Lung fibrosis induced by diquat after intratracheal administration.
Diquat toxicity to lung was evaluated at various intervals after intratracheal administration to rats. Twelve hours after the injection, both type I and type II pneumocytes developed degenerative changes which were similar in nature to those induced by paraquat. A much larger dose of diquat, however, was needed for the changes compared to paraquat, which is known to be actively taken up by the lung. This morphological evidence suggests that diquat may cause alveolar damage by the same mechanism as paraquat, although it is not actively taken up by the lung. Moreover, initial alveolar damage induced by diquat was followed by lung fibrosis, as with paraquat. Since paraquat is a well known fibrogenic agent, the common property of these two agents in alveolar damage may be a key to interpreting the development of lung fibrosis.


Arcobacter spp. in fecal samples from Brazilian farmed caimans (Caiman yacare, Daudin 1802).
The aim of this study was to perform the identification and molecular characterization of Arcobacter cryaerophilus and Arcobacter butzleri isolated from caiman (Caiman yacare), kept at a production farm, in Brazil. Forty fecal samples were analyzed. After isolation and identification, 21/40 strains of A. butzleri and 19/40 strains of A. cryaerophilus were subjected to PCR for potential virulence gene detection. The results of the PCR showed 38/40 strains positive for the cadF, cj1349, ciaB, and tlyA genes, 39/40 strains positive for the pldA gene, and 40/40 strains positive for the mviN gene. None of the strains presented the irgA gene. Hemagglutinin (hecA gene) and hemolysin (hecB) genes were detected in 21/40 and 16/40 strains, respectively. The SE-AFLP showed a great genetic diversity, but some clonally groups were disseminated in various tanks. These data reveal that the strains presented the same virulence traits described from Arcobacter isolated from food-borne disease in humans.


A home visit program for low-income African American children with asthma: Caregivers' perception of asthma triggers and a gap in action.
The goals are to gauge caregivers' knowledge of at-home asthma triggers and identify the areas on which educational campaigns can focus to alleviate a child's asthma symptoms. Families with children with moderate to severe asthmatic symptoms who had been recently hospitalized or in the emergency room were invited to participate in a home visit program. As part of the home visit, caregivers of the asthmatic children were asked a series of questions on asthma triggers and the measures for eliminating the triggers (N = 218). Findings show a gap between caregivers' perception of asthma triggers and the actions to mitigate or avoid such triggers. Overall findings show that home environments were suboptimal for the management and control of child asthma conditions. Knowledge about home triggers as well as the actions and efforts by caregivers and landlords to mitigate these was found to be inadequate. Even when caregivers are aware of the presence of at-home triggers, actions to minimize exposure to the trigger do not always follow due to a lack of power, resource, and knowledge. The findings raise the need for additional research to investigate the reasons for the lack of actions, advocacy for low-income families to live in a healthy environment, continued education and empowerment, and patient/caregiver-doctor partnership. Additionally, the provision of community support through community advocacy and training of culturally competent healthcare providers are needed for the successful management of pediatric asthma among African American children.


[Veterinary Drug 'what'? Various marginal notes by an 'industrial veterinarian'].
A retrospective view of the history of the Veterinary Medicinal Products Act and the current situation of the trade in veterinary drugs is followed by a discussion of a number of changes which will have to be made in the fields of production, packing, distribution and the trade in these drugs. With regard to these last-named items, a connection with the Act on the Practice of Veterinary Medicine should be made. In general it can be stated that the innovating industry is not dissatisfied, but only the actual enforcement of the act will provide genuine replies to questions which are still unanswered.


Randomised controlled trial of a shared care programme for newly referred cancer patients: bridging the gap between general practice and hospital.
To determine the effect of a shared care programme on the attitudes of newly referred cancer patients towards the healthcare system and their health related quality of life and performance status, and to assess patients' reports on contacts with their general practitioner (GP). Department of Oncology at Aarhus University Hospital and general practices. Randomised controlled trial in which patients completed questionnaires at three time points. The shared care programme included transfer of knowledge from the oncologist to the GP, improved communication between the parties, and active patient involvement. 248 consecutive cancer patients recently referred to the department. Patients' attitudes towards the healthcare services, their health related quality of life, performance status, and reports on contacts with their GPs. The shared care programme had a positive effect on patient evaluation of cooperation between the primary and secondary healthcare sectors. The effect was particularly significant in men and in younger patients (18-49 years) who felt they received more care from the GP and were left less in limbo. Young patients in the intervention group rated the GP's knowledge of disease and treatment significantly higher than young patients in the control group. The number of contacts with the GP was significantly higher in the intervention group. The EORTC quality of life questionnaire and performance status showed no significant differences between the two groups. An intersectoral shared care programme in which GPs and patients are actively involved has a positive influence on patients' attitudes towards the healthcare system. Young patients and men particularly benefit from the programme.


Paraaortic lymph node micrometastasis and tumor cell microinvolvement in advanced gastric carcinoma.
BACKGROUND: Paraaortic lymph node dissection in advanced gastric carcinoma is controversial. The purpose of this study was to investigate the incidence and significance of micrometastasis (MM) or tumor cell microinvolvement (TCM) in these critical lymph nodes.METHODS: A total of 2339 lymph nodes, including 390 paraaortic nodes, obtained from 47 patients with advanced gastric carcinoma were examined immunohistochemically, using cytokeratin antibody.RESULTS: Lymph node metastasis was found in 95 of the 390 paraaortic nodes of 14 patients by routine histological examination. MM or TCM was immunohistochemically detected in 45 of the 295 negative paraaortic lymph nodes from 15 of 33 patients (MM, n = 5; TCM, n = 10). The 5-year-survival rate in the paraaortic node-negative group and cytokeratin-positive group was significantly higher that that of the hematoxilin and eosin-positive group. The total number of lymph node metastases by hematoxylin and eosin staining and the pathological lymph node compartments, by cytokeratin-positive nodes, were prognostic factors by multivariate analysis.CONCLUSIONS: We demonstrated a high rate of MM or TCM in the paraaortic lymph nodes and suggest that such harbored metastases are related to the prognosis of patients with advanced gastric carcinoma. On the basis of this study, a multi-institutional study should be considered.


The quantum casimir effect may be a universal force organizing the bilayer structure of the cell membrane.
A mathematic-physical model of the interaction between cell membrane bilayer leaflets is proposed based on the Casimir effect in dielectrics. This model explains why the layers of a lipid membrane gently slide one past another rather than penetrate each other. The presented model reveals the dependence of variations in the free energy of the system on the membrane thickness. This function is characterized by the two close minima corresponding to the different levels of interdigitation of the lipids from neighbor layers. The energy barrier of the compressing transition between the predicted minima is estimated to be 5.7 kT/lipid, and the return energy is estimated to be 3.1 kT/lipid. The proposed model enables estimation of the value of the membrane elastic thickness modulus of compressibility, which is 1.7 × 10⁹ N/m², and the value of the interlayer friction coefficient, which is 1.9 × 10⁸ Ns/m³.


(Z)- and (E)-2-(hydroxymethylcyclopropylidene)-methylpurines and pyrimidines as antiviral agents.
Several Z- and E-methylenecyclopropane nucleoside analogues were synthesized and tested for antiviral activity in vitro against human and murine cytomegalovirus (HCMV, MCMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), hepatitis B virus (HBV), herpes simplex virus types 1 and 2 (HSV-1, HSV-2), human herpesvirus 6 (HHV-6) and human immunodeficiency virus type 1 (HIV-1). The Z-2-amino-6-cyclopropylaminopurine analogue was the most effective agent against HCMV (EC50 or EC90 0.4-2 microM) followed by syncytol and the Z-2,6-diaminopurine analogues (EC50 or EC90 3.4-29 and 11-24 microM, respectively). The latter compound was also a strong inhibitor of MCMV (EC50 0.6 microM). Syncytol was the most potent against EBV (EC50 < 0.41 and 2.5 microM) followed by the Z-2,6-diaminopurine (EC50 1.5 and 6.9 microM) and the Z-2-amino-6-cyclopropyl-aminopurine derivative (EC50 11.8 microM). Syncytol was also most effective against VZV (EC50 3.6 microM). Activity against HSV-1, HSV-2 and HHV-6 was generally lower; synthymol had an EC50 of 2 microM against HSV-1 (ELISA) and 1.3 microM against EBV in Daudi cells but was inactive in other assays. The 2-amino-6-cyclopropylamino analogue displayed EC50 values between 215 and > 74 microM in HSV-1 and HSV-2 assays. 2-Amino-6-cyclopropylaminopurine and 2,6-diaminopurine derivatives were effective against HBV (EC50 2 and 10 microM, respectively), whereas none of the analogues inhibited HIV-1 at a higher virus load. Syncytol and the E isomer were equipotent against EBV in Daudi cells but the E isomer was much less effective in DNA hybridization assays. The E-2,6-diaminopurine analogue and E isomer of synthymol were devoid of antiviral activity.


Indication for endoscopic third ventriculostomy.
Endoscopic third ventriculostomy (ETV) is increasingly prevalent among pediatric neurosurgeons as the initial treatment for hydrocephalus. The combination of ETV and choroid plexus cauterization (ETV/CPC) has improved the success rate among infants with hydrocephalus for whom ETV alone is much less successful. In parts of the developing world where there are economic and human resource constraints, this mode of treatment may be more appropriate than the routine use of shunts, which are prone to failures that require urgent surgical treatment. Here we review indications for the use of ETV or ETV/CPC as the primary treatment for hydrocephalus. Primary treatment of hydrocephalus by ETV can avoid shunt-dependence and its complications for many patients. Optimal results depend upon proper patient selection and the use of combined ETV/CPC when treating infants.


The effects of pulsing magnetic fields on pineal melatonin synthesis in a teleost fish (brook trout, Salvelinus fontinalis).
Based on findings in various mammalian species, where exposure to electromagnetic fields decreased the nocturnal synthesis of the pineal secretory product melatonin, we investigated the effects of magnetic field (MF) exposure in a teleost fish, the brook trout (Salvelinus fontinalis). Fields were generated by Helmholtz coils (maximum flux density 40 microT, frequency 1 Hz, 200 ms on, 800 ms off). Melatonin concentrations were estimated by a specific radioimmunoassay. MF exposure significantly increased night-time pineal (P < 0.001) and serum (P < 0.01) melatonin levels, as compared with the controls. It is suggested that either the pineal glands are directly affected, i.e. by an increased Ca2+-influx into pineal photoreceptors, or that the responses are indirect since induced currents, caused by the rapid rise and decay of the generated MF, may have disturbed the sensory system for electric fields.


