Stability in Pelvic Triple Osteotomies in Children Using Resorbable PLGA Screws for Fixation.
The triple pelvic osteotomy (TPO) is a major redirectional osteotomy used to improve the acetabular coverage of the femoral head in selected pediatric patients with hip disorders. Traditionally the iliac osteotomy is stabilized by metal screws that require a second surgery for removal. Despite favorable results for both adults and children in related pelvic osteotomies, resorbable implants have not previously been used for TPOs.This study aims to suggest a novel modified TPO surgical method in children using resorbable poly lactic-co-glycolic acid (PLGA) screws for fixation and to radiographically evaluate the postoperative stability achieved by these implants in a case series. All patients (n=11) with dysplasia of the hip (2), Perthe disease (5), or Down syndrome (4), who underwent primary TPO surgery during 2013 to 2019, using resorbable PLGA screws for fixation were included. The stability of the osteotomy was evaluated in the postoperative radiograph series using the acetabular index, migration percentage, Sharp's angle and the center-edge angle. The osteotomy angle was introduced as a parameter to confirm the postoperative integrity of the achieved correction. All cases were evaluated until radiographic healing of the iliac osteotomy. Hospital notes were analyzed for complications or local reactions in relation to the implants. In all studied hips, the overall achieved correction was well maintained. The mean (SD) correction achieved, from the preoperative images to the last measurable postoperative image, was a 16.7 degrees decrease for Sharp angle, a 20.9 degrees decrease in acetabular index and a 24.7 degrees increase for the center-edge angle, respectively. There were no complications related to the bioabsorption of the implants. The present findings suggest that the modified TPO method, using resorbable PLGA screws, provides sufficient stability and appears to be a promising alternative to traditional TPO. Avoiding implant removal is a major benefit in a pediatric population. Resorbable screws enable the surgeon to place implants with more degrees of freedom since later implant removal is not a limiting factor. Level IV-case series.


Growth of Cu2ZnSnS4 Nanocrystallites on TiO2 Nanorod Arrays as Novel Extremely Thin Absorber Solar Cell Structure via the Successive-Ion-Layer-Adsorption-Reaction Method.
Cu2ZnSnS4 (CZTS) is an environmentally benign semiconductor with excellent optoelectronic properties that attracts a lot of interest in thin film photovoltaics. In departure from that conventional configuration, we fabricate and test a novel absorber-conductor structure featuring in situ successive-ion-layer-adsorption-reaction (SILAR)-deposited CZTS nanocrystallites as a light absorber on one-dimensional TiO2 (rutile) nanorods as an electron conductor. The effectiveness of the nanoscale heterostructure in visible light harvesting and photoelectron generation is demonstrated with an initial short circuit current density of 3.22 mA/cm(2) and an internal quantum efficiency of ∼60% at the blue light region, revealing great potential in developing CZTS extremely thin absorber (ETA) solar cells.


Evolution of sea-surfing plant propagule as revealed by the genomes of Heritiera mangroves.
Coastal forests, such as mangroves, protect much of the tropical and subtropical coasts. Long-distance dispersal via sea-surfing propagules is essential for coastal plants, but the genomic and molecular basis of sea-surfing plant propagule evolution remains unclear. Heritiera fomes and Heritiera littoralis are two coastal plants with typical buoyant fruits. We de novo sequenced and assembled their high-quality genomes. Our phylogenomic analysis indicates H. littoralis and H. fomes originated (at ~6.08 Mya) just before the start of Quaternary sea-level fluctuations. Whole-genome duplication occurred earlier, permitting gene copy gains in the two species. Many of the expanded gene families are involved in lignin and flavonoid biosynthesis, likely contributing to buoyant fruit emergence. It is repeatedly revealed that one duplicated copy to be under positive selection while the other is not. By examining H. littoralis fruits at three different developmental stages, we found that gene expression levels remain stable from young to intermediate. However, ~1000 genes are up-regulated and ~ 3000 genes are down-regulated as moving to mature. Particularly in fruit epicarps, the upregulation of WRKY12 and E2Fc likely constrains the production of p-Coumaroyl-CoA, the key internal substrate for lignin biosynthesis. Hence, to increase fruit impermeability, methylated lignin biosynthesis is shut down by down-regulating the genes CCoAOMT, F5H, COMT, and CSE, while unmethylated lignins are preferentially produced by upregulating CAD and CCR. Similarly, cutin polymers and cuticular waxes accumulate with high levels before maturation in epicarps. Overall, our genome assemblies and analyses uncovered the genomic evolution and temporal transcriptional regulation of sea-surfing propagule.


Medical management of patients after bariatric surgery: Principles and guidelines.
Obesity is a major and growing health care concern. Large epidemiologic studies that evaluated the relationship between obesity and mortality, observed that a higher body-mass index (BMI) is associated with increased rate of death from several causes, among them cardiovascular disease; which is particularly true for those with morbid obesity. Being overweight was also associated with decreased survival in several studies. Unfortunately, obese subjects are often exposed to public disapproval because of their fatness which significantly affects their psychosocial behavior. All obese patients (BMI ≥ 30 kg/m(2)) should receive counseling on diet, lifestyle, exercise and goals for weight management. Individuals with BMI ≥ 40 kg/m(2) and those with BMI > 35 kg/m(2) with obesity-related comorbidities; who failed diet, exercise, and drug therapy, should be considered for bariatric surgery. In current review article, we will shed light on important medical principles that each surgeon/gastroenterologist needs to know about bariatric surgical procedure, with special concern to the early post operative period. Additionally, we will explain the common complications that usually follow bariatric surgery and elucidate medical guidelines in their management. For the first 24 h after the bariatric surgery, the postoperative priorities include pain management, leakage, nausea and vomiting, intravenous fluid management, pulmonary hygiene, and ambulation. Patients maintain a low calorie liquid diet for the first few postoperative days that is gradually changed to soft solid food diet within two or three weeks following the bariatric surgery. Later, patients should be monitored for postoperative complications. Hypertension, diabetes, dumping syndrome, gastrointestinal and psychosomatic disorders are among the most important medical conditions discussed in this review.


Low-pass parabolic FFT filter for airborne and satellite lidar signal processing.
In order to reduce random errors of the lidar signal inversion, a low-pass parabolic fast Fourier transform filter (PFFTF) was introduced for noise elimination. A compact airborne Raman lidar system was studied, which applied PFFTF to process lidar signals. Mathematics and simulations of PFFTF along with low pass filters, sliding mean filter (SMF), median filter (MF), empirical mode decomposition (EMD) and wavelet transform (WT) were studied, and the practical engineering value of PFFTF for lidar signal processing has been verified. The method has been tested on real lidar signal from Wyoming Cloud Lidar (WCL). Results show that PFFTF has advantages over the other methods. It keeps the high frequency components well and reduces much of the random noise simultaneously for lidar signal processing.


Acute peritoneal dialysis: how to do it.
The decline in the use of acute peritoneal dialysis which has followed the recent advances in extracorporeal renal replacement therapy has left many clinicians unfamiliar with an invaluable therapeutic tool. This article is a timely reminder of both the underlying theory and the practical aspects of this technique.


Leukotriene B4 receptor inhibitor LY293111 induces cell cycle arrest and apoptosis in human anaplastic large-cell lymphoma cells via JNK phosphorylation.
Anaplastic large-cell lymphoma (ALCL) is a heterogeneous lymphoma category in which a subset of cases carry the t(2;5)(p23;q35) or variant translocations resulting in overexpression of anaplastic lymphoma kinase (ALK). LY293111 (2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]-propoxy]-phenoxy] benzoic acid sodium salt) is a leukotriene B4 receptor antagonist, which was found to be safe and tolerable in Phase I clinical trials. In this study, we investigated the potential therapeutic effects and mechanisms of action of LY293111 in ALCL cell lines. LY293111 inhibited proliferation of both ALK(+) and ALK(-) ALCL cell in a dose-dependent fashion and induced complete G(1)-S cell cycle arrest, which was accompanied by upregulation of p27 and downregulation of cyclin E. Pretreatment with LY293111 for 4 h resulted in profound inhibition of serum-induced phosphorylation of extracellular-regulated kinases-1 and 2 and Akt and a concomitant increase in the phosphorylation of the stress-activated kinase c-jun N-terminal kinases (JNK). Simultaneously, LY293111 induced caspase-dependent apoptosis via activation of the intrinsic pathway, including early loss of mitochondrial inner transmembrane potential and the production of reactive oxygen species (ROS), cleavage of caspases-9, -3, poly ADP-ribose polymerase (PARP) and X-linked inhibitor of apoptosis. The phospho-JNK inhibitor SP600125 partially protected Sup-M2 cells from LY293111-induced apoptosis, PARP cleavage and ROS generation, suggesting a role for JNK in LY293111-induced cell death. These results warrant further studies of LY293111 in ALCL.


Illnesses and deaths among persons attending an electronic dance-music festival - New York City, 2013.
Outdoor electronic dance-music festivals (EDMFs) are typically summer events where attendees can dance for hours in hot temperatures. EDMFs have received increased media attention because of their growing popularity and reports of illness among attendees associated with recreational drug use. MDMA (3,4-methylenedioxymethamphetamine) is one of the drugs often used at EDMFs. MDMA causes euphoria and mental stimulation but also can cause serious adverse effects, including hyperthermia, seizures, hyponatremia, rhabdomyolysis, and multiorgan failure. In this report, MDMA and other synthetic drugs commonly used at dance festivals are referred to as "synthetic club drugs." On September 1, 2013, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) received reports of two deaths of attendees at an EDMF (festival A) held August 31-September 1 in NYC. DOHMH conducted an investigation to identify and characterize adverse events resulting in emergency department (ED) visits among festival A attendees and to determine what drugs were associated with these adverse events. The investigation identified 22 cases of adverse events; nine cases were severe, including two deaths. Twenty-one (95%) of the 22 patients had used drugs or alcohol. Of 17 patients with toxicology testing, MDMA and other compounds were identified, most frequently methylone, in 11 patients. Public health messages and strategies regarding adverse health events might reduce illnesses and deaths at EDMFs.


Severity scores in surgery: what for and who needs them? An introduction: definition, aims, classification and evaluation.
Every patient represents a unique and complex situation a clinician has to deal with. In order to cope with this complexity of information, reduction is necessary, especially in communication about diseases or therapy. The first reduction is made when a patient is given a diagnosis which reflects a constellation of similar symptoms. A score also reduces the given amount of clinical data into a one-dimensional value. The primary aim of a score is a systematic comparison between patients and institutions. Scores reduce information to focus on the essentials. They are used for severity classification and prognosis, evaluation of outcome and treatment effects, case-mix adjustments in comparative audits, and economic evaluation. Quality criteria of score systems which should be considered in the development and application are: reliability, validity, measurability, applicability, and clinical relevance. This introductory article gives a brief description of these terms.


