Silencing of UCA1 attenuates the ox-LDL-induced injury of human umbilical vein endothelial cells via miR-873-5p/MAPK8 axis.
LncRNA UCA1 plays a vital role in cardiovascular diseases. Endothelial cell dysfunction is a prerequisite for atherosclerosis (AS) development. However, the pathophysiological role of UCA1 in endothelial cell dysfunction induced by ox-LDL remains obscure. Here, we observed that UCA1 was upregulated in the sera of patients with AS and ox-LDL-treated endothelial cells. UCA1 knockdown dramatically reduced the cell apoptosis induced by ox-LDL and the production of pro-inflammatory cytokines and ROS in endothelial cells. Mechanistically, we found that UCA1 directly targeted miR-873-5p. UCA1 knockdown increased, while UCA1 overexpression decreased the expression of miR-873-5p. Further, we found that mitogen-activated protein kinase 8 (MAPK8) was a downstream target gene of miR-873-5p. MAPK8 overexpression or miR-873-5p knockdown reduced the enhancement of ox-LDL-induced cell apoptosis, oxidative stress, and pro-inflammatory cytokine production conferred by UCA1 knockdown. In conclusion, UCA1 can protect Human Umbilical Vein Endothelial Cells from ox-LDL-induced injury via the miR-873-5p/MAPK8 axis.


A leadership focus on evidence-based practice: tools for successful implementation.
Case managers grapple with best methods to infuse case management evidence into their practice. This article examines the role of each case manager as a leader in evidence-based practice (EBP) and emphasizes proven strategies for case management leaders to move EBP into their case management environment. Special focus is placed on steps to establish a practice culture supportive of EBP, creating the organizational infrastructure to support EBP, and practical tips for success. This article applies to any case management practice setting. Employing a systematic model to move the evidence into the case management practice setting results in improved patient, case manager, and organizational outcomes. Case management service provision based on the established evidence base creates a more legally and ethically sound practice. A change in practice to EBP will increase individual case managers' leadership abilities, thus establishing a stronger and more satisfied employee base. Utilization of a well-planned approach to incorporate evidence into practice results in higher levels of success and improves patient and organizational outcomes.


A basidomycetous hydroxynaphthalene-prenylating enzyme exhibits promiscuity toward prenyl donors.
The fungal prenyltransferase ShPT from Stereum hirsutum was believed to prenylate 4-hydroxybenzyl alcohol and thereby be involved in the vibralactone biosynthesis. In this study, we demonstrate that hydroxynaphthalenes instead of benzyl alcohol or aldehyde were accepted by ShPT for regular C-prenylation in the presence of both dimethylallyl and geranyl diphosphate. Although the natural substrate of ShPT remains unknown, our results provide one additional prenyltransferase from basidiomycetes, which are less studied, in comparison to those from other sources. Furthermore, this study expands the chemical toolbox for regioselective production of prenylated naphthalene derivatives. KEY POINTS: •Basidiomycetous prenyltransferase •Biochemical characterization •A DMATS prenyltransferase prenylating hydroxynaphthalene derivatives.


In vivo desaturation of cis-delta 9-monounsaturated to cis-delta 9,12-diunsaturated alkenylether glycerolipids.
Plants convert lipid-bound cis-n-9 monoenoic to polyenoic fatty acid residues without involvement of corresponding CoA-thioesters. To provide additional evidence for this type of lipid-linked desaturation we incubated sn-1-O- and 2-O-(cis-9)octadecenylglycerol isomers with photoautotrophic cell cultures from tomato. After 14 days the fractions of phosphatidylcholine and monogalactosyldiacylglycerol were isolated and the incorporated glycerol ether backbones released by treatment with LiAlH4 (reduction of ester bonds) and short acid hydrolysis (cleavage of enol ether bonds). High performance liquid chromatography and mass spectroscopy of the products in appropriately derivatized form showed that the (cis-9)octadecenyl group in the sn-1 position of the phospholipid was nearly completely desaturated to a (cis-9,12)octadecadienyl residue having the same double bond arrangement as linoleic acid. In the galactolipid fraction the desaturation had progressed to octadecatrienyl residues. Similarly, the octadecenyl residue in the sn-2 position of the phospholipid was nearly completely desaturated to an octadecadienyl group. These results are unambiguous proof for lipid-linked desaturation by both microsomal and plastidial desaturase systems of plants.


Epoprostenol (prostacyclin) in unstable angina.
The purpose of this randomized, double-blind multicenter trial was to investigate the potential therapeutic effect of epoprostenol (prostacyclin, PGI2) in patients with unstable angina, as compared with placebo, and to investigate the safety of this agent. Of the 184 patients enrolled, 28 did not fit the study criteria; of the remaining 156 patients, 30 received prostacyclin in an open-label fashion. In the double-blind portion of the study, 63 patients each received prostacyclin or placebo. The drug or its vehicle was infused intravenously up to 5 ng/kg/min dose for 72 hours with a tapering off period for the last 12 hours. Both treatment groups from the double-blind portion were comparable in regard to the demographic data, length of infusion, and total dose received. There were no significant differences between the placebo and prostacyclin group in the following clinical endpoints: levels of cardiac enzymes throughout hospitalization period (with the exception of lower SGOT level in the prostacyclin group at day 2), and severity of angina (throughout the study), and at the end of the study (day 30). The number of patients who had congestive heart failure, new myocardial infarction, balloon pump insertion, coronary artery bypass grafting, or percutaneous coronary angioplasty was similar in both groups. Similar results in regard to the efficacy endpoints were also apparent in the prostacyclin group that was treated under open-label fashion. There was also no difference in the New York Heart Association (NYHA) functional status at the end of the double-blind study.(ABSTRACT TRUNCATED AT 250 WORDS)


Protein kinase D complexes with C-Jun N-terminal kinase via activation loop phosphorylation and phosphorylates the C-Jun N-terminus.
Protein kinase D (PKD), a downstream effector of protein kinase C (PKC), is implicated in suppression of the c-Jun N-terminal kinase (JNK) signaling pathway, however, its mechanism of action is unclear. Transphosphorylation of the PKD activation loop at serines 744/748 by a PKC mediated signal transduction pathway enhances its catalytic activity. Here we show that PKD activation loop phosphorylation at serines 744/748 via PKC, or mutation of these serines to glutamic acid (PKD-S744/748E) also results in complex formation with JNK, indicating that suppression of JNK signaling by PKD involves a direct interaction with JNK. Because catalytically active PKD associates with JNK we determined whether it could phosphorylate the c-Jun N-terminus as a potential mechanism by which it suppresses c-Jun Ser 63 phosphorylation when it complexes with JNK. Purified human PKD and either wild-type PKD from phorbol 12, 13-dibutyrate (PDB)-stimulated cells or unstimulated constitutively active PKD (PKD-S744/748E), phosphorylated the c-Jun N-terminus between amino acids 1-89 at sites distinct from those phosphorylated by JNK. These results demonstrate, for the first time, phosphorylation dependent association of PKD with another signaling molecule and reveal a potential mechanism by which PKD could modulate the ability of JNK to phosphorylate c-Jun by phosphorylating alternative sites in the c-Jun N-terminus when it is complexed with JNK.


A de novo microdeletion involving PAFAH1B (LIS1) related to lissencephaly phenotype.
Lissencephaly is a type of the congenital malformation of the brain. Due to the impairments of neuronal migration, patients show absence of brain convolution manifesting smooth brain surfaces. One of the human genes responsible for lissencephaly is the platelet-activating factor acetylhydrolase 1b gene (PAFAH1B; also known as LIS1) located on 17p13.3. Patients with heterozygous deletion of this chromosomal region exhibit lissencephaly. Recently, we encountered a male patient who showed typical lissencephaly. Using a microarray analysis, we identified a 1.3 Mb submicroscopic deletion in 17p13.3. This deletion included PAFAH1B. Both of the parents showed no deletion in this region. Therefore, this was determined to be derived from de novo origin. After obtaining the written informed consent, skin fibroblasts were provided from this patient and disease-specific induced pluripotent stem (iPS) cells were generated and used for medical research (Shimojima K, Okumura A, Hayashi M, Kondo T, Inoue H, and Yamamoto T. CHCHD2 is down-regulated in neuronal cells differentiated from iPS cells derived from patients with lissencephaly. Genomics, in press).


Unwise Relationships and an Unsound Valence Theory: The Chemical Career of Robert Fergus Hunter (1904-1963).
The life of the Imperial College-trained Robert Fergus Hunter (1904-1963) was a Bildungsroman of a gifted chemist who appeared destined for a prominent academic career in organic chemistry. Two circumstances spoiled his chances. In the first place, he became associated with the declining fortunes of the weekly Chemical News. More seriously, as a professor at the Aligarh Muslim University in British India (1930-1936), he published papers on valence theory with the German-Jewish physicist Rudolf Samuel that fatally destroyed his chance of further academic preferment. Instead he became a research chemist in the food and plastics industries. The paper critically assesses Hunter's work on valence and also provides new light on science in India during the 1930s.


Expression of heat shock protein 27 and troponin T and troponin I after naloxone-precipitated morphine withdrawal.
Heat shock protein (Hsp27) renders cardioprotection from stress situations but little is known about its role in myofilaments. In this study we have evaluated the relationship between Hsp27 and troponin response after naloxone-induced morphine withdrawal. Rats were treated with two morphine (75 mg) pellets during six days. Precipitated withdrawal was induced by naloxone on day seven. Hsp27 expression, Hsp27 phosphorylated at serine 82 (Ser82), cardiac troponin T (cTnT), cardiac troponin I (cTnI) and µ-calpain were evaluated by immunoblotting in left ventricle. Hsp, cTnT and cTnI was also evaluated by immunofluorescence procedure. Our results show that enhancement in Hsp27 expression and phosphorylation induced by naloxone-precipitated morphine withdrawal occurs with concomitant increases of cTnT and µ-calpain expression, whereas cTnI was decreased. We also observed co-localization of Hsp27 with cTnT in cardiac tissues. These findings provide new information into the possible role of Hsp27 in the protection of cTnT degradation by µ-calpain (a protease mediating proteolysis of cTnT and cTnI) after morphine withdrawal.


Inhibition by cyclosporin A of IgE production and cyclophosphamide-induced eosinophilia in rats immunized with non-parasite antigens.
Administration of cyclosporin A (CS-A; 25 mg/kg daily) to rats from the time of immunization with ovalbumin (OVA) in complete Freund's adjuvant abolished the production of anti-OVA antibodies, including IgE. Cyclophosphamide (Cy; 150 mg/kg) given 2 days before immunization also inhibited specific antibody production but at the same time induced a striking eosinophilia. Combined administration of both drugs resulted in the inhibition by CS-A of the Cy-induced eosinophilia. The results suggest that IgE synthesis and eosinophil proliferation may be under the control of separate T cell subsets. This rat model may prove useful in studies on the regulation of eosinophil production and the role of these cells in disease processes.