Effects of contraction and insulin on protein synthesis, AMP-activated protein kinase and phosphorylation state of translation factors in rat skeletal muscle.
In rat epitrochlearis skeletal muscle, contraction inhibited the basal and insulin-stimulated rates of protein synthesis by 75 and 70%, respectively, while increasing adenosine monophosphate-activated protein kinase (AMPK) activity. Insulin, on the other hand, stimulated protein synthesis (by 30%) and increased p70 ribosomal protein S6 kinase (p70S6K) Thr389, 40S ribosomal protein S6 (rpS6) Ser235/236, rpS6 Ser240/244 and eukaryotic initiation factor-4E-binding protein-1 (4E-BP1) Thr37/46 phosphorylation over basal values. Electrical stimulation had no effect on mammalian target of rapamycin complex 1 (mTORC1) signalling, as reflected by the lack of reduction in basal levels of p70S6K, rpS6 Ser235/236, rpS6 Ser240/244 and 4E-BP1 phosphorylation, but did antagonize mTORC1 signalling after stimulation of the pathway by insulin. Eukaryotic elongation factor-2 (eEF2) Thr56 phosphorylation increased rapidly on electrical stimulation reaching a maximum at 1 min, whereas AMPK Thr172 phosphorylation slowly increased to reach threefold after 30 min. Eukaryotic elongation factor-2 kinase (eEF2K) was not activated after 30 min of contraction when AMPK was activated. This could not be explained by the expression of a tissue-specific isoform of eEF2K in skeletal muscle lacking the Ser398 AMPK phosphorylation site. Therefore, in this skeletal muscle system, the contraction-induced inhibition of protein synthesis could not be attributed to a reduction in mTORC1 signalling but could be due to an increase in eEF2 phosphorylation independent of AMPK activation.


Pediatric anesthesiology fellow education: is a simulation-based boot camp feasible and valuable?
Pediatric anesthesiologists must manage crises in neonates and children with timely responses and limited margin for error. Teaching the range of relevant skills during a 12-month fellowship is challenging. An experiential simulation-based curriculum can augment acquisition of knowledge and skills. To develop a simulation-based boot camp (BC) for novice pediatric anesthesiology fellows and assess learner perceptions of BC activities. We hypothesize that BC is feasible, not too basic, and well received by fellows. Skills stations, team-based in situ simulations, and group discussions of complex cases were designed. Stations were evaluated by anonymous survey; fellows rated usefulness in improving knowledge, self-confidence, technical skill, and clinical performance using a Likert scale (1 strongly disagree to 5 strongly agree). They were also asked if stations were too basic or too short. Median and interquartile range (IQR) data were calculated and noted as median (IQR). Fellows reported the difficult airway station and simulated scenarios improved knowledge, self-confidence, technical skill, and clinical performance. They disagreed that stations were too basic or too short with exception of the difficult airway session, which was too short [4 (4-3)]. Fellows believed the central line station improved knowledge [4 (4-3)], technical skills [4 (4-4)], self-confidence [4 (4-3)], and clinical performance [4 (4-3)]; scores trended toward neutral likely because the station was perceived as too basic [3.5 (4-3)]. An interactive session on epinephrine and intraosseous lines was valued. Complicated case discussion was of educational value [4 (5-4)], the varied opinions of faculty were helpful [4 (5-4)], and the session was neither too basic [2 (2-2)] nor too short [2 (2-2)]. A simulation-based BC for pediatric anesthesiology fellows was feasible, perceived to improve confidence, knowledge, technical skills, and clinical performance, and was not too basic.


Traditional and laparoscopic appendectomy in adults: outcomes in English NHS hospitals between 1996 and 2006.
This study investigated length of stay, readmission rates, and postoperative mortality in adult patients undergoing traditional and laparoscopic appendectomy in England between April 1, 1996, and March 31, 2006. All procedures coded to the "H01-Emergency Excision of Appendix" procedure code in the Hospital Episode Statistics database were included. Multivariate analyses were used to identify independent predictors of length of hospital stay, 30-day and 365-day mortality. A total of 259,735 procedures were assigned to the H01-Emergency excision of appendix OPCS-4 3-digit code procedure between 1996 and 2006. A laparoscopic technique was employed in 16,315 (6.3%). A greater proportion of deaths occurred in hospital within 30 days of "open" appendectomy surgery (0.25%) compared with procedures utilizing a laparoscopic technique (0.09%, P < 0.001). One-year mortality rates, measured over a 5-year period, were also higher after open surgery (0.64% vs. 0.29%, P < 0.001). Multiple logistic regressions demonstrated that an open operative technique, older age, male gender, and increasing comorbidity were strong independent determinants of early and 1-year postoperative mortality after emergency appendectomy. The duration of stay for patients undergoing open emergency appendectomy exceeded that for patients undergoing the laparoscopic technique (P < 0.001). Patients undergoing a laparoscopic technique were, however, more likely to be readmitted within 28 days of surgery (7.10% vs. 4.95%, P < 0.001). Laparoscopic appendectomy is safe and associated with lower postoperative mortality rates than open procedures. The cost implications are uncertain as this technique is associated with shorter hospital stay but higher subsequent readmission rates.


beta-2-microglobulin. Quantitation by rocket immunoelectrophoresis and evaluation of serum levels in renal transplant patients.
An assay using Laurell rocket immunoelectrophoresis has been developed for quantitation of beta-2-microglobulin (beta 2m) and serial levels of beta 2m have been measured in sera obtained daily from 52 patients following renal transplantation. The RIEP assay was performed using 1% low-endosmosis agarose gels containing 4% polyethylene glycol 6000 and the IgG fraction of rabbit antihuman beta 2m. Elevated beta 2m levels pretransplant fell markedly in the first 48 hr posttransplant in all patients with primary functioning grafts. Base-line control values for serum beta 2m were obtained in patients when stable graft function was established. Serum beta 2m levels increased during renal graft rejection, and significant elevations of serum beta 2m were detected at the onset of all graft rejection episodes as compared with control values. It is suggested that serum beta 2m quantitation by rocket immunoelectrophoresis is a simple and valuable assay to assess posttransplant renal graft function.


Visceral adipose tissue macrophage-targeted TACE silencing to treat obesity-induced type 2 diabetes.
Obesity is an increasingly prevalent global health problem. Due to its close relations with metabolic diseases and cancer, new therapeutic approaches for treating obesity and obesity-induced metabolic diseases are required. Visceral white adipose tissue (WAT) has been closely associated with obesity-induced inflammation and adipose tissue macrophages (ATMs) are responsible for obesity-induced inflammation by releasing inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6. TNF-α converting enzyme (TACE) is a transmembrane enzyme that induces the enzymatic cleavage and release of inflammatory cytokines. In this study, we developed a nonviral gene delivery system consisting of an oligopeptide (ATS-9R) that can selectively target visceral ATMs. In here we shows visceral adipose tissue-dominant inflammatory gene over-expressions in obese mouse and our strategy enabled the preferential delivery of therapeutic genes to visceral ATMs and successfully achieved ATM-targeted gene silencing. Finally, ATS-9R-mediated TACE gene silencing in visceral ATMs alleviated visceral fat inflammation and improved type 2 diabetes by reducing whole body inflammation.


Structure-function relationships in rat brainstem subnucleus interpolaris: III. Local circuit neurons.
Intracellular recording, electrical stimulation, receptive field mapping, and intracellular injection of horseradish peroxidase were used to assess the response properties, collateral projections, and morphology of 44 local circuit (LC) neurons in the subnucleus interpolaris (Sp Vi) of the trigeminal brainstem complex of the rat. LC neurons were defined as those with axons restricted to brainstem areas receiving trigeminal primary afferent fibers. Thus, none were antidromically activated from the thalamus, tectum, or cerebellum, and their axons could be seen terminating exclusively within the trigeminal brainstem complex or reticular formation. All neurons sampled were discharged by innocuous or noxious mechanical stimulation of a restricted portion of the face or mouth. They were classified functionally as sensitive to vibrissae (N = 22), nociceptors (N = 9), guard hairs (N = 7), hairy skin (N = 3), or periodontia (N = 3). Fifty percent of the stained neurons were vibrissa sensitive. Twenty-one of these 22 responded to deflection of only one vibrissa. The remaining functional groups also had small receptive fields. Intracellular staining revealed a consistency in vibrissa-sensitive LC morphology. Somata were small to medium in size and multipolar. Their axons had an initial transverse trajectory and gave off recurrent collaterals which arborized extensively in the region of the soma. The parent axon then bifurcated. One branch traveled rostrally to subnucleus principalis while the other branch traveled caudally to subnucleus caudalis. The branches periodically sent collaterals into regions of the trigeminal complex corresponding to the transverse position of the soma. Dendrites extended 440 +/- 140 microns rostrocaudally, forming a tree with a transverse perimeter of 459 +/- 226 microns. Distal dendrites were thin and sinuous, had few spines, and extensively arborized adjacent to the soma. They ended in multiple swellings connected by slender processes. The stereotyped morphology of vibrissa-sensitive LC neurons differed from the variable morphologies of LC neurons activated by nociceptors, guard hairs, hairy skin, or periodontia. Although no group of neurons in one of these categories displayed a distinguishing morphological characteristic, they collectively had features which distinguished them from the vibrissa-sensitive neurons. Non-vibrissa-responsive neurons generally had more expansive, but less circular, dendritic and recurrent axonal arbors; dendrites had more spines, and axons often sent endings into the reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)


[Patient education and therapy compliance].
The effects of oral health promotion activities depend on the degree of patient compliance, the extent to which a patient's behaviour is in accordance with dental health advice and instructions. Compliance is considered as a complex phenomenon. With the help of theories and models of health behaviour and the results of advertising research and consumer behaviour studies, some views are presented to increase patient compliance in dental practice.


