Potential role of activated platelets in homing of human endothelial progenitor cells to subendothelial matrix.
Endothelial progenitor cells (EPCs) mobilize from the bone marrow in response to tissue injury and participate in vascular repair. However, there is limited data about the homing mechanisms of EPCs to vascular injury sites. Recently animal experiments indicated that platelets play a role in recruitment of EPCs to injury sites. However, data on the possible interaction between platelets and EPCs within the human system are limited. We, therefore, examined in-vitro human platelet-EPC interaction under static and flow conditions. Human EPCs were isolated from donated buffy coats by magnetic microbeads and flow cytometry cell sorting using CD133 and VEGFR-2, respectively, as markers. Platelets were tested in the form of washed platelets, platelet rich plasma or whole blood. EPCs formed heterotypic aggregates with resting platelets under static conditions, an interaction that was greatly enhanced when platelets were activated by collagen, ADP or thrombin-activation peptide. The platelet-EPC interaction was inhibited by antibodies to P-selectin or P-selectin glycoprotein ligand-1 (PSGL-1), but not by antibodies to glycoproteins Ib-IX-V or IIb/IIIa. When perfused over activated platelets under shear stress of 2.5 dyn/cm(2), EPCs tethered to platelayers and either adhered immediately or rolled a short distance before adhering. In addition, platelets promoted the colonization of adherent EPCs in culture conditions. Consistent with recent animal studies, these findings demonstrate that human EPCs interact in vitro with activated platelets under static and flow conditions, mediated through P-selectin-PSGL-1 interaction. This interaction may be a central mechanism for homing of EPCs to vascular injury sites.


Comparison of Hexabrix 320 and Conray 420 for left ventriculography in patients with coronary artery disease.
We compared Hexabrix 320 (580 mOsm kg-1) with Conray 420 (2500 mOsm kg-1) for left ventriculography using a prospective randomised double-blind protocol. One hundred consecutive patients with suspected coronary disease were assigned to Hexabrix (52) or Conray (48) for left ventriculography (dose 10 ml m-2 BSA; flow rate 12 ml s-1). Thirteen patients found Hexabrix unpleasant compared with 24 receiving Conray; overall the feelings of warmth and discomfort were less with Hexabrix than Conray (p less than 0.01 and p less than 0.02 respectively). The incidence of nausea, vomiting, and hypersensitivity was similar. Angiographic quality was better with Conray than with Hexabrix (p less than 0.05). Average changes in heart rate and systolic pressure were similar, though there was greater variation in systolic pressure change after Conray (p less than 0.025). End diastolic pressure increased more after Conray than after Hexabrix (p less than 0.05). These slight advantages of Hexabrix over Conray may be valuable in patients requiring multiple angiograms or in those with impaired cardiac function, but do not justify its use for routine angiography.


Ureteroarterial fistula controlled by intraluminal ureteral occlusion.
A 73-year-old woman underwent a pelvic exenteration for transitional cell carcinoma of the bladder and radiation-induced rectovaginal fistula. The patient had undergone radical hysterectomy and radiotherapy for cervical cancer 30 years earlier. Fifteen months after the operation, she suffered from ureteroaortic fistula, which was controlled by intraluminal ureteral occlusion using Gianturco coils. During 53 months of follow up, she has been free of hemorrhagic episodes.


Client attachment and change in mental health during psychotherapy.
In the current study, we used a naturalistic design to examine how client attachment orientations affect changes in client mental health over the course of treatment. We evaluated session-by-session changes in overall maladjustment levels (derived from the Outcome Questionnaire 45.2) in a sample of 105 adult clients who were seeking therapy at a large, university-based, outpatient psychology training clinic. The primary goal of this study was to investigate how client attachment orientations affected patterns of change in client overall maladjustment scores across time. Because previous findings have suggested that client attachment orientations may be associated with different patterns or differential rates of change, beyond linear changes, we also extended previous research by testing more complex models involving quadratic and cubic changes over the course of therapy. Multilevel modeling analysis revealed that client overall maladjustment scores significantly improved throughout therapy. Results further indicated that client attachment anxiety predicted change in maladjustment during therapy. Attachment avoidance did not predict change in symptoms. With respect to attachment anxiety, we found different patterns of recovery or symptom change throughout therapy for clients with high versus low attachment anxiety. Clients low in attachment anxiety showed consistent improvements and those high in attachment anxiety exhibited low levels of therapeutic change throughout the middle of therapy despite their overall improvements. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Reversible Regulation of Succinate Dehydrogenase by Tools of Photopharmacology.
Succinate dehydrogenase (SDH) is extremely important in metabolic function and biological processes. Modulation of SDH has been reported to be a promising therapeutic target to SDH mutations. Current measures for the regulation of SDH are scarce, and precise and reversible modulation of SDH still remains challenging. Herein, a powerful tool for reversible optical control of SDH was proposed and evaluated utilizing the technology of photopharmacology. We reported photochromic ligands (PCLs), azobenzene-pyrazole amides (APAs), that exert light-dependent inhibition effects on SDH. Physicochemical property tests and biological assays were conducted to demonstrate the feasibility of modulating SDH. In this paper, common agricultural pathogens were used to develop a procedure by which our PCLs could reversibly and precisely control SDH utilizing green light. This research would help us to understand the target-ligand interactions and provide new insights into modulation of SDH.


Cross-species approaches to pathological gambling: a review targeting sex differences, adolescent vulnerability and ecological validity of research tools.
Decision-making plays a pivotal role in daily life as impairments in processes underlying decision-making often lead to an inability to make profitable long-term decisions. As a case in point, pathological gamblers continue gambling despite the fact that this disrupts their personal, professional or financial life. The prevalence of pathological gambling will likely increase in the coming years due to expanding possibilities of on-line gambling through the Internet and increasing liberal attitudes towards gambling. It therefore represents a growing concern for society. Both human and animal studies rapidly advance our knowledge on brain-behaviour processes relevant for understanding normal and pathological gambling behaviour. Here, we review in humans and animals three features of pathological gambling which hitherto have received relatively little attention: (1) sex differences in (the development of) pathological gambling, (2) adolescence as a (putative) sensitive period for (developing) pathological gambling and (3) avenues for improving ecological validity of research tools. Based on these issues we also discuss how research in humans and animals may be brought in line to maximize translational research opportunities.


Vibrio cholerae classical biotype is converted to the viable non-culturable state when cultured with the El Tor biotype.
A unique event in bacterial epidemiology was the emergence of the El Tor biotype of Vibrio cholerae O1 and the subsequent rapid displacement of the existing classical biotype as the predominant cause of epidemic cholera. We demonstrate that when the El Tor and classical biotypes were cocultured in standard laboratory medium a precipitous decline in colony forming units (CFU) of the classical biotype occurred in a contact dependent manner. Several lines of evidence including DNA release, microscopy and flow cytometric analysis indicated that the drastic reduction in CFU of the classical biotype in cocultures was not accompanied by lysis, although when the classical biotype was grown individually in monocultures, lysis of the cells occurred concomitant with decrease in CFU starting from late stationary phase. Furthermore, uptake of a membrane potential sensitive dye and protection of genomic DNA from extracellular DNase strongly suggested that the classical biotype cells in cocultures retained viability in spite of loss of culturability. These results suggest that coculturing the classical biotype with the El Tor biotype protects the former from lysis allowing the cells to remain viable in spite of the loss of culturability. The stationary phase sigma factor RpoS may have a role in the loss of culturability of the classical biotype in cocultures. Although competitive exclusion of closely related strains has been reported for several bacterial species, conversion of the target bacterial population to the viable non-culturable state has not been demonstrated previously and may have important implications in the evolution of bacterial strains.


Outcome of contact tracing for Chlamydia trachomatis in a district general hospital.
The outcome of contact tracing (partner notification) for Chlamydia trachomatis in a district general hospital during the 5-year period between 1991-1995 was surveyed. During the 5-year period 1027 cases of C. trachomatis were diagnosed. The health adviser saw 928 (90%) of cases who reported 1132 (1.2) sexual contacts. Out of 682 sexual contacts sought by the health adviser, 472 (69.5%) were seen. Following a consultation with the health adviser, over two-thirds (86%) of index cases chose to inform their contacts themselves. Over two-thirds (71%) of contacts informed by these index cases were seen. A higher proportion of regular and first or most immediate contacts were seen as a result of contact tracing. A significantly higher proportion of partners of index cases who themselves returned for test of cure were seen. A consultation with the health adviser facilitated uptake of partner notification by the index patients. Patient referral led to a majority of contacts being seen in a genitourinary medicine (GUM) clinic. Follow-up visits by index patients may improve outcome of contact tracing and should continue irrespective of need for test of cure.


Surgical Outcomes for Speech Surgery in 22q11.2 Deletion Syndrome: The Dilemma of Persistent Velopharyngeal Insufficiency After Pharyngeal Flap Operation.
The majority of patients with 22q11.2 deletion syndrome suffer from velopharyngeal insufficiency (VPI). Patients with 22q11.2 deletion syndrome (22qDS) commonly present with a large central velopharyngeal gap in the setting of poor velar and pharyngeal wall motion. The posterior pharyngeal flap is considered the most effective technique to treat VPI in this complex patient group. This study aims to critically evaluate success rates of surgical management of VPI in 22qDS patients and discuss options for management of a failed posterior pharyngeal flap (PPF) with persistent VPI. A systematic review was performed through MEDLINE and Scopus to examine the outcomes of PPF surgery to treat VPI in patients with 22qDS. Complications were defined as persistent VPI, hyponasal speech, and obstructive sleep apnea. To demonstrate an approach to management, the authors outline a recent patient with a failed PPF in this patient population at the authors' institution. The authors comprehensively reviewed 58 articles, 13 of which contained relevant information with extractable data. Of the 159 patients with 22qDS who underwent PPF to treat VPI, successful outcomes were reported in 135 patients (80%; range: 0%-100%). Complications were reported in 14% of patients, with need for revision operations in 3%. Surgical management of VPI in patients with 22qDS is challenging, with variable success rates reported in the literature. If unsuccessful, the surgeon faces additional challenges with the revision surgery including a scarred PPF donor site, distorted palatal recipient site, and further medialization of internal carotid arteries. Surgical revision of a failed PPF requires meticulous preoperative planning and technical execution.