Clinical evaluation of BIOXTRA in relieving signs and symptoms of dry mouth after head and neck radiotherapy of cancer patients at Seyed-al-Shohada Hospital, Isfahan, Iran.
Radiotherapy of head and neck cancers causes acute and chronic xerostomia and acute mucositis. Xerostomia increases risk of radiation caries and affects on oral comfort, fit of prostheses, speech, swallowing, and the growth of caries-producing organisms. Salivary flow rate can be measured by asking patients some questions. There are different types of commercial synthetic saliva such as BIOXTRA, but until now, no one can effectively relieve xerostomia. We tried to design a clinical research on BIOXTRA efficacy for treating xerostomia. In this research, 58 patients with head and neck cancer (except salivary gland cancers) treated in Seyed-al-Shohada Hospital. The patients received at least 40-50 GY; and after 2 months of compilation treatment, they were evaluated by asking about having xerostomia. Before and after treatment with the BIOXTRA, the PH of the oral cavity, candida albicans, and lactobacillus counts measured and documented in laboratory. We used BIOXTRA for 2 weeks, 3 times daily, and then re-evaluated patients with some questions. The counts of candida albicans and lactobacilli statistically significant decreased. Xerostomia for most patients improved clinically during the day and night while PH of the oral cavity increased.


Vascular injuries in compound fractures of the leg with initially adequate circulation.
We carried out a randomised, controlled trial in 157 patients who had isolated severe Gustilo type-IIIa and type-IIIb fractures of the metaphysis or diaphysis of the leg to determine the prevalence of vascular injuries and the role of vascular repair. All patients had stable vital signs and clinically adequate circulation in their legs before operation. In a control group of 64 patients we performed conventional surgery with systematic debridement and primary stabilisation of the fractures. In the trial group of 93 patients the major vessels and nerves adjoining the compound fracture were routinely explored and repaired when necessary after the initial procedure. Two of the 28 control patients (7.1%) with type-IIIb compound fractures had signs of inadequate circulation after the first operation. Both had major vascular injuries which were demonstrated at a second procedure. In the trial group, major vascular injuries were found in two of 54 patients (3.7%) with type-IIIa and 11 of 39 patients (28.2%) with type-IIIb compound fractures. Compared with the control group the trial group showed improved results at both the immediate and long-term follow-up. Routine exploration and early repair of injured major vessels of the leg in severe compound fractures gave encouraging results.


Postgraduate studies in health informatics in Greece.
Health informatics is a well established and important multi-disciplinary and inter-disciplinary field that not only involves informatics but also medicine, nursing, engineering, biology and other-related subjects. A co-ordination of this field at a postgraduate level has become an important issue now in Europe where other European Community programs such as the Telematics for Health Care will require during the Fifth and Sixth Framework Programmes (2000-2006) adequate human resources of higher potential and knowledge. A European M.Sc. course met all the above objectives. The curriculum was developed according to previous experiences in similar programmes. Recently the course has been organised on the basis of an Inter-University nature with the participation of 5 Greek Universities. The paper aims at providing a current description of the academic programme and a brief evaluation of the implementation phase.


Dual-strand tumor suppressor miR-193b-3p and -5p inhibit malignant phenotypes of lung cancer by suppressing their common targets.
Emerging studies suggest that microRNAs (miRNAs) play multiple roles in cancer malignancy, including proliferation and acquisition of metastatic potential. Differentially expressed miRNAs responsible for the malignancy of lung cancer were searched by miRNA microarray using a previously established brain metastatic lung cancer model. Twenty-five miRNAs were down-regulated in brain metastatic lung cancer cells. Among those, miR-193b-3p and -5p were chosen for further studies. Their function in metastatic potential and proliferation was examined using Transwell invasion, wound healing, and colony forming assays. The underlying mechanism of tumor-suppressor miR-193b-3p and -5p was explored using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), Western blot, Argonaute 2-RNA immunoprecipitation (Ago2-RIP), and reporter assays. Both strands of miR-193b were down-regulated in brain metastatic lung cancer cells and in tissues from lung cancer patients. Overexpression of miR-193b-3p and -5p inhibited invasive and migratory activities and diminished clonogenic ability. Conversely, inhibition of miR-193b-3p or -5p increased the metastatic potential and colony forming ability. Cyclin D1 (CCND1), Ajuba LIM Protein (AJUBA), and heart development protein with EGF like domains 1 (HEG1) were identified as common target genes of miR-193b-3p and -5p. A reporter assay and an Ago2-RIP experiment showed that both miRNAs directly bind to the 3' untranslated region (3'UTR) of the target mRNA. Knockdown of target gene reduced the proliferative and metastatic potential of primary and metastatic lung cancer cells. Our results demonstrate miR-193b is a dual-strand tumor suppressor and a novel therapeutic target for lung cancer.


Evaluation of the biliary tree during laparoscopic cholecystectomy: laparoscopic ultrasound versus intraoperative cholangiography: a prospective study of 150 cases.
From November 1994 to March 1996, 150 patients treated by laparoscopic cholecystectomy were included in a prospective study, to compare intraoperative cholangiography (IOC) and laparoscopic ultrasonography (LU). The biliary tree was successively explored by these two methods in the routine detection of common bile duct stones. The feasibility of LU was 100%. Cholangiography was performed only in 125 cases (83%). The time taken for LU was significantly shorter (11.6 vs. 17.6 minutes, p = 0.0001). In this study, common bile duct stones were found in 14 cases (9%). For their detection, results were comparable to LU and IOC. For LU, sensitivity was 80% and specificity 99%; and for IOC, 78 and 97%, respectively. Both examinations combined had a 100% sensitivity and specificity. Laparoscopic ultrasonography failed to recognize the intrapancreatic part of the common bile duct in 25 cases (17%) and did not show anatomic abnormalities detected by IOC. It did, however, detect other unsuspected intraabdominal abnormalities. Although LU is safe, repeatable, and noninvasive, a considerable learning curve is necessary to optimize its efficacy. Comparison of relative cost must be undertaken.


[Clinical and virological correlation between the cerebrospinal fluid and blood of HIV-infected children].
Although the neurological manifestations of HIV infection occur at any age, children with perinatal AIDS are affected earlier and with greater impact. There are no published data about a potential association between HIV encephalopathy and viral load in THE CSF OF the pediatric population. Twenty-three children, aged 7 months to 10 years, were studied as part of a multicenter international study that evaluated double versus triple antiretroviral therapy. Samples of CSF and plasma were collected for HIV RNA measurements on day 0 and on follow-up weeks 8, 16, and 48. Neurological assessments, psychological evaluations, and CT scans were done on admission and at study end. Viral isolates were processed for genotypic resistance. No correlation between viral load in CSF and plasma was detected at study onset. Eighty percent of children had >2 log HIV RNA in CSF at day 0 but only 30% at week 16. Eight subjects responded favorably to therapy and their CSF had undetectable viral load during follow-up determinations. On day 0, 72% of children had identical patterns of genotypic resistance in CSF and plasma samples. At week 48, however, only 11% of these subjects had identical patterns. On day 0, 83% of children had abnormal neurological findings but these alterations declined to 35% at week 48 (p = 0.004). Most children with neurological abnormalities had detectable CSF viral loads (65% vs 17%, p = 0.04). The data generated in this study suggest that CSF and plasma behave as two different body compartments in terms of HIV dynamics and resistance mutants. Presence of neurological abnormalities correlate with detection of HIV in CSF and these alterations improve as therapy decreases CSF viral load. These results underscore the importance of using ARV drugs with good CNS penetration for optimal management of HIV-infected young children.


Prolonged survival time of Daphnia magna exposed to polylactic acid breakdown nanoplastics.
Polylactic acid nanoparticles (PLA NPs) according to food and drug administration are biodegradable and biocompatible polymers that have received a lot of attention due to their natural degradation mechanism. Although there is already available information concerning the effects of PLA microplastic to aquatic organisms, the knowledge about PLA NPs is still vague. In the present study, we analyzed the chemical composition of engineered PLA NPs, daily used PLA items and their breakdown products. We show that PLA breakdown products are oxidized and may contain aldehydes and/or ketones. The breakdown produces nanosized particles, nanoplastics, and possibly other small molecules as lactide or cyclic oligomers. Further, we show that all PLA breakdown nanoplastics extended the survival rate in Daphnia magna in an acute toxicity assay, however, only PLA plastic cup breakdown nanoplastics showed a significant difference compared to a control group.


Bond Graph Model of Cerebral Circulation: Toward Clinically Feasible Systemic Blood Flow Simulations.
We propose a detailed CellML model of the human cerebral circulation that runs faster than real time on a desktop computer and is designed for use in clinical settings when the speed of response is important. A lumped parameter mathematical model, which is based on a one-dimensional formulation of the flow of an incompressible fluid in distensible vessels, is constructed using a bond graph formulation to ensure mass conservation and energy conservation. The model includes arterial vessels with geometric and anatomical data based on the ADAN circulation model. The peripheral beds are represented by lumped parameter compartments. We compare the hemodynamics predicted by the bond graph formulation of the cerebral circulation with that given by a classical one-dimensional Navier-Stokes model working on top of the whole-body ADAN model. Outputs from the bond graph model, including the pressure and flow signatures and blood volumes, are compared with physiological data.


Bundled Consent in US Intensive Care Units.
Bundled consent, the practice of obtaining anticipatory consent for a predefined set of intensive care unit procedures, increases the rate of informed consent conversations and incorporation of patients' wishes into medical decision-making without sacrificing patients' or surrogates' understanding. However, the adoption rate for this practice in academic and nonacademic centers in the United States is unknown. To determine the national prevalence of use of bundled consent in adult intensive care units and opinions related to bundled consent. A random sample of US hospitals with medical/surgical intensive care units was selected from the AHA [American Hospital Association] Guide. One intensive care unit provider (bedside nurse, nurse manager, or physician) from each hospital was asked to self-reportuse of per-procedure consent versus bundled consent, consent rate for intensive care unit procedures, and opinions about bundled consent. Of the 238 hospitals contacted, respondents from 100 (42%) completed the survey; 94% of respondents were nurses. The prevalence of bundled consent use was 15% (95% CI, 9%-24%). Respondents using per-procedure consent were more likely than those using bundled consent to self-report performing invasive procedures without consent. Users of bundled consent unanimously recommended the practice, and 49% of respondents using per-procedure consent reported interest in implementing bundled consent. Bundled consent use is uncommon in academic and nonacademic intensive care units, most likely because of conflicting evidence about the effect on patients and surrogate decision makers. Future work is needed to determine if patients, family members, and providers prefer bundled consent over per-procedure consent.


