Conditional female strategies influence hatching success in a communally nesting iguana.
The decision of females to nest communally has important consequences for reproductive success. While often associated with reduced energetic expenditure, conspecific aggregations also expose females and offspring to conspecific aggression, exploitation, and infanticide. Intrasexual competition pressures are expected to favor the evolution of conditional strategies, which could be based on simple decision rules (i.e., availability of nesting sites and synchronicity with conspecifics) or on a focal individual's condition or status (i.e., body size). Oviparous reptiles that reproduce seasonally and provide limited to no postnatal care provide ideal systems for disentangling social factors that influence different female reproductive tactics from those present in offspring-rearing environments. In this study, we investigated whether nesting strategies in a West Indian rock iguana, Cyclura nubila caymanensis, vary conditionally with reproductive timing or body size, and evaluated consequences for nesting success. Nesting surveys were conducted on Little Cayman, Cayman Islands, British West Indies for four consecutive years. Use of high-density nesting sites was increasingly favored up to seasonal nesting activity peaks, after which nesting was generally restricted to low-density nesting areas. Although larger females were not more likely than smaller females to nest in high-density areas, larger females nested earlier and gained access to priority oviposition sites. Smaller females constructed nests later in the season, apparently foregoing investment in extended nest defense. Late-season nests were also constructed at shallower depths and exhibited shorter incubation periods. While nest depth and incubation length had significant effects on reproductive outcomes, so did local nest densities. Higher densities were associated with significant declines in hatching success, with up to 20% of egg-filled nests experiencing later intrusion by a conspecific. Despite these risks, nests in high-density areas were significantly more successful than elsewhere due to the benefits of greater chamber depths and longer incubation times. These results imply that communal nest sites convey honest signals of habitat quality, but that gaining and defending priority oviposition sites requires competitive ability.


Evaluation of immunogenicity-induced DNA vaccines against different SARS-CoV-2 variants.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic worldwide. As of September 2023, the number of confirmed coronavirus cases has reached over 770 million and caused nearly 7 million deaths. The World Health Organization assigned and informed the characterization of variants of concern (VOCs) to help control the COVID-19 pandemic through global monitoring of circulating viruses. Although many vaccines have been proposed, developing an effective vaccine against variants is still essential to reach the endemic stage of COVID-19. We designed five DNA vaccine candidates composed of the first isolated genotype and major SARS-CoV-2 strains from isolated Korean patients classified as VOCs, such as Alpha, Beta, Gamma, and Delta. To evaluate the immunogenicity of each genotype via homologous and heterologous vaccination, mice were immunized twice within a 3-week interval, and the blood and spleen were collected 1 week after the final vaccination to analyze the immune responses. The group vaccinated with DNA vaccine candidates based on the S genotype and the Alpha and Beta variants elicited both humoral and cellular immune responses, with higher total IgG levels and neutralizing antibody responses than the other groups. In particular, the vaccine candidate based on the Alpha variant induced a highly diverse cytokine response. Additionally, we found that the group subjected to homologous vaccination with the S genotype and heterologous vaccination with S/Alpha induced high total IgG levels and a neutralization antibody response. Homologous vaccination with the S genotype and heterologous vaccination with S/Alpha and S/Beta significantly induced IFN-γ immune responses. The immunogenicity after homologous vaccination with S and Alpha and heterologous vaccination with the S/Alpha candidate was better than that of the other groups, indicating the potential for developing novel DNA vaccines against different SARS-CoV-2 variants.


EWS/FLI is a Master Regulator of Metabolic Reprogramming in Ewing Sarcoma.
Ewing sarcoma is a bone malignancy driven by a translocation event resulting in the fusion protein EWS/FLI1 (EF). EF functions as an aberrant and oncogenic transcription factor that misregulates the expression of thousands of genes. Previous work has focused principally on determining important transcriptional targets of EF, as well as characterizing important regulatory partnerships in EF-dependent transcriptional programs. Less is known, however, about EF-dependent metabolic changes or their role in Ewing sarcoma biology. Therefore, the metabolic effects of silencing EF in Ewing sarcoma cells were determined. Metabolomic analyses revealed distinct separation of metabolic profiles in EF-knockdown versus control-knockdown cells. Mitochondrial stress tests demonstrated that knockdown of EF increased respiratory as well as glycolytic functions. Enzymes and metabolites in several metabolic pathways were altered, including de novo serine synthesis and elements of one-carbon metabolism. Furthermore, phosphoglycerate dehydrogenase (PHGDH) was found to be highly expressed in Ewing sarcoma and correlated with worse patient survival. PHGDH knockdown or pharmacologic inhibition in vitro caused impaired proliferation and cell death. Interestingly, PHGDH modulation also led to elevated histone expression and methylation. These studies demonstrate that the translocation-derived fusion protein EF is a master regulator of metabolic reprogramming in Ewing sarcoma, diverting metabolites toward biosynthesis. As such, these data suggest that the metabolic aberrations induced by EF are important contributors to the oncogenic biology of these tumors.Implications: This previously unexplored role of EWS/FLI1-driven metabolic changes expands the understanding of Ewing sarcoma biology, and has potential to significantly inform development of therapeutic strategies. Mol Cancer Res; 15(11); 1517-30. ©2017 AACR.


Deletion analysis resolves cell-binding and lytic domains of the Pasteurella leukotoxin.
A series of internal deletions in the lktA gene of Pasteurella haemolytica has been constructed. All of the deletions eliminated the lytic activity of the leukotoxin towards the bovine lymphoma cell line, BL-3. Deletions removing segments of the amino-proximal hydrophobic region, which is thought to constitute an essential membrane-spanning domain, were found to agglutinate BL-3 cells. Agglutination was similar to lysis by the wild-type toxin in that it was dependent upon the presence of calcium and required expression of the lktC gene. The agglutinating deletion proteins protected BL-3 cells from lysis by the wild-type toxin in a competitive fashion. This suggests that these mutants bind to a surface feature of the leukocyte which interacts with the native leukotoxin. These findings demonstrate that the cell-binding and lytic domains of the leukotoxin are separable.


spaCI: deciphering spatial cellular communications through adaptive graph model.
Cell-cell communications are vital for biological signalling and play important roles in complex diseases. Recent advances in single-cell spatial transcriptomics (SCST) technologies allow examining the spatial cell communication landscapes and hold the promise for disentangling the complex ligand-receptor (L-R) interactions across cells. However, due to frequent dropout events and noisy signals in SCST data, it is challenging and lack of effective and tailored methods to accurately infer cellular communications. Herein, to decipher the cell-to-cell communications from SCST profiles, we propose a novel adaptive graph model with attention mechanisms named spaCI. spaCI incorporates both spatial locations and gene expression profiles of cells to identify the active L-R signalling axis across neighbouring cells. Through benchmarking with currently available methods, spaCI shows superior performance on both simulation data and real SCST datasets. Furthermore, spaCI is able to identify the upstream transcriptional factors mediating the active L-R interactions. For biological insights, we have applied spaCI to the seqFISH+ data of mouse cortex and the NanoString CosMx Spatial Molecular Imager (SMI) data of non-small cell lung cancer samples. spaCI reveals the hidden L-R interactions from the sparse seqFISH+ data, meanwhile identifies the inconspicuous L-R interactions including THBS1-ITGB1 between fibroblast and tumours in NanoString CosMx SMI data. spaCI further reveals that SMAD3 plays an important role in regulating the crosstalk between fibroblasts and tumours, which contributes to the prognosis of lung cancer patients. Collectively, spaCI addresses the challenges in interrogating SCST data for gaining insights into the underlying cellular communications, thus facilitates the discoveries of disease mechanisms, effective biomarkers and therapeutic targets.


Is art therapy a reliable tool for rehabilitating people suffering from brain/mental diseases?
Whether art therapy can be an effective rehabilitative treatment for people with brain or mental diseases (e.g., dementia, Alzheimer's disease, Parkinson's disease, autism, schizophrenia) is a long-standing and highly debated issue. On the one hand, several observational studies and anecdotal evidence enthusiastically support the effectiveness of arts-based therapy. On the other hand, few rigorous clinical investigations have been performed, and there is too little empirical evidence to allow a full assessment of the risks and benefits of this intervention. Nevertheless, there is a progressively increasing demand for the development of appropriate complementary therapies to improve the personal and social lives of patients with neurodegenerative diseases. This is because conventional medical treatments are aimed at alleviating symptoms but cannot arrest or reverse the degenerative process. Thus, as disease progresses and adverse effects emerge, patients' quality of life dramatically decreases; when this occurs patients seek different forms of intervention. Art therapy is a potentially appealing treatment because of its more holistic approach to healthcare. However, as with any medicine, its effects must be tested by using standard, rigorous scientific approaches. This report describes the current state of research into art therapy and outlines many key factors that future research should consider, all of which are directly or indirectly related to the neural mechanism underlying behavioral changes: brain plasticity. Artistic performance could promote some form of brain plasticity that, to some extent, might compensate for the brain damage caused by the disease.


Bedaquiline, an FDA-approved drug, inhibits mitochondrial ATP production and metastasis in vivo, by targeting the gamma subunit (ATP5F1C) of the ATP synthase.
Here, we provide evidence that high ATP production by the mitochondrial ATP-synthase is a new therapeutic target for anticancer therapy, especially for preventing tumor progression. More specifically, we isolated a subpopulation of ATP-high cancer cells which are phenotypically aggressive and demonstrate increases in proliferation, stemness, anchorage-independence, cell migration, invasion and multi-drug resistance, as well as high antioxidant capacity. Clinically, these findings have important implications for understanding treatment failure and cancer cell dormancy. Using bioinformatic analysis of patient samples, we defined a mitochondrial-related gene signature for metastasis, which features the gamma-subunit of the mitochondrial ATP-synthase (ATP5F1C). The relationship between ATP5F1C protein expression and metastasis was indeed confirmed by immunohistochemistry. Next, we used MDA-MB-231 cells as a model system to functionally validate these findings. Importantly, ATP-high MDA-MB-231 cells showed a nearly fivefold increase in metastatic capacity in vivo. Consistent with these observations, ATP-high cells overexpressed (i) components of mitochondrial complexes I-V, including ATP5F1C, and (ii) markers associated with circulating tumor cells (CTCs) and metastasis, such as EpCAM and VCAM1. Knockdown of ATP5F1C expression significantly reduced ATP-production, anchorage-independent growth, and cell migration, as predicted. Similarly, therapeutic administration of the FDA-approved drug, Bedaquiline, downregulated ATP5F1C expression in vitro and prevented spontaneous metastasis in vivo. In contrast, Bedaquiline had no effect on the growth of non-tumorigenic mammary epithelial cells (MCF10A) or primary tumors in vivo. Taken together, our results suggest that mitochondrial ATP depletion is a new therapeutic strategy for metastasis prophylaxis, to avoid treatment failure. In summary, we conclude that mitochondrial ATP5F1C is a promising new biomarker and molecular target for future drug development, for the prevention of metastatic disease progression.


