Evaluation of Blood Glucose Meter Efficacy in an Antenatal Diabetes Clinic.
The optimal treatment of diabetes in pregnancy requires accurate measurement of blood glucose levels, in order to minimize adverse outcomes for both mother and neonate. Self-monitoring of blood glucose is routinely used to measure glycemic control and to assess whether treatment targets are being met; however, the accuracy of blood glucose meters in pregnancy is unclear. Pregnant women with gestational, type 1, or type 2 diabetes mellitus were eligible to participate. Nonfasting capillary blood glucose levels were measured in duplicate using the BGStar(®) (Sanofi, Sydney, Australia) and FreeStyle Lite(®) (Abbott, Sydney) blood glucose meters. Venous blood samples were collected and analyzed for plasma glucose, hematocrit, and glycated hemoglobin. Capillary blood glucose was compared with plasma glucose and further assessed according to International Organization for Standardization (ISO) 15197:2013 standards. One hundred ten women were recruited, providing 96 samples suitable for analysis. The mean ± SD laboratory plasma glucose level was 4.6 ± 1.4 mmol/L; the BGStar and FreeStyle Lite capillary blood glucose values were 5.3 ± 1.4 mmol/L and 5.0 ± 1.3 mmol/L, respectively. Both meters showed a positive bias (0.42 mmol/L for the FreeStyle Lite and 0.65 mmol/L for the BGStar). Furthermore, neither meter fulfilled the ISO 15197:2013 standards, and there was a nonsignificant improvement in meter performance at blood glucose levels of ≤4.2 mmol/L. Hematocrit did not affect the results of either blood glucose meter. Clarke Error Grid analysis demonstrated that approximately 70% of the results of both meters would lead to appropriate clinical action. The BGStar and FreeStyle Lite blood glucose meters did not meet ISO 15197:2013 recommendations for blood glucose monitoring systems when assessed in a population of women with diabetes in pregnancy. Clinicians should consider this difference in blood glucose readings when making diabetes-related treatment decisions.


[Clostridioides difficile infections].
Here, we describe the epidemiology, diagnostics, and treatment of Clostridioides difficile infection (CDI) in the primary health care setting. CDI is traditionally considered as a healthcare associated infection. However, infections with onset in the community represent a large proportion of CDI. Traditional CDI risk factors apply to the population encountered in general practice: age ≥50 years, malignancy or other underlying disease, hospital admission and/or antibiotic treatment in the past 3 months. Notably, about a third has had no recent antibiotic exposure nor has been admitted to a hospital. Based on diagnostic tests requested by the general practitioner, only half of CDI cases will be diagnosed. In this setting, it is advisable to request a diagnostic C. difficile test for patients with persisting or severe diarrhea and negative tests for traditional enteropathogens (Salmonella, Shigella, Yersinia, Campylobacter), also in the absence of traditional risk factors for CDI.


Iron balance in hemodialysis patients.
Iron deficiency is a frequent complication in chronically hemodialyzed patients because of the significant blood losses associated with this technique. Quantitating iron stores (by marrow examination or serum iron and total iron-binding capacity) on a repetitive basis had been difficult or unreliable, often resulting in failure to recognize iron deficiency superimposed on the existing anemia of chronic renal failure, or overtreating, which can lead to iron excess. Use of the serum ferritin allows easier quantitation of iron stores and, when measured serially in dialysis patients, can predict the emergence of iron deficiency. There was no correlation between serum ferritin levels and serum iron, total iron-binding capacity, or percent transferrin saturation. Iron absorption studies show that food iron absorption is physiologic, increasing when the serum ferritin is below 30 ng/ml, decreasing when more than 300 ng/ml. Treatment of iron deficiency with oral iron compounds increases serum ferritin levels and usually can maintain iron balance.


NDP52 interacts with mitochondrial RNA poly(A) polymerase to promote mitophagy.
Parkin-mediated mitophagy is a quality control pathway that selectively removes damaged mitochondria via the autophagic machinery. Autophagic receptors, which interact with ubiquitin and Atg8 family proteins, contribute to the recognition of damaged mitochondria by autophagosomes. NDP52, an autophagy receptor, is required for autophagic engulfment of damaged mitochondria during mitochondrial uncoupler treatment. The N-terminal SKICH domain and C-terminal zinc finger motif of NDP52 are both required for its function in mitophagy. While the zinc finger motif contributes to poly-ubiquitin binding, the function of the SKICH domain remains unclear. Here, we show that NDP52 interacts with mitochondrial RNA poly(A) polymerase (MTPAP) via the SKICH domain. During mitophagy, NDP52 invades depolarized mitochondria and interacts with MTPAP dependent on the proteasome but independent of ubiquitin binding. Loss of MTPAP reduces NDP52-mediated mitophagy, and the NDP52-MTPAP complex attracts more LC3 than NDP52 alone. These results indicate that NDP52 and MTPAP form an autophagy receptor complex, which enhances autophagic elimination of damaged mitochondria.


Kinetics of apoptotic markers in exogeneously induced apoptosis of EL4 cells.
We investigated the time-dependence of apoptotic events in EL4 cells by monitoring plasma membrane changes in correlation to DNA fragmentation and cell shrinkage. We applied three apoptosis inducers (staurosporine, tubericidine and X-rays) and we looked at various markers to follow the early-to-late apoptotic events: phospholipid translocation (identified through annexin V-fluorescein assay and propidium iodide), lipid package (via merocyanine assay), membrane fluidity and anisotropy (via fluorescent measurements), DNA fragmentation by the fluorescence-labeling test and cell size measurements. The different apoptotic inducers caused different reactions of the cells: staurosporine induced apoptosis most rapidly in a high number of cells, tubercidine triggered apoptosis only in the S phase cells, while X-rays caused a G2/M arrest and subsequently apoptosis. Loss of lipid asymmetry is promptly detectable after one hour of incubation time. The phosphatidylserine translocation, decrease of lipid package and anisotropy, and the increase of membrane fluidity appeared to be based on the same process of lipid asymmetry loss. Therefore, the DNA fragmentation and the cell shrinkage appear to be parallel and independent processes running on different time scales but which are kinetically inter-related. The results indicate different signal steps to apoptosis dependent on inducer characteristics but the kinetics of "early-to-late" apoptosis appears to be a fixed program.