Aerobic training reduces pancreatic fat content and improves β-cell function: A randomized controlled trial using IDEAL-IQ magnetic resonance imaging.
To explore the effects of six months of moderate-intensity aerobic exercise on pancreatic fat content and its impact on β-cell function. A total of 106 patients with type 2 diabetes mellitus were randomized to either a moderate-intensity aerobic training group (three times a week, including 5 min warm-up, 50 min aerobic dancing, and 5 min relaxation, n = 53) or control group (n = 53) with 6-month intervention. The primary endpoint was change in pancreatic fat content. An intention-to-treat analysis was conducted. Eighty-six patients completed the study with 43 patients in the aerobic training group. The average age, HbA1c, and pancreatic fat content for all participants (106 patients) were 66.39 ± 5.59 years, 7.05 ± 1.24%, and 10.35 ± 9.20%, respectively. Nearly half (49.06%) of patients were males. Subjects in the aerobic training group saw a significant reduction in pancreatic fat content when compared to controls (p = 0.001). In logistic regression models containing age, diabetes duration, change in BMI, smoking/drinking status, changes in lipid indices, and other abdominal fat content, only reduction in pancreatic fat content (p < 0.05) was an independent protective factor for β-cell function and HbA1c. Six months of moderate-intensity aerobic training significantly reduced the pancreatic fat content. The reduction of pancreatic fat content was an independent protective factor for β-cell function and HbA1c.


Underwater Sound Propagation from Marine Pile Driving.
Pile driving occurs in a variety of nearshore environments that typically have very shallow-water depths. The propagation of pile-driving sound in water is complex, where sound is directly radiated from the pile as well as through the ground substrate. Piles driven in the ground near water bodies can produce considerable underwater sound energy. This paper presents examples of sound propagation through shallow-water environments. Some of these examples illustrate the substantial variation in sound amplitude over time that can be critical to understand when computing an acoustic-based safety zone for aquatic species.


Pig leukocyte cysteine proteinase inhibitor (PLCPI), a new member of the stefin family.
A new stefin type low-M(r) cysteine proteinase inhibitor (PLCPI) was isolated from pig polymorphonuclear leukocytes as a contaminant of the cathelin sample. The inhibitor consists of 103 amino acids, and its M(r) was calculated to be 11,768. The inhibitor exhibits considerable sequence identity with inhibitors from the stefin family, particularly with human stefin A. The PLCPI is a fast acting inhibitor of papain and cathepsins L and S (k(ass) > or = 1 x 10(6) M-1 x s-1) and forms very tight complexes with these enzymes (Ki < or = 190 pM). The affinity for cathepsins B and H (Ki > or = 125 nM) was lower. These results also show that the inhibitory activity previously ascribed to cathelin was due to the presence of PLCPI.


The efficacy and toxicity of angiogenesis inhibitors for ovarian cancer: a meta-analysis of randomized controlled trials.
To evaluate the efficacy and toxicity of angiogenesis inhibitors for the treatment of ovarian cancer patients, we conducted a meta-analysis of the published literature on this subject. In this meta-analysis, we searched PubMed, EMBASE, Web of Science, and Cochrane Library databases for randomized controlled trials (RCTs). The literature search was performed up to August 12, 2019. The risk of bias of the included studies was evaluated using The Cochrane Collaboration's tool, and the statistical analyses were performed using RevMan 5.3 software. The sensitivity analysis was performed with Stata 12.0 software. 22 RCTs with 11,254 patients were included. Our meta-analysis demonstrates that angiogenesis inhibitors therapy can significantly improve progression-free survival (PFS) (hazard ratio [HR] 0.71, 95% CI 0.63-0.79, I2 = 80%, P < 0.00001) and overall survival (OS) (HR 0.95, 95% CI 0.90-0.99, I2 = 0%, P = 0.03) in ovarian cancer patients. The subgroups results suggest differences in the benefit in OS in first-line treatment (HR 1.00, 95% CI 0.93-1.08, I2 = 0%, P = 0.90) compared with treatment at relapse (HR 0.87, 95% CI 0.81-0.95, I2 = 0%, P = 0.0008). The PFS improved both in first-line treatment (HR 0.87, 95% CI 0.79-0.95, I2 = 60%, P = 0.003) and recurrent treatment (HR 0.60, 95% CI 0.53-0.67, I2 = 57% P < 0.0001) patients. The PFS and OS in recurrent group were prolonged both in the platinum-resistant group(PFS: HR 0.50, 95% CI 0.42-0.60, I2 = 0%, P < 0.00001; OS: HR 0.76, 95% CI 0.62-0.93, I2 = 0%, P = 0.007) and the platinum-sensitive group (PFS: HR 0.58, 95% CI 0.49-0.69, I2 = 64%, P < 0.00001; OS: HR 0.88, 95% CI 0.79-0.99, I2 = 0%, P = 0.03). However, this therapy is associated with a higher risk of common adverse events of grade ≥ 3 (risk ratio [RR]: 1.12; 95% CI 1.07-1.17; I2 = 0%, P = 0.68) such as arterial thromboembolic disease, ascites, diarrhea, gastrointestinal perforations, headache, hemorrhagic, hypertension, hypokalemia, leucopenia, pain, proteinuria, thrombocytopenia, and thrombosis or embolism. This meta-analysis suggests angiogenesis inhibitors may significantly improve PFS and OS of ovarian cancer patients and increase the incidence of common adverse events.


Reproductive activity influences thermoregulation and torpor in pouched mice, Saccostomus campestris.
The Afrotropical pouched mouse Saccostomus campestris displays sexual disparity in the use of daily torpor; males reluctantly enter torpor. We tested the hypothesis that males may compensate for a limited heterothermic capacity with lower basal and resting metabolic rates relative to females. We also investigated the association between gonadal activity (testosterone) and the propensity for daily torpor. Body temperature and oxygen consumption were measured at various ambient temperatures and were compared between sexes under ad libitum and restricted-diet treatments. Whereas no significant sex differences were observed in body temperature and oxygen consumption under ad libitum treatment, there were pronounced differences in heterothermic responses under food restriction. Females employed torpor more frequently and also had lower minimum torpor body temperatures (ca. 25 degrees C) than males (ca. 29 degrees C). Testosterone inhibited torpor in males, whereas the majority of saline-treated animals employed torpor under both ad libitum and restricted-diet treatments. This study demonstrated that the limited capacity of male S. campestris to enter torpor is a consequence of reproductive activity and that opportunistic breeding and the absence of seasonal testes regression compromises the capacity to conserve energy through daily torpor.


Actinomortierella wolfii: Identity and pathology.
Actinomortierella wolfii (Mortierellales), formerly Mortierella wolfii, is a causative agent of bovine systemic infection and abortion. Human infections caused by this species are extremely rare. Here, we present a case of a patient with B-Cell Acute Lymphoblastic Leukemia (B-ALL) who was diagnosed with a rhinocerebral infection caused by this fungus. Amphotericin treatment of the patient proved unsuccessful. This type of disease is otherwise nearly exclusively limited to members of the order Mucorales. The taxonomy of the causative agent is discussed.


Plasma optical modulators for intense lasers.
Optical modulators can have high modulation speed and broad bandwidth, while being compact. However, these optical modulators usually work for low-intensity light beams. Here we present an ultrafast, plasma-based optical modulator, which can directly modulate high-power lasers with intensity up to 10(16) W cm(-2) to produce an extremely broad spectrum with a fractional bandwidth over 100%, extending to the mid-infrared regime in the low-frequency side. This concept relies on two co-propagating laser pulses in a sub-millimetre-scale underdense plasma, where a drive laser pulse first excites an electron plasma wave in its wake while a following carrier laser pulse is modulated by the plasma wave. The laser and plasma parameters suitable for the modulator to work are based on numerical simulations.


An unusual case with myotonia.
We report an unusual case involving a patient with myotonia. A 57-year-old man had multisystemic symptoms including skeletal muscle weakness, atrophy and percussion myotonia, cataract, heart involved, gastrointestinal tract symptoms, and urinary incontinence. The electromyography revealed myotonic discharges. Muscle biopsy showed myopathic features and a striking number of ring fibers. It was genetically proven that the case was not myotonic dystrophy type 1 (DM1) or 2 (DM2). The case might be DM3 or an unusual case of unclassified myopathy with multisystemic damage.


PET/CT Fluoroscopy during PET/CT-Guided Interventions: Initial Experience.
This study assessed the feasibility and functionality of the use of a high-speed image fusion technology to generate and display positron emission tomography (PET)/computed tomography (CT) fluoroscopic images during PET/CT-guided tumor ablation procedures. Thirteen patients underwent 14 PET/CT-guided ablations for the treatment of 20 tumors. A Food and Drug Administration-cleared multimodal image fusion platform received images pushed from a scanner, followed by near-real-time, nonrigid image registration. The most recent intraprocedural PET dataset was fused to each single-rotation CT fluoroscopy dataset as it arrived, and the fused images were displayed on an in-room monitor. PET/CT fluoroscopic images were generated and displayed in all procedures and enabled more confident targeting in 3 procedures. The mean lag time from CT fluoroscopic image acquisition to the in-room display of the fused PET/CT fluoroscopic image was 21 seconds ± 8. The registration accuracy was visually satisfactory in 13 of 14 procedures. In conclusion, PET/CT fluoroscopy was feasible and may have the potential to facilitate PET/CT-guided procedures.


Comparison of the fine structure and physicochemical properties of proso millet (Panicum miliaceum L.) starch from different ecological regions.
Field experiments were conducted to evaluate the morphology, granule size, fine structure, thermal properties, and pasting properties of starch from a waxy (139) and a non-waxy (297) varieties of proso millet grown in Yulin (YY) and Yangling (YL). Compared with the starches from the two varieties grown in YY, the starches from the two varieties grown in YL exhibited higher relative crystallinities, 1045/1022 cm-1 ratio, and amounts of amylopectin long branch chains (APL) but lower 1022/995 cm -1 ratio, amounts of amylopectin short branch chains (APs), and APs/APL ratios. Starches from YL also synthesized long branch-chain amylopectin to enhance intermolecular interactions and form a stable granular structure, which resulted in increased starch gelatinization temperature, enhanced shear resistance, and reduced setback viscosity. Starch from the waxy (139) variety has good application prospects in the food industry because of its high gelatinization temperature and light transmittance and low setback value, which can be ascribed to its extremely low amylose content, polydispersity index, high molecular weight, and dispersed molecular density. It may serve as a reference for applying proso millet starches in the food industry and developing breeding programs to improve starch quality.


