Arbovirus persistence in North-Western Europe: Are mosquitoes the only overwintering pathway?
In some areas in temperate Europe, genomic analyses of mosquito-borne virus outbreaks have revealed the presence of similar virus strains over several years, indicating local overwintering of these viruses. However, it remains unclear how mosquito-borne viruses can persist in winter, when conditions are generally unfavourable for virus circulation. One of the presumed routes of virus persistence is via diapausing mosquitoes. Here, we set out to study whether arbovirus persistence of West Nile virus (WNV), Usutu virus (USUV) and Sindbis virus (SINV) occurs in diapausing mosquitoes in the Netherlands. To this end, mosquito collections were carried out in the winter of 2020 and 2021, in hibernacula located in two areas with previously observed WNV and/or USUV activity. In total, we collected 4200 mosquitoes belonging to four species (Culex pipiens, Culiseta annulata, Anopheles maculipennis s.l., and Culex territans), which were pooled in 490 monospecific pools. These pools were subjected to WNV-, USUV- and SINV-screening using a multiplex real-time RT-PCR assay. All mosquito pools tested negative for the presence of WNV, USUV and SINV RNA. Consequently, we did not find evidence of arbovirus persistence in diapausing mosquitoes in the Netherlands, even though USUV and WNV have re-appeared in birds and/or mosquitoes during the summer seasons of 2020-2022. Concluding, given the persistence of USUV and WNV in the Netherlands and SINV in other temperate regions, this study highlights the importance of further research on (alternative) arbovirus overwintering routes.


Predicted Arabidopsis Interactome Resource and Gene Set Linkage Analysis: A Transcriptomic Analysis Resource.
An advanced functional understanding of omics data is important for elucidating the design logic of physiological processes in plants and effectively controlling desired traits in plants. We present the latest versions of the Predicted Arabidopsis Interactome Resource (PAIR) and of the gene set linkage analysis (GSLA) tool, which enable the interpretation of an observed transcriptomic change (differentially expressed genes [DEGs]) in Arabidopsis (Arabidopsis thaliana) with respect to its functional impact for biological processes. PAIR version 5.0 integrates functional association data between genes in multiple forms and infers 335,301 putative functional interactions. GSLA relies on this high-confidence inferred functional association network to expand our perception of the functional impacts of an observed transcriptomic change. GSLA then interprets the biological significance of the observed DEGs using established biological concepts (annotation terms), describing not only the DEGs themselves but also their potential functional impacts. This unique analytical capability can help researchers gain deeper insights into their experimental results and highlight prospective directions for further investigation. We demonstrate the utility of GSLA with two case studies in which GSLA uncovered how molecular events may have caused physiological changes through their collective functional influence on biological processes. Furthermore, we showed that typical annotation-enrichment tools were unable to produce similar insights to PAIR/GSLA. The PAIR version 5.0-inferred interactome and GSLA Web tool both can be accessed at http://public.synergylab.cn/pair/.


Microbial nitrification in throughfall of a Japanese cedar associated with archaea from the tree canopy.
To investigate the nitrification potential of phyllospheric microbes, we incubated throughfall samples collected under the canopies of Japanese cedar (Cryptomeria japonica) and analyzed the transformation of inorganic nitrogen in the samples. Nitrate concentration increased in the unfiltered throughfall after 4 weeks of incubation, but remained nearly constant in the filtered samples (pore size: 0.2 and 0.4 µm). In the unfiltered samples, δ(18)O and δ(15)N values of nitrate decreased during incubation. In addition, archaeal ammonia monooxygenase subunit A (amoA) genes, which participate in the oxidation of ammonia, were found in the throughfall samples, although betaproteobacterial amoA genes were not detected. The amoA genes recovered from the leaf surface of C. japonica were also from archaea. Conversely, nitrate production, decreased isotope ratios of nitrate, and the presence of amoA genes was not observed in rainfall samples collected from an open area. Thus, the microbial nitrification that occurred in the incubated throughfall is likely due to ammonia-oxidizing archaea that were washed off the tree canopy by precipitation.


[Spinal anesthesia in ambulatory surgery. Extent, routines and patient satisfaction].
Spinal anaesthesia has been used in day-care surgery for a long time, but the fear of past dural puncture headache has limited its use in younger patients. A survey was conducted in order to assess the extent to which spinal anaesthesia is used for day-care surgery, and the routines governing the present practice in Norwegian anaesthetic departments. Information was obtained on the use of spinal anaesthesia for day-care surgery. In half of the anaesthetic departments spinal anaesthesia was used regularly. A large proportion of the departments worked with a lower age limit over 30 years of age for use of spinal anaesthesia. This does not seem to be justified on the basis of the scientific evidence. A prospective patient study revealed that out of 120 day-care patients aged 15 to 45 years who were given spinal anaesthesia, 93% would accept the same kind of anaesthetic again. Based on recent studies, the fear of post dural puncture headache should not preclude the use of spinal anaesthesia as a good alternative to general anaesthesia in day-care surgery.


Syndemic Profiles and Sexual Minority Men's HIV-Risk Behavior: A Latent Class Analysis.
Syndemic theory posits that "syndemic conditions" (e.g., alcohol misuse, polydrug use, suicidality) co-occur among sexual minority men and influence HIV-risk behavior, namely HIV acquisition and transmission risk. To examine how four syndemic conditions cluster among sexual minority men and contribute to HIV-risk behavior, we conducted latent class analysis (LCA) to: (1) classify sexual minority men (n = 937) into subgroups based on their probability of experiencing each syndemic condition; (2) examine the demographic (e.g., race/ethnicity) and social status (e.g., level of socioeconomic distress) characteristics of the most optimally fitting four syndemic classes; (3) examine between-group differences in HIV-risk behavior across classes; and (4) use syndemic class membership to predict HIV-risk behavior with sexual minority men reporting no syndemic conditions as the reference group. The four classes were: (1) no syndemic, (2) alcohol misuse and polydrug use syndemic, (3) polydrug use and HIV syndemic, and (4) alcohol misuse. HIV-risk behavior differed across these latent classes. Demographic and social status characteristics predicted class membership, suggesting that syndemic conditions disproportionately co-occur in vulnerable subpopulations of sexual minority men, such as those experiencing high socioeconomic distress. When predicting HIV-risk behavior, men in the polydrug use and HIV syndemic class were more likely (Adjusted Risk Ratio [ARR] = 2.93, 95% CI: 1.05, 8.21) and men in the alcohol misuse class were less likely (ARR = 0.17, 95% CI: 0.07, 0.44) to report HIV-risk behavior than were men in the no syndemic class. LCA represents a promising methodology to inform the development and delivery of tailored interventions targeting distinct combinations of syndemic conditions to reduce sexual minority men's HIV-risk behavior.


Synchronisation of Giardia lamblia: identification of cell cycle stage-specific genes and a differentiation restriction point.
The intestinal parasite Giardia lamblia undergoes cell differentiations that entail entry into and departure from the replicative cell cycle. The pathophysiology of giardiasis depends directly upon the ability of the trophozoite form to replicate in the host upper small intestine. Thus, cell proliferation is tightly linked to disease. However, studies of cell cycle regulation in Giardia have been hampered by the inability to synchronise cultures. Here we report that Giardia isolates of the major human genotypes A and B can be synchronised using aphidicolin, a mycotoxin that reversibly inhibits replicative DNA polymerases in eukaryotic cells. Aphidicolin arrests Giardia trophozoites in the early DNA synthesis (S) phase of the cell cycle. We identified a set of cell cycle orthologues in the Giardia genome using bioinformatic analyses and showed that synchronised parasites express these genes in a cell cycle stage-specific manner. The synchronisation method also showed that during encystation, exit from the ordinary cell cycle occurs preferentially in G(2) and defines a restriction point for differentiation. Synchronisation opens up possibilities for further molecular and cell biological studies of chromosome replication, mitosis and segregation of the complex cytoskeleton in Giardia.


Protective role of immobilization on ouabain-induced arrhythmias.
The effects of the opioid-type stressor, immobilization, on severity of ouabain-induced cardiac arrhythmias and the possible involvement of serum catecholamines were investigated in rats. Immobilization significantly reduced the number of ventricular premature beats and the incidence of ventricular tachycardia episodes. The arterial serum catecholamine levels (A, NA and DA), measured immediately after the stressor application, were increased significantly and were in negative correlation with the arrhythmia parameters. Both changes were reversed by naloxone (5 mg/kg) treatment after application of immobilization. The effects observed in this study may be attributed to the actions of endogenous opioid peptides released during stress.


Fucosylated Human Milk Oligosaccharides and N-Glycans in the Milk of Chinese Mothers Regulate the Gut Microbiome of Their Breast-Fed Infants during Different Lactation Stages.
The milk glycobiome has a significant impact on the gut microbiota of infants, which plays a pivotal role in health and development. Fucosylated human milk oligosaccharides (HMOs) and N-glycans on milk proteins are beneficial for the development of healthy gut microbiota, and the fucosylation levels of these glycans can be affected by the maternal fucosyltransferase 2 gene (FUT2). Here, we present results of longitudinal research on paired milk and stool samples from 56 Chinese mothers (CMs) and their breast-fed children. Changes of HMOs and fucosylated N-glycans in milk of CMs at different lactation stages were detected, which allowed characterization of the major differences in milk glycans and consequential effects on the gut microbiome of infants according to maternal FUT2 status. Significant differences in the abundance of total and fucosylated HMOs between secretor and nonsecretor CMs were noted, especially during early lactation. Despite a tendency toward decreasing milk protein concentrations, the fucosylation levels of milk N-glycans increased during late lactation. The changes in the levels of fucosylated HMOs and milk N-glycans were highly correlated with the growth of Bifidobacterium spp. and Lactobacillus spp. in the gut of infants during early and later lactation, respectively. Enriched expression of genes encoding glycoside hydrolases, glycosyl transferases, ATP-binding cassette (ABC) transporters, and permeases in infants fed by secretor CMs contributed to the promotion of these bacteria in infants. Our data highlight the important role of fucosylated milk glycans in shaping the gut microbiome of infants and provide a solid foundation for development of "personalized" nutrition for Chinese infants. IMPORTANCE Human milk glycans provide a broad range of carbon sources for gut microbes in infants. Levels of protein glycosylation in human milk vary during lactation and may also be affected by the stages of gestation and lactation and by the secretor status of the mother. This was the first study to evaluate systematically dynamic changes in human milk oligosaccharides and fucosylated N-glycans in the milk of Chinese mothers with different secretor statuses during 6 months of lactation. Given the unique single nucleotide polymorphism site (rs1047781, A385T) on the fucosyltransferase 2 gene among Chinese populations, our report provides a specific insight into the milk glycobiome of Chinese mothers, which may exert effects on the gut microbiota of infants that differ from findings from other study cohorts.


