The permeability of the cGMP-activated channel to organic cations in retinal rods of the tiger salamander.
1. The permeability of the channel activated by guanosine 3',5'-cyclic monophosphate (cGMP) to many organic monovalent cations was determined by recording macroscopic currents in excised inside-out patches of plasma membrane from isolated retinal rod outer segments of the tiger salamander. 2. Current-voltage relations were measured when the NaCl of the bathing medium was replaced by salts of organic cations. Permeability ratios relative to Na+ ions were calculated with the Goldman-Hodgkin-Katz potential equation from the measured changes of reversal potentials. 3. Hydroxylammonium+, hydrazinium+ and methylammonium+, which are molecules of very similar shape and size, permeate the channel with very different permeability ratios: 5.92, 1.99 and 0.60 respectively. 4. Methylated and ethylated ammonium+ compounds were investigated. It was found that, not only methylammonium+, but also dimethylammonium+ and ethylammonium+ were permeant with permeability ratios of 0.6, 0.14 and 0.16 respectively. Trimethylammonium+, tetramethylammonium+, diethylammonium+, triethylammonium+, and tetraethylammonium+ were not permeant. 5. Guanidinium+ and its derivatives formamidinium+, aminoguanidinium+, acetamidinium+ and methylguanidinium+ were all permeant with permeability ratios 1.12, 1.00, 0.63, 0.36 and 0.33 respectively. 6. The cGMP-activated channel was found to be permeable to at least thirteen organic cations. Molecular models of the permeant cations indicate that the cross-section of the narrowest part of the pore must be at least as large as a rectangle of 0.38 x 0.5 nm dimensions.


Optimal delivery of endothelial progenitor cells in a rat model of critical-size bone defects.
Nonunion and segmental bone defects are complex issues in orthopedic trauma. The use of endothelial progenitor cells (EPCs), as part of a cell-based therapy for bone healing is a promising approach. In preclinical studies, culture medium (CM) is commonly used to deliver EPCs to the defect site, which has the potential for immunogenicity in humans. The goal of this study was to find an effective and clinically translatable delivery medium for EPCs. Accordingly, this study compared EPCs delivered in CM, phosphate-buffered saline (PBS), platelet-poor plasma (PPP), and platelet-rich plasma (PRP) in a rat model of femoral critical-size defects. Fischer 344 rats (n = 35) were divided into six groups: EPC+CM, EPC+PBS, EPC+PPP, EPC+PRP, PPP alone, and PRP alone. A 5 mm mid-diaphyseal defect was created in the right femur and stabilized with a miniplate. The defect was filled with a gelatin scaffold impregnated with the corresponding treatment. Radiographic, microcomputed tomography and biomechanical analyses were performed. Overall, regardless of the delivery medium, groups that received EPCs had higher radiographic scores and union rates, higher bone volume, and superior biomechanical properties compared to groups treated with PPP or PRP alone. There were no significant differences in any outcomes between EPC subgroups or between PPP and PRP alone. These results suggest that EPCs are effective in treating segmental defects in a rat model of critical-size defects regardless of the delivery medium used. Consequently, PBS could be the optimal medium for delivering EPCs, given its low cost, ease of preparation, accessibility, noninvasiveness, and nonimmunogenic properties.


BTG1 inhibits malignancy as a novel prognosis signature in endometrial carcinoma.
Endometrial carcinoma (EC) is one of the three major malignant tumors of the female reproductive system. In recent years, the incidence and mortality rate of EC have increased. B-cell translocation gene 1 (BTG1) is an anti-proliferation gene that regulates the occurrence and development of a variety of tumors, but there is no research regarding this gene in EC. Based on The Cancer Genome Atlas (TCGA) database, we used a variety of bioinformatics tools and databases to explore the expression and prognosis of BTG1. We verified expression and prognosis of BTG1 in EC using qRT-PCR and analyzed the relevant clinicopathological parameters. We functionally enriched BTG1 and related genes in EC patients through the bioinformatics website and analyzed miRNA targets of BTG1 and interacting protein networks. Cell proliferation, wound healing, transwell invasion, and cell apoptosis assays were used to detect the effects of BTG1 on the malignant biological behavior of endometrial carcinoma cells (ECCs). The effect of BTG1 on the epithelial-to-mesenchymal transition (EMT) process was detected using western blot. We analyzed the expression and prognosis of BTG1 based on TCGA and found that low expression of BTG1 was associated with poor EC prognosis. The qRT-PCR suggested that BTG1 had low expression in EC. BTG1 expression was significantly correlated with overall survival (OS) shortening. Clinicopathological analysis suggested that expression of BTG1 was related to invasion depth and the International Federation of Gynecology and Obstetrics (FIGO) stage. EC pathological tissue type, fertility history, lymphatic metastasis, menopause, estrogen receptor (ER), progesterone receptor (PR), and age of diagnosis were not related. Functional enrichment analysis showed that BTG1 plays an important role in regulating embryonic development, tumorigenesis, apoptosis, and cell cycle. Biological behavior experiments suggest that BTG1 inhibits proliferation, migration, and invasion of ECCs, and promotes apoptosis of ECCs. Western blot indicated that BTG1 inhibited the EMT process of ECCs. BTG1, as a tumor suppressor gene, plays an important role in the occurrence and development of EC. We believe that BTG1 can be used as a potential prognostic biomarker for EC.


Normal-tension glaucoma is associated with cognitive impairment.
Recent research suggests an association between normal-tension glaucoma (NTG) and dementia. This study investigated whether cognitive impairment is more strongly associated with NTG than high tension glaucoma (HTG) using cognitive screening within an Australiasian Glaucoma Disease Registry. The authors completed a case-control cross-sectional cognitive screening involving 290 age-matched and sex-matched NTG participants and HTG controls aged ≥65 randomly sampled from the Australian and New Zealand Registry of Advanced Glaucoma. Cognitive screening was performed using the Telephone Version of the Montreal Cognitive Assessment (T-MoCA). The T-MoCA omits points requiring visual interpretation, accounting for confounding factors related to vision loss in visually impaired participants. Cognitive impairment was defined by a T-MoCA score of <11/22. Cognition was compared between NTG and HTG participants using predetermined thresholds and absolute screening scores. A total of 290 participants completed cognitive assessment. There were no differences in NTG (n=144) and HTG (n=146) cohort demographics or ocular parameters at baseline. Cognitive impairment was more prevalent in the NTG cohort than the HTG cohort (OR=2.2; 95% CI 1.1 to 6.7, p=0.030). Though a linear trend was also observed between lower absolute T-MoCA scores in the NTG cohort when compared with the HTG cohort, this association was not statistically significant (p=0.108). This study demonstrated an association between NTG status and poor cognition, supporting the hypothesis that there exists a disease association and shared pathoaetiological features between NTG and dementia.


Scintigraphic findings in synovial sarcoma with structural correlation.
Synovial sarcoma is a relatively rare malignant soft tissue tumour. It is highly aggressive, tends to occur in young adults and has a poor prognosis. The scintigraphic findings in 10 patients with histopathologically proven synovial sarcoma were reviewed. Most of the lesions occurred in the extremities and intense uptake of thallium was observed on 30-min and 4-h imaging in almost all cases. Thallium has an important role in the detection of possible metastatic disease and in monitoring response to therapy. The scintigraphic features of synovial sarcoma are presented and correlated with the radiographic findings.


[The woman's status and condom use in Cameroon].
The reasons for the high prevalence of STDs/HIV/AIDS among women are biological, economical and social. It is therefore necessary to carry out studies on the status of women and condom use in order to elucidate the mechanism through which the first variable affects the second. Such studies will also identify the elements to be taken into consideration in the prevention programmes of these diseases in women. In the year 2000, a survey on culture, gender, social behaviour and STDs/AIDS was conducted in Cameroun at Mbalmayo (Central Province) and at Bafoussam (Western Provience) among 1679 men and women of 15-49 years old. Multivariate logistic regression models were used, among others, to show that the woman's status has direct and indirect effects on condom use via age disparity between partners, frequency of discussion among couples on sexuality and the process of decision-making. Results obtained confirm this hypothesis. Communication among couples as well as women empowerment should, therefore, be improved as a strategy for considerably increasing the use of condom among Camerounian women. One of the ways to achieve this is to improve their status. Another way is to assist them during enlightenment campaigns to improve their self-perfection.


CT demonstration of periorbital graft-versus-host disease.
A 13-year-old boy who had undergone allogenic bone marrow transplantation for treatment of acute lymphocytic leukemia presented with bilateral periorbital rash and swelling. A CT scan showed bilateral symmetric periorbital swelling, subconjunctival fluid collections, and lacrimal gland enlargement. The patient was initially treated for presumed cellulitis. However, persistently negative regional cultures (eye, nasopharynx), a rapid response to immunosuppressive therapy after several days of nonresponse to intravenous antibiotic therapy, and ultimately, results of a skin biopsy confirmed the diagnosis of acute graft-versus-host disease.


Analysis of innate and acquired resistance to anti-CD20 antibodies in malignant and nonmalignant B cells.
The anti-CD20 monoclonal antibody, rituximab, provides a significant therapeutic benefit for patients with B-cell disorders. However, response to therapy varies and relapses are common, so an understanding of both inherited and acquired rituximab resistance is needed. In order to identify mechanisms of inherited resistance, sensitive versus resistant individuals were selected from a survey of 92 immortalized lymphoblastoid B-cell lines from normal individuals. Levels of CD20 protein and surface expression were lower in the resistant group. In contrast, CD20 mRNA levels were not correlated with susceptibility, suggesting regulation at a post-transcriptional level. To examine acquired resistance, resistant sublines were selected from both lymphoblastoid as well as lymphoma cell lines. Confirming previous findings, there was significant down-regulation of CD20 protein expression in all the resistant sublines. CD20 mRNA splice variants are reported to be associated with development of resistance. Three splice variants were observed in our cell lines, each lacking the binding epitope for rituximab, but none were associated with rituximab resistance. The second generation anti-CD20 mAb, ofatumumab, was more active compared with rituximab in vitro in the survey of all B-cell lines, mirroring results that have been reported previously with malignant B-cells. These studies show that normal B-lymphoblastoid cell lines can be used to model both innate and acquired mechanisms of resistance. They validate the important role of CD20 expression and enable future genetic studies to identify additional mediators of anti-CD20 mAb resistance.