Heart rate variability.
Heart rate variability is a recognized tool for the estimation of cardiac autonomic modulations. Recently, several studies have advanced the field of heart rate variability in three areas: 1) in technical modes of electrocardiogram processing and heart rate variability assessment, 2) in physiologic understanding and interpretation, and 3) in clinical and practical use. The most recent technical studies concentrate on the analysis of nonlinear aspects of heart period variations and on coherence between electrocardiogram variability and other physiologic factors such as respiration. Principal physiologic investigations studied the components of heart rate variability attributable to the individual limbs of the autonomic nervous system. It is becoming recognized that behavior and responses to the environment, including the psychosocial environment, play an important role in long-term heart rate variability. Established clinical applications of heart rate variability are presently restricted to the assessment of risk after myocardial infarction and to the early diagnosis of diabetic neuropathy. Nevertheless, recent studies indicate that heart rate variability might soon become a similarly powerful tool for risk prediction and monitoring of disease progression in congestive heart failure and for monitoring or reinnervation after heart transplantation.


ETV6 and ETV7: Siblings in hematopoiesis and its disruption in disease.
ETV6 (TEL1) and ETV7 (TEL2) are closely-related members of the ETS family of transcriptional regulators. Both ETV6 and ETV7 have been demonstrated to play key roles in hematopoiesis, particularly with regard to maintenance of hematopoietic stem cells and control of lineage-specific differentiation, with evidence of functional interactions between both proteins. ETV6 has been strongly implicated in the molecular etiology of a number of hematopoietic diseases, including as a tumor suppressor, an oncogenic fusion partner, and an important regulator of thrombopoiesis, but recent evidence has also identified ETV7 as a potential oncogene in certain malignancies. This review provides an overview of ETV6 and ETV7 and their contribution to both normal and disrupted hematopoiesis. It also highlights the key clinical implications of the growing knowledge base regarding ETV6 abnormalities with respect to prognosis and treatment.


Efficient decomposition of benzene over a beta-Ga2O3 photocatalyst under ambient conditions.
A porous beta-Ga2O3 photocatalyst has been successfully prepared. The photocatalyst was characterized by XRD, N2 adsorption-desorption, TEM, UV/vis, and FTIR techniques. The photocatalytic activity of the sample was evaluated by the decomposition of benzene in air under UV light illumination and was compared with that of the commercial titania (Degussa P25) and Pt/P25. Results revealed that the synthesized Ga2O3 was porous beta-Ga2O3 and was highly photoactive for mineralizing benzene and its derivatives (e.g., toluene and ethylbenzene) to CO2 under ambient conditions. The photocatalytic conversion of benzene over beta-Ga2O3 was about 1 order of magnitude higher than that over P25, and no obvious deactivation of beta-Ga2O3 was observed during the prolonged operation of 80 h. The high activity and long-term stability of the Ga2O3 have been ascribed to its stronger oxidative capability and higher specific surface area in comparison with P25.


Brain cell apoptosis inhibition by butylphthalide in Alzheimer's disease model in rats.
The present study was designed to test the hypothesis that butylphthalide protects the brain of Alzheimer's disease (AD) model rats by inhibiting apoptosis. Ninety Sprague-Dawley rats were randomly divided into drug, control and blank groups of 30 rats in each. The rats in the drug and control groups were treated to induce AD. Then, the rats in the drug group were administered with butylphthalide daily, the rats in the AD control group were given normal saline, and the rats in the healthy group were fed routinely. All rats were sacrificed after 30 days; the brain tissues were used for testing for apoptosis by the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling (TUNEL) staining method, for determining mitogen-activated protein kinase (MAPK), ERK and P21 protein by western blot analysis, and their cognate mRNA levels by RT-PCR. The results of the TUNEL staining indicated that apoptosis of the brain tissues of rats in the drug group was significantly less than that in the control group and blank group. The protein expression levels of MAPK in the drug group were significantly lower than that in the control group, but higher than that in the normal healthy group (P<0.05). The mRNA expression levels of MAPK in the drug group were significantly lower than those in the control group, but higher than those in the normal healthy group (P<0.05). Based on these results, butylphthalide showed a protective apoptosis-inhibition effect on the brain tissues of the AD rats and this seems to be a consequence of its inhibition of the expressions of MAPK mRNA and MAPK protein in the brain of the rat.


A prospective comparison of a new, synthetic donor site dressing versus an impregnated gauze dressing.
Three institutions enrolled 38 patients who required bilateral skin graft donor sites into a safety and efficacy study of a new synthetic donor site dressing. Bilateral donor sites were randomized to receive either a new, synthetic donor site dressing or an impregnated gauze dressing. Wounds were assessed by time to healing, pain, and patient preference. Synthetic dressing wounds were treated 7.9 days compared with 10.2 days for gauze dressing wounds (p < 0.001), and synthetic dressing wounds were more completely epithelialized. Visual analogue pain analysis revealed significantly less donor site pain with synthetic dressing (2.94) versus gauze dressing (4.64) (p < 0.001). Synthetic dressing had fewer treatment-related adverse experiences than gauze dressing (2 vs 7) and was judged by recipients to be superior to gauze dressing in comfort, pain relief, cosmetic appeal, ease of ambulation, and overall acceptance.


Preparation and Structural Characterization of Free-Standing Octacalcium-Phosphate-Rich Thin Films.
Free-standing films of calcium phosphates exhibit many favorable properties for tissue engineering. In this work, a thin film of calcium phosphate is prepared in a liposome suspension using the method of ammonia gas diffusion. The thickness of the film is about 10 μm, and the lateral dimensions are on the length scale of millimeter. The results of powder X-ray diffraction and transmission electron microscopy show that the thin films contain the mineral phases of hydroxyapatite and octacalcium phosphate (OCP). Using solid-state NMR spectroscopy, in particular the technique of heteronuclear correlation spectroscopy with variable contact time, the major crystalline phase of the thin film has been confirmed to be OCP.


Absolutely Maximally Entangled States of Seven Qubits Do Not Exist.
Pure multiparticle quantum states are called absolutely maximally entangled if all reduced states obtained by tracing out at least half of the particles are maximally mixed. We provide a method to characterize these states for a general multiparticle system. With that, we prove that a seven-qubit state whose three-body marginals are all maximally mixed, or equivalently, a pure ((7,1,4))_{2} quantum error correcting code, does not exist. Furthermore, we obtain an upper limit on the possible number of maximally mixed three-body marginals and identify the state saturating the bound. This solves the seven-particle problem as the last open case concerning maximally entangled states of qubits.


Epidemiologic evidence regarding predisposing factors to prostate cancer.
In 1990, prostate cancer will be the most common cancer diagnosed in U.S. men and will be the second-leading cause of cancer mortality in these men. One in ten U.S. men will develop prostate cancer in his lifetime. Twenty thousand prostate cancer cases occur each year in men under the age of 65. The average number of years of life lost for a man dying of prostate cancer is nine. In addition, both incidence and mortality of prostate cancer are increasing. A review of the literature regarding prostate cancer is timely in light of recent studies examining possible predisposing factors for this disease. In this review, a framework for understanding genetic and environmental factors which may predispose to prostate cancer is presented. The identification of factors which predispose to clinical prostate cancer offers the possibility of lowering the incidence and mortality of prostate cancer in the United States. Epidemiologic evidence regarding possible predisposing factors to prostate cancer is reviewed.


Comparative study of Amsel's criteria and Nugent scoring for diagnosis of bacterial vaginosis in a tertiary care hospital, Nepal.
The most common pathological cause of abnormal vaginal discharge in reproductive-aged women is bacterial vaginosis (BV). Amsel's criteria and Nugent scoring systems are commonly employed approaches for the diagnosis of BV. Despite the Nugent scoring system being the gold standard method for diagnosing BV, Amsel's criteria are generally preferred in clinical setup owing to the fact Nugent scoring requires considerable time and expert microscopist. This study was conducted to determine the diagnostic value of Amsel's criteria by comparing it with the Nugent scoring system. This was a descriptive cross-sectional study conducted at Tribhuvan University Teaching Hospital, Nepal from October 2016 to September 2017. Vaginal specimens were collected from a total of 141 women presenting with abnormal vaginal discharge. The sensitivity, specificity, positive predictive value, and negative predictive value of Amsel's criteria were calculated, and each component of Amsel's criteria was compared to the Nugent scoring system. The sensitivity, specificity, positive predictive value, and negative predictive value of Amsel's criteria were 50%, 98.2%, 87.5%, and 88.8% respectively. The clue cells showed 100% specificity and vaginal discharge with pH > 4.5 had 89.3% sensitivity while compared with Nugent's scoring system. Amsel's criteria can be used as an adjunct method to Nugent scoring for the diagnosis of BV in the hands of skilled manpower in resources limited countries. The presence of clue cell and positive whiff test of Amsel's criteria shows good match with Nugent's score.


The Impact of Atopic Dermatitis and Corticophobia on the Quality of Family Life.
The aim of the study was to investigate the impact of atopic dermatitis (AD) in children and corticophobia on the quality of family life. Children with AD and their parents were included in a cross-sectional study. The severity of AD was self-assessed using the Patient Oriented-Scoring of Atopic Dermatitis (PO-SCORAD) index, and the severity of corticophobia using the Topical Corticosteroid Phobia (TOPICOP) score, and the general impact of AD on family quality of life using the Family Dermatology Life Quality Index (FDLQI). We included 330 parents, mostly mothers (99.4%) and children with a median age of 3 years (interquartile range, IQR 1.5-5.0 years). The median values of the PO SCORAD index and TOPICOP score were: 19.1 (IQR 13.6-24.1) and 58.3 (IQR 41.7-72.2), respectively. The median FDQLI score was 12 (IQR 7-16). The influence of independent variables such as parental age, child's age, child's gender, family history of allergies, place of residence, parental education, associated allergic disease in the child, PO SCORAD, and the TOPICOP score on the FDLQI was analysed. The significant models were the age of the parents (protective factor), the PO SCORAD index, and the TOPICOP score, which together accounted for 26.1% of the variability of FDLQI. Concusion of the study is that AD in children, its severity, and the parent's fear of chronic corticosteroid treatment impair the quality of family life.


Atrazine photodegradation in aqueous solution induced by interaction of humic acids and iron: photoformation of iron(II) and hydrogen peroxide.
The photochemical formation of Fe(II) and hydrogen peroxide (H 2O 2) coupled with humic acids (HA) was studied to understand the significance of iron cycling in the photodegradation of atrazine under simulated sunlight. The presence of HA significantly enhanced the formation of Fe(II) and H 2O 2, and their subsequent product, hydroxyl radical ( (*)OH), was the main oxidant responsible for the atrazine photodegradation. During 60 h of irradiation, the fraction of iron presented as Fe(II) (Fe(II)/Fe(t)) decreased from 20-32% in the presence of the Fe(III)-HA complex to 10-22% after adding atrazine. The rate of atrazine photodegradation in solutions containing Fe(III) increased with increasing HA concentration, suggesting that the complexation of Fe(III) with HA accelerated the Fe(III)/Fe(II) cycling. Using fluorescence spectrometry, the quenching constant and the percentage of fluorophores participating in the complexation of HA with Fe(III) were estimated by the modified Stern-Volmer equation. Fourier transform infrared spectroscopy (FTIR) offered the direct evidence that Fe(III)-carboxylate complex could be formed by ligand exchange of HA with Fe(III). Based on all the information, a possible reaction mechanism was proposed.