Myeloid HIF-1 attenuates the progression of renal fibrosis in murine obstructive nephropathy.
Hypoxia-inducible factors (HIFs) play an important role in the pathogenesis of renal fibrosis. Although the role of macrophage infiltration in the progression of renal fibrosis is well known, the role of macrophage HIF-1 remains to be revealed. To address this question, myeloid specific conditional HIF-1 knock out mice were subjected to unilateral ureteral obstruction (UUO). Renal interstitial deposition of collagen Ⅲ and mRNA expressions of collagen Ⅰ and collagen Ⅲ were markedly increased at 7 days after UUO and myeloid HIF-1 depletion significantly accelerated these increases. Immunohistochemistry and flow cytometric analysis revealed that renal infiltrating macrophages were increased with duration of UUO but myeloid HIF-1 depletion did not affect these changes. Myeloid HIF-1 depletion did not affect M1 and M2 macrophage phenotype polarization in obstructed kidneys. Renal connective tissue growth factor (CTGF) expression was markedly increased and myeloid HIF-1 depletion further enhanced this increase. Immunomagnetic separation of renal cells revealed that renal CTGF was expressed predominantly in renal cells other than macrophages. It is suggested that myeloid HIF-1 attenuates the progression of renal fibrosis in murine obstructive kidney. Alteration of CTGF expression in renal cells other than macrophages is one of possible mechanisms by which myeloid HIF-1 protected renal fibrosis.


Morphine or oxycodone in cancer pain?
Oxycodone is an opioid analgesic that closely resembles morphine. Oxymorphone, the active metabolite of oxycodone, is formed in a reaction catalyzed by CYP2D6, which is under polymorphic genetic control. The role of oxymorphone in the analgesic effect of oxycodone is not yet clear. In this study, controlled-release (CR) oxycodone and morphine were examined in cancer pain. CR oxycodone and morphine were administered to 45 adult patients with stable pain for 3-6 days after open-label titration in a randomized, double-blind, cross-over trial. Twenty patients were evaluable. Both opioids provided adequate analgesia. The variation in plasma morphine concentrations was higher than that of oxycodone, consistent with the lower bioavailability of morphine. Liver dysfunction affected selectively either oxycodone or morphine metabolism. Three patients with markedly aberrant plasma opioid concentrations are presented. Significant individual variation in morphine and oxycodone metabolism may account for abnormal responses during treatment of chronic cancer pain.


Mechanisms of cognitive-behavioral therapy effects on symptoms of body dysmorphic disorder: a network intervention analysis.
Body dysmorphic disorder (BDD) is a severe and undertreated condition. Although cognitive-behavioral therapy (CBT) is the first-line psychosocial treatment for this common disorder, how the intervention works is insufficiently understood. Specific pathways have been hypothesized, but only one small study has examined the precise nature of treatment effects of CBT, and no prior study has examined the effects of supportive psychotherapy (SPT). This study re-examined a large trial (n = 120) comparing CBT to SPT for BDD. Network intervention analyses were used to explore symptom-level data across time. We computed mixed graphical models at multiple time points to examine relative differences in direct and indirect effects of the two interventions. In the resulting networks, CBT and SPT appeared to differentially target certain symptoms. The largest differences included CBT increasing efforts to disengage from and restructure unhelpful thoughts and resist BDD rituals, while SPT was directly related to improvement in BDD-related insight. Additionally, the time course of differences aligned with the intended targets of CBT; cognitive effects emerged first and behavioral effects second, paralleling cognitive restructuring in earlier sessions and the emphasis on exposure and ritual prevention in later sessions. Differences in favor of CBT were most consistent for behavioral targets. CBT and SPT primarily affected different symptoms. To improve patient care, the field needs a better understanding of how and when BDD treatments and treatment components succeed. Considering patient experiences at the symptom level and over time can aid in refining or reorganizing treatments to better fit patient needs.


Vertical organization of gamma-aminobutyric acid-accumulating intrinsic neuronal systems in monkey cerebral cortex.
Light and electron microscopic methods were used to examine the neurons in the monkey cerebral cortex labeled autoradiographically following the uptake and transport of [3H]-gamma-aminobutyric acid (GABA). Nonpyramidal cell somata in the sensory-motor areas and primary visual area (area 17) were labeled close to the injection site and at distances of 1 to 1.5 mm beyond the injection site, indicating labeling by retrograde axoplasmic transport. This labeling occurred preferentially in the vertical dimension of the cortex. Prior injections of colchicine, an inhibitor of axoplasmic transport, abolished all labeling of somata except those within the injection site. In each area, injections of superficial layers (I to III) produced labeling of clusters of cell somata in layer V, and injections of the deep layers (V and VI) produced labeling of clusters of cell somata in layers II and III. In area 17, injections of the superficial layers produced dense retrograde cell labeling in three bands: in layers IVC, VA, and VI. Vertically oriented chains of silver grains linked the injection sites with the resulting labeled cell clusters. In all areas, the labeling of cells in the horizontal dimension, i.e., on each side of an injection, was insignificant. Electron microscopic examination of labeled neurons confirms that the neurons labeled at a distance from an injection site are nonpyramidal neurons, many with somata so small that they would be mistaken for neuroglial cells light microscopically. They receive few axosomatic synapses, most of which have symmetric membrane thickenings. The vertical chains of silver grains overlie neuronal processes identifiable as both dendrites and myelinated axons, but unmyelinated axons may also be included. The clusters of [3H]GABA-labeled cells are joined to one another and to adjacent unlabeled cells by many junctional complexes, including puncta adherentia and multi-lamellar cisternal complexes. We conclude that groups of GABA-transporting neurons are likely to use GABA as a transmitter and form an inhibitory, bidirectional system of connections that join together cells in superficial and deep layers of functional cortical columns; intrinsic, horizontal GABAergic connections are either far less significant in the organization of the cerebral cortex or are not labeled by this method.(ABSTRACT TRUNCATED AT 400 WORDS)


Prognostic markers in acute leukemia.
The identification of biologic markers for disease outcome in hematopoietic malignancies is essential for the development of "risk-adapted" therapies. Although new prognostic factors are frequently described, their real clinical and biologic impact is often difficult to determine. Factors that influence a marker's true prognostic value include several variables of study design: study size, uniform versus nonuniform patient treatment, methodologic variations, and correlations with other variables. Despite these concerns, several important prognostic factors have emerged in acute leukemias. For example, in acute myeloid leukemia, the multidrug resistant phenotype, whether conferred by the classic P-glycoprotein (multidrug resistance protein 1) or by other mechanisms, and cytogenetics are major prognostic indicators for outcome. In acute lymphoblastic leukemia, markers associated with loss of growth control (loss of tumor suppressor genes, increased proliferative fraction) likewise identify a group of poor-prognosis patients. The delineation of prognostic factors such as these allows for the better identification of patients who may benefit from risk-adapted therapies.


Adipokines as potential biomarkers for type 2 diabetes mellitus in cats.
Type 2 diabetes mellitus (T2DM) is no longer only a disease of humans, but also of domestic animals, and it particularly affects cats. It is increasingly thought that because of its unique characteristics, T2DM may belong not only to the group of metabolic diseases but also to the group of autoimmune diseases. This is due to the involvement of the immune system in the inflammation that occurs with T2DM. Various pro- and anti-inflammatory substances are secreted, especially cytokines in patients with T2DM. Cytokines secreted by adipose tissue are called adipokines, and leptin, adiponectin, resistin, omentin, TNF-α, and IL-6 have been implicated in T2DM. In cats, approximately 90% of diabetic cases are T2DM. Risk factors include older age, male sex, Burmese breed, presence of obesity, and insulin resistance. Diagnosis of a cat requires repeated testing and is complicated compared to human diagnosis. Based on similarities in the pathogenesis of T2DM between humans and cats, adipokines previously proposed as biomarkers for human T2DM may also serve in the diagnosis of this disease in cats.


Inferior Alveolar Plus Buccal Nerve Block Decreases Postoperative Pain Scores at Buccal Mucosal Graft Harvest Site: A Retrospective Analysis.
Postoperative pain at buccal mucosal graft (BMG) harvest site hinders the resumption of food intake. We aim to study the effect of inferior-alveolar nerve block plus buccal nerve block (IANB+BNB) on pain scores. This was a retrospective case-control study performed in a single center from July 2021 to July 2022 (ethics committee approval: T/IM-NF/Urology/23/27). We performed IANB+BNB with a mixture of 5 mL each of 1% lignocaine and 0.25% bupivacaine and 4 mg dexamethasone, in addition to local infiltration of 2% lignocaine and (1:100000) epinephrine combination before harvesting BMG. We retrospectively compared the recorded postoperative pain scores using the visual analog scale (VAS) among patients who received and did not receive IANB+BNB. The time for resumption of pain-free diets and postoperative analgesic requirements was compared. The study groups included 20 patients each and were similar in age and graft size. The VAS scores at 0 hours [1.0 (1.25) vs. 2.5 (3.5); P= .043], 6 hours [2.40 (± 0.69) vs. 4.60 (± 0.97); P= .008], 12 hours [2.50 (± 0.97) vs. 4.80 (± 0.92); P= .008], and 24 hours [3.0 (1.25) vs. 4.5 (1.25); P= .002] were better in the intervention arm. However, the pain beyond the second day was similar. The IANB+BNB group resumed solid food quicker, and the cumulative paracetamol dose required was less [8.9 (± 3.03) vs. 16.2 (± 5.06) g; P= .001]. Fewer patients required opioids. Patients who received IANB+BNB had better pain scores during the first 24 hours following surgery and tolerated solid diet quicker.