Monitoring of low-molecular-weight protein aggregation by CE-SDS as a complementary method to SE-HPLC.
Capillary electrophoresis with sodium dodecyl sulfate (CE-SDS) has long been proven to have excellent performance in the analysis and characterization of therapeutic proteins. However, it is rarely used for the detection of low-molecular-weight proteins or peptides. Our research has proved the ability of CE-SDS to characterize the purity of low-molecular-weight proteins (i.e., <10 kDa) and even polypeptides. In this article, insulin glargine was used as a model protein, and CE-SDS was used to analyze the samples damaged by heating and light exposure. The monomers, dimers, and trimers of insulin glargine were effectively separated, and the results of the mass spectrometry also confirmed the existence of two kinds of insulin aggregates. For comparison, the size-exclusion high-performance liquid chromatography (SE-HPLC) only showed a single aggregate peak. In addition, the denaturation conditions caused only the covalent aggregates to appear in the CE-SDS analysis. These advantages also make CE-SDS an excellent supplementary technology to the traditional SE-HPLC, providing biopharmaceutical analysts with more information.


Incidence, risk factors, and outcomes of post-transplant erythrocytosis after kidney transplantation.
The incidence, risk factors, and outcomes of kidney transplant recipients (KTRs) with post-transplant erythrocytosis (PTE) in the modern era of strong, protocolized immunosuppressive management are unknown. In this study, we aim to identify the incidence and risk factors of PTE and outcomes associated with PTE. This study examined adult KTRs transplanted at our hospital between 01/2001 and 12/2016. Controls were KTRs without PTE and selected in a 1:5 ratio using incident density sampling. Patient survival, graft survival, and vascular thromboembolism (VTE) incidence were outcomes of interest. Of 4,317 kidney transplants during the study period, 214 (5%) had PTE and were compared with controls. In the multivariate analysis, recipients with older age (HR: 0.97, 95% CI 0.96-0.99, p = .001) were less likely to develop PTE, while male gender (HR: 3.2; 95% CI: 1.92-5.3, p < .001) and non-preemptive transplant (HR: 3.86, 95% CI 1.56-9.56, p = .003) were associated with increased risk of PTE. After adjustment for confounding factors, PTE was not associated with patient mortality (HR: 0.99, 95% CI 0.69-1.42, p = .97), graft failure (HR: 1.11, 95% CI 0.68-1.80, p = .69), or VTE (HR: 1.07, 95% CI 0.59-1.96, p = .81). The incidence of PTE is still substantial in this era, but with proper management PTE does not impact patient or graft survival.


Polypoidal choroidal vasculopathy: a review.
More than a quarter century has passed since the original description of polypoidal choroidal vasculopathy (PCV) in 1982 as a peculiar hemorrhagic disorder involving the macula characterized by recurrent subretinal pigment epithelial bleeding. In the ensuing years, numerous reports have described the expanded clinical spectrum of this entity. PCV is the principal vascular composition of patients of pigmented races experiencing neovascular maculopathies, particularly African Americans and Asians. This form of neovascularization is now known to occur in white patients with or without concomitant drusen, and the site of involvement has extended from the peripapillary area to the peripheral fundus. Indocyanine green angiography has made detection of these abnormal vascular changes more reliable and definitive. More precise diagnosis has also led to a better understanding of specific clinical features that distinguish PCV from more typical proliferations of abnormal choroidal vessels. We review the nature of PCV, including its genetic basis, demographic features, histopathology, clinical manifestations, natural course, response to treatments, and the histopathological and genetic bases. We emphasize multimodal ophthalmic imaging of these vessels, in particular fluorescein and indocyanine green angiography and optical coherence tomography.


Quantitative real-time PCR in aDNA research.
Quantitative real-time PCR (qPCR) is a technique that is widely used in the field of ancient DNA (aDNA). Quantitative PCR can be used to optimize aDNA extraction methodologies, to detect PCR inhibition, and to quantify aDNA libraries for use in high-throughput sequencing. In this chapter, we outline factors that need to be considered when developing efficient SYBR Green qPCR assays. We describe how to setup qPCR standards of known copy number and provide some useful tips regarding interpretation of qPCR data generated from aDNA templates.


Monitoring transfusion practice--a computerized procedure.
As the description of transfusion practice over time requires the handling of massive amounts of data, and because the majority of records have until now been paper-based, little is known about the epidemiology of blood transfusion. Furthermore, most previous studies have collected data manually from patient records or from computerized registers created solely for study purposes. We describe a procedure for monitoring transfusion practices based exclusively upon the collection of data from the existing computerized registers. During the calendar years 1997 and 1998, more than 750 000 data records were collected from the blood transfusion registers, diagnosis and procedure registers, and clinical biochemistry registers at two university hospitals. Linking of the data required a unique and consistent identification of all data records. This was made possible by the national Personal Identification Number. In this way more than 98% of all transfusions could be identified and approximately 95% (77 950) could be connected to a principal diagnosis. The described procedure creates new opportunities for studies of transfusion practices both on a large scale and in richness of detail, and we propose to establish a network where transfusion practices data are available and comparable for individual departments, hospitals, whole regions, and possibly nations.


Increase of a form of UDP-glucuronyltransferase glucuronizing various phenolic xenobiotics and the corresponding translatable mRNA in 3-methylcholanthrene-treated rat liver.
Induction of hepatic microsomal UDP-glucuronyltransferase activity toward various phenolic xenobiotics by 3-methylcholanthrene treatment of rats was observed, and the process of the induction was studied. We had previously purified a form of UDP-glucuronyltransferase (called GT-1) having a catalytic activity toward phenolic xenobiotics from liver microsomes of 3-methylcholanthrene-treated rats. The antibodies against GT-1 inhibited the enzyme activity toward those xenobiotics in liver microsomes, and bound to a single protein having a molecular weight of about 54,000 Da (same value as that of GT-1) among microsomal proteins on immunoblotting analysis. The amount of GT-1 protein in hepatic microsomes was found to be increased in close correspondence with the activity increase by 3-methylcholanthrene treatment, by immunoblotting analysis using an uninducible cytochrome P-450 reductase as a negative standard. It was shown by in vitro translation assays that the protein increase described above resulted from the enhancement of the level of translatable mRNA encoding for GT-1. Increases in the amount of the protein immunochemically corresponding to GT-1 in the microsomes from liver of phenobarbital-treated rats and from extrahepatic organs, such as kidney, small intestine, and lung, of phenobarbital- or 3-methylcholanthrene-treated rats were also observed.


Cardiac Magnetic Resonance Quantification of Structure-Function Relationships in Heart Failure.
Classification of heart failure is based on the left ventricular ejection fraction (EF): preserved EF, midrange EF, and reduced EF. There remains an unmet need for further heart failure phenotyping of ventricular structure-function relationships. Because of high spatiotemporal resolution, cardiac magnetic resonance (CMR) remains the reference modality for quantification of ventricular contractile function. The authors aim to highlight novel frameworks, including theranostic use of ferumoxytol, to enable more efficient evaluation of ventricular function in heart failure patients who are also frequently anemic, and to discuss emerging quantitative CMR approaches for evaluation of ventricular structure-function relationships in heart failure.


Integrative analysis of structural variations using short-reads and linked-reads yields highly specific and sensitive predictions.
Genetic diseases are driven by aberrations of the human genome. Identification of such aberrations including structural variations (SVs) is key to our understanding. Conventional short-reads whole genome sequencing (cWGS) can identify SVs to base-pair resolution, but utilizes only short-range information and suffers from high false discovery rate (FDR). Linked-reads sequencing (10XWGS) utilizes long-range information by linkage of short-reads originating from the same large DNA molecule. This can mitigate alignment-based artefacts especially in repetitive regions and should enable better prediction of SVs. However, an unbiased evaluation of this technology is not available. In this study, we performed a comprehensive analysis of different types and sizes of SVs predicted by both the technologies and validated with an independent PCR based approach. The SVs commonly identified by both the technologies were highly specific, while validation rate dropped for uncommon events. A particularly high FDR was observed for SVs only found by 10XWGS. To improve FDR and sensitivity, statistical models for both the technologies were trained. Using our approach, we characterized SVs from the MCF7 cell line and a primary breast cancer tumor with high precision. This approach improves SV prediction and can therefore help in understanding the underlying genetics in various diseases.


Fractional flow reserve in patients with coronary artery disease undergoing TAVI: a prospective analysis.
To determine the true prevalence of CAD in AS patients, to detect changes of the hemodynamic significance of coronary lesions following TAVI, to explore to what extent FFR-positive CAD might influence outcome and finally to develop a management algorithm for this patient subset. From May 2016 to March 2018, diagnostic coronary angiography was performed in 246 patients before TAVI. In the presence of coronary lesions with a diameter stenosis ≥ 50%, FFR was measured. In patients with positive FFR ≤ 0.80, a control angiography was performed 6-8 weeks after TAVI. The study cohort was 81.0 ± 6.1 years old, 48.4% of the patients were male. 53.3% had concomitant CAD. 35.9% of these patients underwent PCI before TAVI due to functionally significant left main CAD and/or severe stenosis ≥ 90%. 31 patients underwent FFR measurements in cumulative 38 coronary lesions. Prior to TAVI, a negative FFR could be detected in 18 lesions, whereas a positive FFR was found in entirely 20 lesions. A control angiography and FFR measurement was performed in cumulative 13 lesions. Comparing the FFR values, there was no significant difference (0.77 ± 0.04 vs. 0.76 ± 0.08; p = 0.11). Concomitant CAD was diagnosed in 53.3% of TAVI patients. FFR did not significantly change after TAVI, confirming the validity of FFR to evaluate coronary lesions in this specific clinical setting. Given the low rates of cardiac adverse events, it might therefore be considered to treat coronary stenoses not involving left main and those with a diameter stenosis < 90% after TAVI.


Porcine epidemic diarrhea in China.
Porcine epidemic diarrhea (PED) is a contagious intestinal disease caused by Porcine epidemic diarrhea virus (PEDV) that characterized by vomiting, diarrhea, and dehydration. PEDV was first identified in the 1980s in China, and since then, it has become one of the most common viral causes of diarrhea. In October 2010, a large-scale outbreak of PED caused by a PEDV variant occurred in China, resulting in tremendous economic losses. This review presents a comprehensive description of PEDV history, prevalence, molecular features, and prevention and control strategies in China.