Narrowband UVB phototherapy in children: A New Zealand experience.
Phototherapy is effective for many dermatoses in adults, but there is a paucity of data for its use in children. To review the efficacy and tolerability of narrowband UVB phototherapy in children at a tertiary centre in New Zealand, and determine if there were any factors that differentiated responders from non-responders. A prospective analysis of children (<16 years old) who had undergone phototherapy over a 15-year period. 116 children received phototherapy with a total of 144 courses. Mean age was 11.0 years with the majority being European and having skin phototype II. Atopic dermatitis was the most common indication for treatment followed by psoriasis, pityriasis lichenoides, nodular prurigo, morphea, vitiligo, urticaria pigmentosa and erythropoietic porphyria. Treatment was effective in the majority of children (72%). Most received only one course. For responders, the mean number of treatments was 32.4. The mean dose per treatment to achieve clearance was 886 mJ/cm(2) and the mean maximum treatment dose per treatment was 1328 mJ/cm(2) . All children tolerated treatment well with 36% developing brief, minimally symptomatic, erythema. Only two children experienced exacerbations of their underlying dermatoses. This study shows that phototherapy is an effective and well-tolerated treatment modality in children.


Vision for perception and vision for action in the primate brain.
Visual systems first evolved not to enable animals to see, but to provide distal sensory control of their movements. Vision as 'sight' is a relative newcomer to the evolutionary landscape, but its emergence has enabled animals to carry out complex cognitive operations on perceptual representations of the world. The two streams of visual processing that have been identified in the primate cerebral cortex are a reflection of these two functions of vision. The dorsal 'action' stream projecting from primary visual cortex to the posterior parietal cortex provides flexible control of more ancient subcortical visuomotor modules for the production of motor acts. The ventral 'perceptual' stream projecting from the primary visual cortex to the temporal lobe provides the rich and detailed representation of the world required for cognitive operations. Both streams process information about the structure of objects and about their spatial locations--and both are subject to the modulatory influences of attention. Each stream, however, uses visual information in different ways. Transformations carried out in the ventral stream permit the formation of perceptual representations that embody the enduring characteristics of objects and their relations; those carried out in the dorsal stream which utilize moment-to-moment information about objects within egocentric frames of reference, mediate the control of skilled actions. Both streams work together in the production of goal-directed behaviour.


DDAVP to prevent rapid correction in hyponatremia.
Correction of hyponatremia can be complicated by brisk free water diuresis with a rise in the serum sodium (s-Na) in excess of the generally accepted rate of 10-15 mmol/l/24 hours. We describe this complication and its treatment with desmopressin (dD-AVP), in a 56-year-old female with severe hyponatremia secondary to polydipsia and antidiuretic (ADH) activity. The patient developed a large free water diuresis with a markedly dilute urine (urine osmolality 61 mmol/kg) and a rise in the serum sodium of 19 mmol/l in 19 hours despite the addition of large volumes of free water intravenously and orally. To reduce the free water excretion, desmopressin (dD-AVP) 8 microg was given intravenously. This resulted in a rise in the urinary osmolality, a reduction in the urine volume, and a 2 mmol/l reduction in the serum sodium. Thereafter, the serum sodium rose 4 mmol/l in 24 hours. There were no neurological sequellae. In cases of appropriate but rapid correction of hyponatremia secondary to rapid free water diuresis, dD-AVP can safely reduce the free water excretion, slow the rate of correction of the serum sodium and simplify the fluid therapy of the patient.


Two initial vaccinations with the Bm86-based Gavacplus vaccine against Rhipicephalus (Boophilus) microplus induce similar reproductive suppression to three initial vaccinations under production conditions.
The cattle tick, Rhipicephalus (Boophilus) microplus, affects livestock production in many regions of the world. Up to now, the widespread use of chemical acaricides has led to the selection of acaricide-resistant ticks and to environmental contamination. Gavacplus is a subunit vaccine based on the recombinant Bm86 tick antigen expressed in yeast, capable to control infestations of R. microplus under controlled and production conditions. The vaccine constitutes the core element of broad control programs against this ectoparasite, in which acquired immunity in cattle to Bm86 is combined with a rational use of acaricides. At present, the conventional vaccine scheme consists of three doses that should be administered at weeks 0, 4 and 7, followed by a booster every six months. In this study we assayed a reduction in the number of the initial doses of Gavacplus, evaluated the time course and the level of bovine anti-Bm86 antibodies elicited, and analyzed the vaccine effect on ticks engorging on immunized cattle under production conditions. Following three different immunization schemes, the bovines developed a strong and specific immune response characterized by elevated anti-Bm86 IgG titers. A reduction in the weight of engorging female ticks, in the weight of the eggs laid and also in R. microplus viable eggs percentage was obtained by using only two doses of Gavacplus administered at weeks 0 and 4, followed by a booster six months later. This reduction did not differ from the results obtained on ticks engorging on cattle immunized at weeks 0, 4 and 7. It was also demonstrated that anti-Bm86 antibody titers over 1:640, measured in bovines immunized at weeks 0 and 4, were sufficient to affect weight and reproductive potential of female ticks as compared with ticks engorging on unvaccinated animals. In addition, no statistically significant differences were detected in the average weight of eggs laid by ticks engorged on immunized cattle that showed anti-Bm86 specific titers in the range of 1:640 to 1:81920. The administration of two initial doses of Gavacplus containing 100 μg of Bm86 antigen to non-immunized cattle under production conditions is sufficient to affect the weight and the reproductive capacity of R. microplus engorging females. According to these results, cattle herds' manipulation and vaccine costs could be potentially reduced with a positive impact on the implementation of integrated control programs against R. microplus.


The contrasting properties of 2 xenogenic erythrocyte-reactive natural antibodies in commercial ducks.
Sera obtained from commercial drakes on days 14 and 38 of age were tested by microtiter for the capacity to agglutinate and lyse rabbit (Rb) and human (HuO) erythrocytes. Three agglutination types, differing by strength, were recognized: HA1 (strong), HA2 (weak), and HA45 (very weak).Two degrees of lysis: L(100) (complete) and L(50) (partial), measured complement activity. Day 14 sera agglutinated Rb (average log(2) titers: HA1 = 1.5, HA2 = 4.1) and lysed Rb (average log(2) titers: L(100) = 2, L(50) = 2.5) but only 8/115 (~9%) agglutinated HuO (HA45 = 0.4) while most (>80%) lysed HuO (average log(2) titers: L(100) = 1.3, L(50) = 1.8). Both Rb and HuO agglutination and lysis titers were higher by d 38. At that age, all ducks lysed HuO and 50% of ducks acquired a capacity to agglutinate these cells with more strength. However, the quality of HuO agglutination could not be differentiated into HA1 or HA2 types. Average d 38 log(2) titers of all measures were Rb: HA1 = 4, HA2 = 8.4, L(100) = 3, and L(50) = 4; and HuO: HA = 2.8, L(100) = 3.9, and L(50) = 1.2. The quality of the Rb agglutination suggested the participation of both IgM and standard-sized IgY antibodies. Lysis of Rb may occur by both classic and alternate complement pathways. The HuO lysis appears to depend primarily on the alternate complement pathway. It is suggested that multiple measurement systems such as these offer a practical way of obtaining information on immunity in experiments where the chief interest lies elsewhere.


Molecular characterization and clonal dynamics of nosocomial blaOXA-23 producing XDR Acinetobacter baumannii.
The emergence of infections associated to new antimicrobial resistance in Acinetobacter baumannii (Ab) genotypes represents a major challenge. In this context, this study aimed to determine the diversity of resistance mechanisms and investigate clonal dissemination and predominant sequence types (STs) in multidrug-resistant Ab strains of clinical (tracheal aspirate, n = 17) and environmental (surface, n = 6) origins. Additionally, the major clones found in clinical (A) and environmental (H) strains had their complete genomes sequenced. All strains were submitted to polymerase chain reactions (PCR) for the detection of the ISAba1/blaOXA-51-like and ISAba1/blaOXA-23-like genes, while the expression of genes encoding the carO porin, AdeABC (adeB), AdeFGH (adeG), and AdeIJK (adeJ) efflux pumps was determined by real time PCR (qPCR). Most of the strains were characterized as extensively drug-resistant (XDR) with high minimal inhibitory concentrations (MICs) detected for tigecycline and carbapenems. Associations between ISAba1/OXA-51 and ISAba1/OXA-23 were observed in 91.3% and 52.2% of the strains, respectively. Only the adeB gene was considered hyper-expressed. Furthermore, most of the strains analyzed by the MuLtilocus Sequence-Typing (MLST) were found to belong to the clonal complex 113 (CC113). In addition, a new ST, ST1399, belonging to CC229, was also discovered herein. Strains analyzed by whole genome sequencing presented resistance genes linked to multidrug-resistance phenotypes and confirmed the presence of Tn2008, which provides high levels carbapenem-resistance.


Variation in Bacterial Respiratory Culture Results in Children With Neurologic Impairment.
To examine bacterial respiratory cultures in children with neurologic impairment (NI) (eg, cerebral palsy), both with and without tracheostomies, who were hospitalized with acute respiratory infections (ARIs) (eg, pneumonia) and to compare culture results across hospitals and age groups. This multicenter retrospective cohort study included ARI hospitalizations for children aged 1 to 18 years with NI between 2007 and 2012 who had a bacterial respiratory culture obtained within 2 days of admission. Data from 5 children's hospitals in the Pediatric Health Information System Plus database were used. Organisms consistent with oral flora and nonspeciated organisms were omitted from analysis. The prevalence of positive respiratory culture results and the prevalence of organisms identified were compared across hospitals and age groups and in subanalyses of children with and without tracheostomies by using generalized estimating equations to account for within-patient clustering. Of 4900 hospitalizations, 693 from 485 children had bacterial respiratory cultures obtained. Of these, 54.5% had positive results, although this varied across hospitals (range 18.6%-83.2%; P < .001). Pseudomonas aeruginosa and Staphylococcus aureus were the most commonly identified organisms across hospitals and age groups and in patients with and without tracheostomies. Large variation in growth prevalence was identified across hospitals but not age groups. The bacteriology of ARI in hospitalized children with NI differs from that of otherwise healthy children. Significant variation in prevalence of positive bacterial respiratory culture results and organism growth were observed across hospitals, which may be secondary to local environmental factors and microbiology reporting practices.