Effort avoidance as a core mechanism of apathy in frontotemporal dementia.
Apathy is a core symptom in patients with behavioural variant frontotemporal dementia (bvFTD). It is defined by the observable reduction in goal-directed behaviour, but the underlying mechanisms are poorly understood. According to decision theory, engagement in goal-directed behaviour depends on a cost-benefit optimization trading off the estimated effort (related to the behaviour) against the expected reward (related to the goal). In this framework, apathy would thus result from either a decreased appetence for reward, or from an increased aversion to effort. Here, we phenotyped the motivational state of 21 patients with bvFTD and 40 matched healthy controls using computational analyses of behavioural responses in a comprehensive series of behavioural tasks, involving both expression of preference (comparing reward value and effort cost) and optimization of performance (adjusting effort production to the reward at stake). The primary finding was an elevated aversion to effort, consistent across preference and performance tasks in patients with bvFTD compared to controls. Within the bvFTD group, effort avoidance was correlated to cortical atrophy in the dorsal anterior cingulate cortex and to apathy score measured on a clinical scale. Thus, our results highlight elevated effort aversion (not reduced reward appetence) as a core dysfunction that might generate apathy in patients with bvFTD. More broadly, they provide novel behavioural tests and computational tools to identify the dysfunctional mechanisms producing motivation deficits in patients with brain damage.


[Effect of oxygen and hypergravitation on alveolar surfactant].
The effect of prolonged exposure (up to 66 hours) to pure oxygen breathing and to short (5-minute) oxygen breathing combined with acceleration (+5Gz) on the surface tension and surface potential of the alveolar washout of the albino rat lungs was determined. Both experimental conditions produced atelectasis and a decrease of the surfactant surface activity. Possible mechanisms of shifts of the surfactant activity under hyperoxia only, and hyperoxia with accelerations are discussed.


Cardiopulmonary toxicity in patients with breast carcinoma during plasma perfusion over immobilized protein A. Pathophysiology of reaction and attenuating methods.
Tumoricidal reactions in dogs with spontaneous breast carcinoma occur after perfusion of plasma over protein A derived from Staphylococcus aureus and immobilized in collodion charcoal. When this treatment was extended to humans with breast cancer, hemodynamic and physiologic changes were noted. The evolution and spectrum of these reactions were evaluated during 47 plasma infusions in five patients. Initial treatment conditions consisting of rapid perfusion of plasma over high quantities of immobilized protein A were employed for 12 treatments in two patients. Within 30 minutes after treatments were begun, mean blood pressure, systemic vascular resistance, and stroke volume increased, as did heart rate, cardiac output, and rectal temperature; however, mean pulmonary artery pressure and total pulmonary resistance did not change. At 90 minutes, hypotension developed (lowest mean blood pressure was 59 +/- 14 mm Hg) that was associated with a decrease in systemic vascular resistance and total pulmonary resistance (536 +/- 66 and 146 +/- 44 dynes . second . cm-5, respectively). Cardiac output increased, tachycardia developed, stroke volume decreased, and rectal temperature increased. During the hypotensive phase, values of creatinine clearance and fractional excretion of sodium diminished. Noncardiogenic pulmonary edema appeared occasionally, with bronchospasm noted once. No hemodynamic changes were seen when saline solution was passaged over protein A immobilized in collodion charcoal or when autologous plasma was given without passage over protein A immobilized in collodion charcoal. Treatment conditions were modified by diminishing protein A quantity and plasma volume and slowing plasma perfusion rate, which resulted in significant attenuation of all cardiopulmonary responses. This report, then, defines for the first time the physiologic basis of the cardiopulmonary toxicity in humans after plasma perfusion over immobilized protein A.


Maternal immunoregulation: interrelationship between alloreactive and anti-self plus conventional antigen T sets of cells.
In a previous paper we reported early immunoregulatory mechanisms involving not only the appearance of progressive suppression but also significant increases in alloreactive T levels in paraaortic lymph nodes (PALN) and spleen, not only in allogeneic but also in syngeneic pregnancies. Taking into account the hypothesis of the superposition of the alloreactive and the anti-self plus conventional antigens T sets of cells, we investigated whether immunization with conventional antigens was able to alter alloreactive T levels. Weekly i.p. doses of rabbit red bloods cells (RRBC) in BALB/c mice resulted in a dose-dependent increase in spleen alloreactivity as determined by graft-versus-host (GvH) assays in strain combinations differing at H-2 level but not in those sharing the same H-2 with BALB/c. The increases could be significantly decreased by an anti-idiotype anti-RRBC serum. Pretreatment with i.p. weekly doses of sheep red blood cells (SRBC) before mating was able to induce dose-dependent fetal damage when the parents differed at the H-2 level. SRBC immunization in one of the uterine horns induced increases in PALN weight which were much higher in progesterone-pseudopregnant than in virgin mice; T alloreactivity was significantly increased in the draining PALN only in pseudopregnant females. These results favour the postulation of the superposition between the alloreactive and the anti-self plus conventional antigens T sets of cells and suggest a possible role for conventional fetal antigens (non H-2) in triggering immunoregulatory mechanisms operating in pregnancy.


Hyperbaric Oxygen Therapy Is an Effective Adjunctive Therapy to Manage Treatment-Resistant Venous Leg Ulcers.
We report five cases of venous leg ulcers (VLU) that were resistant to conservative therapy for 22-119 months and were eventually healed via hyperbaric oxygen therapy (HBOT). In one patient, VLU recurred four times and was managed using HBOT, each time. The VLU sizes ranged from 18 to 68 cm2 before HBOT. HBOT was administered at 2.0 atmospheres absolute with 100% oxygen for 60 min per session, five sessions a week during hospitalization. All VLUs healed after 17-66 sessions of HBOT.


Living with prostate cancer: a mixed-method evaluation of group therapy intervention to alleviate psychological distress in a Canadian setting.
To assess the effects of group therapy focused on the experience of living with prostate cancer (PC) on depression and mental well-being among men with the disease and to explore participant experiences of a guided opportunity to 'speak the unspeakable' as it pertains to living with PC. We used a mixed-method convergent design. Participants completed four validated self-report questionnaires at baseline, immediately after the final session, and at three, six, and 12 months follow-up. A repeated measures mixed-effect model examined the effects of the program on depression, mental well-being, and masculinity. Seven focus groups (n = 37) and 39 semi-structured individual interviews explored participant reactions at follow-up. Thirty-nine (93%) participants completed the questionnaires at all follow-ups. Responses indicated improved mental well-being up to three months (p < 0.01) and a decrease in depressive symptoms to 12 months (p < 0.05). Qualitative analysis revealed how the cohesive group environment alleviated psychological stress, enabled participants to identify significant issues and concerns in their lives, and improved communication and relationship skills that were of value in the group as well as with family and friends. The facilitation was essential to guiding participants to 'speak the unspeakable.' Men with PC who speak of their experience in a group setting with a guided process incorporating features of a life review appear to gain insight into the impact of PC in their lives, experience diminished features of depression and isolation, and enhance their communication skills within the groups as well as with family members and friends.


Extensive Grover's-like eruption with lentiginous 'freckling': report of two cases.
We have described two females with extensive freckling and scaly lesions and conclude that they have a widespread form of Grover's disease associated with lentiginous sun-induced 'freckling'. We report these cases to draw attention to an unusual pattern of Grover's disease that can simulate Darier's disease.


Toxicity and tissue distribution of aminophyline in neonatal and adult mice and rats.
The LD50 of aminophylline in adult mice differed from young mice and rats of both ages, in which the values were remarkably similar (Table 1). With the exception of fat, which had lower concentrations in all groups, tissue concentrations after a 4 mg/kg rectal dose of aminophylline in the 10-day-old animals ranged from 10-20 microng/g as compared to 4-10 microng/g in the adults (Table 2). To evaluate preferential distribution, an analysis of tissue to blood concentration ratios was made. All ratios approximated 1.0 except fat which had a ratio of 0.1-06. The neonates of each species had significantly higher tissue to blood ratios for brain, heart, small intestine, skeletal muscle, and fat (P less than 0.05). Brain to plasma and brain to blood ratios were very similar ranging from 0.4-1.3 in adults versus 0.8-1.7 in neonates. Consideration of the time course indicated a trend toward unit, with the overall ratio in both groups being 1.15 at 2 hr. However, at all earlier time periods the ratios were clearly higher in neonates. Administration of aminophylline intraperitoneally to produce serum concentrations of theophylline far in excess of the 10-20 microng/ml considered to be safe and effective in clinical use did not decrease bilirubin levels in young or old Gunn rats (Fig. 1).


Absence of association between Guillain-Barré syndrome hospitalizations and HPV-vaccine.
In 2008, a school-based human papilloma virus (HPV) vaccination program was implemented in the province of Québec. Grade 4 girls (9-10 years old) are routinely vaccinated and grade 9 to 12 girls (14-17 years old) were eligible for the catch-up vaccination. Vaccine coverage of the targeted cohorts was estimated at 76-81%. To assess if HPV vaccination is associated with an increase in GBS hospitalisation, we compared the hospitalization rates of GBS in HPV vaccination targeted and non-targeted groups. Hospital discharge records with a GBS code as the main diagnosis during the 1999-2014 period were retrieved. Incidence rates according to program eligibility were computed and adjusted relative risk in the targeted groups was estimated by Poisson regression. The overall incidence rate in the 7 to 17 year-olds was 0.73/100,000 p-y. There was no increase in GBS incidence in HPV vaccination targeted groups (adjusted IRR = 0.81, 95%CI: 0.29-2.26). No signal of increase GBS hospitalisation incidence in the HPV-vaccine targeted group was detected in the hospitalisation database.


Rat endo- and mesothelium lack Fc receptors.
The present study is concerned with the interaction of rat endo- and mesothelium with homologous erythrocytes under various conditions of pretreatment and incubation. Its findings show rat endo- and mesothelial cells a) nonadhesive to native or pretreated erythrocytes irrespective of the presence of gamma-globulin in the medium, b) devoid of primary or cryptic receptors sensitive to the Fc segment of the IgG molecule, and c) provided with binding sites at the oxidized glycocalyx which together with receptor groups of modified erythrocytes share the same class of IgG.


Organic nitrates: direct antiplatelet effects and synergism with prostacyclin. Antiplatelet effects of organic nitrates.
Isosorbide dinitrate inhibits platelet function in vivo at concentrations about 10 times lower than in vitro (10(-7)-10(-6) vs. 10(-6)-10(-5) M). We investigated two possible reasons for this difference. Isosorbide dinitrate and its in vivo longer-lived metabolites, isosorbide-2- and isosorbide-5-mononitrate were incubated for 5 min with human platelet-rich plasma or washed platelets; irreversible aggregation was induced with threshold doses of ADP, adrenaline, collagen, arachidonic acid and thrombin, and thromboxane (TX) B2 production was measured by radioimmunoassay. Moreover, the concentration of exogenous prostacyclin required to inhibit platelet aggregation by 50% (IC50) after preincubation with isosorbide dinitrate or vehicle was determined. At 10(-7) M, only isosorbide-2-mononitrate inhibited aggregation (-12%, p less than 0.05) and TX production (-36%, p less than 0.01) by ADP. At 10(-6) M isosorbide-2-mononitrate inhibited aggregation by adrenaline more than the dinitrate (-41% vs. -25%, p less than 0.05). In addition, at supra-threshold doses of all the aggregating agents, isosorbide dinitrate decreased IC50 of prostacyclin from 2.7 +/- 1.2 to 0.36 +/- 0.2 nM. Generation of a platelet-active metabolite and synergism with prostacyclin are new properties of isosorbide dinitrate that may account for antiplatelet effects in vivo.