Digital display use and contact lens wear: Effects on dry eye signs and symptoms.
To assess the potential additive effects of short-term display use and contact lens (CL) wear on the ocular surface and tear film. Thirty-four healthy volunteers (20.87 ± 2.33 years old) participated in this study. Participants' dry eye symptoms, ocular surface, tear film and pupil size were assessed before and after executing a 20-min reading task on a computer and a smartphone with and without CL wear, or with CL wear and artificial tear instillation. Measurements included the Ocular Surface Disease Index (OSDI) questionnaire; 5-item Dry Eye Questionnaire (DEQ-5); tear meniscus height (TMH); noninvasive keratograph break-up time (NIKBUT); bulbar conjunctival redness (BR) and pupil size. Higher symptoms were reported after reading on both displays with and without CLs (p ≤ 0.001) for short periods. BR was higher and NIKBUT shorter after reading on the computer regardless of wearing CLs (p ≤ 0.02 and p ≤ 0.02, respectively), while TMH increased for all conditions (p ≤ 0.02) except for CL computer reading (p = 0.23). Reading with CLs did not lead to greater signs of dry eye (BR, NIKBUT) and symptoms compared with reading unaided (p > 0.05), although a smaller increase in TMH was observed when reading on the computer with CLs (p = 0.005). Artificial tear instillation during CL wear led to a smaller increase in symptoms (p ≤ 0.02), a smaller increase in BR (p ≤ 0.04) and a decrease in NIKBUT (p = 0.02) compared to reading without correction. Disposable CL wear had no additive effects on signs and symptoms of dry eye when using digital devices for short periods. The instillation of artificial tears is an effective strategy for reducing the impact of display use in CL wearers.


Hybrid lipid-biopolymer nanocarrier as a strategy for GBM photodynamic therapy (PDT).
Glioblastoma (GBM) is the most common brain cancer characterized by aggressive and infiltrated tumors. For this, hybrid biopolymer-lipid nanoparticles coated with biopolymers such as chitosan and lipidic nanocarriers (LN) loaded with a photosensitizer (AlClPc) can be used for GBM photodynamic therapy. The chitosan-coated LN exhibited stable physicochemical characteristics and presented as an excellent lipid nanocarrier with highly efficiently encapsulated photosensitizer chloro-aluminum phthalocyanine (AlClPc). LN(AlClPc)Ct0.1% in the presence of light produced more reactive oxygen species and reduced brain tumor cell viability and proliferation. Confirm the effects of in vivo LN applications with photodynamic therapy confirmed that the total brain tumor area decreased without systemic toxicity in mice. These results suggest a promising strategy for future clinical applications to improve brain cancer treatment.


Translation and culture adaptation of the Simplified Diabetes Knowledge Test, the Literacy Assessment for Diabetes and the Diabetes Numeracy Test.
The ability to understand instructions on drug bottles, appointment slips and medical education brochures could be affected by patients' health literacy. Healthcare providers need to be aware of, hence, assess patients' literacy before they develop effective educational strategies for these patients. Many validated instruments have been used to evaluate literacy of diabetic patients in the English language, only a limited number is available in Arabic. To translate and culturally-adapt the Simplified Diabetes Knowledge Test (DKT), the Literacy Assessment for Diabetes (LAD), and the Diabetes Numeracy Test (DNT) for potential use in Arabic-speaking countries. A formal process based on the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines was adopted in translating and culturally adapting the three tools. An expert panel reviewed forward and backward translations of the tools. Ten diabetic patients participated in the cognitive debriefing process to evaluate the tools for clarity, simplicity, and comprehensiveness, and to assess their cultural equivalence. Only minor changes were introduced in tools' design, appearance, and instructions. However, issues identified during the expert panel review and cognitive debriefing led to modifying the tools resulting in item re-wording, addition, deletion or re-arrangement. Terms such as glycosylated hemoglobin, carbohydrates, and infection were adapted to cumulative sugar, starch and microbial inflammation respectively. Issues related to cultural and conceptual equivalence were resolved by replacing words such as kilo instead of pound, and supper instead of dinner, or adding diacritics to the Arabic word for "kidney". The original 43 items of the DNT were reduced to 26, eliminating questions with the same mathematical calculations within each tool domain. A Culturally equivalent version of the Simplified DKT, LAD and DNT have been developed in the Arabic language available to be used in research and clinical practice in the Arabic speaking countries.


Estimation of varying ultrasonic attenuation.
This paper aims to investigate a method of estimating the attenuation and its variation. It is treated as an estimation problem by using modelling techniques known from communication theory. The model includes magnitude and position of specular echoes, a random description of echoes from diffuse reflectors, and a parametric characterization of attenuation. By processing the observed signal only in the time domain, low complexity calculation algorithms are achieved. Results obtained using simulated data indicate that the method works well on both broad-band and narrow-band signals.


Stress coping strategies of Iranian healthcare staff during the COVID-19 pandemic: A cross-sectional study.
The COVID-19 pandemic has exposed healthcare staff to mental distress. Given the importance of applying effective strategies to cope with stress caused by COVID-19, this study aimed to assess the stress-coping strategies of Iranian healthcare providers. This cross-sectional study was performed through a web-based survey. Data collection was done online using a demographic data questionnaire and the short form of Endler and Parker's coping inventory. The mean scores of task-oriented strategies (27.06 ± 5.13) were higher than avoidance-oriented (19.42 ± 5.77) and emotion-oriented strategies (18.45 ± 5.76), and the healthcare workers mainly used task-oriented styles to cope with COVID-19-related stress. There was a significant difference between the score of task-oriented strategy in terms of age groups (P < 0.001), work experience (P = 0.018), level of education (P < 0.001), having children (P = 0.002), and type of hospital (P = 0.028). The score of task-oriented strategies was lower in employees who were in the age group of 20-30 years and had less than 10 years of work experience, and it was higher in employees who had children, worked in private hospitals, and had a master's degree or higher. The score of emotion-oriented strategies in the age group of 51-60 years was significantly lower than other age groups (P < 0.01) and was significantly higher in employees with a bachelor's degree than those with a master's degree or higher (P = 0.017). There was no significant difference between the scores of avoidance-oriented strategies and any socio-demographic variables. According to the findings of this study, young and less experienced employees were more inclined to utilize emotion-oriented coping styles. Therefore, considering appropriate training programs for these employees to apply effective coping strategies is extremely important.


Value and safety of diet modification to control hyperlipidemia in childhood and adolescence. A statement for physicians. Ad Hoc Committee of the Steering Committee for Medical and Community Program of the American Heart Association.
Hyperlipidemia clearly is a risk factor for atherosclerotic disease in adults and very likely contributes to atherogenesis in children. The American Heart Association recommends that children with elevated plasma cholesterol or triglyceride be placed on an appropriate diet in order to reduce their risk of hyperlipidemia and possibly to reduce their risk of atherosclerotic disease when they become adults. Although the evidence does not yet support the recommendation that cholesterol and saturated fat should be reduced in the diet of all children, the public should be advised that such modification appears safe and very likely to be beneficial. Measuring plasma lipids of all children in order to prevent atherosclerotic disease probably is not cost effective. However, children of high risk families should be examined for hyperlipidemia.


Environmental temperature increases plasma GH levels independently of nutritional status in rainbow trout (Oncorhynchus mykiss).
Like many poecilotherms, salmonids exhibit seasonal variations of growth rate in relation with seasonal temperatures and plasma GH level. However, temperature alters other parameters like food intake, which may directly modify the level of plasma GH. In order to determine whether temperature regulates plasma GH levels independently of nutritional status, fish were reared at 8, 12, or 16 degrees C and either fed ad libitum (fish with different food intake) to determine the global effect of temperature, or with the same ration (1.2%/body weight) to observe the temperature effect in fish with the same growth rate. Plasma insulin level was inversely proportional to the temperature (8, 12, and 16 degrees C) in fish fed ad libitum (12.1+/-0.3 ng/ml, 10.9+/-0.3 ng/ml, 9.5+/-0.4 ng/ml; P<0.001) and in restricted fish (14.0+/-0.3 ng/ml, 11.3+/-0.3 ng/ml, 10.0+/-0.2 ng/ml; P<0.0001), probably due to a prolonged nutrient absorption, and delayed recovery of basal insulin level at low temperature. Conversely, temperature did not affect plasma T3 level of fish fed ad libitum (2.5+/-0.2 ng/ml, 2.4+/-0.1 ng/ml, 2.5+/-0.1 ng/ml at 8, 12, and 16 degrees C) while fish fed with the same ration present less T3 at 16 degrees C than at 8 degrees C (1.83+/-0.1 ng/ml versus 1.2+/-0.1 ng/ml; P<0.001) throughout the experiment; these observations indicate that different plasma T3 levels reflect the different nutritional status of the fish. The levels of GH1 and GH2 mRNA, and GH1/GH2 ratio were not different for whatever the temperature or the nutritional status. Pituitary GH content, of fish fed ad libitum did not exhibit obvious differences at 8, 12, or 16 degrees C (254+/-9 ng/g bw, 237+/-18 ng/g bw, 236+/-18 ng/g bw), while fish fed with the same ration have higher pituitary GH contents at 16 degrees C than at 8 degrees C (401+/-30 ng/g bw versus 285+/-25 ng/g bw; P<0.0001). Interestingly, high temperature strongly increases plasma GH levels (2.5+/-0.3 ng/ml at 8 degrees C versus 4.8+/-0.6 ng/ml at 16 degrees C; P<0.0001) to the same extent in both experiments, since at a given temperature average plasma GH was similar between fish fed ad libitum or a restricted diet. Our results, demonstrate that temperature regulates plasma GH levels specifically but not pituitary GH content, nor the levels of GH1 and GH2 mRNA. In addition no differential regulation of both GH genes was evidenced whatever the temperature.


Diagnosis of perigraft seroma formation by use of echocardiography after modified Blalock-Taussig shunt.
Perigraft seroma is a collection of non-secretory fibrous pseudomembrane surrounding a vascular graft, which is a collection of clear, sterile fluid. Thoracal computed tomography, Magnetic Resonance Imaging, and thoracal ultrasonography have been proposed for diagnosis of this pathology. A consecutive modified Blalock-Taussig (m-BT) shunt complicated by perigraft seroma formation, which is diagnosed using a Doppler ultrasonography (US), is presented here.


Agents that stimulate phosphoinositide turnover also elevate cAMP in SK-N-SH human neuroblastoma cells.
Stimulation of m1 and of m3 muscarinic receptors has previously been shown to increase intracellular cAMP levels in a variety of cells. Although the mechanism underlying this response is not fully understood, it has been hypothesized to be secondary to the IP3-mediated rise in intracellular calcium. In order to determine whether other means of elevating intracellular calcium also raise cAMP levels, we stimulated SK-N-SH human neuroblastoma cells with bradykinin or with maitotoxin. Both of these agents stimulated phospholipase C, stimulated inositol phosphate release and elevated cAMP levels, thus demonstrating that this cAMP response is not unique to muscarinic receptor stimulation.