Phosphoproteome analysis reveals a critical role for hedgehog signalling in osteoblast morphological transitions.
The reciprocal and adaptive interactions between cells and substrates governing morphological transitions in the osteoblast compartment remain largely obscure. Here we show that osteoblast cultured in basement membrane matrix (Matrigel™) exhibits significant morphological changes after ten days of culture, and we decided to exploit this situation to investigate the molecular mechanisms responsible for guiding osteoblast morphological transitions. As almost all aspects of cellular physiology are under control of kinases, we generated more or less comprehensive cellular kinome profiles employing PepChip peptide arrays that contain over 1000 consensus substrates of kinase peptide. The results obtained were used to construct interactomes, and these revealed an important role for FoxO in mediating morphological changes of osteoblast, which was validated by Western blot technology when FoxO was significantly up-expressed in response to Matrigel™. As FoxO is a critical protein in canonical hedgehog signalling, we decided to explore the possible involvement of hedgehog signalling during osteoblast morphological changes. It appeared that osteoblast culture in Matrigel™ stimulates release of a substantial amounts Shh while concomitantly inducing upregulation of the expression of the bona fide hedgehog target genes Gli-1 and Patched. Functional confirmation of the relevance of these results for osteoblast morphological transitions came from experiments in which Shh hedgehog signalling was inhibited using the well-established pathway inhibitor cyclopamine (Cyc). In the presence of Cyc, culture of osteoblasts in Matrigel™ is not capable of inducing morphological changes but appears to provoke a proliferative response as evident from the upregulation of Cyclin D3 and cdk4. The most straightforward interpretation of our results is that hedgehog signalling is both necessary and sufficient for membrane matrix-based morphological transitions.


Remediation therapy in patients with alcohol use disorders and neurocognitive disorders: A Pilot Study.
Many alcohol-dependent patients suffer from cognitive impairment of variable severity, manifested by alterations in retrograde and anterograde memory, visuospatial processing, cognitive abilities and attention, some of which are reversible. In this context, cognitive remediation therapies could significantly improve patients' performance; therefore, these are considered a valuable alternative. The aim of this study was to implement cognitive remediation therapy in patients with alcohol dependence and cognitive impairment and evaluate its viability and effectiveness. The participants were sixteen abstinent, alcohol-dependent patients (mean age of 59 years, 63% males) from the Addictive Behaviours Unit of a tertiary hospital. Over 6 months, a nurse led 1-hour weekly sessions (24 sessions in total) during which exercises for improving functional, social and cognitive performance were completed. Patients were assessed at baseline, at the end of the study and 6 months later, using the Mini-Mental State Examination (MMSE) and the Memory Alteration Test (M@T). Their respective scores were 26.4 (SD 3.16), 29 (SD 1.67) and 27 (SD 3.1) for the MMSE and 38.7 (SD 6.81), 45.7 (SD 5.6) and 41.1 (SD 7.86) for the M@T. Changes were assessed with both Friedman and Wilcoxon signed-rank tests, with mostly statistically significant differences (p < 0.05). Assistance and satisfaction were high. Therefore, the therapy was viable, widely accepted and effective.


A critical analysis of surgery for occult tethered cord syndrome.
Tethered cord syndrome (TCS) is an amalgamation of neurological, urological, orthopedic, and dermatologic signs and symptoms with radiographic evidence of a thickened filum and low-lying conus. Surgical sectioning of the filum and disconnection of any tethering entities such as dermal sinus tracts or lipomas has been shown to improve outcomes. The manifestation of TCS symptoms in the absence of a low-lying conus has been referred to as occult tethered cord syndrome (OTCS) and is much less well reviewed in the literature. To date, there has only been one randomized controlled trial examining the effect of intervention in OTCS; therefore, contemporary data is often elicited from limited cohorts. To perform a comprehensive literature review of management in OTCS and evaluate treatment response rates to sectioning of the filum terminale. Seventeen papers met inclusion criteria for our review. Sample sizes ranged from 8 to 60 children, and results were mixed, often dependent on study design, definition of typical OTCS symptoms, and follow-up intervals. Symptomatic improvement was observed in > 50% of patients for all but one study; however, the recurrence rates were highly variable. The data regarding the efficacy of surgical treatment in OTCS is mixed and merits more rigorous scientific examination with strict and clear parameters regarding symptomatic operationalization and follow-up time points to monitor for TCS recurrence.


Perceptions of sex offenders with intellectual disability: A comparison of forensic staff and the general public.
Existing literature suggests that individuals with intellectual disability are not always held accountable for their actions and forensic staff are unlikely to report their sexually harmful behaviour. This research explores how categorization of an offender as having intellectual disability and the framing of an offence as planned or opportunistic, impacts upon ratings of risk, blame and intent by forensic staff and the general public. The impact of pre-existing attitudes towards sex offenders upon these ratings was also considered. Differences are identified between participants' ratings when the offender is categorized as having an intellectual disability. More positive attitudes are associated with lower ratings of several factors. Individuals with overly positive attitudes towards sex offenders could underestimate the risk posed by sex offenders with intellectual disability. These results are important to consider alongside the NHS Transforming Care Agenda.


Identification of Clostridium butyricum and Clostridium beijerinckii by gas-liquid chromatography and sugar fermentation: correlation with DNA homologies and electrophoretic patterns.
Sixty-five strains of clostridia of the butyricum group were studied by DNA-DNA hybridization, electrophoresis of cell proteins, gas-liquid chromatography, and fermentation of glycerol, inositol and ribose. The DNA--DNA hybridization results confirmed that strains of this group belong to two main species, Clostridium butyricum and C. beijerinckii. Five strains did not hybridize with the reference strains of these two species. Most of the strains could be identified by quantitative gas-liquid chromatographic analysis combined with fermentation patterns. The other strains could be identified by their protein electrophoretic patterns.


Sex- and age-dependent association of SLC11A1 polymorphisms with tuberculosis in Chinese: a case control study.
Host genetic factors are important determinants in tuberculosis (TB). The SLC11A1 (or NRAMP1) gene has been studied extensively for genetic association with TB, but with inconsistent findings. In addition, no study has yet looked into the effect of sex and age on the relationship between SLC11A1 polymorphisms and TB. A case-control study was conducted. In total, 278 pulmonary TB patients and 282 sex- and age-matched controls without TB were recruited. All subjects were ethnic Chinese. On the basis of linkage disequilibrium pattern, three genetic markers from SLC11A1 and one from the nearby IL8RB locus were selected and examined for association with TB susceptibility. These markers were genotyped using single strand conformation polymorphism analysis or fragment analysis of amplified products. Statistically significant differences in allele (P = 0.0165, OR = 1.51) and genotype (P = 0.0163, OR = 1.59) frequencies of the linked markers SLC6a/b (classically called D543N and 3'UTR) of the SLC11A1 locus were found between patients and controls. With stratification by sex, positive associations were identified in the female group for both allele (P = 0.0049, OR = 2.54) and genotype (P = 0.0075, OR = 2.74) frequencies. With stratification by age, positive associations were demonstrated in the young age group (age < or =65 years) for both allele (P = 0.0047, OR = 2.52) and genotype (P = 0.0031, OR = 2.92) frequencies. All positive findings remained significant even after correction for multiple comparisons. No significant differences were noted in either the male group or the older age group. No significant differences were found for the other markers (one SLC11A1 marker and one IL8RB marker) either. This study confirmed the association between SLC11A1 and TB susceptibility and demonstrated for the first time that the association was restricted to females and the young age group.


A conserved protein interaction network involving the yeast MAP kinases Fus3 and Kss1.
The Saccharomyces cerevisiae mitogen-activated protein kinases (MAPKs) Fus3 and Kss1 bind to multiple regulators and substrates. We show that mutations in a conserved docking site in these MAPKs (the CD/7m region) disrupt binding to an important subset of their binding partners, including the Ste7 MAPK kinase, the Ste5 adaptor/scaffold protein, and the Dig1 and Dig2 transcriptional repressors. Supporting the possibility that Ste5 and Ste7 bind to the same region of the MAPKs, they partially competed for Fus3 binding. In vivo, some of the MAPK mutants displayed reduced Ste7-dependent phosphorylation, and all of them exhibited multiple defects in mating and pheromone response. The Kss1 mutants were also defective in Kss1-imposed repression of Ste12. We conclude that MAPKs contain a structurally and functionally conserved docking site that mediates an overall positively acting network of interactions with cognate docking sites on their regulators and substrates. Key features of this interaction network appear to have been conserved from yeast to humans.


Cloning, characterization and mapping of the human ATP5E gene, identification of pseudogene ATP5EP1, and definition of the ATP5E motif.
A cDNA encoding the epsilon subunit of human ATP synthase, ATP5E, was isolated from heart, skeletal muscle and spleen cDNA libraries respectively. Its genome structure was characterized as comprising three exons and two introns within a stretch of 5 kb, according to the genomic sequence AL109840. The gene was mapped to human chromosome 20q13.3 between marker D20S173 and 20qter using the radiation hybrid GB4 panel. Northern blot analysis showed that the ATP5E gene was expressed as a single 0.6 kb transcript in all 16 human tissues tested, with a high level present in heart and skeletal muscle. A new conserved motif composed of 24 residues, termed the ATP5E motif [W(R/K)X(5)YX(2)(Y/F)X(3)(C/A)X(4)RX(3)K], was defined on the basis of sequences of ATP synthase epsilon subunits from ten different organisms. In addition, a pseudogene ATP5EP1 was also identified on the basis of genomic sequence AC004066, localized on human chromosome 4q25. By analysing these results combined with the Southern blot patterns of human DNA hybridized with bovine ATP5E cDNA reported previously [Vinas, Powell, Runswick, Iacobazzi and Walker (1990) Biochem. J. 265, 321-326], we provide evidence of yet further homologous sequences (either gene or pseudogene) of ATP5E, in addition to ATP5E and ATP5EP1 in the human genome.


Defective hepatitis B virus DNA molecules detected in a stable integration pattern in a hepatoma cell line, and in induced tumours and derived cell lines.
Hepatitis B virus (HBV) DNA was found to be integrated into seven sites in the DNA of the PLC/PRF/5 hepatoma cell line as determined by digestion with the restriction endonuclease HindIII which does not cut through the viral genome. The integration pattern was stable in the cell line, in tumours induced in athymic mice by this line and in cell lines derived from such tumours. Syntheses of hepatitis B surface antigen and alphafoetoprotein were maintained in the induced tumours and derived cell lines. A defective HBV DNA molecule (approx. 2.8 kilobase pairs) appears to be integrated in a head-to-tail tandem arrangement and it is proposed that such defective molecules may be involved in the process of neoplastic transformation by HBV.


