A novel cytoplasmic tail MXXXL motif mediates the internalization of prostate-specific membrane antigen.
Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed at high levels in prostate cancer and in tumor-associated neovasculature. In this study, we report that PSMA is internalized via a clathrin-dependent endocytic mechanism and that internalization of PSMA is mediated by the five N-terminal amino acids (MWNLL) present in its cytoplasmic tail. Deletion of the cytoplasmic tail abolished PSMA internalization. Mutagenesis of N-terminal amino acid residues at position 2, 3, or 4 to alanine did not affect internalization of PSMA, whereas mutation of amino acid residues 1 or 5 to alanine strongly inhibited internalization. Using a chimeric protein composed of Tac antigen, the alpha-chain of interleukin 2-receptor, fused to the first five amino acids of PSMA (Tac-MWNLL), we found that this sequence is sufficient for PSMA internalization. In addition, inclusion of additional alanines into the MWNLL sequence either in the Tac chimera or the full-length PSMA strongly inhibited internalization. From these results, we suggest that a novel MXXXL motif in the cytoplasmic tail mediates PSMA internalization. We also show that dominant negative micro2 of the adaptor protein (AP)-2 complex strongly inhibits the internalization of PSMA, indicating that AP-2 is involved in the internalization of PSMA mediated by the MXXXL motif.


Pitfalls of stenting coarctation of an angulated right circumflex aortic arch in Goldenhar syndrome.
We report stenting of coarctation of an angulated right circumflex aortic arch (RCAA) using four Cheatham Platinum stents in a child with Goldenhar syndrome. Difficulties in measuring the accurate length of the curved and narrowed transverse aortic arch marked discrepancy between the luminal diameters of the long narrow transverse arch and wide descending thoracic aorta, increased displacement force caused by the 90° bend between the two parts resulted in repeated stent migrations. We discuss the tips to avoid distal stent migration in the setting of an angulated RCAA.


A prospective study in the evaluation of quality of life after vulvar cancer surgery.
The aim of this study was to prospectively monitor the patients' quality of life (QoL) after vulvar cancer surgery. The design was prospective clinical study. The study was set in the Department of Obstetrics and Gynecology, 2nd Medical Faculty of the Charles University and University Hospital Motol, Prague, Czech Republic. A group of 36 patients underwent vulvar cancer surgery: 24 patients were subject to inguinofemoral lymphadenectomy (RAD) and 12 to sentinel lymph node biopsy. To evaluate QoL, the European Organisation for Research and Treatment of Cancer, QoL questionnaires (QLQ-C30 and QLQ-CX24) were administered to patients before and 6 and 12 months after surgery. In patients with vulvar cancer after inguinofemoral lymphadenectomy, increased fatigue and impaired lymphedema were observed. In the group of patients after sentinel lymph node biopsy, none of the QoL variables worsened postoperatively. Comparing both groups 12 months after surgery, the RAD group had significantly worse outcomes in body image and cognitive functioning than the sentinel lymph node biopsy group.Patients in the RAD group, who received adjuvant radiotherapy (n = 13), had worse QoL in symptom experience (P < 0.05) at 6 and 12 months after the surgery than patients without radiotherapy (n = 11). Less radical surgery showed objectively better QoL results.


Fit for purpose: do we have the right tools to sustain NTD elimination?
Priorities for NTD control programmes will shift over the next 10-20 years as the elimination phase reaches the 'end game' for some NTDs, and the recognition that the control of other NTDs is much more problematic. The current goal of scaling up programmes based on preventive chemotherapy (PCT) will alter to sustaining NTD prevention, through sensitive surveillance and rapid response to resurgence. A new suite of tools and approaches will be required for both PCT and Intensive Disease Management (IDM) diseases in this timeframe to enable disease endemic countries to: 1. Sensitively and sustainably survey NTD transmission and prevalence in order to identify and respond quickly to resurgence. 2. Set relevant control targets based not only on epidemiological indicators but also entomological and ecological metrics and use decision support technology to help meet those targets. 3. Implement verified and cost-effective tools to prevent transmission throughout the elimination phase. Liverpool School of Tropical Medicine (LSTM) and partners propose to evaluate and implement existing tools from other disease systems as well as new tools in the pipeline in order to support endemic country ownership in NTD decision-making during the elimination phase and beyond.


Regulation of metabolism in pancreatic ductal adenocarcinoma via nanotechnology-enabled strategies.
Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy with insidious onset and early distal metastasis. Metabolic reprogramming, the autonomous changes in cellular bioenergetics driven by aberrant genetic events and crosstalk between cancer and non-cancer cells in the desmoplastic microenvironment, is pivotal for the rapid progression of PDAC. As an attractive therapeutic target, nucleoside metabolism is regulated by various anti-metabolic drugs for the clinical treatment of PDAC. Despite various challenges, such as poor drug delivery efficiency and off-target side effects, metabolic modification and intervention are emerging as promising strategies for PDAC therapy, enabled by the rapid development of nanotechnology-based drug delivery strategies. In this review, we discuss the metabolic characteristics of PDAC and highlight how the development of nanomedicine has boosted the development of new therapeutics for PDAC by modulating critical targets in metabolic reprogramming.


Overexpression of the cotton trihelix transcription factor GhGT23 in Arabidopsis mediates salt and drought stress tolerance by binding to GT and MYB promoter elements in stress-related genes.
Cotton (Gossypium hirsutum L.) is the world's most economically valuable textile crop. However, cotton plants are often subjected to numerous abiotic stresses that can dramatically limit yield. Trihelix transcription factors (TTFs) play important roles in abiotic stress responses in many plant species, and efforts to better understand their roles in cotton abiotic stress responses are ongoing. In this study, a member of the cotton TTF family (GhGT23) was functionally characterized. This protein contains a SANT domain and is a member of the SIP subfamily of TTF proteins. GhGT23 was significantly (p < 0.05) and highly expressed in cotton fiber compared to relatively low expression in other tissues. A significant (p < 0.05) increase in GhGT23 expression occurred in cotton seedlings within 12 hours of drought, salt, and ABA exposure. The GhGT23 protein localized in the nucleus but exhibited no signs of transactivation activity. GhGT23 overexpression in Arabidopsis conferred enhanced drought and salt stress tolerance. The expression of stress-related genes was higher in transgenic Arabidopsis expressing GhGT23 than in wild-type plants subjected to salt stress. The results of electrophoretic mobility shift assay revealed that GhGT23 could bind to the GT cis-elements GT-1Box (Box II), GT2-Box, GT3-Box, GT-3a (Site1-type), GT-3b, and Box as well as the MYB cis-elements MBS1 and MRE4. Our results demonstrate that GhGT23 positively regulates salt and drought stress responses, possibly by enhancing the expression of stress-related genes.


Trypsin inhibitors demonstrate antioxidant activities, inhibit A549 cell proliferation, and increase activities of reactive oxygen species scavenging enzymes.
Protease inhibitors are one of the most promising and investigated subjects for their role in pharmacognostical and pharmacological studies. This study aimed to investigate antineoplastic and antioxidant activity of trypsin inhibitors (TIs) isolated from three plant sources and their inhibitory role in the cell line. TIs were obtained from different plant sources. Antineoplastic potential on adenocarcinoma human alveolar basal epithelial cell line (A549) and normal Human Embryonic Kidney (HEK) was determined using MTT assay. Activities of antioxidant enzyme, nitric oxide scavenger, superoxide dismutase, glutathione S-transferase, and glutathione peroxidase were assessed in cell lines incubated with and without TIs. The outcome was analyzed by spectrophotometer. TIs showed the higher cytotoxicity on A549 cells as compared to normal HEK cell line. TIs exhibited fair increase in antioxidant enzyme activity in A549 cells as compared to control. This might be one of the strategies of antineoplastic effect in cancer cells. This study has reported the antioxidant and antineoplastic properties of these TIs for the first time in A549 cells (to the best of our knowledge). The results show that TIs possess ability to prevent cancer and diseases caused due to oxidative stress. Therefore, we conclude that TIs can be used as supplements along with the conventional drugs for increased efficacy in the treatment of diseases such as cardiovascular disease, atherosclerosis, and cancer.


Dynamics Correlation Network for Allosteric Switching of PreQ1 Riboswitch.
Riboswitches are a class of metabolism control elements mostly found in bacteria. Due to their fundamental importance in bacteria gene regulation, riboswitches have been proposed as antibacterial drug targets. Prequeuosine (preQ1) is the last free precursor in the biosynthetic pathway of queuosine that is crucial for translation efficiency and fidelity. However, the regulation mechanism for the preQ1 riboswitch remains unclear. Here we constructed fluctuation correlation network based on all-atom molecular dynamics simulations to reveal the regulation mechanism. The results suggest that the correlation network in the bound riboswitch is distinctly different from that in the apo riboswitch. The community network indicates that the information freely transfers from the binding site of preQ1 to the expression platform of the P3 helix in the bound riboswitch and the P3 helix is a bottleneck in the apo riboswitch. Thus, a hypothesis of "preQ1-binding induced allosteric switching" is proposed to link riboswitch and translation regulation. The community networks of mutants support this hypothesis. Finally, a possible allosteric pathway of A50-A51-A52-U10-A11-G12-G56 was also identified based on the shortest path algorithm and confirmed by mutations and network perturbation. The novel fluctuation network analysis method can be used as a general strategy in studies of riboswitch structure-function relationship.


Association between gestation length and lactation performance, lactation curve, calf birth weight and dystocia in Holstein dairy cows in Iran.
In this study, 252,798 lactations on 108,077 cows in 433 herds were used to determine the association between gestation length (GL) and lactation performance, lactation curve, calf birth weight and dystocia in Holstein dairy cows in Iran. The GL averaged 278.1 ± 5.41 d, was categorized as short (SGL; at 1 SD below the population mean), average (AGL; the population mean ± 1 SD), or long (LGL; at least 1 SD above the population mean). Factors including parity, calf gender and calving season were associated with the GL. Primiparous cows with SGL had less lactation performance than those with longer GL; however, there was no difference between those with AGL and LGL. Multiparous cows with longer GL always had more partial and 305-d lactation performance. Primiparous cows with SGL produced less milk at the beginning of lactation and at the peak than those with AGL or LGL; inverse trends were found for lactation persistency, upward and downward slopes of the lactation curve. Within multiparous, a direct relationship was found between GL and the peak yield, where cows with longer GL always produced more milk at the peak. Multiparous cows with SGL produced less milk at the beginning of lactation, reached their peaks later, had higher lactation persistency and showed a lower upward slope of lactation curve than those with AGL or LGL. There was a direct relationship between GL and calf birth weight, where cows with longer GL had calves with more weight at the birth. Within primiparous, cows with SGL had the lowest and those with LGL had the highest rate of dystocia. However, multiparous cows with AGL had a lower rate of dystocia than those with SGL or LGL. Although there was a direct relationship between GL and lactation performance, intermediate GL seems optimal when considering dystocia.


