate estimation. Recoveries were 93 +/- 11% and the inter-batch coefficient of variation for 31 determinations at an oxalate level of 24 mumol/l was 10%. The assay is linear up to 300 mumol/l with a detection limit of 2 mumol/l. The reference range, based on results from 25 healthy volunteers, was defined as less than 2-5 mumol/l which is similar to levels established for the in vivo isotope dilution technique. The assay has an added advantage over the latter method, which requires a urine collection, in that it can be applied to plasma from anuric patients. A linear correlation (r = 0.68, p less than 0.001) was found between plasma oxalate and serum creatinine in individuals with varying degrees of renal failure.


"I don't want to die like that ...": the impact of significant others' death quality on advance care planning.
I examine whether 5 aspects of a significant other's death quality (pain, decision-making capacity, location, problems with end-of life care, and preparation) affect whether one does advance care planning (ACP). I also identify specific aspects of others' deaths that respondents say triggered their own planning. Data are from the New Jersey End of Life study, a survey of 305 adults age 55+ seeking care at 2 major New Jersey medical centers. I estimate multivariate logistic regression models for a subsample of 253 participants who recently lost a loved one and provide descriptive findings from an open-ended question regarding the motivation for one's ACP. Multivariate analyses revealed "positive" role model effects; persons who witnessed significant others' deaths that occurred at home, were free of problems associated with end-of-life care, and where advance directives were used are more likely to make end-of-life preparations. Open-ended data showed that 19% cited others' deaths as the main trigger for their own planning, with most citing negative factors (pain, connection to machines, coma) that they hoped to avoid. Practitioners should encourage patients to use conversations about others' deaths as springboards for discussions about one's own end-of-life care, and to engage in ACP together with family. Implications for health care reform are highlighted.


Occurrence of epidermal growth factor receptors in benign and malignant ovarian tumors and normal ovarian tissues: an immunohistochemical study.
Epidermal growth factor receptor (EGF-R) was studied with monoclonal antibody 2E9 on 50 ovarian tumors of various histological types and 10 non-tumorous ovarian tissues by immunohistochemistry. Enhanced expression was observed in 26/50 (52%) of the tumors. Only 25 out of 46 epithelial tumors (54%) showed positivity in epithelial tumor cells. Staining was cytoplasmic in all cases. No correlation was established between EGF-R expression and the histological type of the epithelial tumor. Apart from EGF-R expression in tumor cells, low immunoreactivity was also observed in stromal and endothelial cells in both normal and tumorous ovarian tissues. Furthermore in 8/9 specimens containing necrotic areas, EGF-R was noticed in these areas as well. Both of the latter observations may have impact on the evaluation of the prognostic value of EGF-R activity in tumors, when based on EGF-R measurements using biochemical binding studies. We therefore recommend that EGF-R is measured with both methods in studies regarding its clinical value.


Novel 1,4-dihydropyridine induces apoptosis in human cancer cells through overexpression of Sirtuin1.
1,4-Dihydropyridines (1,4-DHPs) are important as a class of heterocyclic compounds that exhibit wide range of biological actions. Many of its derivatives are already characterized as medicinally important drugs and used worldwide. In this study, we have screened some novel Hantzsch 1,4-DHP compounds using both in silico (QSAR and Pharmacophore) and in vitro (cytotoxic screening). 1,4-DHP showed selective cytotoxicity against five human cancerous cell lines; A375, A549, HeLa, HepG2 and SH-SY5Y but limited effect towards normal skin keratinocyte (HaCaT), lung fibroblast (WL-38) and healthy peripheral blood mononuclear cells. In A375 and HepG2 cells, one of the 1,4-DHP derivative (DHP-8) was found to inhibit cell proliferation, and simultaneously increased the apoptotic population as well as mitochondrial membrane depolarization. Furthermore, the mitochondrial signal was triggered with the activation of cleaved Caspase9, Caspase3 and PARP. The treatment with DHP-8 also increased the expression level of SIRT1, subsequently decreasing the level of pAKTser473 and survivin. Reduced pAKTser473 expression led to decrease the phosphorylated inactive form of GSK3βser9 and as a result, proteasomal degradation of Mcl-1 occurred in both the cell lines. Here, we suggest that the apoptotic effect of DHP-8 in A375 and HepG2 cells was mediated by AKT and survivin pathways through SIRT1 activation. The involvement of DHP-8 in SIRT1 activation was further verified by co-treatment of nicotinamide with DHP-8 in both A375 and HepG2 cells. Overall, this study emphasizes the possible potential and therapeutic role of DHP-8 in skin and liver cancer.


Social and psycho-intellectual outcome following radical removal of craniopharyngiomas in childhood. A prospective series.
A prospective study on childhood craniopharyngiomas (CPs) was conducted from 1994 to 1998 to appreciate the pre- and postoperative clinical, endocrine, mental, and intellectual status of the patients and to determine the incidence and severity of the postoperative hypothalamic syndrome. The series included 14 consecutive CPs. Twelve were retrochiasmatic and intraventricular, and two were partly prechiasmatic and extraventricular. All were treated with the aim of "total" removal. The removal was "total" in nine cases but incomplete in the other five. Immediate postoperative follow-up was uncomplicated in all cases. At 2-year follow-up, the two children with an extraventricular CP and a "total" tumor removal were intellectually normal, had no hypothalamic syndrome, and attended normal school with good results. The 12 others, although still intellectually normal, were more or less severely affected by a hypothalamic syndrome which altered their social insertion and caused academic failure. The authors conclude from this study that radical surgery should be reserved to extraventricular CPs only.


Pinworm diversity in free-ranging howler monkeys (Alouatta spp.) in Mexico: Morphological and molecular evidence for two new Trypanoxyuris species (Nematoda: Oxyuridae).
Two new species of Trypanoxyuris are described from the intestine of free-ranging howler monkeys in Mexico, Trypanoxyuris multilabiatus n. sp. from the mantled howler Alouatta palliata, and Trypanoxyuris pigrae n. sp. from the black howler Alouatta pigra. An integrative taxonomic approach is followed, where conspicuous morphological traits and phylogenetic trees based on DNA sequences are used to test the validity of the two new species. The mitochondrial cytochrome oxidase subunit 1 gene, and the nuclear ribosomal 18S and 28S rRNA genes were used for evolutionary analyses, with the concatenated dataset of all three genes used for maximum likelihood and Bayesian phylogenetic analyses. The two new species of pinworms from howler monkeys were morphologically distinct and formed reciprocally monophyletic lineages in molecular phylogenetic trees. The three species from howler monkeys, T. multilabiatus n. sp., T. pigrae n. sp., and Trypanoxyuris minutus, formed a monophyletic group with high bootstrap and posterior probability support values. Phylogenetic patterns inferred from sequence data support the hypothesis of a close evolutionary association between these primate hosts and their pinworm parasites. The results suggest that the diversity of pinworm parasites from Neotropical primates might be underestimated.