Fv-1 regulation of lymphoma development and of thymic ecotropic and xenotropic MuLV expression in mice of the AKR/J x RF/J cross.
The incidence of spontaneous thymic lymphoma has been studied in crosses between AKR/J and RF/J mice. AKR mice develop a high incidence of this disease. RF mice transmit a marked resistance to development of the disease to F1 hybrid mice of the AKR x RF cross. This resistance is associated with a reduction of endogenous ecotropic and xenotropic MuLV expression in the prelymphomatous thymus. The RF gene governing the coordinate suppression of these three phenotypes has been mapped to the Fv-1 locus. These results indicate that the particular Fv-1 allele of AKR mice provides a permissive genetic background for endogenous ecotropic and xenotropic MuLV expression and that these viral activities may be etiologically involved in the development of spontaneous thymic lymphoma in the mouse.


Benefits of providing nesting material as a form of environmental enrichment for mice.
Husbandry conditions in a laboratory environment can be barren and monotonous. Improving those conditions by providing opportunities for laboratory mice to engage in species-specific behavior can improve their mental and physical well-being. Giving the animals choices and control over their environment is key to reducing stress. Nesting is a normal behavior of mice, and giving mice nesting opportunities allows them to choose how and where to create their nest and provides them a means of thermoregulation in their microenvironment.


Rational Inference of Beliefs and Desires From Emotional Expressions.
We investigated people's ability to infer others' mental states from their emotional reactions, manipulating whether agents wanted, expected, and caused an outcome. Participants recovered agents' desires throughout. When the agent observed, but did not cause the outcome, participants' ability to recover the agent's beliefs depended on the evidence they got (i.e., her reaction only to the actual outcome or to both the expected and actual outcomes; Experiments 1 and 2). When the agent caused the event, participants' judgments also depended on the probability of the action (Experiments 3 and 4); when actions were improbable given the mental states, people failed to recover the agent's beliefs even when they saw her react to both the anticipated and actual outcomes. A Bayesian model captured human performance throughout (rs ≥ .95), consistent with the proposal that people rationally integrate information about others' actions and emotional reactions to infer their unobservable mental states.


CT-guided stereotactic targeting accuracy of osteoid osteoma.
The aim of this study was to evaluate the CT-guided stereotactic targeting accuracy for radiofrequency ablation of osteoid osteoma (OO), a small, benign but painful osseous lesion. Patient and extremity were fixed in a vacuum cushion. The OO was targeted using an optical navigation system with a stereotactic targeting device. For evaluation of targeting errors, the control CT with the needle in place was fused with the planning CT. In 16 consecutive patients, nine OOs in the femur, four in the tibia, one in the spine, one in the ulna and one in the pubic bone were successfully targeted without complications. The mean ± SD lateral targeting error was 2.6 ± 1.7 mm at the needle entry and 1.9 ± 1.2 mm at the needle tip, and the mean angular error was 2.0 ± 1.3°. Stereotaxy allows for accurate and safe targeting of OOs in various bone regions.


Construction of Genomic and Sub-Genomic Dengue Infectious Replicons.
Dengue replicons are powerful tools used in studying virus biology as well as in high-throughput screening of drug candidates. Replicon constructs are developed as genomic (consists of all the viral protein genes) or sub-genomic (consists of only nonstructural protein genes) and are used to study various aspects of the virus life cycle such as genome replication and virus assembly. In addition, a replicon usually includes a reporter gene used in monitoring virus replication. In this chapter, we provide methods to develop both genomic and sub-genomic dengue replicons with a luciferase reporter and describe different assays to utilize these systems.


Effects of aerobic exercise training on hemodynamic responses during psychosocial stress in normotensive and borderline hypertensive type A men: a preliminary report.
This study assessed the effects of aerobic exercise training on cardiovascular responses to a 5-min reaction time competition task. Twenty-seven Type A men (aged 30-56) participated in this randomized study in which 14 underwent supervised aerobic training and 13 strength training, with sessions scheduled three times per week for 12 consecutive weeks. Aerobic exercise training was associated with a 13.6% increase in VO2max compared to 2.9% for the strength group. The effects of aerobic exercise training were most evident in subjects whose initial casual blood pressure readings fell in the borderline hypertensive range (N = 5). These individuals exhibited a general reduction in diastolic blood pressure (i.e., during rest, competition, and recovery) which was associated with a fall in both heart rate and total peripheral vascular resistance. Furthermore, diastolic pressure reactivity to the competition task was attenuated in borderline hypertensive subjects who underwent aerobic conditioning. These data are interpreted as preliminary findings suggesting that borderline hypertensives may be particularly responsive to the cardiovascular benefits of aerobic conditioning. For patients who have progressed to this stage of hypertensive disease, aerobic exercise may be of ameliorative value.


The role of Hex in hemangioblast and hematopoietic development.
The orphan homeobox gene Hex has been shown to be critical for normal murine liver development using Hex-/- mice. Because of the early lethality of the Hex-/- mice, however, in vitro embryonic stem cell differentiation assays were employed to elucidate the role of Hex in murine hematopoiesis. These studies revealed that Hex is not required for hemangioblast development but is required in a dose-dependent fashion for hemangioblast differentiation to definitive hematopoietic progenitors. Contained here are the methods needed to conduct embryonic stem cell-derived in vitro hematopoietic assays.


Gender-based violence experiences among Palestinian women during the COVID-19 pandemic: mental health professionals' perceptions and concerns.
In a geopolitically at-risk environment, such as Palestine, gender-based violence (GBV) is still a crucial problem rooted in discriminatory laws and traditional habits exacerbated by the ongoing Israeli military occupation. Moreover, the lack of updated data makes it difficult to grasp the magnitude of the phenomenon entirely; the purpose of the current study was to explore mental health professionals' perceptions and concerns on GBV among Palestinian women during the COVID-19 pandemic. Participants in the study were 30 Mental Health Professionals (MHP) selected using convenience and snowball sampling techniques from among MHP in northern West Bank, Palestine. A thematic content analysis revealed seven main themes of GBV during the pandemic. Palestinian MHP reported that the increased number of GBV cases among women during the COVID-19, quarantine, physical distancing measures, and closure of non-essential services significantly heightened the risks of GBV among Palestinian women. Moreover, Palestinian women involved with or married to older men or married at a very young age were at risk of GBV more than others. Results of qualitative analysis also showed that Israeli occupation and the political violence characterizing the area for decades (including restriction of movement, house demolitions, separation of family members, etc.) have also exacerbated and increased GBV in the occupied Palestinian territories. Improving intervention skills and supervision services among Palestinian MHP to help women who face GBV is recommended. Moreover, additional research should be conducted to explore the risk and potential factors of GBV, agency, and coping strategies to deal with GBV.


Assessing the toxicity of cell-bound microcystins on freshwater pelagic and benthic invertebrates.
Cyanobacterial harmful algal blooms dominated by Microcystis frequently produce microcystins, a family of toxins capable of inflicting harm to pelagic and benthic freshwater invertebrates. Research on the effect of microcystins on invertebrates is inconclusive; from one perspective, studies suggest invertebrates can coexist in toxic blooms; however, studies have also measured negative food-associated effects from microcystins. To test the latter perspective, we examined the reproduction, growth, and survival of laboratory-cultured Ceriodaphnia dubia, Daphnia magna, and Hexagenia spp. exposed to cell-bound microcystins through a series of life-cycle bioassays. Test organisms were exposed to a concentration gradient ranging from 0.5 μg L-1 to 300 μg L-1 microcystins, which corresponds to values typically found in freshwaters during bloom season. Lethal concentrations in C. dubia (LC50 = 5.53 μg L-1) and D. magna (LC50 = 85.72 μg L-1) exposed to microcystins were among the lowest recorded to date, and reproductive effects were observed at concentrations as low as 2.5 μg L-1. Length of D. magna was significantly impacted in microcystin treatments great than 2.5 μg L-1. No lethality or growth impairments were observed in Hexagenia. This information will improve our understanding of the risks posed by microcystins to food webs in freshwaters.


Development and Validation of the Pediatric Charcot-Marie-Tooth Disease Quality of Life Outcome Measure.
Charcot-Marie-Tooth disease (CMT) reduces health-related quality of life (QOL), especially in children. Defining QOL in pediatric CMT can help physicians monitor disease burden clinically and in trials. We identified items pertaining to QOL in children with CMT and conducted validation studies to develop a pediatric CMT-specific QOL outcome measure (pCMT-QOL). Development and validation of the pCMT-QOL patient-reported outcome measure were iterative, involving identifying relevant domains, item pool generation, prospective pilot testing and clinical assessments, structured focus-group interviews, and psychometric testing. Testing was conducted in children with CMT seen at participating sites from the USA, United Kingdom, and Australia. We conducted systematic literature reviews and analysis of generic QOL measures to identify 6 domains relevant to QOL in children with CMT. Sixty items corresponding to those domains were developed de novo, or identified from literature review and CMT-specific modification of items from the pediatric Neuro-QOL measures. The draft version underwent prospective feasibility and face content validity assessments to develop a working version of the pCMT-QOL measure. From 2010 to 2016, the pCMT-QOL working version was administered to 398 children aged 8 to 18 years seen at the participating study sites of the Inherited Neuropathies Consortium. The resulting data underwent rigorous psychometric analysis, including factor analysis, test-retest reliability, internal consistency, convergent validity, item response theory analysis, and longitudinal analysis, to develop the final pCMT-QOL patient-reported outcome measure. The pCMT-QOL patient-reported outcome measure is a reliable, valid, and sensitive measure of health-related QOL for children with CMT. ANN NEUROL 2021;89:369-379.


[Drug interactions in diabetic patients].
Many diabetic patients take medications which can interfere with the effect of insulin or oral antidiabetic agents. Glucocorticoid administration is not contraindicated in diabetic subjects, but it usually necessitates a pharmacotherapic adjustment. Most of the other potential diabetogenic drugs do not show evidence of any significant changes in glycaemic control in diabetic individuals; however, their prescription does require appropriate monitoring of blood glucose. Low dose combined oral contraceptives have little or no effect on blood glucose level; however, their prescription is not recommended in diabetic patients because of modifications in haemostasis and lipid metabolism. Oestrogen replacement therapy in post-menopausal women does not reduce glucose tolerance and it may reduce the risk of cardiovascular disease. Drug interactions which induce hypoglycaemia affect mostly non-insulin-dependent diabetic patients who take sulphonylureas. Combined insulin and sulphonylurea therapy is sometimes prescribed in poorly controlled type II diabetes. The efficacy of this combination is modest compared to insulin therapy alone. The influence of human insulin on symptoms and awareness of hypoglycaemia has been debated for several years. Today, the literature survey does not really support the hypothesis that the risk of severe hypoglycaemia is increased after transferring diabetic patients from animal insulin to human insulin. Many medications induce other side effects (e.g. orthostatic hypotension, hyperkaliemia, impotence...) in patients with diabetic complications.