N-Propionylated group B meningococcal polysaccharide mimics a unique bactericidal capsular epitope in group B Neisseria meningitidis.
The N-propionylated group B meningococcal polysaccharide (NPrGBMP) mimics a unique protective epitope on the surface of group B meningococci (GBM) and Escherichia coli K1. Using a series of monoclonal antibodies (mAbs) induced by the NPrGBMP-monomeric tetanus toxoid (TT) conjugate vaccine it was demonstrated that mAbs having specificities for both extended and conventional short segments of the NPrGBMP were formed, but only the former were bactericidal, and/or gave passive protection against live challenge by GBM. The failure of mAbs specific for short epitopes to protect was further established when (NeuPr)4-TT was used as the vaccine. Of all the mAbs produced that were specific for short internal segments of the NPrGBMP, none were protective, despite the fact that most of them cross-react with the GBM capsular polysaccharide. In contrast, most of the protective mAbs produced by NPrGBMP- TT did not recognize the group B meningococcal polysaccharide (GBMP) unless it was present in its aggregated high molecular weight form. The bactericidal epitope mimicked by the NPrGBMP was shown to be ubiquitous in the capsule of both GBM and E. coli K1 using immunogold labeling techniques and, because of its unique properties, its identification could be significant in the development of a comprehensive conjugate vaccine against group B meningococcal meningitis. This is because most known human alpha(2-8)-polysialic acid self-antigens can be accommodated in 30-50 alpha(2-8)-linked sialic acid residues, which is roughly equivalent to an 11-kD length of the GBMP. It has been hypothesized that the formation of the protective epitope on the surface of GBM is due to the interaction of helical segments of the GBMP with another molecule and that the protective epitope is mimicked by the NPrGBMP. Support for the above hypothesis is provided by the fact that the protective NPrGBMP epitope has a similar unusual length dependency to that of the GBMP epitope.


Metabolic Inflexibility Is an Early Marker of Bed-Rest-Induced Glucose Intolerance Even When Fat Mass Is Stable.
The effects of energy-balanced bed rest on metabolic flexibility have not been thoroughly examined. We investigated the effects of 21 days of bed rest, with and without whey protein supplementation, on metabolic flexibility while maintaining energy balance. We hypothesized that protein supplementation mitigates metabolic inflexibility by preventing muscle atrophy. Randomized crossover longitudinal study conducted at the German Aerospace Center, Cologne, Germany. Ten healthy men were randomly assigned to dietary countermeasure or isocaloric control diet during a 21-day bed rest. Before and at the end of the bed rest, metabolic flexibility was assessed during a meal test. Secondary outcomes were glucose tolerance by oral glucose tolerance test, body composition by dual energy X-ray absorptiometry, ectopic fat storage by magnetic resonance imaging, and inflammation and oxidative stress markers. Bed rest decreased the ability to switch from fat to carbohydrate oxidation when transitioning from fasted to fed states (i.e., metabolic inflexibility), antioxidant capacity, fat-free mass (FFM), and muscle insulin sensitivity along with greater fat deposition in muscle (P < 0.05 for all). Changes in fasting insulin and inflammation were not observed. However, glucose tolerance was reduced during acute overfeeding. Protein supplementation did not prevent FFM loss and metabolic alterations. Physical inactivity triggers metabolic inflexibility, even when energy balance is maintained. Although reduced insulin sensitivity and increased fat deposition were observed at the muscle level, systemic glucose intolerance was detected only in response to a moderately high-fat meal. This finding supports the role of physical inactivity in metabolic inflexibility and suggests that metabolic inflexibility precedes systemic glucose intolerance.


An insect anti-antiaphrodisiac.
Passive mechanisms of mate guarding are used by males to promote sperm precedence with little cost, but these tactics can be disadvantageous for their mates and other males. Mated females of the plant bug Lygus hesperus are rendered temporarily unattractive by seminal fluids containing myristyl acetate and geranylgeranyl acetate. These antiaphrodisiac pheromones are gradually released from the female's gonopore, declining until they no longer suppress male courtship. Because starting quantities of these compounds can vary widely, the repellant signal becomes less reliable over time. Evidence was found of a complimentary mechanism that more accurately conveys female mating status. Once inside the female, geranylgeranyl acetate is progressively converted to geranylgeraniol then externalized. Geranylgeraniol counteracts the antiaphrodisiac effect despite having no inherent attractant properties of its own. This is the first evidence for such an anti-antiaphrodisiac pheromone, adding a new element to the communication mechanisms regulating reproductive behaviors.


Flow sorting of antigen-binding B cell subsets.
Antigen binding was used as a probe in the definition of functional B cell heterogeneity. Unprimed, anti-Thy 1 and complement-treated spleen cells were stained with fluorescent trinitrophenylated bovine serum albumin (FL-TNP-BSA). These cells were sorted, fluorescence negative from fluorescence positive, by using a multiparameter cell sorter and assayed for precursor frequency in antibody responses to TNP by limiting dilution analysis. The cells that bound FL-TNP-BSA were demonstrated to be enriched for antibody-forming precursors to the antigens TNP-lipopolysaccharide (LPS), TNP-sheep red blood cells (SRBC), and TNP- or DNP-Ficoll, whereas the fluorescence negative cells were depleted for these responses. B cells that bound FL-TNP-BSA were then sorted into populations that bound a moderate or high amount of FL-TNP-BSA. The B cells responsive to TNP-LPS and TNP-SRBC were present in both the moderate and high binding populations. In contrast, the B cells responsive to TNP- or DNP-Ficoll were present only in the cells that bound a moderate amount of FL-TNP-BSA. These experiments suggest that there is a population of B cells in adult mouse spleen that binds large amounts of antigen, and that can respond to antigen carried on LPS or SRBC but not carried on Ficoll.


Taxonomy-based partitioning of the Gene Ontology.
The Gene Ontology (GO) project is a collaborative effort to construct ontologies which facilitate biologically meaningful annotation of gene products. In some situations, only a generic or a species-specific subset of all GO terms is required to annotate and analyze the results of a particular biomedical experiment. We show that by defining explicit links between terms in the GO and terms in the Taxonomy of Species (TS) it is possible to automatically create partitions of the GO according to various taxonomic criteria. Our framework is based on three logically defined relations--validity, specificity, and relevance--used to link terms in the Gene Ontology with terms in the Taxonomy. The major advantages of this approach, as compared to the traditional GO slims methodology, are: unambiguous semantics of GO-TS annotations, significant reduction of the effort needed to manually select GO terms appropriate for a particular taxonomic context, ability to generate views of the GO even for taxa for which no explicit links with GO terms exist, logical consistency of such views, and automated updates of TS-dependent GO subsets. Incorporation of the proposed framework into the GO may improve the usability of the ontology for those scientists who focus their research on a particular species or a specific class of organisms.


MACROARCHITECTONIC PECULIARITIES OF LONG BONES IN THE LOWER EXTREMITY.
Сontemporary forensic practice requires evaluation of the influence of long bones macroarchitecture on the mechanics of their destruction in case of blunt injuries, which finally might enhance validity and evidence of expert's reports. Therefore objective of the study is obtaining new scientific knowledge concerning macroarchitectural characteristics of the major portions of long bones of the lower limbs, detection of their influence on the regularities of destructive processes of bones in case of blunt injuries. 128 cases with fractures of the lower extremity long bones were examined from forensic-medical practical work, removed from male and female bio mannequins aged from 18 to 65 while conducting forensic expertise. The main morphological parameters (circumference, compact osseous tissue thickness, size and square of the medullar canal) characterizing macroarchitectonics of the femoral, tibial and fibular bones are studied. Their importance and role in occurring fractures of the given bones in forensic practical work are indicated. Different portions of the lower limb long bones possess considerable amount of the structural-functional characteristics. The sizes of the medullar canal (in the form of medullar parameter) and its square influence on the formation of fracture the most considerably among macroarchitectural characteristics.


Case Report: Encephalitis, with Brainstem Involvement, Following Checkpoint Inhibitor Therapy in Metastatic Melanoma.
Checkpoint inhibitors are increasingly being used in the treatment of malignant melanoma and other cancers. With the use of such therapies, autoimmune-mediated adverse events in the central and peripheral nervous system are likely to occur more frequently. We report a unique case of brainstem encephalitis with a sudden lethal outcome following ipilimumab and pembrolizumab therapy in a patient with malignant melanoma. The autopsy showed a diffuse nodular activation of microglia in the whole encephalon with prominent intraparenchymal and perivascular lymphocytic infiltration of the brainstem. Non-infectious brainstem encephalitis is a well-recognized subset of paraneoplastic encephalitis. Brainstem involvement is usually accompanied by a wide spectrum of signs and symptoms, which were not observed in this case. The timing of the clinical symptoms as well as the histopathological findings suggest an autoimmune-adverse event of ipilimumab and pembrolizumab administration rather than a paraneoplastic disorder. In the presence of neurological symptoms, immediate cessation of the immunotherapy and immunosuppressive therapy may lead to successful therapeutic intervention, as described in previous reports. Therefore, it is crucial that physicians are aware of the possible side effects of immunotherapies on the nervous system. Metastatic melanoma patients treated with the anti-CTLA-4 inhibitor ipilimumab have a high utilization of various types of health care services, such as inpatient hospital stays or doctor visits. There are differences across countries regarding patterns of health care utilization and economic burden of the disease. Health care services are used more frequently after patients experience progression of their disease. The study highlights that better therapies leading to durable response in patients with metastatic melanoma have the potential to decrease health care costs and patient burden in terms of hospitalizations and other health care services.