Multiple hepatic metastases of cardiac angiosarcoma.
The differential diagnosis of hepatic focal lesions is challenging because the etiology can be inflammatory, infectious, and even neoplastic. A rare cause of metastatic liver nodules is cardiac angiosarcoma. We report a case of this tumor, which was diagnosed only after autopsy. A 26-year-old Caucasian man was admitted for progressive dyspnea and cough over the past 3 weeks. Physical examination showed only hypophonetic heart sounds. Laboratory analysis demonstrated anemia and elevated inflammatory markers, despite normal biochemical parameters and liver function. Transthoracic echocardiography revealed massive pericardial effusion. Abdomen computed tomography (CT) showed multiple hepatic nodules, the largest of which measured 3 cm, but the percutaneous biopsy revealed only lobular necrosis and perisinusoidal fibrosis without granulomas or neoplastic cells. During hospitalization, the patient had fever and night sweats with weight loss, and empiric treatment for extrapulmonary tuberculosis associated with corticosteroids was initiated. The outpatient follow-up revealed complete improvement of the pericardial effusion, but maintenance of the liver lesions. After 2 months of hospital discharge, the patient was readmitted with hemorrhagic shock due to bleeding liver lesions, which were evidenced by CT. Embolization of the right hepatic artery was performed, but the patient soon died. The autopsy revealed a primary cardiac angiosarcoma with multiple hepatic metastases, rupture of the Glisson's capsule and laceration of the liver. The case shows how important and difficult the diagnosis of focal liver lesions is, since it may result in an unexpected fatal outcome.


The association of anti-CD74 antibody with spondyloarthropathies.
The etiopathogenesis of spondyloarthropathies (SpA) is still unclear. Recently, anti-CD74 antibody has been suspected to play a role in SpA etiopathogenesis. This study aimed to examine the levels of anti-CD74 antibody in patients with SpA and investigate their association with disease activity. This study was conducted using data from patients who were treated at the departments of rheumatology and gastroenterology between June 2013 and November 2013. The demographic and clinical characteristics of the participants and their serum IgG-type antibodies against anti-CD74 were analyzed. We analyzed 111 patients with ankylosing spondylitis (AS), 108 patients with inflammatory bowel disease (IBD), and 101 healthy controls. The rate of human leukocyte antigen-B27 positivity was 86.5% in patients with AS and 21.3% in patients with IBD. The mean levels of anti-CD74 antibodies in the AS, IBD, and control groups were 6.99±3.24 ng/mL, 6.25±3.34 ng/mL, and 7.83±4.72 ng/mL, respectively. Anti-CD74 levels were higher in healthy controls than in patients with IBD (p=0.009). There was no significant difference in anti-CD74 levels between the AS and IBD groups and the AS and control groups. In addition, there was no correlation between anti-CD74 levels and disease activity. This study could not find an association between anti-CD74 levels and SpA in Turkish patients.


Experimental metolachlor toxicosis in Nubian goats in the Sudan.
Six out of 15 Nubian goats kids were given single oral doses of metolachlor (Dual 720 EC) at 2,000 or 500 mg/kg liveweight and died within 1 h of the dosing. Other 6 goats were given daily oral doses at 200 or 25 mg/kg and died or were slaughtered between days 8 and 25. In goats receiving single doses, the signs of poisoning were convulsive episodes, incoordination of movement, tremors, severe muscular spasms, stiffness, profuse salivation, respiratory distress, abnormal posture and recumbency. In goats receiving metolachlor at daily doses, the signs were similar, but developed slowly. Increases in the activities of serum AST and GGT and in the concentration of urea, and decreases in total protein concentration were correlated with clinical changes and lesions.


Expandable cages increase the risk of intraoperative subsidence but do not improve perioperative outcomes in single level transforaminal lumbar interbody fusion.
Expandable cages (EXP) are being more frequently utilized in transforaminal lumbar interbody fusions (TLIF). EXP were designed to reduce complications related to neurological retraction, enable better lordosis restoration, and improve ease of insertion, particularly in the advent of minimally invasive surgical (MIS) techniques, however they are exponentially more expensive than the nonexpandable (NE) alternative. To investigate the clinical results of expandable cages in single level TLIF. Retrospective review at a single institution. Two hundred and fifty-two single level TLIFs from 2012 to 2018 were included. Clinical characteristics, perioperative and neurologic complication rates, and radiographic measures. Patients ≥18 years of age who underwent single level TLIF with minimum 1 year follow-up were included. clinical characteristics, perioperative and neurologic complications. Radiographic analysis included pelvic incidence-lumbar lordosis (PI-LL) mismatch, segmental lumbar lordosis (LL) mismatch, disc height restoration, and subsidence ≥2 mm. Statistical analysis included independent t tests and chi-square analysis. For nonparametric variables, Mann-Whitney U test and Spearman partial correlation were utilized. Multivariate regression was performed to assess relationships between surgical variables and recorded outcomes. For univariate analysis significance was set at p<.05. Due to the multiple comparisons being made, significance for regressions was set at p<.025 utilizing Bonferroni correction. Two hundred and fifty-two TLIFs between 2012 and 2018 were included, with 152 NE (54.6% female, mean age 59.28±14.19, mean body mass index (BMI) 28.65±5.38, mean Charlson Comorbidity Index (CCI) 2.20±1.89) and 100 EXP (48% female, mean age 58.81±11.70, mean BMI 28.68±6.06, mean CCI 1.99±1.66) with no significant differences in demographics. Patients instrumented with EXP cages had a shorter length of stay (3.11±2.06 days EXP vs. 4.01±2.64 days NE; Z=-4.189, p<.001) and a lower estimated blood loss (201.31±189.41 mL EXP vs. 377.82±364.06 mL NE; Z=-6.449, p<.001). There were significantly more MIS-TLIF cases and bone morphogenic protein (BMP) use in the EXP group (88% MIS, p<.001 and 60% BMP, p<.001) as illustrated in Table 1. There were no significant differences between the EXP and NE groups in rates of radiculitis and neuropraxia. In multivariate regression analysis, EXP were not associated with a difference in perioperative outcomes or complications. Radiographic analyses demonstrated that the EXP group had a lower PI-LL mismatch than the NE cage group at baseline (3.75±13.81° EXP vs. 12.75±15.81° NE; p=.001) and at 1 year follow-up (3.81±12.84° EXP vs. 8.23±12.73° NE; p=.046), but change in regional and segmental alignment was not significantly different between groups. Multivariate regression demonstrated that EXP use was a risk factor for intraoperative subsidence (2.729[1.185-6.281]; p=.018). Once technique was controlled for, TLIFs utilizing EXP do not have significantly improved neurologic or radiographic outcomes compared with NE. EXP increase risk of intraoperative subsidence. These results question the value of the EXP given the higher cost.


Alu and L1 sequence distributions in Xq24-q28 and their comparative utility in YAC contig assembly and verification.
The contents of Alu- and L1-containing TaqI restriction fragments were assessed by Southern blot analyses across YAC contigs already assembled by other means and localized within Xq24-q28. Fingerprinting patterns of YACs in contigs were concordant, and using software based on that of M. V. Olson et al. (1986, Proc. Natl. Acad. Sci. USA 83: 7826) to analyze digitized data on fragment sizes, fingerprinting itself could establish matches among about 40% of a test group of 435 YACs. At 100-kb resolution, both repetitive elements were found throughout the region, with no apparent enrichment of Alu or L1 in DNA of G compared to that found in R bands. However, consistent with a random overall distribution, delimited regions of up to 100 kb contained clusters of repetitive elements. The local concentrations may help to account for the reported differential hybridization of Alu and L1 probes to segments of metaphase chromosomes.


The Attitudes and Practices of General Practitioners about the Use of Chaperones in Melbourne, Australia.
Introduction. To consider the use of medical chaperones during certain clinical examinations is important whether one practises as a specialist, nurse, medical student, or generalist. Chaperones have been used by doctors conducting intimate examinations for many years but their true extent remains largely unknown. Until recently, there was no national guidance in Australia. Aim. To explore the attitudes and practices of general practitioners (GP) regarding their use of chaperones in urban Melbourne, Australia. Method. Qualitative two focus groups involving seventeen GPs from two locations. Discussions were audio-taped, transcribed verbatim and analysed. Results. Common themes and subthemes emerged which were grouped into three main areas: (a) practitioner-related, (b) patient-related and (c) practice related. Discussion. This is the first study from an Australian primary care perspective to gauge the attitudes and experiences of GPs on their use of chaperones. It will provide vital information to inform the next step of extending this research to a national GP audience. From an international perspective, this study provides an excellent template for other primary care clinicians to conduct research in this important field of doctor-patient relationship.


Catch assemblages in the small-scale trap fishery with relation to hydrographic features of a tropical bay in the Gulf of Thailand.
Catches from the small-scale trap fishery in Bandon Bay, Suratthani, Thailand, were monitored from 14 sites around the Bay, then disturbance to aquatic communities and catch assemblage were examined. At the same time, the hydrographical features of the bay were surveyed. The study was conducted throughout 2019 except in December, when a tropical cyclone made sampling impossible. In total, 17,373 animals from 118 species or species groups of aquatic animals were collected. The main target of the fishery, blue swimming crab Portunus pelagicus, contributed about 10% of the total catch in terms of number; meanwhile, another crab, Charybdis affinis, was the most dominant species (41% of total). W-statistics of Abundance-Biomass Comparison curves ranged between -0.025 and 0.031, indicating light disturbance to the communities in this fishing ground. The catch assemblage, based on number in catch composition, were divided into three main clusters and six sub-clusters by using the self-organizing map (SOM) technique. The SOM results showed that the catch assemblages differed based largely on temporal variation. The hydrographic features of Bandon Bay at times exhibited a layered structure and had strong spatial variation. The bay's current system was governed by motion of tidal currents; meanwhile, the circulation was governed by monsoonal wind and freshwater discharges. Tidal current was strong and ranged between approximately 0.6 m to 2.2 m. Water within the bay was always warmer than the outer sea. High water temperature was observed two times during the year: during monsoon transition 1 (April to May) and transition 2 (October). Salinity showed great spatial and temporal variation, differing by more than 5-10 ppt horizontally. It was possible to use these dynamic hydrological features of Bandon Bay to explain assemblage patterns of the trap-net catches.