[Validating and standardizing children's box and block test normal values].
Evaluating gross motor skills forms part of a child's functional examination. The box and block test is a simple, useful method for evaluating upper limb functionality. This study was aimed at validating and standardising the test's normal values in 6 to 11 year-old Colombian children. The test was used on 411 children from two schools in Bogotá catering for children different socioeconomic classes. A questionnaire directed towards parents and teachers was used for evaluating the children's performance on every-day life and school-related activities for validating the construct; correlation with the test was established. Data related to 386 children (55.4% male) was analysed; 67.9% of these children were attending a public school and 90.2% had right dominance. Average test score with the right hand was 60.9 and 57.8 with the left hand. Girls' average test scores were significantly higher. A table was constructed from (and showing) the average values, standard deviation and range of normality. A positive correlation was found regarding test result with age and every-day life activities and the teachers' appreciation of children's scholastic abilities. The test was reliable, having 0.84 intraclass correlation for the right hand and 0.83 for the left hand.


Macromolecular recognition and macroscopic interactions by cyclodextrins.
Herein macromolecular recognition by cyclodextrins (CDs) is summarized. Recognition of macromolecules by CDs is classified as main-chain recognition or side-chain recognition. We found that CDs form inclusion complexes with various polymers with high selectivity. Polyrotaxanes in which many CDs are entrapped in a polymer chain were prepared. Tubular polymers were prepared from the polyrotaxanes. CDs were found to recognize side-chains of polymers selectively. CD host polymers were found to form gels with guest polymers in water. These gels showed self-healing properties. When azobenzene was used as a guest, the gel showed sol-gel transition by photoirradiation. When ferrocene was used, redox-responsive gels were obtained. Macroscopic self-assembly through molecular recognition has been discovered. Photoswitchable gel association and dissociation have been observed.


Antioxidant regulatory mechanisms in neutrophils and lymphocytes after intense exercise.
The aims of this study were to assess the effects of a swimming session on the peripheral blood neutrophil and lymphocyte pro- and antioxidant system, identify any differences between the sexes and the regulatory mechanisms that might induce the immune cell adaptive response to exercise. Twenty-four swimmers (15 males, 9 females) participated in a one-hour swimming session at 75-80% of their maximal capacity. The session induced neutrophilia and decreased antioxidant enzyme activities and ascorbate levels in neutrophils. Malondialdehyde rose in neutrophils in males and females, whereas the carbonyl index only increased in males. Lymphocyte glutathione peroxidase activity was higher in males at baseline and rose as a consequence of exercise. The exercise decreased uncoupling protein-3 and Bcl-2 gene expression. The expression of PPARgamma coactivator-1 alpha (PGC-1alpha) correlated positively with that of sirtuin 3 (SIRT3) and catalase. In summary, a swimming session of one hour at 75-80% of maximal capacity produced oxidative damage in neutrophils and induced the antioxidant defences in lymphocytes. PGC-1alpha and SIRT3 appear to be key effectors of this adaptive response in lymphocytes. Both the neutrophil and lymphocyte response to exercise were slightly weaker in females than males.


The complete mitochondrial genome of a planarian flatworm Girardia tigrina (Tricladida: Dugesiidae).
Girardia tigrina, a freshwater planarian species native to America and introduced to other continents, has been usually used as model organism in many research fields of biology. In this study, we determined the complete mitochondrial genome of G. tigrina using next-generation sequencing (NGS). The complete mitogenome was 15,938 bp in length, with 36 genes, including 12 protein-coding genes, 2 ribosomal RNAs and 22 transfer RNAs, and ATP8 was absent in the mitogenome of G. tigrina as in the mitogenomes of some other flatworms. The maximum-likelihood phylogenetic tree suggested that G. tigrina was closely related to genus Dugesia in the clade of Tricladida.


Trenbolone acetate induced changes in the genital tract of male pigs.
Eleven entire and twelve castrated male pigs were implanted with trenbolone acetate and the effects of the treatment on genital tract macro- and microscopical modifications were evaluated and compared to non-implanted animals. In entire male pigs a reduction of testicular weight and size was observed as a consequence of the treatment (< 0.001), but no important modifications were found in bulbourethral gland and seminal vesicles macroscopically. Castrated non-implanted males had bulbourethral gland atrophy (P < 0.01), while castrated implanted ones showed similar development to entire males. As for vesicular glands there were no significant differences among the four groups under study. Histological study of prostate has demonstrated structural modifications. As a consequence of the treatment glandular lumen was increased (P < 0.05), and most parenchyma was occupied by polymorphous cysts.


The importance of informational, clinical and personal support in patient experience with total knee replacement: a qualitative investigation.
Total knee arthroplasty (TKA) is the most frequently performed joint replacement surgery in North America. Patient perspectives on TKA have been investigated in various ways, including finding as many as 20% of TKA patients are dissatisfied with their surgical outcomes. Understanding the patient experience with TKA broadly and in relation to patient satisfaction is a key gap in existing literature. We report on the qualitative component of a mixed methods prospective cohort study examining patient experience and satisfaction post-TKA for adults in British Columbia, Canada. Data collection consisted of 45 in-depth interviews about individuals' knee surgery experiences conducted eight months after surgery. Analysis consisted of thematic coding by multiple coders. Participants' descriptions of their TKA experiences were primarily concerned with support, or the provision of aid and assistance. Support was insufficient when their expectations of support were not met; unmet support expectations led to an overall negative TKA experience. Support operated in three key domains: (1) informational support, (2) clinical support, and (3) personal support. Key sources of informational and clinical support included pre-optimisation clinics, surgeons, and physiotherapists. Key topics for informational support included pain, pain management, and recovery trajectories. Personal support was provided by family, friends, other TKA patients, employers, and themselves. Patient needs and expectations for support are shaped both before and after TKA surgery. Patients with an overall positive TKA experience had improvement in their knee pain, stiffness or functioning post-TKA, had their major expectations and needs for support met during their TKA recovery, and believed that any significant future expectations or needs for ongoing support would be adequately met. In contrast, patients with an overall negative TKA experience had at least one major expectation or need for support not met during their TKA recovery, even in cases where they had good TKA outcomes. Suggested interventions to improve the experience of persons receiving TKA include an expanded patient navigator model, revised pre-surgery educational materials, particularly around pain expectations and management, and comprehensive sharing of other patients' TKA experience.


Enhanced current rectification and self-powered photoresponse in multilayer p-MoTe2/n-MoS2 van der Waals heterojunctions.
Vertically stacked van der Waals (vdW) heterojunctions based on two-dimensional (2D) transition metal dichalcogenides (TMDs) have attracted a great deal of attention and have created a powerful new material platform for novel, high-performance electronic and optoelectronic devices. Here, we report the construction of multilayer p-MoTe2/n-MoS2 vdW heterostructures with remarkable rectification behavior, self-powered photoresponse and distinct photosensitivity at different laser wavelengths and power densities. Field effect transistors (FETs) fabricated by MoTe2/MoS2 heterojunctions exhibit excellent gate-tunable rectification behavior and p-n junction transport characteristics, with the n-type dominating. The MoTe2/MoS2 heterojunction devices generate a self-powered photocurrent at zero bias voltage with a considerable on-off ratio reaching ∼780 and achieve a stable and fast photoresponse, due to the type-II band alignment facilitating efficient electron-hole separation. Utilizing the advantages of a p-n junction with type-II band alignment, this MoTe2/MoS2 vdW heterostructure provides more opportunities for future electronic and optoelectronic applications.


Effects of miR-33 Deficiency on Metabolic and Cardiovascular Diseases: Implications for Therapeutic Intervention.
MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally inhibit gene expression. These small molecules are involved in several biological conditions such as inflammation, cell growth and proliferation, and regulation of energy metabolism. In the context of metabolic and cardiovascular diseases, miR-33 is of particular interest as it has been implicated in the regulation of lipid and glucose metabolism. This miRNA is located in introns harboured in the genes encoding sterol regulatory element-binding protein (SREBP)-1 and SREBP-2, which are key transcription factors involved in lipid biosynthesis and cholesterol efflux. This review outlines the role of miR-33 in a range of metabolic and cardiovascular pathologies, such as dyslipidaemia, nonalcoholic fatty liver disease (NAFLD), obesity, diabetes, atherosclerosis, and abdominal aortic aneurysm (AAA), and it provides discussion about the effectiveness of miR-33 deficiency as a possible therapeutic strategy to prevent the development of these diseases.


Interleukin-1 beta, interleukin-1 receptor antagonist, and soluble interleukin-1 receptor type II secretion in chronic fatigue syndrome.
Chronic fatigue syndrome is a condition that affects women in disproportionate numbers, and that is often exacerbated in the premenstrual period and following physical exertion. The signs and symptoms, which include fatigue, myalgia, and low-grade fever, are similar to those experienced by patients infused with cytokines such as interleukin-1. The present study was carried out to test the hypotheses that (1) cellular secretion of interleukin-1 beta (IL-1 beta), interleukin-1 receptor antagonist (IL-1Ra), and soluble interleukin-1 receptor type II (IL-1sRII) is abnormal in female CFS patients compared to age- and activity-matched controls; (2) that these abnormalities may be evident only at certain times in the menstrual cycle; and (3) that physical exertion (stepping up and down on a platform for 15 min) may accentuate differences between these groups. Isolated peripheral blood mononuclear cells from healthy women, but not CFS patients, exhibited significant menstrual cycle-related differences in IL-1 beta secretion that were related to estradiol and progesterone levels (R2 = 0.65, P < 0.01). IL-1Ra secretion for CFS patients was twofold higher than controls during the follicular phase (P = 0.023), but luteal-phase levels were similar between groups. In both phases of the menstrual cycle, IL-1sRII release was significantly higher for CFS patients compared to controls (P = 0.002). The only changes that might be attributable to exertion occurred in the control subjects during the follicular phase, who exhibited an increase in IL-1 beta secretion 48 hr after the stress (P = 0.020). These results suggest that an abnormality exists in IL-1 beta secretion in CFS patients that may be related to altered sensitivity to estradiol and progesterone. Furthermore, the increased release of IL-1Ra and sIL-1RII by cells from CFS patients is consistent with the hypothesis that CFS is associated with chronic, low-level activation of the immune system.