[Pathogenetic significance of methicillin resistant Staphylococcus aureus (MRSA) in chronic wounds].
The colonisation and infection with methicillin-resistant staphylococcus aureus (MRSA) represent an interdisciplinary problem especially in the treatment of chronic wounds. To prevent medical wound-healing centres of becoming vectors for further epidemics it makes sense to take regular bacterial smears of all patients with chronic wounds to identify, isolate and treat patients with MRSA colonisation or infection. Especially infections should only be treated after microbiological diagnostics had been done to allow systemic treatment with antibiotics in accordance with the specific resistances. Otherwise the uncritical use of broad-spectrum- or reserve-antibiotics supports the critical development of further resistances.


Shear stress-induced MMP1 and PDE2A expressions in coronary atherosclerosis.
Biomechanical stress plays an essential role in coronary atherosclerosis (CAS), however, inter-relations between mechanical conditions and gene expressions remain unclear. We constructed finite element model of CAS to map human wall shear stress (WSS). Biopsy aortic tissue samples were obtained from 3 CAS patients. Gene expression pattern in CAS was analyzed by GEO datasets. Immunofluorescence staining and western blot confirmed protein expression and localization. Peak WSS was significantly increased in the vessel stenosis of CAS at 0.25 s (mean 55.1 Pa). Analyses results of GSE76275 showed matrix metalloproteinases1 (MMP1) and phosphodiesterase-2A (PDE2A) up-regulation in endothelial shear responsiveness, which was further validated and localized in vascular endothelial cells, smooth muscle cells and other cells by double immunofluorescence staining. Western blotting assay demonstrated up-regulation of MMP1 and PDE2A expression dependent on the WSS. MMP1 and PDE2A up-regulations rely on increased WSS in development and risk of CAS, suggesting that their elevation may be potential target for diagnosis and treatment (Fig. 3, Ref. 28).


The role of the antitragicus muscle in plical folding of the pinna.
The antitragicus is one of six intrinsic muscles of the external ear. This study examined the anatomical variations of the muscle and its association with prominent ears. Twenty-seven consecutive patients presenting for correction of prominent ears were recruited into the study. In each case, the antihelical fold was assessed preoperatively by a single investigator. A standard anterior cartilage scoring otoplasty was performed, and the presence and quality of the antitragicus muscle were assessed by a second investigator. For statistical analysis, the qualitative assessment of the fold and the muscle was given a numerical value. It was then possible to plot the qualitative assessment of the fold against the muscle, and correlations between muscle and fold were calculated. The presence of the muscle was associated with an absent antihelical fold, whereas a well-defined antihelical fold was associated with an absent muscle (p < 0.0001). The authors propose that the presence of a well-formed antitragicus muscle, which exerts an anterior pull on the cauda helicis, contributes to the poor development of the antihelical fold.


Soluble, prolonged-acting insulin derivatives. III. Degree of protraction, crystallizability and chemical stability of insulins substituted in positions A21, B13, B23, B27 and B30.
It was previously demonstrated that insulins to which positive charge has been added by substituting B13 glutamic acid with a glutamine residue, B27 threonine with an arginine or lysine residue, and by blocking the C-terminal carboxyl group of the B-chain by amidation, featured a prolonged absorption from the subcutis of rabbits and pigs after injection in solution at acidic pH. The phenomenon is ascribed to a low solubility combined with the readiness by which these analogs crystallize as the injectant is being neutralized in the tissue. However, acid solutions of insulin are chemically unstable as A21 asparagine both deamidates to aspartic acid and takes part in formation of covalent dimers via alpha-amino groups of other molecules. In order to circumvent the instability, substitutions were introduced in position A21, in addition to those in B13, B27 and B30, challenging the fact that A21 asparagine has been conserved in this position throughout the evolution. Biological potency was retained when glycine, serine, threonine, aspartic acid, histidine and arginine were introduced in this position, although to a varying degree. In the crystal structure of insulin a hydrogen bond bridges the alpha-nitrogen of A21 with the backbone carbonyl of B23 glycine. In order to investigate the importance of this hydrogen bond for biological activity a gene for the single-chain precursor B-chain(1-29)-Ala-Ala-Lys-A-chain(1-21) featuring an A21 proline was synthesized. However, this single-chain precursor failed to be properly produced by yeast, pointing to the formation of this hydrogen bond as an essential step in the folding process. The stability of the A21-substituted analogs in acid solutions (pH 3-4) with respect to deamidation and formation of dimers was approximately 5-10 times higher than that of human insulin in neutral solution. The rate of absorption of most insulins is decreased by increasing the Zn2+ concentration of the preparation. However, one analog with A21 glycine showed first-order absorption kinetics in pigs with a half-life of approximately 25 h, independent of the Zn2+ concentration. The day-to-day variation of the absorption of this analog was significantly lower than that of the conventional insulin suspensions, a property that might render such an insulin useful in the attempts to improve glucose control in diabetics by a more predictable delivery of basal insulin.


An investigation on the level of awareness, attitude, and interest among medicine, dentistry, and pharmacy students toward their majors on entering university: The case of Islamic Azad University, Tehran medical sciences branch.
Having awareness, interest, and positive attitude toward one's fields of study leads to the development of a compatibility between demands and expectations on the one hand and future career on the other hand. This study was carried out to determine the level of awareness, attitude, and interest of medicine, dentistry, and pharmacy students of Islamic Azad University, Tehran Medical Sciences Branch toward their own field of study on entering university. This research is a basic descriptive study conducted on 273 students who had just entered university. This study was performed using census. Data collection instrument was a four-part questionnaire which included demographic information, and questions measuring students' awareness, attitude, and interest. With regard to their field of study, there was no statistically significant difference in the average of students' awareness (P = 0.731). The attitude of medicine students was significantly more positive than pharmacy and dentistry students (P < 0.001), and the attitude of dentistry students was significantly more positive than that of pharmacy students (P = 0.460). Medical students' interest level was significantly higher than that of pharmacy and dentistry students (P < 0.05), and the interest level of dentistry students was significantly greater than the interest level of pharmacy students (P = 024/0). There was a statistically significant positive relationship between awareness and attitude and between awareness and interest in all of the study subjects (P < 0.001). The study results indicated that having a high level of awareness toward one's major led students studying in medicine, dentistry, and pharmacy to experience a more positive attitude and a higher level of interest. Thus, before entering the university, academic counseling will be beneficial for acquiring a better understanding of most majors, a goal which could be provided through school, social media, and family.


Centre-based care is a significant predictor of lower body mass index in early childhood: Longitudinal evidence from Chile.
The prevalence of childhood overweight has increased by approximately 50% in the past three decades, becoming a major public health concern worldwide. In Chile, an upper middle-income country, about 38% of children between two and four years of age are overweight, almost double the average in Latin America and the Caribbean. Various environmental and individual factors, and their interactions, affect childhood weight. Emerging evidence suggests childcare may also matter. Because the public provision of centre-based care is growing, childcare may be a useful policy tool to help prevent childhood overweight. Using a nationally representative longitudinal survey of ~ 15 000 children in Chile (2010 and 2012), we estimated whether the type of child care (centre-based or maternal) a child attended at age 24 to 36 months was a significant predictor of the child's sex-and-age-specific body-mass-index (BMI) at age 36-48 months. We restricted our sample to children in full-time maternal care at baseline (12-24 months of age; n = 1273), but tested the robustness of results with the full sample. We compared children in centre-based care and in maternal care using difference-in-difference estimators and propensity score matching, and adjusted our estimates using child, family, and neighborhood characteristics. Children attending centre-based care had 0.27 SD lower BMI than children in maternal care at follow-up (P < 0.05). We found suggestive evidence this association may be modulated by the child's socioeconomic status and by how frequently the child watched television: we found smaller BMI changes for children at the bottom 80% of socioeconomic status (P < 0.05) and also for children who frequently watched television (P < 0.10). Our results were robust to various model specifications. Our findings suggest centre-based care programs, with adequate regulation and enforcement, may be a useful support to help curb the early childhood overweight epidemic, in addition to known effects in labor supply and child development.


[Cerebral salt wasting syndrome in bacterial meningitis].
Subarachnoid hemorrhage is the most common cause of cerebral salt wasting syndrome. There are few reports of this condition in infectious meningitis. We describe a patient with hyponatremia and bacterial meningitis. Hyponatremia rapidly improved after administration of sodium chloride. The purpose of this report is to alert clinicians to the fact that hyponatremic patients with central nervous system disease do not necessarily have a syndrome of inappropriate secretion of antidiuretic hormone (SIADH), but may have cerebral salt wasting syndrome. By contrast with SIADH, the treatment requires saline administration.


Synthesis of Highly Functionalized Spirobutenolides via a Nitroalkane-Mediated Ring Contraction of 2-Oxobenzo[ h]chromenes through Denitration.
A facile synthesis of highly functionalized spirobutenolides was carried out by a nitroalkane carbanion-induced ring opening and relactonization via a denitration reaction of 2-oxo-5,6-dihydro-2 H-benzo[ h]chromene-3-carbonitriles and 2-oxo-2,5-dihydrothiochromeno[4,3- b]pyran-3-carbonitriles. However, when nitroethane was used as a nucleophile source in lieu of nitromethane, a mixture of ( E)- and ( Z)-isomers of the corresponding spirobutenolides was obtained in a different ratio. The structure and geometry of the product were confirmed by single-crystal X-ray diffraction. The isolated ( E)- and ( Z)-butenolides with the treatment with sodium ethoxide in DMF at room temperature provided highly substituted trienes via an allylic ring opening followed by decarboxylation.


Impact of psychiatric symptomatology on neuropsychological assessment performance in persons with TBI: A comparison of OEF/OIF veteran and civilian samples.
To assess whether increased incidence of post-traumatic stress disorder and depressive symptomatology in veterans with combat-related traumatic brain injury might help account for neurocognitive impairment relative to civilians with traumatic brain injury. Neuropsychological assessment data of 53 Operation Enduring Freedom/Operation Iraqi Freedom veterans and 48 civilians with positive history of traumatic brain injury were analyzed to assess differences with respect to cognitive performance. Retrospective analysis of data including neurocognitive test performance and self-reported symptoms of post-traumatic stress disorder and depression. Results showed worse neurocognitive performance (i.e. RBANS Total Index score) in the veteran sample relative to the civilian sample [F(1,99) = 3.92, p = .05, ƞ2 = .04], particularly on tasks measuring attentional capabilities [F(1,99) = 9.18, p = .003, ƞ2 = .09]. Additional analyses found that after controlling for post-traumatic stress disorder symptomatology, differences were no longer significant. Broad correlations between measures also showcased attenuated relationships after controlling for both post-traumatic stress disorder and depressive symptomatology using partial correlations Conclusion: Findings suggest that the presence of post-traumatic stress disorder and depressive symptomatology negatively impacts cognitive performance across neuropsychological assessment above and beyond deficits related to traumatic brain injury.