Nosocomial post-traumatic cutaneous mucormycosis: a systematic review.
Mucormycosis is a rare, rapidly fatal opportunistic invasive fungal infection occurring in immunocompromised patients. Primary cutaneous mucormycosis usually follows direct inoculation of fungal spores at the site of damaged or traumatized skin. We report a case of fatal nosocomial post-traumatic cutaneous mucormycosis in a diabetic patient and we performed a systematic review of reported cases of nosocomial post-traumatic cutaneous mucormycosis to describe their demographic profile, predisposing factors, treatment and outcome.


Does genotype predict phenotype in Rett syndrome?
Mutations in the X-linked gene encoding the methyl-CpG binding protein MeCP2 are the primary cause of classic and atypical Rett syndrome and have recently been shown to contribute to other neurodevelopmental disorders of varying severity. To determine whether there are molecular correlates to the phenotypic heterogeneity, numerous groups have performed genotype-phenotype correlation studies. These studies have yielded conflicting results, in part because they used different criteria for determining severity and classifying mutations. Evolution of the phenotype with age and variable expressivity arising from individual variability in X-chromosome inactivation patterns are among other reasons the findings varied. Nonetheless, evidence of differences in the phenotypic consequences of specific types of mutations is emerging. This review analyzes the available literature and makes recommendations for future studies.


An okadaic acid fragment analogue prevents nicotine-induced resistance to cisplatin by recovering PP2A activity in non-small cell lung cancer cells.
We herein report the design, synthesis, and functional impact of an okadaic acid (OA) small analogue, ITH12680, which restores the activity of phosphoprotein phosphatase 2A (PP2A), whose deficient activity has been implicated in nicotine-mediated tumor progression and chemoresistance in non-small cell lung cancer (NSCLC). For its design, we paid attention to the structure of the PP2A-OA complex, where the C16-C38 OA fragment confers PP2A affinity and selectivity, but it is not involved in the inhibitory effect. Confirming this hypothesis, PP2A activity was not inhibited by ITH12680. By contrast, the compound partially restored OA-exerted PP2A inhibition in vitro. Moreover, flow cytometry and immunoblotting experiments revealed that ITH12680 reversed nicotine-induced cisplatin resistance in NSCLC cells, as it prevented nicotine-induced reduction of Bax expression and inhibited nicotine-mediated activation of cell survival and proliferation kinases, Akt and ERK1/2. Our findings suggest that the rescue of nicotine-inhibited PP2A activity could diminish the resistance to cisplatin treatment observed in NSCLC patients who continue smoking.


Toward Benchmark-Quality Ab Initio Predictions for 3d Transition Metal Electrocatalysts: A Comparison of CCSD(T) and ph-AFQMC.
Generating accurate ab initio ionization energies for transition metal complexes is an important step toward the accurate computational description of their electrocatalytic reactions. Benchmark-quality data is required for testing existing theoretical methods and developing new ones but is complicated to obtain for many transition metal compounds due to the potential presence of both strong dynamical and static electron correlation. In this regime, it is questionable whether the so-called gold standard, coupled cluster with singles, doubles, and perturbative triples (CCSD(T)), provides the desired level of accuracy─roughly 1-3 kcal/mol. In this work, we compiled a test set of 28 3d metal-containing molecules relevant to homogeneous electrocatalysis (termed 3dTMV) and computed their vertical ionization energies (ionization potentials) with CCSD(T) and phaseless auxiliary-field quantum Monte Carlo (ph-AFQMC) in the def2-SVP basis set. A substantial effort has been made to converge away the phaseless bias in the ph-AFQMC reference values. We assess a wide variety of multireference diagnostics and find that spin-symmetry breaking of the CCSD wave function and the PBE0 density functional correlate well with our analysis of multiconfigurational wave functions. We propose quantitative criteria based on symmetry breaking to delineate correlation regimes inside of which appropriately performed CCSD(T) can produce mean absolute deviations from the ph-AFQMC reference values of roughly 2 kcal/mol or less and outside of which CCSD(T) is expected to fail. We also present a preliminary assessment of density functional theory (DFT) functionals on the 3dTMV set.


The health belief model and contraceptive behavior: limits to the application of a conceptual framework.
The Health Belief Model is an inadequate conceptual framework for explaining the motivational dynamics of acceptance or rejection of contraception, although it does satisfy criteria of a good theory in explaining individual disease prevention behavior. Cues to action are the variables in the Model most clearly applicable to contraceptive behavior. The motivational variables, which are more important to the Model, are ambiguous at best is this area, however.


Semantic relations and repetition of items enhance the free recall of words by multiple sclerosis patients.
We compared 25 patients with multiple sclerosis (MS) and 24 normal controls on a test of free recall of words. Some lists contained words that were all unrelated, while in others the intermediary words were semantically related. In another set, the mid-list words were repeated across the lists, or, in addition to the repetition, were semantically associated. Immediate recall was assessed using these lists. Delayed recall was assessed using different lists (delay-unrelated and delay-related) after distractor tasks. Recency was not affected in MS patients, but the primacy effect was lower than in controls, this effect being interpreted as due to a deficiency in articulatory rehearsal. The delay interval after each list abolished recency in both groups and resulted in impaired recall in MS patients. However the patients, like the controls, benefited from semantic relations in the middle of the lists and from spaced repetition of words across the lists, in either immediate and delayed recall. The enhancing effects of word relatedness and of spaced repetition are seen as being due to automatic processes preserved in MS patients.