Lipopolysaccharide down-regulates inducible nitric oxide synthase expression in swine heart in vivo.
Studies of the regulation of iNOS expression have provided many contradictory results. Comparing iNOS expression profile between cell types or organs of the same animal under the same experimental conditions may provide an explanation for these conflicting results. We have examined iNOS mRNA and protein expression in heart and liver of the same group of pigs. We found that there is a sharp difference in iNOS expression between heart and liver. The iNOS mRNA and protein was constitutively expressed in the heart at high level, but was not detectable in the liver of the same control animal. Lipopolysaccharide (LPS, 100 microg/kg, i.v.) caused a marked iNOS induction in the liver, but significantly down-regulated iNOS expression in the heart. This differential iNOS expression appears to be physiologically relevant, since LPS and the iNOS inhibitor, S-methylisothiourea, exerted different effects on hepatic and myocardial blood flow. Our data demonstrate a fundamental difference in iNOS regulation in the heart and liver of swine, and may explain the contradictory data on the regulation of iNOS expression.


LOB Domain Proteins: Beyond Lateral Organ Boundaries.
LATERAL ORGAN BOUNDARIES DOMAIN (LBD) proteins defined by a conserved LATERAL ORGAN BOUNDARIES (LOB) domain are key regulators of plant organ development. Recent studies have expanded their functional diversity beyond the definition of lateral organ boundaries to pollen development, plant regeneration, photomorphogenesis, pathogen response, and specific developmental functions in non-model plants, such as poplar and legumes. The identification of a range of upstream regulators, protein partners, and downstream targets of LBD family members has unraveled the molecular networks of LBD-dependent processes. Moreover, it has been demonstrated that LBD proteins have essential roles in integrating developmental changes in response to phytohormone signaling or environmental cues. As we discuss here, these novel discoveries of LBD functions and their molecular contexts promote a better understanding of this plant-specific transcription factor family.


Predicting difficult intubation: the hyomental distance ultrasound evaluation is superior to the thyromental distance.
Hyomental distance (HMD), an anatomical feature of the upper airway, can be measured precisely by ultrasonography. But the sensitivity and specificity of HMD compared to thyromental distance (TMD) to predict difficult airways is still unknown. A case-cohort study was conducted. The written informed consent was obtained. Elective surgery adult patients undergoing general anaesthesia and tracheal intubation were recruited. The other inclusion criteria were: no maxillofacial deformity, trauma, airway stenosis, known difficult airway. The exclusion criteria were: tracheal intubations or operations were canceled, or patients' data were missing. HMD ultrasound measurements of patients in a sniffing position and other usual airway evaluations were performed before general anaesthesia induction. The primary outcome was the intubation difficulty level. Predictive values were calculated. We successfully enrolled 2357 patients (62 difficult intubation patients) in the cohort study for analysis. The area under the receiver operating characteristic curve (AUC) of the HMD and TMD for predicting difficult intubation was 0.86 (95% CI, 0.84-0.87) and 0.77 (95% CI, 0.75-0.78) respectively (comparison: P < 0.001). With an optimal cut-off value of HMD ≤ 4.9 cm, we observed a sensitivity and specificity of 0.90 (95% CI, 0.80-0.96) and 0.73 (95% CI, 0.71-0.75). Meanwhile, with TMD ≤ 7.0 cm, the sensitivity and specificity were 0.77 (95% CI, 0.65-0.87) and 0.65 (95% CI, 0.63-0.67) respectively. In comparison to TMD, HMD measured by ultrasound was more sensitive in predicting difficult intubation.


Carbohydrate-binding protein 35: molecular cloning and expression of a recombinant polypeptide with lectin activity in Escherichia coli.
Affinity-purified antibodies directed against carbohydrate-binding protein 35 (CBP35), a galactose-specific lectin, were used to screen a lambda gt 11 expression library derived from mRNA of 3T3 fibroblasts. This screening yielded several putative clones containing cDNA for CBP35, one of which was characterized in terms of its expression of a fusion protein containing beta-galactosidase and CBP35 sequences. Limited proteolysis of lysates containing the fusion protein, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting with anti-CBP35, yielded a peptide mapping pattern comparable to that obtained from parallel treatment of authentic CBP35. Such a limited proteolysis followed by affinity chromatography on a Sepharose column coupled with galactose also yielded a 30-kDa polypeptide that exhibited carbohydrate-binding activity. This polypeptide can be immunoblotted with anti-CBP35, but not with antibodies directed against beta-galactosidase. These results indicate that we have identified a cDNA clone for CBP35 that yields a recombinant polypeptide with lectin activity produced in Escherichia coli. Using this cDNA clone as a probe, Northern-blot analysis showed an increased expression of the CBP35 gene when quiescent 3T3 cells were activated by the addition of serum growth factors.


In silico analysis of koranimine, a cyclic imine compound from Peribacillus frigoritolerans reveals potential nematicidal activity.
Pine wilt disease (PWD) is a destructive vector-borne forest disease caused by the nematode Bursaphelenchus xylophilus. To date, several options are available for the management of pine wilt disease; however constant development and search for natural products with potential nematicidal activity are imperative to diversify management options and to cope with the possible future emergence of resistance in parasitic nematodes. Here, a combined metabolomics and genomics approach was employed to investigate the chemical repertoire and biosynthetic potential of the bacterial endophyte Peribacillus frigoritolerans BE93, previously characterized to exhibit nematicidal activity against B. xylophilus. Feature-based molecular networking revealed the presence of diverse secondary metabolites. A cyclic imine heptapeptide, koranimine, was found to be among the most abundant secondary metabolites produced. Genome mining displayed the presence of several putative biosynthetic gene clusters (BGCs), including a dedicated non-ribosomal peptide synthase (NRPS) BGC for koranimine. Given the non-ribosomal peptide nature of koranimine, in silico molecular docking analysis was conducted to investigate its potential nematicidal activity against the target receptor ivermectin-sensitive invertebrate α glutamate-gated chloride channel (GluCl). Results revealed the binding of koranimine at the allosteric site of the channel-the ivermectin binding site. Moreover, the ligand-receptor interactions observed were mostly shared between koranimine and ivermectin when bound to the α GluCl receptor thus, suggesting a possibly shared mechanism of potential nematicidal activity. This study highlights the efficiency of combined metabolomics and genomics approach in the identification of candidate compounds.