First discovery of Holocene cryptotephra in Amazonia.
The use of volcanic ash layers for dating and correlation (tephrochronology) is widely applied in the study of past environmental changes. We describe the first cryptotephra (non-visible volcanic ash horizon) to be identified in the Amazon basin, which is tentatively attributed to a source in the Ecuadorian Eastern Cordillera (0-1°S, 78-79°W), some 500-600 km away from our field site in the Peruvian Amazon. Our discovery 1) indicates that the Amazon basin has been subject to volcanic ash fallout during the recent past; 2) highlights the opportunities for using cryptotephras to date palaeoenvironmental records in the Amazon basin and 3) indicates that cryptotephra layers are preserved in a dynamic Amazonian peatland, suggesting that similar layers are likely to be present in other peat sequences that are important for palaeoenvironmental reconstruction. The discovery of cryptotephra in an Amazonian peatland provides a baseline for further investigation of Amazonian tephrochronology and the potential impacts of volcanism on vegetation.


Ethical parameters of challenge studies inducing psychosis with ketamine.
Researchers routinely induce psychosis in healthy volunteers via ketamine infusion to expand their knowledge of schizophrenia. We question the ethics of the nature and procedures of such studies. We also address safeguards for ethically conducting and reporting such pursuits, including recruitment, screening, available treatment, and follow-up.


Enantioselective synthesis of (S)-3-carboxy-4-((carboxy)difluoromethyl)phenylalanine in protected form and its incorporation into a PTP-1B-directed tripeptide.
Recent findings have shown that, when expressed in the tripeptide platform, 'Fmoc-Glu-Xxx-Leu-amide', the phosphotyrosyl mimetic (pTyr), Xxx=(S)-3-carboxy-4-(carboxymethyl)-Phe, provides higher PTP-1B affinity than that obtained with Xxx=(S)-difluorophosphonomethyl-Phe (F(2)Pmp). This was of note, since difluorophosphonomethyl-containing pTyr mimetics have typically exhibited higher PTP-inhibitory potencies than carboxy-based mimetics, indicating the potential value of 3-carboxy-4-(carboxymethyl)-Phe as a starting point for further analogue development. Therefore, relying on precedence that alpha-fluorination often enhances PTP-1B affinity, (S)-3-carboxy-4-((carboxy)difluoromethyl)-Phe was designed as a PTP-1B-directed pTyr mimetic. Reported herein is the synthesis of this new amino acid analogue through application of commercially available Williams chiral auxiliary. The target was prepared in an orthogonally protected form suitable for peptide synthesis according to Fmoc chemistries and utilization for the synthesis of a PTP-1B-directed tripeptide bearing the sequence indicated above. Biological evaluation with in vitro PTP-1B assays indicated nearly total loss of affinity for this peptide. Evidence is provided that the unexpected deleterious effect of fluorination is probably not related to pK(a) effects.


Dual-modified liposome codelivery of doxorubicin and vincristine improve targeting and therapeutic efficacy of glioma.
Therapeutic outcome for the treatment of glioma was often limited due to drug resistance and low permeability of drug across the multiple physiological barriers, including the blood-brain barrier (BBB), and the blood-tumor barrier (BTB). In order to overcome these hurdles, we designed T7 and DA7R dual peptides-modified liposomes (abbreviated as T7/DA7R-LS) to efficiently co-delivery doxorubicin (DOX) and vincristine (VCR) to glioma in this study. T7 is a seven-peptide ligand of transferrin receptors (TfR) capable of circumventing the BBB and then targeting glioma. DA7R is a d-peptide ligand of vascular endothelial growth factor receptor 2 (VEGFR 2) overexpressed on angiogenesis, presenting excellent glioma-homing property. By combining the dual-targeting delivery effect, the dual-modified liposomes displayed higher glioma localization than that of single ligand-modified liposomes or free drug. After loading with DOX and VCR, T7/DA7R-LS showed the most favorable antiglioma effect in vivo. In conclusion, this dual-targeting, co-delivery strategy provides a potential method for improving brain drug delivery and antiglioma treatment efficacy.


A new nonlinear mixture response surface paradigm for the study of synergism: a three drug example.
A flexible approach to response surface modeling for the study of the joint action of three active anticancer agents is used to model a complex pattern of synergism, additivity and antagonism in an in vitro cell growth assay. The method for determining a useful nonlinear response surface model depends upon a series of steps using appropriate scaling of drug concentrations and effects, raw data modeling, and hierarchical parameter modeling. The method is applied to a very large in vitro study of the combined effect of Trimetrexate (TMQ), LY309887 (LY), and Tomudex (TDX) on inhibition of cancer cell growth. The base model employed for modeling dose-response effect is the four parameter Hill equation [1]. In the hierarchical aspect of the final model, the base Hill model is treated as a function of the total amount of the three drug mixture and the Hill parameters, background B, dose for 50% effect D50, and slope m, are understood as functions of the three drug fractions. The parameters are modeled using the canonical mixture polynomials from the mixture experiment methodologies introduced by Scheff [2]. We label the model generated a Nonlinear Mixture Amount model with control observations, or zero amounts, an "NLMAZ" model. This modeling paradigm provides for the first time an effective statistical approach to modeling complex patterns of local synergism, additivity, and antagonism in the same data set, the possibility of including additional experimental components beyond those in the mixture, and the capability of modeling three or more drugs.


Kisspeptin and GPR54: discovery of a novel pathway in reproduction.
In order to find novel modulators of gonadotrophin-releasing hormone (GnRH) secretion, genetic tools were employed in patients with idiopathic hypogonadotrophic hypogonadism (IHH). Mutations in a G-protein coupled receptor, GPR54, were identified, making this receptor a genetic determinant and indisputable gatekeeper of normal reproductive function. This article places these investigations into historical context and reviews some of the new findings relevant to this pathway.


Monoclonal antibody characterization of a chymotrypsin-like molecule on neutrophil membrane associated with cellular activation.
Monoclonal antibody 1-15 (Ab 1-15), is a murine anti-human neutrophil (PMN) IgG1 that inhibits PMN effector responses to N-formyl-met-leu-phe (FMLP) and phorbol myristate acetate. In this study, the effects of Ab 1-15 on PMN membrane-related functions were characterized: Ab 1-15 inhibited PMN superoxide (O-2) response to FMLP by 60% (P less than 0.005) without effect on the onset or duration of O-2 production. This inhibition of O-2 response was associated with a significant inhibition of PMN chymotrypsin-like, but not trypsin-like, protease activity. Cell fractionation studies indicated the presence of an Ab 1-15 inhibitable, chymotryptic neutral protease activity in PMN membranes. In studies of Ab 1-15 effects on membrane-related second messenger pathways, Ab 1-15 augmented both FMLP- and isoproterenol-induced intracellular cAMP accumulation, whereas alpha-chymotrypsin decreased PMN cAMP response to these stimuli. Our data suggest that the function-inhibiting, anti-PMN monoclonal Ab 1-15 defines a PMN chymotryptic enzyme on the membrane surface that is involved in regulation of two membrane-related functions, O-2 generation and cAMP generation.


The pharmacokinetic and pharmacodynamic properties of biphasic insulin Aspart 70 (BIAsp 70) are significantly different from those of biphasic insulin Aspart 30 (BIAsp 30).
To evaluate the pharmacokinetic and pharmacodynamic properties of two different formulations of premixed analogue (mixed biphasic insulin aspart [BIAsp]), BIAsp 30 (30 % soluble insulin aspart [IAsp] and 70 % protaminated IAsp) and BIAsp 70 (70 % soluble IAsp and 30 % protaminated IAsp), in patients with type 1 diabetes using a 12-hour euglycaemic clamp technique. In this randomised, double-blind, two-period crossover trial, 27 patients with type 1 diabetes received 7 days of treatment with BIAsp 30 three times daily (TID) and 7 days of treatment with BIAsp 70 TID, with a 2 - 6 week washout period between treatment periods. At the start (day 1) and end (day 8) of each treatment period, 12-hour serum IAsp profiles and glucose infusion rate (GIR) profiles were determined during an overnight euglycaemic clamp following subcutaneous (sc) administration of a single 0.3 U/kg dose of trial insulin. All pharmacokinetic and pharmacodynamic endpoints were derived from individual serum IAsp and GIR profiles. The larger fraction of soluble IAsp in BIAsp 70 compared with BIAsp 30 resulted in greater metabolic effect during the initial post-dosing phase (0 - 6 hours) and decreased activity during the late phase (6 - 12 hours). On day 8, AUC (GIR 0 - 6 hours) was 16 % greater for BIAsp 70 than for BIAsp 30 (p = 0.016) and AUC (GIR 6 - 12 hours) was 90 % (p < 0.001) greater for BIAsp 30 relative to BIAsp 70, reflecting the increased proportion of intermediate-acting (protamine co-crystallised) IAsp in BIAsp 30. Overall metabolic effect (AUC (GIR 0 - 12 hours)) was similar for both insulin formulations on day 8 (Ratio, BIAsp 30:BIAsp 70 = 1.04, p = 0.538). Likewise, the larger fraction of soluble IAsp in BIAsp 70 compared with BIAsp 30 resulted in greater exposure to IAsp during the initial post-dosing phase (0 - 6 hours) and a smaller exposure to IAsp during the late phase (6 - 12 hours). On day 8, AUC (IAsp 0 - 6 hours) was 59 % (p < 0.001) greater for BIAsp 70 than for BIAsp 30, and AUC (IAsp 6 - 12 hours) was 61 % (p < 0.001) greater for BIAsp 30 than for BIAsp 70, reflecting the increased proportion of intermediate-acting (protamine co-crystallised) IAsp in BIAsp 30. However, the overall IAsp exposure (AUC 0 - 12 hours) on day 8 was significantly greater for BIAsp 70 than for BIAsp 30 (Ratio, BIAsp 30:BIAsp 70 = 0.73, p < 0.001). The GIR profiles on day 8 were similar to those on day 1. Serum IAsp profiles on day 8 showed a slight increase compared with day 1. The different proportions of soluble and protaminated IAsp result in differences in the pharmacokinetic and pharmacodynamic properties of BIAsp 30 and BIAsp 70. The pharmacokinetic and pharmacodynamic differences observed may allow for flexibility and individualised treatment regimens in patients with diabetes, while maintaining a limited number of daily injections.