Spontaneous vegetation encroachment upon bauxite residue (red mud) as an indicator and facilitator of in situ remediation processes.
The spontaneous colonization of a bauxite residue (alumina refining tailings) deposit by local vegetation in Linden, Guyana, over 30 years, indicates that natural weathering processes can ameliorate tailings to the extent that it can support vegetation. Samples were collected from vegetated and unvegetated areas to investigate the relationships between bauxite residue properties and vegetation cover. Compared to unvegetated areas, bauxite residue in vegetated areas had lower pH (mean pH 7.9 vs 10.9), lower alkalinity (mean titratable alkalinity 0.4 vs 1.4 mol H(+) kg(-1)), lower electrical conductivity (mean EC 0.3 vs 2.1 mS cm(-1)), lower total Al (mean Al2O3 19.8 vs 25.8% wt) and Na (mean Na2O 0.9 vs 3.7% wt), and less sodalite and calcite. Accumulation of N, NH4(+), and organic C occurred under vegetation, demonstrating the capacity for plants to modify residue to suit their requirements as a soil-like growth medium. Aeolian redistribution of coarse grained tailings appeared to support vegetation establishment by providing a thin zone of enhanced drainage at the surface. Natural pedogenic processes may be supplemented by irrigation, enhanced drainage, and incorporation of sand and organic matter at other tailings deposits to accelerate the remediation process and achieve similar results in a shorter time frame.


Expression and activity of a house-fly cytochrome P450, CYP6D1, in Drosophila melanogaster.
The cytochrome P450 system of animals comprises many individual cytochromes P450 in addition to a single cytochrome P450 reductase and cytochrome b5. Although individual genes of the cytochrome P450 superfamily are highly diverged, the P450 reductase and cytochrome b(5) remain more conserved across taxa. Here, we describe the transformation of Drosophila melanogaster with a house-fly-specific cytochrome P450, CYP6D1. Functional activity of ectopically expressed cytochromes P450 requires successful interaction between the transgenic P450 and the requisite coenzymes of the host organism. Transformed Drosophila, but not controls, contained CYP6D1 protein as identified by protein immunoblotting, elevated total P450 and elevated CYP6D1 enzymatic activity. These data demonstrate that house-fly CYP6D1 can interact with low to moderate efficiency with Drosophila P450 reductase and cytochrome b(5).


Study of early nerve lesions in mice infected with M. leprae.
The present study is of quantitative histology in immunologically intact mice inoculated with M. leprae. Total twelve sciatic nerves are studied. The fibres are grouped as large, medium and small sized fibres. Initially there is loss of small size fibres. At later stages there is involvement of all sized fibres and ultimately Wallerian type of degeneration sets in. The process of regeneration is more active than that of human leprosy of tuberculoid type. This study adds a new dimension in understanding the pathogenesis of leprosy.


Graph-Driven Diffusion and Random Walk Schemes for Image Segmentation.
We propose graph-driven approaches to image segmentation by developing diffusion processes defined on arbitrary graphs. We formulate a solution to the image segmentation problem modeled as the result of infectious wavefronts propagating on an image-driven graph where pixels correspond to nodes of an arbitrary graph. By relating the popular Susceptible - Infected - Recovered epidemic propagation model to the Random Walker algorithm, we develop the Normalized Random Walker and a lazy random walker variant. The underlying iterative solutions of these methods are derived as the result of infections transmitted on this arbitrary graph. The main idea is to incorporate a degree-aware term into the original Random Walker algorithm in order to account for the node centrality of every neighboring node and to weigh the contribution of every neighbor to the underlying diffusion process. Our lazy random walk variant models the tendency of patients or nodes to resist changes in their infection status. We also show how previous work can be naturally extended to take advantage of this degreeaware term which enables the design of other novel methods. Through an extensive experimental analysis, we demonstrate the reliability of our approach, its small computational burden and the dimensionality reduction capabilities of graph-driven approaches. Without applying any regular grid constraint, the proposed graph clustering scheme allows us to consider pixellevel, node-level approaches and multidimensional input data by naturally integrating the importance of each node to the final clustering or segmentation solution. A software release containing implementations of this work and supplementary material can be found at: http://cvsp.cs.ntua.gr/research/GraphClustering/.


Nobel lecture. Self-splicing and enzymatic activity of an intervening sequence RNA from Tetrahymena.
A living cell requires thousands of different chemical reactions to utilize energy, move, grow, respond to external stimuli and reproduce itself. While these reactions take place spontaneously, they rarely proceed at a rate fast enough for life. Enzymes, biological catalysts found in all cells, greatly accelerate the rates of these chemical reactions and impart on them extraordinary specificity. In 1926, James B. Summer crystallized the enzyme urease and found that it was a protein. Skeptics argued that the enzymatic activity might reside in a trace component of the preparation rather than in the protein (Haldane, 1930), and it took another decade for the generality of Summer's finding to be established. As more and more examples of protein enzymes were found, it began to appear that biological catalysis would be exclusively the realm of proteins. In 1981 and 1982, my research group and I found a case in which RNA, a form of genetic material, was able to cleave and rejoin its own nucleotide linkages. This self-splicing RNA provided the first example of a catalytic active site formed of ribonucleic acid. This lecture gives a personal view of the events that led to our realization of RNA self-splicing and the catalytic potential of RNA. It provides yet another illustration of the circuitous path by which scientific inquiry often proceeds. The decision to expand so many words describing the early experiments means that much of our current knowledge about the system will not be mentioned. For a more comprehensive view of the mechanism and structure of the Tetrahymena self-splicing RNA and RNA catalysis in general, the reader is directed to a number of recent reviews (Cech & Bass, 1986: Cech, 1987, 1988a, 1990; Burke, 1988; Altman, 1989). Possible medical and pharmaceutical implications of RNA catalysis have also been described recently (Cech, 1988b).


Cascade Testing for Hereditary Cancer Syndromes: Should We Move Toward Direct Relative Contact? A Systematic Review and Meta-Analysis.
Evidence-based guidelines recommend cascade genetic counseling and testing for hereditary cancer syndromes, providing relatives the opportunity for early detection and prevention of cancer. The current standard is for patients to contact and encourage relatives (patient-mediated contact) to undergo counseling and testing. Direct relative contact by the medical team or testing laboratory has shown promise but is complicated by privacy laws and lack of infrastructure. We sought to compare outcomes associated with patient-mediated and direct relative contact for hereditary cancer cascade genetic counseling and testing in the first meta-analysis on this topic. We conducted a systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO No.: CRD42020134276). We searched key electronic databases to identify studies evaluating hereditary cancer cascade testing. Eligible trials were subjected to meta-analysis. Eighty-seven studies met inclusion criteria. Among relatives included in the meta-analysis, 48% (95% CI, 38 to 58) underwent cascade genetic counseling and 41% (95% CI, 34 to 48) cascade genetic testing. Compared with the patient-mediated approach, direct relative contact resulted in significantly higher uptake of genetic counseling for all relatives (63% [95% CI, 49 to 75] v 35% [95% CI, 24 to 48]) and genetic testing for first-degree relatives (62% [95% CI, 49 to 73] v 40% [95% CI, 32 to 48]). Methods of direct contact included telephone calls, letters, and e-mails; respective rates of genetic testing completion were 61% (95% CI, 51 to 70), 48% (95% CI, 37 to 59), and 48% (95% CI, 45 to 50). Most relatives at risk for hereditary cancer do not undergo cascade genetic counseling and testing, forgoing potentially life-saving medical interventions. Compared with patient-mediated contact, direct relative contact increased rates of cascade genetic counseling and testing, arguing for a shift in the care delivery paradigm, to be confirmed by randomized controlled trials.


Placental protein 14 production by human Fallopian tube epithelial cells in vitro.
We studied the in-vitro secretory function of non-polarized and polarized cultured Fallopian tube epithelial cells by measurement of the placental protein 14 (PP14) secretion in primary cultures and subcultures from Fallopian tubes obtained from eight premenopausal women in different phases of the ovarian cycle. Primary cultures were established in minimal essential medium in Earle's salts supplemented with fetal bovine serum and the cells were subcultured for six passages, in the polarized cell cultures, the cells being seeded on an extracellular matrix system. Cell freezing was carried out using 10% dimethyl sulphoxide. PP14 secretion into the culture media was measured by a radioimmunoassay using 125I-PP14 as label and rabbit anti-human PP14 serum. There was a large amount of PP14 secretion into the culture media in primary cultures, the secretion decreasing considerably after subculture 1. PP14 secretion after subculture 2 was not different from the control values. Polarized and non-polarized cells secreted similar amounts of PP14 and frozen-thawed cells did not appear to secrete PP14. Epithelial cells from Fallopian tubes obtained at different phases of the ovarian cycle did not appear to show any difference in PP14 secretion rates. Our data suggest that the in-vitro secretion of PP14 by human Fallopian tube epithelial cells is adversely affected by cell ageing and freezing.


Approach to Evaluating the Multimorbid Patient with Cardiovascular Disease Undergoing Noncardiac Surgery.
Older patients undergo more inpatient and outpatient procedures than do younger individuals, and their risk of suffering undesired outcomes is greater. The performance of a productive preoperative assessment entails more than the application of the sundry clinical practice guidelines relating to a patient's various medical diagnoses. A better approach involves adoption of a physiologically integrated, whole-person assessment that takes into account the patient's cognitive function, mood, physical function and mobility (including the possibility of frailty), social support, nutritional status, and medication use. This article outlines such an approach and highlights the many gaps in the current evidence base.