The HF epidemic: the need for new treatment strategies.
The incidence of heart failure is increasing, particularly in older patients. Clinical trials often do not reflect community practice where patients are older and have more co-morbid conditions. Therapeutic agents need to be at least neutral in their effects on these other conditions. Current therapy in heart failure includes angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and diuretics, with advanced heart failure patients receiving spironolactone and possibly digitalis. Ongoing clinical trials are testing more effective inhibition of the renin-angiotensin-aldosterone system (RAAS) with highly selective angiotensin II (Ang II) receptor blockers (ARBs) such as valsartan. Future trials should study diverse racial groups and the elderly, particularly those with preserved systolic function. These should ideally be large multicentre studies with internal substudies to examine mechanisms of heart failure.


Economic evaluations of mental health interventions in criminal justice.
Mental health interventions targeting crime perpetrators are available. An overview of the current scenario of their economic benefits will help policy decisions. To provide an update on economic evidence for mental health interventions in criminal justice, and to identify challenges and responses in using economic evidence to inform policy. Narrative review with an analysis frame that organises evidence around four points on the criminal justice system pathway: (a) point of contact; (b) post-arrest; (c) incarceration/punishment and (d) post-incarceration. There is a paucity of high-quality economic evidence, especially from cost-benefit analyses. However, there is some evidence of cost-effectiveness in support of interventions at the point of incarceration, such as cognitive behavioural therapy, multisystemic therapy for juvenile delinquents, therapeutic communities, electronic monitoring and telepsychiatry in forensic psychiatry settings. There is also evidence that post-incarceration interventions such as assertive community treatment can be cost-effective. There remain large evidence gaps. There are also challenges in turning economic evidence on mental health interventions in criminal justice into policy changes and improved practice, such as hidden costs, silo budgeting and delayed pay-off. Research incorporating multi-sectoral costs and benefits recommended by health economics and health technology assessment groups should be prioritised to support difficult resource allocation decisions faced by policy makers.


Three new species of the genus Lasianobia Hampson, 1905 (Lepidoptera, Noctuidae) from China, with a revised checklist for the genus.
Three new species of Lasianobia Hampson, 1905 are described from China: Lasianobia dvoraki Saldaitis, Volynkin Truuverk, sp. nov. (W Sichuan), Lasianobia labranga Saldaitis, Volynkin Truuverk, sp. nov. (SW Gansu) and Lasianobia qinghana Saldaitis, Volynkin Truuverk, sp. nov. (Qinghai). Adults and male genitalia of these new species and their relatives are illustrated, and a generic check list presented.


Impact of genetic polymorphisms on opioid misuse: a scoping review.
We conducted a scoping review on genetic polymorphisms associated with opioid intake-related adverse patient outcomes including behavioral, physiological and clinical outcomes. We searched for studies on Medline®, EMBASE®, CINAHL®, Psychinfo® and SNPedia® from January 2006 to January 2018. Our study identified 33 genes and 71 SNPs associated with opioid-intake related adverse patient outcomes: four studies showing associations of nine SNPs with clinical events (e.g., arrhythmia, length of stay and deaths); six studies showing associations of 13 SNPs with respiratory depression and 25 studies showing associations of 50 SNPs with opioid misuse behaviors. Available pharmacogenetic-tests covered polymorphisms associated with opioids metabolism and ignored polymorphisms associated with opioids transport, receptor-binding and signaling that were linked with respiratory depression and misuse behaviors.


Acute Disseminated Encephalomyelitis Associated With Chronic Cannabis Abuse.
Acute disseminated encephalomyelitis (ADEM) is a rare monophasic immune-mediated inflammatory disorder characterized by multifocal demyelinating lesions of the central nervous system. Clinically, it is distinguished by a variety of acute neurological deficits, including varying degrees of mental state changes and white matter abnormalities detected by magnetic resonance imaging (MRI). We present a challenging case of a young woman who developed ADEM as a result of chronic cannabis abuse. This, to the best of our knowledge, is the second case report of ADEM linked to cannabis abuse.


BACE1 and cholinesterase inhibitory activities of Nelumbo nucifera embryos.
The aim of the present study was to evaluate the comparative anti-Alzheimer's disease (AD) activities of different parts of Nelumbo nucifera (leaves, de-embryo seeds, embryos, rhizomes, and stamens) in order to determine the selectivity and efficient use of its individual components. Anti-AD activities of different parts of N. nucifera were evaluated via inhibitory activities on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) along with scavenging activity on peroxynitrite (ONOO(-)). Among the evaluated parts of N. nucifera, the embryo extract exhibited significant inhibitory potential against BACE1 and BChE as well as scavenging activity against ONOO(-). Thus, the embryo extract was selected for detailed investigation on anti-AD activity using BACE1- and ChEs-inhibitory assays. Among the different solvent-soluble fractions, the dichloromethane (CH2Cl2), ethyl acetate (EtOAc), and n-butanol (n-BuOH) fractions showed promising ChEs and BACE1 inhibitory activities. Repeated column chromatography of the CH2Cl2, EtOAc and n-BuOH fractions yielded compounds 1-5, which were neferine (1), liensinine (2), vitexin (3), quercetin 3-O-glucoside (4) and northalifoline (5). Compound 2 exhibited potent inhibitory activities on BACE1, AChE, and BChE with respective IC50 values of 6.37 ± 0.13, 0.34 ± 0.02, and 9.96 ± 0.47 µM. Likewise, compound 1 showed potent inhibitory activities on BACE1, AChE, and BChE with IC50 values of 28.51 ± 4.04, 14.19 ± 1.46, and 37.18 ± 0.59 µM, respectively; the IC50 values of 3 were 19.25 ± 3.03, 16.62 ± 1.43, and 11.53 ± 2.21 µM, respectively. In conclusion, we identified potent ChEs- and BACE1-inhibitory activities of N. nucifera as well as its isolated constituents, which may be further explored to develop therapeutic and preventive agents for AD and oxidative stress related diseases.


Ultrasound evaluation of liver disease in cystic fibrosis as part of an annual assessment clinic: a 9-year review.
To review 9 years of annual assessment data in cystic fibrosis (CF) and evaluate the frequency of hepatobiliary abnormalities and the correlation between ultrasound and biochemical findings. Over a 9-year period (1990-99), 168 children (age range 1-18 years) with CF have undergone an annual assessment which has included clinical, biochemical and ultrasonographic evaluation of the hepatobiliary system. We have retrospectively reviewed the sequential ultrasound reports and correlated them with the contemporaneous biochemical results. A total of 725 ultrasound examinations were performed over the review period. Sixty patients had at least one examination showing an abnormality of liver echo texture and in 39 patients this was a persisting finding. Seven patients (4.2%) developed frank cirrhotic change on ultrasound criteria, while 15 patients (8.9%) had evidence of persistent splenomegaly. Gall-bladder calculi were present in 4.8%. In 176 examinations (24%) there was disparity between the ultrasound findings and aspartate aminotransferase (AST) levels. In 3.0% of cases (five patients) there were persisting abnormalities of liver echo texture and persisting splenomegaly with a normal range AST value. No perfect method of assessing hepatobiliary involvement in CF is currently available. Ultrasonographic and biochemical assessment may reflect different aspects of disease progression. Routine use of ultrasound in annual assessment allows identification of a minority of patients with liver changes but with normal biochemistry.


Withdrawal Phenomena: A Concept Analysis for the Development of a Nursing Diagnosis.
This study explored the concept of withdrawal phenomena from the perspective of nurses, with the aim of developing a nursing diagnosis. Concept analysis was used as the framework of the study, a systematized review was conducted to identify relevant studies, and interpretation was based on qualitative content analysis. Specifying aspects, defining characteristics, related factors, and risk factors were extracted and classified into categories. Thirteen studies were identified as a basis for the construction of two nursing diagnoses: "withdrawal phenomena" and "risk of withdrawal complications." The proposed nursing diagnoses require further discussion. The NANDA International Diagnosis Development Committee was asked to examine the proposed diagnoses. However, it was too early to determine implications for nursing practice based on the results of this study.


Functionalisation of Polyvinylpyrrolidone on Gold Nanoparticles Enhances Its Anti-Amyloidogenic Propensity towards Hen Egg White Lysozyme.
Protein amyloids are characterized by aggregates that usually consist of fibres containing misfolded proteins and having a cross β-sheet conformation. These aggregates can eventually lead to several degenerative diseases like Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Huntington's disease and Parkinson's disease. The present study describes the effect of chemically synthesized polyvinylpyrrolidone (PVP)-conjugated gold nanoparticles (PVP-AuNps) on hen egg white lysozyme (HEWL) amyloids. The synthesized nanoparticles have been characterized using various biophysical techniques like Ultraviolet-Visible (UV-Vis) Spectroscopy, Transmission electron microscopy (TEM), X-ray diffraction (XRD) analysis, dynamic light scattering (DLS), zeta-potential measurement and Fourier transform infrared spectroscopy (FTIR). The aggregation studies showed that PVP acts as a partial inhibitor of HEWL amyloidogenesis. However, when conjugated to gold nanoparticle surface, it leads to complete inhibition of amyloid formation. Apart from inhibition, PVP-conjugated gold nanoparticles also exhibited a significant disaggregation effect on mature amyloids and hence can be exploited as an effective therapeutic agent against hereditary systemic amyloidosis.


Controlling superstructural ordering in the clathrate-I Ba8M16P30 (M = Cu, Zn) through the formation of metal-metal bonds.
Order-disorder-order phase transitions in the clathrate-I Ba8Cu16P30 were induced and controlled by aliovalent substitutions of Zn into the framework. Unaltered Ba8Cu16P30 crystallizes in an ordered orthorhombic (Pbcn) clathrate-I superstructure that maintains complete segregation of metal and phosphorus atoms over 23 different crystallographic positions in the clathrate framework. The driving force for the formation of this Pbcn superstructure is the avoidance of Cu-Cu bonds. This superstructure is preserved upon aliovalent substitution of Zn for Cu in Ba8Cu16-x Zn x P30 with 0 < x < 1.6 (10% Zn/Mtotal), but vanishes at greater substitution concentrations. Higher Zn concentrations (up to 35% Zn/Mtotal) resulted in the additional substitution of Zn for P in Ba8M16+y P30-y (M = Cu, Zn) with 0 ≤ y ≤ 1. This causes the formation of Cu-Zn bonds in the framework, leading to a collapse of the orthorhombic superstructure into the more common cubic subcell of clathrate-I (Pm3n). In the resulting cubic phases, each clathrate framework position is jointly occupied by three different elements: Cu, Zn, and P. Detailed structural characterization of the Ba-Cu-Zn-P clathrates-I via single crystal X-ray diffraction, joint synchrotron X-ray and neutron powder diffractions, pair distribution function analysis, electron diffraction and high-resolution electron microscopy, along with elemental analysis, indicates that local ordering is present in the cubic clathrate framework, suggesting the evolution of Cu-Zn bonds. For the compounds with the highest Zn content, a disorder-order transformation is detected due to the formation of another superstructure with trigonal symmetry and Cu-Zn bonds in the clathrate-I framework. It is shown that small changes in the composition, synthesis, and crystal structure have significant impacts on the structural and transport properties of Zn-substituted Ba8Cu16P30.