Collaboration between nurses and agricultural teachers to prevent adolescent agricultural injuries: the Agricultural Disability Awareness and Risk Education Model.
Nearly 2 million children live or work on America's farms and ranches. Despite the increasing mechanization of production agriculture in the United States, children still constitute a considerable portion of the work force on farms and ranches. When adjusted for actual work exposure time, adolescent injury rates on agricultural establishments surpass those of adults (Castillo, D. N., Landen, D. D., & Layne, L. A. (1994). American Journal of Public Health, 84, 646-649). This project, headed by two public health nurses, developed and tested an agricultural safety curriculum [Agricultural Disability Awareness and Risk Education (AgDARE)] for use in high school agriculture classes. Students who participated in AgDARE scored significantly higher in farm safety attitude and intent to change work behavior than the control group. School and public health nurses, working together with agriculture teachers, may make an effective team in reducing injuries among teen agricultural workers.


Nitric Oxide Induction in Peritoneal Macrophages by a 1,2,3-Triazole Derivative Improves Its Efficacy upon Leishmania amazonensis In Vitro Infection.
1,2,3-Triazole is one of the most flexible chemical scaffolds broadly used in various fields. Here, we report the antileishmanial activity of 1,2,3-triazole derivatives, the ultrastructural alterations induced by their treatment, and the nitric oxide (NO) modulation effect on their efficacy against Leishmania amazonensis in vitro infection. After the screening of eleven compounds, compound 4 exhibited better results against L. amazonensis promastigotes (IC50 = 15.52 ± 3.782 μM) and intracellular amastigotes (IC50 = 4.10 ± 1.136 μM), 50% cytotoxicity concentration at 84.01 ± 3.064 μM against BALB/c peritoneal macrophages, and 20.49-fold selectivity for the parasite over the cells. Compound 4 induced ultrastructural mitochondrial alterations and lipid inclusions in L. amazonensis promastigotes, upregulated tumor necrosis factor α, interleukin (IL)-1β, IL-6, IL-12, and IL-10 messenger RNA expressions, and enhanced the NO production, verified by nitrite (p = 0.0095) and inducible nitric oxide synthase expression (p = 0.0049) quantification, which played an important role in its activity against intramacrophagic L. amazonensis. In silico prediction in association with antileishmanial activity results showed compound 4 as a hit compound with promising potential for further studies of new leishmaniasis treatment options.


all-S,S-dioxygenated star oligothiophenes.
Star-shaped oligothiophenes are promising materials for applications in the organic electronics field. For the first time, a range of star-oligothiophenes was oxidized to the corresponding all-S,S-dioxides by using the HOF·CH(3)CN complex. These materials exhibit considerable thermal stability and red-shift absorptions in the UV/vis relative to the parent compounds.


Computerized assessment of sustained attention: interactive effects of task demand, noise, and anxiety.
In a sample of 163 college undergraduates, the effects of task demand, noise, and anxiety on Continuous Performance Test (CPT) errors were evaluated with multiple regression and multivariate analysis of variance. Results indicated significantly more omission errors on the difficult task. Complex interaction effects of noise and self-reported anxiety yielded more omissions in quiet intermittent white noise, particularly for high-anxious subjects performing the difficult task. Anxiety levels tended to increase from pretest to posttest, particularly for low-anxious subjects in the quiet, difficult-task condition, while a decrease was seen for high-anxious subjects in the loud, easy-task condition. Commission errors were unrelated to any predictor variables, suggesting that "attention" cannot be considered a unitary phenomenon. The variety of direct and interactive effects on vigilance performance underscore the need for clinicians to use a variety of measures to assess attentional skills, to avoid diagnosis of attention deficits on the basis of a single computerized task performance, and to rule out anxiety and other contributors to poor vigilance task performance.


Aggressive surgical policies in a retrospectively reviewed single-institution case series of retroperitoneal soft tissue sarcoma patients.
To explore whether the adoption of a systematic attempt to perform wider resections may lead to prognostic improvements in retroperitoneal soft tissue sarcoma (RSTS). Two hundred eighty-eight consecutive patients who were surgically treated at a single referral center were analyzed. Because a shift toward a systematic, more aggressive surgical approach (ie, liberal en bloc resection of adjacent organs) was in place from 2002 onward, patients were divided in two groups accordingly. Overall survival, crude cumulative incidence (CCI) of local recurrence, and distant metastases were estimated. Univariable and multivariable analyses were carried out. Patients who underwent operation in the early period had a 5-year local recurrence rate of 48% compared with 28% for patients who were treated in the recent period. The number of distant metastases was greater in the recent group (22% v 13%), and overall survival was similar. In addition to the period of treatment, important independent determinants for local recurrence-free survival were histologic grade, histologic subtype, and radiation therapy. Overall, liposarcomas and grades 1 to 2 tumors had the greatest local benefit at 5 years. In a single institution, the adoption of a policy of more liberal visceral en bloc resections was paralleled by greater local control. This benefit might translate into a prognostic improvement only on a longer follow-up for patients with a more indolent disease, whereas systemic failures seem to be the main problem in high-grade tumors. Radiation therapy could add some additional benefit to local outcome and possibly to survival.


[Therapeutic alternatives in case of failure of first-line treatment of intestinal helminthiasis in adults].
Development of antiparasite medications over the last 15 years has greatly reduced the number of treatment failures for intestinal helminthiasis. Benzimidazole derivatives, ivermectine, praziquantel and triclabendazole are easy to use, well tolerated and generally curative. First-line treatment are currently so reliable that failure should lead first to investigation of possible "false failure" causes such as misdiagnosis, poor identification of the parasite, inadequate or incorrect treatment, and repeat contamination, before concluding that genuine parasite resistance is involved and that alternative therapy is needed. Nitazoxanide is an alternative treatment for fascioliasis and teniasis. Albendazole can be beneficial for taeniasis and strongyloidiasis. Metronidazole can be effective for fascioliasis. Artemisinine derivatives are useful for schistosomiasis. Combined therapies are necessary for refractory ankylostomiasis.


Synthetic chemically modified mRNA (modRNA): toward a new technology platform for cardiovascular biology and medicine.
Over the past two decades, a host of new molecular pathways have been uncovered that guide mammalian heart development and disease. The ability to genetically manipulate these pathways in vivo have largely been dependent on the generation of genetically engineered mouse model systems or the transfer of exogenous genes in a variety of DNA vectors (plasmid, adenoviral, adeno-associated viruses, antisense oligonucleotides, etc.). Recently, a new approach to manipulate the gene program of the adult mammalian heart has been reported that will quickly allow the high-efficiency expression of virtually any protein in the intact heart of mouse, rat, porcine, nonhuman primate, and human heart cells via the generation of chemically modified mRNA (modRNA). The technology platform has important implications for delineating the specific paracrine cues that drive human cardiogenesis, and the pathways that might trigger heart regeneration via the rapid generation of modRNA libraries of paracrine factors for direct in vivo administration. In addition, the strategy can be extended to a variety of other cardiovascular tissues and solid organs across multiple species, and recent improvements in the core technology have supported moving toward the first human studies of modRNA in the next 2 years. These recent advances are reviewed along with projections of the potential impact of the technology for a host of other biomedical problems in the cardiovascular system.


Caenorhabditis elegans inositol 5-phosphatase homolog negatively regulates inositol 1,4,5-triphosphate signaling in ovulation.
Ovulation in Caenorhabditis elegans requires inositol 1,4,5-triphosphate (IP(3)) signaling activated by the epidermal growth factor (EGF)-receptor homolog LET-23. We generated a deletion mutant of a type I 5-phosphatase, ipp-5, and found a novel ovulation phenotype whereby the spermatheca hyperextends to engulf two oocytes per ovulation cycle. The temporal and spatial expression of IPP-5 is consistent with its proposed inhibition of IP(3) signaling in the adult spermatheca. ipp-5 acts downstream of let-23, and interacts with let-23-mediated IP(3) signaling pathway genes. We infer that IPP-5 negatively regulates IP(3) signaling to ensure proper spermathecal contraction.


G6PD testing and radical cure for Plasmodium vivax in Cambodia: A mixed methods implementation study.
Cambodia aims to eliminate malaria by 2025, however tackling Plasmodium vivax (P.v) presents multiple challenges. The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency has prevented the deployment of 8-aminoquinolones for "radical cure", due to the risk of severe haemolysis. Patients with P. vivax have therefore continued to experience recurrent relapses leading to cumulative health and socioeconomic burden. The recent advent of point of care testing for G6PD deficiency has made radical cure a possibility, however at the time of the study lack of operational experience and guidance meant that they had not been introduced. This study therefore aimed to design, implement and evaluate a new care pathway for the radical cure of P.vivax. This implementation study took place in Pursat province, Western Cambodia. The interventions were co-developed with key stakeholders at the national, district, and local level, through a continuous process of consultations as well as formal meetings. Mixed methods were used to evaluate the feasibility of the intervention including its uptake (G6PD testing rate and the initiation of primaquine treatment according to G6PD status); adherence (self-reported); and acceptability, using quantitative analysis of primary and secondary data as well as focus group discussions and key informant interviews. The co-development process resulted in the design of a new care pathway with supporting interventions, and a phased approach to their implementation. Patients diagnosed with P.v infection by Village Malaria Workers (VMWs) were referred to local health centres for point-of-care G6PD testing and initiation of radical cure treatment with 14-day or 8-week primaquine regimens depending on G6PD status. VMWs carried out follow-up in the community on days 3, 7 and 14. Supporting interventions included training, community sensitisation, and the development of a smartphone and tablet application to aid referral, follow-up and surveillance. The testing rate was low initially but increased rapidly over time, reflecting the deliberately cautious phased approach to implementation. In total 626 adults received G6PD testing, for a total of 675 episodes. Of these 555 occurred in patients with normal G6PD activity and nearly all (549/555, 98.8%) were initiated on PQ14. Of the 120 with deficient/intermediate G6PD activity 61 (50.8%) were initiated on PQ8W. Self-reported adherence was high (100% and 95.1% respectively). No severe adverse events were reported. The pathway was found to be highly acceptable by both staff and patients. The supporting interventions and gradual introduction were critical to success. Challenges included travel to remote areas and mobility of P.v patients. The new care pathway with supporting interventions was highly feasible with high levels of uptake, adherence and acceptability in this setting where high prevalence of G6PD deficiency is high and there is a well-established network of VMWs. Scaling up of the P.v radical cure programme is currently underway in Cambodia and a decline in reduction in the burden of malaria is being seen, bringing Cambodia a step closer to elimination.