Massive intravascular hemolysis in a patient infected by a Clostridium perfringens.
Clostridium perfringens infection is a very rare cause of massive intravascular hemolysis, but it should always be kept in mind, since only early treatment can rescue patients from an otherwise rapidly fatal outcome. We report a case of a 78-year-old diabetic male who was admitted complaining of general fatigue, dark red urine, and vomiting. His blood revealed massive hemolysis. Computer tomography demonstrated huge liver abscess in the right lobe of the liver. About 1 h after admission, he suddenly fell into a critical condition. He died 3 h after admission in spite of intensive care and resuscitation. Clostridium perfringens was detected from the blood taken before death and from liver abscess by biopsy after death. We concluded that this patient died of acute massive intravascular hemolysis in septicemia caused by Clostridium perfringens infection.


Targeting cardiac hypertrophy: toward a causal heart failure therapy.
Cardiac hypertrophy is commonly observed in conditions of increased hemodynamic or metabolic stress. This hypertrophy is not compensatory but rather reflects activation of maladaptive cellular processes that promote disease progression. Myocardial hypertrophy serves as a diagnostic and prognostic marker of cardiac remodeling, and underlying regulatory processes have provided effective therapeutic targets to slow disease progression and improve outcome. We review hypertrophic signaling pathways in cardiomyocytes and discuss established and novel targets for pharmacological intervention. New drugs in the pipeline include the third generation aldosterone antagonists (PF-03882845 and BAY94-8862) and biased angiotensin II receptor agonists. Furthermore, different approaches to stimulate cGMP-dependent protective signaling are currently evaluated in clinical trials, including the combination of the vasopeptidase neprilysin inhibitor and an angiotensin receptor blocker (ARNi). In an overview on cardiomyocyte hypertrophic signaling, we also highlight emerging experimental treatment concepts such as inhibition of Ca-mediated transcriptional regulation, adeno-associated viruses for sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA2a), PI3 kinase gene transfer and microRNA-based therapy. We conclude that antihypertrophic therapy extends beyond blocking the classical β-adrenergic and renin-angiotensin-aldosterone system-dependent signaling cascades, although new therapies require clinical validation regarding outcome.


Improving Website Hyperlink Structure Using Server Logs.
Good websites should be easy to navigate via hyperlinks, yet maintaining a high-quality link structure is difficult. Identifying pairs of pages that should be linked may be hard for human editors, especially if the site is large and changes frequently. Further, given a set of useful link candidates, the task of incorporating them into the site can be expensive, since it typically involves humans editing pages. In the light of these challenges, it is desirable to develop data-driven methods for automating the link placement task. Here we develop an approach for automatically finding useful hyperlinks to add to a website. We show that passively collected server logs, beyond telling us which existing links are useful, also contain implicit signals indicating which nonexistent links would be useful if they were to be introduced. We leverage these signals to model the future usefulness of yet nonexistent links. Based on our model, we define the problem of link placement under budget constraints and propose an efficient algorithm for solving it. We demonstrate the effectiveness of our approach by evaluating it on Wikipedia, a large website for which we have access to both server logs (used for finding useful new links) and the complete revision history (containing a ground truth of new links). As our method is based exclusively on standard server logs, it may also be applied to any other website, as we show with the example of the biomedical research site Simtk.


A comparison of sex steroid concentration levels in the vitreous and serum of patients with vitreoretinal diseases.
The purpose of this study was to compare steroid hormone concentration levels in the vitreous and serum of vitreoretinal disease patients to elucidate the possibility of neurosteroid production in the retina. Serum and vitreous samples were collected from vitrectomy patients, and estradiol (E2) and testosterone (T) concentrations were measured using electro-chemiluminescence immunoassay. We measured E2 in epiretinal membrane (ERM, n = 14), macular hole (MH, n = 18), proliferative diabetic retinopathy (PDR, n = 20), and retinal detachment (RD, n = 19) cases, and T in ERM (n = 14), MH (n = 17), PDR (n = 13), and RD (n = 17) cases. No statistically significant age differences existed among the groups. Mean respective E2 concentrations (pg/ml) in the male/female vitreous were ERM: 6.67±4.04/18.82±7.10, MH: 10.3±7.02/17.00±4.8, PDR: 4.2±3.05/15.83±3.46, and RD: 10.00±4.58/16.06±4.57, while those in serum were ERM: 31.67±5.51/5.82±1.08, MH: 21.00±8.89/7.53±3.2, PDR: 29.20±7.07/12.75±10.62, and RD: 24.33±6.51/7.5±4.42. E2 concentrations were significantly higher (P<0.001) in the male serum than vitreous, yet significantly higher in the female vitreous than serum. Mean respective T concentrations (ng/ml) in the male/female vitreous were ERM: 0.15±0.03/0.15±0.01, MH: 0.15±0.01/0.15±0.01, PDR: 0.15±0.03/0.16±0.12, and RD: 0.14±0.01/0.17±0.08, while those in serum were ERM: 4.54±1.46/0.16±0.01, MH: 8.04±2.29/0.16±0.10, PDR: 5.14±1.54/0.22±0.11, and RD: 3.24±0.75/0.17±0.10. T concentrations were high in the male serum, yet extremely low in the male and female vitreous and female serum. High concentrations of E2 were found in the vitreous, and women, in particular, exhibited significantly higher concentrations in the vitreous than in the serum. This finding suggests the possibility that in vitreoretinal disease cases, the synthesis of E2 is increased locally only in female eyes.


The hupC gene product is a component of the electron transport system for hydrogen oxidation in Pseudomonas hydrogenovora.
The hydrogenase gene cluster containing nine genes (hupSLCDFGHIJ) was identified by sequencing of an 8.8-kb DNA region from Pseudomonas hydrogenovora. To investigate the function of the hupC gene product, we isolated a hupC-null mutant (HID3) of P. hydrogenovora by introducing an in-frame deletion into the hupC. The mutant, HID3, could not grow autotrophically but retained half the level of hydrogenase activity of the wild-type strain. Results of the oxygen consumption test and Western blot analysis revealed that the hupC gene product is a b-type cytochrome but not involved in the hydrogenase maturation process.


Using blood hemoglobin for blood analysis.
This paper demonstrates that the spectrophotometric properties of blood hemoglobin (Hb) can be used for the direct determination of biochemical compounds in blood. Glucose is used as a model, but the methodology can be applied to many other compounds (only a previous enzymatic reaction producing H(2)O(2) is needed). In order to develop the method, a model relating the Hb absorbance variation during the reaction with the glucose concentration has been developed to provide theoretical support for the method and to predict its application to other compounds. In addition, clear blood samples need to be prepared without pre-treatment and lateral reactions of H(2)O(2) with other blood constituents need to be blocked; this has been achieved with 100 : 1 v/v blood dilution in bi-distilled water and azide addition. The linear response range of the method can be fitted between 2 and 540 mg dL(-1) glucose relative to the original blood sample (RSD about 4%, 70 mg dL(-1)). The analyte concentration can be obtained by an absolute calibration method or by the standard addition method; both have been applied for direct glucose determination in several blood samples and good correlations with those obtained by an automatic analyzer have been obtained.


Effect of lowest harmonic rank on fundamental-frequency difference limens varies with fundamental frequency.
This study investigated the relationship between fundamental frequency difference limens (F0DLs) and the lowest harmonic number present over a wide range of F0s (30-2000 Hz) for 12-component harmonic complex tones that were presented in either sine or random phase. For fundamental frequencies (F0s) between 100 and 400 Hz, a transition from low (∼1%) to high (∼5%) F0DLs occurred as the lowest harmonic number increased from about seven to ten, in line with earlier studies. At lower and higher F0s, the transition between low and high F0DLs occurred at lower harmonic numbers. The worsening performance at low F0s was reasonably well predicted by the expected decrease in spectral resolution below about 500 Hz. At higher F0s, the degradation in performance at lower harmonic numbers could not be predicted by changes in spectral resolution but remained relatively good (<2%-3%) in some conditions, even when all harmonics were above 8 kHz, confirming that F0 can be extracted from harmonics even when temporal envelope or fine-structure cues are weak or absent.


Lipoprotein (a) phenotypes in south Indian patients with coronary artery disease.
Plasma lipoprotein (a) levels in the Indian population are varied; this study was undertaken to determine the relationship between plasma lipoprotein (a) levels and their phenotypes in a group of south Indian patients with coronary artery disease. A total of 104 patients with angiographically proven coronary artery disease were compared with 104 age- and sex-matched controls with no risk factors such as hypertension, diabetes and smoking. Lipoprotein (a) levels were measured by an in-house ELISA method and its phenotyping was done by SDS agarose gel electrophoresis. Plasma lipoprotein (a) levels were significantly elevated in patients with coronary artery disease as compared to controls (33.4+/-26.1 mg/dl v. 21.4+/-12.8 mg/dl; p<0.01). Lipoprotein (a) phenotyping showed that low-molecular weight isoforms were found only in 19.2% of the patients with coronary artery disease and their plasma lipoprotein (a) levels were significantly elevated compared to coronary artery disease patients with higher molecular weight isoforms (50.9+/-34.2 mg/dl v. 29.24+/-20.06 mg/dl; p<0.001). Plasma lipoprotein (a) levels are significantly elevated in patients with coronary artery disease as compared to controls. The commoner phenotype in a South Indian population is the larger apolipoprotein (a). in which the lipoprotein (a) levels are lower. Hence the contribution of lipoprotein (a) phenotype to the lipoprotein (a) levels in our population, if any, is modest.