Trick or Treat? Licorice-Induced Hypokalemia: A Case Report.
The by-products of black licorice metabolism are toxic in high concentrations. Patients who consume large quantities of black licorice are at risk of developing an acquired syndrome of apparent mineralocorticoid excess. This presents clinically as hypertension, hypernatremia, and hypokalemia. Here, we present the unique case of a 74-year-old woman with a past medical history of neurogenic orthostatic hypotension, on fludrocortisone, who presented to the emergency department with asymptomatic hypokalemia (2.4 mmol/L) as detected in outpatient laboratory studies. During her hospital stay, it was discovered that the patient was consuming excessive amounts of black licorice. With this information, the synergistic interaction of fludrocortisone and black licorice was recognized as the cause of the patient's severe hypokalemia. The patient's fludrocortisone was stopped and she was treated with multiple courses of potassium repletion. Upon discharge, her fludrocortisone was discontinued, and she was prescribed midodrine to treat her neurogenic orthostatic hypertension. While small amounts of black licorice are safe, excessive licorice consumption can cause severe disease. Our case presents an opportunity to appreciate the plethora of etiologies for severe hypokalemia and the importance of taking a thorough patient history to avoid potentially fatal clinical outcomes.


De novo active sites for resurrected Precambrian enzymes.
Protein engineering studies often suggest the emergence of completely new enzyme functionalities to be highly improbable. However, enzymes likely catalysed many different reactions already in the last universal common ancestor. Mechanisms for the emergence of completely new active sites must therefore either plausibly exist or at least have existed at the primordial protein stage. Here, we use resurrected Precambrian proteins as scaffolds for protein engineering and demonstrate that a new active site can be generated through a single hydrophobic-to-ionizable amino acid replacement that generates a partially buried group with perturbed physico-chemical properties. We provide experimental and computational evidence that conformational flexibility can assist the emergence and subsequent evolution of new active sites by improving substrate and transition-state binding, through the sampling of many potentially productive conformations. Our results suggest a mechanism for the emergence of primordial enzymes and highlight the potential of ancestral reconstruction as a tool for protein engineering.


Evolution of gene expression patterns in a model of branching morphogenesis.
Branching morphogenesis of the ureteric bud in response to unknown signals from the metanephric mesenchyme gives rise to the urinary collecting system and, via inductive signals from the ureteric bud, to recruitment of nephrons from undifferentiated mesenchyme. An established cell culture model for this process employs cells of ureteric bud origin (UB) cultured in extracellular matrix and stimulated with conditioned media (BSN-CM) from a metanephric mesenchymal cell line (H. Sakurai, E. J. Barros, T. Tsukamoto, J. Barasch, and S. K. Nigam. Proc. Natl. Acad. Sci. USA 94: 6279-6284, 1997.). In the presence of BSN-CM, the UB cells form branching tubular structures reminiscent of the branching ureteric bud. The pattern of gene regulation in this model of branching morphogenesis of the kidney collecting system was investigated using high-density cDNA arrays. Software and analytical methods were developed for the quantification and clustering of genes. With the use of a computational method termed "vector analysis," genes were clustered according to the direction and magnitude of differential expression in n-dimensional log-space. Changes in gene expression in response to the BSN-CM consisted primarily of differential expression of transcription factors with previously described roles in morphogenesis, downregulation of pro-apoptotic genes accompanied by upregulation of anti-apoptotic genes, and upregulation of a small group of secreted products including growth factors, cytokines, and extracellular proteinases. Changes in expression are discussed in the context of a general model for epithelial branching morphogenesis. In addition, the cDNA arrays were used to survey expression of epithelial markers and secreted factors in UB and BSN cells, confirming the largely epithelial character of the former and largely mesenchymal character of the later. Specific morphologies (cellular processes, branching multicellular cords, etc.) were shown to correlate with the expression of different, but overlapping, genomic subsets, suggesting differences in morphogenetic mechanisms at these various steps in the evolution of branching tubules.


Double-stranded DNA induces the phosphorylation of several proteins including the 90 000 mol. wt. heat-shock protein in animal cell extracts.
Double-stranded DNA (dsDNA) induces the transfer of phosphate from ATP to several proteins in extracts of widely divergent eukaryotic cells. Extracts of HeLa cells, rabbit reticulocytes, Xenopus eggs and Arbacia eggs all show dsDNA-dependent protein phosphorylation. The mechanism is specific for dsDNA and will not respond to either RNA or single-stranded DNA. One of the proteins which is phosphorylated in response to dsDNA has a subunit mol. wt. of 90 000 and has been identified as a heat-shock protein (hsp90). Although mouse cell extracts were shown to contain hsp90, they failed to show a dsDNA-dependent protein phosphorylation. The observation that dsDNA can modulate the phosphorylation of a set of proteins raises the possibility that dsDNA may play a role as a cellular regulatory signal.


Electrosurgical bipolar vessel sealing versus conventional clamping and suturing for total abdominal hysterectomy.
To compare the use of Electrosurgical bipolar vessel sealing LigaSure™ small jaw instrument (LSJI) with conventional suture ligation in total abdominal hysterectomy (TAH). In this retrospective study 80 patients who underwent hysterectomy in the Gynecology and Obstetrics Department of Gulhane Education and Research Hospital between April 2017 and August 2018 were included. Two different groups that underwent Electrosurgical bipolar vessel sealing LigaSure™ small jaw instrument (LSJI) and conventional suture ligation in hysterectomy operation were analyzed retrospectively. The parameters evaluated and compared between the two groups include operation time, intraoperative blood loss, duration of hospitalization and incision length. Among the parameters we compared between the two groups, there was no statistically significant difference between the amount of intraoperative blood loss (p:0.68) and the incision length (p:0.65). Among the parameters we compared between the two groups, a statistically significant difference was observed between the operation time (p:0.016) and the duration of hospitalization (p:0.01). Our comparison of LSJI vs. conventional ligation in hysterectomy revealed a significant difference only in operative time, where surgeries involving conventional ligation were shorter. On the other hand, incision length was evaluated in our study which has not been addressed in previous studies. There is also a need for multi-center studies that include more patients and evaluate cost-effectiveness.


Stroke and intracranial venous thrombosis during pregnancy and puerperium.
To determine nationally representative estimates of the incidence of stroke and intracranial venous thrombosis during pregnancy and the puerperium, and to identify potential risk factors for these conditions. National Hospital Discharge Survey data were analyzed for the period 1979 to 1991. Nationally representative estimates of risk were calculated by age, race, presence of pregnancy-related hypertension, census region, hospital ownership, and number of hospital beds. Multivariate models were developed using logistic regression. There were an estimated 8,918 cases of stroke and 5,723 cases of intracranial venous thrombosis during pregnancy and the puerperium in the United States among 50,264,631 deliveries, giving risks of 17.7 cases of stroke and 11.4 cases of intracranial venous thrombosis per 100,000 deliveries. In the multivariate models, stroke was associated strongly with pregnancy-related hypertension, larger hospital size, and proprietary hospital ownership, and inversely associated with living in the South. Intracranial venous thrombosis was associated with maternal age. Stroke and intracranial venous thrombosis are relatively common complications of pregnancy and the puerperium. Collectively, rates for these conditions are about 50% greater for the entire period of pregnancy and the puerperium than for the immediate peripartum period.


High sensitivity temperature measurement via mask-free hybrid polymer long period fiber grating.
Long-period fiber gratings (LPFGs) are useful for environmental sensing under conditions of high corrosiveness and electromagnetic interference. Most LPFGs are fabricated by coherent or high-power UV illumination of an optical fiber under an amplitude mask, resulting in narrow and environmentally-dependent band rejection. We present a hybrid LPFG waveguide fabricated without an amplitude mask through polymer self-assembly under low-power incoherent UV illumination, which demonstrates high-temperature sensitivity in its transmission spectrum compared to LPFG sensors based purely on silica waveguides. A sensitivity of 1.5 nm °C -1 is obtained experimentally for attenuation near 1180 nm, and a sensitivity of 4.5 nm °C -1 with a low random error was obtained with a composite of attenuation bands. Finite element method simulations and coupling mode theory reveal this to be due to a thermo-optic coefficient one order of magnitude greater than that of fused silica. The device has potential for a simple and inexpensive transmission intensity based temperature sensor consisting of an infrared light source, the LPFG, a bandpass filter, and a photodiode.


[Curcumin suppresses invasiveness and migration of human glioma cells in vitro by inhibiting HDGF/β-catenin complex].
To investigate the effect of curcumin on the invasion and migration of human glioma cells in vitro and explore the molecular mechanisms. MTT assay was used for screening the optimal curcumin concentrations. The effects of curcumin on the invasion and metastasis of human glioma cell lines U251 and LN229 were tested using Transwell assay, Boyden assay and wound-healing assays. The expression of the related proteins and their interactions were determined using Western blotting and coimmunoprecipitation assay. Curcumin at the concentration of 20 μmol/L for 48 h was used as the optimal condition for subsequent cell treatment. In the two glioma cell lines, curcumin significantly suppressed the invasion and migration of the cells (P < 0.05) and lowered the expressions of hepatoma-derived growth factor (HDGF), Ncadherin, vimentin, Snail and Slug, but increased the expression of E-cadherin. Interference of HDGF in curcumin-treated glioma cells synergistically inhibited the epithelial-mesenchymal transition (EMT) signals, while overexpression of HDGF significantly reversed the inhibitory effect of curcumin on EMT; curcumin treatment could significantly reduce the binding of HDGF to β-catenin. Curcumin suppresses EMT signal by reducing HDGF/β-catenin complex and thereby lowers the migration and invasion abilities of human glioma cells in vitro.


Chronic progredient diffuse alveolar damage probably related to exposure to herbicides.
Clinical history and wedge biopsy specimen findings of a Vietnam veteran suffering from progressive severe tissue damage of lung are presented. The patient served as a soldier in defoliated areas for 2 years and developed severe chest pain and dyspnoea with chronic postnasal dripping, maxillary sinusitis and allergic asthmoid bronchitis with pronounced obstructions and eosinophilia. Recurrent onsets of symptoms over a period of 10 years led to wedge biopsies of the left upper lobe, right lower lobe and mediastinal lymph node. Histology is consistent with chronic, slightly progressive diffuse alveolar damage including moderate interstitial fibrosis. Total destruction of mediastinal lymph node with deposits of amorphous material and foreign body giant cells were noted. Histology findings and clinical course favor hypersensitivity reaction of lung and congestion of exogeneous material probably related to exposure to herbicides.