Feasibility of gastric electrical stimulation by use of endoscopically placed electrodes.
Gastric electrical stimulation (GES), which has been reported to have therapeutic potentials for gastroparesis and obesity, involves the surgical placement of electrodes with the patient under general anesthesia. New methods are needed for implanting GES electrodes in a safer and more feasible way. Our purpose was to investigate the safety and feasibility of placing electrodes endoscopically for GES. A pilot study. Six female hound dogs that weighed 13 to 22 kg. Endoscopically placed electrodes passed through the abdomen and the stomach wall. The study was performed in dogs surgically implanted with gastric serosal electrodes and endoscopically implanted electrodes. The experiment consisted of a 30-minute baseline, a 30-minute GES, and a 30-minute recovery. GES was performed through endoscopically placed electrodes. Gastric slow waves were simultaneously recorded with the serosal electrodes and the endoscopically placed electrodes. (1) The slow wave frequency recorded from the endoscopically placed electrodes was significantly correlated with that from the serosal electrodes (r = 0.97, P < .002). (2) GES through the endoscopically placed electrodes was able to entrain gastric slow waves. (3) No gastric leakage into the abdominal cavity was noted and the dogs were healthy and comfortable. (4) The endoscopically placed electrodes remained for 2 to 3 weeks. The fixation of the electrodes needs to be improved for longer-term uses. GES may be accomplished without surgery by inserting the electrode wire through the abdomen under endoscopy. The study results indicate that the endoscopically placed electrodes are effective for GES and do not result in any adverse events.


Expectations and Experience of Children with Unilateral Cochlear Implantation: A Parental Perspective.
To find out parental expectations regarding outcomes of unilateral cochlear implantation prior to surgery and experience received by them after cochlear implantation and 1 year of regular auditory verbal therapy, with respect to the communication abilities, social skills and participation. Total of 200 parents of hearing impaired children participated in the study. A closed ended questionnaire containing 13 questions were used to collect the data. The participants were instructed to complete all the questions provided based on their expectations and experiences. The descriptive statistics were used to determine the frequency and percentage. Among 200 parents, almost all (95%) of the parents expected to have improvement in all the subscale of communication abilities, social skills and participation. 68.5% of the parents experienced improvement in their child's communication abilities, such as, response to quiet sounds, repetition of words without seeing speaker's face, elimination of use of gestures, easy communication and verbal expression for needs, thoughts and feelings. 76% of the parents experienced improvement in social skills and participations, such as, good relationship with elders, siblings and peers, making friends outside the family, actively participating in the activity done by other children and easily accepted by peers in the classroom. A large number of parents met with their expectations and a small proportion of families were found to be disappointed due to high hopes and unrealistic expectation before implantation, which had adverse effect on the children's performance.


Quantitative analysis of yeast fermentation process using Raman spectroscopy: Comparison of CARS and VCPA for variable selection.
Yeast is one of the most widely used microbial species in the field of microbiology, and it is crucial that rapid and accurate monitoring of its process. Therefore, this study presents a method using Raman spectroscopy for quantitative analysis of yeast fermentation process. First, a ProSP-Micro2000K Raman measuring system used to obtain the Raman spectra of eight batches of yeast samples during fermentation, and the spectra obtained were pretreated using Savitzky-Golay (SG) smoothing filter and standard normal variate (SNV). Then, two variable selection methods, which were competitive adaptive reweighted sampling (CARS) and variable combination population analysis (VCPA), were compared to search the preprocessed Raman spectroscopy characteristic wavenumber. Finally, support vector machine (SVM) was employed to construct a quantitative monitoring model of yeast fermentation process based on variables from the selected characteristic wavenumbers. The results revealed that the VCPA-SVM model showed the best prediction result with 14 selected characteristic wavelength variables. The coefficient of determination (RP2) of the optimal model was 0.979, while the root mean square error of prediction (RMSEP) was 0.108 in the validation set. The overall results demonstrate that the Raman spectroscopy integrated with chemometric approaches could be utilized as a rapid method to monitor the process of yeast cultivations.


From circular strategies to actions: 65 European circular building cases and their decarbonisation potential.
The application of the circular economy (CE) in the building industry is critical for achieving the carbon reduction goals defined in the Paris Agreement and is increasingly promoted through European policies. In recent years, CE strategies have been applied and tested in numerous building projects in practice. However, insights into their application and decarbonisation potential are limited. This study analysed and visualised 65 novel real-world cases of new build, renovation, and demolition projects in Europe compiled from academic and grey literature. Cases were analysed regarding the circular solution applied, level of application in buildings, and decarbonisation potential reported, making this study one of the first comprehensive studies on the application and decarbonisation potential of circular strategies in the building industry in practice. The identified challenges of using LCA for CE assessment in buildings are discussed and methodological approaches for future research are suggested.


Starvation induced cholesterogenesis in hepatic and extra hepatic tissues of climbing Perch, Anabas testudineus (Bloch).
Cholesterol is a structural lipid, which may be differentially utilized or synthesized in response to stress or during insulin deficient states such as starvation. In the present investigation we estimated the levels of cholesterol in Anabas testudineus, which was subjected to brief (15 days) and prolonged fasting (60 days). Tissues such as liver, kidney, brain, accessory respiratory organ, pectoral and lateral line muscle were selected for the study. Cholesterol content was estimated by the Crawford method (1958). Both the starvation regimes showed a significant increase in cholesterol levels in almost all the tissues, but for liver, which strangely showed an insignificant decline during the short-term starvation. This overall upsurge in cholesterol levels observed in all extra hepatic tissues may be attributed to the synthesis of stress hormones such as glucocorticoids, which may promote gluconeogenesis and adrenocorticoids, which may help the animal to combat the stressful condition of starvation. Anabas adapted well to starvation stress and survived all throughout the experimental period.


Use of antihypertensive medication and formation of de novo intracranial aneurysms.
Hypertension is a risk factor for subarachnoid hemorrhage and is also considered a risk factor for saccular intracranial aneurysm (sIA) formation. However, there is little direct evidence that antihypertensive medication will reduce sIA formation. The impact of antihypertensive medication on de novo sIA formation was studied in an angiographically followed cohort of 1419 patients. Patients were identified from our population-based Kuopio Intracranial Aneurysm Database, and data on the purchases of antihypertensive medication were obtained from a national registry. Univariate and multivariate analyses were used to investigate the risk factors. Of the 966 sIA patients who were prescribed with antihypertensive medication, 841 patients used the medication regularly; 20 of them had de novo sIA. One hundred and twenty-five patients used the medication irregularly and 12 of them developed de novo sIAs. Four hundred and fifty-three patients did not use antihypertensive medication even though 27 of them had a diagnosis of hypertension, and 10 of them developed de novo sIAs. In the multivariate analysis antihypertensive medication did not significantly reduce de novo sIA formation (hazard ratio [HR] 1.60, 95% confidence interval [CI] 0.84-3.06). Age at primary diagnosis (HR: 0.95, 95%: CI 0.93-0.98) and smoking history (HR: 5.53, 95% CI: 2.77-11.05) were significant risk factors for de novo sIA formation. Also, irregular usage of antihypertensive medication was a significant risk factor (HR: 3.84, 95% CI: 1.59-9.29) for de novo sIA formation. Antihypertensive agents were not associated with a reduction of de novo sIA formation, but irregular use of antihypertensive agents was associated with an increased risk of de novo sIA formation.


Support for a three-dimensional structure predicting a Cys-Glu-Lys catalytic triad for Pseudomonas aeruginosa amidase comes from site-directed mutagenesis and mutations altering substrate specificity.
The aliphatic amidase from Pseudomonas aeruginosa belongs to the nitrilase superfamily, and Cys(166) is the nucleophile of the catalytic mechanism. A model of amidase was built by comparative modelling using the crystal structure of the worm nitrilase-fragile histidine triad fusion protein (NitFhit; Protein Data Bank accession number 1EMS) as a template. The amidase model predicted a catalytic triad (Cys-Glu-Lys) situated at the bottom of a pocket and identical with the presumptive catalytic triad of NitFhit. Three-dimensional models for other amidases belonging to the nitrilase superfamily also predicted Cys-Glu-Lys catalytic triads. Support for the structure for the P. aeruginosa amidase came from site-direct mutagenesis and from the locations of amino acid residues that altered substrate specificity or binding when mutated.


Proteomic profiling identifies the inorganic pyrophosphatase (PPA1) protein as a potential biomarker of metastasis in laryngeal squamous cell carcinoma.
Relapse and metastasis are the main causes of unfavorable outcome in head and neck cancers. Whereas, understanding of the molecular background of these processes is far from being complete. Therefore, in this study we aimed to identify potential biomarker candidates of relapse and metastasis in laryngeal squamous cell carcinoma (LSCC) by combining the 2D electrophoresis based protein screen and immunohistochemical analysis of candidate proteins. We screened three groups of LSCC cell lines derived from primary tumors, recurrent tumors and metastases and identified seven proteins that differed significantly in relative abundance between the analyzed groups. Among the identified proteins were the heat shock proteins HSP60 and HSP70 that were significantly downregulated both in recurrences- and metastases-derived cell lines but not in primary tumor-derived cell lines. Moreover, we identified significant upregulation of the annexin V, calreticulin and the inorganic pyrophosphatase (PPA1) exclusively in the metastases-derived cell lines. As these upregulated proteins could potentially become novel biomarkers of metastasis, we have compared their abundance in primary tumor LSCC N(0) cases, primary tumor LSCC N(+) cases as well as in LSCC metastases N(+). Our results show an intense increase of cytoplasmic PPA1 abundance in the N(+) (p = 0.000042) compared to the N(0) group. In summary, we show a group of proteins deregulated in recurrences and metastases of LSCC. Moreover, we suggest the PPA1 protein as a potential new biomarker for metastasis in this cancer.