The detection and antimicrobial susceptibility profile of Shigella isolates from meat and swab samples at butchers' shops in Gondar town, Northwest Ethiopia.
Food borne pathogens are major causes of deaths, illnesses and billions of dollars of expenses. The burden of food borne illness is worsened by the ever increasing rate of antimicrobial resistance microbes. Shigella, a bacterial pathogen associated with food, is reported to account for higher prevalence rates of food borne illness in different settings. A cross-sectional study was conducted from February 10 to June 30, 2013, at the butcher houses of Gondar town in the Northwest of Ethiopia to assess the prevalence and antimicrobial susceptibility pattern of Shigella. Cattle raw meat and swab samples from selected critical control points, including knives, chopping boards, and the hands and noses of butchers, were collected and analyzed. The identification of Shigella was carried out using colony characteristics, the Gram reaction, and biochemical tests. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disc diffusion method. The overall hygienic status of the butcher shops was also assessed using a checklist. An observational analysis revealed that the sanitary condition of the butcher shops and their premises was poor. Of 306 samples screened, 10.5% were positive for Shigella. Approximately 7.4% of meat samples and 10.2% of swab samples were contaminated with Shigella. Out of the total Shigella isolates, 90.6%, 46.9%, 18.8% and 9.4% were resistant to ampicillin, amoxicillin, ceftriaxone and tetracycline, respectively. A multidrug resistance pattern was recorded in 27.8% of the isolates. In conclusion, the safety of meat sold at Gondar butchers houses was poor. The identified Shigella isolates showed high levels of drug resistance and multidrug resistance patterns for commonly used antimicrobials in veterinary and human medicine. Practicing wise use of antimicrobials and strict sanitary interventions at different critical control points is strongly recommended, in addition to further in-depth studies to prevent unprecedented consequences from shigellosis.


Electroacupuncture at PC6 (Neiguan) Attenuates Angina Pectoris in Rats with Myocardial Ischemia-Reperfusion Injury Through Regulating the Alternative Splicing of the Major Inhibitory Neurotransmitter Receptor GABRG2.
Angina pectoris is the most common manifestation of coronary heart disease, causing suffering in patients. Electroacupuncture at PC6 can effectively alleviate angina by regulating the expression of genes, whether the alternative splicing (AS) of genes is affected by acupuncture is still unknown. We established a rat model of myocardial ischemia-reperfusion by coronary artery ligation and confirmed electroacupuncture alleviated the abnormal discharge caused by angina pectoris measured in EMG electromyograms. Analysis of the GSE61840 dataset established that AS events were altered after I/R and regulated by electroacupuncture. I/R decreased the expression of splicing factor Nova1 while electroacupuncture rescued it. Further experiments in dorsal root ganglion cells showed Nova1 regulated the AS of the GABRG2, specifically on its exon 9 where an important phosphorylation site is present. In vivo, results also showed that electroacupuncture can restore AS of GABRG2. Our results proved that electroacupuncture alleviates angina results by regulating alternative splicing.


NFAT inhibitor tributylhexadecylphosphoniumbromide, ameliorates high fructose induced insulin resistance and nephropathy.
High fructose diet (HFrD)-induced insulin resistance (IR) has been reported to be associated with an increase in albuminuria, glomerular hypertrophy and inflammation in kidney. However, the molecular mechanisms associated with high fructose-induced IR and renal dysfunction are still unclear. In the present study, we have investigated the role of nuclear factor of activated T-cell (NFAT) and its inhibitor, Tributylhexadecylphosphoniumbromide (THPB) in high fructose-induced IR and renal injury. NFAT inhibition by THPB treatment significantly improved HFrD-induced insulin resistance. Treatment with THPB markedly reduced high fructose diet-induced protein expression of NFATc4, PTEN and also alleviated expression of inflammatory markers in kidneys of HFrD rats. Further, THPB treatment not only improved acute ANG II responses but also repressed the processes of renal fibrosis, ECM accumulation, foot process effacement and renal apoptosis in HFrD rats. Taken together, we for the first time provide evidence that HFrD -induced insulin resistance and renal injury is associated with dysregulated NFATc4/PTEN signalling and THPB prevents this dysregulation through inhibition of NFATc4. Thus, targeting NFATc4 can be a novel therapeutic approach for preventing HFrD induced- IR and renal injury.


Pseudocarcinomatous Squamous Hyperplasia Involving Bone: A Diagnostic Pitfall Mimicking Squamous Cell Carcinoma.
Pseudocarcinomatous squamous hyperplasia (PSH) within the bone is uncommon and closely mimics well-differentiated squamous cell carcinoma (SCC). It arises from cutaneous or mucosal surfaces and grows directly into the bone. This study analyzes a large series of PSH and discusses the clinicopathologic features that facilitate its distinction from SCC. Cases were identified from the surgical pathology files between 1985 and 2020. The 31 cases included 21 males, 9 females, 1 unknown sex; who were 20 to 87 years old (average: 59 y). Sites included mandible-17, maxilla-5, toes-4, and 1 case from finger, femur, tibia, ischium, and unknown. Fourteen patients had a history of SCC, 13 treated with resection and chemoradiation and developed infected osteoradionecrosis, 4-medication-related osteonecrosis, 3-peripheral vascular disease, and diabetes mellitus, 3-trauma, 3-osteomyelitis, 3-unknown, and 1-hematologic malignancy. All cases exhibited severe osteomyelitis and nests of reactive keratinizing squamous epithelium that matured towards the bone surface, lacked significant atypia, or mitotic activity but permeated the medullary cavity. Patients with previous SCC developed PSH after 2 months to 8 years (average: 4 y). Nineteen of 30 patients had follow-up (2 to 48 mo, average: 17 mo); 6 patients experienced repeated debridements over 2 months to 1 year; no patient developed SCC. PSH involving bone is infrequent, complicates severe osteomyelitis, and is often therapy related. The clinical findings are usually not concerning for malignancy, however, the histologic findings are an important diagnostic pitfall because they mimic SCC.


Oral and systemic effects of prolonged minocycline therapy.
The following case report shows the unfortunate side effects of minocycline therapy used in the management of facial acne. All three features of discoloration affecting the skin, bone and dentition were found. A 46-year-old patient presented with adult onset discoloration of the dentition following prolonged minocycline therapy. In addition, oral and cutaneous pigmentation were noted. Unfortunately, the undesirable cosmetic appearance of facial acne was exchanged for permanent discoloration of the dentition. When considering prolonged minocycline therapy, patients would benefit from dialogue between the medical and dental practitioners, so that the risk of this potential side effect can be assessed in a more informed way.


Personalized estimates of morphometric similarity in multiple sclerosis and neuromyelitis optica spectrum disorders.
Brain morphometric alterations involve multiple brain regions on progression of the disease in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) and exhibit age-related degenerative changes during the pathological aging. Recent advance in brain morphometry as measured using MRI have leveraged Person-Based Similarity Index (PBSI) approach to assess the extent of within-diagnosis similarity or heterogeneity of brain neuroanatomical profiles between individuals of healthy populations and validate in neuropsychiatric disorders. Brain morphometric changes throughout the lifespan would be invaluable for understanding regional variability of age-related structural degeneration and the substrate of inflammatory demyelinating disease. Here, we aimed to quantify the neuroanatomical profiles with PBSI measures of cortical thickness (CT) and subcortical volumes (SV) in 263 MS, 207 NMOSD, and 338 healthy controls (HC) from six separate central datasets (aged 11-80). We explored the between-group comparisons of PBSI measures, as well as the advancing age and sex effects on PBSI measures. Compared to NMOSD, MS showed a lower extent of within-diagnosis similarity. Significant differences in regional contributions to PBSI score were observed in 29 brain regions between MS and NMOSD (P < 0.05/164, Bonferroni corrected), of which bilateral cerebellum in MS and bilateral parahippocampal gyrus in NMOSD represented the highest divergence between the two patient groups, with a high similarity effect within each group. The PBSI scores were generally lower with advancing age, but their associations showed different patterns depending on the age range. For MS, CT profiles were significantly negatively correlated with age until the early 30 s (ρ = -0.265, P = 0.030), while for NMOSD, SV profiles were significantly negatively correlated with age with 51 year-old and older (ρ = -0.365, P = 0.008). The current study suggests that PBSI approach could be used to quantify the variation in brain morphometric changes in CNS inflammatory demyelinating disease, and exhibited a greater neuroanatomical heterogeneity pattern in MS compared with NMOSD. Our results reveal that, as an MR marker, PBSI may be sensitive to distribute the disease-associated grey matter diversity and complexity. Disease-driven production of regionally selective and age stage-dependency changes in the neuroanatomical profile of MS and NMOSD should be considered to facilitate the prediction of clinical outcomes and assessment of treatment responses.