A rare case of concomitant sicca keratopathy and ipsilateral central facial palsy in Wallenberg's dorsolateral medullary syndrome.
Objective: To describe a patient with a right-sided supranuclear facial palsy and concomitant sicca keratopathy of the right eye following right-sided dorsolateral medullary infarction. Methods: Our patient underwent a complete ophthalmologic and neurologic examination including biomicroscopy, fundus examination, cranial nerve examination, Shirmer I test, and magnetic resonance imaging of the brain. Results: A 61-year-old woman presented in emergency with a central facial nerve palsy on the right side and truncal ataxia. Neurologic assessment revealed a concurrent dysphagia, dysarthria, hypoesthesia of the right face, and weakness of the right upper limb. Magnetic resonance imaging of the brain showed an old left-sided cerebellar infarction, but a recent ischemic infarction at the level of the right dorsolateral medulla oblongata was the cause of our patient's current problems. One month after diagnosis of the right-sided dorsolateral medullary syndrome, there were complaints of ocular irritation and a diminished visual acuity in the right eye. Biomicroscopy showed a sicca keratopathy with nearly complete absence of tear secretion on the Shirmer I test, but with normal eye closure and preserved corneal reflexes and sensitivity. Conclusion: A dorsolateral medullary syndrome can have a variable expression in symptomatology. Our case is special because of the combination of an ipsilateral supranuclear facial palsy with normal upper facial muscle function together with an ipsilateral sicca keratopathy as a result of a nearly absent tear secretion. We hypothesized that the mechanism underlying the patient's sicca keratopathy ipsilateral to the supranuclear facial palsy involved the superior salivatory nucleus, which is situated in the caudal pons inferiorly of the motor facial nucleus and is most probably affected by a superior extension of the infarcted area in the right medulla oblongata.


Drosophila X-Linked Genes Have Lower Translation Rates than Autosomal Genes.
In Drosophila, X-linked and autosomal genes achieve comparable expression at the mRNA level. Whether comparable X-autosome gene expression is realized at the translational and, ultimately, the protein levels is, however, unknown. Previous studies suggest the possibility of higher translation rates for X-linked genes owing to stronger usage of preferred codons. In this study, we use public ribosome profiling data from Drosophila melanogaster to infer translation rates on the X chromosome versus the autosomes. We find that X-linked genes have consistently lower ribosome densities than autosomal genes in S2 cells, early embryos, eggs, and mature oocytes. Surprisingly, the lower ribosome densities of X-linked genes are not consistent with faster translation elongation but instead imply slower translation initiation. In particular, X-linked genes have sequence features known to slow translation initiation such as stronger mRNA structure near start codons and longer 5'-UTRs. Comparison to outgroup species suggests that stronger mRNA structure is an evolved feature of Drosophila X chromosomes. Finally, we find that the magnitude of the X-autosome difference in ribosome densities is smaller for genes encoding members of protein complexes, suggesting that stoichiometry constrains the evolution of translation rates. In sum, our analyses suggest that Drosophila X-linked genes have evolved lower translation rates than autosomal genes despite stronger usage of preferred codons.


Radiotherapy-Associated Cutaneous Mastocytosis in a Patient With Breast Carcinoma. Case Report and Review of the Literature.
Mast cell skin disease is rarely described after external beam radiation therapy in patients with breast carcinoma, with only 7 previous reports in the literature. Skin changes typically occur within (but are not limited to) the radiation field. We present a 64-year-old woman with postradiotherapy cutaneous mastocytosis on the left breast and adjacent chest wall. The clinical and laboratory findings in all reported patients, including the current case, are reviewed. No clear mechanism has been presented to explain disease pathogenesis; although, mast cell accumulation secondary to local mediators produced in response to radiation damage and/or koebnerization phenomenon have been proposed. Cutaneous/systemic mastocytosis is not widely recognized and may be underdiagnosed in the setting of postradiation for breast cancer. It is important for clinicians and pathologists to be aware of this diagnosis for patients presenting with rashes after radiotherapy.


Aquatic physical therapy for children with developmental coordination disorder: a pilot randomized controlled trial.
Aquatic therapy is an intervention for children with Developmental Coordination Disorder (DCD) that has not been investigated formally. This was a pilot randomized controlled trial to investigate the feasibility and preliminary effectiveness of an aquatic therapy program to improve motor skills of children with DCD. Thirteen children (mean age 7 years 1 month; 10 males) with DCD were randomly allocated to receive either six sessions of aquatic therapy (once weekly session of 30 min for 6-8 weeks) or to a wait-list (control group). The intervention and measures were demonstrated to be feasible, but barriers, such as limited appointment times and accessibility, were encountered. Analysis of covariance indicated that at posttest, mean scores on the Movement Assessment Battery were higher for children who received aquatic therapy compared to those on the wait-list (p = .057). Similar trends were noted on the physical competence portion of the Pictorial Scale of Perceived Competence and Social Acceptance (p = .058). Participation levels, as measured by a parent questionnaire, showed improvement for both groups. Potential facilitators and barriers to implementation of an aquatic therapy for children with DCD are discussed.


Fragility Fractures in Patients with Rheumatoid Arthritis and Osteoarthritis Compared with the General Population.
To determine the rate ratios of hip and distal radius fractures in patients with rheumatoid arthritis (RA), hip osteoarthritis (OA), and knee OA. Cohort study using healthcare data (1998-2012) covering the entire population of the Skåne region of Sweden. We found an increased rate of hip fracture in both female [standardized fracture rate ratio (SFR) 1.54, 95% CI 1.40-1.70] and male patients with RA (SFR 1.81, 95% CI 1.51-2.17). The hip fracture rate in female OA was reduced by 10-20%, and trochanteric fracture tended to have a higher rate ratio compared with the cervical. The 50-80% increased rate of hip fracture adds to the total burden of RA while the shifted distribution of cervical/trochanteric fractures in OA is in support of subchondral bone alterations.