A centrosomal inclusion (striped nebulous body) in pinealocytes of the golden hamster.
Electron microscopy has revealed the presence of a special cytoplasmic body in the centrosomal area of pinealocytes of the golden hamster, Mesocricetus auratus. It consists of branching electron-dense ribbons embedded in a flocculent matrix of moderate electron density, and is tentatively named the 'striped nebulous body' (SNB). The dense ribbon usually appears as a thick band accompanied by a parallel thin one to one side. The SNB is not bounded by a membrane, and is roughly round or kidney-shaped. Closely associated with the SNB are centrioles, microtubular sheaves and striated fibrils, the latter two being centriolar derivatives. The observations suggest that the SNB might be formed by the amalgamation of these microtubular sheaves and striated fibrils. In golden hamsters, pinealocytes often have multiple centrioles and centriolar derivatives. The SNB of adult hamsters is seen in the pinealocytes of both sexes, irrespective of the season of the year and the activity of the pineal gland. The functional significance of this body remains to be studied.


Protective effect and granuloma down-modulation promoted by RP44 antigen a fructose 1,6 bisphosphate aldolase of Schistosoma mansoni.
A Schistosoma mansoni adult worm cDNA expression library was screened using rabbit IgG against PIII, an adult worm protein fraction, already known to possess protective and immunomodulating effects to a challenge infection in mice. A positive cDNA clone was selected and characterized. The cDNA screened encodes a protein (P44) with an ORF of 1089 bp and an amino acid sequence of 363 residues with a predictable molecular weight of 44 kDa. The P44 amino acid sequence exhibits 100% identity to the fructose 1,6 bisphosphate aldolase of S. mansoni, 66% to Homo sapiens and 66% to Mus musculus. The cDNA was cloned into a pGEX-4T-3 vector and expressed in Escherichia coli as a fusion protein (GST/P44). Mice vaccinated with recombinant P44 were able to develop high levels of IgG or IgG1 and displayed low levels of IgG2a isotype. Moreover, immunization of mice with this antigen induced a significant protection of 57% against a challenge infection and significant decrease in hepatic granuloma formation. Our results demonstrate that granuloma modulation can be targeted for pathology elimination through vaccination. This represents an advance in schistosome vaccinology and allows for the development of a therapeutic as well as a prophylactic vaccine.


Photoaffinity labeling and characterization of isolated inositol 1,3,4,5-tetrakisphosphate- and inositol hexakisphosphate-binding proteins.
We have isolated high affinity inositol (1,3,4,5)-tetrakisphosphate (IP4)- and inositol hexakisphosphate (IP6)-binding proteins from detergent-solubilized rat brain membranes using a P1-tethered IP4 derivative linked to an Affi-Gel support. To determine the identity, binding characteristics, and distribution of the individual IP4 recognition sites, we have synthesized an IP4 photoaffinity label probe, 125I-(D,L)-1-O-[N-(4-azidosalicyloxy)-3-aminopropyl-1-phospho]- IP4 (125I-ASA-IP4). Two apparently distinct IP4-binding proteins (IP4BP), isolated with the IP4 affinity column, display high affinity and selectivity for IP4 over inositol trisphosphate (IP3), inositol pentakisphosphate (IP5), and IP6. The first IP4-binding protein (IP4BP1) which has a KD for IP4 of 4 nM, is comprised of a protein at 182 kDa which is specifically photolabeled with high affinity by 125I-ASA-IP4. The second, IP4BP2, has an affinity for IP4 of 1.5 nM and contains proteins at 84 and 174 kDa, both of which are specifically photoaffinity labeled. A putative IP6-binding protein (IP6BP), also isolated with the IP4 affinity column, binds IP6 with a KD of 14 nM and comprises three proteins of 115, 105, and 50 kDa. The 115- and 105-kDa subunits, but not the 50-kDa subunit, specifically incorporate the photolabel. The IP4BP (182, 174, and 84 kDa) and IP6BP (115 and 105 kDa) proteins are specifically photolabeled in the crude membrane, partially purified, and purified fractions. These receptor-binding proteins vary in inositol phosphate specificity and in the effects of pH, Ca2+, and heparin on IP4 photoaffinity labeling. In addition, IP4BP and IP6BP are enriched in the brain but differ in their regional localizations within the brain.


Opsomyoclonus and neuroblastoma. Response to ACTH.
Children with neuroblastoma whose opsomyoclonus recurs or persists after initial surgery should be carefully evaluated for tumor. If no tumor is detectable, therapy with ACTH should be considered in patients whose symptomatology is severe enough to compromise normal development.


Sleep-disordered breathing and effectiveness of cardiac resynchronization therapy in heart failure patients: gender differences?
This study evaluated heart failure (HF) patients who underwent cardiac resynchronization therapy (CRT) and who had device-documented sleep-disordered breathing (SDB). We found gender differences in acute changes in SDB due to CRT impact. SDB typically occurs in HF patients. However, the role of SDB and its response to CRT in HF patients, as well as the relation with gender are currently not fully researched. Among 63 consecutive patients who received CRT with an SDB algorithm, 23 patients documented SDB at one-month cardiac device interrogation and represented our population. We defined a Sleep apnoea Severity SCore(SSSC), and consequently, patients were categorized to have mild, moderate, and severe sleep apnoea syndrome divided into two groups: Group-1: 18 males (78%); Group-2: 5 females (22%). We evaluated the variation of apnoea burden and CRT response based on gender differences. A significantly higher proportion of patients in the male group were non-responders to CRT at 12-months follow-up (p = 0.076) while in the female population 5/5 patients (100%) were responders to CRT at the same follow-up time (p = 0.021). Among Group-2 subjects, we documented a significant linear decrease in SSSC(p > 0,01) while in Group-1 the CRT effect on SSSC was variable. At 12-months follow-up, the difference in SSSC between the two groups was statistically significant (p < 0.001). Our study reports a correlation between CRT response and sleep apnoea burden considering gender differences. In particular, HF-women responders to CRT demonstrate a significant linear decrease in sleep apnoea burden determined through a device algorithm, when compared to a similar male population. Further research is needed to confirm these findings.


Value of immunonutrition in patients undergoing pancreatic resection: a trial sequential meta-analysis.
The benefits of immunonutrition (IM) in patients who underwent pancreatic surgery are unclear. A meta-analysis of randomized clinical trials (RCTs) comparing IM with standard nutrition (SN) in pancreatic surgery was carried out. A random-effects trial sequential meta-analysis was made, reporting Risk Ratio (RR), mean difference (MD), and required information size (RIS). If RIS was reached, false negative (type II error) and positive results (type I error) could be excluded. The endpoints were morbidity, mortality, infectious complication, postoperative pancreatic fistula (POPF) rates, and length of stay (LOS). The meta-analysis includes 6 RCTs and 477 patients. Morbidity (RR 0.77; 0.26 to 2.25), mortality (RR 0.90; 0.76 to 1.07), and POPF rates were similar. The RISs were 17,316, 7,417, and 464,006, suggesting a type II error. Infectious complications were lower in the IM group, with a RR of 0.54 (0.36-0.79; 95 CI). The LOS was shorter in IM (MD -0.3 days; -0.6 to -0.1). For both, the RISs were reached, excluding type I error. The IM can reduce infectious complications and LOS The small differences in mortality, morbidity, and POPF make it impossible to exclude type II error due to large RISs.


Ultrasonographic shear wave elastography of the thyroid in patients with sickle cell anemia.
Although thyroid radiology has been conducted in patients with sickle cell anemia (SCA), to our knowledge, there is no report of thyroid gland assessment using ultrasonographic shear wave elastography (US-SWE). To determine values for ultrasonographic US-SWE of the thyroid in patients with SCA and correlations between thyroid elasticity and biochemical variables used to evaluate thyroid function. Prospective case-control observational study of 36 patients with SCA and 33 healthy volunteer controls. US-SWE measurements of thyroid gland parenchyma and biochemical parameters of the participants were obtained and compared, and the diagnostic accuracy of elasticity was determined. The thyroid volume was smaller in patients with SCA than that in controls (P = 0.001). Compared with the controls, the patients with SCA had significantly lower serum levels of free triiodothyronine (fT3) (P = 0.004) and thyroglobulin (Tg) (P = 0.001) and significantly higher levels of thyroid-stimulating hormone (P = 0.028). Thyroid stiffness was significantly higher in the left lobe (LL) of the patients with SCA than in the controls (P = 0.003). In the patients with SCA, we found a significant correlation between right lobe (RL) and LL stiffness and serum levels of Tg (RL [r = -0.439] and LL [r = -0.484]; P = 0.021) and fT3 (RL [r = -0.463] and LL [r = -0.386]; P = 0.012). Receiver operating characteristic (ROC) curve analysis of thyroid elasticity that represented a diagnosis of SCA found a cutoff of >7.31 kPa, a sensitivity of 52.0%, and a specificity of 72.0% for the RL (P = 0.316, area under the curve [AUC] 0.570), and a cutoff of >8.06 kPa, a sensitivity of 58.0%, and a specificity of 84.0% for the LL (P = 0.011, AUC 0.680). US-SWE can be used to follow up thyroid changes in patients with SCA.


Mass spectrometry-based proteomics as an emerging tool in clinical laboratories.
Mass spectrometry (MS)-based proteomics have been increasingly implemented in various disciplines of laboratory medicine to identify and quantify biomolecules in a variety of biological specimens. MS-based proteomics is continuously expanding and widely applied in biomarker discovery for early detection, prognosis and markers for treatment response prediction and monitoring. Furthermore, making these advanced tests more accessible and affordable will have the greatest healthcare benefit.This review article highlights the new paradigms MS-based clinical proteomics has created in microbiology laboratories, cancer research and diagnosis of metabolic disorders. The technique is preferred over conventional methods in disease detection and therapy monitoring for its combined advantages in multiplexing capacity, remarkable analytical specificity and sensitivity and low turnaround time.Despite the achievements in the development and adoption of a number of MS-based clinical proteomics practices, more are expected to undergo transition from bench to bedside in the near future. The review provides insights from early trials and recent progresses (mainly covering literature from the NCBI database) in the application of proteomics in clinical laboratories.


Factors associated with the undertriage of patients with abdominal pain in an emergency room.
The triage process lasts for a very short time, which can result in over-triage and under-triage. Studies have explored factors related to under-triage among trauma patients. In Korea, the clinical characteristics and severity of cases of under-triaged patients have been investigated. However, there is limited research on the under-triage of patients experiencing abdominal pain. Therefore, this study aimed to determine the under-triage rate of emergency department (ED) patients with abdominal pain, as well as the factors associated with their under-triage. The participants of this retrospective cohort study were 3,030 adult patients at a single tertiary hospital in Korea, who were brought to the ED for abdominal pain as the chief complaint. Participants' general characteristics, pain-related information, and environmental information were obtained from their electronic medical records. The under-triage rate of ED patients with abdominal pain was 31.0%. Factors related to the under-triage of these patients were sex, age, visit route, time from the onset of the pain to the visit, location of pain, and intensity of pain. These findings provide a foundation for the understanding and mitigation of under-triage in EDs through the identification of factors associated with under-triage in patients with abdominal pain.