Prospective, multicenter, randomized trial to compare incidence of new-onset diabetes mellitus and glucose metabolism in patients receiving cyclosporine microemulsion versus tacrolimus after de novo kidney transplantation.
New-onset diabetes mellitus (NODM) is associated with increased risk of graft failure and death in renal transplant recipients. Some clinical studies have indicated that NODM risk is higher with tacrolimus than cyclosporine, but no comparative trial has used American Diabetic Association (ADA)/World Health Organization (WHO) criteria for diagnosis of diabetes mellitus. The Diabetes Incidence After Renal Transplantation, Neoral C2 Monitoring Versus Tacrolimus (DIRECT) study is a 6-month open-label, multicenter trial comparing the impact of tacrolimus and Neoral (cyclosporine microemulsion) on glucose metabolism in 700 de novo kidney transplant recipients, based on ADA/WHO criteria. Patients are randomized to tacrolimus (C0 monitoring) or Neoral (C2 monitoring), stratified by baseline diabetic status and ethnicity. All patients receive basiliximab, corticosteroids, and mycophenolate mofetil or enteric-coated mycophenolate acid (myfortic). Pooled interim 3-month results from a subset of 115 patients receiving either tacrolimus or Neoral showed that the primary efficacy end-point (biopsy-proven acute rejection [BPAR], graft loss or death) occurred in 11 patients (10%). There were four graft losses and only one death, which occurred after graft loss. Eight patients experienced BPAR (7.3%). Among 99 patients who were nondiabetic at baseline, 14 developed NODM by month 3, 17 developed impaired fasting glucose or impaired glucose tolerance, and another 5 patients received hypoglycemic treatment for at least 14 consecutive days or at the month 3 visit, resulting in a 36% incidence of impaired glucose metabolism. At 3 months, median GFR (Nankivell) was 63.7 mL/min; median serum creatinine was 137 micromol/L. Full complete results are expected in December 2005.


Predictors of overall survival among patients treated with sirolimus/tacrolimus vs methotrexate/tacrolimus for GvHD prevention.
Sirolimus (SIR)/tacrolimus (TAC) is an alternative to methotrexate (MTX)/TAC. However, rational selection among these GvHD prophylaxis approaches to optimize survival of individual patients is not possible based on current evidence. We compared SIR/TAC (n=293) to MTX/TAC (n=414). The primary objective was to identify unique predictors of overall survival (OS). Secondary objective was to compare acute and chronic GvHD, relapse, non-relapse mortality, thrombotic microangiopathy (TMA), hepatic veno-occlusive disease (VOD/SOS), and acute kidney injury. Day 100 grades II-IV acute GvHD was significantly reduced in SIR/TAC vs MTX/TAC group (63 vs 73%, P=0.02). An interaction between GvHD prophylaxis groups and comorbidity index (hematopoietic cell transplantation (HCT)-CI) significantly impacted OS. Patients with HCT-CI⩾4 had significantly worse OS with MTX/TAC (HR 1.86, 95% CI 1.14-3.04, P=0.01) while no such effect was seen for SIR/TAC (HR 0.78, 95% CI 0.48-1.26, P=0.31). Other end points did not significantly differ between groups except TMA and VOD/SOS were increased in the SIR/TAC group, but excess death from these complications was not observed. We conclude, GvHD prophylaxis approach of SIR/TAC is associated with reduced grades II-IV acute GvHD, comparable toxicity profile to MTX/TAC, and improved OS among patients with HCT-CI⩾4.


Placement of three-pin head holders in the Concorde position.
To reevaluate the Concorde position with different surgical interventions to the posterior fossa and cervical pathology and to improve patient comfort in the Concorde position through obtuse angle placement of the three-pin holder while the patient is in the supine position. Twenty-nine patients with posterior fossa pathology or cervical pathology were included in this study. All patients were operated in the Concorde position. The three-pin holder was placed with an obtuse angle while the patient was in the supine position as shown in figure 1a. The angle between the handle of the three-pin holder and the floor was measured in the supine and prone positions as shown in Figure 1A,B. The average angle between the floor and the handle of the three-pin holder in the supine position and the Concorde position was 135 degrees (SD +/- 5.45) and 95 degrees (SD +/- 3.26) respectively (Figure 4) All the patient's body including the shoulders was within the borders of the operation table. The placement of three-pin holders with an obtuse angle in the supine position provides three advantages: easier manipulation during neck flexion especially for cervical vertebral pathology, much less body weight loading on the three-pin holders during surgery, and less flexion of the neck to expose pathology located in the cervical or posterior fossa region.


Three-dimensional analysis of the vascular system in the rat spinal cord with scanning electron microscopy of vascular corrosion casts. Part 2: Acute spinal cord injury.
The purpose of this study was to investigate the vascular mechanisms involved in the pathophysiology of acute spinal cord injury. Vascular corrosion casts of traumatized rat spinal cords at C7-T1 were inspected by scanning electron microscopy. Nineteen rats were subjected to a 51g acute clip compression at C8-T1 and then underwent transcardial perfusion with polyester resin at 15 minutes, 4 hours, or 24 hours after injury. The injured spinal cord appeared almost avascular at the compression site, although the large vessels on the surface of the spinal cord were all intact. The sulcal arteries at the injury site frequently showed constriction, and the impressions of endothelial nuclei were more slender and less distinct in the constricted arterial casts. Extravasation of the injected resin at the injury site was observed most frequently in the 15-minute group. Poorly filled distal branches of the sulcal arteries were seen at the injury site in every group. Indeed, it was concluded that the disruption and occlusion of the sulcal arteries and their branches accounted for a considerable amount of the posttraumatic ischemia of the cord. Occlusion of the sulcal arteries in the anterior median sulcus at the injury site was more frequently observed in the 24-hour group than in earlier groups. This observation suggests that there was a progressive circulatory disturbance of the damaged sulcal arteries at the injury site. The 4- and 24-hour groups showed avascular areas extending longitudinally from the injury site in the posterior columns, probably the result of hemorrhage and venous obstruction.


Variations in ovarian steroid levels during the luteal phase of the menstrual cycle.
1. Six subjects were investigated during the luteal phase of the menstrual cycle to determine whether the ovarian steroids, estrogen and progesterone were released in an episodic manner. 2. Analysis of plasma obtained every 20 min. during a normal working day provided no evidence for pulsatile release of either steroid although values were lower in the afternoon than in the morning (p less than 0.001). A good correlation (r=0.908) was obtained for the release of both hormones. 3. Cortisol secretion was inversely related to that of the ovarian steroids.


Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL).
A 44-year-old Caucasian man presented with seizures and cognitive impairment. He had marked retinal drusen, and MR brain scan showed features of cerebral small vessel disease; he was diagnosed with a leukoencephalopathy of uncertain cause. He died at the age of 46 years and postmortem brain examination showed widespread small vessel changes described as a vasculopathy of unknown cause. Seven years postmortem, whole-genome sequencing identified a homozygous nonsense HTRA1 mutation (p.Arg302Ter), giving a retrospective diagnosis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy.


Prediction of gradients in fibrous subaortic stenosis by continuous wave two-dimensional Doppler echocardiography: animal studies.
The purpose of this study was to assess the accuracy of continuous wave, two-dimensional Doppler echocardiography for predicting pressure gradients across discrete subaortic stenoses. Twenty-three Newfoundland dogs with subaortic stenosis were studied by closed chest Doppler interrogation of aortic velocity from an apical view of the left ventricular outflow tract simultaneously with measurements of pressure gradient during cardiac catheterization. Continuous mode Doppler interrogation was used with two-dimensional echographic guidance (Irex model IIIB) to compare the Doppler-derived maximal velocity with the pressure gradient across the obstruction at rest and after provocation with amyl nitrite inhalation and isoproterenol infusion. The maximal velocities recorded by Doppler ranged from 98 to 539 cm/s and correlated with hemodynamic gradients ranging from 3 to 123 mm Hg (r = 0.92, SEE = 37 cm/s). Doppler velocities were converted to gradients using a simplification of the Bernoulli relation (gradient = 4 X maximal velocity2); the resulting Doppler-derived gradients also correlated closely with the catheterization-measured pressure gradients (r = 0.95, SEE = 7.1 mm Hg). The predictive capability of Doppler echocardiography for estimating the pressure gradient across fibromuscular subaortic obstructions in this group of dogs with a spectrum of disease similar to that found in human beings was validated. The results also indicate that Doppler methods may have clinical applications in patients with subaortic stenosis.


Surgical treatment of recurrent groin hernia.
Recurrent groin hernia is not uncommon in Taiwan. Subsequent surgical repairs are difficult, due to cicartrization and deterioration of the inguinal floor. In this report, the intermediate and long-term outcomes of 212 patients with recurrent groin hernias who underwent surgical repair within a 10-year period were analyzed in order to assess the effectiveness of two modified repair techniques. Patients with unilateral first-time recurrent hernia (UR; n = 87) were treated by a modified Shouldice technique using an inguinal approach. Those with bilateral or multiple recurrences (MRs; n = 125) were treated with giant prosthetic reinforcement of the visceral sac (GPRVS, Stoppa operation) using a midline preperitoneal approach. Complete exploration of the groin floor on the side of recurrence revealed a high rate of direct space defects (UR, 41.5%; MR, 65%) and multiple posterior wall defects (UR, 29.9%; MR, 30%). In the UR group, a 4 x 10-cm preperitoneal prosthetic mesh was incorporated to reinforce the repair. For MR patients, I reduced the transverse dimension of the mesh prosthesis by 2 cm compared with the original Stoppa protocol; to reduce crinkling, the average dimensions were 23 x 14 cm. Complications in the UR group included testicular atrophy (3 patients) and femoral vein thrombosis (1). Complications in the MR group were transient scrotal fluid accumulation (9 patients), fatal perioperative acute myocardial infarction (1), and failure of the peritoneum to grow over the mesh (1). The average hospital stay was 3 days in the UR group and 6 days in the MR group. The long-term follow-up (1-9 years) revealed a 5.7% re-recurrence rate with an 86.2% follow-up rate in the UR group, and a 1.9% re-recurrence rate with an 86.6% follow-up rate in the UR group. I conclude that GPRVS is an excellent treatment for URs, but the transverse dimension of the prosthetic mesh should be reduced for Taiwanese subjects. However, for first-time MRs, a modified Shouldice technique with incorporation of a preperitoneal prosthetic mesh is still recommended. The surgical dissection is less extensive and the hospital stay is shorter, while the re-recurrence rate is acceptably low.


Substrate-binding ability of Escherichia coli ribonucleic acid polymerase in relation to its protein composition.
Interaction between Escherichia coli RNA polymerase and its substrates, the nucleoside triphosphates, was studied by gel-filtration and dialysis-rate-measurement techniques. 2. The holoenzyme bound variable amounts of ATP and GTP. There was no correlation between substrate-binding ability and enzyme activity of different enzyme preparations. 3. The core enzyme bound a maximum of 0.1 mol of ATP/mol of enzyme. The dissociation constant of this interaction was of the order of 1 X 10(-5)M. The core enzyme did not bind GTP. 4. A protein of mol.wt. 60000, which was eluted in the first fraction during phosphocellulose column chromatography of the holoenzyme, bound appreciable amounts of ATP. The dissociation constant of this interaction was of the order of 3 X 10(-5)-5 X 10(-6)M. 5. Evidence presented shows that this protein, and not the sigma factor, is responsible for the observed variation in the ATP-binding ability of the holoenzyme.