[Current state and prospects for gene therapy of Duchenne muscular dystrophy in the world and in Russia].
Failure of drug therapy of Duchenne muscular dystrophy (DMD) stimulated intense search for adequate methods of gene therapy (GT) which would ensure effective delivery of the dystrophin (D) gene, its long-term persistence in transfected cells, and its expression in muscle fibers. The main results of the experimental GT of DMD with the use of viral and nonviral delivery of the D gene into muscles of biological models are discussed. Delivery of a mini-gene of D with a specific muscle promoter using a modified adenoassociated virus is currently the most promising method, which will soon be available for clinical trials. The main results of the studies on the DMD GT in Russia are summarized. The results of experiments on genetic transfection of mdx mice with marker genes and various constructions with the D gene are outlined. The genes are delivered into muscles by means of gene gun, electroporation, viral oligopeptides, liposomes, microspheres, lactoferine, and other nonviral vehicles. It is emphasized that consolidation of funds and efforts of all Russian laboratories dealing with gene and cell therapy of DMD are necessary to complete the experiments and start clinical trials.


Health economic evaluation in Greece.
There is a growing volume of literature on health economic evaluation, with this form of analysis becoming increasingly influential at the decision-making level worldwide. The purpose of this study was to review the current state of health economic evaluation in Greece, with a view to uncovering reasons why its use in this country is limited. A search of the NHS Economic Evaluation Database was undertaken. The search included cost, cost-of-illness, cost-minimization, cost-effectiveness, cost-consequences, cost-utility, and cost-benefit analyses and was narrowed only to Greek authors undertaking solo or joint health economic evaluation in Greece. The search revealed that, in Greece, very little health economic evaluation has been undertaken. The main reason for the lack of interest is that the current chaotic healthcare system structure and financing does not provide the appropriate incentives to stimulate a powerful interest in this type of research. This condition is a result of the lack of a long-term national health policy and the hesitation of the present and past Greek governments to date to proceed to large-scale reforms because of political considerations. The Greek governments have also been content with the good health indicators being achieved. Even if it is accepted that good health prevails in Greece, slower economic growth rates, an ageing population, and the continuous immigration will place increasing pressure on healthcare resources and will necessitate a more rational use of these resources. Health economic evaluation, by weighing benefits against costs, therefore, has an important role to play.


Dental dilemmas: can psychiatry help?
An overlap exists between dentsitry and psychiatry. The dentist, whose role is inevitably of considerable psychological significance, should be aware of the common psychiatric "disease entities", notably depressive illness, which can present through dental symptoms. Such disorders seldom respond to dental manoeuvers per se but often respond to psychiatric treatment. Some specific psychodental syndromes are described and illustrative case histories are given.


Are transplantation antigens stable constituents on human renal allografts?
The majority of cadaveric kidney transplants suffer at most one rejection episode, thereafter the postoperative course is usually uneventful. The remaining transplants have repeated rejections terminating often in prolonged irreversible rejection and transplant removal. We have been curious about this difference and analysed whether the two types of grafts display equally the major histocompatibility (MHC) antigens on their surface. Using monospecific rabbit antisera to HLA-ABC and -DR and/or alloantisera directed to allelic determinants of HLA-A and -B, we were unable to demonstrate the MHC antigens in most of the 'well-functioning' kidneys whereas these antigens were almost regularly present on the vascular endothelial cells of transplants with repeated and irreversible rejections.


Physique as a risk factor for ulnar variance in elite female gymnasts.
The aims of this study were: 1) to determine ulnar variance variability of elite, female gymnasts; 2) to evaluate the relationship between ulnar variance and physique, maturity status, and training characteristics of these gymnasts. All 156 skeletally immature female gymnasts were participants at the World Championships Artistic Gymnastics, Rotterdam, The Netherlands, in 1987. Chronological ages varied between 13.1 and 20.6 yr (mean = 15.9 +/- 1.3 yr). A large set of anthropometric dimensions was taken and somatotype was determined by the Heath-Carter technique. Skeletal age was assessed by the Tanner-Whitehouse II method. Menarcheal status and training data were collected by questionnaire. Ulnar variance was determined according to Hafner et al. Gymnasts differ significantly from reference girls with respect to physique and maturational status: gymnasts were smaller and delayed in skeletal maturity with about 1.5 yr. For those who had attained menarche, mean age at menarche was 15.1 +/- 1.3 yr. Ulnar variance shows a normal distribution in the gymnasts, ranging from -10.5 mm to +5.9 mm, which is somewhat more positive, i.e., an ulnar overgrowth, than reference wrists. The relationship between ulnar variance and somatic and maturational features suggests that female gymnasts who are more mature and have a physique characterized as relatively tall with a high lean body mass are at greater risk for developing a positive ulnar variance. No relationship between ulnar variance and training characteristics was evident. It is concluded that the observed positive ulnar variance in this sample of elite female gymnasts is less pronounced than originally stated in most "case reports."


Schmorl's node mimicking metastasis in a patient with breast cancer: diagnosis with 99mTC methylene diphosphonate SPECT-CT.
Schmorl's node (SN) is a common entity characterized by protrusion of intervertebral disc material through a break in the subchondral end plate of a vertebral body. They can show increased 99mTC methylene diphosphonate uptake on bone scintigraphy mimicking metastasis and can be symptomatic. Differentiation of SN from metastasis is essential for appropriate patient management. Here, we present a case where increased 99mTC methylene diphosphonate uptake in a dorsal vertebra was found to be because of SN by using single-photon emission computed tomography-computed tomography.


Expression of DR antigens on early human progenitors of neutrophilic and eosinophilic colonies in diffusion chambers (CFUd).
Incubation of the non-adherent low density cells from normal human bone marrow with an antiserum to DR antigens markedly inhibited their capacity to form granulocytic colonies in fibrin clot diffusion chambers implanted intraperitoneally into irradiated mice. The inhibitory effect of antiserum was abrogated after absorption of antiserum with B cells. Inhibition was obtained both with and without complement treatment. Neutrophilic colony formation exhibited a higher sensitivity to diluted antiserum to DR antigens as compared with eosinophilic colony formation. These results suggest that DR determinants are expressed on the neutrophilic and eosinophilic progenitor cells (CFUd) which give rise to colonies in diffusion chambers.


Visualization of hydrophobic polyelectrolytes using atomic force microscopy in solution.
We have used atomic force microscopy to study the morphology of hydrophobic polyelectrolytes adsorbed on surfaces. The polyelectrolytes consisted of polystyrene sulfonate (PSS) chains made with three charge densities: 32%, 67%, and 92%. They were adsorbed on two types of surfaces: mica, and phospholipid bilayers made of mixed neutral and cationic lipids. We show that the chains with a low charge density (32%) are collapsed in spherical globules while highly charged chains (67% and 92%) are fully extended. End-to-end distances and contour lengths of the extended chains were measured. Statistical analysis shows that the persistence length of these chains depends on the surface where they adsorb. On lipid bilayers, highly ordered monolayers are formed upon increase of the proportion of cationic phospholipids. These results show that highly charged PSS chains behave in a similar manner than the stiffer, hydrophilic DNA when adsorbed on surfaces. It could lead to the design of new types of nanostructured surfaces using polyelectrolyte molecules synthesized with specific properties.


Case Report: Experience and Lesson From Postpartum Ruptured Abdominal Aortic Aneurysm.
With rapid progression and extremely high mortality brought by the ruptured aneurysm, abdominal aortic aneurysm is one of the most dangerous diseases in the field of vascular surgery. The incidence of abdominal aortic aneurysms in pregnant women is low. Because of the insidious nature of the disease, it is not easily recognized and can be easily misdiagnosed by obstetricians, which can lead to serious adverse outcomes. In this study, we aim to draw attention to this disease and raise awareness among obstetricians about this disease in pregnant women by retrospectively analyzing a rescue case of ruptured abdominal aortic aneurysm after delivery. By reporting the experience and lessons learned from this case, we aim to improve preoperative diagnosis and treatment rates, reduce missed diagnosis, and improve the prognostic outcome of patients.


Ruthenium-decorated lipid vesicles: light-induced release of [Ru(terpy)(bpy)(OH2)]2+ and thermal back coordination.
Electrostatic forces play an important role in the interaction between large transition metal complexes and lipid bilayers. In this work, a thioether-cholestanol hybrid ligand (4) was synthesized, which coordinates to ruthenium(II) via its sulfur atom and intercalates into lipid bilayers via its apolar tail. By mixing its ruthenium complex [Ru(terpy)(bpy)(4)](2+) (terpy = 2,2';6',2''-terpyridine; bpy = 2,2'-bipyridine) with either the negatively charged lipid dimyristoylphosphatidylglycerol (DMPG) or with the zwitterionic lipid dimyristoylphosphatidylcholine (DMPC), large unilamellar vesicles decorated with ruthenium polypyridyl complexes are formed. Upon visible light irradiation the ruthenium-sulfur coordination bond is selectively broken, releasing the ruthenium fragment as the free aqua complex [Ru(terpy)(bpy)(OH(2))](2+). The photochemical quantum yield under blue light irradiation (452 nm) is 0.0074(8) for DMPG vesicles and 0.0073(8) for DMPC vesicles (at 25 °C), which is not significantly different from similar homogeneous systems. Dynamic light scattering and cryo-TEM pictures show that the size and shape of the vesicles are not perturbed by light irradiation. Depending on the charge of the lipids, the cationic aqua complex either strongly interacts with the membrane (DMPG) or diffuses away from it (DMPC). Back coordination of [Ru(terpy)(bpy)(OH(2))](2+) to the thioether-decorated vesicles takes place only at DMPG bilayers with high ligand concentrations (25 mol %) and elevated temperatures (70 °C). During this process, partial vesicle fusion was also observed. We discuss the potential of such ruthenium-decorated vesicles in the context of light-controlled molecular motion and light-triggered drug delivery.


[Extracorporeal lithotripsy of upper urinary tract stones in children].
The objective of this study was to evaluate the efficacy of extracorporeal lithotripsy for the treatment of urinary stones in children. From November 2002 to November 2004, 34 children from the department of paediatric urology of Rabat children's hospital, aged 3 to 15 years (mean age: 6 years), including 15 children under the age of 6 years, were treated for symptomatic urinary stones in the extracorporeal lithotripsy centre with a Lithostar Multiline lithotriptor adapted to the treatment of adults as well as children, even very young children. At the time of treatment, all 34 children had normal blood pressure, normal blood urea and creatinine, normal clotting parameters, sterile urine and no urinary tract obstruction. All children under the age of 6 years were treated under ketamine sedation. Treatment required a variable number of sessions from 1 to 3 (mean: 1.5) and concerned 38 stones: 30 renal stones including 6 staghorn and 8 ureteric stones. The number of impacts delivered per session ranged from 1,500 to 3,500 for renal stones (mean: 2,500 impacts), with a maximum of 5,000 impacts for ureteric stones (mean: 3,250 impacts). Three months after the last lithotripsy session, 30 patients presented no fragments. No lesion of the treated kidney or adjacent organs was demonstrated on follow-up ultrasound performed 3 to 6 months after treatment. Evaluation of the results confirms the efficacy of extracorporeal lithotripsy for the treatment of even very large urinary stones in children, even in very young children. Extracorporeal lithotripsy is now the first-line treatment for-urinary stones in children.