Impaired retrieval processes evident during visual working memory in schizophrenia.
Prominent working memory (WM) deficits have been observed in people with schizophrenia (PSZ) across multiple sensory modalities, including the visuospatial realm. Electrophysiological abnormalities noted during early visual processing as well as later cognitive functions in PSZ may underlie deficiencies in WM ability, though the mechanisms linking behavior to neural responses are not well understood. WM dysfunction has also been observed in biological relatives of PSZ (REL) and therefore may be a manifestation of genetic liability for the disorder. We administered a delayed response visuospatial WM task to 23 PSZ, 30 of their REL, and 37 healthy controls (CTRL) to better understand the contributions of neural abnormalities to WM performance deficits associated with schizophrenia. PSZ performed more poorly on the WM task and failed to effectively process distractor stimuli as well as CTRL and REL. N1 electrophysiological responses to probes during retrieval differentiated the type and locations of stimuli presented during encoding in CTRL. Retrieval N1 responses in PSZ, however, failed to do so, while retrieval responses in REL showed more pronounced differentiation of stimulus features during encoding. Furthermore, neural responses during retrieval predicted behavioral performance in PSZ and REL, but not CTRL. These results suggest that retrieval processes are particularly important to efficient visuospatial WM function in PSZ and REL, and support further investigation of WM retrieval as a potential target for improving overall WM function through clinical intervention.


Relaxin therapy reverses large artery remodeling and improves arterial compliance in senescent spontaneously hypertensive rats.
Hypertension and aging are associated with large artery structural remodeling and stiffening, which are known to increase cardiovascular risk. Relaxin is a peptide hormone with potent antifibrotic action in multiple organs. Although relaxin is able to reduce peripheral vascular resistance and improve arterial compliance in rats, it remains unclear whether the improvement in compliance is indirectly attributed to a vasodilatory action or whether relaxin is able to reverse arterial remodeling and stiffening directly in aged hypertensive animals. Senescent spontaneously hypertensive rats (17 months old) were treated with relaxin for 2 weeks (0.5 mg/kg per day) followed by a 1-week washout period. We determined large artery compliance using in vivo and in vitro techniques and quantified arterial remodeling by morphological and chemical means. Relaxin therapy significantly reversed aortic remodeling (ie, increases in vessel size, wall thickness, and collagen content) and improved arterial compliance, effects independent of its vasodilatory action. In relaxin-treated spontaneously hypertensive rats, arterial collagen content showed a greater reduction (-31%; P<0.05) than that of elastin (-8%), resulting in an increased elastin:collagen ratio (0.63+/-0.03 versus 0.47+/-0.02; P<0.05). In conclusion, our results demonstrated that relaxin is potent in mediating reversal of arterial remodeling and improving arterial structural compliance in aged hypertensive rats.


Widespread expression of human alpha 1-antitrypsin in transgenic mice revealed by in situ hybridization.
In situ hybridization is a powerful means of identifying sites of gene expression. We used this technique to examine the spatial and developmental control of transcription of the human alpha 1-antitrypsin (alpha 1 AT) gene in transgenic mice carrying this gene and extensive 5'- and 3'-flanking sequences. In addition to expression in yolk sac and liver, human alpha 1AT RNA was detected in gut, stomach, pancreas, nasal epithelium, pharynx, bronchi, spinal ganglia, and ossifying cartilage of transgenic fetuses at 14.5 days post coitum (dpc). In transgenic adults, expression was no longer found in the pancreas but was found in the kidney and salivary gland. In each tissue, expression was confined to a specific cell population. This pattern of alpha 1AT expression was found to correlate with that seen in several fetal and adult human tissues. These results suggest a wider role of alpha 1AT in human physiology and development than previously suspected, and they demonstrated the potential value of this approach in delineating the physiological role of human proteins. Expression of the endogenous alpha 1AT gene in mice was confined to a limited, but overlapping, set of tissues, suggesting that the cis-acting DNA sequences that regulate the expression of the human and mouse genes interact differently with transcription factors present in mouse cells.


Synergistic Effect of Nano-Silica and Intumescent Flame Retardant on the Fire Reaction Properties of Polypropylene Composites.
Silica nanoparticles (nano-silica) were used as synergistic agents with ammonium polyphosphate (APP) and pentaerythritol (PER) to enhance flame retardancy of polypropylene (PP) in this research. The composites were prepared using a melt-mixing method. The influences of nano-silica on the fire performance of composites were thoroughly discussed, which promotes understanding of nano-silica on the flame-retardant performance of polypropylene composite. Scanning electron microscope (SEM) and energy-dispersive spectrometer (EDS) results indicated that the nano-silica with a diameter of about 95 ± 3.9 nm were dispersed favorably in the composite matrix, which might elevate its synergistic effect with intumescent flame retardant and improve the flame retardancy of polypropylene composite. The synergistic effects between nano-silica and intumescent flame retardant on PP composites were studied using the limiting oxygen index (LOI), UL-94 test, and cone calorimeter test (CCT). The total amount of flame retardant was maintained at 30%. When the dosage of nano-silica was 1 wt.%, the LOI value of PP/IFR/Si1.0 composite reached 27.3% and its UL-94 classification reached V-1. Based on the parameters of the CCT, the introduction of nano-silica induced composites with depressed heat release rate (HRR) and peak heat release rate (PHRR). The PHRR of PP/IFR/Si0.5 was only 295.8 kW/m2, which was 17% lower than that of PP/IFR. Moreover, the time to PHRR of PP/IFR/Si0.5 was delayed to 396 s, which was about 36 s later than that without nano-silica. EDS was used to quantitatively analyze the distribution of silica in charred residue. The EDS results indicated that the silica tended to accumulate on the surface during the fire. The surface accumulation characteristic of silica endows it with the enhanced flame-retardant properties of polypropylene composite at a very small dosage (as low as 1 wt.%).


Functional analysis of methylthioribose kinase genes in plants.
Through a biochemical and a genetic approach, we have identified several plant genes encoding methylthioribose (MTR) kinase, an enzyme involved in recycling of methionine through the methylthioadenosine (MTA) cycle. OsMTK1, an MTR kinase from rice (Oryza sativa), is 48.6 kD in size and shows cooperative kinetics with a V(max) of 4.9 pmol/min and a K0.5 of 16.8 microm. MTR kinase genes are the first genes to be identified from the MTA cycle in plants. Insertional mutagenesis of the unique AtMTK gene in Arabidopsis (Arabidopsis thaliana) resulted in an inability of plants to grow on MTA as a supplemental sulfur source. MTK knock-out plants were not impaired in growth under standard conditions, indicating that the MTA cycle is a nonessential metabolic pathway in Arabidopsis when sulfur levels are replete. In rice, OsMTK genes were strongly up-regulated in shoots and roots when plants were exposed to sulfur starvation. Gene expression was largely unaffected by lack of nitrogen or iron in the nutrient solution, indicating that OsMTK regulation was linked specifically to sulfur metabolism.


Genetics of dementia.
Neurodegenerative adult-onset dementias are complex and multifactorial diseases that are most commonly caused by environmental, genetic, or mixed environmental and genetic factors. Regarding the genetic causes, a variety of phenotypes may present. This article reviews several of the genetic risk factors for the most common dementias encountered in neurology. Practical implications of genetic testing and pharmacogenomic considerations for clinical practice are also discussed.


TLR4/ MyD88/NF-κB signaling pathway involved in the protective effect of diacerein against lung fibrosis in rats.
Pulmonary fibrosis (PF) is an inescapable problem. Diacerein, a chondro-protective drug, has antioxidant and anti-inflammatory effects. Its effect on PF injury has not yet been fully clarified. Therefore, the current study aimed to detect its protective effect on lung tissue with the explanation of possible underlying mechanisms. Adult male albino rats were assigned to four groups: control group, diacerein control group, PF non-treated group, and PF diacerein pretreated group. Lung tissue oxidative stress parameters, inflammatory biomarkers mainly Toll-like receptors-4 (TLR4), and myeloid differentiation factor 88 (MyD88) levels were determined. Histopathological examination of lung tissue and immunohistochemical studies of nuclear factor-kappa B (NF-κB), and transforming growth factor- β (TGF-β) were also done. Diacerein pretreatment has the ability to restore the PF damaging effect, proved by the reduction of the oxidative stress and lung tissue inflammation via downregulation of TLR4/NF-κB signaling pathway together with the restoration of TGF-β level and improvement of the histopathological and immunohistochemical study findings in the lung tissue. These results suggested the protective effect of diacerein on PF relies on its antioxidant and anti-inflammatory effects reducing TLR4/NF-κB signaling pathway.


An Ecotype of Neorickettsia risticii Causing Potomac Horse Fever in Canada.
Neorickettsia (formerly Ehrlichia) risticii is an obligatory intracellular bacterium of digenetic trematodes. When a horse accidentally ingests aquatic insects containing encysted trematodes infected with N. risticii, the bacterium is transmitted from trematodes to horse cells and causes an acute and often fatal disease called Potomac horse fever (PHF). Since the discovery of N. risticii in the United States in 1984, using immunofluorescence and PCR assays, PHF has been increasingly recognized throughout North America and South America. However, so far, there exist only a few stable N. risticii culture isolates, all of which are from horses within the United States, and the strain diversity and environmental spreading and distribution of pathogenic N. risticii strains remain poorly understood. This paper reports the isolation of N. risticii from the blood of a horse with acute PHF in Ontario, Canada. Intracellular N. risticii colonies were detected in P388D1 cells after 47 days of culturing and 8 days after the addition of rapamycin. Molecular phylogenetic analysis based on amino acid sequences of major surface proteins P51 and Ssa1 showed that this isolate is distinct from any previously sequenced strains but closely related to midwestern U.S. strains. This is the first Canadian strain cultured, and a new method was developed to reactivate dormant N. risticii to improve culture isolation. Neorickettsia risticii is an environmental bacterium that lives inside flukes that are parasitic to aquatic snails, insects, and bats. When a horse accidentally ingests insects harboring flukes infected with N. risticii, the bacterium is transmitted to the horse and causes an acute and often fatal disease called Potomac horse fever. Although the disease has been increasingly recognized throughout North and South America, N. risticii has not been cultured outside the United States. This paper reports the first Canadian strain cultured and a new method to effectively culture isolate N. risticii from the horse blood sample. Molecular analysis showed that the genotype of this Canadian strain is distinct from previously sequenced strains but closely related to midwestern U.S. strains. Culture isolation of N. risticii strains would confirm the geographic presence of pathogenic N. risticii, help elucidate N. risticii strain diversity and environmental spreading and distribution, and improve diagnosis and development of vaccines for this dreadful disease.