Serum C3 and C4 levels and complement-dependent antibody-mediated cytotoxic activity of islet cell surface antibody in type 1 (insulin-dependent) diabetic children.
The role of complement in the pathogenesis of diabetes was studied in 31 Type 1 (insulin-dependent) diabetic children by assaying serum islet cell surface antibody, C3, C4 and serum complement-dependent antibody-mediated cytotoxicity. Nine of 21 islet cell surface antibody-positive children were within 5 months of disease onset and showed significantly lower serum C3 and C4 levels than either 1 year later or the remainder of the islet cell surface antibody-positive children at 6-12 months after disease onset. The overall trend of all islet cell surface antibody-positive diabetic children within 1 year of disease onset was toward increased serum C3 and C4 levels as the disease progressed. Serum C4 concentration and complement-dependent antibody-mediated cytotoxicity which showed an initial negative correlation were uncorrelated 1 year later. Four children who were initially strongly islet cell surface antibody-positive but negative 1 year later also exhibited significantly higher (p less than 0.05) mean serum C4 levels after 1 year. There was a significant decrease in complement-dependent antibody-mediated cytotoxicity when sera from the diabetic children were treated with either ethylene glycol tetra-acetic acid or ethylene diamine tetra-acetic acid. These data strongly suggest that complement-dependent antibody-mediated cytotoxicity induced by the classical complement pathway involving an islet cell surface antibody may play an important role in the pathogenesis of Type 1 diabetes.


Identification of critical amino acid residues for human iNOS functional activity.
Nitric oxide (NO) is a short-lived signaling molecule that mediates a variety of biological functions, including vascular homeostasis, neurotransmission, antimicrobial defense and antitumor activities. Three known NOS isoforms (eNOS, nNOS and iNOS) have been cloned and sequenced. Here, we show that upon expression in Escherichia coli using a novel expression vector, an iNOS sequence containing three mutations (A805D, F831S and L832P) within the iNOS reductase domain produced very little functionally active iNOS protein compared to the wild type (wt) iNOS. Each of these point mutations also was individually constructed into the wt iNOS sequence. The activity of the iNOS protein containing the A805D mutation was comparable to wt, while a drastic reduction in iNOS activity was observed for the F831S and L832P mutants. A comparison of the molecular models of the reductase domain of the wt and mutant iNOS revealed a reduced core packing density for the F831S and L832P mutations compared to wt. In addition, the modeling also suggests altered hydrogen bonding, van der Waals and hydrophobic interactions of these mutants.


Avelumab versus standard second line treatment chemotherapy in metastatic colorectal cancer patients with microsatellite instability: The SAMCO-PRODIGE 54 randomised phase II trial.
Immune checkpoint inhibitors have failed in treating metastatic colorectal cancer (mCRC) patients except those with dMMR/MSI tumors. However, until very recently we had only non-comparative promising data in this population with anti-programmed cell death 1/ programmed cell death ligand 1 (PD1/PD-L1) antibodies alone or combined with anti- cytotoxic T-lymphocyte-associated protein 4 (CTLA4) antibodies. This comparative phase II trial (NCT03186326), conducted in more than 100 centers in France, will include dMMR/MSI mCRC patients with progression after a first-line treatment with chemotherapy ± targeted therapies, to evaluate efficacy and safety of the anti-PDL1 Avelumab versus a standard second-line treatment. Main inclusion criteria were patients aged 18 to 75 years, ECOG performance status ≤2, dMMR/MSI mCRC and failure of a standard first-line regimen. Patient will be randomised to receive Avelumab 10 mg/kg versus standard second-line doublet chemotherapy plus a targeted agent according to tumor RAS status. Patients will be followed for 4 years. A gain of 5 months in median PFS is expected in favour of the Avelumab arm (12 vs 7 months; HR=0.58). Secondary endpoints include objective response rate, overall survival, quality of life and toxicity. In addition, circulating tumour DNA and microbiota will be explored to test their potential prognostic and predictive values. The study was opened in March 2018.


Purification and properties of the dnaJ replication protein of Escherichia coli.
The Escherichia coli dnaJ gene was originally discovered because mutations in it blocked bacteriophage lambda DNA replication. Some of these mutations were subsequently shown to interfere with bacterial growth at high temperature, suggesting that dnaJ is an essential protein for the host as well. The first step in purifying the dnaJ protein was to overproduce it at least 50-fold by subcloning its gene into the pMOB45 runaway plasmid. The second step was the development of an in vitro system to assay for its activity. A Fraction II extract from dnaJ259 mutant bacteria was shown to be unable to replicate lambda dv DNA unless supplemented with an exogenous source of wild-type dnaJ protein. Using this complementation assay we purified the dnaJ protein to homogeneity from the membrane fraction of an overproducing strain of bacteria. The purified dnaJ protein was shown to be a basic (pI 8.5), yet hydrophobic, protein of Mr 37,000 and 76,000 under denaturing and native conditions, respectively, and to exhibit affinity for both single- and double-stranded DNA. Using a partially purified lambda dv replication system dependent on the presence of the lambda O and P initiator proteins and at least the host dnaB, dnaG, dnaJ, dnaK, single-stranded DNA-binding protein, gyrase, RNA polymerase holoenzyme, and DNA polymerase III holoenzyme, we have shown that the dnaJ protein is required at a very early step in the DNA replication process.


Modeling of activity of cyclic urea HIV-1 protease inhibitors using regularized-artificial neural networks.
Artificial neural networks (ANNs) were used to model both inhibition of HIV-1 protease (K(i)) and inhibition of HIV replication (IC90) for 55 cyclic urea derivatives using constitutional and 2D descriptors. As a preliminary step, linear dependences were established by multiple linear regression (MLR) approaches, selecting the relevant descriptors by genetic algorithm (GA) feature selection. For ANN models non-linear GA feature selection was also applied. Non-linear modeling of K(i) overcame the results of the linear one using four properties, keeping in mind standard Pearson R correlation coefficients (0.931 vs. 0.862) and leave one out (LOO) cross-validation analysis (Q(LOO)2 = 0.703 vs. 0.510). On the other hand, IC90 modeling was insoluble by a linear approach: no predictive model was achieved; however, a non-linear relation was encountered according to statistic results (R = 0.891; Q(LOO)2 = 0.568). The best non-linear models suggested the influence of the presence of nitrogen atoms and the molecular volume distribution in the inhibitor structures on the HIV-1 protease inhibition as well as that the inhibition of HIV replication was dependent on the occurrence of five-member rings. Finally, inhibitors were well distributed regarding its activity levels in a Kohonen self-organizing map built using the input variables of the best non-linear models.


Corrigendum: The possible correlation between serum GRB2 levels and carotid atherosclerosis in patients with type 2 diabetes mellitus.
[This corrects the article DOI: 10.3389/fendo.2022.963191.].


Endoplasmic reticulum stress regulates cell injury in lipopolysaccharide-induced nerve cells.
Sepsis-associated encephalopathy (SAE) is a common complication of sepsis, and excessive endoplasmic reticulum (ER) stress is closely correlated with the cell injury caused by sepsis. This study aimed to analyze the possible role of ER stress in SAE cell models. PC12 and MES23.5 cells were treated with increasing concentrations of lipopolysaccharides (LPS). The Cell Counting Kit-8 assay was used to detect cell viability and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to assess cell apoptosis. In addition, the protein expression levels of ER stress markers [GRP78, CHOP, inositol-requiring enzyme 1 (IRE1), and PKR-like ER kinase (PERK)] and apoptosis-related proteins (Bax, Bcl-2, caspase-3, and cleaved caspase-3) were analyzed using western blotting. LPS treatment activated ER stress markers in both the PC12 and MES23.5 cells. The overexpression of GRP78 significantly reduced cell viability and enhanced cell apoptosis in a time-dependent manner. An ER stress inhibitor, 4-PBA, significantly enhanced cell viability and inhibited the cell apoptosis induced by LPS. Therefore, an enhanced unfolded protein response (UPR) and UPR suppression may regulate cell apoptosis. UPR was shown to be involved in regulating LPS-induced neuron injury. UPR could be a potential therapeutic target in SAE.


[Maxillary sinus lifting, bone graft and simultaneous placement of implants: reports of 9 cases].
To study the effect of maxillary sinus floor lifting by bone graft for immediate implantation. 10 maxillary sinus underwent sinus floor bone graft and 12 simultaneously implants placement. There were no implants loose or lost; X-ray examination showed well osseointegration and no maxillary sinustitus. Sinus floors were lifted 5-10mm, with a mean value of 7.5mm. All the implants placement had been repaired in 6 to 7 months postoperatively. Maxillary sinus floor bone graft with simultaneous placement of implant is predictable.


Pregnancy in a combined liver and kidney transplant recipient with type 1 primary hyperoxaluria.
Little is known about pregnancy outcomes in multiple organ transplant recipients. We present a case of pregnancy in a patient after liver and kidney transplantation for the genetic disorder of type 1 primary hyperoxaluria. A 14-year-old Hispanic teenager presented with end-stage renal disease and had a kidney biopsy that revealed hyperoxaluria. A liver biopsy revealed type 1 primary hyperoxaluria. After a year of dialysis and worsening renal status, she underwent a combined orthotopic liver and kidney transplant. The patient subsequently became pregnant, but she required no antihypertensive therapy throughout the prenatal or postpartum period and showed no signs of renal or liver graft rejection. She delivered by cesarean at 38 weeks. Combined liver and kidney transplant recipients who become pregnant can have a successful outcome.


Nanocomposites of epoxy with one-dimensional fibrous poly(ε-caprolactam) nanocrystals via crystallization-driven self-assembly.
In this contribution, we reported the preparation of nanocomposites of epoxy with one-dimensional (1D) poly(ε-caprolactam) (PA6) nanocrystals via crystallization-driven self-assembly. First, a novel diblock copolymer composed of poly(ethylene oxide) and poly(ε-caprolactam) subchains (PEO-b-PA6) was synthesized via the anionic ring-opening polymerization (ROP) of ε-caprolactam. It was found that the PEO-b-PA6 diblocks displayed crystallization-driven self-assembly (CDSA) behavior in the selective solvents (e.g., water); the 1D fibrous nanocrystals of PA6 were obtained via CDSA approach. Such a CDSA behavior was utilized to generate 1D fibrous PA6 nanocrystals into epoxy thermosets. In this case, the epoxy precursors were used as the solvent selective for PEO subchain of the diblock. Notably, the 1D fibrous PA6 nanocrystals were generated in the epoxy precursors via the CDSA approach. Upon curing, the nanocomposites (i.e., the nanostructured thermosets containing PA6 nanocrystals) were successfully obtained. It was found that epoxy thermoset was significantly nanoreinforced by the PA6 nanocrystals. In the meantime, the fracture toughness of the materials was significantly improved with the incorporation of 1D fibrous PA6 nanocrystals.