Trans-chalcone and quercetin down-regulate fatty acid synthase gene expression and reduce ergosterol content in the human pathogenic dermatophyte Trichophyton rubrum.
Fatty acid synthase (FAS) is a promising antifungal target due to its marked structural differences between fungal and mammalian cells. The aim of this study was to evaluate the antifungal activity of flavonoids described in the scientific literature as FAS inhibitors (quercetin, trans-chalcone, ellagic acid, luteolin, galangin, and genistein) against the dermatophyte Trichophyton rubrum and their effects on fatty acid and ergosterol synthesis. The antifungal activity of the natural products was tested by the microdilution assay for determination of the minimum inhibitory concentration (MIC). The effect of the compounds on the cell membrane was evaluated using a protoplast regeneration assay. Ergosterol content was quantified by spectrophotometry. Inhibition of FAS by flavonoids was evaluated by an enzymatic assay to determine IC50 values. Quantitative RT-PCR was used to measure transcription levels of the FAS1 and ERG6 genes involved in fatty acid and ergosterol biosynthesis, respectively, during exposure of T. rubrum to the flavonoids tested. The flavonoids quercetin and trans-chalcone were effective against T. rubrum, with MICs of 125 and 7.5 μg/mL for the wild-type strain (MYA3108) and of 63 and 1.9 μg/mL for the ABC transporter mutant strain (ΔTruMDR2), respectively. The MICs of the fluconazole and cerulenin controls were 63 and 125 μg/mL for the wild-type strain and 30 and 15 μg/mL for the mutant strain, respectively. Quercetin and trans-chalcone also reduced ergosterol content in the two strains, indicating that interference with fatty acid and ergosterol synthesis caused cell membrane disruption. The MIC of quercetin reduced the number of regenerated protoplasts by 30.26% (wild-type strain) and by 91.66% (mutant strain). Half the MIC (0.5 MIC) of quercetin did not reduce the number of regenerated wild-type fungal colonies, but caused a 36.19% reduction in the number of mutant strain protoplasts. In contrast, the MIC and 0.5 MIC of trans-chalcone and cerulenin drastically reduced protoplast regeneration in the two strains. The FAS1 gene was repressed in the presence of MICs of quercetin, trans-chalcone, fluconazole and cerulenin. The ERG6 gene was induced in the presence of MICs of fluconazole and cerulenin and was repressed in the presence of MICs of trans-chalcone and quercetin. Trans-chalcone and quercetin inhibited the enzymatic activity of FAS, with IC50 values of 68.23 and 17.1 μg/mL, respectively. Trans-chalcone and quercetin showed antifungal activity against T. rubrum, reducing ergosterol levels and modulating the expression of FAS1 and ERG6.


Dose-response relation between dietary sodium and blood pressure: a meta-regression analysis of 133 randomized controlled trials.
The projected reduced mortality effect of reduced sodium intake in model-based studies conflicts with the observed increased mortality associated with low sodium intake in population studies. This may reflect an overestimation of the dose-response relation between sodium reduction (SR) and blood pressure (BP) used in mortality modeling studies. The present meta-regression analysis sought to estimate the dose-response relations between SR and BP in study groups with mean BP above or below the 75th percentile of the general population. Based on a literature search from 1 January 1946 to 11 April 2018, we identified 133 randomized controlled trials allocating healthy or hypertensive individuals to SR or usual sodium intake. Multivariable regression analyses of the mean SR versus the mean blood pressure effect adjusted for effect modifiers were performed. In study groups with mean BP above the 75th percentile [131/78 mm Hg systolic BP (SBP)/diastolic BP (DBP)], there was strong evidence of a linear dose-response relation between SR and BP. For SBP, the dose-response relation was -7.7 mm Hg/100 mmol SR (95% CI: -10.4, -5.0), and for DBP it was -3.0 mm Hg/100 mmol SR (95% CI: -4.6, -1.4). In study groups with mean BP ≤ 131/78 mm Hg, the relation between SR and BP was weak. For SBP it was -1.46 mm Hg/100 mmol SR (95% CI: -2.7, -0.20) and for DBP it was: -0.07 mm Hg/100 mmol SR (95% CI: -1.5, 1.4). Only study groups with a BP in the highest 25th percentile of the population showed a clinically significant drop in BP with SR. The policy of lowering dietary sodium intake in the general population may need to be reframed to target patients with hypertension. This study was registered at PROSPERO 2015 as CRD42015017773.


Performance and Consistency of Circulating Warm Water Blankets for Rodents.
General anesthesia as used for rodent research can have adverse effects on physiologic mechanisms. Thermoregulation is often greatly inhibited, with resultant deleterious effects on cardiac and respiratory function. These potential effects can be mitigated by providing external heat support. The circulating warm water blanket and associated heat pump are often used in rodent procedures. The current study demonstrated that the heating pump and water blanket require quality control assessment to ensure adequate function. Our data showed that of the 6 pumps tested, 5 were able to achieve a temperature that met or exceeded the documented thermoneutral zone for mice. Pumps required 20 min of warming to reach their maximal attainable temperatures for the designated user setting. Although the pumps reached a temperature that was sufficient to provide external thermal support, only 1 of the 6 pumps reached the temperature that was set by the user during the trial. Surface temperatures across the water blanket were recorded to analyze whether a difference in heat support was influenced by animal placement along the water blanket; however, the location points did not yield statistically different results. Two pumps were eliminated from the study due to failure to pass the preparation phase of the trial. The results of this study support the need for facilities to establish quality control measures to ensure that heat support systems are functioning at a level required to maintain normothermia during anesthetic procedures.


Simulating the impact of Addiction Consult Services in the context of drug supply contamination, hospitalizations, and drug-related mortality.
Illicitly manufactured fentanyl (IMF) is increasing in international drug supply chains, and IMF-related opioid overdose deaths are rising in North America. Hospitalizations among patients with opioid use disorder (OUD) are also rising; and, hospitalized patients are at increased risk of overdose and death following hospital discharge. Hospitalization is a key opportunity to engage patients with OUD. Addiction consult services (ACS) can provide effective treatment for patients hospitalized with OUD. This study aims to estimate the effect of increasing IMF contamination on drug-related death among patients hospitalized with OUD, and simulate the role of ACS expansion to mitigate these effects. We used a Markov model to mirror care systems for adult patients hospitalized with OUD in Oregon, from the time of hospital admission through 12-months post-discharge, and simulated patients through modeled care systems to evaluate the expansion of Addiction Consult Services in the context of increasing IMF in the drug supply. In a simulated cohort of 10,000 patients, we estimate that 537 patients would die from drug-related causes within 12-months of hospital discharge. In the context of increased IMF in the drug supply, this estimate increased to 913. ACS referral at baseline was 4%; increasing ACS referral to accommodate 10%, 50%, or 100% of hospitalized OUD patients in the state reduces drug-related deaths to 904, 849, and 780, respectively. The number needed to treat for ACS to avoid one drug-related death in the context of increased IMF was 73. Hospitals should expand interventions to help reduce IMF-related opioid overdoses, including through implementation of ACS. In the context of rising IMF-related deaths, ACS expansion could help connect patients to treatment, offer harm reduction interventions, or both, which can help reduce the risk of opioid-related death.


The Role of Diacylglycerol Kinase in the Amelioration of Diabetic Nephropathy.
The drastic increase in the number of patients with diabetes and its complications is a global issue. Diabetic nephropathy, the leading cause of chronic kidney disease, significantly affects patients' quality of life and medical expenses. Furthermore, there are limited drugs for treating diabetic nephropathy patients. Impaired lipid signaling, especially abnormal protein kinase C (PKC) activation by de novo-synthesized diacylglycerol (DG) under high blood glucose, is one of the causes of diabetic nephropathy. DG kinase (DGK) is an enzyme that phosphorylates DG and generates phosphatidic acid, i.e., DGK can inhibit PKC activation under diabetic conditions. Indeed, it has been proven that DGK activation ameliorates diabetic nephropathy. In this review, we summarize the involvement of PKC and DGK in diabetic nephropathy as therapeutic targets, and its mechanisms, by referring to our recent study.


Risk of a new benzodiazepine prescription in relation to recent hospitalization.
To determine if recent hospital admission was associated with new outpatient prescribing of benzodiazepines among community-dwelling older people. Nested case-control study using administrative data sets of the provincial health insurance board. Province of Quebec. Cases were 4127 community-dwelling older people who were newly dispensed a benzodiazepine during an 8-month period in 1990. Controls were 16,486 community-dwelling older people who were dispensed any drug (except a benzodiazepine) on the same day as the case-defining index prescription. EXPOSURE AND OUTCOME MEASURES: Admission to an acute care hospital within a 30-day period before a new dispensing of a benzodiazepine. Other variables measured were patient age, gender, number of ambulatory physician visits, healthcare region, Chronic Disease Score (CDS), and use of drugs for depression and psychosis. Cases were more than three times as likely as controls to have been hospitalized in the 30-day period before the index date (adjusted odds ratio (OR) 3.09; 95% CI, 2.78-3.45). The use of prescription drugs for physical health problems modified this association in that cases who used more medication were also more likely to receive a new benzodiazepine prescription following a recent hospital admission (adjusted OR 4.09; 95% CI, 3.59-4.65 when the CDS was equal to 5 vs adjusted OR 1.96; 95% CI, 1.66-2.31 when the CDS was equal to 0). Recent hospitalization confers an increased risk of a new outpatient benzodiazepine prescription among community-dwelling older people in Quebec. Those who use more medication, and who may be more vulnerable to drug-related adverse events, are more likely to be newly dispensed a benzodiazepine following a recent, acute-care hospital admission.


Peroxidase activity of mitochondrial cytochrome c oxidase.
Mitochondrial cytochrome c oxidase is able to oxidize various aromatic compounds like o-dianisidine, benzidine and its derivatives (diaminobenzidine, etc.), p-phenylenediamine, as well as amidopyrine, melatonin, and some other pharmacologically and physiologically active substances via the peroxidase, but not the oxidase mechanism. Although specific peroxidase activity of cytochrome c oxidase is low compared with classical peroxidases, its activity may be of physiological or pathophysiological significance due to the presence of rather high concentrations of this enzyme in all tissues, as well as specific localization of the enzyme in the mitochondrial membrane favoring accumulation of hydrophobic aromatic substances.