Diagnostic Immunohistochemistry: what can go wrong?
Although immunohistochemistry (IHC) has become an integral component of the surgical pathology laboratory and practice, it remains a subspecialty in search of a definition. The rapid expansion of this discipline is continually contributing to the struggle of interested pathologists and technologists to identify the proper working conditions of antibody reagents and the right choice of detection systems and instrumentations. Training programs have not, for the most part, successfully incorporated IHC in their curricula. Thus, pitfalls in diagnostic IHC, in our opinion, are becoming more frequent than they used to. In this review, we highlight and attempt to provide solutions for the most common pitfalls in diagnostic IHC as it relates to the routine practice of surgical pathology.


Familial mineralocorticoid induced hypertension in the sultanate of oman.
In Oman, many hypertensive patients with a family history of the disease respond to treatment with spironolactone, a mineralocorticoid receptor (MC-R) blocking agent thus suggesting a high prevalence of mineralocorticoid (MC) induced disease. The aim of this study was to document the prevalence of MC induced disease in patients with a positive family history of hypertension (HTN). Serum calcium, potassium, creatinine, aldosterone and renin levels were measured under standard conditions in all patients together with an abdominal ultrasound scan and an adrenal computed tomography (CT) scan in four patients. In this small study, we show that 18 of the 27 patients (66%) had undetectable (suppressed) renin levels with usually normal aldosterone values (14 patients) and respond to treatment with spironoactone. We suggest that MC induced hypertension is likely to be common in the Middle East. In evolutionary terms, this makes sense as the ability to conserve salt in hot climates might be expected to confer a definite survival advantage.


Detection of regional myocardial ischaemia by a novel 80-electrode body surface Delta map in patients presenting to the emergency department with cardiac-sounding chest pain.
Presentation with acute chest pain is common, but the conventional 12-lead ECG has limitations in the detection of regional myocardial ischaemia. The previously described method of the body surface mapping system (BSM) Delta map, derived from an 80-electrode BSM, as well as a novel parameter total ischaemic burden (IB), may offer improved diagnostic sensitivity and specificity in patients with myocardial ischaemia. The feasibility of using the novel BSM Delta map technique, and IB, for transient regional myocardial ischaemia was assessed in comparison with 12-lead ECG in 49 patients presenting to the emergency department (ED) with cardiac-sounding chest pain. The sensitivity and specificity of 12-lead ECG for the diagnosis of acute coronary syndrome (ACS) was 67 and 55%, respectively, positive likelihood ratio (+LR) 1.52 [95% confidence interval (CI) 0.86, 2.70] and negative likelihood ratio (-LR) 0.58 [95% CI 0.30, 1.12]. The sensitivity and specificity of the BSM Delta map for the diagnosis of ACS was 71 and 78%, +LR 3.19 [95% CI 1.31, 7.80], -LR 0.37 [95% CI 0.20, 0.68]. There was a significantly positive correlation between peak troponin-I concentration and IB (r=0.437; P<0.002). This pilot study confirms the feasibility of using the Delta map for the diagnosis of ACS in patients presenting to the ED with cardiac-sounding chest pain and suggests that it has promising diagnostic accuracy and has superior sensitivity and specificity to the 12-lead ECG. The novel parameter of IB shows a significant correlation with troponin-I and is a promising tool for describing the extent of ischaemia. The use of the BSM Delta map in the ED setting could improve the diagnosis of clinically important ischaemic heart disease and furthermore presents the result in an intuitive manner, requiring little specialist experience. Further larger scale study is now warranted.


The Outcome and Economic Viability of Embryo Production Using IVF and SOV Techniques in the Wagyu Breed of Cattle.
The Japanese black cattle breed (Wagyu) has an improved metabolism, which allows them to have a higher marbling score when compared with other cattle breeds. However, this may affect other aspects of the animal's physiology, including hormone secretion and their reproductive success, such as their response to synchronization protocols and embryo production. Therefore, the objectives of this study were to test a superovulation protocol (SOV) developed with low doses of FSH and to evaluate the outcome and economic viability of embryo production using the SOV and in vitro fertilization (IVF) approaches in the Wagyu cattle breed. For that, ten Wagyu cows were submitted to five SOVs over a period of 15 months using a standard protocol: CIDR + 3 mg estradiol benzoate (D0), 35 mg FSH (Folltropin®) a.m. and p.m. (D4), 35 mg Folltropin® a.m. and 20 mg p.m. (D5), 20 mg Folltropin® a.m. and 10 mg p.m. (D6), 10 mg Folltropin® and 0.5 mg cloprostenol, both a.m. and p.m., + CIDR removal (D7), 0.05 mg GnRH + insemination 12 and 24 h after (D8) and embryo collection + 0.5 mg of cloprostenol (D16). Thirty days after each SOV, a follicular aspiration was conducted to produce IVF embryos without any pre-synchronization using standard semen in the same group of animals. The average number of embryos produced was 7.63 ± 5.61 (SOV) and 4.52 ± 2.44 (IVF) (p = 0.303). There was no significant correlation between the number of embryos produced by the different techniques (SOV and IVF), indicating that cows that respond well to SOV did not respond well to IVF and vice versa (r = 0.379, p = 0.529). The total cost of each embryo produced by SOV was R$215.00 and R$410.00 for IVF. Therefore, cows that produce less than five embryos by SOV are not economically viable due their lack of response to FSH, and the use of IVF in those animals may be more effective.


The HML's new field deployable, high-resolution whole body counter.
The Human Monitoring Laboratory has found an alternate use for a hyperpure germanium field deployable instrument that was originally designed to be used in a search and identify mode for contraband radioactive material. The instrument, the Ortec Detective, becomes a fully functional spectroscopy system when connected to a laptop computer. In this configuration it can be used as a high-resolution portable whole body counter. This work has determined that the instrument has adequate sensitivity for emergency response with respect to fission and activation products, but not actinides. The use of Monte Carlo simulations has allowed the HML to calibrate the instrument, partially optimize the counting geometry, and develop a calibration curve that is a function of photon energy and a person's size. Similarly for thyroid counting, a function has been found that fits counting efficiency to a person's height. The MDA's are a few kilo Becquerels for fission and activation products for a 5-min count in an unshielded environment using a male subject.


Plasticity of mouse renal collecting duct in response to potassium depletion.
Plasticity of mouse renal collecting duct in response to potassium depletion.--Renal collecting ducts are the main sites for regulation of whole body potassium balance. Changes in dietary intake of potassium induce pleiotropic adaptations of collecting duct cells, which include alterations of ion and water transport properties along with an hypertrophic response. To study the pleiotropic adaptation of the outer medullary collecting duct (OMCD) to dietary potassium depletion, we combined functional studies of renal function (ion, water, and acid/base handling), analysis of OMCD hypertrophy (electron microscopy) and hyperplasia (PCNA labeling), and large scale analysis of gene expression (transcriptome analysis). The transcriptome of OMCD was compared in mice fed either a normal or a potassium-depleted diet for 3 days using serial analysis of gene expression (SAGE) adapted for downsized extracts. SAGE is based on the generation of transcript-specific tag libraries. Approximately 20,000 tags corresponding to 10,000 different molecular species were sequenced in each library. Among the 186 tags differentially expressed (P < 0.05) between the two libraries, 120 were overexpressed and 66 were downregulated. The SAGE expression profile obtained in the control library was representative of different functional classes of proteins and of the two cell types (principal and alpha-intercalated cells) constituting the OMCD. Combined with gene expression analysis, results of functional and morphological studies allowed us to identify candidate genes for distinct physiological processes modified by potassium depletion: sodium, potassium, and water handling, hyperplasia and hypertrophy. Finally, comparison of mouse and human OMCD transcriptomes allowed us to address the question of the relevance of the mouse as a model for human physiology and pathophysiology.


Role of estrogen in nitric oxide- and prostaglandin-dependent modulation of vascular conductance during treadmill locomotion in rats.
Endothelial production of nitric oxide (NO) and prostaglandins (PG) may be greater in females than in males, increasing vasodilatory responses in females. Does sex influence the cardiovascular responses to dynamic exercise through estrogen-dependent modulation of NO and PG vasodilatory pathways? After the administration of hexamethonium, we assessed terminal aortic blood flow (TAQ), mean arterial pressure (MAP), and hindlimb vascular conductance (VC) in four groups of rats (6 males, 5 females, 5 ovariectomized females, and 6 ovariectomized females with chronic estrogen supplementation) during graded mild-intensity treadmill locomotion (5-15 m/min, 0 degrees grade, 2 min). All rats repeated exercise after cyclooxygenase inhibition (indomethacin) and then again after NO synthase inhibition (nitro-l-arginine methyl ester) to examine the roles of NO and PG. Regression analysis was used to determine the influence of sex and plasma 17beta-estradiol on TAQ, MAP, and VC. The analysis revealed that female sex did not influence TAQ but reduced MAP and increased VC at rest and during exercise conditions. Plasma 17beta-estradiol (measured by immunoassay) significantly decreased MAP and increased TAQ and VC, irrespective of sex. Cyclooxygenase inhibition eliminated the significant association between MAP and estrogen, suggesting that estrogenic modulation occurred through PG-dependent processes. In contrast, the significant influence of estrogen on TAQ and VC was eliminated after NO synthase inhibition. On the basis of the overall findings of this study, estrogen influenced the vascular responses to dynamic exercise through PG- and NO-dependent pathways, but this occurred independent of sex.