Heterotopic ossification in central nervous system-injured patients following closed nailing of femoral fractures.
Heterotopic ossification at the site of insertion of an intramedullary nail was observed in five central nervous system-injured patients with femoral fractures. Three of these patients experienced a reduction in the range of motion of the ipsilateral hip joint, which in two improved with physical therapy. Patients with central nervous system injury who have closed interlocking intramedullary nail fixation may be at increased risk of heterotopic ossification at the surgical site.


Effects of dimethylarsinic and dimethylarsinous acid on evoked synaptic potentials in hippocampal slices of young and adult rats.
In this study, the effects of pentavalent dimethylarsinic acid ((CH(3))(2)AsO(OH); DMA(V)) and trivalent dimethylarsinous acid ((CH(3))(2)As(OH); DMA(III)) on synaptic transmission generated by the excitatory Schaffer collateral-CA1 synapse were tested in hippocampal slices of young (14-21 day-old) and adult (2-4 month-old) rats. Both compounds were applied in concentrations of 1 to 100 micromol/l. DMA(V) had no effect on the amplitudes of evoked fEPSPs or the induction of LTP recorded from the CA1 dendritic region either in adult or in young rats. However, application of DMA(III) significantly reduced the amplitudes of evoked fEPSPs in a concentration-dependent manner with a total depression following application of 100 micromol/l DMA(III) in adult and 10 micromol/l DMA(III) in young rats. Moreover, DMA(III) significantly affected the LTP-induction. Application of 10 micromol/l DMA(III) resulted in a complete failure of the postsynaptic potentiation of the fEPSP amplitudes in slices taken both from adult and young rats. The depressant effect was not reversible after a 30-min washout of the DMA(III). In slices of young rats, the depressant effects of DMA(III) were more pronounced than in those taken from adult ones. Compared to the (absent) effect of DMA(V) on synaptic transmission, the trivalent compound possesses a considerably higher neurotoxic potential.


Rational design of inorganic dielectric materials with expected permittivity.
Techniques for rapid design of dielectric materials with appropriate permittivity for many important technological applications are urgently needed. It is found that functional structure blocks (FSBs) are helpful in rational design of inorganic dielectrics with expected permittivity. To achieve this, coordination polyhedra are parameterized as FSBs and a simple empirical model to evaluate permittivity based on these FSB parameters is proposed. Using this model, a wide range of examples including ferroelectric, high/low permittivity materials are discussed, resulting in several candidate materials for experimental follow-up.


The Hybrid Aesthetic Functional (HAF) Appliance: A Less Visible Proposal for Functional Orthodontics.
In modern orthodontics, aesthetics appear to have a decisive influence on orthodontic appliance preferences and acceptability. This paper reports the early application of a newly emerged functional device with enhanced aesthetics in a Class II treatment. Patient perspectives and technical considerations are discussed along with recommendations for further design development. It can be assumed that the use of thermoplastic material-based appliances may meet both the therapeutic and aesthetic demands of young age groups.


Innovative endovascular defibrillator lead use in superior vena cava obstruction.
We describe an unusual case of severe heart failure (HF) and rapid atrial fibrillation (AF) improved through ablation and pacemaker implant despite superior vena cava obstruction (SVCO). SVCO precluded upper body venous access to the heart for procedural rate control. Both AV Junctional ablation and permanent endovascular lead placement were achieved through the inferior vena cava (IVC). Clinical improvement from NYHA Class IV to Class II HF was observed with effective nonpharmacologic ventricular rate control. HF patients with rapid AF and SVCO can achieve ventricular rate control through lower body venous access to the heart utilizing 100-cm endovascular defibrillator rate sensing leads.


Antidiabetic effect of a new peptide from Squalus mitsukurii liver (S-8300) in alloxan-diabetes.
1. The purpose of the present study was to evaluate the antidiabetic effect of S-8300 in alloxan diabetic mice. 2. Diabetes was induced by single intravenous injection of alloxan (60 mg/kg bodyweight). 3. The effects of S-8300 on diabetic mice were investigated by observing changes in the glycometabolic index (fasting plasma glucose, glycosylated haemoglobin), the lipometabolic index (triglyceride, cholesterol, free fatty acids), anti-oxidant index (superoxide dismutase, malondialdehyde) and in the degree of injury of beta-cells in the pancreatic islets. 4. A significant decrease in fasting plasma glucose, glycosylated haemoglobin, triglycerides, cholesterol, free fatty acids in the plasma and malondialdehyde in the tissues, as well as a significant increase in the activity of superoxide dismutase, was observed in diabetic mice treated with 10, 3 and 1 mg/kg S-8300. 5. Treatment with S-8300 also attenuated the degree of injury of beta-cells. 6. A comparison was made between the action of S-8300 and 6 U/kg insulin. The effects of S-8300 were similar to those of insulin.


Probing Conformational Dynamics of Antibodies with Geometric Simulations.
This chapter describes the application of constrained geometric simulations for prediction of antibody structural dynamics. We utilize constrained geometric simulations method FRODAN, which is a low computational complexity alternative to molecular dynamics (MD) simulations that can rapidly explore flexible motions in protein structures. FRODAN is highly suited for conformational dynamics analysis of large proteins, complexes, intrinsically disordered proteins, and dynamics that occurs on longer biologically relevant time scales that are normally inaccessible to classical MD simulations. This approach predicts protein dynamics at an all-atom scale while retaining realistic covalent bonding, maintaining dihedral angles in energetically good conformations while avoiding steric clashes in addition to performing other geometric and stereochemical criteria checks. In this chapter, we apply FRODAN to showcase its applicability for probing functionally relevant dynamics of IgG2a, including large-amplitude domain-domain motions and motions of complementarity determining region (CDR) loops. As was suggested in previous experimental studies, our simulations show that antibodies can explore a large range of conformational space.


SLO, SLO, quick, quick, slow: calcium-activated potassium channels as regulators of Caenorhabditis elegans behaviour and targets for anthelmintics.
Large-conductance calcium and voltage-activated potassium channels, termed SLO-1 (or BK), are pivotal players in the regulation of cell excitability across the animal phyla. Furthermore, emerging evidence indicates that these channels are key mediators of a number of neuroactive drugs, including the most recent new anthelmintic, the cyclo-octadepsipeptide emodepside. Detailed reviews of the structure, function and pharmacology of BK channels have recently been provided (Salkoff et al. in Nat Rev Neurosci 7:921-931, 2006; Ghatta et al. in Pharmacol Ther 110:103-116, 2006) and therefore these aspects will only briefly be covered here. The purpose of this review is to discuss how SLO-1 channels might function as regulators of neural transmission and network activity. In particular, we focus on the role of SLO-1 in the regulation of Caenorhabditis elegans behaviour and highlight the role of this channel as an effector for pleiotropic actions of neuroactive drugs, including emodepside. On the premise that C. elegans is a 'model nematode' with respect to many aspects of neural function, the intention is that this might inform a broader understanding of the role of these channels in the nematodes and their potential as novel anthelmintic targets.


Adults attending private physiotherapy practices seek diagnosis, pain relief, improved function, education and prevention: a survey.
How important are different aspects of physiotherapy care to patients presenting to a primary care physiotherapist? Are patient factors (eg, age and gender) associated with how important different aspects of physiotherapy care are to individual patients? A cross-sectional survey with consecutive recruitment. A total of 500 adults aged≥18years who presented to a primary care physiotherapist. Participants were recruited from 10 private practices within the Sydney metropolitan area. Participants completed a survey assessing how important five aspects of physiotherapy care were in their initial decision to present to a primary care physiotherapist. These aspects were: diagnosis; information and education; treatment for pain relief; treatment to improve function; and prevention. The survey also collected characteristics of the patients and information about their presentation to the physiotherapist, to assess whether these factors were associated with the aspects of physiotherapy care that they considered most important. A total of 500 surveys were completed, with a response rate of 94%. All five aspects of physiotherapy care were considered either 'quite important' or 'extremely important' by most participants (diagnosis 65%; information and education 68%; pain relief 89%; improved function 93%; prevention 90%). Patient factors were associated with the participants' ratings of importance. Female participants and those with spinal pain more commonly rated pain relief as highly important. Participants with lower educational levels were more likely to rate diagnosis and information and education as important. This study demonstrated that most patients presenting to primary care physiotherapists value all aspects of physiotherapy care and do not simply want treatment for pain. Patient characteristics were associated with what individual patients considered the most important reason for presenting to a private primary care physiotherapist. [McRae M, Hancock MJ (2017) Adults attending private physiotherapy practices seek diagnosis, pain relief, improved function, education and prevention: a survey. Journal of Physiotherapy 63: 250-256].


LncRNA PTCSC3 and lncRNA HULC Negatively Affect Each Other to Regulate Cancer Cell Invasion and Migration in Gastric Cancer [Retraction].
[This retracts the article DOI: 10.2147/CMAR.S254944.].


Quality of residential facilities in Italy: satisfaction and quality of life of residents with schizophrenia spectrum disorders.
Recovery and human rights promotion for people with Schizophrenia Spectrum Disorders (SSDs) is fundamental to provide good care in Residential Facilities (RFs). However, there is a concern about rehabilitation ethos in RFs. This study aimed to investigate the care quality of Italian RFs, the quality of life (QoL) and care experience of residents with SSD. Fourty-eight RFs were assessed using a quality assessment tool (QuIRC-SA) and 161 residents with SSD were enrolled. Seventeen RFs provided high intensity rehabilitation (SRP1), 15 medium intensity (SRP2), and 16 medium-low level support (SRP3). Staff-rated tools measured psychiatric symptoms and psychosocial functioning; user-rated tools assessed QoL and satisfaction with services. RFs comparisons were made using ANOVA and Chi-squared. Over two-thirds patients (41.5 y.o., SD 9.7) were male. Seventy-six were recruited from SRP1 services, 48 from SRP2, and 27 from SRP3. The lowest QuIRC-SA scoring was Recovery Based Practice (45.8%), and the highest was promotion of Human Rights (58.4%). SRP2 had the lowest QuIRC-SA ratings and SRP3 the highest. Residents had similar psychopathology (p = 0.140) and functioning (p = 0.537). SRP3 residents were more employed (18.9%) than SRP1 (7.9%) or SRP2 (2.2%) ones, and had less severe negative symptoms (p = 0.016) and better QoL (p = 0.020) than SRP2 residents. There were no differences in the RF therapeutic milieu and their satisfaction with care. Residents of the lowest supported RFs in Italy had less severe negative symptoms, better QoL and more employment than others. The lowest ratings for Recovery Based Practice across all RFs suggest more work is needed to improve recovery.