Surface roughness and microhardness of enamel white spot lesions treated with different treatment methods.
To analyse the surface roughness and microhardness of artificial enamel white spot lesions before and after WSL formation, after treatment (Opalsutre™ microabrasion, Sylc® bioactive glass, and ICON® resin infiltration), and after pH cycling with the help of the profilometer surface roughness tester and the digital Vickers microhardness tester. Seventy-five extracted molars were used to acquire one hundred specimens. 50 specimens were randomly assigned to five groups (n = 10) for the surface roughness study: 1) Sound group, 2) WSL group, 3) micro abrasion (MA; Opalustre, Ultradent, South Jordan, UT, USA), 4) bioactive glass 45S5 Sylc powder (Sylc; Denfotex Research Ltd, Inverkeithing, UK), and 5) ICON resin infiltration (ICON; DMG, Hamburg, Germany). An additional 25 specimens were used to obtain 50 enamel slabs for the surface microhardness study, which were also assigned to the same groups. All groups underwent a final stage of pH cycling. Surface roughness and surface microhardness measurements were performed at different stages for all groups. Regarding surface roughness, ICON significantly reduced the surface roughness compared to Opalustre and Sylc, with no significant difference between Opalustre and Sylc. In terms of surface microhardness, ICON showed the highest improvement, followed by Sylc and then Opalustre. Both surface roughness and microhardness were significantly affected by demineralization, partially improved after treatment, and then regressed significantly after pH cycling. ICON resin infiltrant can be considered as a superior treatment option for improving surface roughness and microhardness, while Opalustre demonstrated relatively the poorest performance compared to the other treatment options. It is noteworthy that the pH cycling procedure had an adverse impact irrespective of the treatment option used.


Testing an Animal Welfare Assessment Protocol for Growing-Rabbits Reared for Meat Production Based on the Welfare Quality Approach.
The objective of the present study is to present an animal welfare assessment protocol for growing-rabbits for discussion after its implementation in 32 farms from Spain and Portugal. The protocol comprises the principles of Good Feeding, Good Housing, Good Health and Appropriate Behaviour of the Welfare Quality protocols and includes 36 welfare parameters. Overall, the protocol showed a good capacity for discrimination between farms, with scores ranging 44 to 82 points. The protocol seems reliable for the assessment of animal welfare after proper training of auditors. However, for the criteria social behaviour and other behaviours, further research is needed to ascertain if the methodology and times of observation used are appropriate. Some farms had high mortality rates with a low prevalence of health problems, while others had low mortality rates with high prevalence of health problems due to different managements of culling. The protocol should be improved, to impede farms with high mortality rates but a low prevalence of health issues the day of the audit from obtaining better scores than the second type of farms, by limiting the compensation in key measures. The main points to be solved in the growing-rabbit farms were: to provide more space to the animals; register the number of animals culled accurately; change cervical dislocation for another killing method and provide the farmers training in animal welfare.


Risk factors for HPV detection in archival Pap smears. A population-based study from Greenland and Denmark.
The most important risk factor for cervical cancer is genital infection with certain types of human papillomavirus (HPV). The presence of HPV was studied in archival smears from a random sample of women living in Greenland (GW) and Denmark (DW) having, respectively, a high risk and an intermediate risk for cervical cancer. Risk factors were also examined of the original 126 Danish and 129 Greenlandic archived smears collected during October and November 1988. 125 were located from each country including all abnormal smears. HPV DNA was isolated from the smears and detected by means of a consensus polymerase chain reaction (PCR) detecting a broad spectrum of genital HPV types. HPV was detected in all the abnormal smears and in 22 and 33% respectively of the cytological normal smears from DW and GW. Risk of HPV was significantly higher in smears from women who started sexual life relatively recently (respectively, < or = 4 and < or = 6 years ago in DW and GW) compared with > or = 10 years ago (adjusted prevalence-OR: 9.3; 95% CI: 2.2-39.2 in DW and 5.9; 95% CI: 1.4-25.3 in GW). Among other important risk factors were age in both areas, lifetime number of sex partners and current smoking in DW and ever and gonorrhoea in GW. This study confirms the usefulness of the method as all abnormal smears were positive and, furthermore, the predictors for HPV presence in the normal smears corroborate with those found in recent studies of HPV in fresh cervical swabs. Thus, this method can be useful for large-scale epidemiological studies of HPV DNA in already sampled material.


An approach to a selection system for adenosine-deaminase-positive (ADA+) cells and detection of rat ADA+ "revertants".
We have substituted deoxyadenosine or adenosine for hypoxanthine in the standard HAT selection system in an attempt to select for ADA-normal (ADA+) cells. ADA- human lymphoid line cells could not utilize deoxyadenosine as an alternative to hypoxanthine as a purine source (DAT) and failed to grow but were only somewhat inhibited in growth when adenosine was substituted for hypoxanthine (AAT). In contrast, ADA+ cells utilized adenosine or deoxyadenosine as efficiently as hypoxanthine as a purine source. Growth in DAT, but not in HAT, of an artificial mixture of one ADA+ human lymphoid cells in 1,000 ADA- cells resulted in enrichment of ADA+ cells to 25-86% of total cells. When we grew a rat ADA- cell line in two variations of the DAT system, we detected at least three electrophoretically different ADA+ patterns, one of which corresponded to normal rat ADA. These could represent "revertants."


A Narrative Review of Flutamide in Juvenile Nasopharyngeal Angiofibroma.
The detection of androgen receptors within Juvenile Nasopharyngeal Angiofibroma (JNA) has prompted investigation of the role of Flutamide. The aim of this review is to evaluate Flutamide as a possible neo-adjuvant treatment for JNA. Literature searches were conducted using MEDLINE, EMBASE and Web of Science. The Joanna Briggs Institute (JBI) checklist was used to assess risk of bias. The Oxford Centre of Evidence-Based Medicine (OCEBM) Levels of Evidence was used to stratify the evidence level. Literature searches were conducted using MEDLINE, EMBASE and Web of Science. Flutamide as neo-adjuvant treatment potentially causes a reduction in JNA tumor volume by ≥ 25%. Based on the current limited evidence, Flutamide has a limited role in JNA management and further research is required. Its utilization should only follow discussion with the patient, their families, and within the multidisciplinary team.


Hypertension in Sudanese individuals and associated risk factors: the critical intersection between salt and sugar intake.
Hypertension is common problem across the globe. The aim of this study was to assess the prevalence of hypertension and impact of salt and sugar intake in Sudanese population. A descriptive cross sectional study, included 323 of participants in Khartoum state. The data collection was performed to gather demographic information, physical activity and dietary habits. In addition to measurement of blood pressure (BP), weight and height measurement for calculation of body mass index (BMI). Among the 323 respondents (males were 171), 29 (9%) are known hypertensive, 60 (18.6%) are diagnosed to be hypertensive. Therefore, the prevalence of hypertension is 27.6%. Hypertension was significantly associated with male sex, increasing age, obesity, low physical activity, salt and sugar intake. Logistic regression analysis showed that increasing age, obesity and high sugar intake are absolute predictors for hypertension in Sudanese population. The prevalence of hypertension was 27.6%. Hypertension in Sudanese individuals was associated with high sugar and salt intake, obesity and increase in age. Therefore, decreasing sugar and salt intake should be advocated by health authorities and the public in Sudan.


Bladder augmentation with small intestinal submucosa leads to unsatisfactory long-term results.
To evaluate the use of small intestinal submucosa (SIS) for bladder augmentation in a series of select patients. Six patients (age 6.5-15.4, mean 9.8 years) underwent bladder augmentation with SIS: one after a cloacal exstrophy repair, one after multiple surgery of the bladder because of vesicoureteral reflux, two with spina bifida, two after bladder exstrophy repair. All suffered from a microbladder with a mean volume of 61.5 ml (range 15-120, 7-36% of expected bladder capacity for age). Preoperative bladder compliance ranged from 1.0 to 3.3 (mean 1.3) ml/cmH2O. Follow-up time ranged from 4.6 to 33.5 (mean 24.4) months. An increase of bladder volume was achieved in four patients (53-370 ml, 16-95% of expected bladder capacity for age). Bladder compliance postoperatively ranged from 0.9 to 5.6 (mean 3.0) ml/cmH2O. Histological examinations showed a complete conversion of SIS, leaving irregular urothelial lining and bladder wall containing muscular, vascular and relatively thick connective tissue in four patients and regular urothelium in two patients. Major complications were bladder stones in two patients and a bladder rupture in one patient. Bladder augmentation with SIS in humans failed to fulfill the hopes raised by animal studies. Due to the insufficient increase in bladder compliance and therefore failure to accomplish sufficient protection of the upper urinary tract, bladder augmentation with SIS cannot be recommended as a substitute for enterocystoplasty.


An attentional grasp reflex in patients with Alzheimer's disease.
Motor and visual grasp reflexes often occur as part of the symptomatology of Alzheimer's disease (AD). Similar grasp reflexes may also be associated with the impaired performance of AD patients on tasks which require direction of visual attention without eye movements. The covert orienting of visual attention task (COVAT) requires subjects to keep their eyes fixed on a central point and manually respond to the appearance of a peripheral target in one of two locations in the left or right visual field. Before the target appears, a cue is presented at either the target location or the contralateral location to the target, although the nature of the cue is not known until the target appears. We hypothesised that the attentional grasp reflex would become evident in patients with AD when attentional shifts away from the cue were required but there was no target for the shift present. Twelve patients who met the clinical criteria for AD and 12 age and education matched controls were administered three COVAT conditions in which the target appeared at the cued location with either an 80, 50 or 20% probability. For the 80 and 50% probability conditions. RTs for targets at the cued location were significantly faster than RTs for targets contralateral to the cue in both AD subjects and controls indicating that AD subjects were able to disengage attention when there was a target for the attentional shift. For the 20% probability condition, control subjects showed significantly faster RTs for targets appearing contralateral to the cue than for targets at the cued location indicating that when they expected the target to appear in the opposite visual field to the cue, they could initiate the shift of attention before the target appeared. However, AD subjects continued to show significantly faster RTs for targets at the cued location than for targets appearing contralateral to the cue, despite the high probability that targets would not occur at the cued location. This suggests that the covert redirection of attention away from a peripheral visual cue could not be initiated until the contralateral target appeared. Taken together these results suggest an attentional grap reflex in patients with AD.