Blockade of late stages of autoimmune diabetes by inhibition of the receptor for advanced glycation end products.
Ligation of the receptor for advanced glycation end products (RAGE) occurs during inflammation. Engagement of RAGE results in enhanced expression of addressins and it is therefore, not surprising that previous studies have shown a role of RAGE/ligand interactions in immune responses including cell/cell contact but the role of RAGE in spontaneous autoimmunity has not been clearly defined. To study the role of RAGE/ligand interactions in autoimmune diabetes, we tested the ability of soluble RAGE, a scavenger of RAGE ligands, in late stages of diabetes development in the NOD mouse-disease transferred with diabetogenic T cells and recurrent disease in NOD/scid recipients of syngeneic islet transplants. RAGE expression was detected on CD4(+), CD8(+), and B cells from diabetic mice and transferred to NOD/scid recipients. RAGE and its ligand, S100B, were found in the islets of NOD/scid mice that developed diabetes. Treatment of recipient NOD/scid mice with soluble RAGE prevented transfer of diabetes and delayed recurrent disease in syngeneic islet transplants. RAGE blockade was associated with increased expression of IL-10 and TGF-beta in the islets from protected mice. RAGE blockade reduced the transfer of disease with enriched T cells, but had no effect when diabetes was transferred with the activated CD4(+) T cell clone, BDC2.5. We conclude that RAGE/ligand interactions are involved in the differentiation of T cells to a mature pathogenic phenotype during the late stages of the development of diabetes.


Assessing the Source-to-Stream Transport of Benzotriazoles during Rainfall and Snowmelt in Urban and Agricultural Watersheds.
While benzotriazoles (BTs) are ubiquitous in urban waters, their sources and transport remain poorly characterized. We aimed to elucidate the origin and hydrological pathways of BTs in Toronto, Canada, by quantifying three BTs, electrical conductivity, and δ18O in high-frequency streamwater samples taken during two rainfall and one snowmelt event in two watersheds with contrasting levels of urbanization. Average concentrations of total BTs (∑BT) were 1.3 to 110 times higher in the more urbanized Mimico Creek watershed relative to the primarily agricultural and suburban Little Rouge Creek. Strong correlations between upstream density of major roads and total BT concentrations or BT composition within all events implicate vehicle fluids as the key source of BTs in both watersheds. Sustained historical releases of BTs within the Mimico Creek watershed have likely led to elevated ∑BT in groundwater, with elevated concentrations observed during baseflow that are diluted by rainfall and surface runoff. In contrast, relatively constant concentrations, caused by mixing of equally contaminated baseflow and rainfall/surface runoff, are observed in the Little Rouge Creek throughout storm hydrographs, with an occasional first flush occurring at a subsite draining suburban land. During snowmelt, buildup of BTs in roadside snowpiles and preferential partitioning of BTs to the liquid phase of a melting snowpack leads to early peaks in ∑BT in both streams, except the sites in the Little Rouge Creek with low levels of vehicle traffic. Overall, a history of BT release and land use associated with urbanization have led to higher levels of BTs in urban areas and provide a glimpse into future BT dynamics in mixed use, (sub)urbanizing areas.


Malaria in Korea.
Malaria was steadily decreasing in Korea except in certain counties of the mountainous and hilly areas, in the 1960s. Judging from the present epidemiological, social and economic conditions, it can be said with confidence that malaria with "unstable" characteristic in the Republic of Korea has already been disappeared. No doubt, the causes of the disappearance of malaria are complex. Certainly improved living conditions and life style; better medical and educational facilities in the wake of a rapid economic development could all have some role. On the other hand, the disappearance of malaria without large scale control operations could be ascribed to the two main factors: one is malaria case detection and simultaneous drug therapy available through the nation-wide passive case detection network during the 1960s and the other is rapidly improved farming practices begun in 1970s, which resulted in the use of a huge quantity of pesticides and other chemicals for agriculture, which, in turn, might affect local anopheline vectors which were originally not effective ones any way.


Advances in Understanding the Fate and Effects of Oil from Accidental Spills in the United States Beginning with the Exxon Valdez.
Scientific studies of the environmental effects of oil spills in the United States have produced a steady stream of unexpected discoveries countering prior and often simplistic assumptions. In this brief review, I present how major discoveries from scientific studies of oil spill effects on marine ecosystems and environments, beginning with the 1989 Exxon Valdez, have led to a more informed appreciation for the complexity and the severity of the damage that major spills can do to marine ecosystems and to an increasing recognition that our ability to evaluate those damages is very limited, resulting in a structural bias toward underestimation of adverse environmental effects.


RBBP6 increases radioresistance and serves as a therapeutic target for preoperative radiotherapy in colorectal cancer.
Radiotherapy (RT) can be used as preoperative treatment to downstage initially unresectable locally rectal carcinoma, but radioresistance and recurrence remain significant problems. Retinoblastoma binding protein 6 (RBBP6) has been implicated in the regulation of cell cycle, apoptosis and chemoresistance both in vitro and in vivo. The present study investigated whether the inhibition of RBBP6 expression would improve radiosensitivity in human colorectal cancer cells. After SW620 and HT29 cells were exposed to radiation, the levels of RBBP6 mRNA and protein increased over time in both cells. Moreover, a significant reduction in clonogenic survival and a decrease in cell viability in parallel with an obvious increase in cell apoptosis were demonstrated in irradiated RBBP6-knockdown cells. Transfection with RBBP6 shRNA improved the levels of G2-M phase arrest, which blocked the cells in a more radiosensitive period of the cell cycle. These observations indicated that cell cycle and apoptosis mechanisms may be connected with tumor cell survival following radiotherapy. In vivo, the tumor growth rate of nude mice in the RBBP6-knockdown group was significantly slower than that in other groups. These results indicated that RBBP6 overexpression could resist colorectal cancer cells against radiation by regulating cell cycle and apoptosis pathways, and inhibition of RBBP6 could enhance radiosensitivity of human colorectal cancer.


Rifampin.
In 1971, rifampin was approved for treatment of pulmonary tuberculosis and asymptomatic carriers of Neisseria meningitidis. At present, the approved indications remain the same. However, rifampin in conjunction with at least one other antituberculous drug may be of great value in therapy of extrapulmonary tuberculosis and infections due to other susceptible mycobacteria. In addition, results of clinical trials in leprosy have been highly encouraging. Rifampin appears to induce light chain proteinuria in a majority of patients and has been implicated in suppression of both humoral and cell-mediated immune responses. However, these effects appear to have been of little consequence to treated patients. A variety of possibly immunologically mediated reactions to rifampin has been closely associated with irregular administration of the drug. These reactions and hepatic toxcity may be preventable in many patients. Rifampin or one of its congeners, alone or in combination with other antibiotics, may prove useful in treatment of various infectious, and possibly malignant, diseases.