Microfluidic on-demand droplet generation, storage, retrieval, and merging for single-cell pairing.
A multifunctional microfluidic platform combining on-demand aqueous-phase droplet generation, multi-droplet storage, and controlled merging of droplets selected from a storage library in a single integrated microfluidic device is described. A unique aspect of the technology is a microfluidic trap design comprising a droplet trap chamber and lateral bypass channels integrated with a microvalve that supports the capture and merger of multiple droplets over a wide range of individual droplet sizes. A storage unit comprising an array of microfluidic traps operates in a first-in first-out manner, allowing droplets stored within the library to be analyzed before sequentially delivering selected droplets to a downstream merging zone, while shunting other droplets to waste. Performance of the microfluidic trap is investigated for variations in bypass/chamber hydrodynamic resistance ratio, micro-chamber geometry, trapped droplet volume, and overall flow rate. The integrated microfluidic platform is then utilized to demonstrate the operational steps necessary for cell-based assays requiring the isolation of defined cell populations with single cell resolution, including encapsulation of individual cells within an aqueous-phase droplet carrier, screening or incubation of the immobilized cell-encapsulated droplets, and generation of controlled combinations of individual cells through the sequential droplet merging process. Beyond its utility for cell analysis, the presented platform represents a versatile approach to robust droplet generation, storage, and merging for use in a wide range of droplet-based microfluidics applications.


Impact of early aggressive nutrition on retinal development in premature infants.
The normal retinal development is interrupted by preterm birth and a retinopathy of prematurity (ROP) may develop as its consequence. ROP is characterized by aberrant vessel formation in the retina as a response to multiple risk factors influencing the process of retinal angiogenesis. Insulin-like growth factor I (IGF-1) and vascular endothelial growth factor (VEGF) play an important role in the process of normal retinal vascularization. Insufficient nutrition during the first 4 postnatal weeks results in low serum levels of IGF-1, which is essential for correct retinal vessels formation, ensuring survival of the newly formed endothelial cells. Low IGF-1 level results in stop of angiogenesis in the retina, leaving it avascular and prompting the onset of ROP. Keeping the newborns in a positive energetic balance by providing enough nutrients and energy has a beneficial impact on their growth, neurodevelopment and decreased incidence of ROP. The best way to achieve this is the early parenteral nutrition with the high content of nutrients combined with early enteral feeding by the own mother´s breast milk. Multiple studies confirmed the safety and efficacy of early aggressive nutrition but information about its long-term effects on the metabolism, growth and development is still needed.


Functional significance of three basic N-terminal amino acids of alfalfa mosaic virus coat protein.
Infection of tobacco protoplasts with mutant alfalfa mosaic virus (AMV) RNAs indicated that three basic amino acids in the N-terminus of AMV coat protein are important for the biological activity of the coat protein in the beginning of infection. Substitution of alanines for lysines at position 14 or 17 in the coat protein resulted in a 5- or 10-fold reduction in the activity of the protein, respectively. However, substitution of alanine for arginine at position 18 entirely abolished activity. Arginine 18 was also required for the coat protein to bind to the 3' noncoding region of the virus RNA in vitro, whereas lysine 14 or 17 was not required. Thus, these results indicate that arginine 18 is essential for the activity of the coat protein in early infection and that binding of the coat protein to AMV RNA correlates with activity.


PC12 cells utilize the homophilic binding site of L1 for cell-cell adhesion but L1-alphavbeta3 interaction for neurite outgrowth.
Treatment of PC12 cells with nerve growth factor induces their differentiation into sympathetic neuron-like cells and the concomitant expression of the neural cell adhesion molecule L1, a member of the Ig superfamily. To investigate the mechanism of L1-stimulated neurite outgrowth in PC12 cells, substrate-immobilized fusion proteins containing different extracellular domains of L1 were assayed for their neuritogenic activity. Surprisingly, domain Ig2 of L1, which was previously found to contain both homophilic binding and neuritogenic activities, failed to promote neurite outgrowth. In contrast, L1-Ig6 stimulated neurite outgrowth from PC12 cells. Despite this, homotypic binding of PC12 cells was significantly inhibited by antibodies against L1-Ig2, indicating that L1-L1 binding contributed to the intercellular adhesiveness of PC12 cells, but L1-stimulated neurite outgrowth depends on heterophilic interactions. Thus, PC12 cells provide a valuable model for the study of these two distinct functions of L1. Mutagenesis of L1-Ig6 highlighted the importance of the Arg-Gly-Asp motif in this domain for neuritogenesis. Inhibition studies using cyclic Arg-Gly-Asp-containing peptide and anti-integrin antibodies suggested the involvement of alphavbeta3 integrin. Furthermore, neurite outgrowth stimulated by L1-Ig6 was inhibited by lavendustin A and the MEK inhibitor PD98059, suggesting a signaling pathway that involves tyrosine kinase activation and the mitogen-activated protein kinase cascade.


The past, present and future of cyber-physical systems: a focus on models.
This paper is about better engineering of cyber-physical systems (CPSs) through better models. Deterministic models have historically proven extremely useful and arguably form the kingpin of the industrial revolution and the digital and information technology revolutions. Key deterministic models that have proven successful include differential equations, synchronous digital logic and single-threaded imperative programs. Cyber-physical systems, however, combine these models in such a way that determinism is not preserved. Two projects show that deterministic CPS models with faithful physical realizations are possible and practical. The first project is PRET, which shows that the timing precision of synchronous digital logic can be practically made available at the software level of abstraction. The second project is Ptides (programming temporally-integrated distributed embedded systems), which shows that deterministic models for distributed cyber-physical systems have practical faithful realizations. These projects are existence proofs that deterministic CPS models are possible and practical.


[Gene expression profiling in human mesothelioma cells using DNA microarray and high-density filter array technologies].
Although the use of asbestos has been banned in most industrialized countries, it is still a major public health concern. Asbestos fibers are mutagenic and carcinogenic for humans, classified as "carcinogen category 1 (T, R45: can cause the cancer)" in the 25th adaptation of the directive 67/548/EEC. In France, asbestos is thought to be responsible each year for many pulmonary diseases: pleural plaque, bronchogenic carcinoma and mesothelioma (malignant tumor of pleura). In order to better understand the transformation process of pleural cells, we compared the gene expression of mesothelium cells (Met-5A) and mesothelioma cells (MSTO-211H) using high-density filter array (588 genes) and microarray (6.969 genes). Results of both technologies were compared and expression levels of several genes were confirmed by quantitative RT-PCR. Data analysis with GemtoolsTM 2.4 software allows us hierarchical classification of genes of known functions by enzyme, function and pathway clusters and leads to characterize both malignant and normal phenotypes. Finally, the comparison between the two cell lines provides new markers of mesothelioma and pleura. They could be useful for diagnostic, prognostic and therapeutic.


Modification of tumor cell sensitivity to antineoplastic agents lonidamine and bouvardin (NSC 259968) at elevated temperatures.
Lymphocytic leukemia P388 and Sarcoma-180 cells were exposed to various concentrations (0.01 mM to 0.04 mM) of lonidamine at 37 degrees C and 43 degrees C for 30 min and 60 min in vitro. Similarly combined effect of lonidamine and bouvardin on these tumor cells was also assessed at 37 degrees C and 43 degrees C. The effect was evaluated by comparing the rate of 3H-thymidine incorporation in treated cells to that of control cells. It was observed that at 37 degrees C lonidamine did not exert cytotoxic effect on P388 cells at prescribed time interval. Sarcoma-180 cells, however, showed significant sensitivity to the drug at 37 degrees C. Lonidamine exhibited greater cytotoxicity at 43 degrees C towards both P388 and Sarcoma-180 cells at 30 and 60 min exposure. Lonidamine also enhanced cytotoxicity of bouvardin in P388 and reversed the natural resistance of Sarcoma-180 cells to bouvardin at 37 degrees C.


Deep Learning to Unveil Correlations between Urban Landscape and Population Health.
The global healthcare landscape is continuously changing throughout the world as technology advances, leading to a gradual change in lifestyle. Several diseases such as asthma and cardiovascular conditions are becoming more diffuse, due to a rise in pollution exposure and a more sedentary lifestyle. Healthcare providers deal with increasing new challenges, and thanks to fast-developing big data technologies, they can be faced with systems that provide direct support to citizens. In this context, within the EU-funded Participatory Urban Living for Sustainable Environments (PULSE) project, we are implementing a data analytic platform designed to provide public health decision makers with advanced approaches, to jointly analyze maps and geospatial information with healthcare and air pollution data. In this paper we describe a component of such platforms, which couples deep learning analysis of urban geospatial images with healthcare indexes collected by the 500 Cities project. By applying a pre-learned deep Neural Network architecture, satellite images of New York City are analyzed and latent feature variables are extracted. These features are used to derive clusters, which are correlated with healthcare indicators by means of a multivariate classification model. Thanks to this pipeline, it is possible to show that, in New York City, health care indexes are significantly correlated to the urban landscape. This pipeline can serve as a basis to ease urban planning, since the same interventions can be organized on similar areas, even if geographically distant.


[Split brain and the problem of interhemispheric relations].
For the last 15-20 years the study of interhemispheric relations made a big progress. This progress was facilitated by use of new methods in combination with midsagittal sections of comissural connections at different levels. An assumption is made that interhemispheric exchange of sensory information is of certain importance for the short-term memory and for compensatory mechanisms of the brain. The importance of hemispheric interaction for coordinated motor reactions and for subtle spatial orientation of animals is determined. Observation of patients with surgically dissected brain is a big contribution to further study of interhemispheric relations.