Chlordiazepoxide reduces in vivo serotonin release in the basal ganglia of encéphale isolé but not anesthetized cats: evidence for a dorsal raphe site of action.
By using a push-pull cannula technique and an isotopic method for the estimation of [3H]serotonin continuously synthetized from [3H]tryptophan, the effects of a benzodiazepine, chlordiazepoxide, were investigated on the in vivo release of [3H]serotonin in the cat basal ganglia. Chlordiazepoxide injection (10 mg/kg i.p.) decreased striatal and nigral [3H]serotonin release and enhanced the [3H]amine release in the dorsal raphe. These changes were blocked by the continuous superfusion of the dorsal raphe with Ro 15-1788 (10(-5) M), a benzodiazepine receptor antagonist. Chlordiazepoxide (10(-5) M) applied to the dorsal raphe reduced nigral [3H]serotonin release while decreasing [3H]serotonin release locally in the dorsal raphe. Furthermore, the superfusion of serotonergic nerve terminals of the substantia nigra or the caudate nucleus with chlordiazepoxide (10(-5) M) never altered the local release of [3H]serotonin. These data strongly suggest that the (inhibitory) influences exerted by chlordiazepoxide on serotonergic transmission more likely involved cell bodies and/or dendrites rather than terminals of serotonergic neurons. Chlordiazepoxide-induced changes in [3H]serotonin release were only observed in "encéphale isolé" and not in halothane-anesthetized cats. Further experiments revealed that GABAergic neurons of the dorsal raphe could participate to such a differential reactivity of serotonergic cells to chlordiazepoxide. For instance, [3H]gamma-aminobutyric acid release in the dorsal raphe was enhanced by halothane anesthesia. These findings further suggest the possibility that the influence exerted by benzodiazepines on serotonergic transmission, perhaps through a gamma-aminobutyric acid-dependent process, can significantly be involved in the pharmacological actions of these drugs.


Silencing of epithelial CXCL12 expression by DNA hypermethylation promotes colonic carcinoma metastasis.
Cellular metastasis is the most detrimental step in carcinoma disease progression, yet the mechanisms that regulate this process are poorly understood. CXCL12 and its receptor CXCR4 are co-expressed in several tissues and cell types throughout the body and play essential roles in development. Disruption of either gene causes embryonic lethality due to similar defects. Post-natally, CXCL12 signaling has a wide range of effects on CXCR4-expressing cells, including the directed migration of leukocytes, lymphocytes and hematopoietic stem cells. Recently, this signaling axis has also been described as an important regulator of directed carcinoma cell metastasis. We show herein that while CXCR4 expression remains consistent, constitutive colonic epithelial expression of CXCL12 is silenced by DNA hypermethylation in primary colorectal carcinomas as well as colorectal carcinoma-derived cell lines. Inhibition of DNA methyltransferase (Dnmt) enzymes with 5-aza-2'-deoxycytidine or genetic ablation of both Dnmt1 and Dnmt3b prevented promoter methylation and restored CXCL12 expression. Re-expression of functional, endogenous CXCL12 in colorectal carcinoma cells dramatically reduced metastatic tumor formation in mice, as well as foci formation in soft agar. Decreased metastasis was correlated with increased caspase activity in cells re-expressing CXCL12. These data constitute the unique observation that silencing CXCL12 within colonic carcinoma cells greatly enhances their metastatic potential.


Behçet's disease with a large intracardiac thrombus: a case report.
Behçet's disease is recognised as a chronic multisystem disorder with vasculitis as its underlying pathological process. Cardiac involvement is rare and often associated with poor prognosis. A case of a 33 year old man with Behçet's disease, presenting with a large right ventricle and right atrial thrombus, is reported. Two dimensional (cross sectional), colour Doppler, and transoesophageal echocardiography, angiography, computed tomography, and magnetic resonance imaging were used to diagnose the disease. With cyclophosphamide and dexamethasone treatment, the cardiac lesions progressively resolved.


Potassium transport by rabbit descending colon, in vitro.
Studies of the bidirectional fluxes of K across segments of rabbit descending colon indicate that: a) when the tissue is short-circuited, the net flux does not differ significantly from zero under control conditions and in the presence of aldosterone; and b) the bidirectional fluxes of K conform to the Ussing flux-ratio equation over a wide range of transepithelial electrochemical potential differences. These and other findings strongly suggest that the movements of K across the epithelium are restricted to paracellular routes and are entirely passive. Studies dealing with the mechanism of homocellular K transport indicate that: a) K is actively transported into the cells across the basolateral membranes against an electrochemical potential difference of approximately 30 mV; and b) the active uptake of K may be mediated by a rheogenic Na-K exchange pump that is also responsible for transcellular Na transport. These results are entirely consistent with the model proposed by Koefoed-Johnson and Ussing for isolated frog skin.


Duodenal Ulcer Induced by Hem-o-Lok clip after Reduced Port Laparoscopic Cholecystectomy.
The patient was a 66-year-old woman who had undergone laparoscopic cholecystectomy (Lap-C) secondary to chronic cholecystitis status post endoscopic choledocholithotomy 13 months previously. During surgery, Hem-o-Lok clips were used to control the cystic duct and the cystic artery. Due to the presence of extensive adhesions of the cystic duct and surrounding tissue, the surgeons had difficulty in debriding the area. Thirteen months after Lap-C, the patient underwent a screening esophagogastroduodenoscopy (EGD), which demonstrated clip appearance at the inferior wall of the first part of the duodenum. In the EGD, duodenal erosions and edema were observed around the clip. We appreciated that endoscopic clip removal would be difficult because of the presence of severe adhesions and inflammation of the duodenal bulb. On clinical examination of the patient, no major abnormalities or physical findings were noted. Therefore, we decided not to attempt to remove the clip. The patient was treated with an oral proton pump inhibitor to prevent extensive duodenal mucosal injury. Two months later, we repeated the EGD, which revealed that the clip was no longer present, and the duodenum was covered with normal mucosa surrounding the scar.


[Malnutrition in anorexia nervosa: psychosomatic approach and multidisciplinary treatment].
Using the quantitative and statistical method to study the psychopathology of this disorder, we feel that melancholy underlies all anorexia, a structural psychological failing in the primary narcissistic personality instituted at the beginning of life. Melancholy entails its opposite, mania, manifested in anorexia through exhausting physical exercise and a perpetual binge-purge cycle, with continuous vomiting that damages teeth and the oesophagus, leading to malnutrition, dependence on laxatives, colic and inflammation of the anus. Amenorrhea increases the levels of cortisol, thus facilitating osteoporosis. Other symptoms observed include: cold skin, pain on sitting, lanugo, hair loss, low blood pressure, bradycardia, prolapses of the mitral valve or pericardial effusion. Less commonly, oedema or anaemia, despite the sufficient intake of iron and proteins. Sleep disorders and abandonment of normal activities have also been reported. Population of 30 patients previously diagnosed as having anorexia nervosa according to DSM-IV or CIE-10 parameters, without election by gender, either institutionalized or attending day hospital. Over 18 years of age and with their mental personality structure somewhat consolidated so that the results would not be altered by a lack of stability in this variable. This is a first exploratory statistical analysis with a transverse description of only 30 anorexic patients without any contrasting control group and is therefore not conclusive. The variables will have to be adjusted through larger subsequent studies to weigh up our observations. From melancholic mania, the patients feel unique and special, through being able to go so long without eating. There is a corporal pleasure in all asceticism, as consumption modifies the perception of enjoyment. This triumph in solitude may recycle the anorexic eating pathology and turn it into something hard to reverse. Poor self-esteem often surrounds this condition. Patients, fixated on the maternal image, tend to undervalue their own, unable to withstand the development of the body or the internal tension this entails. Controlled exercise, improved nutrition and hormone treatment are currently the combined therapies applied in AN, with agreement being reached with patients on a specific personal diet of low volume, attempting to ensure the necessary minimum of fat and carbohydrates. With simultaneous psychological attention through an integral multidisciplinary approach in order to reduce the high prevalence of partially treated cases that accumulate over time.


Preclamol and parkinsonian fluctuations.
Preclamol, the (-)enantiomer of 3-PPP (= 3(3-hydroxyphenyl)-N-n-propyl piperidine), has a selective dopamine autoreceptor- and postsynaptic mixed agonist-antagonist profile. Its action on patients with disabling on-off parkinsonian fluctuations has been studied and compared with those of placebo and subcutaneous apomorphine. Preclamol had a mild but unequivocal antiakinetic effect, less than that caused by subcutaneous apomorphine, but it provoked less dyskinesia. Further studies to explore the therapeutic potential of preclamol seem justified.


A new index for the analysis of heart rate variability dynamics: characterization and application.
A new index for the analysis of the heart rate variability (HRV) dynamics is presented. The proposed index (acceleration change index (ACI)) characterizes the sign of the differences of a time series. A theoretical study shows an expression that relates ACI and the autocorrelation function of the time series. This formula is tested and validated with different simulated time series (uncorrelated noise, sinusoidal and fractional Brownian motion). Next, ACI is applied to RR time series from healthy subjects showing that ACI decreases with periodic controlled breathing, increases during exercise, and it has a lower value at night than during the day. In a preliminary study, ACI has been shown to be lower in healthy subjects than in patients who had suffered a myocardial infarction one month previously. ACI can be employed as a fast and robust new marker of the HRV dynamics.


Understanding cardiopulmonary resuscitation decision making: perspectives of seriously ill hospitalized patients and family members.
To improve communication and decision making related to cardiopulmonary resuscitation (CPR), a greater understanding of the perspectives of hospitalized patients with advanced diseases and their family members are needed. In five Canadian hospitals, we administered a face-to-face questionnaire to older inpatients with end-stage cancer and advanced medical diseases and, where possible, to one of their family members, regarding information needs, the deliberation process, and their preferred decisional role. A total of 440 of 569 patients (78%) and 160 of 176 available caregivers (91%) agreed to participate. Most patients (61%) had thought about what treatment they wanted if their heart stopped, few patients (11.3%) could describe more than two components of CPR, and only 2.7% of patients thought that the success rate of CPR was < 10%. A minority of patients (34%) had discussed CPR with their physician; 37% did not want to discuss their preferences with their doctor. Patients who felt that end-of-life issues were relevant to them were 5.5 times more likely to want a discussion with the physician regarding resuscitation (odds ratio, 5.5; 95% confidence interval, 2.5 to 12.0). The preferred role in decision making was variable, but most patients (59.7%) and family members (81.6%) preferred some degree of shared decision making that included the family member. There were no significant differences between cancer and medical patients in their preferred decisional role. Seriously ill hospitalized patients have poor knowledge about CPR, and variable preferences for deliberation and their role in the decision-making process regarding their treatment. Strategies that improve understanding of CPR and foster discussions that involve patients, family members, and physicians in the decision-making process may improve the quantity and quality of communication and decision making about CPR.