Update of national diagnostic reference levels for adult CT in Switzerland and assessment of radiation dose reduction since 2010.
To update the national diagnostic reference levels (DRLs) for adult CT in Switzerland using dose management software and to compare them to the previous Swiss DRLs from 2010. CT dose data from 14 radiological institutes with a total of 50 CT scanners were collected with locally installed dose management software between 2014 and 2017. Data were assigned to 15 defined master protocols. Data cleaning steps were developed and adjusted individually for each participating institute and protocol. The DRLs for each master protocol were calculated as the 75th percentile of the distribution of the median volume computed tomography dose index (CTDIvol) and dose-length product (DLP) values per CT scanner. In total, 220,269 CT exams were available after data cleaning. Updated DRLs showed a clear trend towards lower doses compared with previous DRLs. The average relative change in the DRLs for CTDIvol was - 30% (0 to - 47%) and - 22% for DLP (+ 20 to - 40%). The largest relative decrease in the DRL for DLP was observed for the cervical spine protocol (- 40%), the two chest protocols (chest, - 37%; and exclusion of pulmonary embolism, - 33%), and the two neck protocols (neck, - 32%; and carotid angiography, - 28%). The DRLs for other protocols, for example the head and the abdomen-pelvis protocol, showed smaller relative changes (- 11% and - 17%). The updated national DRLs are substantially lower than the previous values from 2010, demonstrating technological progress and the efforts of the radiological community to lower CT radiation exposure. • Dose management software allows the establishment of DRLs based on big data. • Updated Swiss DRLs for adult CT are substantially lower compared with those from 2010. • Swiss DRLs are low compared with other national DRLs.


TKIs combined with chemotherapy followed by allo-HSCT in Philadelphia chromosome-positive myelodysplastic syndrome: A case report and literature review.
Philadelphia chromosome (Ph) positive myelodysplastic syndrome (MDS) is a very rare disease. At present, the specific role of Ph in MDS is not clear, but such patients seem to have a poor prognosis, so the disease deserves attention. Here, we describe the history of a woman with Ph-positive MDS and perform a systematic review of related literature. We report a 38-year-old woman with Ph-positive MDS. She received chemotherapy with decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor (DCAG) combined with imatinib mesylate and achieved a bone marrow remission. She then underwent an allogeneic hematopoietic stem cell transplant. The condition is good and no recurrence of the disease has been observed. Ph-positive MDS is a very rare disease. Ph may aid in the malignant progression of MDS leaving such patients with a very poor prognosis. Tyrosine kinase inhibitors (TKIs) plus chemotherapy followed by allogeneic hematopoietic stem cell transplantation has provided these patients with satisfactory outcomes.


A 27-GAUGE TROCAR-ASSISTED INTRASCLERAL INTRAOCULAR LENS FIXATION TECHNIQUE USING A SILICONE MICROTUBE.
This study aimed to describe a novel technique to facilitate intrascleral fixation of the intraocular lens (IOL). Two 27-gauge trocars were placed at an angle of 180° and a distance of 2 mm from the corneal limbus. A silicone microtube with an external diameter of 0.2 mm was introduced through a sclerocorneal incision and withdrawn via a trocar using retinal forceps. The tips of the IOL haptics were connected to the microtube. After the implantation of the IOL into the chamber, the haptics were externalized through the scleral site by pulling the microtubes. Each tip of the haptics was flanged and buried into the scleral tunnel. The IOL was successfully placed with this method without any complications. This study presented a novel technique for intrascleral IOL fixation using a silicone microtube. We believe that our technique might increase surgical safety and help decrease the operative time for both anterior and posterior segment techniques.


Erratic electricity supply (Dumsor) and anxiety disorders among university students in Ghana: a cross sectional study.
Ghana is currently experiencing electricity supply crisis that is believed to have some impact on the mental wellbeing of the population, especially among university students that have become increasingly dependent on uninterrupted electricity supply to fully function academically. There is no known study that explores the link between infrequent electricity supply and generalized anxiety disorders in sub-Saharan Africa. This study aimed to explore that link and determine the proportion of university students whose anxiety levels may be influenced by the electricity supply crisis that the country is experiencing at the moment. This exploratory study used the Generalized Anxiety Disorder 7-item scale (GAD-7) to conduct the study on the University of Ghana campus. The likelihood ratio (LR) test and Fisher's Exact tests were used to determine any association between the electricity supply crisis and anxiety levels among students. Unadjusted odds ratio and corresponding confidence intervals were estimated and ordinal logistic regression technique was used for the effect of covariates on anxiety. Overall, nearly 26 % of students interviewed felt nervous, anxious or on edge almost every day due to the erratic power supply. The proportion of students determined to be classified having minimal, mild, moderate and severe anxiety due to the erratic power supply was 24.2, 30.7, 22.1 and 23.1 % respectively. Students were significantly more likely to be anxious if the frequency of power outage increased (OR 1.36; CI 1.23-1.49). Our finding in this study suggests that although the erratic power supply does not allude to any clinical confirmation of the students having anxiety disorders, it does point to a fact that even in a resource-poor country like Ghana, where constant supply of electricity is not always guaranteed, students may not be entirely immune to the health and well-being implications of failures in some sectors of the economy such as power supply.


Ocular manifestations and complications of acute methyl alcohol intoxication.
The ocular manifestations of acute methyl alcohol intoxication were studied in 24 men during an outbreak in Port Moresby, Papua New Guinea. The visual acuity, pupillary reactions to light, fundal appearances and visual fields were recorded in all patients within 72 hours of ingestion of methanol and again three months later. Three groups were identified. Nine patients had no ocular abnormality (Group 1). Seven patients had only transient ocular abnormalities (Group 2). Eight patients had permanent ocular abnormalities (Group 3). Transient abnormalities included peripapillary oedema, optic disc hyperaemia, diminished pupillary reactions to light, and central scotomata. Permanent ocular abnormalities included optic disc pallor, attenuation of arterioles, sheathing of arterioles, diminished pupillary reaction to light, diminished visual acuity, central scotomata, and other nerve fibre bundle defects. Complete blindness occurred in two patients, while severe visula deficit resulted in four others. The incidence of permanent ocular abnormalities was found to correlate with the incidence of metabolic acidosis (P less than 0.01), and with the stated volume of methanol consumed (P less than 0.05). An inverse correlation was found between stated volume of methanol consumed and onset of blurred vision. The difficulties in management and rehabilitation of these patients are discussed.