A Pygopus 2-Histone Interaction Is Critical for Cancer Cell Dedifferentiation and Progression in Malignant Breast Cancer.
Pygopus 2 (Pygo2) is a coactivator of Wnt/β-catenin signaling that can bind bi- or trimethylated lysine 4 of histone-3 (H3K4me2/3) and participate in chromatin reading and writing. It remains unknown whether the Pygo2-H3K4me2/3 association has a functional relevance in breast cancer progression in vivo. To investigate the functional relevance of histone-binding activity of Pygo2 in malignant progression of breast cancer, we generated a knock-in mouse model where binding of Pygo2 to H3K4me2/3 was rendered ineffective. Loss of Pygo2-histone interaction resulted in smaller, differentiated, and less metastatic tumors, due, in part, to decreased canonical Wnt/β-catenin signaling. RNA- and ATAC-sequencing analyses of tumor-derived cell lines revealed downregulation of TGFβ signaling and upregulation of differentiation pathways such as PDGFR signaling. Increased differentiation correlated with a luminal cell fate that could be reversed by inhibition of PDGFR activity. Mechanistically, the Pygo2-histone interaction potentiated Wnt/β-catenin signaling, in part, by repressing the expression of Wnt signaling antagonists. Furthermore, Pygo2 and β-catenin regulated the expression of miR-29 family members, which, in turn, repressed PDGFR expression to promote dedifferentiation of wild-type Pygo2 mammary epithelial tumor cells. Collectively, these results demonstrate that the histone binding function of Pygo2 is important for driving dedifferentiation and malignancy of breast tumors, and loss of this binding activates various differentiation pathways that attenuate primary tumor growth and metastasis formation. Interfering with the Pygo2-H3K4me2/3 interaction may therefore serve as an attractive therapeutic target for metastatic breast cancer. SIGNIFICANCE: Pygo2 represents a potential therapeutic target in metastatic breast cancer, as its histone-binding capability promotes β-catenin-mediated Wnt signaling and transcriptional control in breast cancer cell dedifferentiation, EMT, and metastasis.


The Incidence of Road Traffic Crashes Among Young People Aged 15-20 Years: Differences in Behavior, Lifestyle and Sociodemographic Indices in the Galilee and the Golan.
Background: Adolescent injuries and fatalities constitute a world health concern and present a major public health burden. Of all childhood injuries in Israel 61.8% occur during road traffic crashes. The risk of being injured or killed in a road traffic crash is especially high among individuals deemed to have a low socio-economic status, but, there also exist crucial risk factors for road traffic crashes that are intrinsic social determinants of health, including behavior, lifestyle, education and employment. These associations are explored in this study. Aim: To examine the contribution of socioeconomic inequalities to the incidence of road traffic crashes among adolescents living in the Galilee and the Golan. Methods: A large retrospective study of trauma records (N = 3293) of 15-20-year-old patients who were injured in road traffic crashes and admitted to Ziv Medical Center between 2004 and 2015 was performed. These patients were subcategorized according to their home address. Using census data and other databases associations between socioeconomic inequalities, intrinsic social determinants and the prevalence of road crashes were investigated. Results: Road traffic crashes in the Galilee and the Golan are more frequent among residents of low socioeconomic areas. Fifty-five percent of drivers are from the areas of lowest socioeconomic level (levels 2 to 4) and are responsible for 60% of the road traffic injuries admitted to Ziv Medical Center (p < 0.001). In contrast, 42% of drivers are from areas of medium socioeconomic level (levels 5 and 6) but are responsible for only 35% of road traffic injuries (p < 0.001). Young women in the Galilee and the Golan are less likely to be involved in road traffic crashes-35.8% compared to 64.2% in young men. Conclusions: This research has shown that youth, male gender, socioeconomic status, education level and the quality of road infrastructure are important factors in the incidence of road traffic crashes in the Galilee and the Golan. This should be taken into consideration by policy makers in order to develop appropriate interventions in road safety targeted at multiple levels.


Serum lipid level in Iraqi patients with psoriasis.
Psoriasis is a chronic inflammatory and proliferative dermatosis. Previous studies have demonstrated that patients with psoriasis may have an increased risk of occlusive vascular disease. High serum lipid level has been suggested in the pathogenesis of this phenomenon. In this study, the authors assess the lipid profile in Iraqi patients with psoriasis and compare it with that of nonaffected persons. This study was designed and conducted as a cross-sectional study with 50 cases in the patient group and 50 patients in the control group. It was performed in the department of dermatology at Al-Sadr Teaching Hospital in Najaf, Iraq. The lipid profile, including serum levels of triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein, were assessed in both groups. The patient and control groups each consisted of 39 men and 11 women. The serum triglyceride, cholesterol, LDL, and very LDL levels were significantly higher in psoriatic patients (P < .05) but not for high-density lipoprotein (P >.05). Serum lipid level was found to be significantly higher in Iraqi patients with psoriasis. It may be useful to do early screening and treatment ofhyperlipidemia in psoriasis to prevent atherosclerosis and its complications.


Study of the function of Escherichia coli ribosomal RNA through site-directed mutagenesis.
Various approaches have been developed to study how mutations in Escherichia coli ribosomal RNA affect the function of the ribosome. Most of them are in vivo approaches, where mutations are introduced in a specialized plasmid harboring the ribosomal RNA genes. The mutated plasmids are then expressed in an appropriate host, where they can confer resistance to antibiotics whose target is the ribosome. Conditions can be used where the host ribosomal RNA genes or the host ribosomes are selectively inactivated, and the effect of the mutations on ribosome assembly and function can be studied. Another approach, which has been developed mainly with 16S ribosomal RNA, can be used entirely in vitro. In this approach, a plasmid has been constructed which contains the 16S ribosomal RNA gene under control of a T7 promoter. Mutations can be introduced in the 16S ribosomal RNA sequence and the mutated 16S ribosomal RNAs are produced by in vitro transcription. It is then possible to investigate how the mutations affect the assembly of the 16S ribosomal RNA into 30S subunits and the activity of the reconstituted 30S subunits in cell-free protein synthesis assays. Although these approaches are recent, they have already provided a large body of interesting information, relating specific RNA sequences to interactions with ribosomal proteins, to ribosome function, and to its response to antibiotics.


Saudi center for organ transplantation: activities and achievements.
The reported annual incidence of ESRD in the Kingdom is 100-120 patients per million population. The first dialysis unit in Saudi Arabia was set up in 1971 and since then rapid advances have been made in the Kingdom in the field of renal replacement therapy. There are currently 103 centers offering dialysis to about 4500 patients. The National Kidney Foundation was established in 1985 to implement a cadaveric organ transplant program and to co-ordinate the renal care facilities in the Kingdom. This center was renamed as Saudi Center for Organ Transplantation (SCOT) in 1993 in order to encompass transplantation of organs other than the kidney as well. A real impetus was given in the year 1982 with the approval handed over by Islamic scholars on the concept of brain-death and organ transplantation. From 1979, when the first renal transplant was performed till end of 1994, more than 1600 renal transplants have been performed in 13 transplant centers in Saudi Arabia. Also, 49 liver, 57 heart, 45 heart valve, 121 cornea, 4 pancreas, 4 lung, and 100 bone marrow transplants have been performed in the Kingdom. Despite these achievements, there is still a large gap between demand and supply and efforts are ongoing to improve the donor pool and bridge this gap.


Specific route mapping visualized with GFP of single-file streaming contralateral and systemic metastasis of Lewis lung carcinoma cells beginning within hours of orthotopic implantation [correction of implantion].
In this study, we visualized the origin of Lewis lung carcinoma metastasis after transducing tumor cells with green fluorescent protein (GFP) and transplanting them orthotopically in the middle lobe of the right lung of nude mice. Metastasis was visualized in live tissue at single cell resolution by GFP-expression as early as 18 h post-tumor transplant. At this time, single-file streaming lung carcinoma cells already had invaded inferiorly via a tubular lymphatic structure crossing the lower lobes of the lung to the ipsilateral diaphragmatic surface. By post-implantation day 2, the ipsilateral lower lobes of the lung were involved with metastatic cells. By post-implantation day 3, the ipsilateral lower lobes of the lung and the ipsilateral diaphragmatic surface were highly involved with streaming metastatic cells trafficking in single file. By day 4 post-implantation, cancer cells invaded across the diaphragm to the contralateral diaphragmatic surface. Metastatic cells then invaded superiorly through a lymphatic vessel to involve the contralateral mediastinal lymph nodes. In this model of lung cancer, the origin of metastasis was an inferior invasion from the implanted tumor via a lymphatic duct to the ipsilateral diaphragmatic surface. The cancer cells from this site invaded on the surface of the diaphragm to the contralateral diaphragmatic surface and proceeded superiorly through a lymphatic duct to contralateral lymph nodes. Other organs such as the kidneys and the adrenal glands later became involved with metastasis with the contralateral mediastinal lymph nodes as the source. The use of GFP and the highly metastatic orthotopic lung cancer model allowed the visualization of the origin of metastasis at the single-cell level and demonstrated the critical role of lymphatic ducts and the diaphragmatic surface as the path to the contralateral side.


Modeling decay rates of dead wood in a neotropical forest.
Variation of dead wood decay rates among tropical trees remains one source of uncertainty in global models of the carbon cycle. Taking advantage of a broad forest plot network surveyed for tree mortality over a 23-year period, we measured the remaining fraction of boles from 367 dead trees from 26 neotropical species widely varying in wood density (0.23-1.24 g cm(-3)) and tree circumference at death time (31.5-272.0 cm). We modeled decay rates within a Bayesian framework assuming a first order differential equation to model the decomposition process and tested for the effects of forest management (selective logging vs. unexploited), of mode of death (standing vs. downed) and of topographical levels (bottomlands vs. hillsides vs. hilltops) on wood decay rates. The general decay model predicts the observed remaining fraction of dead wood (R2 = 60%) with only two biological predictors: tree circumference at death time and wood specific density. Neither selective logging nor local topography had a differential effect on wood decay rates. Including the mode of death into the model revealed that standing dead trees decomposed faster than downed dead trees, but the gain of model accuracy remains rather marginal. Overall, these results suggest that the release of carbon from tropical dead trees to the atmosphere can be simply estimated using tree circumference at death time and wood density.