Candida and Torulopsis: a blinded evaluation of use of pseudohypha formation as basis for identification of medically important yeasts.
Seventy yeast isolates representing species in the genera Candida and Torulopsis but excluding Candida albicans were examined in three laboratories for production of pseudohyphae in Dalmau cultures. The microscopic morphology of the isolates was scrutinized by four individuals experienced in yeast identification and three inexperienced persons, all of whom were blinded as to the putative identification of the yeasts. For 49 (70%) of the 70 isolates, the seven observers recorded comparable scores for morphology, but 5 (7%) of the isolates showed extreme variation in recorded morphologies, from true hyphae formed to no pseudohyphae formed. Isolates of Candida parapsilosis and Torulopsis glabrata consistently did and did not form pseudohyphae, respectively: however, other Candida and Torulopsis spp. did not always express their expected morphologies. In 48 (19%) of 252 readings (seven observers), 36 isolates of Candida spp. were scored as forming no pseudohyphae, and in 22 (9.2%) of 238 readings, 34 isolates of Torulopsis spp. were recorded as forming true hyphae or pseudohyphae. These results show that pseudohypha formation is not a reliable characteristic for identification of yeasts at the genus level; we suggest that the merger of Torulopsis spp. into the genus Candida should be finally accepted.


Neutral transition metal hydrides as acids in hydrogen bonding and proton transfer: media polarity and specific solvation effects.
Structural, spectroscopic, and electronic features of weak hydrogen-bonded complexes of CpM(CO)(3)H (M = Mo (1a), W (1b)) hydrides with organic bases (phosphine oxides R(3)PO (R = n-C(8)H(17), NMe(2)), amines NMe(3), NEt(3), and pyridine) are determined experimentally (variable temperature IR) and computationally (DFT/M05). The intermediacy of these complexes in reversible proton transfer is shown, and the thermodynamic parameters (DeltaH degrees , DeltaS degrees ) of each reaction step are determined in hexane. Assignment of the product ion pair structure is made with the help of the frequency calculations. The solvent effects were studied experimentally using IR spectroscopy in CH(2)Cl(2), THF, and CH(3)CN and computationally using conductor-like polarizable continuum model (CPCM) calculations. This complementary approach reveals the particular importance of specific solvation for the hydrogen-bond formation step. The strength of the hydrogen bond between hydrides 1 and the model bases is similar to that of the M-H...X hydrogen bond between 1 and THF (X = O) or CH(3)CN (X = N) or between CH(2)Cl(2) and the same bases. The latter competitive weak interactions lower the activities of both the hydrides and the bases in the proton transfer reaction. In this way, these secondary effects shift the proton transfer equilibrium and lead to the counterintuitive hampering of proton transfer upon solvent change from hexane to moderately polar CH(2)Cl(2) or THF.


Nonlinear blind source separation using a radial basis function network.
This paper proposes a novel neural-network approach to blind source separation in nonlinear mixture. The approach utilizes a radial basis function (RBF) neural-network to approximate the inverse of the nonlinear mixing mapping which is assumed to exist and able to be approximated using an RBF network. A contrast function which consists of the mutual information and partial moments of the outputs of the separation system, is defined to separate the nonlinear mixture. The minimization of the contrast function results in the independence of the outputs with desirable moments such that the original sources are separated properly. Two learning algorithms for the parametric RBF network are developed by using the stochastic gradient descent method and an unsupervised clustering method. By virtue of the RBF neural network, this proposed approach takes advantage of high learning convergence rate of weights in the hidden layer and output layer, natural unsupervised learning characteristics, modular structure, and universal approximation capability. Simulation results are presented to demonstrate the feasibility, robustness, and computability of the proposed method.


The impact of race/ethnicity on mother-to-child HIV transmission in the United States in Pediatric AIDS Clinical Trials Group Protocol 316.
The present analysis was designed to determine whether race/ethnicity was independently associated with mother-to-child HIV-1 transmission risk in subjects enrolled in a trial of 2-dose intra-partum nevirapine in combination with standard antiretroviral therapy and to determine what factors, including race/ethnicity, predicted maternal viral suppression at the time of delivery. Women enrolled in Pediatric AIDS Clinical Trials Group (PACTG) 316 from sites in the United States and Puerto Rico were included. Distribution of selected maternal disease and treatment characteristics was assessed by race/ethnicity category. Logistic regression models were fit to evaluate possible association of factors with HIV transmission and with viral load at delivery. Variables associated with the outcome at P < 0.05 level were retained in the final models. Of 1052 women randomized at PACTG sites, 891 were included in the present analysis: 572 (64%) were black; 206 (23%) were Hispanic; and 113 (13%) were white. All women who had infected infants were black or Hispanic (11/572 and 3/206, respectively), whereas none of the women identified as white had an infected infant (0/113). This difference was not statistically significant (P = 0.54). White women had higher entry CD4 cell counts and lower HIV-1 RNA at delivery than women of other races/ethnicities. Black and Hispanic women were more likely than white women to start therapy during their current pregnancy but did not initiate prenatal care later. In bivariate models that included antiretroviral type and variables that had values of P < or = 0.25 in univariate analysis, time of antiretroviral initiation, time of prenatal care initiation, and race/ethnicity each retained significance in predicting viral suppression at delivery. Race/ethnicity remained predictive of viral suppression at delivery in a multivariate model incorporating all of these variables (P = 0.01). Higher HIV-1 RNA and lower CD4 cell counts in women identified as black or Hispanic have significant implications for the health of these women and their newborns. Race/ethnicity is significant in predicting viral suppression at the time of delivery.


The Biocompatibility of Cyanoacrylate Tissue Adhesive in Conjunction with a Collagen Membrane for Providing Soft and Hard Tissue Regeneration in Extraction Socket Preservation Procedures.
This clinical investigation was performed to determine the efficacy of cyanoacrylate tissue adhesive to enhance soft and hard tissue healing of extraction wounds requiring a regenerative effort. Fourteen patients requiring a total of 25 tooth extractions were selected. Twenty sockets were treated with cyanoacrylate tissue adhesive over an exposed collagen barrier membrane without altering the mucogingival junction, while five extraction sockets were allowed to heal by the secondary healing intention as well but without tissue adhesive application. The results were evaluated with emphasis on soft tissue color and form as well as bone surface morphology. All sites received dental implants. There was a clear advantage to using cyanoacrylate tissue adhesive as a protective mechanism over an exposed collagen barrier membrane.


Effects of hormonal contraceptives on milk volume and infant growth. WHO Special Programme of Research, Development and Research Training in Human Reproduction Task force on oral contraceptives.
WHO conducted a three-centre study in Hungary and Thailand to evaluate the effects of hormonal contraception on lactation and infant growth. Women choosing oral contraceptives were randomly assigned to a combined oral contraceptive containing 30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel (N = 86) or a progestin-only preparation containing 75 micrograms dl-norgestrel (N = 85). Identical packaging and treatment schedules allowed double-blind observation. One-hundred-and-eleven women using no contraception or non-hormonal methods acted as controls. In the two Thai centres 59 women using depot-medroxyprogesterone acetate formed an additional comparison group. All subjects were healthy women with normal deliveries, whose infants had normal birth weights and satisfactory growth in the neonatal period. Breast milk volume was determined by pump expression using standardized procedures. Information was obtained on nursing frequency and supplementation, infant growth and morbidity. Pretreatment observations at 6 weeks post-partum were used as a baseline, and subjects were followed-up at 9, 12, 16, 20 and 24 weeks post-partum. Women using combined oral contraceptives had a decline in milk volume within 6 weeks of initiating treatment, whereas no significant decrease was observed in the other treatment groups. After 18 weeks of treatment, combined oral contraceptive users experienced a 41.9% decline in milk volume, compared to 12.0% with progestin-only minipills and 6.1% in the non-hormonal controls. The prevalence of complementary feeding and withdrawals due to inadequate milk supply were comparable in the four treatment groups. However, data were not available on the daily amounts of complementary feeds. There were no significant differences in growth of infants between treatment groups. Thus, women may have compensated for declines in milk volume by more supplementary feeding or by more prolonged and intense suckling episodes. We conclude that 30 micrograms estrogen-containing combined oral contraceptives impair milk secretion, but in the selected healthy group of mothers and children studied with the prevailing level of supplementary feeding, this did not adversely affect infant growth.


Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study.
Standard first-line treatment of metastatic triple-negative breast cancer (mTNBC) is chemotherapy. However, outcomes are poor, and new treatment options are needed. In cohort B of the phase II KEYNOTE-086 study, we evaluated pembrolizumab as first-line therapy for patients with PD-L1-positive mTNBC. Eligible patients had centrally confirmed mTNBC, no prior systemic anticancer therapy for metastatic disease, measurable disease at baseline per RECIST v1.1 by central review, no radiographic evidence of central nervous system metastases, and a tumor PD-L1 combined positive score ≥1. Patients received pembrolizumab 200 mg intravenously every 3 weeks for up to 2 years. The primary end point was safety. Secondary end points included objective response rate, disease control rate (percentage of patients with complete or partial response or stable disease for ≥24 weeks), duration of response, progression-free survival and overall survival. All 84 patients enrolled were women, and 73 (86.9%) received prior (neo)adjuvant therapy. Fifty-three (63.1%) patients had treatment-related adverse events (AEs), including 8 patients (9.5%) with grade 3 severity; no patients experienced grade 4 AEs or died because of treatment-related AEs. Four patients had a complete response and 14 had a partial response, for an objective response rate of 21.4% (95% CI 13.9-31.4). Of the 13 patients with stable disease, 2 had stable disease lasting ≥24 weeks, for a disease control rate of 23.8% (95% CI 15.9-34.0). At data cut-off, 8 of 18 (44.4%) responses were ongoing, and median duration of response was 10.4 months (range 4.2 to 19.2+). Median progression-free survival was 2.1 months (95% CI 2.0-2.2), and median overall survival was 18.0 months (95% CI 12.9-23.0). Pembrolizumab monotherapy had a manageable safety profile and showed durable antitumor activity as first-line therapy for patients with PD-L1-positive mTNBC. ClinicalTrials.gov, NCT02447003.