Cost-utility analysis of the UPRIGHT intervention promoting resilience in adolescents.
As mental health in adulthood is related to mental status during adolescence, school-based interventions have been proposed to improve resilience. The objective of this study was to build a simulation model representing the natural history of mental disorders in childhood, adolescence and youth to estimate the cost-effectiveness of the UPRIGHT school-based intervention in promoting resilience and mental health in adolescence. We built a discrete event simulation model fed with real-world data (cumulative incidence disaggregated into eight clusters) from the Basque Health Service database (609,381 individuals) to calculate utilities (quality-adjusted life years [QALYs]) and costs for the general population in two scenarios (base case and intervention). The model translated changes in the wellbeing of adolescents into different risks of mental illnesses for a time horizon of 30 years. The number of cases of anxiety was estimated to fall by 5,125 or 9,592 and those of depression by 1,269 and 2,165 if the effect of the intervention lasted 2 or 5 years respectively. From a healthcare system perspective, the intervention was cost-effective for all cases considered with incremental cost-utility ratios always lower than €10,000/QALY and dominant for some subgroups. The intervention was always dominant when including indirect and non-medical costs (societal perspective). Although the primary analysis of the trial did not did not detect significant differences, the UPRIGHT intervention promoting positive mental health was dominant in the economic evaluation from the societal perspective. Promoting resilience was more cost-effective in the most deprived group. Despite a lack of information about the spillover effect in some sectors, the economic evaluation framework developed principally for pharmacoeconomics can be applied to interventions to promote resilience in adolescents. As prevention of mental health disorders is even more necessary in the post-coronavirus disease-19 era, such evaluation is essential to assess whether investment in mental health promotion would be good value for money by avoiding costs for healthcare providers and other stakeholders.


Role of the paraventricular nucleus in the reflex diuresis to pulmonary lymphatic obstruction in rabbits.
The changes in urine flow and renal sympathetic nerve activity (RSNA) due to pulmonary lymphatic obstruction (PLO) were examined in anesthetized, artificially ventilated New Zealand white rabbits. PLO was produced by pressurizing an isolated pouch created in the right external jugular vein at the points of entry of the right lymphatic ducts. During this maneuver, urine flow increased from 8.5 ± 0.3 mL/10 min to 12 ± 0.5 mL/10 min (P < 0.0001) and RSNA increased from 24.0 ± 4 to 40.0 ± 5 μV·s (P < 0.0001). Bilateral lesioning of the paraventricular nucleus (PVN) of the hypothalamus or cervical vagotomy abolished these responses. PLO increased c-fos gene expression in the PVN. The increase in urine flow due to PLO was attenuated by muscimol and abolished by kynurenic acid microinjections into the PVN. The results show that (i) neurons in the PVN are an important relay site in the reflex arc, which is activated by PLO; and (ii) this activation is regulated by glutamatergic and partly by GABAergic input to the PVN.


Mesonia oceanica sp. nov., isolated from oceans during the Tara oceans expedition, with a preference for mesopelagic waters.
Strain ISS653T, isolated from Atlantic seawater, is a yellow pigmented, non-motile, Gram-reaction-negative rod-shaped bacterium, strictly aerobic and chemoorganotrophic, slightly halophilic (1-15 % NaCl) and mesophilic (4-37 °C), oxidase- and catalase-positive and proteolytic. Its major cellular fatty acids are iso-C15 : 0, iso-C15 : 0 2-OH, and iso-C17 : 0 3-OH; the major identified phospholipid is phosphatidylethanolamine and the major respiratory quinone is MK6. Genome size is 4.28 Mbp and DNA G+C content is 34.9 mol%. 16S rRNA gene sequence similarity places the strain among members of the family Flavobacteriaceae, with the type strains of Mesonia phycicola (93.2 %), Salegentibacter mishustinae (93.1 %) and Mesonia mobilis (92.9 %) as closest relatives. Average amino acid identity (AAI) and average nucleotide identity (ANI) indices show highest values with M. mobilis (81 % AAI; 78.9 % ANI), M. phycicola (76 % AAI; 76.3 % ANI), Mesonia maritima (72 % AAI, 74.9 % ANI), Mesonia hippocampi (64 % AAI, 70.8 % ANI) and Mesonia algae (68 % AAI; 72.2 % ANI). Phylogenomic analysis using the Up-to-date-Bacterial Core Gene set (UBCG) merges strain ISS653T in a clade with species of the genus Mesonia. We conclude that strain ISS653T represents a novel species of the genus Mesonia for which we propose the name Mesonia oceanica sp. nov., and strain ISS653T (=CECT 9532T=LMG 31236T) as the type strain. A second strain of the species, ISS1889 (=CECT 30008) was isolated from Pacific Ocean seawater. Data obtained throughout the Tara oceans expedition indicate that the species is more abundant in the mesopelagic dark ocean than in the photic layer and it is more frequent in the South Pacific, Indian and North Atlantic oceans.


Entire genome of a strain of human immunodeficiency virus type 1 with a deletion of nef that was recovered 20 years after primary infection: large pool of proviruses with deletions of env.
We report the complete sequence analysis of the provirus harbored in a long-term nonprogressor (patient SG1) 20 years after the first infection with a human immunodeficiency virus type 1 strain lacking nef. The sequencing showed large deletions in the nef-nef and nef-U3 regions. Except for vpu, all of the other accessory genes were intact. The gag and pol genes did not show significant alterations. We found large deletions in env, spanning the V1, V2, V3, V4, and V5 regions. We believe that, when down-regulation of the class 1 major histocompatibility complex molecules is inhibited by the lack of nef function, the cells containing Env-defective molecules evade cytotoxic T lymphocyte killing and accumulate progressively.