Cardiovascular Risk in Rheumatoid Arthritis and Mechanistic Links: From Pathophysiology to Treatment.
Rheumatoid arthritis (RA) is an autoimmune inflammatory arthritis. Inflammation, however, can spread beyond the joints to involve other organs. During the past few years, it has been well recognized that RA associates with increased risk for cardiovascular (CV) disease (CVD) compared with the general population. This seems to be due not only to the increased occurrence in RA of classical CVD risk factors and comorbidities like smoking, obesity, hypertension, diabetes, metabolic syndrome, and others but also to the inflammatory burden that RA itself carries. This is not unexpected given the strong links between inflammation and atherosclerosis and CVD. It has been shown that inflammatory cytokines which are present in abundance in RA play a significant role in every step of plaque formation and rupture. Most of the therapeutic regimes used in RA treatment seem to offer significant benefits to that end. However, more studies are needed to clarify the effect of these drugs on various parameters, including the lipid profile. Of note, although pharmacological intervention significantly helps reduce the inflammatory burden and therefore the CVD risk, control of the so-called classical risk factors is equally important. Herein, we review the current evidence for the underlying pathogenic mechanisms linking inflammation with CVD in the context of RA and reflect on the possible impact of treatments used in RA.


Glans penis reconstruction with the pedicled deep inferior epigastric artery perforator flap.
This is a report on a novel technique of neoglans reconstruction in a patient with an amputated glans penis as a result of a gunshot injury. A pedicled deep inferior epigastric artery perforator (DIEAP) flap measuring 7 x 4 cm and centralizing the uppermost perforators in the right abdominal region was used. The distal penile skin was used to elongate the urethra. A subcutaneous tunnel was created alongside the penis and underneath the mons pubis. The flap was passed through this tunnel, fashioned into the shape of a glans, and secured in place around the neourethra. The patient had a satisfactory neoglans and a functional urethra at 4-month follow-up. The pedicled DIEAP flap is a suitable option for reconstruction of the glans penis.


Chromosomal characteristics and non-random distribution of sister chromatid exchanges in lymphoblastoid cell lines isolated from acute leukemias.
Serial cytogenetic characteristics of four lymphoblastoid cell lines derived from the peripheral blood of four patients with acute leukemia are presented, including G and C banding techniques and the analysis of sister chromatid exchanges by means of FPG technique. One of these lines turned into predominantly diploid although originally pseudodiploid, while the other three changed from diploid to heteroploid ones during prolonged cultivation, with the appearance of a marker chromosome in one of them. The mean number of sister chromatid exchanges per mitosis (9.6) did not differ from the control value obtained in short-term cultivations of lymphocytes of healthy subjects. All lines showed a significantly increased number of sister chromatid exchanges in the B group chromosomes. The contribution of FPG technique for the study of cell kinetics is briefly discussed.


Nucleotide sequence and genetic characterization of the novel IncQ-like plasmid pIE1107.
The analysis of the complete nucleotide sequence of the small resistance plasmid pIE1107 revealed a close similarity to the well-known IncQ plasmids. Highly conserved replication proteins and nearly identical origins of replication (oriV) suggest equivalent functions in the related replication systems. However, pIE1107 contains two copies of IncQ-oriV-like DNA which are slightly different regarding the iterons. Upon deletion of a silent copy of IncQ-oriV-like DNA the resulting plasmid is fully compatible with IncQ plasmids, indicating that there is no mutual communication between the replication control of the respective replicons. Experiments with cloned oriV DNA strongly suggest that the replication initiation protein of pIE1107 has specialized into the distinct target-iterons of its own oriV which differs only by a few nucleotides from the oriV of IncQ plasmids. Implications from the apparent highly specific protein-DNA recognition and from the incompatibility properties of pIE1107 for the evolution of a family of compatible, IncQ-like plasmids are discussed.


Flexible manipulation of Omb levels in the endogenous expression region of Drosophila wing by combinational overexpression and suppression strategy.
Manipulating an exogenous or endogenous gene of interest at a defined level is critical for a wide variety of experiments. The Gal4/UAS system has been widely used to direct gene expression for studying complex genetic and biological problems in Drosophila melanogaster and other model organisms. Driven by a given tissue-specific Gal4, expressing UAS-transgene or UAS-RNAi (RNA interference) could be used to up- or down-regulate target gene expression, respectively. However, the efficiency of the Gal4/UAS system is roughly predefined by properties of transposon vector constructs and the insertion site in the transgenic stock. Here, we describe a simple way to modulate optomotor blind (omb) expression levels in its endogenous expression region of the wing disc. We co-expressed UAS-omb and UAS-omb-RNAi together under the control of dpp-Gal4 driver which is expressed in the omb expression region of the wing pouch. The repression effect is more sensitive to temperature than that of overexpression. At low temperature, overexpression plays a dominant role but the efficiency is attenuated by UAS-omb-RNAi. In contrast, at high temperature RNAi predominates in gene expression regulation. By this strategy, we could manipulate omb expression levels at a moderate level. It allows us to manipulate omb expression levels in the same tissue between overexpression and repression at different stages by temperature control.


DNA content distribution of mouse cells following infection with polyoma virus.
Infection of primary to tertiary mouse embryo fibroblasts or mouse kidney cells with polyoma virus leads to stimulation of cellular DNA synthesis. When either confluent or growing mouse cells were infected, the monolayer cells were found to accumulate cells with a DNA content of S and G2/M phases of the cell cycle as assayed by flow cytometry. A similar pattern of DNA content was also observed in cells in the supernatant, which are probably cells replicating virus and dying. When compared with control cells, the infected monolayer and supernatant cells exhibited a population (5-27%) with a > G2 DNA content. The increase in DNA content of these > G2 cells was calculated to be an average of 26.7%, which is probably due to viral DNA. Polyoma contrasts with another papovavirus, SV40, which stimulates cells into DNA synthesis, with the majority of cells attaining a > G2/tetraploid DNA content, suggesting that there are differences in polyploidization between these two viruses.


Comprehensive discovery of DNA motifs in 349 human cells and tissues reveals new features of motifs.
Comprehensive motif discovery under experimental conditions is critical for the global understanding of gene regulation. To generate a nearly complete list of human DNA motifs under given conditions, we employed a novel approach to de novo discover significant co-occurring DNA motifs in 349 human DNase I hypersensitive site datasets. We predicted 845 to 1325 motifs in each dataset, for a total of 2684 non-redundant motifs. These 2684 motifs contained 54.02 to 75.95% of the known motifs in seven large collections including TRANSFAC. In each dataset, we also discovered 43 663 to 2 013 288 motif modules, groups of motifs with their binding sites co-occurring in a significant number of short DNA regions. Compared with known interacting transcription factors in eight resources, the predicted motif modules on average included 84.23% of known interacting motifs. We further showed new features of the predicted motifs, such as motifs enriched in proximal regions rarely overlapped with motifs enriched in distal regions, motifs enriched in 5' distal regions were often enriched in 3' distal regions, etc. Finally, we observed that the 2684 predicted motifs classified the cell or tissue types of the datasets with an accuracy of 81.29%. The resources generated in this study are available at http://server.cs.ucf.edu/predrem/.


[Determination of streptomycin and dihydrostreptomycin residues in tomato paste by tandem dual solid phase extraction column-liquid chromatography-tandem mass spectrometry].
The method was specifically developed for the simultaneous determination of streptomycin and dihydrostreptomycin residues in tomato paste by tandem dual solid phase extraction (SPE) column cleanup-liquid chromatography-tandem mass spectrometry. The residues were extracted from the samples with phosphate buffer solution (pH 4). The cleanup was performed by the way of dispersive solid phase extraction and tandem dual solid phase extraction column. The polar chromatographic column was used to complete the separation of the analytes under gradient elution and the analytes were detected in multiple reaction monitoring (MRM) mode via positive electrospray ionization (ESI +). The external standard calibration curves were used for the quantification. The linear ranges were from 0.01 to 0.2 mg/L with a good linear relationship (r > 0.999) for streptomycin and dihydrostreptomycin. The limit of quantification (LOQs) was 0.02 mg/kg for the both analytes. The recovery range was from 71% to 101% with the relative standard deviations (RSDs) between 2.3% and 15%. It was indicated that this method is accurate, easier, more sensitive, and has a better purification effect in the monitoring and analysis. The method is accurate and specific to monitor and analyze of streptomycin and dihydrostreptomycin residues in tomato paste and its products.


Double umbilical cord blood transplant: more than a cell dose?
Cord blood transplant (CBT) is characterized by the limited amount of hematopoietic stem cells (HSCs), and exhibits higher incidence of engraftment failure. Transplant using two (double) CB units (DCBT) is the most promising strategy to date to augment the total transplanted HSC dose. DCBT increases the availability of transplant to adults, for whom there is only a small chance of finding a matched CB suitable for a single unit transplant. Better selection of CB units, optimization of conditioning regimen, and GVHD prophylaxis are important to further improve DCBT outcomes. In this review we attempt to summarize recent progress in the field of DCBT, to present the strategies applied, and to point out directions for the future.


Preventing progression in men with mild symptoms of benign prostatic hyperplasia: a potential role for phytotherapy.
Prevalence of benign prostate hyperplasia (BPH) is increasing with the aging population worldwide. Throughout the 20th century, men with minimally symptomatic BPH were generally advised to defer treatment. Treatment deferral or watchful waiting has always appeared reasonable because mild lower urinary tract symptoms suggestive of bladder outlet obstruction are not bothersome and are often regarded as part of the aging process, progression is usually slow, and symptoms often regress spontaneously. This review examines the evidence of the natural history of BPH, highlighting the group of patients with mild symptoms, the risk factors for progression, and the potential role of phytotherapy in this group of men.


The LINC Between Mechanical Forces and Chromatin.
The heart continually senses and responds to mechanical stimuli that balance cardiac structure and activity. Tensile forces, compressive forces, and shear stress are sensed by the different cardiac cell types and converted into signals instructing proper heart morphogenesis, postnatal growth, and function. Defects in mechanotransduction, the ability of cells to convert mechanical stimuli into biochemical signals, are implicated in cardiovascular disease development and progression. In this review, we summarize the current knowledge on how mechanical forces are transduced to chromatin through the tensed actomyosin cytoskeleton, the linker of nucleoskeleton and cytoskeleton (LINC) complex and the nuclear lamina. We also discuss the functional significance of the LINC complex in cardiovascular disease.