Inferential modeling and predictive feedback control in real-time motion compensation using the treatment couch during radiotherapy.
Tumor motion induced by respiration presents a challenge to the reliable delivery of conformal radiation treatments. Real-time motion compensation represents the technologically most challenging clinical solution but has the potential to overcome the limitations of existing methods. The performance of a real-time couch-based motion compensation system is mainly dependent on two aspects: the ability to infer the internal anatomical position and the performance of the feedback control system. In this paper, we propose two novel methods for the two aspects respectively, and then combine the proposed methods into one system. To accurately estimate the internal tumor position, we present partial-least squares (PLS) regression to predict the position of the diaphragm using skin-based motion surrogates. Four radio-opaque markers were placed on the abdomen of patients who underwent fluoroscopic imaging of the diaphragm. The coordinates of the markers served as input variables and the position of the diaphragm served as the output variable. PLS resulted in lower prediction errors compared with standard multiple linear regression (MLR). The performance of the feedback control system depends on the system dynamics and dead time (delay between the initiation and execution of the control action). While the dynamics of the system can be inverted in a feedback control system, the dead time cannot be inverted. To overcome the dead time of the system, we propose a predictive feedback control system by incorporating forward prediction using least-mean-square (LMS) and recursive least square (RLS) filtering into the couch-based control system. Motion data were obtained using a skin-based marker. The proposed predictive feedback control system was benchmarked against pure feedback control (no forward prediction) and resulted in a significant performance gain. Finally, we combined the PLS inference model and the predictive feedback control to evaluate the overall performance of the feedback control system. Our results show that, with the tumor motion unknown but inferred by skin-based markers through the PLS model, the predictive feedback control system was able to effectively compensate intra-fraction motion.


Nurses' perceptions of why medication administration errors occur.
Nurses play a key role in medication administration in hospital settings. Five categories of reasons for medication errors were identified in a survey of 1,384 nurses. These categories include physician, systems, pharmacy, individual, and knowledge-related factors. In this article, issues surrounding the occurrence and prevention of medication errors are discussed.


Transcriptome analysis of the Aspergillus nidulans AtmA (ATM, Ataxia-Telangiectasia mutated) null mutant.
ATM is a phosphatidyl-3-kinase-related protein kinase that functions as a central regulator of DNA damage response in eukaryotes. In humans, mutations in ATM cause the devastating neurodegenerative disease Ataxia-Telangiectasia. Previously, we characterized the homologue of ATM (AtmA) in the filamentous fungus Aspergillus nidulans. In addition to its expected role in the DNA damage response, we found that AtmA is also required for polarized hyphal growth. Our results suggested that AtmA probably regulates the function and/or localization of landmark proteins required for the formation of a polarity axis. Here, we extended these studies by investigating which pathways are influenced by AtmA during proliferation and polar growth by comparatively determining the transcriptional profile of A. nidulans wild-type and DeltaatmA mutant strains in different growth conditions. Our results indicate an important role of the pentose phosphate pathway in the fungal proliferation during endogenous DNA damage and polar growth monitored by the AtmA kinase. Furthermore, we identified several genes that have decreased mRNA expression in the DeltaatmA mutant that are involved in the formation of a polarized hyphae and control of polar growth; in the synthesis of phosphatidic acid (e.g. phospholipase D); in the ergosterol biosynthesis (plasma membrane microdomains, lipid rafts); and in intracellular trafficking.


Polymorphisms of the ApoE (Apolipoprotein E) gene and their influence on dyslipidemia in HIV-1-infected individuals.
The purpose of this retrospective case-control study was to investigate the frequency of Apolipoprotein E (ApoE) polymorphisms and their influence on antiretroviral therapy (ART)-induced lipodystrophy or dyslipidemia in HIV-infected Thai patients. The clinical characteristics and frequencies of ApoE genotypes were compared between the case (moderate to severe lipodystrophy, n = 67) and control (absent to mild lipodystrophy, n = 18) groups. The ApoE genotype frequencies among the 85 participants were 2.35% (n = 2) for E2/E2, 20% (n = 17) for E2/E3, 9.41% (n = 8) for E2/E4, 36.47% (n = 31) for E3/E3, 30.59% (n = 26) for E3/E4, and 1.18% (n = 1) for E4/E4. None of the ApoE genotypes showed association with ART-induced lipodystrophy. However, the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-cholesterol), and ApoB were lower in patients carrying the E2 allele but higher in E4 carriers. Interestingly, the ratios between TC and high-density lipoprotein (TC/HDL cholesterol ratio) and ApoB/ApoA-I ratio were significantly higher in the case group. Patients carrying the E2 allele displayed protective lipid profile, while those carrying E4 appeared to be at higher risk of dyslipidemia. In conclusion, ApoE polymorphisms were not associated with lipodystrophy in patients undergoing antiretroviral therapy but influenced lipid alteration.


Protein-Protein interaction network analyses of human WNT proteins involved in neural development.
WNT proteins are involved from initial of neural tissue specification to the end of cell fate determination and organ development. The present work was carried out to understand the involvement of different WNT isoforms (WNT3a, WNT5a and WNT7b) in neural development. A total of 718, 546 and 1004 PPIs for WNT3a, WNT5a and WNT7b respectively, were predicted by STRING database with confidence score more than 0.400. A network carrying all the selected PPIs of targeted proteins was constructed by using Cytoscape by assigning source node, target node and combined score as edge attribute. A total 2268 interactions of WNT3a, WNT5a and WNT7b were predicted to be involved in multiple signaling pathways and developmental processes. 43 of 2268 PPIs were refined after analyzing role of targeted proteins specifically in brain and neural development. WNT3a, WNT5a and WNT7a were predicted to be interacting with 18, 17 and 11 proteins, respectively, with average node degree score of 1.89, 2.12 and 1.82 respectively. The CytoHubba algorithm identified WNT3a, WNT5a, and WNT7b as hub proteins in neural development ranked on the basis of EPC (Edge Percolated Component) score of 9.352, 9.258 and 8.387.


Head positioning for anterior circulation aneurysms microsurgery.
To study the ideal patient's head positioning for the anterior circulation aneurysms microsurgery. We divided the study in two parts. Firstly, 10 fresh cadaveric heads were positioned and dissected in order to ideally expose the anterior circulation aneurysm sites. Afterwards, 110 patients were submitted to anterior circulation aneurysms microsurgery. During the surgery, the patient's head was positioned accordingly to the aneurysm location and the results from the cadaveric study. The effectiveness of the position was noted. We could determine mainly two patterns for head positioning for the anterior circulation aneurysms. The best surgical exposure is related to specific head positions. The proper angle of microscopic view may minimize neurovascular injury and brain retraction.


Feasibility of determining asphalt pavement condition from falling weight deflectometer test and finite element model updating.
Determination of pavement internal condition from a non-destructive field test is a persistent topic for its practical necessity and difficulty. It is essentially an inverse problem calibrating pavement material and structural properties from pavement responses. Considering the intrinsic complexity of asphalt pavement materials (e.g., time and temperature dependencies of asphalt mixture and stress dependency of unbound granular materials), this problem has become a typical high-dimensional optimization problem with a large and diverse set of calibrated parameters. This study investigated the feasibility of artificial intelligence-based finite element model updating in addressing this problem, and focused on the accuracy as well as stability of the backcalculated results. For a comprehensive evaluation of this method, the effects of its components such as the surrogate model representing the pavement system, the applied pavement response, the optimization algorithm and the backcalculation scheme were characterized. Finally, we found that the sensitivity of applied pavement responses to thebackcalculated pavement condition, the number of applied pavement responses and the balance between the backcalculated pavement condition and the applied test were of significant importance to achieving accurate and stable backcalculation results. Corresponding modifications were recommended to be conducted in future research for improving the performance of the proposed backcalculation method. This article is part of the theme issue 'Artificial intelligence in failure analysis of transportation infrastructure and materials'.


Refolding of Escherichia coli outer membrane protein F in detergent creates LPS-free trimers and asymmetric dimers.
The Escherichia coli OmpF (outer-membrane protein F; matrix porin) is a homotrimeric beta-barrel and a member of the bacterial porin superfamily. It is the best characterized porin protein, but has resisted attempts to refold it efficiently in vitro. In the present paper, we report the discovery of detergent-based folding conditions, including dodecylglucoside, which can create pure samples of trimeric OmpF. Whereas outer membrane LPS (lipopolysaccharide) is clearly required for in vivo folding, the artificially refolded and LPS-free trimer has properties identical with those of the outer-membrane-derived form. Thus LPS is not required either for in vitro folding or for structural integrity. Dimeric forms of OmpF have been observed in vivo and are proposed to be folding intermediates. In vitro, dimers occur transiently in refolding of trimeric OmpF and, in the presence of dodecylmaltoside, pure dimer can be prepared. This form has less beta-structure by CD and shows lower thermal stability than the trimer. Study of these proteins at the single-molecule level is possible because each OmpF subunit forms a distinct ion channel. Whereas each trimer contains three channels of equal conductance, each dimer always contains two distinct channel sizes. This provides clear evidence that the two otherwise identical monomers adopt different structures in the dimer and indicates that the asymmetric interaction, characteristic of C3 symmetry, is formed at the dimer stage. This asymmetric dimer may be generally relevant to the folding of oligomeric proteins with odd numbers of subunits such as aspartate transcarbamoylase.


Two cases of feline malignant craniopharyngioma.
Tumors at the cranial base in 2 cats (a 9 1/2-year-old, castrated male Chinchilla and a 7-year-old, castrated male American Shorthair) were diagnosed as malignant craniopharyngioma. The tumor lesion was histopathologically divided into four parts: 1) a small acinus part, in which relatively large cells with a pale cytoplasm composed small acini; 2) a duct part, in which small cuboidal cells composed ducts; 3) a cyst part, in which there were large cysts lined with flat cells; and 4) a pavement part, in which large multi-angular-shaped cells proliferated in a pavement pattern. The epithelial cells of some parts were positive for keratin by immunohistochemistry. Histopathologic findings of the present feline cases were identical to those of malignant craniopharyngioma in other animal species.