Consumption of Whey in Combination with Dairy Medium-Chain Fatty Acids (MCFAs) may Reduce Lipid Storage due to Urinary Loss of Tricarboxylic Acid Cycle Intermediates and Increased Rates of MCFAs Oxidation.
The aim of the paper is to investigate whether changes in the metabolome could explain observed changes in body composition in overweight adults after consumption of butter with high level of medium-chain fatty acids (MCFAs) in combination with casein or whey. With GC-TOF and LC-Q/MS, metabolites in plasma and urine from a 12-week randomized double-blinded human intervention including 52-abdominally overweight adults were analyzed. The participants consumed 63 g per day of milk fat (high or low in MCFAs) and 60 g per day of protein (whey or casein). Urinary loss of the tricarboxylic acid cycle metabolites and a concomitantly increase of glycerol in blood were observed in the whey + high-MCFAs group, indicating potential lower anabolic processes, such as lipogenesis, by draining substrates. High intake of MCFAs resulted in elevated level of urinary adipic (independently of protein type) and plasma sebacic acid (with whey), indicating a potential increase in oxidation of MCFAs, which might lead to energy loss. The type of protein showed highest effect on the overall metabolic profiles, but ω-oxidation of MCFAs in the liver seemed to be the main reason for the observed reduction in body fat mass after consumption of high MCFAs, independent of type of protein.


Gentamicin induces LAMB3 nonsense mutation readthrough and restores functional laminin 332 in junctional epidermolysis bullosa.
Herlitz junctional epidermolysis bullosa (H-JEB) is an incurable, devastating, and mostly fatal inherited skin disease for which there is only supportive care. H-JEB is caused by loss-of-function mutations in LAMA3, LAMB3, or LAMC2, leading to complete loss of laminin 332, the major component of anchoring filaments, which mediate epidermal-dermal adherence. LAMB3 (laminin β3) mutations account for 80% of patients with H-JEB, and ∼95% of H-JEB-associated LAMB3 mutations are nonsense mutations leading to premature termination codons (PTCs). In this study, we evaluated the ability of gentamicin to induce PTC readthrough in H-JEB laminin β3-null keratinocytes transfected with expression vectors encoding eight different LAMB3 nonsense mutations. We found that gentamicin induced PTC readthrough in all eight nonsense mutations tested. We next used lentiviral vectors to generate stably transduced H-JEB cells with the R635X and C290X nonsense mutations. Incubation of these cell lines with various concentrations of gentamicin resulted in the synthesis and secretion of full-length laminin β3 in a dose-dependent and sustained manner. Importantly, the gentamicin-induced laminin β3 led to the restoration of laminin 332 assembly, secretion, and deposition within the dermal/epidermal junction, as well as proper polarization of α6β4 integrin in basal keratinocytes, as assessed by immunoblot analysis, immunofluorescent microscopy, and an in vitro 3D skin equivalent model. Finally, newly restored laminin 332 corrected the abnormal cellular phenotype of H-JEB cells by reversing abnormal cell morphology, poor growth potential, poor cell-substratum adhesion, and hypermotility. Therefore, gentamicin may offer a therapy for H-JEB and other inherited skin diseases caused by PTC mutations.


[Experimental study of the effect of pulsed infrared laser radiation on skeletal muscle regeneration after mechanical trauma].
Impulse infrared laser radiation (0.89 microm) was examined for effect on regeneration of cross-cut musculus gastrocnemius in adult rats (ten 3-min exposures, 2-3 procedures weekly for one month after the operation, modulating frequency 10 Hz, total course dose 3.6 J/cm2). Histological, morphometric and biochemical parameters of muscular regenerates as well as biochemical serum indices show enhanced regeneration of the skeletal muscle. Formation of the muscular organ ends earlier vs untreated muscles. This was accompanied with more active sclerotization of the muscular regenerate.


Teamwork and Safety Attitudes in Complex Aortic Surgery at a Dutch Hospital: Cross-Sectional Survey Study.
Improving teamwork in surgery is a complex goal and difficult to achieve. Human factors questionnaires, such as the Safety Attitudes Questionnaire (SAQ), can help us understand medical teamwork and may assist in achieving this goal. This paper aimed to assess local team and safety culture in a cardiovascular surgery setting to understand how purposeful teamwork improvements can be reached. Two cardiovascular surgical teams performing complex aortic treatments were assessed: an endovascular-treatment team (ETT) and an open-treatment team (OTT). Both teams answered an online version of the SAQ Dutch Edition (SAQ-NL) consisting of 30 questions related to six different domains of safety: teamwork climate, safety climate, job satisfaction, stress recognition, perceptions of management, and working conditions. In addition, one open-ended question was posed to gain more insight into the completed questionnaires. The SAQ-NL was completed by all 23 ETT members and all 13 OTT members. Team composition was comparable for both teams: 57% and 62% males, respectively, and 48% and 54% physicians, respectively. All participants worked for 10 years or more in health care. SAQ-NL mean scores were comparable between both teams, with important differences found between the physicians and nonphysicians of the ETT. Nonphysicians were less positive about the safety climate, job satisfaction, and working climate domains than were the physicians (P<.05). Additional education on performed procedures, more conjoined team training, as well as a hybrid operating room were suggested by participants as important areas of improvement. Nonphysicians of a local team performing complex endovascular aortic aneurysm surgery perceived safety climate, job satisfaction, and working conditions less positively than did physicians from the same team. Open-ended questions suggested that this is related to a lack of adequate conjoined training, lack of adequate education, and lack of an adequate operating room. With added open-ended questions, the SAQ-NL appears to be an assessment tool that allows for developing strategies that are instrumental in improving quality of care.


Gene Microarray Integrated with High-Throughput Proteomics for the Discovery of Transthyretin in Rhabdomyolysis-Induced Acute Kidney Injury.
Rhabdomyolysis, one of the leading causes of acute kidney injury (AKI), develops after trauma, drug toxicity, infections, burns, and physical exertion. The aim of this study was to investigate differences in gene and protein expression to elucidate the pathogenesis of rhabdomyolysis (RM)-induced AKI. In this study, we used glycerol induced renal injury as a model of RM-induced AKI. Affymetrix U133 plus 2.0 microarrays were used to perform gene microarray analysis. Isobaric tagging with related and absolute quantitation (iTRAQ) labeling mass spectrometry (MS) was applied to screen and identify differentially expressed proteins between RM-induced AKI and normal murine renal tissue. Verification experiments included immunohistochemistry (IHC), real-time PCR, Western blotting, and the measurement of ATP and ROS production. HK-2 cells were incubated in vitro with ferrous myoglobin and pcDNA-TTR, followed by assays to detect cell proliferation, ROS and apoptosis. According to gene microarray and iTRAQ-MS analysis, we screened 17 common elements. After multiple analyses, we selected transthyretin (TTR) as our focus and investigated TTR in the kidney. Verification experiments with IHC confirmed differential expression levels of TTR proteins. Furthermore, Western blotting showed a stepwise decrease in TTR in AKI renal tissues. Cell-based experiments showed that overexpression of TTR could improve HK-2 cell viability and inhibit apoptosis. TTR reduced apoptosis by decreasing the accumulation of reactive oxygen species (ROS). This study reports a possible mechanism for RM-induced AKI and suggests that reductions in TTR could increase the generation of ROS and induce apoptosis. TTR may be a potentially valuable target for RM-induced AKI.


Microbiological outcomes following mupirocin nasal washes for symptomatic, Staphylococcus aureus-positive chronic rhinosinusitis following endoscopic sinus surgery.
Persistent infection following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) is a frustrating entity for the patient and rhinologist alike. Mupirocin nasal washes have been proposed as an efficacious treatment in such patients. Two small studies have reported excellent short-term posttreatment outcomes; however, the long-term microbiological outcomes following treatment are not known; likewise, the rate of mupirocin-resistance following treatment has not been explored. This was a retrospective chart review of 61 patients with Staphylococcus aureus (S. aureus)-positive surgically-recalcitrant CRS having undergone 0.05% mupirocin nasal rinse treatment, twice daily for 4 weeks. Specific outcomes reported included posttreatment culture results, time to first posttreatment S. aureus culture, and mupirocin-sensitivity following treatment. Of 57 patients meeting minimal posttreatment follow-up criteria, 42 (73.7%) progressed to microbiological failure by subsequently cultured S. aureus. Mean time to first positive culture was 144 days. Of the 42 patients who progressed to microbiological relapse, full antibiotic sensitivity data was available for 41; of these, only 1 was found to subsequently harbor a mupirocin-resistant strain of S. aureus, thus yielding a posttreatment resistance rate of 2.4%. Treatment with mupirocin nasal washes in S. aureus-positive, surgically recalcitrant CRS has a high microbiological failure rate, with 73.7% of patients subsequently re-culturing S. aureus. Our current treatment regime of 0.05% nasal washes twice daily for 4 weeks is associated with a posttreatment resistance rate that is consistent with other studies of topical mupirocin use, suggesting that mupirocin washes are no more likely to induce resistance than nasal vestibule decolonization in the high-risk medical or surgical patient.


Genetic and epigenetic mechanisms of epilepsy: a review.
Epilepsy is a common episodic neurological disorder or condition characterized by recurrent epileptic seizures, and genetics seems to play a key role in its etiology. Early linkage studies have localized multiple loci that may harbor susceptibility genes to epilepsy, and mutational analyses have detected a number of mutations involved in both ion channel and nonion channel genes in patients with idiopathic epilepsy. Genome-wide studies of epilepsy have found copy number variants at 2q24.2-q24.3, 7q11.22, 15q11.2-q13.3, and 16p13.11-p13.2, some of which disrupt multiple genes, such as NRXN1, AUTS2, NLGN1, CNTNAP2, GRIN2A, PRRT2, NIPA2, and BMP5, implicated for neurodevelopmental disorders, including intellectual disability and autism. Unfortunately, only a few common genetic variants have been associated with epilepsy. Recent exome-sequencing studies have found some genetic mutations, most of which are located in nonion channel genes such as the LGI1, PRRT2, EFHC1, PRICKLE, RBFOX1, and DEPDC5 and in probands with rare forms of familial epilepsy, and some of these genes are involved with the neurodevelopment. Since epigenetics plays a role in neuronal function from embryogenesis and early brain development to tissue-specific gene expression, epigenetic regulation may contribute to the genetic mechanism of neurodevelopment through which a gene and the environment interacting with each other affect the development of epilepsy. This review focused on the analytic tools used to identify epilepsy and then provided a summary of recent linkage and association findings, indicating the existence of novel genes on several chromosomes for further understanding of the biology of epilepsy.


Characterization of semiconductor photocatalysts.
The long-standing popularity of semiconductor photocatalysis due to its great potential in a variety of applications has resulted in the creation of numerous semiconductor photocatalysts, which stimulated the development of various characterization methods. This review aims to summarize the main characterization methods for assessing the most important properties of semiconductor photocatalysts, including their chemical composition (elemental composition, and chemical state/structure), physical properties (physical structure, crystallographic properties, optical absorption, charge dynamics, defects, and colloidal and thermal stability), and band structure (band gap, band edges/band edge offsets, and Fermi level). The discussion on each of these methods starts with a concise presentation of its fundamentals followed by carefully selected examples. At the end, a chart correlating the properties of a semiconductor with its potential characterization methods as well as outlook are provided. Overall, the aim of this review article is to help materials chemists and physicists, particularly students, in selecting suitable techniques for the characterization of semiconductor photocatalysts and potentially other relevant materials.