Uptake of intermittent preventive treatment with sulphadoxine-pyrimethamine for malaria during pregnancy and pregnancy outcomes: a cross-sectional study in Geita district, North-Western Tanzania.
Malaria infection during pregnancy is associated with adverse outcomes in sub-Saharan Africa (SSA). For this reason, the World Health Organization currently recommends intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) at each scheduled antenatal care (ANC) visit. In Tanzania, the revised IPTp policy was adopted in 2013 but the level of uptake and its association with pregnancy outcomes remains unknown. A cross-sectional study was conducted among singleton pregnant women who delivered in two selected health facilities of Geita district, northwestern Tanzania. Self-reported uptake of SP was verified using the ANC card and was recorded. Placental and peripheral blood was collected for diagnosis of malaria by microscopy and rapid diagnostic tests (RDTs). Gestational age was estimated based on last menstrual period or Ballard score. Infant birth weights were recorded within 24 hours of delivery. Of 431 participants, 167 (38.75%), 134 (31.09%), 104 (24.23%), and 26 (6.03%) reported taking none, one, two, and ≥ three doses of SP during pregnancy, respectively. The uptake of ≥ three doses of IPTp-SP among delivering women at Geita hospital and Katoro health centre was 9.06% and 1.2%, respectively. The overall prevalence of malaria in pregnancy by RDT, peripheral and placental smears was 19.5%, 29.7% and 37.6% respectively. The prevalence of placental parasitaemia was higher for women who delivered at Katoro Health Centre (41.57%) than those who delivered at Geita hospital (35.09%). The uptake of ≥ three doses of SP was associated with reduced odds of having placental malaria (adjusted odds ratio (AOR) = 0.31, p = 0.039) compared to < three doses. Women with placental parasitaemia were five times more likely to have delivered pre-term (AOR = 4.67, p = 0.002) and had lower mean birth weight infants than their uninfected counterparts (mean difference = 82 g, p = 0.039). The uptake of ≥ three doses of IPTp-SP is low in the present study area. Placental parasitaemia is prevalent and is associated with adverse birth outcomes. Receipt of ≥ three doses of IPTp-SP reduced the odds of placental parasitaemia. Thus, increased efforts towards scale-up and continuous evaluation of IPTp-SP efficacy is recommended.


Hemostatic changes in dogs with naturally occurring sepsis.
Sepsis is a frequent source of morbidity and mortality in critically ill patients. The goal of this case control study was to measure hemostatic changes in dogs with naturally occurring sepsis. Blood was collected within 24 hours of admission from 20 dogs that fulfilled the criteria for sepsis. Sepsis was defined as histologic or microbiological confirmation of infection and 2 or more of the following criteria: hypo- or hyperthermia, tachycardia, tachypnea, or leukopenia, leukocytosis, or > 3% bands. Culture and sensitivities were performed on appropriate samples from all septic dogs. Twenty-eight control dogs were enrolled on the basis of normal results of physical examination, CBC, serum biochemistry, and coagulation profile. Plasma samples were analyzed for prothrombin time (PT), partial thromboplastin time (PTT), fibrin(ogen) degradation products (FDP), D-dimer (DD) concentrations, antithrombin (AT) activity, and protein C (PC) activity. Data were compared between groups by chi-square or independent t-tests. PC (P < .001) and AT (P < .001) activities were significantly lower in dogs with sepsis compared to controls. Dogs with sepsis had significantly higher PT (P = .007), PTT (P = .005), D-dimer (P = .005), and FDP (P = .001) compared to controls. Platelet counts were not significantly different between groups. Ten of the 20 septic dogs (50%) died, but no association was identified between any of the measured variables and outcome. These findings are consistent with previous studies in animals with experimentally induced disease and in clinical studies of humans. On the basis of these results, further investigation of the role of AT and PC in canine sepsis is warranted.


Caspofungin: a review of its use in the treatment of fungal infections.
Caspofungin (Cancidas) is the first of a new class of antifungal agents, the echinocandins, that inhibit the synthesis of the fungal cell wall component beta-(1,3)-D-glucan. Caspofungin is administered once daily by slow intravenous infusion and is used to treat infections caused by Candida spp. and Aspergillus spp. Caspofungin is a valuable new antifungal agent with a novel mechanism of action. In comparative clinical trials, caspofungin was no less effective than liposomal amphotericin B in the empirical treatment of neutropenic patients with persistent fever, amphotericin B deoxycholate in the treatment of invasive candidiasis or fluconazole in the treatment of oesophageal candidiasis. Caspofungin also displayed broadly similar efficacy to amphotericin B deoxycholate in oesophageal or oropharyngeal candidiasis and was effective as salvage therapy in patients with invasive aspergillosis who were refractory to or intolerant of standard therapy. The tolerability profile of caspofungin was similar to that of fluconazole and superior to that of amphotericin B deoxycholate and liposomal amphotericin B. Therefore, in the appropriate indications, caspofungin is a viable alternative to amphotericin B deoxycholate, liposomal amphotericin B or fluconazole.


[Clinical Efficacy of Second-generation Tyrosine Kinase Inhibitor in Treating Chronic Myeloid Leukemia].
To evaluate the efficacy of second-generation tyrosine kinase inhibitor (TKI) in treating chronic myeloid leukemia (CML). A total of 97 patients with CML were enrolled. The patients were treated with TKI and monitored with complete blood count, cytogenetic and molecular indicators during the course of therapy. Survival analysis was performed to evaluate its clinical efficacy. The treatment achieved 97.9% complete hematologic response (CHR), 63.9% major cytogenetic response (MCyR), 60.0% complete cytogenetic response (CCyR) and 44.3% major molecular response (MMR) rates. Apart from CHR, better effects were shown in those indicators during chronic phase compared with progressive phase (P < 0.05). The 1-year, 2-year, 3-year and 5-year overall survival (OS) rate was (90.6 ± 3.0)%, (80.1 ± 4.5)%, (77.5 ± 5.0)% and (64.6 ± 9.3)%, respectively, compared with an event-free survival (EFS) rate of (81.1 ± 4.0)%, (64.4 ± 5.3)%, (56.4 ± 6.0)% and (46.2 ± 8.2)%, respectively. The patients had a 1-year, 2-year, 3-year and 5-year progession-free survival (PFS) rate of (87.4 ± 3.4)%, (73.2 ± 4.9)%, (68.9 ± 5.5)% and (57.4 ± 8.7)%, respectively. A difference between chronic phase (better results) and progressive phase (P < 0.05) was also found in survival indicators. The first-line TKI therapy had 100% CHR, 95% MCyR, 95% CCyR and 70% MMR, compared with 97.3% CHR, 56.8% MCyR, 48.6% CCyR and 36.5% MMR for the second-line TKI therapy. Apart from CHR, the first-line therapy produced better results than the seond-line therapy (P < 0.05). CML patients in chronic phase and first-line use of TKI have better outcomes.


Promising effects of gingerol against toxins: A review article.
Ginger is a medicinal and valuable culinary plant. Gingerols, as an active constituent in the fresh ginger rhizomes of Zingiber officinale, exhibit several promising pharmacological properties. This comprehensive literature review was performed to assess gingerol's protective and therapeutic efficacy against the various chemical, natural, and radiational stimuli. Another objective of this study was to investigate the mechanism of anti-inflammatory, antioxidant, and antiapoptotic properties of gingerol. It should be noted that the data were gathered from in vivo and in vitro experimental studies. Gingerols can exert their protective activity through different mechanisms and cell signaling pathways. For example, these are mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-kB), Wnt/β-catenin, nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE), transforming growth factor beta1/Smad3 (TGF-β1/Smad3), and extracellular signal-related kinase/cAMP-response element-binding protein (ERK/CREB). We hope that more researchers can benefit from this review to conduct preclinical and clinical studies, treat cancer, inflammation, and attenuate the side effects of drugs and industrial pollutants.


Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients.
In 46,XY disorders of sex development, 5α-reductase deficiency is rare and is not usually the first-intention diagnosis in newborn ambiguous genitalia, contrary to partial androgen insensitivity syndrome. Yet the cause of ambiguous genitalia may guide sex assignment, and rapid, precise diagnosis of 5α-reductase deficiency is essential. The aim of the study was to describe relevant data for clinical diagnosis, biological investigation, and molecular determination from 55 patients with srd5A2 mutations identified in our laboratory over 20 yr to improve early diagnosis. The study was performed at Montpellier University Hospital. We studied a cohort of 55 patients with srd5A2 gene mutations. Genetic analysis of srd5A2 was conducted. Clitoromegaly (49.1%) and microphallus with various degrees of hypospadias (32.7%) were frequent phenotypes. Female external genitalia (7.3%) and isolated micropenis (3.6%) were rare. Seventy-two percent of patients were initially assigned to female gender; five of them (12.5%) switched to male sex in peripuberty. Over 72% of patients were considered for 5α-reductase deficiency diagnosis when the testosterone/dihydrotestosterone cutoff was 10. In 55 patients (with 20 having a history of consanguinity), we identified 33 different mutations. Five have never been reported: p.G32S, p.Y91H, p.G104E, p.F223S, and c.461delT. Homozygous mutations were present in 69.1% of cases, compound heterozygous mutations in 25.5%, and compound heterozygous mutations alone with the V89L polymorphism in 5.4%. Exons 1 and 4 were most affected, with 35.8 and 21.7% mutant alleles per exon, respectively. In the largest cohort to date, we demonstrate a wide spectrum of phenotypes and biological profiles in patients with 5α-reductase deficiency, whatever their geographical or ethnic origins.


MiR-372-3p inhibits the growth and metastasis of osteosarcoma cells by targeting FXYD6.
Growing evidence has suggested that dysregulation of miR-372-3p may contribute to tumor development and progression in various tumors. However, the function of miR-372-3p in osteosarcoma has not been investigated. In the present study, we aimed to study the effects of miR-372-3p on osteosarcoma cell proliferation and metastasis and its regulation on FXYD6. The expression levels of miR-372-3p and FXYD6 mRNA were quantified by RT-PCR in human osteosarcoma cell lines and tissues. The effects of miR-372-3p up-regulation on osteosarcoma cell proliferation and metastasis were assessed by MTT, wound healing assay and transwell assay. Finally, the potential regulatory effect of miR-372-3p on FXYD6 expression was confirmed. Our data showed that miR-372-3p was downregulated in osteosarcoma tissues compared with matched normal tissues, and the expression level of miR-372-3p was significantly lower in osteosarcoma cell lines in comparison with the normal human osteoblastic cell line. Transfection with the miR-372-3p mimic enhanced the osteosarcoma proliferation and metastasis. In vivo assay indicated that forced expression of miR-372-3p significantly suppressed tumor growth. Then, Bioinformatics prediction and experimental validation results confirmed that the function of miR-372-3p was achieved by targeting FXYD6 expression. Our findings revealed that miR-372-3p served as a tumor suppressor gene by targeting FXYD6 in osteosarcoma. Thus, miR-372-3 might be a potential therapeutic method for osteosarcoma.