Progress in temporal bone histopathology. I. Semithin 3-5 micron sectioning of undecalcified human temporal bone after plastic embedding.
Prior to embedding a human temporal bone in methylmethacrylate the plane of sectioning is determined through CT-scanning. A new technique of micro-slicing, plastic embedding and semithin sectioning of undecalcified human temporal bone is described.


Proline and glycinebetaine accumulation by Spartina alterniflora Loisel. in response to NaCl and nitrogen in a controlled environment.
The interaction of salinity and nitrogen availability on the growth and accumulation of proline and glycinebetaine by Spartina alterniflora Loisel. grown in hydroponic solution in controlled environements was investigated. Growth of shoots was reduced by increasing salinity and enhanced at higher nitrogen levels. Proline was accumulated when a threshold salinity was reached. At higher nitrogen levels, the threshold salinity to induce proline accumulation was lowered and the amount of proline accumulated was enhanced. Glycinebetaine content was higher in plants grown at higher nitrogen levels, but was less affected by salinity and nitrogen levels than proline. Glycinebetaine contents were approximately 10 times higher than proline contents. When plants that were non-stressed for 1 month were exposed to salinity stress, proline and glycinebetaine increased immediately and reached a plateau in 1-2 days. After the removal of salinity stress, proline disappeared rapidly but glycinebetaine content remained unchanged. Unlike NaCl, neither proline nor glycinebetaine had a significant effect on the in vitro activity of malate dehydrogenase activity from leaves.


Panhypopituitarism and anemia secondary to traumatic fracture of the sella turcica.
A case of a 27 year old man who developed anemia after fracture of the sella turcica is reported. The diagnosis of anterior pituitary insufficiency was made by a combined provocative test with TRH, LHRH, and insulin. The anemia was characterized by a hypocellular bone marrow which appeared to be functioning only in the thoracic-lumbar vertebrae, an absence of measurable erythropoietic activity, and by the return to normal of the hematological findings after hormonal replacement therapy. This patient had the highly unusual combination of proven panhypopituitarism and significant anemia resulting from a distinct fracture of the sella turcica.


Retroportal hepaticojejunostomy for extended resection of hilar bile ducts.
High hepatic duct resection sometimes is unavoidable in achieving curative resection of hilar cholangiocarcinoma, as tumor cells can extend further than expected along the bile ducts from the macroscopically evident cancer. In patients undergoing left hemihepatectomy with caudate lobectomy whose bile duct must be severed at the subsegmental bile duct levels, the orifices of the posterior bile ducts would lie behind the right portal vein. Conventional hepaticojejunostomy would be risky in such cases because an anastomosis performed in the usual manner would be subjected to strain. Instead, between 2002 and 2004, three patients underwent retroportal hepaticojejunostomy using a jejunal limb mobilized and positioned behind the hepatoduodenal ligament. Primary tumors were classified as type IV in the Bismuth-Corlette classification. Tension-free hepaticojejunal anastomosis was performed successfully in all three patients; insufficiency of the hepaticojejunostomy did not develop. Neither early nor late complications directly related to this method occurred. Retroportal hepaticojejunostomy, thus, permits more peripheral resection of the hepatic duct while providing a sufficient operative field for safe, tension-free anastomosis. This technique is very useful for patients undergoing left hemihepatectomy requiring high hilar resection of the bile duct.


Ranitidine inhibits adrenergic transmission in the rat isolated anococcygeus muscle.
1. The effects of ranitidine on adrenergic transmission in the rat isolated anococcygeus muscle were investigated. 2. Cumulative doses (2-8 mmol/L) or ranitidine produced a concentration-dependent inhibition of motor responses of the rat isolated anococcygeus muscle evoked by field stimulation (20-25 V, 10 Hz for 10 s, 1 ms pulse width) every 2 min, but also potentiated the contractile response to exogenous noradrenaline (5 mumol/L). The inhibited motor responses recovered rapidly and completely after washing out ranitidine. 3. 4-Aminopyridine (100 mumol/L) effectively reversed the partially inhibited (55% or greater) motor responses. 4. The results strongly suggest that ranitidine can inhibit adrenergic transmission in the anococcygeus muscle by a prejunctional mechanism with, presumably, consequent development of supersensitivity of the effector cells to noradrenaline.


Spatial variation and associated factors of deworming among children aged 24 to 59 months in Ethiopia: spatial and multilevel logistic analysis.
Intestinal parasitic infection is one of the neglected tropical diseases (NTD) which is mainly concentrated in developing countries. Gastrointestinal parasitic infections are diseases of poverty, which mainly affects children living in tropical and subtropical regions like Ethiopia. Deworming to children aged 24-59 months of age is one of the strategic initiatives to halt the global burden of intestinal parasitosis among under-five children. The information generated at local levels like hotspot areas (clusters with a high proportion of poor deworming uptake) that were identified in this study could help decision-makers to develop location-based interventional strategies. This study was aimed to assess the spatial variation and factors associated with poor deworming uptake among children aged 24-59 months in Ethiopia using evidence from the 2016 Ethiopian Demographic Health Survey (EDHS). To explore, create, visualize and edit the spatial information of poor uptake of deworming medication, ArcGIS version 10.8 software was used. The spatial pattern of poor deworming uptake was determined using global spatial autocorrelation. Purely spatial scan statistic was used to identify statistically significant hotspot areas using SaTScan™ version 9.7 software. Multilevel logistic regression analysis was fitted to identify factors associated with poor deworming uptake in Ethiopia. Variables with a p-value< 0.2 in the bivariable regression were considered for multivariable regression analysis. Adjusted odds ratio with a 95% confidence interval (CI) and p-value < 0.05 were used to declare the statistical significance of each factor. The spatial pattern of poor deworming uptake in Ethiopia was non-random, i.e. clustered. The most likely cluster was found concentrated in most parts of Somali and East Oromia. Variables like being born from an uneducated mother ((Adjusted Odds Ratio (AOR) = 1.65; 95% CI: 1.16-2.36)), being born from an unemployed mother (AOR = 1. 1.43; 95% CI: 1.19-1.74), being delivered at home (AOR = 1.60 95% CI: 1.27, 2.02), diarrhea in the last 2 weeks (AOR = 0.68, 95%CI: 0.51, 0.90), and region of residency were the significant variables associated with poor deworming medication uptake among children aged to 24 to 59 months in Ethiopia. The spatial pattern of poor deworming uptake was non-random in Ethiopia. Variables like educational status, employment, distance, place of delivery, diarrhea and region of living were found associated with poor deworming uptake. Tailoring interventional programs based on identified clusters is recommended to minimize this unfavorable deworming uptake.