Effect of smoking on lipid profile and lipid peroxidation in normal subjects.
The aim of the present study was to assess the association between smoking and the alteration in plasma concentration of lipid profile and lipid peroxides. Fourteen smokers and 11 age matched control were enrolled. Plasma levels of fasting cholesterol, triglycerides, lipoprotein cholesterol and malondialdehyde were estimated. In smokers the levels of total cholesterol, LDL cholesterol, Non-HDL cholesterol and MDA were significantly elevated when compared with the controls. The atherogenic index as indicated by various risk ratios were also found to be increased in smokers as compared to controls. These findings indicate that current smokers are at a pro- atherogenic state and as in other countries, in India smokers require particular attention in terms of public health interventions.


Laboratory diagnosis of lupus anticoagulants--effect of residual platelets in plasma, assessed by Staclot LA and silica clotting time.
Residual platelets in plasma are considered detrimental after freezing-thawing, as phospholipids released from ruptured platelets may quench lupus anticoagulants (LA). We aimed at assessing the effect of residual platelets after freezing-thawing plasmas tested with two procedures for LA. Blood from 52 patients suspected of having LA were centrifuged at 2,500 g. Plasmas were subdivided into 2 aliquots. One was filtered to remove residual platelets and both were frozen and stored at -70 degrees C. Silica clotting time (SCT) at low and high phospholipid concentrations and Staclot LA with and without Hexagonal phospholipids were performed on thawed plasmas. Plasmas were considered LA-positive when both SCT and Staclot LA performed on filtered plasmas were diagnostic for LA. Forty-two of 52 plasmas fulfilled the diagnostic criteria and were retained for subsequent analysis. SCT on non-filtered plasmas was diagnostic for LA in 42 of 42 plasmas. Though the median (range) percentage correction recorded after phospholipids addition for filtered plasmas, i.e., 67% (36%-83%) was reduced to 54% (25%-81%) for non-filtered plasmas (p <0.001), it was still above the cut-off (i.e., 20.9%). Staclot LA on non-filtered plasmas was diagnostic for LA in 42 of 42 plasmas. Though the median (range) clotting time difference recorded after phospholipid addition for filtered plasmas, i.e., 40.8 (10-103.5) s was reduced to 31.7 (2.8-88.8) s for non-filtered plasmas (p <0.001), it was still above the cut-off (i. e., 1.7 s). In conclusion, residual platelets do not affect the diagnostic efficacy of SCT and Staclot LA. However, the fact that the percentage correction for SCT and the clotting time difference for Staclot LA are reduced by residual platelets, suggests that weak LA may be lost upon freezing-thawing non-filtered plasmas.


Cytological evaluation correlates poorly with histological diagnosis of vulvar neoplasias.
To determine whether cytological smears of the vulva correlate with vulvar biopsies of vulvar intraepithelial neoplasias (VINs). A retrospective chart review (1995-2000) was performed to identify cases of VIN and vulvar carcinoma and to correlate vulvar Pap smears with biopsy results. Four hundred vulvar Pap smears were identified. Fifty of these patients had concomitant vulvar biopsies, and these cases constitute our study group. Twenty-two of these 50 women had biopsy-proven VIN or vulvar carcinoma. Only 7 (32%) of 22 patients with biopsy-proven disease had a vulvar Pap smear significant for VIN or vulvar carcinoma. The kappa statistic was 0.30 (95% CI=0.08-0.52), indicating poor agreement between vulvar cytology and biopsy results. Vulvar cytological evaluation did not correlate well with tissue diagnosis of VIN; and thus, our findings do not support the use of vulvar cytology in the clinical management of VIN.


The current situation of the anti-malaria programme in Thailand.
The activities of the Malaria Control Programme in Thailand have reduced the mortality rate of 351 per 100,000 population in 1947 to 3.9 per 100,000 population in 1986. Over the same period the morbidity rate showed a reduction from 286 per 1,000 population to 5.0 per 1,000 population. The steady decrease in mortality and morbidity in the last few years is attributed to the expansion of primary health care delivery and the establishment and strengthening of 480 malaria clinics providing prompt diagnosis and treatment. Difficulties are being experienced in maintaining and improving the malaria situation. These include multi-drug resistance of Plasmodium falciparum, exophilic tendencies of primary anopheline vectors and continual population migration. A country-wide service of village volunteers has been established and a great deal of emphasis is being given to personal protection. The combination drug mefloquine-sulfadoxine-pyrimethamine was introduced into the country as first line drug for the treatment of falciparum malaria.


Fibroblast heterogeneity in the healing wound.
Although fibroblasts are traditionally described as static cells providing framework and support for tissues, there is an accumulating body of evidence showing that fibroblasts are a dynamic cell type which exist in functionally and morphologically heterogeneous subpopulations. Fibroblast subsets have been shown to play a critical role in the production and regulation of extracellular matrix components, in wound repair and regeneration, and have been implicated in the pathogenesis of fibrotic conditions. We have reviewed the evidence supporting heterogeneity of fibroblasts from pulmonary, periodontal, and dermal tissues. In addition, we will explore the role fibroblast subpopulations may play in the complex process of wound repair and regeneration.


To step or not to step? How biochemistry and mechanics influence processivity in Kinesin and Eg5.
Conventional kinesin and Eg5 are essential nanoscale motor proteins. Single-molecule and presteady-state kinetic experiments indicate that both motors use similar strategies to generate movement along microtubules, despite having distinctly different in vivo functions. Single molecules of kinesin, a long-distance cargo transporter, are highly processive, binding the microtubule and taking 100 or more sequential steps at velocities of up to 700 nm/s before dissociating, whereas Eg5, a motor active in mitotic spindle assembly, is also processive, but takes fewer steps at a slower rate. By dissecting the structural, biochemical and mechanical features of these proteins, we hope to learn how kinesin and Eg5 are optimized for their specific biological tasks, while gaining insight into how biochemical energy is converted into mechanical work.


Taxonomy and Phylogeny of Four New Species in Absidia (Cunninghamellaceae, Mucorales) From China.
Four new species within the genus Absidia, A. globospora, A. medulla, A. turgida, and A. zonata, are proposed based on a combination of morphological traits, physiological features, and molecular evidences. A. globospora is characterized by globose sporangiospores, a 1.0- to 3.5-μm-long papillary projection on columellae, and sympodial sporangiophores. A. medulla is characterized by cylindrical to oval sporangiospores, a 1.0- to 4.5-μm-long bacilliform projection on columellae, and spine-like rhizoids. A. turgida is characterized by variable sporangiospores, up to 9.5-μm-long clavate projections on columellae, and swollen top of the projection and inflated hyphae. A. zonata is characterized by cylindrical to oval sporangiospores, a 2.0- to 3.5-μm-long spinous projection on columellae, and as many as eight whorled sporangiophores. Phylogenetic analyses based on sequences of internal transcribed spacer rDNA and D1-D2 domains of LSU rDNA support the novelty of these four species within the Absidia. All new species are illustrated, and an identification key to all the known species of Absidia in China is included.


Specialized home care for patients with AIDS: an experiment in Rotterdam, The Netherlands.
Patients with AIDs are permanently dependent on medical and technical nursing care. During a certain phase of the disease some of the patients have to visit the out-patient clinic of the hospital for regular treatment. It was noticed that AIDS patients find these visits a severe burden. Therefore in Rotterdam an experiment has been started to provide them the technical-medical and nursing care at home instead of at the out-patient clinic. During the experiment, specialized hospital nurses visited the patients at home. They worked in close collaboration with the community nurses. An exploratory study was carried out to assess the prospects and difficulties of this new kind of home care for AIDS patients from a medical, psycho-social and organizational point of view. The results suggested that it is possible to relocate the technical-medical and nursing care from the out-patient clinic to the patients' home. This specialized home care is seen as desirable from the perspectives of the AIDS patients and informal and professional caregivers. However, some organizational aspects, like the co-ordination and communication among caregivers and the availability of the specialized hospital nurses during the weekend, must be improved in the future.


A novel lid seal evaluation: the Korb-Blackie light test.
To develop a clinical method to qualitatively evaluate whether a compromised moisture seal is possible even when the lids are apparently closed and to compare these findings with symptoms of ocular discomfort on awakening. Patients (n=116) were fully consented and enrolled. The Korb-Blackie lid-light evaluation was performed by placing a transilluminator against the relaxed, closed, outer upper eyelids of semi-reclined patients. The amount of visible light emanating from the lid area between the lashes was quantified on a scale of 0 to 3, where 0=no light, 1=minimal, 2=moderate, and 3=severe for temporal, central, and nasal sections of the eyelids. Eye discomfort on awakening was quantified on a scale of 0 to 2 (0=no discomfort, 1=mild, and 2=significant discomfort). Data are presented for right eyes only. The mean age of the patients was 52.6±16.8 years. The central lid section had a positive lid-light score (54.3%), significantly more frequently than the nasal (37.9%) or temporal (21.6%) lid sections (P<0.0001). Patients with a positive lid-light evaluation were significantly more likely to have symptoms of discomfort on awakening (P<0.0001). Light emanating from between "closed" lids during the Korb-Blackie lid-light evaluation is associated with symptoms of ocular discomfort on awakening. These symptoms of discomfort may be linked to the inability of the lids to achieve an adequate seal to prevent subtle ocular surface desiccation during sleeping.


Stimulants and antidepressant pharmacokinetics in hyperactive children.
Psychopharmacological treatment of attention-deficit hyperactivity disorder (ADHD), is well established. The central nervous system stimulants, especially dextroamphetamine and methylphenidate, are the drugs of choice. Response is rapid, consistent and predictable. Most children respond to one or the other when a trial of both stimulants are given across wide dose ranges (Elia et al. 1991). The efficacy of pemoline is also well established, but its variable onset and duration of action in children has made it a secondary treatment. Tricyclic antidepressants also produce rapid behavioral effects in ADHD, at doses less than those used for depression. Adverse effects are a limiting factor for continued treatment as well as the fact that beneficial effects are often short-lived.