Direct optical sensors: principles and selected applications.
In the field of bio and chemosensors a large number of detection principles has been published within the last decade. These detection principles are based either on the observation of fluorescence-labelled systems or on direct optical detection in the heterogeneous phase. Direct optical detection can be measured by remission (absorption of reflected radiation, opt(r)odes), by measuring micro-refractivity, or measuring interference. In the last case either Mach-Zehnder interferometers or measurement of changes in the physical thickness of the layer (measuring micro-reflectivity) caused, e.g., by swelling effects in polymers (due to interaction with analytes) or in bioassays (due to affinity reactions) also play an important role. Here, an overview of methods of microrefractometric and microreflectometric principles is given and benefits and drawbacks of the various approaches are demonstrated using samples from the chemo and biosensor field. The quality of sensors does not just depend on transduction principles but on the total sensor system defined by this transduction, the sensitive layer, data acquisition electronics, and evaluation software. The intention of this article is, therefore, to demonstrate the essentials of the interaction of these parts within the system, and the focus is on optical sensing using planar transducers, because fibre optical sensors have been reviewed in this journal only recently. Lack of selectivity of chemosensors can be compensated either by the use of sensor arrays or by evaluating time-resolved measurements of analyte/sensitive layer interaction. In both cases chemometrics enables the quantification of analyte mixtures. These data-processing methods have also been successfully applied to antibody/antigen interactions even using cross-reactive antibodies. Because miniaturisation and parallelisation are essential approaches in recent years, some aspects and current trends, especially for bio-applications, will be discussed. Miniaturisation is especially well covered in the literature.


Glyoxalase II: molecular characteristics, kinetics and mechanism.
The mechanism that has been proposed for glyoxalase II [36] is summarized in Figure 3. It involves direct nucleophilic attack of an active-site histidine on the thiol ester substrate to form an acyl-imidazole intermediate which then rapidly hydrolyses. This is consistent with the known susceptibility of thiol esters to aminolysis and with the lability of acyl-imidazoles [47].


A Recombinant 47-kDa Outer Membrane Protein Induces an Immune Response against Orientia tsutsugamushi Strain Boryong.
We investigated the 47-kDa outer membrane protein (OMP), which is a periplasmic serine protease and an antigenic major surface protein of Orientia tsutsugamushi, as a vaccine candidate. We developed a conventional subunit vaccine expressing recombinant 47-kDa OMP (rec47) and a DNA vaccine (p47). In mouse immunization experiments, intranasal immunization with rec47 alone or with rec47 plus heat-labile enterotoxin B subunit from Escherichia coli or plus cholera toxin (CT) as adjuvants induced a higher amount of rec47-specific antibodies than intramuscular immunization with p47 alone or with p47 plus pBOOST2-samIRF7/3 (pB) as adjuvant. Moreover, the combination of rec47 and CT induced a strong cellular immune response to 47-kDa OMP, as demonstrated by a spleen cell proliferation assay, and also induced Th1- and Th2-type cytokine production, as demonstrated by a cytokine enzyme-linked immunosorbent assay. Intranasal immunization with rec47 plus CT was the most effective method for the induction of humoral and cell-mediated immune responses. Furthermore, relatively strong protection against homologous O. tsutsugamushi strain Boryong challenge was observed in mice immunized with rec47 plus CT. Therefore, 47-kDa OMP is an attractive candidate for developing a prophylactic vaccine against scrub typhus by O. tsutsugamushi infection.


CONSTANS is a photoperiod regulated activator of flowering in sorghum.
Sorghum genotypes used for grain production in temperate regions are photoperiod insensitive and flower early avoiding adverse environments during the reproductive phase. In contrast, energy sorghum hybrids are highly photoperiod sensitive with extended vegetative phases in long days, resulting in enhanced biomass accumulation. SbPRR37 and SbGHD7 contribute to photoperiod sensitivity in sorghum by repressing expression of SbEHD1 and FT-like genes, thereby delaying flowering in long days with minimal influence in short days (PNAS_108:16469-16474, 2011; Plant Genome_in press, 2014). The GIGANTEA (GI)-CONSTANS (CO)-FLOWERING LOCUS T (FT) pathway regulates flowering time in Arabidopsis and the grasses (J Exp Bot_62:2453-2463, 2011). In long day flowering plants, such as Arabidopsis and barley, CONSTANS activates FT expression and flowering in long days. In rice, a short day flowering plant, Hd1, the ortholog of CONSTANS, activates flowering in short days and represses flowering in long days. Quantitative trait loci (QTL) that modify flowering time in sorghum were identified by screening Recombinant Inbred Lines (RILs) derived from BTx642 and Tx7000 in long days, short days, and under field conditions. Analysis of the flowering time QTL on SBI-10 revealed that BTx642 encodes a recessive CONSTANS allele containing a His106Tyr substitution in B-box 2 known to inactivate CONSTANS in Arabidopsis thaliana. Genetic analysis characterized sorghum CONSTANS as a floral activator that promotes flowering by inducing the expression of EARLY HEADING DATE 1 (SbEHD1) and sorghum orthologs of the maize FT genes ZCN8 (SbCN8) and ZCN12 (SbCN12). The floral repressor PSEUDORESPONSE REGULATOR PROTEIN 37 (PRR37) inhibits sorghum CONSTANS activity and flowering in long days. Sorghum CONSTANS is an activator of flowering that is repressed post-transcriptionally in long days by the floral inhibitor PRR37, contributing to photoperiod sensitive flowering in Sorghum bicolor, a short day plant.


Tn6198, a novel transposon containing the trimethoprim resistance gene dfrG embedded into a Tn916 element in Listeria monocytogenes.
To characterize Tn6198, a novel conjugative transposon from the clinical Listeria monocytogenes strain TTH-2007, which contains the tetracycline and trimethoprim resistance genes tet(M) and dfrG, respectively, and to assess its transferability in vitro and in situ. The complete sequence of Tn6198 was determined using a primer walking strategy. Horizontal gene transfer studies were performed by filter matings, as well as on the surface of smear-ripened cheese and smoked salmon. The presence of Tn916-like circular intermediates was determined by PCR. Antibiotic resistance was determined by the broth microdilution method and microarray hybridization. Sequencing of Tn6198 revealed that a 3.3 kb fragment containing dfrG was integrated between open reading frames 23 and 24 of Tn916. Furthermore, an additional copy of Tn916 was present in L. monocytogenes TTH-2007. Both elements were transferred simultaneously and separately in vitro to recipients L. monocytogenes 10403S and Enterococcus faecalis JH2-2 by conjugation, resulting in either tetracycline- and trimethoprim-resistant or solely tetracycline-resistant transconjugants. On the surface of cheese and salmon, only L. monocytogenes 10403S transconjugants were detected. This study reports the first Tn916-like element associated with a trimethoprim resistance gene, as well as the first fully characterized transposon conferring multidrug resistance in L. monocytogenes. This is of concern, as trimethoprim is administered to listeriosis patients with β-lactam allergy and as Tn6198 has a large potential for dissemination, indicated by both intra-species and inter-genus transfer.


Kaempferol Attenuates Myocardial Ischemic Injury via Inhibition of MAPK Signaling Pathway in Experimental Model of Myocardial Ischemia-Reperfusion Injury.
Kaempferol (KMP), a dietary flavonoid, has antioxidant, anti-inflammatory, and antiapoptotic effects. Hence, we investigated the effect of KMP in ischemia-reperfusion (IR) model of myocardial injury in rats. We studied male albino Wistar rats that were divided into sham, IR-control, KMP-20 + IR, and KMP 20 per se groups. KMP (20 mg/kg; i.p.) was administered daily to rats for the period of 15 days, and, on the 15th day, ischemia was produced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed; heart was removed and processed for biochemical, morphological, and molecular studies. KMP pretreatment significantly ameliorated IR injury by maintaining cardiac function, normalizing oxidative stress, and preserving morphological alterations. Furthermore, there was a decrease in the level of inflammatory markers (TNF-α, IL-6, and NFκB), inhibition of active JNK and p38 proteins, and activation of ERK1/ERK2, a prosurvival kinase. Additionally, it also attenuated apoptosis by reducing the expression of proapoptotic proteins (Bax and Caspase-3), TUNEL positive cells, and increased level of antiapoptotic proteins (Bcl-2). In conclusion, KMP protected against IR injury by attenuating inflammation and apoptosis through the modulation of MAPK pathway.


p300-mediated acetylation stabilizes the Th-inducing POK factor.
The lineage-specifying factor Th-inducing POK (ThPOK) directs the intrathymic differentiation of CD4 T cells. Although the regulation of ThPOK at the transcription level has been extensively studied, specific posttranslational modifications regulating the activity of ThPOK have not been addressed. In this paper, we show that ThPOK is an unstable protein that is more readily degraded in CD8 T cells compared with CD4 T cells. Among the various proteins that bind ThPOK, acetyltransferase p300 specifically promotes the acetylation of ThPOK at K210, K216, and K339, outcompeting ubiquitination, thereby stabilizing the protein. In CD4 T cells, attenuation of p300-mediated acetylation promotes the degradation of ThPOK. In contrast, mutation of lysines 210, 216, and 339 to arginines stabilizes ThPOK and enhances its ability to suppress the expression of CD8 molecule and cytotoxic effectors in CD8 T cells. Our results reveal an essential role of p300-mediated acetylation in regulating the stability of ThPOK and suggest that such regulation may play a part in CD4/CD8 lineage differentiation.


Mecamylamine (a nicotine antagonist) for smoking cessation.
Mecamylamine is a nicotine antagonist (that is it blocks the effect of nicotine). The rationale for its use in smoking cessation is that it may block the rewarding effect of nicotine and thus reduce the urge to smoke. The objective of this review was to determine the effectiveness of mecamylamine in promoting smoking cessation, either alone or in combination with nicotine replacement therapy. We searched the Cochrane Tobacco Addiction Group trials register. Randomised trials of mecamylamine, either alone or in combination with nicotine replacement therapy, which reported smoking cessation rates at least six months after intervention. We extracted data in duplicate on the type of subjects, the dose and duration of the mecamylamine and nicotine treatments, side-effects of treatment, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was sustained abstinence from smoking (biochemically validated) after at least six months follow-up in patients smoking at baseline. Smokers lost to follow-up were regarded as being continuing smokers. Because of the preliminary nature of available data, we did not perform meta-analysis but report the results narratively. We identified two studies, both from the same investigators. In a study of 48 volunteers, a combination of mecamylamine plus nicotine patch was more effective than nicotine patch alone (abstinence rate at one year 37.5% vs 4.2%). In a second study, 80 volunteers were treated for four weeks prior to cessation with one of four treatments: 1. Nicotine patch plus mecamylamine capsules 2. Nicotine alone 3. Mecamylamine alone 4. No active drug. All four groups received combination treatment with nicotine and mecamylamine after the scheduled quit date. The abstinence rates in these four groups were respectively 40%, 20%, 15% and 15%. The higher abstinence rate in the group treated with combination therapy was not statistically significant. The authors reported a statistically significant benefit of mecamylamine using Kaplan-Meier survival analysis. In the doses used, mecamylamine was well tolerated, although up to 40% of subjects required reductions in dose, usually because of constipation. Data from two small studies suggest that the combination of nicotine and mecamylamine may be superior to nicotine alone in promoting smoking cessation. However, these results require confirmation in larger studies before the treatment can be recommended clinically.