[Physician responsibility for patient education in relation to unconventional methods of treatment].
The fact is to go on record that, the greater the danger involved in the application of an unconventional method and the less familiar this method, the greater the physician's obligation to inform the patient of its nature and gravity. This obligation increases or decreases in indirect proportion to the amount of relevant information available in classical medicine on the method. It further increases with degree of certainty in current medical knowledge. It is however only possible for the patient to exercise his right of self-determination if he is also familiar with the physicians's obligation to inform.


Does left ventricular function predict cardiac outcome in Anderson-Fabry disease?
In Anderson-Fabry disease (AFD) the impact of left ventricular (LV) function on cardiac outcome is unknown. Noninvasive LV pressure-strain loop analysis is a new echocardiographic method to estimate myocardial work (MW). We aimed to evaluate whether LV function was associated with outcome and whether MW had a prognostic value in AFD. Ninety-six AFD patients (41.8 ± 14.7 years, 43.7% males) with normal LV ejection fraction were retrospectively evaluated. Inclusion criteria were sinus rhythm and ≥ 2-year follow-up. Standard echocardiography measurements, myocardial mechano-energetic efficiency (MEE) index, global longitudinal strain (GLS) and MW were evaluated. Adverse cardiac events were defined as composite of cardiac death, malignant ventricular tachycardia, atrial fibrillation and severe heart failure development. During a median follow-up of 63 months (interquartile range 37-85), 14 events occurred. Patient age, cardiac biomarkers, LV mass index, left atrium volume, E/Ea ratio, LV ejection fraction, MEE index, GLS and all MW indices were significantly related to adverse outcome at univariate analysis. After adjustment for clinical and echocardiographic parameters, which were significant at univariate analysis, GLS and MW resulted independent predictors of adverse events (p < 0.01). By ROC curve analysis, constructive MW ≤ 1513 mmHg% showed the highest sensitivity and specificity in predicting adverse outcome (92.9% and 86.6%, respectively). MW did not improve the predictive value of a model including clinical data, LV diastolic function and GLS. LV function impairment (both systolic and diastolic) is associated with adverse events in AFD. MW does not provide additive information over clinical features and systolic and diastolic function.


Comparison of two different loading doses of milrinone for weaning from cardiopulmonary bypass.
To compare the hemodynamic effects, pharmacokinetic profiles, and the need for vasoactive agents between a low (20 micrograms/kg during 15 minutes [group 1; n = 10]) and a high (40 micrograms/kg during 15 minutes [group 2; n = 10]) loading dose of milrinone. Prospective, randomized, double-blind. University hospital. Twenty patients scheduled for elective coronary artery surgery. Weaning from CPB was achieved using a strict protocol. After atrioventricular pacing at 90 beats per minute and preload optimalization, a first weaning attempt was started with only calcium and nitroglycerin as support. If this attempt was unsuccessful (cardiac index < 2L/min/m2), CPB was reinitiated and weaning level 2 was prepared, consisting of inotropic support with milrinone. Patients received either the low (group 1) or the high (group 2) loading dose of milrinone. After the end of the loading dose, a continuous infusion of milrinone of 0.5 micrograms/kg/min was started in both groups. Both groups were comparable regarding preoperative and intraoperative data. Hemodynamic data were comparable in both groups at each time of measurement (p = 0.941). The need for vasoactive medication (norepinephrine [NE]) in order to keep mean arterial pressure > or = 50 mm Hg was significantly higher in group 2 (p = 0.004). Need for NE during the loading infusion was 9.6 +/- 4.9 micrograms (mean +/- SEM) in group 1 and 41.6 +/- 7.6 micrograms in group 2 (p = 0.004). Need for NE during the immediate post-CPB period was also higher in group 2 (16.0 +/- 10.4 micrograms in group 1 and 232.5 +/- 82.8 micrograms in group 2 (p = 0.002)). Plasma clearance of milrinone after CPB was less in both groups than in healthy volunteers. However, clearance of milrinone was significantly higher in group 2 (p = 0.006), and consequently, half-life of milrinone was significantly less in group 2 (p = 0.007). The present results demonstrate that when milrinone is used during weaning from CPB, a loading dose of 20 micrograms/kg provided to similar hemodynamic support a loading dose of 40 micrograms/kg. The need for vasoconstrictive medication was significantly less in the group with the low loading dose.


Genomic organization of ribosomal DNA and related sequences inTriturus.
The ribosomal RNA genes ofTriturus vulgaris meridionalis are clustered at variable and often multiple chromosomal loci. The rDNA repeats exhibit only a limited and discrete length heterogeneity which is accounted for by the non-transcribed spacer (NTS). Interestingly, sequences homologous to the NTS are clustered outside the ribosomal loci. Clones containing such 'non ribosomal sequences' have been isolated from a genomic library ofT. v. meridionalis and analyzed by restriction mapping. These sequences appear to consist mostly of repetitive Bam HI fragments ranging from 500 bp to 1000 bp. The Bam HI fragments are internally repetitious and highly homologous to each other.


Corrigendum: Development and initial validation of a clinical measure to assess symptoms of post-stroke depression in stroke patients at the rehabilitation stage.
[This corrects the article DOI: 10.3389/fpsyg.2022.928257.].


The synthesis of neurotensin antagonist SR 48692 for prostate cancer research.
An improved synthesis of the molecule SR 48692 is presented and its use as a neurotensin antagonist biological probe for use in cancer research is described. The preparation includes an number of enhanced chemical conversions and strategies to overcome some of the limiting synthetic transformations in the original chemical route.


The long-term effect of a partial whey hydrolysate formula on the prophylaxis of atopic disease.
At the age of 5 years, the prevalence of atopic manifestations was analysed in 58 formula-fed "at risk" infants because of a history of atopic disease in at least two first degree relatives. Infants were randomly assigned to receive either a partial whey-hydrolysate formula (n: 28) or a regular cow's milk formula (n: 30) during the first 6 months of life; thereafter, feeding was unrestricted. Only non-breastfed infants were included. The groups did not differ in risk factors or in known confounding factors possibly influencing the incidence of manifestations suggestive of atopic disease. At 6 months, the prevalence of cow's milk protein (CMP) sensitivity was significantly decreased in the hydrolysate group (7% versus 43%; P: 0.002). At the age of 12 (21% versus 53%; P: 0.029), 36 (25% versus 57%; P: 0.018) and 60 months (29% versus 60%; P: 0.016) there was still a significant difference in the number of atopic manifestations, if calculated cumulatively. There was no difference between the groups if only the new cases after the age of 6 months were considered. Eczema was less frequent in the whey-hydrolysate group, but only during the 1st year of life, suggesting a decreased prevalence of CMP sensitivity. During the first 6 months, diarrhoea of non-infectious origin occurred in 8/30 infants (27%) of the adapted formula group, and in no infant in the hydrolysate group. "Colic as single manifestation" was considered of "allergic" origin in 1/28 infants in the hydrolysate group, and in 4/30 infants in the adapted formula group.(ABSTRACT TRUNCATED AT 250 WORDS)