Comparison between subjective and objective assessments of the cervix before induction of labour.
The aim of the study was to compare the pre-induction cervical assessment by Bishop's score with the transvaginal ultrasound cervical length as predictors of the induction-delivery interval (IDI) and the success of induction. This prospective study included 104 women with singleton pregnancies who were booked for induction of labour at term over a period of 3 years. Transvaginal ultrasound measurement of the cervical length and Bishop's Score were performed by different operators. Data were collected on parity, gestational age, methods of induction, Bishop's score, ultrasound cervical length measurements, IDI and mode of delivery. A total of 87 women (83.7%) delivered vaginally and 17 (16.3%) delivered by caesarean section. Linear regression models demonstrated that ultrasound cervical length was a better indicator of IDI than Bishop's score. The adjusted R2 for the regression including ultrasound cervical length was 0.87 compared with a value of 0.67 for the model including Bishop's score. Although logistic regression analysis confirmed that cervical effacement was the best component of Bishop's score to predict the mode of delivery, ultrasound cervical length assessment provided better prediction. Receiver operating characteristic curve showed that the optimised cut-off value for prediction of vaginal delivery was < or =3.4 cm for the cervical length and >5 for the Bishop's score. At those optimised cut-off values the cervical length predicted vaginal delivery with sensitivity of 62.1% (95% CI [51%, 72.3%]) and specificity of 100% (95% CI [80.5%, 100%]) while the Bishop's score predicted vaginal delivery with a sensitivity of 23% (95% CI [14.6%, 33.2%]) and specificity of 88.2% (95% CI [63.5%, 98.5%]). Further analysis showed that ultrasound cervical length has a higher sensitivity in prediction of vaginal delivery in multiparous than nulliparous women (85.1% compared with 35%) at a cut-off value of < or =3.4 cm. On the other hand, it has a higher sensitivity in nulliparous comparable with multiparous women (85.3% compared with 30%) in prediction of IDI at a cut-off value of >3.5 cm. In conclusion, transvaginal ultrasound cervical length assessment is better than Bishop's score in predicting the IDI and the success of induction of labour.


In vitro susceptibility and resistance phenotypes in contemporary Citrobacter isolates in a University Hospital in Crete, Greece.
Data on Citrobacter spp. susceptibility are scarce. We sought to study the evolution in the susceptibility of 385 Citrobacter spp. at the University Hospital of Heraklion, Crete, Greece during a six-year period (2010-2015). Non-duplicate strains isolated from inpatients (intensive care unit, oncology, surgery, internal medicine, paediatrics) and outpatients were studied using Vitek 2. Phenotypic confirmatory tests were applied for detection of β-lactamases and aminoglycoside modifying enzymes. C. freundii (172, 44.7%) and C. koseri (166, 43.1%) were the most commonly isolated species. C. braakii (34), C. amalonaticus (6), C. youngae (6) and C. sedlakii (1) were the remaining isolates. Colistin and fosfomycin were the most active antibiotics (both 99.2%) followed by carbapenems (99%) aminoglycosides (96.6-98.4%), tigecycline (96.1%), cefepime (94.8%), ciprofloxacin (94.3%), tetracycline (92.7%), trimethoprim/sulphamethoxazole (91.4%), chloramphenicol (88.1%), piperacillin/tazobactam (86.5%) and 3rd generation cephalosporins (85.7%). C. freundii were more resistant than C. koseri. Antibiotic resistance did not increase during the study period for most antibiotics. Lower susceptibility to all antibiotics was observed among multi-drug resistant (MDR) strains. AmpC was the most common resistant mechanism (10.9%); carbapenemases (1.3%) and aminoglycoside modifying enzymes (2.9%) were also detected. All AmpC producers were resistant to cephalosporins but not to carbapenems. In all but one isolates aminoglycoside resistance was accompanied by acquired β-lactamases. Although Citrobacter species in general were susceptible, antibiotic susceptibility testing is required for the detection of resistant isolates.


Gravidas' responses to realtime ultrasound fetal image.
One hundred women in various stages of pregnancy were questioned before and after viewing their fetuses through realtime ultrasonographic scanning. For the majority of these women, perceptions of the fetus changed following this visualization. Viewing gave some a greater sense of attachment to the fetus, but for a few, this attachment also gave a greater sense of vulnerability with regard to the outcome of the pregnancy.


Adrenocortical Carcinoma Treated by CyberKnife.
Adrenocortical carcinoma is a rare malignancy with a poor prognosis. The effective treatment for advanced cancer remains unknown. A 61-year-old woman underwent CyberKnife treatment on a large adrenocortical carcinoma and tumor emboli in both pulmonary arteries. Follow-up positron emission tomography scanning with fluorodeoxyglucose (FDG) revealed that the FDG uptake was greatly decreased in all the tumors, and the hormone levels were also decreased. CyberKnife is a safe and effective treatment option for the non-operative large advanced adrenocortical carcinoma.


Sluggish anion transport provides good kinetic stability to the anhydrous anti-perovskite solid electrolyte Li3OCl.
Some lithium oxyhalides have been proposed as low-cost solid electrolytes for having room-temperature Li+ conductivity close to commercial liquid electrolytes, but with the advantages of enabling higher energy densities through the use of the Li metal anode and not being flammable. However, the stability of anhydrous anti-perovskite lithium oxyhalides, such as Li3OCl, is not well understood yet: whereas theoretical calculations show they should decompose into lithium halides and Li2O (except at high temperatures), there is no experimental evidence of such decomposition. Thus, here we use a combination of analytical calculations and force-field-based atomistic modelling to investigate the role of kinetics in the stability of anhydrous Li3OCl. The results show that due to sluggish Cl- and O2- transport this material has good kinetic stability below ∼400 K under high concentration gradients, below ∼450 K under typical cell voltages, and at all temperatures against local composition fluctuations. Furthermore, the good kinetic stability explains the apparent discrepancy between theoretical thermodynamics calculations and experimental observations and contributes to enlighten the nature and extent of this material's stability. The methods presented here can also be extended to other battery materials that are predicted to decompose, to access the safe temperature range they can undergo without degrading.


Single nucleotide polymorphisms in C-type lectin genes, clustered in the IBD2 and IBD6 susceptibility loci, may play a role in the pathogenesis of inflammatory bowel diseases.
The balance between microbes and host defence mechanisms at the mucosal frontier plays an important, yet unclarified role in the pathogenesis of inflammatory bowel disease (IBD). The importance of microorganisms in IBD is supported by the association of IBD with mutations in pattern recognition receptors (PRRs) such as NOD2 and TLR4. We aimed to examine whether polymorphisms in another type of PRRs, the so-called C-type lectin receptors (CLRs), are associated with IBD. Growing insights into the pathogenetic role of NOD2 mutations in Crohn's disease (CD) and the fact that the majority of CLR-encoding genes are located in IBD susceptibility loci provide strong arguments for further exploration of the role of CLRs in IBD. In this study, we selected four single nucleotide polymorphisms (SNPs) in different CLRs to determine whether there could be a role for these CLRs in IBD. Functional SNPs in the genes coding for the candidate CLRs DC-SIGN, LLT1, DCIR and MGL were examined. Genotyping of all SNPs was performed at the Academic Medical Center. In this study, around 1572 samples were included from a maximum of 621 CD patients, 457 ulcerative colitis (UC) patients and 586 healthy controls (HCs). No association was found between our IBD cohort and the candidate SNPs for DC-SIGN (CD/HC: P=0.25 and UC/HC: P=0.36), DCIR (CD/HC: P=0.22 and UC/HC: P=0.41) and MGL (CD/HC: P=0.37 and UC/HC: P=0.25). However, one polymorphism in LLT1 was found to be associated with our CD population (P<0.034). Our UC cohort was not associated with the variation in LLT1 (P=0.33). LLT1 is a ligand for the recently discovered CD161. CD161 is a new surface marker for human interleukin (IL)-17-producing Th17 cells. The Th17 phenotype has been linked to CD by the fact that IL-22, IL-17 and IL-23 receptor levels are increased in CD. The signal transduction pathways involving LLT1 and CD161 are not completely clarified and are currently under investigation in our laboratory.


Increased nasal breathing decreases snoring and improves oxygen saturation during sleep apnoea.
For many years ENT-specialists have performed surgery to create a good air passage in patients with different kinds of nasal deformities. When having a blocked nose one realizes the importance of being able to breathe through the nose. By moving the nasal wings aside with the fingers, or the medical device Nozovent, most people experience that it is easier to breathe through the nose than ever before, which can also be shown with rhinomanometry. When it is easier to inhale there is less energy in the air passing the palate which means less risk for vibrations creating snoring sounds. In different studies it has been possible to show that snoring can be decreased or prevented when the nasal dilator Nozovent is used. It has also been shown to result in a decrease of the sleep apnoea index and improvement of arterial oxygen saturation during sleep apnoea.


[Transjugular intrahepatic portosystemic stent shunts].
We studied the clinical and procedural results of transjugular intrahepatic portosystemic stent shunts (TIPSS) procedures in 16 patients, of whom 13 were male, 3 female, with mean age of 48 years (range 24-66). All patients had cirrhosis with portal hypertension and varices. Twelve patients had recurrent bleeding for gastroesophageal varices. The results showed that shunts were successful in 14 of the 16 patients, and that no death was due to the procedure. Portal vein pressure was reduced from 3.98 +/- 0.24 kPa before shunting to 2.40 +/- 0.16 kPa after shunting. Doppler ultrasound revealed that the maximum blood flow velocity in the main portal vein increased from 14.0 +/- 4.5 cm/s to 48.0 +/- 16.5 cm/s. The mean follow-up time in the successful cases was 4.5 months (range, 2-7.5). The shunt patency was determined with color Doppler ultrasound in 13 patients, and occlusion of the tract was found in one. Mild ascites resolved in 4 patients; varices disappeared in 7 patients and abated in 6. No bleeding or encephalopathy was noted during the follow-up. The results suggested that TIPSS is an safe and effective method for portal decompression in the treatment of variceal hemorrhage, and that the key to TIPSS is understanding of the 3-dimensional relationships between hepatic and portal veins. To achieve an adequate shunt, we recommend that stent with 12 mm in diameter should be used.