Co-prevalence of human Papillomaviruses (HPV) and Epstein-Barr virus (EBV) in healthy blood donors from diverse nationalities in Qatar.
Infections by both human oncoviruses, human Papillomaviruses (HPV) and Epstein-Barr virus (EBV) are very common in the adult human population and are associated with various malignancies. While HPV is generally transmitted sexually or via skin-to-skin contact, EBV is frequently transmitted by oral secretions, blood transfusions and organ transplants. This study aims to determine the prevalence and circulating genotypes of HPV and EBV in healthy blood donors in Qatar. We explored the co-prevalence of high-risk HPVs and EBV in 378 males and only 7 females blood donors of different nationalities (mainly from Qatar, Egypt, Syria, Jordan, Pakistan, and India) residing in Qatar, using polymerase chain reaction (PCR). DNA was extracted from the buffy coat and genotyping was performed using PCR and nested-PCR targeting E6 and E7 as well as LMP-1 of HPV and EBV, respectively. We found that from the total number of 385 cases of healthy blood donors studied, 54.8% and 61% of the samples are HPVs and EBV positive, respectively. Additionally, our data revealed that the co-presence of both high-risk HPVs and EBV is 40.4% of the total samples. More significantly, this study pointed out for the first time that the most frequent high-risk HPV types in Qatar are 59 (54.8%), 31 (53.7%), 52 (49.1%), 51 (48.6%), 58 (47%) and 35 (45.5%), while the most commonly expressed low-risk HPV types are 53 (50.6%), 11 (45.5), 73 (41.7%) and 6 (41.3%), with all the cases showing multiple HPVs infection. In this study, we demonstrated for the first time that HPV and EBV are commonly co-present in healthy blood donors in Qatar. On the other hand, it is important to highlight that these oncoviruses can also be co-present in several types of human cancers where they can cooperate in the initiation and/or progression of these cancers. Therefore, more studies regarding the co-presence of these oncoviruses and their interaction are necessary to understand their cooperative role in human diseases.


[Profile, competencies and digital fluency of nurses in the Professional Improvement Program].
A descriptive exploratory study conducted in the city of São Paulo, which aimed to identify the profile, competencies and digital fluency of nurses in the Professional Improvement Program in handling technology at work. The population, composed by 60 nurses in the program, answered a questionnaire with data about profile, digital fluency and professional competencies. The participants were found to be: 95.0% female, 61.7% between 23 and 25 years old, 75.0% from public schools, 58.3% enrolled in cardiovascular nursing, 98.3% had contact with computing resources during graduation, 100.0% had a computer at home, 86.7% accessed the internet daily, 96.7% used Messenger and 58.3% had an intermediate level of knowledge and skill in computing. Professional competencies required for technology management referred to knowing how to be innovative, creative, and updated to identify and manage software and to use technological resources.


Systemic therapy of gallbladder cancer: review of first line, maintenance, neoadjuvant and second line therapy specific to gallbladder cancer.
Gallbladder cancer is the most common malignant cancer of the biliary tract and is distinct from other forms of biliary tract cancer in several of its risk factors and molecular aberrations. Locally advanced, unresectable and metastatic gallbladder cancer is associated with a poor prognosis and systemic chemotherapy is the main form of treatment available to these patients. This review is focused on the available evidence supporting the use of first-line chemotherapy specifically for gallbladder cancer. Numerous non-randomised studies have been published and certain forms of monotherapy and combination therapy can both lead to response rates (RRs) of approximately 40% and may prove to affect overall survival, most notably a recent phase II study of triplet therapy with gemcitabine, cisplatin and nab-paclitaxel. There are however relatively few randomised phases II and III studies on which to base recommendations, but they do demonstrate significant survival advantages of gemcitabine-containing combination therapies over best supportive care and chemotherapeutic monotherapy. The ABC-02 trial established the combination of gemcitabine and cisplatin as standard therapy in 2010, but more recent phase III studies reported as conference papers may support alternative, gemcitabine-containing doublet chemotherapy regimens such as gemcitabine in combination with oxaliplatin or S1. This manuscript also highlights the available data from studies examining maintenance chemotherapy, biomarkers, neoadjuvant therapy and second line studies in gallbladder cancer; unfortunately, there is insufficient evidence to make recommendations in these regards. The prognosis for unresectable and metastatic gallbladder cancer remains poor, and biomarkers for stratifying patients to particular first line therapies are not defined. This might be improved by gallbladder cancer specific analysis and reporting, and making histological primary specific data available publicly for further analysis.


Effects of View Layout on Situated Analytics for Multiple-View Representations in Immersive Visualization.
Multiple-view (MV) representations enabling multi-perspective exploration of large and complex data are often employed on 2D displays. The technique also shows great potential in addressing complex analytic tasks in immersive visualization. However, although useful, the design space of MV representations in immersive visualization lacks in deep exploration. In this paper, we propose a new perspective to this line of research, by examining the effects of view layout for MV representations on situated analytics. Specifically, we disentangle situated analytics in perspectives of situatedness regarding spatial relationship between visual representations and physical referents, and analytics regarding cross-view data analysis including filtering, refocusing, and connecting tasks. Through an in-depth analysis of existing layout paradigms, we summarize design trade-offs for achieving high situatedness and effective analytics simultaneously. We then distill a list of design requirements for a desired layout that balances situatedness and analytics, and develop a prototype system with an automatic layout adaptation method to fulfill the requirements. The method mainly includes a cylindrical paradigm for egocentric reference frame, and a force-directed method for proper view-view, view-user, and view-referent proximities and high view visibility. We conducted a formal user study that compares layouts by our method with linked and embedded layouts. Quantitative results show that participants finished filtering- and connecting-centered tasks significantly faster with our layouts, and user feedback confirms high usability of the prototype system.


Patient handoffs: standardized and reliable measurement tools remain elusive.
Numerous quality improvement projects on patient handoffs have been conducted, yet standardized, reliable measurement tools remain elusive. The literature review, which yielded approximately 400 relevant articles, led to the identification of seven primary functions for patient handoffs, each of which implies different interventions to improve them: (1) Framing 1, information processing is the most prevalent in the patient handoff literature; (2) Framing 2, stereotypical narratives, emphasizes highlighting deviations from typical narratives, such as a patient who is allergic to the preferred antibiotic for treating his or her diagnosed condition; (3) Framing 3, resilience, takes advantage of the transparency of the thought processes revealed through the conversation to identify erroneous assumptions and actions; (4) Framing 4, accountability, emphasizes the transfer of responsibility and authority; (5) Framing 5, social interaction, considers the perspective of the participants in the exchange; (6) Framing 6, distributed cognition, addresses how a transfer to a new care provider affects a network of specialized practitioners performing dedicated roles who may or may not be transitioning at the same time; (7) Framing 7, cultural norms, relates to how group values (instantiated as social norms for acceptable behavior) in an organization or suborganization are negotiated and maintained over time. The diversity of handoff measurement approaches suggests a lack of consensus about the primary purpose of a handoff, as well as about what interventions are most promising for improving handoff processes. Recognizing that there are simultaneously multiple purposes for handoffs is a critical precursor to quality improvement.


Acupuncture for depression?: A systematic review of systematic reviews.
Acupuncture is often advocated as a treatment for depression, and several trials have tested its effectiveness. Their results are contradictory and even systematic reviews of these data do not arrive at uniform conclusions. The aim of this review is to critically evaluate all systematic reviews of the subject with a view of assisting clinical decisions. Thirteen electronic databases were searched to identify all relevant articles. Data of these systematic reviews and the primary studies they included were extracted independently by the two authors according to predefined criteria. Eight systematic reviews including seventy-one primary studies were found. Five of the reviews arrived at positive conclusions and three did not. All the positive reviews and most of the positive primary studies originated from China. There are reasons to believe that these reviews are less than reliable. In conclusion, the effectiveness of acupuncture as a treatment of depression remains unproven and the authors' findings are consistent with acupuncture effects in depression being indistinguishable from placebo effects.


Surveys of the salt content in UK bread: progress made and further reductions possible.
To explore the salt reductions made over time in packaged bread sold in the UK, the biggest contributor of salt to the UK diet. Cross-sectional surveys were carried out on the salt content of breads available in UK supermarkets in 2001(40 products), 2006 (138) and 2011 (203). The primary outcome measure was the change in salt content per 100 g over time. Further measures included the proportion of products meeting salt targets and differences between brands and bread types. The average salt level of bread was 1.23±0.19 g/100 g in 2001, 1.05±0.16 in 2006 and 0.98±0.13 in 2011. This shows a reduction in salt/100 g of ≈20% between 2001 and 2011. In the 18 products which were surveyed in all 3 years, there was a significant reduction of 17% (p<0.05). Supermarket own brand bread was found to be lower in salt compared with branded bread (0.95 g/100 g compared with 1.04 g/100 g in 2011). The number of products meeting the 2012 targets increased from 28% in 2001 to 71% in 2011 (p<0.001). This study shows that the salt content of bread has been progressively reduced over time, contributing to the evidence base that a target-based approach to salt reduction can lead to reductions being made. A wide variation in salt levels was found with many products already meeting the 2012 targets, indicating that further reductions can be made. This requires further progressive lower targets to be set, so that the UK can continue to lead the world in salt reduction and save the maximum number of lives.