Nitrogenase X: Mössbauer and EPR studies on reversibly oxidized MoFe protein from Azotobacter vinelandii OP. Nature of the iron centers.
Under anaerobic conditions the molybdenum-iron protein (MoFe protein) from Azotobacter vinelandii can be reversibly oxidized with thionine. Electron paramagnetic resonance studies reveal that the oxidation proceeds in two distinct phases: the MoFe protein can be oxidized by four electrons without loss of the EPR signal from the S = 3/2 cofactor centers. A second oxidation step, involving two electrons, leads to the disappearance of the cofactor EPR signal. In order to correlate the events during the thionine titration with redox reactions involving individual iron centers we have studied the MoFe proteins from A vinelandii and Clostridium pasteurianum with Mössbauer spectroscopy. Spectra were taken in the temperature range from 1.5 K to 200 K in applied magnetic fields of up to 54 kG. Analysis of the Mössbauer data allows us to draw three major conclusions: (1) the holoprotein contains 30 +/- 2 iron atoms. (2) Most probably, 12 iron atoms belong to two, apparently identical, iron clusters (labeled M) which we have shown previously to be structural components of the iron and molybdenum containing cofactor of nitrogenase. The M-centers can be stabilized in three distinct oxidation states, MOXe- in equilibrium MNe- in equilibrium MR. The diamagnetic (S = 0) state MOX is attained by oxidation of the native state MN with either thionine or oxygen. MR is observed under nitrogen fixing conditions. (3) The data strongly suggest that 16 iron atoms are associated with four iron centers which we propose to call P-clusters. Each P-cluster contains four spin-coupled iron atoms. In the native protein the P-clusters are in the diamagnetic state PN, yielding the Mössbauer signature which we have labeled previously 'components D and Fe2+'. Three irons of the D-type and one iron of the Fe2+-type appear to comprise a P-cluster. A one-electron oxidation yields the paramagnetic state POX. Although the state POX is characterized by half-integral electronic spin a peculiar combination of zero-field splitting parameters and spin relaxation renders this state EPR-silent. Spectroscopically, the P-clusters are novel structures; there is, however, evidence that they are closely related to familiar 4Fe-4S centers.


Gimme shelter: The effect of rocks and moonlight on occupancy and activity pattern of an endangered rodent, the garden dormouse Eliomys quercinus.
Information on spatial behaviour and temporal activity patterns is paramount for the conservation of animal species. This is particularly true for endangered taxa that are threatened by ongoing climatic and environmental changes. The garden dormouse Eliomys quercinus is a native European rodent (family Gliridae), whose populations are declining throughout the Continent. Notwithstanding this, neither International nor National laws explicitly require mandatory monitoring of populations. As a result, compelling information on the spatiotemporal behaviour of dormouse is lacking. We aimed to fill this gap by investigating occupancy patterns in relation to environmental features and activity rhythms in relation to moonlit nights in an Alpine population of dormouse within the Stelvio National Park, northern Italy. Data were collected between May and October 2015. Twenty camera-traps were deployed in a 500 ha coniferous forest, using a random tessellation approach; camera trap data were analyzed with occupancy models and kernel smoothers. Camera-traps provided a reliable assessment of the presence of the garden dormouse, with only 1 % of false absence and a high detection probability (68 %). The occurrence of the garden dormouse was positively influenced by the percentage of rock coverage on the ground. The species showed a strictly nocturnal behaviour, with an activity peak before midnight, negatively related to moonlit nights. The use of rocky areas for nesting, shelter site and thigmotactic movements and moonlight avoidance may represent adaptations of the garden dormouse to avoid predation risk. Our results shed some light on the habitat requirement of a poorly known, near-threatened species, and provide baseline information for future monitoring and conservation activities.


Hypervirulent Klebsiella pneumoniae as Unexpected Cause of Fatal Outbreak in Captive Marmosets, Brazil.
After the sudden death of captive marmosets in São Paulo, Brazil, we conducted a histologic and microbiologic study. We found hyperacute septicemia caused by hypermucoviscous sequence type 86 K2 Klebsiella pneumoniae. We implemented prophylactic antimicrobial therapy, selected dedicated staff for marmoset interactions, and sanitized the animals' fruit to successfully control this outbreak.


Laissez-Faire Leadership and Affective Commitment: the Roles of Leader-Member Exchange and Subordinate Relational Self-concept.
Although the detrimental effects of laissez-faire leadership are well documented, research on the underlying mechanisms and the boundary conditions associated with these effects remains scarce. Using the identity orientation framework and social exchange theory, we propose that employees with stronger relational self-concepts are more likely to be affected by laissez-faire leadership. As these employees define themselves through dyadic relationships, they may react more negatively to laissez-faire leadership by diminishing their contributions to mutual goals and reducing their affective organizational commitment. These predictions were tested within a three-wave longitudinal study through structural equations modeling analyses with full information maximum likelihood estimation on a sample of employees from multiple organizations (N = 449). As predicted, the relational self-concept was associated with a stronger negative effect of laissez-faire leadership on the contribution dimension of leader-member exchange and a stronger negative indirect effect on affective organizational commitment. The implications of these findings for our understanding of the mechanisms related to laissez-faire leadership are discussed.


Transcription termination and 3'-End processing of the spliced leader RNA in kinetoplastids.
Addition of a 39-nucleotide (nt) spliced leader (SL) by trans splicing is a basic requirement for all trypanosome nuclear mRNAs. The SL RNA in Leishmania tarentolae is a 96-nt precursor transcript synthesized by a polymerase that resembles polymerase II most closely. To analyze SL RNA genesis, we mutated SL RNA intron structures and sequence elements: stem-loops II and III, the Sm-binding site, and the downstream T tract. Using an exon-tagged SL RNA gene, we examined the phenotypes produced by a second-site 10-bp linker scan mutagenic series and directed mutagenesis. Here we report that transcription is terminated by the T tract, which is common to the 3' end of all kinetoplastid SL RNA genes, and that more than six T's are required for efficient termination in vivo. We describe mutants whose SL RNAs end in the T tract or appear to lack efficient termination but can generate wild-type 3' ends. Transcriptionally active nuclear extracts show staggered products in the T tract, directed by eight or more T's. The in vivo and in vitro data suggest that SL RNA transcription termination is staggered in the T tract and is followed by nucleolytic processing to generate the mature 3' end. We show that the Sm-binding site and stem-loop III structures are necessary for correct 3'-end formation. Thus, we have defined the transcription termination element for the SL RNA gene. The termination mechanism differs from that of vertebrate small nuclear RNA genes and the SL RNA homologue in Ascaris.