A quality improvement study on calcium and vitamin D supplementation in long-term care.
The objectives of this study were to evaluate the impact of a quality improvement (QI) study on improving calcium and vitamin D supplementation in a long-term care setting. Retrospective chart review. An academic long-term care facility that specializes in dementia care in St Louis, MO. Participants consisted of 83 long-term care residents. The quality improvement team created an educational letter that was signed by the medical director and sent to the facilities' primary care physicians. This letter provided clinicians with the rationale and method to achieve adequate calcium supplementation, assess vitamin D status, and provide adequate vitamin D supplementation in our long-term care setting. Following the letter, the facility pharmacist reviewed the orders during monthly medication reviews and faxed requests to the primary care physicians for appropriate supplements or laboratory tests when necessary. We reviewed the charts for the presence of calcium supplementation orders, vitamin D levels, and vitamin D supplementation before and after our QI intervention. Of the 83 resident charts that were reviewed, only 37 (44.6%) had calcium supplementation, 19 (22.8%) had assessment of their vitamin D status, and 29 (34.9%) had ongoing vitamin D supplementation prior to implementation of the study. After the QI intervention, calcium supplementation was present in 66 residents (79.5%), vitamin D status had been assessed in 61 residents (73.4%), and vitamin D supplementation had been initiated in 65 residents (78.3%). These changes were statistically significant (P < .05). A quality improvement project that used an educational letter from the medical director combined with a medication and laboratory review by the pharmacist was able to increase the number of residents in our long-term care setting with calcium supplementation, increase the number of residents who had vitamin D status assessed, identify many residents with low vitamin D levels, and increase supplementation of vitamin D when indicated.


Main characteristics of Hungarian twin and multiple births in official statistics.
Since 1876, statistical data on twin and multiple (TAM) births and deliveries have been registered in Hungary. Although there were some years during this 138-year period when twin births and deliveries were left out of the statistics, the trends can be followed, except for the period of World War II. The trends of twinning over the past four decades are summarized in this article, relying on official statistical data since 1970. Notably, the TAM birth rate rose following the Act CLIV of 1997 on Health. The Act provided state support for assisted reproductive treatments (ART), which spectacularly increased the ratio of twins - and especially of triplets - among live births. The trend has turned around since 2009-2010, and a decreasing era of TAM births seems to have begun. This article discusses some of the main and most interesting findings connected with TAM births, including twinning rates associated with different age groups, educational level, and actual place of residence by mothers, and the number of previous pregnancies of the mother. Ratios of live born males compared with live born females, lengths and weights at birth both among twins and singletons, and infant mortality rates have been calculated from the data. Twinning rates are higher in the western counties, the capital and its suburbs, and lower in the eastern counties.


Porcine neutrophil function in the presence of virulent and avirulent Salmonella choleraesuis.
Porcine polymorphonuclear leukocytes (PMNLs) may be activated by bacteria to begin phagocytosis followed by oxidative and non-oxidative mechanisms of killing. The purpose of this study was to identify differences between virulent and avirulent Salmonella choleraesuis (S. choleraesuis) strains, 38 and 9 respectively, in their interactions with porcine PMNLs using five different assays. (1) Staphylococcus aureus (S. aureus) ingestion was determined by exposure of porcine PMNLs to a mixture of S. choleraesuis and 125I labeled S. aureus. There was a 2.98% and 22.20% decrease in S. aureus ingestion by mouse-avirulent S. choleraesuis 9 and mouse-virulent S. choleraesuis 38 respectively. (2) Iodination of proteins was done by exposing zymosan stimulated porcine PMNLs to S. choleraesuis in the presence of 125I and measuring its incorporation into porcine PMNL proteins. This assay indicated a 73.7% and 74.7% decrease in iodination by S. choleraesuis 9 and S. choleraesuis 38, respectively. (3) Cytochrome c reduction was performed by using porcine PMNLs, zymosan, and S. choleraesuis to determine the bacterial effect on superoxide anion production. S. choleraesuis 9 and S. choleraesuis 38 inhibited superoxide anion production by 78.0% and 92.6%, respectively. (4) Lactoferrin release from porcine PMNLs was measured by an ELISA using the supernatant from the cytochrome c assay. Results indicate a 52.0% and 61.0% increase in lactoferrin release by S. choleraesuis 9 and 38 respectively. (5) The bactericidal assay was performed by counting cfus of S. choleraesuis after preliminary incubation with porcine PMNLs, followed by killing of extracellular S. choleraesuis and lysis of porcine PMNLs. Survival of S. choleraesuis 9 and E. coli (control) were 7.50% and 1.37%, respectively, in contrast to 52.62% survival of the virulent S. choleraesuis 38. These results indicate that both strains inhibited protein iodination and caused a slight increase in lactoferrin release, but the virulent S. choleraesuis 38 inhibited S. aureus ingestion, cytochrome c reduction, and survived porcine PMNL killing more effectively than the avirulent S. choleraesuis 9.


Linking community-based monitoring to water policy: Perceptions of citizen scientists.
This paper examines the relationships between Community-Based Water Monitoring (CBM) and government-led water initiatives. Drawing on a cross-Canada survey of over one hundred organizations, we explore the reasons why communities undertake CBM, the monitoring protocols they follow, and the extent to which CBM program members feel their findings are incorporated into formal (i.e., government-led) decision-making processes. Our results indicate that despite following standardized and credible monitoring protocols, fewer than half of CBM organizations report that their data is being used to inform water policy at any level of government. Moreover, respondents report higher rates of cooperation and data-sharing between CBM organizations themselves than between CBM organizations and their respective governments. These findings are significant, because many governments continue to express support for CBM. We explore the barriers between CBM data collection and government policy, and suggest that structural barriers include lack of multi-year funding, inconsistent protocols, and poor communication. More broadly, we argue that the distinction between formal and informal programming is unclear, and that addressing known CBM challenges will rely on a change in perception: CBM cannot simply be a less expensive alternative to government-driven data collection.


A multi-stage model for fundamental functional properties in primary visual cortex.
Many neurons in mammalian primary visual cortex have properties such as sharp tuning for contour orientation, strong selectivity for motion direction, and insensitivity to stimulus polarity, that are not shared with their sub-cortical counterparts. Successful models have been developed for a number of these properties but in one case, direction selectivity, there is no consensus about underlying mechanisms. We here define a model that accounts for many of the empirical observations concerning direction selectivity. The model describes a single column of cat primary visual cortex and comprises a series of processing stages. Each neuron in the first cortical stage receives input from a small number of on-centre and off-centre relay cells in the lateral geniculate nucleus. Consistent with recent physiological evidence, the off-centre inputs to cortex precede the on-centre inputs by a small (∼4 ms) interval, and it is this difference that confers direction selectivity on model neurons. We show that the resulting model successfully matches the following empirical data: the proportion of cells that are direction selective; tilted spatiotemporal receptive fields; phase advance in the response to a stationary contrast-reversing grating stepped across the receptive field. The model also accounts for several other fundamental properties. Receptive fields have elongated subregions, orientation selectivity is strong, and the distribution of orientation tuning bandwidth across neurons is similar to that seen in the laboratory. Finally, neurons in the first stage have properties corresponding to simple cells, and more complex-like cells emerge in later stages. The results therefore show that a simple feed-forward model can account for a number of the fundamental properties of primary visual cortex.


Multidimensional Quantum Mechanical Modeling of Electron Transfer and Electronic Coherence in Plant Cryptochromes: The Role of Initial Bath Conditions.
A multidimensional quantum mechanical protocol is used to describe the photoinduced electron transfer and electronic coherence in plant cryptochromes without any semiempirical, e.g., experimentally obtained, parameters. Starting from a two-level spin-boson Hamiltonian we look at the effect that the initial photoinduced nuclear bath distribution has on an intermediate step of this biological electron transfer cascade for two idealized cases. The first assumes a slow equilibration of the nuclear bath with respect to the previous electron transfer step that leads to an ultrafast decay with little temperature dependence; while the second assumes a prior fast bath equilibration on the donor potential energy surface leading to a much slower decay, which contrarily displays a high temperature dependence and a better agreement with previous theoretical and experimental results. Beyond Marcus and semiclassical pictures these results unravel the strong impact that the presence or not of equilibrium initial conditions has on the electronic population and coherence dynamics at the quantum dynamics level in this and conceivably in other biological electron transfer cascades.


Diagnosis and management of cataracts in infancy and childhood.
Congenital and developmental cataracts are a major cause of visual impairment in children. They may occur as an isolated ocular finding in an otherwise healthy child or as part of a hereditary syndrome or congenital nongenetic disease. Management of significant unilateral and bilateral congenital cataracts involves early patient identification and evaluation followed by prompt surgery. Appropriate optical rehabilitation and occlusion therapy for amblyopia must begin shortly thereafter. The visual prognosis of a congenital cataract is poorer in unilateral than in bilateral cases and in total than in partial cataracts. Visual rehabilitation is also poorer in those cases in which the cataract is associated with other ocular abnormalities.


How does hydroxyl introduction influence the double helical structure: the stabilization of an altritol nucleic acid:ribonucleic acid duplex.
Altritol nucleic acids (ANAs) are a promising new tool in the development of artificial small interfering ribonucleic acids (siRNAs) for therapeutical applications. To mimic the siRNA:messenger RNA (mRNA) interactions, the crystal structure of the ANA:RNA construct a(CCGUAAUGCC-P):r(GGCAUUACGG) was determined to 1.96 Å resolution which revealed the hybrid to form an A-type helix. As this A-form is a major requirement in the RNAi process, this crystal structure confirms the potential of altritol-modified siRNAs. Moreover, in the ANA strands, a new type of intrastrand interactions was found between the O2' hydroxyl group of one residue and the sugar ring O4' atom of the next residue. These interactions were further investigated by quantum chemical methods. Besides hydration effects, these intrastrand hydrogen bonds may also contribute to the stability of ANA:RNA duplexes.


Differential regulation of cranial and cardiac neural crest by serum response factor and its cofactors.
Serum response factor (SRF) is an essential transcription factor that influences many cellular processes including cell proliferation, migration, and differentiation. SRF directly regulates and is required for immediate early gene (IEG) and actin cytoskeleton-related gene expression. SRF coordinates these competing transcription programs through discrete sets of cofactors, the ternary complex factors (TCFs) and myocardin-related transcription factors (MRTFs). The relative contribution of these two programs to in vivo SRF activity and mutant phenotypes is not fully understood. To study how SRF utilizes its cofactors during development, we generated a knock-in SrfaI allele in mice harboring point mutations that disrupt SRF-MRTF-DNA complex formation but leave SRF-TCF activity unaffected. Homozygous SrfaI/aI mutants die at E10.5 with notable cardiovascular phenotypes, and neural crest conditional mutants succumb at birth to defects of the cardiac outflow tract but display none of the craniofacial phenotypes associated with complete loss of SRF in that lineage. Our studies further support an important role for MRTF mediating SRF function in cardiac neural crest and suggest new mechanisms by which SRF regulates transcription during development.