Impact of decision aids used during clinical encounters on clinician outcomes and consultation length: a systematic review.
Clinicians' satisfaction with encounter decision aids is an important component in facilitating implementation of these tools. We aimed to determine the impact of decision aids supporting shared decision making (SDM) during the clinical encounter on clinician outcomes. We searched nine databases from inception to June 2017. Randomised clinical trials (RCTs) of decision aids used during clinical encounters with an unaided control group were eligible for inclusion. Due to heterogeneity among included studies, we used a narrative evidence synthesis approach. Twenty-five papers met inclusion criteria including 22 RCTs and 3 qualitative or mixed-methods studies nested in an RCT, together representing 23 unique trials. These trials evaluated healthcare decisions for cardiovascular prevention and treatment (n=8), treatment of diabetes mellitus (n=3), treatment of osteoporosis (n=2), treatment of depression (n=2), antibiotics to treat acute respiratory infections (n=3), cancer prevention and treatment (n=4) and prenatal diagnosis (n=1). Clinician outcomes were measured in only a minority of studies. Clinicians' satisfaction with decision making was assessed in only 8 (and only 2 of them showed statistically significantly greater satisfaction with the decision aid); only three trials asked if clinicians would recommend the decision aid to colleagues and only five asked if clinicians would use decision aids in the future. Outpatient consultations were not prolonged when a decision aid was used in 9 out of 13 trials. The overall strength of the evidence was low, with the major risk of bias related to lack of blinding of participants and/or outcome assessors. Decision aids can improve clinicians' satisfaction with medical decision making and provide helpful information without affecting length of consultation time. Most SDM trials, however, omit outcomes related to clinicians' perspective on the decision making process or the likelihood of using a decision aid in the future.


Copper(I)-Phosphine Polypyridyl Complexes: Synthesis, Characterization, DNA/HSA Binding Study, and Antiproliferative Activity.
A series of copper(I)-phosphine polypyridyl complexes have been investigated as potential antitumor agents. The complexes [Cu(PPh3)2dpq]NO3 (2), [Cu(PPh3)2dppz]NO3 (3), [Cu(PPh3)2dppa]NO3 (4), and [Cu(PPh3)2dppme]NO3 (5) were synthesized by the reaction of [Cu(PPh3)2NO3] with the respective planar ligand under mild conditions. These copper complexes were fully characterized by elemental analysis, molar conductivity, FAB-MS, and NMR, UV-vis, and IR spectroscopies. Interactions between these copper(I)-phosphine polypyridyl complexes and DNA have been investigated using various spectroscopic techniques and analytical methods, such as UV-vis titrations, thermal denaturation, circular dichroism, viscosity measurements, gel electrophoresis, and competitive fluorescent intercalator displacement assays. The results of our studies suggest that these copper(I) complexes interact with DNA in an intercalative way. Furthermore, their high protein binding affinities toward human serum albumin were determined by fluorescence studies. Additionally, cytotoxicity analyses of all complexes against several tumor cell lines (human breast, MCF-7; human lung, A549; and human prostate, DU-145) and non-tumor cell lines (Chinese hamster lung, V79-4; and human lung, MRC-5) were performed. The results revealed that copper(I)-phosphine polypyridyl complexes are more cytotoxic than the corresponding planar ligand and also showed to be more active than cisplatin. A good correlation was observed between the cytostatic activity and lipophilicity of the copper(I) complexes studied here.


Atomic force microscopy with a 12-electrode piezoelectric tube scanner.
This paper presents a piezoelectric tube scanner with a novel electrode pattern and describes how it may be used for simultaneous sensing and actuation. The electrodes are arranged such that the tube is driven in an antisymmetrical manner, resulting in a collocated system suitable for positive position feedback (PPF). A PPF controller is designed to damp the scanner's resonance. Piezoelectric strain-induced voltage is used as measurement. The device is then installed into an atomic force microscope to obtain open- and closed-loop images of a grating at 10, 15.6, and 31 Hz scan rates. The closed-loop images are noticeably superior to the open-loop images, illustrating the effectiveness of the proposed scanner when used simultaneously as a sensor and an actuator.


Water Spinach, Ipomoea aquatic (Convolvulaceae), Ameliorates Lead Toxicity by Inhibiting Oxidative Stress and Apoptosis.
Ipomoea aquatica (Convolvulaceae), an aquatic edible plant, is traditionally used against heavy metal toxicity in India. The current study intended to explore the protective role of edible (aqueous) extract of I. aquatica (AEIA) against experimentally induced Pb-intoxication. The cytoprotective role of AEIA was measured on mouse hepatocytes by cell viability assay followed by Hoechst staining and flow cytometric assay. The effect on ROS production, lipid peroxidation, protein carbonylation, intracellular redox status were measured after incubating the hepatocytes with Pb-acetate (6.8 μM) along with AEIA (400 μg/ml). The effects on the expressions of apoptotic signal proteins were estimated by western blotting. The protective role of AEIA was measured by in vivo assay in mice. Haematological, serum biochemical, tissue redox status, Pb bioaccumulation and histological parameters were evaluated to estimate the protective role of AEIA (100 mg/kg) against Pb-acetate (5 mg/kg) intoxication. Pb-acetate treated hepatocytes showed a gradual reduction of cell viability dose-dependently with an IC50 value of 6.8 μM. Pb-acetate treated hepatocytes exhibited significantly enhanced levels (p < 0.01) of ROS production, lipid peroxidation, protein carbonylation with concomitant depletion (p < 0.01) of antioxidant enzymes and GSH. However, AEIA treatment could significantly restore the aforementioned parameters in murine hepatocytes near to normalcy. Besides, AEIA significantly reversed (p < 0.05-0.01) the alterations of transcription levels of apoptotic proteins viz. Bcl 2, Bad, Cyt C, Apaf-1, cleaved caspases [caspase 3, caspase 8 and caspase 9], Fas and Bid. In in vivo bioassay, Pb-acetate treatment caused significantly high intracellular Pb burden and oxidative pressure in the kidney, liver, heart, brain and testes in mice. In addition, the haematological and serum biochemical factors were changed significantly in Pb-acetate-treated animals. AEIA treatment restored significantly the evaluated-parameters to the near-normal position. The extract may offer the protective effect via counteracting with Pb mediated oxidative stress and/or promoting the elimination of Pb by chelating. The presence of substantial quantities of flavonoids, phenolics and saponins would be responsible for the overall protective effect.


Apparently enhanced visual information processing in female fragile X carriers: preliminary findings.
Eighteen normally intelligent adult female fragile X carriers were tested with the "de Sonneville Visual Attention Tasks," a computer-based set of reaction-time experiments, in order to assess different aspects of their attention capacity. The subject group was compared with a group of 48 adults, who were not known to be fragile X carriers. We publish preliminary results of this study. These show that the fragile X carriers have significantly faster reaction times at a substantial number of the tests. This suggests that normally intelligent female fragile X carriers might process simple visual information, such as the targets offered in these reaction time experiments, at a faster rate than control women.


Congenital transmission of Trypanosoma cruzi in Europe (Spain): a case report.
Here we report a documented case of congenital transmission of Trypanosoma cruzi from a Bolivian mother with chronic Chagas disease living in Spain. The serology and blood nested polymerase chain reaction (PCR) were positive for the mother, and amastigote forms were observed in histopathological study of the placenta and umbilical cord. Direct examination, culture, and nested PCR were positive in the blood of the neonate. At the age of 8 days, the neonate began treatment with 5-7.5 mg/kg/day of benznidazol, which was continued for 60 days. Direct examination, blood culture, and nested PCR were negative to T. cruzi 20 days after the start of treatment and remained negative 4 and 7 months thereafter. Serological tests were negative at 4 months. To detect congenital infection and initiate early treatment of infected newborns, protocols are required to detect Chagas disease in pregnant women who migrate from endemic to non-endemic areas.


LINC00667: A Novel Vital Oncogenic LincRNA.
Long intergenic noncoding RNAs (lincRNAs) have a variety of properties that differ from those of messenger RNAs (mRNAs) encoding proteins. Long intergenic nonprotein coding RNA 667 (LINC00667) is a non-coding transcript located on chromosome 18p11.31. Recently, many studies have found that LINC00667 can enhance the progression of various cancers and play a key part in a lot of diseases, such as tumorigenesis. Therefore, LINC00667 can be recognized as a potential biomarker and therapeutic target. So, we reviewed the biological functions, relevant mechanisms, as well as clinical significance of LINC00667 in several human cancers in detail.


Negative Electron Transfer Dissociation Sequencing of 3-O-Sulfation-Containing Heparan Sulfate Oligosaccharides.
Among dissociation methods, negative electron transfer dissociation (NETD) has been proven the most useful for glycosaminoglycan (GAG) sequencing because it produces informative fragmentation, a low degree of sulfate losses, high sensitivity, and translatability to multiple instrument types. The challenge, however, is to distinguish positional sulfation. In particular, NETD has been reported to fail to differentiate 4-O- versus 6-O-sulfation in chondroitin sulfate decasaccharide. This raised the concern of whether NETD is able to differentiate the rare 3-O-sulfation from predominant 6-O-sulfation in heparan sulfate (HS) oligosaccharides. Here, we report that NETD generates highly informative spectra that differentiate sites of O-sulfation on glucosamine residues, enabling structural characterizations of synthetic HS isomers containing 3-O-sulfation. Further, lyase-resistant 3-O-sulfated tetrasaccharides from natural sources were successfully sequenced. Notably, for all of the oligosaccharides in this study, the successful sequencing is based on NETD tandem mass spectra of commonly observed deprotonated precursor ions without derivatization or metal cation adduction, simplifying the experimental workflow and data interpretation. These results demonstrate the potential of NETD as a sensitive analytical tool for detailed, high-throughput structural analysis of highly sulfated GAGs. Graphical Abstract.


Severe hyponatraemia during sepsis and marijuana addiction.
The authors report a 29-year-old kidney transplant patient who presented, four episodes of severe hyponatraemia associated with sepsis from 2006 to 2010. He was a long-term user of marijuana. The association between severe recurrent hyponatraemia during sepsis and marijuana addiction might not be casual, since experimental data show that vasopressin release induced by sepsis is modulated by the endocannabinoid system.


The Role of Cyclin-Dependent Kinase 4/6 Inhibitors Treatment in Oligometastatic Breast Cancer: A Case Report on a Possible Curative Intent Strategy.
A small but important subset of patients with metastatic breast cancer has an oligometastatic disease. Some of these patients are highly responsive to systemic therapy and have the potential to achieve complete remission with treatment. However, it remains to be clarified the best locoregional and systemic treatment strategy for such patients and what features can determine whose patients are the best candidates. We also don't know what will be the role of cyclin-dependent kinase 4/6 inhibitors in those cases. We report the case of a 41-year-old woman with HR-positive/HER2-negative oligometastatic breast cancer who, after an excellent response to systemic treatment with palbociclib, anastrozole, and goserelin, underwent breast surgery and liver metastasectomy. After completing three years of systemic treatment, the CDK inhibitor was discontinued, maintaining the hormone therapy. The patient remained under regular follow-up with no evidence of disease after eight months.