Combined therapy with cyclodextrin/allopregnanolone and miglustat improves motor but not cognitive functions in Niemann-Pick Type C1 mice.
Niemann-Pick Type C1 (NPC1) is an autosomal recessive disorder characterized by the accumulation of cholesterol and glycosphingolipids. Combination-treatment utilizing cyclodextrin, allopregnanolone and miglustat (CYCLO/ALLO/miglustat) can ameliorate NPC1 disease in a mutant mouse model. The present study was designed to add behavioral analysis in NPC1 mutant mice upon CYCLO/ALLO/miglustat therapy. NPC1 mutant (BALB/cJ NPC1NIH) and control mice were used. For the combination treatment mice were injected with CYCLO/ALLO weekly, starting at P7. The miglustat injection was performed daily from P10 till P23. Starting at P23, miglustat was added to the powdered chow. For the sham treatment of control and mutant mice the same schedule was used with 0.9% NaCl injection. Locomotor activity was assessed in open field, elevated plus maze and accelerod tests. For assessment of spatial learning and memory the Morris water maze test was conducted. Electron microscopy has been performed to support the behavioral data. The sham-treated mutant mice exhibited motor impairments in all performed tests. In the water maze the sham-treated mutants exhibited impairment in remembering the location of the hidden platform. CYCLO/ALLO/miglustat treatment positively influenced motor dysfunction: total distance and number of visits significantly increased, and accelerod performance improved. The spatial learning, however, did not benefit from therapy. At the morphological level, an excessive accumulation of electron-dense material was seen in the cerebellar Purkinje cells of mutant mice. A regression of these autophagosomal inclusions was seen upon therapy. CYCLO/ALLO/miglustat therapy ameliorates motor but not cognitive deficits in NPC1 mutant mice, suggesting unequal vulnerability of different brain areas to the treatment.


Quality of Sexual Life Questionnaire (QVS): a reliable, sensitive and reproducible instrument to assess quality of life in subjects with erectile dysfunction.
A French quality of life questionnaire specific to erectile dysfunction (ED), 'QVS' for 'Questionnaire de Vie Sexuelle', has been developed. This paper describes its validation: item reduction and reliability (internal consistency and reproducibility), construct validity and criterion validity (clinical, discriminant and concurrent). The initial 40-item questionnaire was administered once to 316 ED and 117 control subjects, and twice (D0 and D7) to 104 ED and 29 control subjects. Item reduction gave a 27-item questionnaire with three scales (Sexual Life, Skills and Psychosocial Well-being) and four scores (one score for each scale and a Global Index). Psychometric analyses demonstrated the reliability and the validity of the QVS. The questionnaire was able to discriminate patients according to the presence or severity of ED. The Skills scale was the least sensitive. Analysis of responsiveness to change over time still needs to be addressed to consider the questionnaire as a fully validated instrument.


[B-cell targeted therapy for children and adolescents with rheumatic diseases].
The introduction of cytokine-targeted therapies has significantly improved the treatment options of rheumatic diseases; however, some patients are also refractory to these treatment measures. The B cells play a central role in the pathogenesis of many rheumatic diseases and B-cell targeted therapies are a promising option as second-line medication for treating patients with a refractory disease course. Randomized controlled trials analyzing the efficacy of B-cell directed therapies for childhood rheumatic diseases have not yet been performed. The use of the B-cell depleting antibody rituximab showed positive results in non-controlled case series of juvenile systemic lupus erythematosus (SLE) patients. Patients with a refractory disease course of oligoarticular or polyarticular juvenile idiopathic arthritis might also benefit from B-cell depletion using rituximab. The B cell-targeting therapies for the treatment of childhood rheumatic diseases should be initiated and closely supervised by a pediatric rheumatologist.


The effect of sewage sludge fertilization on the concentration of PAHs in urban soils.
This paper analyses sources of sixteen PAHs - polycyclic aromatic hydrocarbons in urbanized areas by using selected diagnostic ratios. Simultaneously, an attempt was made to determine how sewage sludge changes PAHs content in urbanized areas soils. In the experiment three lawns along the main roads in Bialystok with different traffic intensity, three doses of sewage sludge and two years of study were considered. There was no effect of fertilization with sewage sludge on the sum of 16 PAHs in urban soil samples, nevertheless, the sum of 16 PAHs was reduced from 2.6 in 2011 to 2.3 mg/kg in 2012. Among 16 tested PAHs compounds, benzo[a]pyrene was the most dominant compound in samples collected in both years - about 15% of all PAHs. The results suggest that application of sludge into the soil did not influence the concentration of 2-3-ring, 4-ring and 5-6-ring PAHs. For the objects fertilized with a dose 150.0 Mg/ha, of sludge the total sum of potentially carcinogenic PAHs in the urban soil lowered by approximately 68% in comparison with the control plots. PAHs contamination of the urban soil samples resulted from the influence of coal, petroleum and biomass combustion. Moreover, PAHs can enter soil via at mospheric deposition.


The assessment of digital vessel disease by dynamic hand scanning.
A method of assessing hand and digital vessel perfusion is described. It involves an intravenous injection of Tc99m pertechnetate with monitoring of the isotope uptake in the hands and fingers by a gamma camera equipped with a small computer. The technique allows visual evaluation of the arterial supply and a means of quantifying digital perfusion. An evaluation of the technique in normal hands, in patients with digital vessel disease from vibration trauma, Raynaud's and embolism from an ulnar artery aneurysm is described. The potential of the technique in quantifying response to treatment is illustrated by sequential isotope hand scans in a patient treated for obliterative disease of the fingers.


Impairment of peripheral nerve regeneration by insufficient activation of the HGF/c-Met/c-Jun pathway in aged mice.
Aging in the peripheral nervous system (PNS) leads to its dysfunction and lowers regenerative capacity after injury. Based on the pro-regenerative effect of hepatocyte growth factor (HGF) in injured peripheral nerves, we investigated whether this growth factor is involved in the age-related degeneration of the PNS. We observed that the capacity for nerve regeneration was significantly reduced under aging conditions as indicated by the decreased level of SCG10-positive axons. Functional recovery was also impaired. We further tested whether the HGF/c-Met pathway was involved, and the activation of the c-Met receptor upon nerve injury was significantly reduced, whereas the production of HGF protein was still comparable to that in young mice. Moreover, the phosphorylation and expression of c-Jun, a key regeneration-associated gene, was also lowered in aged animals. In addition, exogenous administration of the HGF expressing plasmid DNA significantly ameliorated the pain-like behavior in young animals, however, such analgesic activity was impaired in aged mice. These data suggested that the HGF/c-Met pathway might be involved in the age-related impairment of regenerative capacity in the PNS.


Environmental toxicology: polychlorinated biphenyls impair TNF-alpha release in vitro.
Tumour necrosis factor (TNF-alpha) was induced by bacterial lipopolysaccharides (LPS)/phytohemagglutin (PHA) stimulated human whole blood in vitro. Levels of TNF-alpha were evaluated by enzyme-linked immunosorbent assay. Blood samples treated with polychlorinated biphenyls (PCB 77, PCB 126) exhibited impairment of TNF-alpha release: 50 pg/microl PCB reduced by up to 66% and 500 pg/microl PCB reduced by up to 93% the TNF-alpha release compared with the controls.