Radiation dose measurements in coronary CT angiography.
Coronary computed tomography (CT) angiography is associated with high radiation dose and this has raised serious concerns in the literature. Awareness of various parameters for dose estimates and measurements of coronary CT angiography plays an important role in increasing our understanding of the radiation exposure to patients, thus, contributing to the implementation of dose-saving strategies. This article provides an overview of the radiation dose quantity and its measurement during coronary CT angiography procedures.


In-Depth Analysis of Glycoprotein Sialylation in Serum Using a Dual-Functional Material with Superior Hydrophilicity and Switchable Surface Charge.
Sialylation typically occurs at the terminal of glycans, and its aberration often correlates with diseases including neurological diseases and cancer. However, the analysis of glycoprotein sialylation in complex biological samples is still challenging due to their low abundance. Herein, a histidine-bonded silica (HBS) material with a hydrophilic interaction and switchable surface charge was fabricated to enrich sialylated glycopeptides (SGPs) from the digest of proteomics samples. High selectivity toward SGPs was obtained by combining the superior hydrophilicity and switchable-charge characteristics. During the enrichment of sialylated glycopeptides from bovine fetuin digest, seven glycopeptides were detected even at the ratio of 1:5000 with the nonsialylated glycopeptides, demonstrating the high specificity of SGP enrichment by using HBS material. Then, HBS material was further utilized to selectively enrich SGPs from the protein digest of human serum, and 487 glycosites were identified from only 2 μL of human serum; 92.0% of the glycopeptides contained at least one sialic acid, indicating good performance for SGP enrichment by using HBS material. Furthermore, the prepared HBS material also has great potential applications in the analysis of glycoprotein sialylation from other complex biological samples.


Morphometric comparison of human spinal cord anterior horn cells between the cervical and lumbar levels.
Morphometric comparisons of anterior horn cells (AHCs) were conducted between cervical and lumbar spinal cords in 29 cadavers. The sizes of the AHCs were always larger at the lumbar level than at cervical level irrespective of the age of the spicemens, but a decrease in size with age was observed at both levels. The correlation coefficient shows a larger decrease in numbers and volumes at lumbar level than at cervical level.


Dipole source localization of interictal epileptiform activity in temporal lobe epilepsy with medial temporal lesion.
Dipole sources of interictal epileptiform activities recorded by conventional electroencephalogram (EEG) were estimated using the dipole tracing method. Four cases of temporal lobe epilepsy with medial temporal lesions were studied. Two patients with hippocampal sclerosis, one patient with granulation in the hippocampus and one patient with cavernous angioma were involved in the study. Interictal epileptiform activities were classified into two patterns according to the topography of spikes. They were widespread spikes over the parasagittal electrodes (parasagittal spikes) and restricted spikes at the temporal electrodes (temporal spikes). Dipole sources of parasagittal spikes were localized in the medio-basal temporal lobe with vertically orientated vector moment. Dipole sources of temporal spikes were localized in the medio-basal temporal lobe with horizontally orientated vector moment. Locations of dipoles and directions of vector moments were consistent with topography and polarity of spikes. The difference in the two patterns of interictal epileptiform activities was derived from the difference in the direction of the vector moment of dipole sources. There was no difference in the location of dipole sources. Both the dipole sources and the lesions were localized in the same medio-basal temporal lobe. Dipole tracing was very useful in localizing the dipole sources of interictal epileptiform activities and in understanding the neurophysiological background.


Automation in haemostasis.
Automatia, an ancient Greece goddess of luck who makes things happen by themselves and on her own will without human engagement, is present in our daily life in the medical laboratory. Automation has been introduced and perfected by clinical chemistry and since then expanded into other fields such as haematology, immunology, molecular biology and also coagulation testing. The initial small and relatively simple standalone instruments have been replaced by more complex systems that allow for multitasking. Integration of automated coagulation testing into total laboratory automation has become possible in the most recent years. Automation has many strengths and opportunities if weaknesses and threats are respected. On the positive side, standardization, reduction of errors, reduction of cost and increase of throughput are clearly beneficial. Dependence on manufacturers, high initiation cost and somewhat expensive maintenance are less favourable factors. The modern lab and especially the todays lab technicians and academic personnel in the laboratory do not add value for the doctor and his patients by spending lots of time behind the machines. In the future the lab needs to contribute at the bedside suggesting laboratory testing and providing support and interpretation of the obtained results. The human factor will continue to play an important role in testing in haemostasis yet under different circumstances.


A 195Pt NMR study on zero-magnetic-field splitting and the phosphorescence properties in the excited triplet states of cyclometalated platinum(ii) complexes.
We report the factors governing zero-magnetic-field splitting (zfs) in the lowest-energy electronically excited triplet (T1) states of cyclometalated platinum(ii) complexes, whose zfs energies between the lowest- (φ1) and highest-energy spin-sublevels (φ3) in the T1 states (ΔEzfs) are already known: [Pt(bhq)(dpm)] (1Pt), [Pt(thpy)(acac)] (2Pt), [Pt(ppy)(acac)] (3Pt), cis-[Pt(thpy)2 (4Pt), and cis-[Pt(ppy)2] (5Pt), where bhq, dpm, thpy, acac, and ppy are benzo[h]quinoline, dipivaloylmethane, 2-(2-thienyl)pyridine, acetylacetone, and 2-phenylpyridine, respectively. As one of the important findings, we show the relationship between the ΔEzfs and 195Pt NMR chemical shifts of the five Pt(ii) complexes. The implications of the ΔEzfs values on the emission properties of the Pt(ii) complexes in acetonitrile at 293 K are also discussed. In particular, we demonstrate that the radiative rate constants of the Pt(ii) complexes correlate with both ΔEzfs and 195Pt NMR chemical shifts.


Multi-frequency bioelectrical impedance analysis for assessing fat mass and fat-free mass in stroke or transient ischaemic attack patients.
Dual energy X-ray absorptiometry (DEXA) is considered as the reference method in assessing fat-free and fat mass but is costly and not a pragmatic option in daily clinical practice. If devices based on multi-frequency bioelectrical impedance analysis (MF-BIA), which are cheaper and portable, are valid and reliable in measuring body composition, these could be used in routine clinical practice in nutritional management of patients and populations where malnutrition is prevalent. A study of MF-BIA against DEXA in assessing fat-free and fat mass, and two internal validation studies of MF-BIA were conducted. Bland & Altman analysis to assess comparison against DEXA and Cronbach's α for internal validity were carried out. Ten participants (mean age 66 years; 70% men) with a recent stroke or transient ischaemic attack (TIA) were recruited to assess against DEXA and the first internal validation. The second internal validation was based on 80 pairs of MF-BIA measurements in 40 stroke patients (mean age 70.3 years; 55% men) assessed at hospital admission and on discharge. There was a strong correlation between MF-BIA and DEXA (correlation coefficient was 0.88 for fat-free mass and 0.77 for fat mass). According to Bland & Altman analysis, MF-BIA and DEXA fat-free and fat mass estimates were similar. Internal consistency was high with Cronbach's-α >0.9. MF-BIA can be reliably used in stroke and TIA patients. The feasibility, clinical and cost effectiveness of MF-BIA in routine monitoring and management of malnutrition in stroke and TIA patients with high prevalence of nutritional deficits is worthy of further evaluation.


Surgical restoration of arm and hand function in people with tetraplegia.
Improved hand and arm function is the most sought after function for people living with a cervical spinal cord injury (SCI). Surgical techniques have been established to increase upper extremity function for tetraplegics, focusing on restoring elbow extension, wrist movement, and hand opening and closing. Additionally, more innovative treatments that have been developed (implanted neuroprostheses and nerve transfers) provide more options for improving function and quality of life. One of the most important steps in the process of restoring upper extremity function in people with tetraplegia is identifying appropriate candidates - typically those with American Spinal Injury Association (ASIA) motor level C5 or greater. Secondary complications of SCI can pose barriers to restoring function, particularly upper extremity spasticity. A novel approach to managing spasticity through high-frequency alternating currents designed to block unwanted spasticity is being researched at the Cleveland FES Center and may improve the impact of reconstructive surgery for these individuals. The impact of these surgeries is best measured within the framework of the World Health Organization's International Classification of Function, Disability and Health. Outcome measures should be chosen to reflect changes within the domains of body functions and structures, activity, and participation. There is a need to strengthen the evidence in the area of reconstructive procedures for people with tetraplegia. Research continues to advance, providing more options for improved function in this population than ever before. The contribution of well-designed outcome studies to this evidence base will ultimately help to address the complications surrounding access to the procedures.


MRI of the lung (2/3). Why … when … how?
Among the modalities for lung imaging, proton magnetic resonance imaging (MRI) has been the latest to be introduced into clinical practice. Its value to replace X-ray and computed tomography (CT) when radiation exposure or iodinated contrast material is contra-indicated is well acknowledged: i.e. for paediatric patients and pregnant women or for scientific use. One of the reasons why MRI of the lung is still rarely used, except in a few centres, is the lack of consistent protocols customised to clinical needs. This article makes non-vendor-specific protocol suggestions for general use with state-of-the-art MRI scanners, based on the available literature and a consensus discussion within a panel of experts experienced in lung MRI. Various sequences have been successfully tested within scientific or clinical environments. MRI of the lung with appropriate combinations of these sequences comprises morphological and functional imaging aspects in a single examination. It serves in difficult clinical problems encountered in daily routine, such as assessment of the mediastinum and chest wall, and even might challenge molecular imaging techniques in the near future. This article helps new users to implement appropriate protocols on their own MRI platforms. Main Messages • MRI of the lung can be readily performed on state-of-the-art 1.5-T MRI scanners. • Protocol suggestions based on the available literature facilitate its use for routine • MRI offers solutions for complicated thoracic masses with atelectasis and chest wall invasion. • MRI is an option for paediatrics and science when CT is contra-indicated.


Subsequent pregnancy and prognosis in breast cancer survivors.
An increase in the incidence of breast cancer in women aged < 40 years in conjunction with a pronounced shift towards later childbearing has been reported in recent years. Because survival from breast cancer in women of childbearing age has significantly improved, they are often concerned whether subsequent pregnancy will alter their risk of disease recurrence. In the modern era, the prognosis of pregnancy-associated breast cancer is comparable to non-pregnancy-associated breast cancer and women can bear children after breast cancer treatment without compromising their survival. Therefore, they should not be discouraged from becoming pregnant, and currently the usual waiting time of at least 2 years after the diagnosis of breast cancer is recommended. However, a small, nonsignificant adverse effect of pregnancy on breast carcinoma prognosis among women who conceive within 12 months of breast cancer diagnosis and a higher risk of relapse in women younger than 35 up to 5 years of the diagnosis may be found. Fortunately, for women with localized disease, earlier conception up to six months after completing their treatment seems unlikely to reduce their survival. Ongoing and future prospective studies evaluating the risks associated with pregnancy in young breast cancer survivors are required.