Consumption of Bifidobacterium animalis subsp. lactis BB-12 in yogurt reduced expression of TLR-2 on peripheral blood-derived monocytes and pro-inflammatory cytokine secretion in young adults.
Probiotic bacteria modulate immune parameters and inflammatory outcomes. Emerging evidence demonstrates that the matrix used to deliver probiotics may influence the efficacy of probiotic interventions in vivo. The aims of the current study were to evaluate (1) the effect of one species, Bifidobacterium animalis subsp. lactis BB-12 at a dose of log10 ± 0.5 CFUs/day on immune responses in a randomized, partially blinded, 4-period crossover, free-living study, and (2) whether the immune response to BB-12 differed depending on the delivery matrix. Healthy adults (n = 30) aged 18-40 years were recruited and received four treatments in a random order: (A) yogurt smoothie alone; smoothie with BB-12 added (B) before or (C) after yogurt fermentation, or (D) BB-12 given in capsule form. At baseline and after each 4-week treatment, peripheral blood mononuclear cells (PBMCs) were isolated, and functional and phenotypic marker expression was assessed. BB-12 interacted with peripheral myeloid cells via Toll-like receptor 2 (TLR-2). The percentage of CD14+HLA-DR+ cells in peripheral blood was increased in male participants by all yogurt-containing treatments compared to baseline (p = 0.0356). Participants who consumed yogurt smoothie with BB-12 added post-fermentation had significantly lower expression of TLR-2 on CD14+HLA-DR+ cells (p = 0.0186) and reduction in TNF-α secretion from BB-12- (p = 0.0490) or LPS-stimulated (p = 0.0387) PBMCs compared to baseline. These findings not only demonstrate a potential anti-inflammatory effect of BB-12 in healthy adults, but also indicate that the delivery matrix influences the immunomodulatory properties of BB-12.


Research of Antibiotic Residues and Bacterial Strain's Antibiotic Resistance Profile in the Liquid Effluents Evacuated in Nature by Two CHUs and a Mixed WWTP of Ouagadougou (Burkina Faso).
In Burkina Faso, suspicions have been raised that hospital liquid effluents are a source of microbiological contaminants in surface waters of urban and peri-urban areas. This study aimed to determine the antibiotic residues and the antibiotic resistance phenotype of potential pathogenic bacteria in the hospital liquid effluents discharged into nature by the CHUs Bogodogo, Yalgado Ouédraogo and the WWTS of Kossodo. Fifteen samples of liquid effluents discharged into nature were collected. Antibiotic residues were identified by HPLC. A wavelength of 254 nm for the UV detector was set. Antibiotic testing was realized according to CASFM 2019 recommendations. Three molecules including Amoxicillin, Chloramphenicol and Ceftriaxone were detected in 13 samples. The strains characterized were 06 E. coli, 09 Pseudomonas spp, 05 Staphylococcus aureus and 04 Salmonella spp. Thus, none of the strains was resistant to Imipenem, but they were resistant to Amoxiclav with rates of 83.33% (E. coli), 88.88% (Pseudomonas spp) and 100% (Staphylococcus aureus and Salmonella spp). Ouagadougou hospital liquid effluents discharged into nature are contaminated with antibiotic residues and potential pathogenic bacteria.


Iridoid glycoside biosynthesis in Penstemon secundiflorus. Another H-5, H-9 trans-iridoid glycoside.
Isolation and characterization of the new iridoid 10-hydroxy-(5 alpha H)-6-epidihydrocornin from Penstemon secundiflorus (Scrophulariaceae) is described. In biosynthetic experiments, deoxyloganic acid was incorporated into the trans-fused iridoid glycosides (5 alpha H)-6-epidihydrocornin and 10-hydroxy-(5 alpha H)-6-epidihydrocornin in P. secundiflorus. Formation of the trans-fused compounds is therefore a late event in the biosynthesis and does not occur during iridoid formation by cyclization of the open chain monoterpene precursor. In the same plant, 8-epideoxyloganic acid was not incorporated into the trans-iridoids. Deoxyloganic acid was also incorporated into 10-hydroxyhastatoside (which bears an 8 beta-methyl group), while 8-epideoxyloganic acid was incorporated into penstemoside (with an 8 alpha-methyl group). Thus, iridoid biosynthetic pathways leading from both deoxyloganic acid and 8-epideoxyloganic acid were found in the same plant.


Safety and Efficacy of Everolimus Rescue Treatment After Pediatric Living Donor Liver Transplantation.
Everolimus (EVR) is a derivative of sirolimus with a similar mechanism of action. The safety and efficacy of EVR after pediatric living donor liver transplantation (LDLT) are currently unknown. The purpose of this study was to examine the safety and efficacy of EVR as rescue therapy after pediatric LDLT. This study included patients younger than 19 years of age who received EVR after LDLT at our institution. EVR was administered as rescue treatment in addition to tacrolimus. In 21 patients, EVR dose, trough level, outcomes, and adverse effects were assessed. Original diseases of patients consisted of biliary atresia (n = 11), Alagille syndrome (n = 3), fulminant hepatitis (n = 3), hepatoblastoma (n = 2), and other (n = 2). Mean age at transplant was 2.0 years (range 0.6-6.2 years). Mean age at initial EVR administration was 8.0 years (range 0.9-18.9 years). Indications for EVR use were graft fibrosis (n = 8), refractory acute cellular rejection (n = 5), renal sparing (n = 4), hepatoblastoma (n = 2), and chronic rejection (CR) (n = 2). Mean duration of administration was 17.1 months (range 2.1-60.4 months). Mean dose was 0.5 mg/m2 twice daily. Mean EVR trough level was 2.5 ng/mL (range 1.5-5.0 ng/mL). Liver function improved and fibrosis did not progress in all patients with CR. However, 14 patients (67%) experienced adverse effects that required EVR dose reduction or discontinuation. EVR is tolerable for pediatric patients after LDLT with dose adjustment. EVR had a certain effect to relieve progression on CR. Further follow-up is required.


Sphingosine 1-phosphate - A double edged sword in the brain.
The physiological functions of sphingosine 1-phosphate (S1P) and its pathological roles in various diseases are increasingly being elucidated. Particularly, a growing body of literature has implicated S1P in the pathogenesis of brain related disorders. With the deciphering of more intricate aspects of S1P signalling, there is also a need to reconsider the notion of S1P only as a determinant of cell survival and proliferation. Further the concept of 'S1P-ceramide' balance as the controlling switch of cellular fate and functions needs to be refined. In this review, we focus on the brain related functions of S1P with special focus on its role in synaptic transmission, neuronal autophagy and neuroinflammation. The review also attempts to bring out the multi-faceted nature of S1P signalling aspects that makes it a 'double edged sword'. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.


DFT study of the mechanism of hydroamination of ethylene with ammonia catalyzed by diplatinum(II) complexes: inner- or outer-sphere?
A detailed analysis of the reaction profiles of the hydroamination reaction between ethylene and ammonia catalyzed by the diplatinum(II) [{Pt(NH(2))(μ-H)(PPh(3))}(2)] complex is presented herein using density functional theory computational techniques. The coordinatively unsaturated 14e T-shaped [Pt(NH(2))(PPh(3))H] species resulted from the dissociation of the diplatinum [{Pt(NH(2))(μ-H)(PPh(3))}(2)] precatalyst are identified as the active catalytic species. All possible reaction pathways that constitute the entire catalytic cycle have exhaustively been investigated. Overall, the rate-determining step of all catalytic cycles constructed was found to be the oxidative addition of ammonia that leads to the regeneration of the catalyst. According to the energy span model, the outer-sphere mechanism for the hydroamination of ethylene with ammonia catalyzed by the diplatinum complexes is favored over the inner-sphere one, whereas TOF values are in favor of the inner-sphere mechanism.


Equal tension in all four strands of a semitendinosus graft with a low profile tibial fixation device (Cobra LFD).
The article introduces a novel tibia fixation device, the Cobra Ligament Fixation Device (Cobra LFD), for anterior cruciate ligament reconstruction. The Cobra LFD has a low profile and is hooked upon the cortical bone of tibia. It is useful either for primary ACL reconstruction or for ACL revision surgery, mainly for fixation of hamstring grafts. Fixation in the cortical bone is of great importance, in particular for revision cases. Besides technical aspects, we also present the 4-year follow-up of 15 cases of ACL revision surgery, where the Cobra LFD has been used for the tibia fixation.


Usefulness of a template-based anterolateral thigh flap for reconstruction of head and neck defects.
One of the challenges in head and neck reconstruction is to have an adequate understanding of the three-dimensionalities of the defects created after resections due to the high variability of clinical scenarios. Consequently, it is essential to design the flap to match the requirements of the defect in order to facilitate the insetting and to achieve a successful outcome. The anterolateral thigh flap (ALT) is a robust and versatile flap commonly used in head and neck reconstruction. In this study the authors use a hand-made template as a tool to customize ALT flaps and its variations to fit more accurately the different shapes, volume, and components of the resulting defects. The aim of this study is to describe in detail this surgical approach and present the clinical experience in 100 consecutive cases using a template-based ALT flaps in head and neck reconstruction. A retrospective review was performed on all microvascular head and neck reconstruction cases between January 2013 and December 2017 in our institution where a template-based ALT flap design was performed. We describe in detail the surgical technique used and present the clinical outcomes. In addition, we analyzed the use of different designs of the ALT flaps including different flap components in relation to the location of the defect. One hundred reconstructions for head and neck defects were performed in 97 patients. Seven types of ALT free flaps were performed: fasciocutaneous (46%), suprafascial (8%), adipofascial (9%), vastus lateralis muscle (3%), composite fasciocutaneous/adipofascial (9%), chimeric flaps (21%), and vascularized nerve grafts (4%). Oropharyngeal and periauricular defects were mostly reconstructed with fasciocutanoues design. In more complex three-dimensional defects such as skull base or midface defects, a chimeric flap was selected. In all cases the used of template facilitated the insetting of the free flap. The total flap loss was 2%. Customization of ALT flaps using intraoperative templates is a useful method for flap design which facilitates fitting of the flap to a variety of defects in head and neck reconstruction.