Botulinum toxin as adjunctive therapy in refractory laryngeal granuloma.
This study evaluated the role of botulinum toxin type A in the treatment of refractory laryngeal granulomas. Retrospective clinical review at a tertiary care hospital. Seven patients with vocal process granulomas underwent percutaneous injection of botulinum toxin into both vocal folds, performed in an office setting. Total doses ranged from 10 to 25 U, divided between both vocal folds. All patients experienced resolution of their granulomas over two to seven weeks. No patient developed aspiration pneumonia. All patients experienced hoarseness secondary to the injections, but voice quality returned to baseline in all patients as the toxin was degraded. Botulinum toxin is safe and effective therapy in resolving vocal process granulomas in patients refractory to traditional therapy. The optimal treatment dose remains to be determined. Percutaneous botulinum toxin injection is helpful in resolving laryngeal granulomas.


Mucor amphibiorum infection in platypus (Ornithorhynchus anatinus) from Tasmania.
Mucor amphibiorum, a fungus previously isolated from frogs and toads, is reported from free-living platypus, Ornithorhynchus anatinus, from rivers in northern Tasmania. This fungus is responsible for the severe ulcerative skin condition originally described by Munday and Peel (1983). Mucor amphibiorum was isolated from dermal lesions on four separate occasions. The gross and histopathological appearance of the fungal lesions were similar to the earlier description. In vivo this fungus develops as spherical forms containing a number of daughter spherules; no mycelia are seen in tissue sections. By contrast, the in vitro growth consists of aerial aseptate mycelia and sporangia, features typical of the genus Mucor. This is the first report of this organism causing a fatal disease in a mammal. Susceptibility to infection may be due to the platypus having a body temperature of 32 C while the maximum temperature for growth of M. amphibiorum is 36 C.


[Aneurysmal bone cysts of the spinal canal].
Aneurysmal bone cysts (ABC) are rare bone tumors of controversial pathogenesis. In 15% of cases, they are localized in the vertebrae. Despite the absence of anaplasia, their volume and localization are often responsible for incomplete surgical resection. The authors present 5 cases of primary vertebral ABC, 4 females and one male, localized in cervical (3 cases), dorsal (1 case) and lumbar (1 case) spine. Symptoms included rachialgia and torticollis. Radiological and histopathological examination disclosed the typical features of ABC. Pre-operative embolization (in 3 cases) and surgery (complete exeresis in all cases except one) were the therapeutic procedures. During a 39 month median period of follow-up, there was one local recurrence. The only case of incomplete exeresis show not did any evidence of progression until 36 months after operation.


Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials.
Risankizumab is a humanised IgG1 monoclonal antibody that binds to the p19 subunit of interleukin-23, inhibiting this key cytokine and its role in psoriatic inflammation. We aimed to assess the efficacy and safety of risankizumab compared with placebo or ustekinumab in patients with moderate-to-severe chronic plaque psoriasis. UltIMMa-1 and UltIMMa-2 were replicate phase 3, randomised, double-blind, placebo-controlled and active comparator-controlled trials done at 139 sites in Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Japan, Mexico, Poland, Portugal, South Korea, Spain, and the USA. Eligible patients were 18 years or older, with moderate-to-severe chronic plaque psoriasis. In each study, patients were stratified by weight and previous exposure to tumour necrosis factor inhibitor and randomly assigned (3:1:1) by use of interactive response technology to receive 150 mg risankizumab, 45 mg or 90 mg ustekinumab (weight-based per label), or placebo. Following the 16-week double-blind treatment period (part A), patients initially assigned to placebo switched to 150 mg risankizumab at week 16; other patients continued their originally randomised treatment (part B, double-blind, weeks 16-52). Study drug was administered subcutaneously at weeks 0 and 4 during part A and at weeks 16, 28, and 40 during part B. Co-primary endpoints were proportions of patients achieving a 90% improvement in the Psoriasis Area Severity Index (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16 (non-responder imputation). All efficacy analyses were done in the intention-to-treat population. These trials are registered with ClinicalTrials.gov, numbers NCT02684370 (UltIMMa-1) and NCT02684357 (UltIMMa-2), and have been completed. Between Feb 24, 2016, and Aug 31, 2016, 506 patients in UltIMMa-1 were randomly assigned to receive 150 mg risankizumab (n=304), 45 mg or 90 mg ustekinumab (n=100), or placebo (n=102). Between March 1, 2016, and Aug 30, 2016, 491 patients in UltIMMa-2 were randomly assigned to receive 150 mg risankizumab (n=294), 45 mg or 90 mg ustekinumab (n=99), or placebo (n=98). Co-primary endpoints were met for both studies. At week 16 of UltIMMa-1, PASI 90 was achieved by 229 (75·3%) patients receiving risankizumab versus five (4·9%) receiving placebo (placebo-adjusted difference 70·3% [95% CI 64·0-76·7]) and 42 (42·0%) receiving ustekinumab (ustekinumab-adjusted difference 33·5% [22·7-44·3]; p<0·0001 vs placebo and ustekinumab). At week 16 of UltIMMa-2, PASI 90 was achieved by 220 (74·8%) patients receiving risankizumab versus two (2·0%) receiving placebo (placebo-adjusted difference 72·5% [95% CI 66·8-78·2]) and 47 (47·5%) receiving ustekinumab (ustekinumab-adjusted difference 27·6% [16·7-38·5]; p<0·0001 vs placebo and ustekinumab). In UltIMMa-1, sPGA 0 or 1 at week 16 was achieved by 267 (87·8%) patients receiving risankizumab versus eight (7·8%) receiving placebo (placebo-adjusted difference 79·9% [95% CI 73·5-86·3]) and 63 (63·0%) receiving ustekinumab (ustekinumab-adjusted difference 25·1% [15·2-35·0]; p<0·0001 vs placebo and ustekinumab). In UltIMMa-2, 246 (83·7%) patients receiving risankizumab versus five (5·1%) receiving placebo (placebo-adjusted difference 78·5% [95% CI 72·4-84·5]) and 61 (61·6%) receiving ustekinumab achieved sPGA 0 or 1 at week 16 (ustekinumab-adjusted difference 22·3% [12·0-32·5]; p<0·0001 vs placebo and ustekinumab). The frequency of treatment-emergent adverse events in UltIMMa-1 and UltIMMa-2 was similar across risankizumab (part A: 151 [49·7%] of 304 and 134 [45·6%] of 294; part B: 182 [61·3%] of 297 and 162 [55·7%] of 291), placebo (part A: 52 [51·0%] of 102 and 45 [45·9%] of 98), ustekinumab (part A: 50 [50·0%] of 100 and 53 [53·5%] of 99; part B: 66 [66·7%] of 99 and 70 [74·5%] of 94), and placebo to risankizumab (part B: 65 [67·0%] of 97 and 61 [64·9%] of 94) treatment groups throughout the study duration. Risankizumab showed superior efficacy to both placebo and ustekinumab in the treatment of moderate-to-severe plaque psoriasis. Treatment-emergent adverse event profiles were similar across treatment groups and there were no unexpected safety findings. AbbVie and Boehringer Ingelheim.


Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma Cells.
Methylation of lysine residues on histone tail is a dynamic epigenetic modification that plays a key role in chromatin structure and gene regulation. Members of the KDM5 (also known as JARID1) sub-family are 2-oxoglutarate (2-OG) and Fe2+-dependent oxygenases acting as histone 3 lysine 4 trimethyl (H3K4me3) demethylases, regulating proliferation, stem cell self-renewal, and differentiation. Here we present the characterization of KDOAM-25, an inhibitor of KDM5 enzymes. KDOAM-25 shows biochemical half maximal inhibitory concentration values of <100 nM for KDM5A-D in vitro, high selectivity toward other 2-OG oxygenases sub-families, and no off-target activity on a panel of 55 receptors and enzymes. In human cell assay systems, KDOAM-25 has a half maximal effective concentration of ∼50 μM and good selectivity toward other demethylases. KDM5B is overexpressed in multiple myeloma and negatively correlated with the overall survival. Multiple myeloma MM1S cells treated with KDOAM-25 show increased global H3K4 methylation at transcriptional start sites and impaired proliferation.


Mediating role of borderline personality disorder traits in the effects of childhood maltreatment on suicidal behaviour among mood disorder patients.
Substantial evidence supports an association between childhood maltreatment and suicidal behaviour. However, few studies have examined factors mediating this relationship among patients with unipolar or bipolar mood disorders. Depressive disorder and bipolar disorder (ICD-10-DCR) patients (n=287) from the Helsinki University Psychiatric Consortium (HUPC) Study were surveyed on self-reported childhood experiences, current depressive symptoms, borderline personality disorder traits, and lifetime suicidal behaviour. Psychiatric records served to complement the information on suicide attempts. We examined by formal mediation analyses whether (1) the effect of childhood maltreatment on suicidal behaviour is mediated through borderline personality disorder traits and (2) the mediation effect differs between lifetime suicidal ideation and lifetime suicide attempts. The impact of childhood maltreatment in multivariate models on either lifetime suicidal ideation or lifetime suicide attempts showed comparable total effects. In formal mediation analyses, borderline personality disorder traits mediated all of the total effect of childhood maltreatment on lifetime suicide attempts, but only one fifth of the total effect on lifetime suicidal ideation. The mediation effect was stronger for lifetime suicide attempts than for lifetime suicidal ideation (P=0.002) and independent of current depressive symptoms. The mechanisms of the effect of childhood maltreatment on suicidal ideation versus suicide attempts may diverge among psychiatric patients with mood disorders. Borderline personality disorder traits may contribute to these mechanisms, although the influence appears considerably stronger for suicide attempts than for suicidal ideation.


Identification of radiation-induced microRNA transcriptome by next-generation massively parallel sequencing.
Gene regulation in cells exposed to ionizing radiation (IR) occurs at the transcriptional and post-transcriptional levels. Recent studies have suggested that micro-RNA (miRNA) play a significant role in post-transcriptional gene regulation in irradiated cells. miRNA are RNA molecules 18-24 nucleotides in length that are involved in negatively regulating the stability or translation of target messenger RNA. Previous studies from our laboratory have shown that the expression of various miRNA is altered in IR-treated cells. In the present study we monitored genome-wide expression changes of miRNA transcriptome by massively parallel sequencing of human cells irradiated with X-rays. The baseline expression of 402 miRNA indicated a wide range of modulation without exposure to IR. Differences in the expression of many miRNA were observed in a time-dependent fashion following radiation treatment. The Short Time-series Expression Miner (STEM) clustering tool was used to characterize 190 miRNA to six statistically significant temporal expression profiles. miR-19b and miR-93 were induced and miR-222, miR-92a, and miR-941 were repressed after radiation treatment. miR-142-3p, miR-142-5p, miR-107, miR-106b, miR-191, miR-21, miR-26a, miR-182, miR-16, miR-146a, miR-22 and miR-30e exhibited two peaks of induction: one at 8 h and the other at 24 h post-irradiation. miR-378, miR-let-7a, miR-let-7g, miR-let-7f, miR-103b, miR-486-3p, miR-423-5p, miR-4448, miR-3607-5p, miR-20b, miR-130b, miR-155, miR-181, miR-30d and miR-378c were induced only at the 8-h time-point. This catalogue of the inventory of miRNA that are modulated as a response to radiation exposure will be useful for explaining the mechanisms of gene regulation under conditions of stress.


Dexterity testing as a predictor of oral care ability.
To examine a spectrum of elderly people to determine if hand function/dexterity measures can predict oral care ability. A series of dental, hand function, and dexterity measures were assessed by blinded examiners. Plaque scores were used as the criterion standard to assess plaque removal ability. A convenience sample of 52, predominately male, elderly patients were recruited from the patient population of the Portland Veteran Affairs Medical Center and a community nursing home. Entry into the study required that the patient be able to give consent, be age 65 or older, have a minimum of six contiguous teeth or a minimum of 12 teeth total, be medically stable, have grossly adequate vision, and be able to hear and understand spoken instructions. The primary outcome measure was plaque score, as defined by the Turesky modification of the Quigley-Hein index. This was related to four dexterity tests (Jebsen-Taylor Hand Function test, Nine-hole Peg test, Box and Block test, Toothbrushing Ability test), a grip strength measure, and a cognitive measure (Allen Cognitive Level Test). Oral hygiene was significantly impaired among institutionalized elderly compared with outpatient elderly (P < 0.001), as was dexterity (P < 0.001). All dexterity tests correlated significantly with plaque score (Spearman rho: 0.49-0.77; P < 0.000). Forward stepwise regression analysis identified the Toothbrushing Ability Test (P < 0.0001) and the time spent brushing (P = 0.007) as the most significant predictors of plaque score. Results suggest oral hygiene ability is decreased among long term care residents, that dexterity tests can help identify patients unable to perform adequate oral self-care, and that these tests could be used to estimate brushing ability among elderly compromised patients.