Low Rates of Gastrointestinal and Non-Gastrointestinal Complications for Screening or Surveillance Colonoscopies in a Population-Based Study.
The full spectrum of serious non-gastrointestinal post-colonoscopy complications has not been well characterized. We analyzed rates of and factors associated with adverse post-colonoscopy gastrointestinal (GI) and non-gastrointestinal events (cardiovascular, pulmonary, or infectious) attributable to screening or surveillance colonoscopy (S-colo) and non-screening or non-surveillance colonoscopy (NS-colo). We performed a population-based study of colonoscopy complications using databases from California hospital-owned and nonhospital-owned ambulatory facilities, emergency departments, and hospitals from January 1, 2005 through December 31, 2011. We identified patients who underwent S-colo (1.58 million), NS-colo (1.22 million), or low-risk comparator procedures (joint injection, aspiration, lithotripsy; arthroscopy, carpal tunnel; or cataract; 2.02 million) in California's Ambulatory Services Databases. We identified patients who developed adverse events within 30 days, and factors associated with these events, through patient-level linkage to California's Emergency Department and Inpatient Databases. After S-colo, the numbers of lower GI bleeding, perforation, myocardial infarction, and ischemic stroke per 10,000-persons were 5.3 (95% confidence interval [CI], 4.8-5.9), 2.9 (95% CI, 2.5-3.3), 2.5 (95% CI, 2.1-2.9), and 4.7 (95% CI, 4.1-5.2) without biopsy or intervention; with biopsy or intervention, numbers per 10,000-persons were 36.4 (95% CI, 35.1-37.6), 6.3 (95% CI, 5.8-6.8), 4.2 (95% CI, 3.8-4.7), and 9.1 (95% CI, 8.5-9.7). Rates of dysrhythmia were higher. After NS-colo, event rates were substantially higher. Most serious complications led to hospitalization, and most GI complications occurred within 14 days of colonoscopy. Ranges of adjusted odds ratios for serious GI complications, myocardial infarction, ischemic stroke, and serious pulmonary events after S-colo vs comparator procedures were 2.18 (95% CI, 2.02-2.36) to 5.13 (95% CI, 4.81-5.47), 0.67 (95% CI, 0.56-0.81) to 0.99 (95% CI, 0.83-1.19), 0.66 (95% CI, 0.59-0.75) to 1.13 (95% CI, 0.99-1.29), and 0.64 (95% CI, 0.61-0.68) to 1.05 (95% CI, 0.98-1.11). Biopsy or intervention, comorbidity, black race, low income, public insurance, and NS-colo were associated with post-colonoscopy adverse events. In a population-based study in California, we found that following S-colo, rates of serious GI adverse events were low but clinically relevant, and that rates of myocardial infarction, stroke, and serious pulmonary events were no higher than after low-risk comparator procedures. Rates of myocardial infarction are similar to, but rates of stroke are higher than, those reported for the general population.


Surface layers of Eubacterium yurii subsp. yurii and their possible role in test-tube brush formation and iron acquisition.
Eubacterium yurii subsp. yurii is an anaerobic, gram-positive rod. On isolation E. yurii forms cellular arrangements resembling test-tube brushes (TTB). Although TTB decreased in size and number on repeated laboratory subculture in enriched media, media poor in available iron enhanced formation of these. Plasmids were not demonstrated, even after chloramphenicol enhancement. To characterise the nature and possible physiological roles of the structures of the TTB, they were examined by transmission electronmicroscopy (TEM) with thin-section, negative-staining, shadow-casting, freeze-etching and freeze-fracturing techniques, and by scanning electronmicroscopy (SEM). Previous studies by phase-contrast microscopy revealed an amorphous core, the size of which varied in direct proportion to the number of associated bacterial cells. Thin sections of the TTB showed a gram-positive cell wall with additional surface layers. Negative staining, shadow casting and freeze etching revealed a surface layer comprising subunits in tetragonal array (P4 symmetry). Shadow casting showed also that the outermost layer of the cells was composed of fibrillar structures closely associated with but distinct from, the tetragonal layer. The fibrils extended from the cell surface in clumps or strands. The presence of these fibrils was confirmed by the freeze-fracture technique and SEM. Chemical analysis of the core material of the TTB showed it to be low in carbohydrate (0.06%) and protein (0.2%). Energy-dispersive X-ray spectrometry showed that the core was composed mostly of iron.(ABSTRACT TRUNCATED AT 250 WORDS)


Connectome-based prediction of eating disorder-associated symptomatology.
Despite increasing knowledge on the neuroimaging patterns of eating disorder (ED) symptoms in non-clinical populations, studies using whole-brain machine learning to identify connectome-based neuromarkers of ED symptomatology are absent. This study examined the association of connectivity within and between large-scale functional networks with specific symptomatic behaviors and cognitions using connectome-based predictive modeling (CPM). CPM with ten-fold cross-validation was carried out to probe functional networks that were predictive of ED-associated symptomatology, including body image concerns, binge eating, and compensatory behaviors, within the discovery sample of 660 participants. The predictive ability of the identified networks was validated using an independent sample of 821 participants. The connectivity predictive of body image concerns was identified within and between networks implicated in cognitive control (frontoparietal and medial frontal), reward sensitivity (subcortical), and visual perception (visual). Crucially, the set of connections in the positive network related to body image concerns identified in one sample was generalized to predict body image concerns in an independent sample, suggesting the replicability of this effect. These findings point to the feasibility of using the functional connectome to predict ED symptomatology in the general population and provide the first evidence that functional interplay among distributed networks predicts body shape/weight concerns.


An HIV Envelope gp120-Fc Fusion Protein Elicits Effector Antibody Responses in Rhesus Macaques.
A goal for HIV prevention programs is to develop safe, effective vaccines that elicit durable and broadly protective antibodies. Many vaccine programs focus on the immune responses to critical epitopes in the gp120 portion of HIV envelope glycoprotein (Env) and seek to improve the quality and quantity of antibodies by altering the sequence, conformation, oligomerization, or glycosylation of gp120 to activate appropriate germ line B cells and mimic the subsequent maturation pathways seen in infected individuals. As a complement to these strategies, we developed dimeric fusion protein immunogens consisting of HIVBaL gp120 monomer attached to a Gly/Ser linker that is, in turn, fused to one half of the dimeric Fc domain from rhesus macaque IgG1 (Env-rFc). We envisioned that Env-rFc may mimic some aspects of immune complexes by binding Fc gamma receptors (FcγRs) on immune cells to increase the strength, breadth, and durability of Env-specific antibody responses. The Env-rFc retained a capacity to bind both cell surface CD4 and FcγRs. In a rhesus macaque immunization study, Env-rFc elicited higher gp120 binding antibody titers than Env and elicited antibodies that recognize CD4-induced epitopes. Env-rFc also induced antibodies capable of neutralizing tier 1A HIV pseudotyped viruses and mediating antibody-dependent cellular cytotoxicity, outcomes not observed with monomeric gp120 in our study. Serum antibodies produced in Env-rFc-immunized macaques had increased durability compared to that of Env monomer immunization. Our work suggests that adding IgG1 Fc to Env-based immunogens may stimulate increased effector capacity in the immune sera and improve the protective serum antibody response.


Revised phylogenetic relationships among herpesviruses isolated from sturgeons.
Initial phylogenetic comparisons based on a region of the DNA polymerase of seven herpes-like viruses found in sturgeons in North America and Europe indicated the presence of three distinct clades. A revised phylogenetic analysis of the same viruses, based on corrected DNA polymerase sequences and newly obtained sequence data from the putative ATP subunit of the terminase gene, indicate only two clades. These two clades correspond to the historical designations given to these herpes-like viruses from white sturgeon Acipenser transmontanus: white sturgeon herpesvirus type 1 (WSHV-1) and type 2 (WSHV-2). The identification of putative terminase gene sequences for all seven herpes-like viruses from sturgeons confirms their affinity with the family Herpesviridae (because this gene is unique to herpesviruses) and more distantly with T4-like bacteriophages. The two clades of sturgeon herpesviruses are therefore appropriately designated as Acipenserid herpesviruses 1 and 2, which correspond to the previous common names of white sturgeon herpesvirus types 1 and 2.


What is leaky can be risky: a study of the integrity of hospital gloves.
One thousand six-hundred and eighteen medical gloves were tested to determine whether, with current increased demands, these gloves are of high quality, i.e., free of leaks. The risk of exposure to potentially infected fluids when using leaky gloves was also estimated. Using a four-stage leak test, no significant difference was found between 64 of 790 (8.1%, range 0% to 44.4%) unsterile latex gloves and 11 of 210 (5.2%, range 1.7% to 21.7%) unsterile vinyl gloves (p = .21). Sterile surgical gloves (7 of 618, 1.13% [range 0% to 3%]) had fewer leaks compared to unsterile latex and vinyl gloves combined (p less than .0001). The safranin test was positive in 27 of 28 (96.4%) leaky gloves tested, indicating a high risk of exposure to potentially infected fluids when leaky gloves are used. Because of these findings, elements of "universal precautions" such as changing gloves after each patient contact and good handwashing after using gloves should be carefully observed. There is a need for the Food and Drug Administration to establish more stringent guidelines for manufacturing gloves and to verify compliance with these guidelines.


Gaze, goals and growing up: Effects on imitative grasping.
Developmental differences in the use of social-attention cues to imitation were examined among children aged 3 and 6 years old (n = 58) and adults (n = 29). In each of 20 trials, participants watched a model grasp two objects simultaneously and move them together. On every trial, the model directed her gaze towards only one of the objects. Some object pairs were related and had a clear functional relationship (e.g., flower, vase), while others were functionally unrelated (e.g., cardboard square, ladybug). Owing to attentional effects of eye gaze, it was expected that all participants would more faithfully imitate the grasp on the gazed-at object than the object not gazed-at. Children were expected to imitate less faithfully on trials with functionally related objects than those without, due to goal-hierarchy effects. Results support effects of eye gaze on imitation of grasping. Children's grasping accuracy on functionally related and functionally unrelated trials was similar, but they were more likely to only use one hand on trials where the object pairs were functionally related than unrelated. Implications for theories of imitation are discussed.