Classification of Patients with Coronary Microvascular Dysfunction.
While coronary microvascular dysfunction (CMD) is a major cause of ischemia, it is very challenging to diagnose due to lack of CMD-specific screening measures. CMD has been identified as one of the five priority areas of investigation in a 2014 National Research Consensus Conference on Gender-Specific Research in Emergency Care. In this study, we utilized methods from machine learning that leverage structured and unstructured narratives in clinical notes to detect patients with CMD. We have shown that structured data are not sufficient to detect CMD and integrating unstructured data in the computational model boosts the performance significantly.


Forceps and vacuum extraction.
The proper use of forceps or vacuum extractor, or both, remains a safe and effective modality in achieving the universal goal of a healthy mother and baby. Their use requires continued experience, sharing of information, and possibly attention to subtleties of design. This review looks at the current situation with special emphasis on side effects and selection issues as found in the recent literature.


Plexiform neurofibroma (Hamartoma) of the median nerve: A two-case report.
Plexiform neurofibroma is a benign peripheral nerve-sheath tumor, rarely involving major nerves of the extremities. In the literature, there are no clear treatment strategies for plexiform neurofibroma of major peripheral nerves. Our experience encountered two patients with plexiform neurofibroma of the median nerve, presenting with a palmar mass and symptoms of carpal tunnel compression. Preoperatively, plexiform neurofibroma was diagnosed on MRI and clinical examination. Both patients also experienced significant neurological deterioration, with finger numbness and increased nerve/tumor size. Potential malignant transformation was also considered. For these reasons, resection of the involved area of the nerve and repair were indicated. In both patients, intraoperative pathological diagnosis was plexiform neurofibroma. The 45-year-old male patient refused further surgery after carpal tunnel release, which was performed under axillary block. One year postoperatively, nerve compression symptoms decreased moderately. In the other patient, a 7-year-old boy, a significantly enlarged area of the median nerve was resected, and neurorrhaphy was performed. One year postoperatively, median nerve motor-sensory functions recovered completely. Four years postoperatively, no enlargement of the residual tumor was observed.


Circumcision in children with penile block alone.
Surgical procedures in children are usually performed with the patient under general anesthesia. For circumcision and additional dorsal penile nerve block is used for postoperative analgesia. We retrospectively evaluated dorsal penile nerve block as the only analgesic technique for the relief of intraoperative pain in children undergoing circumcision. For 6 months dorsal penile nerve block was performed in 454 children 3 to 11 years old (mean 8.15 +/- 2.08 years) as the sole preoperative anesthesia. All boys were considered to have had good preoperative analgesia. No major complications were reported. Block related hematoma was noted in 12 patients (2.6%) and mild local edema occurred in 83 (18.3%). There was no excessive bleeding and hemostasis was easily achieved. The overall average operating time was 7.2 +/- 2.6 minutes (range 6 to 25). General anesthesia was added in 13 patients, representing a dorsal penile nerve block failure rate of 2.9%. Four boys suffered from erratic pain, while no objective cause of failure was recorded in the remaining 9. Average patient age was 5.8 +/- 2.2 years (range 3 to 10) in the 13 boys and 8.2 +/- 2 years (range 3 to 11) in the remaining 441 patients (p < 0.001). Failure was more frequent in children 3 to 5 years old (15.5%) than in those older than 6 years (1.5%, p < 0.05). Average operating time was 20.7 +/- 2.8 minutes (range 15 to 25) in the 13 children and 6.8 +/- 1.1 minutes (range 6 to 15) in the remaining 441 (p < 0.001). During the recovery period, only children from the general anesthesia group suffered from nausea and vomiting (9), and pain, agitation and fear (6 boys 3 to 6 years old). Average recovery room time was 38.7 +/- 7.4 minutes (range 30 to 60) in children with dorsal penile nerve block alone and 95 +/- 9.8 minutes (range 85 to 120) in those with additional general anesthesia (p < 0.001). We conclude that dorsal penile nerve block alone provides good intraoperative analgesia for circumcision in children, particularly those older than 6 years.


Translation, validation of the EORTC esophageal cancer quality-of-life questionnaire for Japanese with esophageal squamous cell carcinoma: analysis in thoraco-laparoscopic esophagectomy versus open esophagectomy.
The aim of this study is to develop and examine the reliability and validity of the Japanese version of the European Organization for Research and Treatment of Cancer quality-of-life questionnaire-esophageal cancer (OES18) module for its use in Japan. We followed a two-phase process to translate the questionnaire, according to the guidelines of the European Organization for Research and Treatment of Cancer OES18. Phase 1: the first intermediary Japanese version was produced according to European Organization for Research and Treatment of Cancer quality-of-life unit translation project guidelines. The second intermediary version was the result of a backward translation project and two peer-to-peer discussion by healthcare professionals. Phase 2: the final Japanese version was produced after focus group discussions with team members and semistructured interviews. Fifty patients with esophageal squamous cell carcinoma, who had undergone curative thoracic esophagectomy, participated in the study. The Japanese translated version of quality-of-life questionnaire-OES18 yielded cultural adaptation and validation scores whose reliability was confirmed by internal consistency tests. Convergent validity was moderate to high (from r = 0.671-0.903; P < 0.01), whereas discriminant validity was acceptably low. Significant reduction in pain-scale values was noted postoperatively in the thoracoscopic approach when compared with the thoracotomy approach (scale value: 9.62 vs. 12.71; P = 0.04). We developed the Japanese version of quality-of-life questionnaire-OES18. This module has good psychometric validity and recommended to assess the health-related quality of life in Japanese patients.


[Thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in soft-tissue sarcoma versus capecitabine potential].
Expression of thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) can predict for clinical outcome of fluoropyrimidine-based therapy and there is every likelihood that relevant tumors will respond. High TP expression was observed in 35 (42%) patients with soft-tissue sarcoma. Seven out of 26 (27%) such patients revealed molecular phenotype prognostically favorable for capecitabine therapy. More clinical research is required to assess the efficacy of capecitabine-based therapy.


The evolution and genetic diversity of avian influenza A(H9N2) viruses in Cambodia, 2015 - 2016.
Low pathogenic A(H9N2) subtype avian influenza viruses (AIVs) were originally detected in Cambodian poultry in 2013, and now circulate endemically. We sequenced and characterised 64 A(H9N2) AIVs detected in Cambodian poultry (chickens and ducks) from January 2015 to May 2016. All A(H9) viruses collected in 2015 and 2016 belonged to a new BJ/94-like h9-4.2.5 sub-lineage that emerged in the region during or after 2013, and was distinct to previously detected Cambodian viruses. Overall, there was a reduction of genetic diversity of H9N2 since 2013, however two genotypes were detected in circulation, P and V, with extensive reassortment between the viruses. Phylogenetic analysis showed a close relationship between A(H9N2) AIVs detected in Cambodian and Vietnamese poultry, highlighting cross-border trade/movement of live, domestic poultry between the countries. Wild birds may also play a role in A(H9N2) transmission in the region. Some genes of the Cambodian isolates frequently clustered with zoonotic A(H7N9), A(H9N2) and A(H10N8) viruses, suggesting a common ecology. Molecular analysis showed 100% of viruses contained the hemagglutinin (HA) Q226L substitution, which favours mammalian receptor type binding. All viruses were susceptible to the neuraminidase inhibitor antivirals; however, 41% contained the matrix (M2) S31N substitution associated with resistance to adamantanes. Overall, Cambodian A(H9N2) viruses possessed factors known to increase zoonotic potential, and therefore their evolution should be continually monitored.


Variations in cardiac implantable electronic device surveillance and ancillary testing in the paediatric and congenital heart disease population: an international multi-centre survey from the Paediatric and Congenital Electrophysiology Society.
Expert guidance from scientific societies and regulatory agencies recommend a framework of principles for frequency of in-person evaluations and remote monitoring for patients with cardiac implantable electronic devices. However, there are limited data regarding adherence to recommendations among paediatric electrophysiologists, and there are no data regarding cardiac implantable electronic device-related ancillary testing. To assess current clinical practices for cardiac implantable electronic device in-person evaluation, remote monitoring, and cardiac implantable electronic device-related ancillary testing, the Paediatric and Congenital Electrophysiology Society members were surveyed. The main outcome measures were variations in frequency of in person evaluation, frequency of remote monitoring, and cardiac implantable electronic device-related ancillary testing. All respondents performed in-person evaluation at least once a year, but <50% of respondents performed an in-person evaluation within 2 weeks of cardiac implantable electronic device implantation. Remote monitoring was performed every 3 months for pacemakers and implantable cardioverter defibrillators by 71 and 75% respondents, respectively. Follow-up echocardiography was performed every 2-3 years by 53% respondents for patients with >50% ventricular pacing. Majority of respondents (75%) did not perform either an exercise stress test or ambulatory Holter monitoring or chest X-ray (65%) after cardiac implantable electronic device implantation. This survey identified significant practice variations in cardiac implantable electronic device in- person evaluation, remote monitoring, and ancillary testing practices among paediatric electrophysiologists. Cardiac implantable electronic device management may be optimised by development of a paediatric-specific guidelines for follow-up and ancillary testing.


The synaptic drive from the spinal locomotor network to motoneurons in the newborn rat.
The nature of the synaptic drive from the locomotor spinal network onto the motoneurons was studied in the newborn rat. For this purpose, an in vitro isolated spinal cord preparation of newborn rat was used. The recording chamber was partitioned with Vaseline walls to separate the L1/L2 lumbar segments, in which the spinal locomotor network is located, from the motoneurons in the lower lumbar segments. Locomoter-like activity was induced by bath-applying a mixture of serotonin and NMDA to segments L1/L2. In this way, the synaptic activity could be modified at the lower lumbar level without affecting the motor pattern. The drive elicited onto the motoneurons during sequences of locomoter-like activity, which was monitored by performing intracellular recordings, consisting of an inhibitory component followed by an excitatory component. The inhibitory synaptic volley was reversed at a membrane potential of --60 mV with K acetate electrodes, whereas it was shifted toward positive values with KCl electrodes. The glycinergic blocker strychnine, bath-applied to segments L3/L5, blocked the inhibitory drive without affecting the rhythmic activity, whereas it disrupted the locomoter-like activity when bath-applied to segments L1/L2. The inhibitory part of the drive was more sensitive than the excitatory part to changes in the membrane potential. The excitatory phase was mixed and consisted of an NMDA and a non-NMDA component, which were sensitive to 2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione, respectively. It was concluded that the locomotor network located in segments L1/L2 sends a biphasic projection to the various groups of motoneurons located along the lumbar spinal cord.