High-nuclearity mixed-chelate ferric complexes from a new family of polynuclear precursors.
The syntheses, structures, and magnetochemical characterization of two novel mixed-chelate undeca- and dodecanuclear ferric complexes are reported. Preformed tri- and pentanuclear ferric complexes that possess tridentate Schiff base (L2- and (L'2-) and acetate ligands were reacted with 1,1,1-tris(hydroxymethyl)ethane (H3thme) to afford [Fe11O3(OH)(O2CMe)8(thme)2(L)6] (1) and [Fe12O4(O2CMe)8(thme)2(NH2(CH2)2O)2(L')6] (2), respectively, following structural agglomeration and rearrangement associated with ligand substitution. The incorporation of more than one type of ligand that can both chelate and bridge the Fe centers gives rise to the complicated molecular structures displayed by 1 and 2. As a result of the tripodal conformation of thme3-, the cores of both molecules incorporate several face-shared defect {Fe3O4}+ cuboidal subunits. Variable-temperature dc and ac magnetic susceptibility studies, together with low-temperature magnetization measurements, are consistent with S = 5/2 and S = 0 ground-state spins for 1 and 2, respectively, and suggest that excited states with higher spin values lie relatively close in energy to the ground state for both species. Low-temperature micro-SQUID measurements on oriented single crystals of 1 confirm the easy-axis type magnetic anisotropy suggested by conventional SQUID magnetometry. However magnetization hysteresis is not observed down to 0.04 K, which is ascribed to rapid quantum tunneling of the magnetization associated with transverse interactions.


Design and photophysical properties of zinc(II) porphyrin-containing dendrons linked to a central artificial special pair.
The click chemistry synthesis and photophysical properties, notably photo-induced energy and electron transfers between the central core and the peripheral chromophores of a series of artificial special pair-dendron systems (dendron = G1, G2, G3; Gx = zinc(II) tetra-meso-arylporphyrin-containing polyimides) built upon a central core of dimethylxanthenebis(metal(II) porphyrin) (metal = zinc, copper), are reported. The dendrons act as singlet and triplet energy acceptors or donors, depending on the dendrimeric systems. The presence of the paramagnetic d(9) copper(II) in the dendrimers promotes singlet-triplet energy transfer from the zinc(II) tetra-meso-arylporphyrin to the bis(copper(II) porphyrin) unit and slow triplet-triplet energy transfer from the central bis(copper(II) porphyrin) fragment to the peripheral zinc(II) tetra-meso-arylporphyrin. If bis(zinc(II) porphyrin) is the central core, evidence for chain folding is observed; this is unambiguously demonstrated by the presence of triplet-triplet energy transfer in the heterobimetallic systems, a process that can only occur at short distances.


Follow-up non-attendance after long-bone fractures in a low-resource setting: a prospective study of predictors and interventions to increase attendance rates.
While the majority of traumatic injuries occur in low- and middle-income countries, the published literature comes chiefly from high-income countries due to poor follow-up. Clinical and radiographic post-surgical trauma follow-up is essential to high-quality research and objective monitoring for healing and/or complications. This study aimed to identify the predictors of follow-up non-attendance in a low-resource setting and investigate the extent to which interventional efforts based on mobile phone technology (MPT) and home visits improved the follow-up rates for fractures treated with SIGN nails. This was a prospective study of 594 patients with long-bone fractures. Socio-demographic (e.g. age, gender, marital status, education level, etc.) and clinical (e.g. fracture type, concomitant injuries, comorbidity, etc.) data were collected on each patient. Before discharge, the importance of follow-up was explained to patients and their relations. They were encouraged to attend even if they felt well. Their residential addresses and telephone numbers were validated and securely stored. Patients who missed their appointments were contacted by phone. Those who failed to honour 2 or 3 rescheduled appointments were visited in their home. The patients were divided into those who returned for the primarily scheduled follow-up without prompting (volition group) and those who did not come (non-attenders). Univariate analyses and binary logistic regression were conducted to determine the significant predictors of non-attendance. The proportion of patients in the volition group reduced from 96.1% at 6 weeks to 53.0% at 12 weeks and 39.2% at 6 months. However, interventional efforts increased these values to 98.5%, 92.5%, and 72.4% respectively. Walking unaided before the primarily scheduled 12-week appointment was the major reason for not attending the follow-up. Education, occupation, post-operative length of hospital stay (PLOS) and infection were significantly associated with non-attendance but younger age, long distances from the hospital, being separated or divorced, difficulty paying the in-patient care bill, closed fracture, having no (or a non-limb) concomitant injury, achieving painless weight bearing ≤ 6 weeks post-operatively and needing no additional surgery were independent predictors of non-attendance. Our study sheds light on the predictors of follow-up non-attendance and demonstrates how interventional efforts improved attendance rates in a low-resource setting. In addition, efforts that better the socio-economic status of people such as more-encompassing health insurance coverage and greater work flexibility can improve the follow-up attendance rates.


A Framework for Integrating Environmental and Occupational Health and Primary Care in a Postdisaster Context.
Integration of environmental and occupational health (EOH) into primary care settings is a critical step to addressing the EOH concerns of a community, particularly in a postdisaster context. Several barriers to EOH integration exist at the physician, patient, and health care system levels. This article presents a framework for improving the health system's capacity to address EOH after the Deepwater Horizon oil spill and illustrates its application in the Environmental and Occupational Health Education and Referral (EOHER) program. This program worked with 11 Federally Qualified Health Center systems in the Gulf Coast region to try to address the EOH concerns of community members and to assist primary care providers to better understand the impact of EOH factors on their patients' health. The framework uses a 3-pronged approach to (1) foster coordination between primary care and EOH facilities through a referral network and peer consultations, (2) increase physician capacity in EOH issues through continuing education and training, and (3) conduct outreach to community members about EOH issues. The EOHER program highlighted the importance of building strong partnerships with community members and other relevant organizations, as well as high organizational capacity and effective leadership to enable EOH integration into primary care settings. Physicians in the EOHER program were constrained in their ability to engage with EOH issues due to competing patient needs and time constraints, indicating the need to improve physicians' ability to assess which patients are at high risk for EOH exposures and to efficiently take environmental and occupational histories. This article highlights the importance of addressing EOH barriers at multiple levels and provides a model that can be applied to promote community health, particularly in the context of future natural or technological disasters.


LpMab-23: A Cancer-Specific Monoclonal Antibody Against Human Podoplanin.
Human podoplanin (hPDPN), the ligand of C-type lectin-like receptor-2, is involved in cancer metastasis. Until now, many monoclonal antibodies (mAbs) have been established against hPDPN. However, it is still difficult to develop a cancer-specific mAb (CasMab) against hPDPN because the protein sequence of hPDPN expressed in cancer cells is the same as that in normal cells. Herein, we report LpMab-23 of the mouse IgG1 subclass, a novel CasMab against hPDPN. In an immunohistochemical analysis, LpMab-23 reacted with tumor cells of human oral cancer, but did not react with normal cells such as lymphatic endothelial cells (LECs). In contrast, LpMab-17, another anti-hPDPN mAb, reacted with both tumor cells and LECs. Furthermore, flow cytometric analysis revealed that LpMab-23 reacted with hPDPN-expressing cancer cell lines (LN319, RERF-LC-AI/hPDPN, Y-MESO-14/hPDPN, and HSC3/hPDPN) but showed little reaction with normal cells (LECs and HEK-293T), although another anti-hPDPN mAb, LpMab-7, reacted with both hPDPN-expressing cancer cells and normal cells, indicating that LpMab-23 is a CasMab against hPDPN.


[Experimental development of immunity to pertussis].
Experiments on animals inoculated intracerebrally with B. pertussis culture No 18-323, serovar 1.2.3, revealed that among sera against B. pertussis strains of different serovars sera against the strains of serovar 1 showed the highest protective potency, and sera against the strains of serovar 1.2 showed the lowest protective potency. In active immunization experiments vaccines from the strains of serovar 1 proved to be least effective, while the immunogenic properties of vaccines from the strains of serovar 1.2 were found to be most pronounced. Since this discrepancy in the above results is due to the fact that the strains of serovar 1 in small doses were unable to create a stable focus of antigenic stimulation, it is not expedient to include strains belonging to serovars other than 1.2 into vaccinal preparations.


Protease Inhibition Improves Healing of The Vaginal Wall after Obstetrical Injury: Results from a Preclinical Animal Model.
Vaginal delivery with obstetrical trauma is a risk factor for pelvic organ prolapse later in life. Loss of fibulin-5 (FBLN5), an elastogenesis-promoting cellular matrix protein, results in prolapse in mice. Here, we evaluated effects of pregnancy, parturition, and obstetrical injury on FBLN5 content, elastic fibers, biomechanics, and histomorphology of the vaginal wall in rats. Further, we analyzed the effects of actinonin, a protease inhibitor, on obstetrical injury of the vaginal wall. Vaginal FBLN5 decreased significantly in pregnancy, and injury resulted in further downregulation. Stiffness of the vaginal wall decreased 82% in pregnant rats and 74% (p = 0.019) with injury relative to uninjured vaginal delivery controls at 3d. Actinonin ameliorated loss of FBLN5, rescued injury-induced loss of elastic fibers and biomechanical properties after parturition, and reduced the area of injury 10-fold. We conclude that pregnancy and parturition have a profound impact on vaginal FBLN5 and biomechanics of the vaginal wall. Further, obstetrical injury has significant deleterious impact on recovery of the vaginal wall from pregnancy. Actinonin, a non-specific matrix metalloprotease inhibitor, improved recovery of the parturient vaginal wall after obstetrical injury.


Childhood multiple sclerosis: clinical features and recent developments on treatment choices and outcomes.
Multiple sclerosis (MS) is an inflammatory idiopathic autoimmune disease causing demyelination of central nervous system (CNS). The incidence of pediatric MS is relatively rare, affecting 0.2 to 0.64/100,000 subjects; cases with MS onset before age 10-12 years, account for less than 1% of all MS cases, while 2.7 to 10.5% of all MS cases worldwide are seen in children <18 years of age, with a strong female preponderance. The disease course of MS varies from a benign type with relatively low level of disability after a long duration (15 years) of the disease, to a malignant type of MS with severe disability or even death within few months following onset. Diagnostic criteria for pediatric MS include ≥ 2 clinical events involving more areas of CNS inflammation in the absence of encephalopathy, separated by > 30 days, along with the involvement of brainstem. Pediatric MS generally presents relapsing-remittent form of MS, with majority of the patients recovering from the first attack. Major histocompatibility complex, more specifically, mutations in the human leukocyte antigen (HLA) DRB1*15 allele, are considered most important genetic factors that are contributory to the disease. Treatment choices for pediatric MS include many disease-modifying therapies (DMT) that are currently being used for adult MS and these are interferon-β 1a/1b (IFN-β1a/1b), glatiramer acetate, teriflunomide, dimethyl fumarate, alemtuzumab, etc. However, most of these have not gone through complete testing in randomized, placebo-controlled clinical trials for pediatric MS and are being prescribed off-label by clinicians. As these studies are progressing, it is important to address if these approaches of treating pediatric MS patients have any long-term impact on patients, in particular, physical, cognitive, developmental and social outcomes of the children.