Clinical predictors of endotracheal intubation in patients presenting to the emergency department with angioedema.
The objective of this study is to identify predictors of airway compromise among patients presenting to the emergency department with angioedema in order to develop and validate a risk score to augment clinician gestalt regarding need for intubation. Retrospective chart review of emergency department patients with a diagnosis of angioedema. After data extraction they were randomly divided into a training and test set. The training set was used to identify factors associated with intubation and to develop a model and risk score to predict intubation. The model and risk score were then applied to the test set. A total of 594 patients were included. Past medical history of hypertension, presence of shortness of breath, drooling, and anterior tongue or pharyngeal swelling were independent predictors included in our final model and risk score. The Area Under the Curve for the Receiver Operator Characteristic curve was 87.55% (83.42%-91.69%) for the training set and 86.1% (77.62%-94.60%) for the test set. A simple scoring algorithm may aid in predicting angioedema patients at high and low risk for intubation. External validation of this score is necessary before wide-spread adoption of this decision aid.


Live Imaging of Border Cell Migration in Drosophila.
Border cells are a cluster of cells that migrate from the anterior tip of the Drosophila egg chamber to the border of the oocyte in stage 9. They serve as a useful model to study collective cell migration in a native tissue environment. Here we describe a protocol for preparing ex vivo egg chamber cultures from transgenic flies expressing fluorescent proteins in the border cells, and using confocal microscopy to take a multi-positional time-lapse movie. We include an image analysis method for tracking border cell cluster dynamics as well as tracking individual cell movements.


Loss of the cystine/glutamate antiporter in melanoma abrogates tumor metastasis and markedly increases survival rates of mice.
The cystine/glutamate antiporter, system xc- , is essential for the efficient uptake of cystine into cells. Interest in the mechanisms of system xc- function soared with the recognition that system xc- presents the most upstream node of ferroptosis, a recently described form of regulated necrosis relevant for degenerative diseases and cancer. Since targeting system xc- hold the great potential to efficiently combat tumor growth and metastasis of certain tumors, we disrupted the substrate-specific subunit of system xc- , xCT (SLC7A11) in the highly metastatic mouse B16F10 melanoma cell line and assessed the impact on tumor growth and metastasis. Subcutaneous injection of tumor cells into the syngeneic B16F10 mouse melanoma model uncovered a marked decrease in the tumor-forming ability and growth of KO cells compared to control cell lines. Strikingly, the metastatic potential of KO cells was markedly reduced as shown in several in vivo models of experimental and spontaneous metastasis. Accordingly, survival rates of KO tumor-bearing mice were significantly prolonged in contrast to those transplanted with control cells. Analyzing the in vitro ability of KO and control B16F10 cells in terms of endothelial cell adhesion and spheroid formation revealed that xCT expression indeed plays an important role during metastasis. Hence, system xc- emerges to be essential for tumor metastasis in mice, thus qualifying as a highly attractive anticancer drug target, particularly in light of its dispensable role for normal life in mice.


Chemokines as novel therapeutic targets in inflammatory diseases.
Chemokines and their receptors are a large family of inflammatory molecules responsible for a number of biological functions, including the accumulation of leukocytes at tissue sites. Over the past 10 years, a number of studies have indicated a role for chemokines and chemokine receptors in the pathophysiology of several inflammatory diseases, examples of which are multiple sclerosis, atherosclerosis, rheumatoid arthritis, and gastrointestinal diseases including hepatic disease. For this reason, it is not surprising that modulation of their pharmacology could be a prime target for drug discovery. This commentary provides a brief synopsis of our current knowledge of the role of chemokines and their receptors in the inflammatory process, and highlights the pros and possibly cons of chemokine and chemokine receptor antagonism in the therapeutic approach to several inflammatory diseases.


Carbohydrate formation in rewetted terrestrial cyanobacteria.
In the terrestrial cyanobacterium Nostoc commune Vauch. formation of carbohydrate polymers was measured upon rewetting the mats in a light-dark regime. To discriminate between carbohydrates of different physiological function, total carbohydrate was determined as anthrone-reactive material (ARM) and storage carbohydrate (glycogen) assayed by an enzymic test. In the dry thalli glycogen was found to represent less than one tenth of the ARM. After rewetting an increase of total carbohydrate was observed in illuminated samples. Only glycogen, however, showed a regular pattern of synthesis and degradation during a 12:12 h light-dark cycle. This indicates that most carbohydrates detected by anthrone belong to the metabolically inert sheath material.When illuminated colonies were kept submerged after rewetting glycogen was hydrolyzed indicative of being used in the rapid recovery of cellular functions as observed in rewetted colonies. Apparently, photosynthesis allowed for net glycogen synthesis only, provided the mats were sufficiently aerated. These findings give evidence that the (carbohydrate) sheath plays an important role in water retention in an organism bound to a terrestrial habitat.


The impact of traffic-related air pollution on lung function status and respiratory symptoms among children in Klang Valley, Malaysia.
Increasing the range of vehicles on traffic roads in the urban area has led to traffic-related air pollution (TRAP) and is currently becoming the main concern for health, especially among children. The study aimed to determine associations between TRAP and respiratory health, also to identify the main factors that influenced them. A cross-sectional comparative study was carried out among children in high and low traffic areas. Air quality monitoring was conducted in six primary schools. A set of standardized questionnaires was distributed to obtain respondents' exposure history and respiratory health symptoms, while spirometry test was carried out to determine the lung function status. There were associations between TRAP and abnormality of FEV1% among children. NO2 was the main predictor that influenced both chest tightness and abnormality of FEV1%. Children exposed to a high level of traffic-related air pollution have an increased risk of respiratory symptoms and abnormality of lung function.


The effects of mobile phones on pacemaker function.
The electromagnetic field generated by different systems have well-recognized adverse effects on pacemaker functions. The aim of this study is to evaluate the adverse effects of mobile phones on pacemaker functions. A total of 679 patients with permanent pacemakers were enrolled in this study. The study was performed in two steps. Pacemaker lead polarity was unipolar in the first step and bipolar in the second step. Pacemaker sensitivity was first at nominal values, it was then reduced to the minimal value for that pacemaker and tested again. Two mobile phones were symmetrically located on both sides of the pacemaker pocket with the antennas being equidistant at 50, 30, 20 and 10 cm and in close contact with the pocket. The tests were performed when both mobiles were opened, on stand-by, were receiving a call, during the call and were closed. Thirty-seven patients with pacemakers were adversely affected (5.5%) (33 VVI-R pacemakers were converted to asynchronous mode, and 3 were inhibited, 1 DDD-R pacemaker developed ventricular triggering). When the lead polarity was unipolar, the rate of adverse effect was higher when compared to the bipolar state (4.12% and 1.40%, p<0.01). The increase in sensitivity was not an independent factor on the rate of being affected (p>0.05). The rate of observing an adverse effect increased as the pacemaker got older (p<0.05). Mobile phones might have adverse effects on pacemaker functions under certain conditions. This does not result in any symptoms other than the inhibition of pacemakers, and pacemaker functions return to normal when the mobile phones are removed away from the patient.


Stability constants for the formation of lead chloride complexes as a function of temperature and ionic strength.
The stability constants for the formation of lead (Pb2+) with chloride [Formula: see text] have been determined using a spectrophotometric method in NaClO4 solutions as a function of ionic strength (0-6 m) and temperature (15-45 °C). The results have been fitted to the equations: [Formula: see text] with standard errors of 0.05, 0.04 and 0.06, respectively. The thermodynamic values of log β1, logβ2 and logβ3 at 25.0 °C and the enthalpies of formation of PbCl+, PbCl20 and PbCl3- are in good agreement with literature values. We have combined our results with the earlier work of Seward (1984) to yield thermodynamic constants that are valid from 15 to 300 °C: [Formula: see text] with standard errors of 0.05, 0.08 and 0.10, respectively.


Pneumatosis cystoides intestinalis and intramural intestinal gas.
Gas in the bowel wall is an unusual but important finding on an abdominal radiograph. The so-called "benign form," pneumatosis cystoides intestinalis, may be asymptomatic or may cause a variety of symptoms and can result in a bowel obstruction or a sterile pneumoperitoneum. On the other hand, intramural intestinal gas may represent severe underlying disease such as necrotizing enterocolitis or mesenteric vascular occlusion. This finding should be sought when examining abdominal radiographs. A thorough appreciation of the clinical significance of this unusual entity is necessary to make timely therapeutic decisions.


Banded Sleeve Gastrectomy vs Non-banded Sleeve Gastrectomy: a Systematic review and Meta-analysis.
Banded sleeve gastrectomy (BSG) was developed to restrict progressive dilation of the gastric sleeve, which remains a commonly implicated reason for weight regain following SG. The present study attempted to perform a systematic review and meta-analysis comparing the two procedures. Literature search was performed across PubMed and Google Scholar, using the keywords "Banded Sleeve Gastrectomy", "Sleeve gastrectomy", "Banded", "BSG" and "LSG". It yielded 4267 articles, six of which have been included in this review. Better weight loss outcomes at 3 and 5 years are noted following BSG, with a margin of 6.39% and 9.97% in %TWL at respective time points. No difference in impact on co-morbidities was noted. A revision rate of 7.1% was seen after BSG, with increased regurgitation as the most common indication.


Peripheral, but not local or intracerebroventricular, administration of benzodiazepines attenuates evoked activity of locus coeruleus neurons.
To determine whether benzodiazepine receptors in the locus coeruleus (LC) regulate the firing of LC neurons, the effects of systemic, intracerebroventricular, and local administration of various benzodiazepines on LC activity were compared. Systemic administration of diazepam, chlordiazepoxide, and alprazolam in anesthetized rats markedly attenuated sensory-evoked activity of LC neurons while also suppressing, but to a lesser degree, spontaneous LC firing rates. When microinfused into the LC region, diazepam, chlordiazepoxide, and alprazolam reduced spontaneous LC firing rates to the same extent observed following systemic administration; however, unlike systemic administration, infusion of benzodiazepines into the LC failed to attenuate evoked LC activity. Similarly, intracerebroventricular administration of diazepam and chlordiazepoxide suppressed spontaneous, but not evoked, LC activity. These findings indicate that benzodiazepines suppress spontaneous LC firing by stimulating benzodiazepine receptors in the LC while attenuating evoked LC activity by stimulating benzodiazepine receptors that are neither in the LC nor accessible to benzodiazepines introduced into the ventricular system.