Altered de novo sphingolipid biosynthesis is involved in the serum deprivation-induced cell death in LLC-PK1 cells.
Fumonisin B1, a specific inhibitor of ceramide synthase, and ISPI (Myriocin), a serine palmitoyltransferase inhibitor, modulate the de novo sphingolipid biosynthesis pathway. This study was conducted to determine whether serum deprivation-induced cell death is regulated by de novo sphingolipid biosynthesis in pig kidney LLC-PK1 cells. Serum withdrawal from the culture medium produced cell death in LLC-PK1 cells. Fumonisin B1 at concentrations ranging from 5 M to 30 M delayed until 48 h this cell death resulting from the absence of fetal bovine serum (FBS) in cell culture. Pretreatment of cultured cells with fumonisin B1 in the presence of serum for 24 h increased by approximately 70% this cytoprotective activity of fumonisin B1 against serum deprivation-induced cell death. Serum deprivation increased sphingolipid biosynthesis threefold compared to 5% serum-enriched culture. Fumonisin B1 at 5-30 M lowered the content of total complex sphingolipids to levels of 50% and 77% of the content in serum-enriched culture, although the concentration of intracellular free sphinganine was elevated. ISP1 alone at greater than 1 nM concentration reduced total complex sphingolipid content to values in LLC-PK1 cells grown in the presence of 5% FBS. The results suggest that the de novo complex sphingolipid biosynthesis modulated by either fumonisin B1 or ISP1 may regulate serum deprivation-induced cell death in LLC-PK1 cells.


[Nomograms for determining the parameters for a probabilistic model of radiosensitivity].
Nomograms are introduced for the determination, from the experimental survival curves, of a and b parameters of the probabilistic model of cell radiosensitivity (proposed by Kapul'tsevich, 1978). The parameter errors are estimated too. Some examples of using these nomograms for bacteria, yeast and mammalian cells are considered.


Beryllium coordination chemistry and its implications on the understanding of metal induced immune responses.
The inhalation of beryllium and its compounds can cause the development of chronic beryllium disease in susceptible individuals. This is caused by a distinct autoimmune process. Here, beryllium coordination compounds with biomimetic ligands are discussed, which are used to understand the coordination of Be2+ in the body and its effect on biomolecules. The advances in the development of precursors for the directed synthesis of these coordination complexes are presented as well as the potential use of non-aqueous solvents for these investigations.


Igniting interest in prevention: using firefighter focus groups to inform implementation and enhancement of an urban canvassing program.
Smoke alarm canvassing is recognized as an empirically based, effective intervention for increasing access to and the presence of smoke alarms in homes. We sought to inform the implementation of an intervention designed to enhance an existing fire department smoke alarm canvassing program through an empirically grounded, participatory process. We conducted a series of focus groups with fire union leaders and firefighters involved with the canvassing program in 1 US city, shared the results with the participants, and presented the resulting recommendations to fire department leadership. This research occurred in Baltimore, Maryland. Focus group participants included firefighters who participate in the Fire Department's smoke alarm canvassing program and representatives from the local firefighters' union. The focus groups sought to capture firefighters' experiences with and opinions about the canvassing program and how to improve it as well as challenges to canvassing work. We conducted 10 focus groups with 65 participants. Firefighters' perspectives on the canvassing program and their recommendations for improving it were expressed through 3 categories of themes concerning program management, canvassing challenges, and attitudes about the program and the community. We also discuss the process of presenting these findings and recommendations to the participants and the fire department leadership, and describe how implementation of some of the recommendations has progressed. Both the process and outcomes of this formative work inform how to develop and implement community-based public health interventions in real-world settings through academic-community partnerships. The findings also have implications for how canvassing programs are being implemented.


Differences in Toxic Response Induced by Three Variants of the Diarrheic Shellfish Poisoning Phycotoxins in Human Intestinal Epithelial Caco-2 Cells.
Diarrheic shellfish poisoning (DSP) is caused by the consumption of shellfish contaminated with a group of phycotoxins that includes okadaic acid (OA), dinophysistoxin-1 (DTX-1), and dinophysistoxin-2 (DTX-2). These toxins are inhibitors of serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A), but show distinct levels of toxicity. Aside from a difference in protein phosphatases (PP) inhibition potency that would explain these differences in toxicity, others mechanisms of action are thought to be involved. Therefore, we investigated and compared which mechanisms are involved in the toxicity of these three analogues. As the intestine is one of the target organs, we studied the transcriptomic profiles of human intestinal epithelial Caco-2 cells exposed to OA, DTX-1, and DTX-2. The pathways specifically affected by each toxin treatment were further confirmed through the expression of key genes and markers of toxicity. Our results did not identify any distinct biological mechanism for OA and DTX-2. However, only DTX-1 induced up-regulation of the MAPK transduction signalling pathway, and down-regulation of gene products involved in the regulation of DNA repair. As a consequence, based on transcriptomic results, we demonstrated that the higher toxicity of DTX-1 compared to OA and DTX-2 was consistent with certain specific pathways involved in intestinal cell response.


Self-referenced method for terahertz wave time-domain spectroscopy.
The method allows retrieval of the absorbance of a sample without the need for a reference measurement. The method measures the dynamic variation of frequency resolution as the waveform is being acquired. In terahertz wave time-domain spectroscopy, the frequency resolution increases as the temporal window increases. Therefore, narrow absorption peaks will appear in the spectrum when the temporal window is long enough to resolve the peak. By measuring the dynamic values of each frequency component at specific points in time, a reference value and a peak value are extracted and, hence, the self-referenced is achieved. In addition, the method provides a mechanism to remove the effects of echoes, which enables arbitrary temporal window length and, thus, achieves high-resolution frequency. Examples of extraction of the water vapor lines and resonant features in gas and semiconductors are demonstrated in transmission and reflection geometries.


Hypotension on admission in patients with isolated traumatic brain injury: contemporary examination of the incidence and outcomes using a national registry.
This study was primarily aimed at establishing the incidence and impact of hypotension in patients with blunt traumatic brain injury based on National Trauma Registry Database. A retrospective cohort study using the National Trauma Registry was conducted. Patients with TBI following blunt mechanisms of injury were examined, comparing those with and without hypotension (SBP < 90 mm Hg) on arrival. During the period from 1998 to 2017, the registry included 437.354 blunt trauma patients. Of them, 7818 patients were hemodynamically unstable (SBP < 90 mm Hg) on admission. 513 met the inclusion criteria. Significant percentages of patients with high grade injures (ISS≥16) and low admission's GCS 3-12 (46% vs 16.4%), were found in the group of hypotensive TBI patients (p<0.0001). 323 (62.9%) patients had head AIS score 3-4 and only 190 (37.1%) patients AIS 5-6 (p<0.0001). Mortality in the hypotensive TBI group was 32.3%, whereas 6.1% patients died in the TBI hemodynamically stable group (p<0.0001). TBI patients presenting with hypotension represent an appreciable portion blunt trauma patients. Prompt brain CT, expedient efforts at optimal resuscitation and possibly early inotropic and vasopressors agents use may have an impact on final outcome in these patients.


The impact of educational interventions for patients living with indwelling urinary catheters: A scoping review.
Aim: To explore the impact of educational interventions for patients living with indwelling urinary catheters. Methods: Systematic scoping review in accordance with PRISMA guidelines, guided by Cochrane methodology, quality appraisal using Centre for Evidence-Based Medicine (CEBM) Joanna Briggs Institute (JBI), GRADE criteria and Quality Improvement Minimum Quality Criteria Set Version 1.0 (QI-MQCS V 1.0) tools. Studies (n = 446) were retrieved from CINAHL, Cochrane Library, Scopus and Medline from 2000 to 2020. Results: A total of 15 primary research studies were included in the narrative thematic synthesis, nine were from the USA, two from Australia, two from the UK, one from Italy and one from Turkey. These 15 studies were published between 2003 and 2019 and accounted for 19918 patients with an age range 15-99 years. Study design varied; there were 11 quantitative and 4 qualitative studies. Studies were of low-moderate quality. A total of four themes were identified; (i) information needs of patients living with long-term catheters; (ii) core learning content and educational approaches; (iii) feasibility and effectiveness of educational interventions to reduce complications and improve quality of life; and (iv) common outcome measures. Conclusion: The dissemination of information and the delivery of urinary catheter education to patients is inadequate. Core components of educational interventions should address fluid intake, bowel management, hygiene and self-monitoring/management, including adverse events. There is a need for future robust trials of educational and self-management interventions to improve the quality of life of patients living with indwelling urinary catheters in the community. Impact: This review addressed the educational needs of patients living with indwelling urinary catheters and the impact of educational interventions. Despite the heterogeneity in educational interventions, all studies included in this review reported the specific approach undertaken was effective in minimising catheter-associated complications and improving the quality of life of patients.


Clinical significance of TMPRSS4 in prostate cancer.
Transmembrane protease serine 4 (TMPRSS4) is a type-II transmembrane serine protease that plays an important role in the migration of cancer cells. This study aimed to investigate both the expression of TMPRSS4 and its clinical significance in prostate cancer. The expression of TMPRSS4 was evaluated in 73 pairs of prostate cancer and adjacent non-cancerous tissues by immunohistochemistry. The level of TMPRSS4 in prostate cancer tissues was significantly higher than that in adjacent non-cancerous tissues. High TMPRSS4 expression was significantly associated with advanced TNM stage and LNM. No association between TMPRSS4 expression and progression-free survival was observed in all patients. Stratified analyses according to clinical features revealed that patients with low TMPRSS4 expression had poor prognosis compared with those with high TMPRSS4 expression in subjects not receiving neoadjuvant chemotherapy. In conclusion, TMPRSS4 showed abnormal expression in prostate cancer tissues. TMPRSS4 may be a potential prognostic biomarker for prostate cancer patients who did not undergo neoadjuvant chemotherapy.


Long-term regulation of male fertility by norethisterone enanthate 'epididymal' implants: effect on libido and fertility of rabbits.
Bilateral insertion of silastic capsules releasing 38-44 micrograms norethisterone enanthate/24 h into the epididymal fat-pads was found to induce complete azoospermia leading to infertility in adult male rabbits 8 weeks after insertion of the progestin implants. The treatment did not exert any inhibitory effects on the libido and sexual behaviour of the animals as judged by objective parameters of mating. Further, the failure of the hormone-releasing implants was not found to exert any adverse effects on the embryos and pregnancy as indicated by the delivery of normal pups to females mated with implant-bearing males 3 weeks after the insertion of 'epididymal' implants.