Postnatal development of the endothelial system of the rat cerebellum using immunohistochemical techniques.
The development of the endothelial system of the rat cerebellum was studied by immunohistochemical techniques with two antibodies specific of two membrane antigens characteristic of 'mature' endothelial cells. It appears that the maturation of endothelial cells is very late in the rat cerebellum. This absence of a fully endothelial barrier in cerebella of young rats could explain the extreme sensitivity of this part of the central nervous system to various agents.


The impacts of anthropogenic factors on the environment in Nigeria.
Generally speaking, there has been a consensus on the primary drivers of anthropogenic induced environmental degradation. However, little progress has been made in determining the magnitude of the impacts, particularly in developing countries. This creates a lacuna that needs to be filled up. The purpose of this study therefore is to ascertain the degree of anthropogenic induced environmental impacts in Nigeria. To achieve the aim, fossil fuel consumption was used as a surrogate for carbon dioxide emissions while the magnitude of the impacts was determined by regression statistics and the STIRPAT model. The results show that only three variables, namely population, affluence and urbanization, were statistically significant and that the regression model accounts for 60% of the variation in the environmental impacts. However, population and affluence, which have ecological elasticities of 1.699 and 2.709, respectively, are the most important anthropogenic drivers of environmental impacts in Nigeria while urbanization, with an elasticity of -0.570, reduces the effect of the impacts. This implies that modernization brings about a reduction in environmental impacts. The paper therefore makes a significant contribution to knowledge by successfully testing the STIRPAT model in this part of the world and by being the first application of the model at political units below the regional or nation states.


Comparative permeation studies for delta-aminolevulinic acid and its n-butylester through stratum corneum and artificial skin constructs.
The improvement of the permeation properties through excised human stratum corneum and artificial skin constructs (ASC) of delta-aminolevulinic-n-butylester (ABE) compared with delta-aminolevulinic acid (ALA) was investigated. For this purpose the permeated amounts of each substance were determined depending on time in a Franz diffusion cell experiment with stratum corneum and ASC, respectively. Furthermore the barrier properties of ASC were compared with those of stratum corneum. Detection of both substances was performed by high-performance liquid chromatography (HPLC) analysis. For the determination of ABE a new HPLC method was developed. ABE could be determined with the new HPLC method with sufficient sensitivity (detection limit: 0.1 microg/ml) after derivatisation with o-phthalaldehyde (OPA). Stratum corneum and ASC were more permeable for ABE than for ALA. The permeation coefficient P of ABE through stratum corneum was nearly ten-fold higher than that of ALA. Using ASC as permeation barrier the permeation coefficient of ABE was about 22-fold higher than that of ALA. ABE and ALA permeated 142-fold and 64-fold, respectively, faster through ASC than through stratum corneum.


Laparoscopic adjustable gastric banding: an attractive option.
Bariatric surgery is the only effective treatment producing sustained weight loss and reduction in comorbidities in the morbidly obese. Laparoscopic adjustable gastric banding (LAGB) has evolved considerably in techniques of insertion and band management since the initial descriptions in the early 1990s. Major advantages of LAGB include lower perioperative morbidity and mortality, adjust-ability, and reversibility. Although weight loss occurs more slowly than after gastric bypass, end results are comparable.


Mobilization of technetium from reduced sediments under seawater inundation and intrusion scenarios.
Predicted sea level rise would increase the vulnerability of low lying coastal legacy nuclear sites to inundation and intrusion with oxygenated seawater. This could have a significant impact on the mobility of redox-sensitive radionuclides such as Tc. Here, batch and column experiments were used to simulate and investigate the effect of these processes on the mobilization of Tc from sediments under a range of geochemically reduced conditions. Batch experiments showed that only a small proportion of Tc was rapidly (within 5 days) released from the sediments into seawater and groundwater. The subsequent Tc release was slowest and ultimately limited to the greatest extent (17%) in initially Fe-reducing sediments, when they were reoxidized in seawater. Thus, the cycling of iron and the impact of the water chemistry on iron mineralogy were important for hindering Tc release. Column experiments showed that iron minerals were less effective at retarding Tc release under flow-through conditions. Kinetically controlled and solubility limited Fe dissolution led to ongoing Tc release from the sediments; i.e. the retarding effect of iron phases was temporary, and significantly more Tc was mobilized (79-93%) compared with the batch experiments (17-45%). These results demonstrate the potential for Tc(IV) to be oxidized and mobilized from sediments at coastal nuclear sites resulting from predicted intrusion and inundation with oxic seawater.


Search for a correlation between familial allergy to cocksfoot pollen and HLA antigens.
Twelve families comprising 62 individuals, 31 allergic to grasses, were examined. No significant correlation between pollinosis and the HLA system was observed. However, there was a close correlation between cocksfoot skin tests and the RAST (p less than 10(-6)).


Deficiency in Melanocortin 1 Receptor Signaling Predisposes to Vascular Endothelial Dysfunction and Increased Arterial Stiffness in Mice and Humans.
The melanocortin 1 receptor (MC1-R) is expressed by vascular endothelial cells and shown to enhance nitric oxide (NO) availability and vasodilator function on pharmacological stimulation. However, the physiological role of MC1-R in the endothelium and its contribution to vascular homeostasis remain unresolved. We investigated whether a lack of functional MC1-R signaling carries a phenotype with predisposition to vascular abnormalities. Recessive yellow mice (MC1R(e/e)), deficient in MC1-R signaling, and their wild-type littermates were studied for morphology and functional characteristics of the aorta. MC1R(e/e) mice showed increased collagen deposition and arterial stiffness accompanied by an elevation in pulse pressure. Contractile capacity and NO-dependent vasodilatation were impaired in the aorta of MC1R(e/e) mice supported by findings of decreased NO availability. These mice also displayed elevated levels of systemic and local cytokines. Exposing the mice to high-sodium diet or acute endotoxemia revealed increased susceptibility to inflammation-driven vascular dysfunction. Finally, we investigated whether a similar phenotype can be found in healthy human subjects carrying variant MC1-R alleles known to attenuate receptor function. In a longitudinal analysis of 2001 subjects with genotype and ultrasound data (The Cardiovascular Risk in Young Finns Study), weak MC1-R function was associated with lower flow-mediated dilatation response of the brachial artery and increased carotid artery stiffness. The present study demonstrates that deficiency in MC1-R signaling is associated with increased arterial stiffness and impairment in endothelium-dependent vasodilatation, suggesting a physiological role for MC1-R in the regulation of arterial tone.


Peanut and Amaranthus leucocarpus lectins discriminate between memory and naive/quiescent porcine lymphocytes.
Lectins are relevant tools to isolate and characterize different cellular sub-populations. In this work, we used the lectins Arachis hypogaea (Peanut agglutinin, PNA) and Amaranthus leucocarpus (ALL), specific for Galss1, 3GalNAc, to characterize naive and memory lymphocytes from pigs, experimentally infected with the porcine rubulavirus (RvP). Our results showed that both lectins recognized preferentially lymphocytes with the CD4(+)CD8(+) phenotype (P<0.05). The phenotypic analysis of the cells recognized by these lectins indicated that PNA(+) lymphocytes showed higher rate of the CD29 antigen (PNA(+)CD29(high)) than ALL(+) (ALL(+)CD29(low)). The number of PNA(+)CD29(high) lymphocytes increased after 8 weeks of experimental infection with RvP, and most of the ALL(+)CD29(low) cells became CD29(middle). PNA(+) lymphocytes isolated from infected pigs proliferated after stimulation with the RvP, whereas ALL(+) cells did not. In vitro assays indicated that the ALL(+) cells from previously infected pigs diminished from 7.5 +/- 2 to 0.5 +/- 0.3% after RvP stimulation; whereas PNA(+) cells increased from 4 +/- 1 to 42 +/- 2%, whereas no modification in ALL(+) or PNA(+) cellular population was identified in lymphocytes from naive animals after RvP stimulation. Our results suggest that the cellular distribution/organization of the O-glycosydically linked glycans on lymphocytes may correlate with biological functions, and that PNA could be a tool to isolate specifically porcine memory T cell subsets, whereas ALL could be useful to isolate naive/quiescent T lymphocytes.


Investigation on the relationship between cannabinoid CB1 and opioid receptors in gastrointestinal motility in mice.
1. This study investigated whether (a) cannabinoid CB(1) receptor knockout (CB(1)(-/-)) mice displayed altered gastrointestinal transit and (b) cannabinoid CB(1) and opioid receptors functionally interact in the regulation of gastrointestinal transit. 2. Gastrointestinal transit was assessed by the Whole Gastrointestinal Transit, measuring the excretion time of an intragastrically administered marker (whole intestine), and the Upper Gastrointestinal Transit, measuring the distance covered by the marker in the small intestine. 3. CB(1)(-/-) and homozygous CB(1)(+/+) (CB(1)(+/+)) mice did not differ in both whole gut and small intestine transit. CB(1)(-/-) and CB(1)(+/+) mice were equally responsive to the inhibitory effect of morphine (10 mg kg(-1)) and loperamide (3 mg kg(-1)) on whole gut transit.4. Additionally, in CD1 mice the cannabinoid CB(1) receptor antagonist, rimonabant (0-0.5 mg kg(-1)), failed to block the inhibitory effect of morphine (0-1.25 mg kg(-1)) and loperamide (0-0.5 mg kg(-1)) on transit in small and whole intestine. Similarly, the opioid receptor antagonists, naloxone (0-1 mg kg(-1)) and naltrexone (0-10 mg kg(-1)), failed to block the inhibitory effect of the cannabinoid WIN 55,212-2 (0-3 mg kg(-1)) on transit in small and whole intestine.5. These results suggest that (a) compensatory mechanisms likely developed in CB(1)(-/-) mice to overcome the lack of inhibitory function of endocannabinoid system; (b) cannabinoid and opioid receptor systems did not interact in regulating gastrointestinal transit in mice.


Behavioral and electrophysiological consequences of deafferentation following chronic constriction of the infraorbital nerve in adult rats.
Deafferentation of the hind paw following sciatic nerve injury results in behavioral changes, such as autotomy, suggestive of persistent, spontaneous pain. The effects of deafferentation involving trigeminal nerves have, however, received less attention. Here, alterations in trigeminal ganglion neuronal activity and mechanically evoked and spontaneous behavior were studied in adult rats after a chronic constriction injury of the infraorbital nerve (ION). Compared to sham-operated rats, most rats with ION damage were unresponsive to mechanical stimulation of the mystacial vibrissae up to 56 days after surgery. Increased facial grooming was observed only in rats with chronic ION constriction 10 days after surgery. Free-ranging behavior was similar to that of sham-injury animals. In contrast, increases in the number of spontaneously active trigeminal ganglion neurones were observed in those rats with ION injuries at both 3 and 56 days. These data suggest that chronic constrictive injuries of the ION resulting in prolonged loss of low-threshold input from the periphery lead to only transient behavioral changes, despite the presence of spontaneous activity in trigeminal sensory neurones.