Altered Functional Connectivity Density in Young Survivors of Acute Lymphoblastic Leukemia Using Resting-State fMRI.
Using functional connectivity density (FCD) mapping measured by resting-state functional magnetic resonance imaging (rs-fMRI), an ultrafast data-driven graph theory approach, we attempted to study the abnormalities in neural activity of young survivors of acute lymphoblastic leukemia (ALL) and to explore the neuropathological evidence of chemotherapy-related cognitive impairment of patients. Twenty young survivors of ALL and 18 well-matched healthy controls (HCs) were recruited in this study. All ALL patients and healthy controls underwent rs-fMRI scans and completed neurocognitive testing. The between-group differences in short-range and long-range FCD were calculated by the option of degree centrality (DC) in MATLAB software after preprocessing. The correlations between the FCD value and each of the neurocognitive outcomes were analyzed in the ALL patients. The group-averaged FCD maps showed similar spatial patterns between the two groups. Compared with the HCs, ALL patients showed decreased long-range FCD in regions of the bilateral lingual gyrus, cingulate cortex, hippocampal gyrus, and right calcarine fissure. Simultaneously, decreased regions in the short-range FCD map were the bilateral lingual gyrus, cingulate cortex, parahippocampal gyrus and right calcarine fissure. Increased functional connectivity (FC) was observed between the region with decreased long-range FCD and the posterior cerebellar lobe, and decreased FC was observed between the region and the middle occipital gyrus, cuneus and lingual gyrus. Thus, there existed no brain areas with increased FCD. The decreased short-range FCD value of ALL patients was positively correlated with the score on the Digit Span Test (Forward), and the increased FC value was negatively correlated with the score on the Trail Making Test part A. Our results suggest the altered functional connectivity of young survivors of ALL in the posterior region of the brain and posterior lobe of the cerebellum. Alterations in spontaneous neuronal activity seem to parallel the neurocognitive testing, which indicates that the rs-fMRI could be used as a neuroimaging marker for neurological impairment in ALL patients.


Dynamic covalent assembly and disassembly of nanoparticle aggregates.
The quantitative assembly and disassembly of a new type of dynamic covalent nanoparticle (NP) building block is reported. In situ spectroscopic characterization reveals constitutionally adaptive NP-bound monolayers of boronate esters. Ditopic linker molecules are used to produce covalently connected AuNP assemblies, displaying open dendritic morphologies, and which, despite being linked by covalent bonds, can be fully disassembled on application of an appropriate chemical stimulus.


Self-assembly of responsive multilayered DNA nanocages.
Here we report the assembly of multilayered DNA nanocages. The layers can be separated in response to a chemical cue, ATP. This is an effort to increase the structural complexity of DNA nanocages. The structures have been characterized by native polyacrylamide gel electrophoresis, atomic force microscopy, and cryogenic electron microscopy. We envision that the layer-by-layer assembly strategy used in this study can be easily applied to other DNA nanocages to form Russian-doll-like semisolid structures, while the chemically activated layer separation makes a contribution to the development of "smart" DNA nanocages.


Endometriosis of the appendix with decidual polyp formation: a rare cause of acute appendicitis during pregnancy.
We report a case of a 28-year-old female, Grava 2, Para I, Ab. 0, who presented acute abdominal pain on the 21st week of her gestation. A diagnosis of acute appendicitis was entertained and an appendectomy performed. The pathologic specimen revealed an inflamed appendix with endometriosis and a marked decidual reaction. A decidual polyp, which occluded most of the appendiceal lumen, is proposed as a rare cause of acute appendicitis during pregnancy.


Non-invasive ventilation during surgery under neuraxial anaesthesia: a pathophysiological perspective on application and benefits and a systematic literature review.
Unlike general anaesthesia, neuraxial anaesthesia (NA) reduces the burden and risk of respiratory adverse events in the post-operative period. However, both patients affected by chronic obstructive pulmonary disease (COPD) and chest wall disorders and/or neuromuscular diseases may experience the development or the worsening of respiratory failure, even during surgery performed under NA; this latter negatively affects the function of accessory respiratory muscles, resulting in a blunted central response to hypercapnia and possibly in an exacerbation of cardiac dysfunction (NA-induced relative hypovolemia). According to European Respiratory Society (ERS) and American Thoracic Society (ATS) guidelines, non-invasive ventilation (NIV) is effective in the post-operative period for the treatment of both impaired pulmonary gas exchange and ventilation, while the intra-operative use of NIV in association with NA is just anecdotally reported in the literature. Whilst NIV does not assure a protected patent airway and requires the patient's cooperation, it is a handy tool during surgery under NA: NIV is reported to be successful for treatment of acute respiratory failure; it may be delivered through the patient's home ventilator, may reverse hypoventilation induced by sedatives or inadvertent spread of anaesthetic up to cervical dermatomes, and allow the avoidance of intubation in patients affected by chronic respiratory failure, prolonging the time of non-invasiveness of respiratory support (i.e., neuromuscular patients needing surgery). All these advantages could make NIV preferable to oxygen in carefully selected patients.


Characterization of hepatitis A virus capsid proteins with antisera raised to recombinant antigens.
The capsid proteins of hepatitis A virus (HAV) were expressed as fusion proteins of beta-galactosidase in E. coli using the expression vector lambda gt11. Four fusion proteins were stably expressed and used to immunize rabbits to obtain mono-specific antisera. The antisera were unable to neutralize viral infectivity or react with HAV by radioimmunoassay. Three of the antisera were able to recognize HAV antigens in infected BS-C-1 cells by immunofluorescence and denatured capsid proteins by immunoblot analysis. The antisera were used to investigate the migration of the capsid proteins in gels by immunoblot analysis using standard SDS-PAGE conditions and in gels containing urea. The migration of VP1 and VP3 correlated with their molecular weights predicted from the nucleotide sequence and was consistent in either the presence or absence of urea. However, VP2 migrated with an apparent molecular weight significantly higher than the predicted value and, in gels containing urea, migrated as a doublet. It is proposed that the upper band of this doublet represents VP0, the proteolytic precursor of VP2 and VP4. The relative molecular mass (Mr) of VP4 was estimated to be less than 1 kDa, which is substantially lower than the 2.5 kDa predicted from the nucleotide sequence.


Abolition of ischemic response to atrial pacing following aortocoronary bypass surgery.
To determine the effect of successful aortocoronary bypass surgery (ACBS) on left ventricular (LV) function, the ischemic response to right atrial pacing (RAP) was studied in 22 angina patients before and 3.8 +/- 1.1 months after surgery. All patients were free of angina after ACBS and had at least one patent graft. Before ACBS, RAP induced angina in 15 patients (Group 1) but not in 7 patients (Group 2). After ACBS, no patient had angina with RAP despite the increased maximum rate of pacing. Post-pacing LV end-diastolic pressure (LVEDP) after ACBS decreased in Group 1 from 25 +/- 6 to 15 +/- 6 mm Hg (P less than 0.01), but not in Group 2. Changes in ejection fraction, cardiac output, resting LVEDP, or LVEDP after LV angiography were not significant in either group and were therefore not useful in evaluating the result of ACBS. However the ischemic response to right atrial pacing was abolished by successful aortocoronary bypass surgery, suggesting improved myocardial perfusion during stress.


Impact of the design of neonatal intensive care units on neonates, staff, and families: a systematic literature review.
Newborn intensive care is for critically ill newborns requiring constant and continuous care and supervision. The survival rates of critically ill infants and hospitalization in neonatal intensive care units (NICUs) have improved over the past 2 decades because of technological advances in neonatology. The design of NICUs may also have implications for the health of babies, parents, and staff. It is important therefore to articulate the design features of NICU that are associated with improved outcomes. The aim of this study was to explore the main features of the NICU design and to determine the advantages and limitations of the designs in terms of outcomes for babies, parents, and staff, predominately nurses. A systematic review of English-language, peer-reviewed articles was conducted for a period of 10 years, up to January 2011. Four online library databases and a number of relevant professional Web sites were searched using key words. There were 2 main designs of NICUs: open bay and single-family room. The open-bay environment develops communication and interaction with medical staff and nurses and has the ability to monitor multiple infants simultaneously. The single-family rooms were deemed superior for patient care and parent satisfaction. Key factors associated with improved outcomes included increased privacy, increased parental involvement in patient care, assistance with infection control, noise control, improved sleep, decreased length of hospital stay, and reduced rehospitalization. The design of NICUs has implications for babies, parents, and staff. An understanding of the positive design features needs to be considered by health service planners, managers, and those who design such specialized units.


Effect of calcium supplementation on pregnancy-induced hypertension and preeclampsia: a meta-analysis of randomized controlled trials.
To review the effect of calcium supplementation during pregnancy on blood pressure, preeclampsia, and adverse outcomes of pregnancy. We searched MEDLINE and EMBASE for 1966 to May 1994. We contacted authors of eligible trials to ensure accuracy and completeness of data and to identify unpublished trials. Fourteen randomized trials involving 2459 women were eligible. Reviewers working independently in pairs abstracted data and assessed validity according to six quality criteria. Each trial yielded differences in blood pressure change between calcium supplementation and control groups that we weighted by the inverse of the variance. The pooled analysis showed a reduction in systolic blood pressure of -5.40 mm Hg (95% confidence interval [CI], -7.81 to -3.00 mm Hg; P<.001) and in diastolic blood pressure of -3.44 mm Hg (95% CI, -5.20 to -1.68 mm Hg; P<.001). The odds ratio for preeclampsia in women with calcium supplementation compared with placebo was 0.38 (95% CI, 0.22 to 0.65). Calcium supplementation during pregnancy leads to an important reduction in systolic and diastolic blood pressure and preeclampsia. While pregnant women at risk of preeclampsia should consider taking calcium, many more patient events are needed to confirm calcium's impact on maternal and fetal morbidity.


Structure and mechanical properties of poly(D,L-lactic acid)/poly(epsilon -caprolactone) blends.
A series of blends of the biodegradable polymers poly(D,L-lactic acid) and poly( epsilon -caprolactone) were prepared by varying mass fraction across the range of compositions. Tensile testing was performed at room temperature using an extensometer and the elastic modulus was calculated for each blend. The blends were also tested to failure, and the strain-at-failure and yield stress recorded. While the blend has been shown to have a lower critical solution temperature, the mechanical properties were insensitive to the annealing conditions. Scanning electron microscopy was used to characterize the blend microstructure and poor adhesion was observed at the interface between blend components. Differential scanning calorimetry was performed but the results were somewhat variable, indicating this blend may have complex phase behavior that depends sensitively on the method of preparation. However, nuclear magnetic resonance data indicate the two components are phase separated. A percolation model is used to explain the observed mechanical data and the results are consistent with the predictions of the Kerner-Uemura-Takayangi model. The results of these experiments demonstrate the utility of polymer blending in tuning material properties.