An experimental solution to the "missing hydrogens" question surrounding the macropolyhedral 19-vertex boron hydride monoanion [B19H22]-, a simplification of its synthesis, and its use as an intermediate in the first example of syn-B18H22 to anti-B18H22 isomer conversion.
The macropolyhedral [B(19)H(22)](-) monoanion 1 and the dianion [B(19)H(21)](2-) 2 are synthesized in consistent 86-92% yields by the reaction of [PSH](+)[syn-B(18)H(21)](-) with BH(3)(SMe(2)) in 1,2-Cl(2)C(2)H(4) at 72 degrees C. ['PS' is an abbreviation for 'Proton Sponge', 1,8-bis-(dimethylamino)naphthalene. 'PSH' is its protonated derivative.] The molecular structures of 1 and 2 were elucidated as their [PS{BH(2)}](+) and [PS{BH(2)}](2)(+) salts 1a and 2a by single-crystal X-ray diffraction studies, in which all atoms were located, and supported by mass spectrometric analyses together with calculations of the cluster molecular geometries (ab ignitio and/or DFT) and of (11)B chemical shifts based on GIAO-DFT shielding tensors. Acidification of dianion 2 with CF(3)COOH in acetonitrile, H(2)SO(4) in dichloromethane, or aqueous HCl results in the clean formation of the monoanion [B(19)H(22)](-) 1. Conversely, shaking a concentrated acetonitrile solution of 1 in 0.5 M aqueous NaOH cleanly yields the [B(19)H(21)](2-) dianion 2. Reaction of a dichloromethane solution of 1 with a 36% aqueous solution of HCHO in the presence of H(2)SO(4) quantitatively converts 1 at room temperature to a 1:1 mixture of the syn- and anti-isomers of B(18)H(22). This cluster dismantling process is the first example of a syn- to anti-B(18)H(22) isomer conversion.


Brain endothelial cell expression of SPARCL-1 is specific to chronic multiple sclerosis lesions and is regulated by inflammatory mediators in vitro.
Cell matrix modulating protein SPARCL-1 is highly expressed by astrocytes during CNS development and following acute CNS damage. Applying NanoLC-MS/MS to CSF of RRMS and SPMS patients, we identified SPARCL-1 as differentially expressed between these two stages of MS, suggesting a potential as CSF biomarker to differentiate RRMS from SPMS and a role in MS pathogenesis. This study examines the potential of SPARCL-1 as CSF biomarker discriminating RRMS from SPMS in three independent cohorts (n = 249), analyses its expression pattern in MS lesions (n = 26), and studies its regulation in cultured human brain microvasculature endothelial cells (BEC) after exposure to MS-relevant inflammatory mediators. SPARCL-1 expression in CSF was significantly higher in SPMS compared to RRMS in a Dutch cohort of 76 patients. This finding was not replicated in 2 additional cohorts of MS patients from Sweden (n = 81) and Switzerland (n = 92). In chronic MS lesions, but not active lesions or NAWM, a vessel expression pattern of SPARCL-1 was observed in addition to the expression by astrocytes. EC were found to express SPARCL-1 in chronic MS lesions, and SPARCL-1 expression was regulated by MS-relevant inflammatory mediators in cultured human BEC. Conflicting results of SPARCL-1's differential expression in CSF of three independent cohorts of RRMS and SPMS patients precludes its use as biomarker for disease progression. The expression of SPARCL-1 by BEC in chronic MS lesions together with its regulation by inflammatory mediators in vitro suggest a role for SPARCL-1 in MS neuropathology, possibly at the brain vascular level.


Physical adsorption and oxidation of ultra-thin MoS2crystals: insights into surface engineering for 2D electronics and beyond.
The oxidation mechanism of atomically thin molybdenum disulfide (MoS2) plays a critical role in its nanoelectronics, optoelectronics, and catalytic applications, where devices often operate in an elevated thermal environment. In this study, we systematically investigate the oxidation of mono- and few-layer MoS2flakes in the air at temperatures ranging from 23 °C to 525 °C and relative humidities of 10%-60% by using atomic force microscopy (AFM), Raman spectroscopy and x-ray photoelectron spectroscopy. Our study reveals the formation of a uniform nanometer-thick physical adsorption layer on the surface of MoS2, which is attributed to the adsorption of ambient moisture. This physical adsorption layer acts as a thermal shield of the underlying MoS2lattice to enhance its thermal stability and can be effectively removed by an AFM tip scanning in contact mode or annealing at 400 °C. Our study shows that high-temperature thermal annealing and AFM tip-based cleaning result in chemical adsorption on sulfur vacancies in MoS2, leading to p-type doping. Our study highlights the importance of humidity control in ensuring reliable and optimal performance for MoS2-based electronic and electrochemical devices and provides crucial insights into the surface engineering of MoS2, which are relevant to the study of other two-dimensional transition metal dichalcogenide materials and their applications.


A Case in the Bipolar Spectrum.
It has been reported that the correct diagnosis and treatment are delayed when subsyndromal bipolar mood disorder symptoms are overlooked. Patients in this spectrum are reported to have a diminished level of functioning, and these patients fail to accept their diagnosis; therefore, there is a low level of treatment adherence. This case report focuses on the diagnosis and treatment of a patient in the bipolar spectrum.


Release of nitric oxide and expression of constitutive nitric oxide synthase of human endothelial cells: enhancement by a 14-membered ring macrolide.
A 14-membered ring macrolide, erythromycin, acts not only as an antibacterial but also as an anti-inflammatory agent. We have previously reported that erythromycin modulates neutrophil functions and ameliorates neutrophil-induced endothelial cell damage through the action of cyclic AMP-dependent protein kinase (PKA) and nitric oxide (NO). We investigated the effect of erythromycin on human endothelial cell functions. Erythromycin enhanced intracellular calcium ion concentration ([Ca2+]i) of endothelial cells and NO release from endothelial cells. The enhancement of NO release from endothelial cells by erythromycin was abolished by addition of EGTA in the medium and was partially reduced by addition of H-89, an inhibitor of PKA. These results suggest that erythromycin enhances NO release from endothelial cells through the action of PKA and [Ca2+]i. In addition, constitutive NO synthase (cNOS) protein expression of endothelial cells was dose-dependently enhanced by treatment with erythromycin, which might also contribute to the enhancement of NO release from endothelial cells by erythromycin. The effect of erythromycin as an anti-inflammatory agent might be partially mediated through the enhancement of NO release from endothelial cells and the drug might be a useful tool for the investigation of cNOS of endothelial cells.


Studies on the prevalence and the transmission of lung and stomach nematodes of the wild boar (Sus scrofa) in France.
Five species of lung nematodes (Metastrongylus asymmetricus, M. confusus, M. elongatus, M. pudendotectus, M. salmi) and two species of stomach nematodes (Ascarops strongylina, Physocephalus sexalatus) were found in the wild boars (Sus scrofa) in France. Prevalence of lung nematodes was 92% (no significant difference between closed reserve and open areas could be demonstrated) and 97% for stomach nematodes. In both cases, intensity of infection was significantly greater in young wild boars (age less than 1 yr) than in the older animals. The importance of intermediate hosts in the transmission of these infections is emphasized by the increased prevalences and intensities in certain high risk areas and during certain seasons.


Effect of CCL2 siRNA on proliferation and apoptosis in the U251 human glioma cell line.
Glioma is one of the most common types of tumor of the central nervous system. Increased expression of C‑C motif chemokine 2 (CCL2) has previously been observed in various types of cancer. The effect of CCL2 small interfering (si)RNA on the proliferation, angiogenesis and apoptosis of the glioma cell line U251 was investigated in the present study. Data on CCL2 expression in glioma and normal tissues were obtained from The Cancer Genome Atlas. A total of 30 patients with glioma were enrolled in the present study. Cell proliferation was measured using a Cell Counting kit‑8 assay, while cellular apoptosis and cell cycle distribution were examined using flow cytometric analysis. The reverse transcription‑quantitative polymerase chain reaction and western blot analysis were used to measure the expression levels of biological pathway‑associated proteins caspase‑3, caspase‑7, tumor necrosis factor receptor superfamily member 10C (TNFRSF10C), growth regulated α protein (CXCL1), C‑X‑C motif chemokine 2 (CXCL2), C‑X‑C chemokine receptor type 2 (CXCR2), vascular endothelial growth factor (VEGF)A, VEGFB and VEGF. In addition, the mechanism of cellular apoptosis was analyzed by examining the phosphorylation of extracellular signal‑related kinase (ERK)1/2 and p38 mitogen‑activated protein kinase (p38) in cells treated with the C‑C chemokine receptor type 2 inhibitor RS‑102895. CCL2 was observed to be expressed in the glioma cell line U251 and was inhibited by CCL2 siRNA. Cells transfected with CCL2 siRNA exhibited inhibited cell proliferation, cell cycle arrest and increased cellular apoptosis. The expression levels of the apoptosis‑associated proteins caspase‑3, caspase‑7 and TNFRSF10C were observed to be downregulated, in addition to those of the angiogenesis‑associated proteins CXCL1, CXCL2, CXCR2, VEGFA, VEGFB and VEGF. The decrease in the rate of phosphorylation of ERK1/2 and p38 demonstrated the involvement of the mitogen‑activated protein kinase/ERK pathway in apoptosis. In conclusion, CCL2 siRNA exhibited effective inhibition of cell proliferation and angiogenesis in the glioma cell line U251, which may provide a theoretical basis for the use of CCL2 in in vivo research and clinical treatment as a novel anticancer agent.


A deep learning approach to estimate stress distribution: a fast and accurate surrogate of finite-element analysis.
Structural finite-element analysis (FEA) has been widely used to study the biomechanics of human tissues and organs, as well as tissue-medical device interactions, and treatment strategies. However, patient-specific FEA models usually require complex procedures to set up and long computing times to obtain final simulation results, preventing prompt feedback to clinicians in time-sensitive clinical applications. In this study, by using machine learning techniques, we developed a deep learning (DL) model to directly estimate the stress distributions of the aorta. The DL model was designed and trained to take the input of FEA and directly output the aortic wall stress distributions, bypassing the FEA calculation process. The trained DL model is capable of predicting the stress distributions with average errors of 0.492% and 0.891% in the Von Mises stress distribution and peak Von Mises stress, respectively. This study marks, to our knowledge, the first study that demonstrates the feasibility and great potential of using the DL technique as a fast and accurate surrogate of FEA for stress analysis.