On the origins of parasite-extended phenotypes.
Parasites that adaptively manipulate the behavior of their host are among the most exciting adaptations that we can find in nature. The behavior of the host can become an extended phenotype of the parasites within animals such that the success and failure of the parasite's genome rely on precise change of the host's behavior. Evolutionary biology was borne from the close attention of naturalists such as Wallace and Darwin to phenotypic variation in seeking to understand the origins of new species. In this essay, I argue that we also need to think about the origins of parasite-extended phenotypes. This is a more difficult task than understanding the evolution of textbook examples of novelty such as the eyes of vertebrates or the hooves of horses. However, new tools such as phylogenomics provide an important opportunity to make significant progress in understanding the extended phenotypes of parasites. Knowing the origins of parasite-extended phenotypes is important as a goal all by itself. But the knowledge gained will also help us understand why complex manipulation is so rare and to identify the evolutionary tipping points driving its appearance.


Recombinant α-Klotho may be prophylactic and therapeutic for acute to chronic kidney disease progression and uremic cardiomyopathy.
α-Klotho is highly expressed in the kidney, and its extracellular domain is cleaved and released into the circulation. Chronic kidney disease (CKD) is a state of α-Klotho deficiency, which exerts multiple negative systemic effects on numerous organs including the cardiovascular system. Since acute kidney injury (AKI) greatly escalates the risk of CKD development, we explored the effect of α-Klotho on prevention and treatment on post-AKI to CKD progression and cardiovascular disease. Therein, ischemia reperfusion injury-induced AKI was followed by early administration of recombinant α-Klotho or vehicle starting one day and continued for four days after kidney injury (CKD prevention protocol). A CKD model was generated by unilateral nephrectomy plus contralateral ischemia reperfusion injury. Late administration of α-Klotho in this model was started four weeks after injury and sustained for 12 weeks (CKD treatment protocol). The prevention protocol precluded AKI to CKD progression and protected the heart from cardiac remodeling in the post-AKI model. One important effect of exogenous α-Klotho therapy was the restoration of endogenous α-Klotho levels long after the cessation of exogenous α-Klotho therapy. The treatment protocol still effectively improved renal function and attenuated cardiac remodeling in CKD, although these parameters did not completely return to normal. In addition, α-Klotho administration also attenuated high phosphate diet-induced renal and cardiac fibrosis, and improved renal and cardiac function in the absence of pre-existing renal disease. Thus, recombinant α-Klotho protein is safe and efficacious, and might be a promising prophylactic or therapeutic option for prevention or retardation of AKI-to-CKD progression and uremic cardiomyopathy.


Di-μ-thio-cyanato-κN:S;κS:N-bis-[bis-(2-methyl-1H-benzimidazole-κN)(thio-cyanato-κN)cadmium(II)].
The title compound, [Cd(2)(NCS)(4)(C(8)H(8)N(2))(4)], is a centrosymmetric dinuclear cadmium(II) complex in which each two metal ions are linked by a pair of thio-cyanate N:S-bridges. Two 2-methyl-benzimidazole N-atom donors and one terminal thio-cyanate N atom complete a highly distorted square-pyramidal geometry around the Cd atom. In the crystal structure, two N-H⋯S hydrogen-bonding inter-actions occur, resulting in a three-dimensional polymeric structure. The apical 2-methyl-benzimidazole ring and its symmetry-related counterpart are arranged in an anti-parallel manner with a centroid-centroid separation of 3.6050 (14) Å, indicative of a π-π inter-action.


Marine biodiversity in South Africa: an evaluation of current states of knowledge.
Continental South Africa has a coastline of some 3,650 km and an Exclusive Economic Zone (EEZ) of just over 1 million km(2). Waters in the EEZ extend to a depth of 5,700 m, with more than 65% deeper than 2,000 m. Despite its status as a developing nation, South Africa has a relatively strong history of marine taxonomic research and maintains comprehensive and well-curated museum collections totaling over 291,000 records. Over 3 million locality records from more than 23,000 species have been lodged in the regional AfrOBIS (African Ocean Biogeographic Information System) data center (which stores data from a wider African region). A large number of regional guides to the marine fauna and flora are also available and are listed. The currently recorded marine biota of South Africa numbers at least 12,914 species, although many taxa, particularly those of small body size, remain poorly documented. The coastal zone is relatively well sampled with some 2,500 samples of benthic invertebrate communities have been taken by grab, dredge, or trawl. Almost none of these samples, however, were collected after 1980, and over 99% of existing samples are from depths shallower than 1,000 m--indeed 83% are from less than 100 m. The abyssal zone thus remains almost completely unexplored. South Africa has a fairly large industrial fishing industry, of which the largest fisheries are the pelagic (pilchard and anchovy) and demersal (hake) sectors, both focused on the west and south coasts. The east coast has fewer, smaller commercial fisheries, but a high coastal population density, resulting in intense exploitation of inshore resources by recreational and subsistence fishers, and this has resulted in the overexploitation of many coastal fish and invertebrate stocks. South Africa has a small aquaculture industry rearing mussels, oysters, prawns, and abalone-the latter two in land-based facilities. Compared with many other developing countries, South Africa has a well-conserved coastline, 23% of which is under formal protection, however deeper waters are almost entirely excluded from conservation areas. Marine pollution is confined mainly to the densely populated KwaZulu-Natal coast and the urban centers of Cape Town and Port Elizabeth. Over 120 introduced or cryptogenic marine species have been recorded, but most of these are confined to the few harbors and sheltered sites along the coast.


Tissue extraction of DNA and RNA and analysis by the polymerase chain reaction.
Several DNA extraction techniques were quantitatively and qualitatively compared using both fresh and paraffin wax embedded tissue and their suitability investigated for providing DNA and RNA for the polymerase chain reaction (PCR). A one hour incubation with proteinase K was the most efficient DNA extraction procedure for fresh tissue. For paraffin wax embedded tissue a five day incubation with proteinase K was required to produce good yields of DNA. Incubation with sodium dodecyl sulphate produced very poor yields, while boiling produced 20% as much DNA as long enzyme digestion. DNA extracted by these methods was suitable for the PCR amplification of a single copy gene. Proteinase K digestion also produced considerable amounts of RNA which has previously been shown to be suitable for PCR analysis. A delay before fixation had no effect on the amount of DNA obtained while fixation in Carnoy's reagent results in a much better preservation of DNA than formalin fixation, allowing greater yields to be extracted.


Intravenous Glibenclamide Reduces Lesional Water Uptake in Large Hemispheric Infarction.
Background and Purpose- Prior studies have shown a linear relationship between computed tomography (CT)-derived radiodensity and water uptake, or brain edema, within stroke lesions. To test the hypothesis that intravenous glibenclamide (glyburide; BIIB093) reduces ischemic brain water uptake, we quantified the lesional net water uptake (NWU) on serial CT scans from patients enrolled in the phase 2 GAMES-RP Trial (Glyburide Advantage in Malignant Edema and Stroke). Methods- This was a post hoc exploratory analysis of the GAMES-RP study. Noncontrast CT scans performed between admission and day 7 (n=264) were analyzed in the GAMES-RP modified intention-to-treat sample. Quantitative change in CT radiodensity (ie, NWU) and midline shift (MLS) was measured. The gray and white matter NWU were also examined separately. Repeated-measures mixed-effects models were used to assess the effect of intravenous glibenclamide on MLS or NWU. Results- A median of 3 CT scans (interquartile range, 2-4) were performed per patient during the first 7 days after stroke. In a repeated-measures regression model, greater NWU was associated with increased MLS (β=0.23; 95% CI, 0.20-0.26; P<0.001). Treatment with intravenous glibenclamide was associated with reduced NWU (β=-2.80; 95% CI, -5.07 to -0.53; P=0.016) and reduced MLS (β=-1.50; 95% CI, -2.71 to -0.28; P=0.016). Treatment with intravenous glibenclamide reduced both gray and white matter water uptake. In mediation analysis, gray matter NWU (β=0.15; 95% CI, 0.11-0.20; P<0.001) contributed to a greater proportion of MLS mass effect, as compared with white matter NWU (β=0.08; 95% CI, 0.03-0.13; P=0.001). Conclusions- In this phase 2 post hoc analysis, intravenous glibenclamide reduced both water accumulation and mass effect after large hemispheric infarction. This study demonstrates NWU is a quantitative and modifiable biomarker of ischemic brain edema accumulation. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01794182.


Photobiomodulation prevents DNA fragmentation of alveolar epithelial cells and alters the mRNA levels of caspase 3 and Bcl-2 genes in acute lung injury.
Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are defined as pulmonary inflammation that could occur from sepsis and lead to pulmonary permeability and alveolar edema making them life-threatening diseases. Photobiomodulation (PBM) properties have been widely described in the literature in several inflammatory diseases; although the mechanisms of action are not always clear, this could be a possible treatment for ARDS/ALI. Thus, the aim of this study was to evaluate the mRNA levels from caspase-3 and BCL-2 genes and DNA fragmentation in lung tissue from Wistar rats affected by ALI and subjected to photobiomodulation by exposure to a low power infrared laser (808 nm; 100 mW; 3.571 W cm-2; four points per lung). Adult male Wistar rats were randomized into 6 groups (n = 5, for each group): control, PBM10 (10 J cm-2, 2 J and 2 seconds), PBM20 (20 J cm-2, 5 J and 5 seconds), ALI, ALI + PBM10 and ALI + PBM20. ALI was induced by intraperitoneal Escherichia coli lipopolysaccharide injection. Lung samples were collected and divided for mRNA expression of caspase-3 and Bcl-2 and DNA fragmentation quantifications. Data show that caspase-3 mRNA levels are reduced and Bcl-2 mRNA levels increased in ALI after low power infrared laser exposure when compared to the non-exposed ALI group. DNA fragmentation increased in inflammatory infiltrate cells and reduced in alveolar cells. Our research shows that photobiomodulation can alter relative mRNA levels in genes involved in the apoptotic process and DNA fragmentation in inflammatory and alveolar cells after lipopolysaccharide-induced acute lung injury. Also, inflammatory cell apoptosis is part of the photobiomodulation effects induced by exposure to a low power infrared laser.