Perspective: Drawing on Findings From Critical Illness to Explain Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
We propose an initial explanation for how myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) could originate and perpetuate by drawing on findings from critical illness research. Specifically, we combine emerging findings regarding (a) hypoperfusion and endotheliopathy, and (b) intestinal injury in these illnesses with our previously published hypothesis about the role of (c) pituitary suppression, and (d) low thyroid hormone function associated with redox imbalance in ME/CFS. Moreover, we describe interlinkages between these pathophysiological mechanisms as well as "vicious cycles" involving cytokines and inflammation that may contribute to explain the chronic nature of these illnesses. This paper summarizes and expands on our previous publications about the relevance of findings from critical illness for ME/CFS. New knowledge on diagnostics, prognostics and treatment strategies could be gained through active collaboration between critical illness and ME/CFS researchers, which could lead to improved outcomes for both conditions.


Prevalence of Potentially Inappropriate Medication use in older drivers.
Potentially Inappropriate Medication (PIM) use has been studied in a variety of older adult populations across the world. We sought to examine the prevalence and correlates of PIM use in older drivers. We applied the American Geriatrics Society 2015 Beers Criteria to baseline data collected from the "brown-bag" review of medications for participants of the Longitudinal Research on Aging Drivers (LongROAD) study to examine the prevalence and correlates of PIM use in a geographically diverse, community-dwelling sample of older drivers (n = 2949). Proportions of participants who used one or more PIMs according to the American Geriatrics Society 2015 Beers Criteria, and estimated odds ratios (ORs) and 95% confidence intervals (CIs) of PIM use associated with participant characteristics were calculated. Overall, 18.5% of the older drivers studied used one or more PIM. The most commonly used therapeutic category of PIM was benzodiazepines (accounting for 16.6% of the total PIMs identified), followed by nonbenzodiazepine hypnotics (15.2%), antidepressants (15.2%), and first-generation antihistamines (10.5%). Compared to older drivers on four or fewer medications, the adjusted ORs of PIM use were 2.43 (95% CI 1.68-3.51) for those on 5-7 medications, 4.19 (95% CI 2.95-5.93) for those on 8-11 medications, and 8.01 (95% CI 5.71-11.23) for those on ≥12 medications. Older drivers who were female, white, or living in urban areas were at significantly heightened risk of PIM use. About one in five older drivers uses PIMs. Commonly used PIMs are medications known to impair driving ability and increase crash risk. Implementation of evidence-based interventions to reduce PIM use in older drivers may confer both health and safety benefits. Not applicable.


Transcatheter aortic valve implantation in patients with rheumatic aortic stenosis.
Rheumatic heart disease (RHD) accounts for the highest number of deaths from valvular heart disease globally. Yet, rheumatic aortic stenosis (AS) was excluded from landmark studies investigating the safety and efficacy of transcatheter aortic valve implantation (TAVI). We aimed to describe the clinical and anatomical characteristics of patients with rheumatic AS undergoing TAVI, and to compare procedural and clinical outcomes with patients undergoing TAVI for degenerative AS. In a prospective TAVI registry, patients with rheumatic AS were identified based on International Classification of Diseases version 10 codes and/or a documented history of acute rheumatic fever and/or the World Heart Federation criteria for echocardiographic diagnosis of RHD, and were propensity score-matched in a 1:4 ratio to patients with degenerative AS. Among 2329 patients undergoing TAVI, 105 (4.5%) had rheumatic AS. Compared with patients with degenerative AS, patients with rheumatic AS were more commonly female, older, had higher surgical risk and more commonly suffered from multivalvular heart disease. In the unmatched cohort, both technical success (85.7% vs 85.9%, p=0.887) and 1-year cardiovascular mortality (10.0% vs 8.6%; HR 1.16, 95% CI 0.61 to 2.18, p=0.656) were comparable between patients with rheumatic and degenerative AS. In contrast, patients with rheumatic AS had lower rates of 30-day and 1-year cardiovascular mortality compared with matched patients with degenerative AS (1.9% vs 8.9%, adjusted HR (HRadj) 0.18, 95% CI 0.04 to 0.80, p=0.024; and 10.0% vs 20.3%, HRadj 0.44, 95% CI 0.24 to 0.84, p=0.012, respectively). TAVI may be a safe and effective treatment strategy for selected elderly patients with rheumatic AS. NCT01368250.


RADA-16-based Self-assembled Peptide Nanofiber Scaffolds Loaded with TGF-β1 Enhance the Chondrogenic Differentiation Potential of BMSCs In vitro.
At present, cartilage repair does not offer ideal efficacy. Fortunately, recent studies have claimed that RADA-16 peptide is an attractive therapeutic strategy for repairing cartilage defects. Therefore, this study tried to explore the effect of RADA-16 loaded with transforming growth factor-beta (TGF-β) 1 on cartilage differentiation of bone marrow mesenchymal stem cells (BMSCs). First, the RADA-16 peptide was synthesized by solid phase peptide, and a well-defined hydrogel was formed by supramolecular peptide self-assembly. Then, TGF-β1 (loading concentration of 10 ng/mL) was loaded into RADA-16, with scanning electron microscopy to observe the morphology of the TGF-β1/RADA-16 hydrogel and detect its related properties. Next, BMSCs were isolated from bone marrow samples and identified. TGF-β1/RADA-16 was co-cultured with L929, BMSCs, and C28/I2 cells, respectively, and the survival and proliferation ability of the cells was determined by live/dead cell staining and MTT assay. Chondrogenic differentiation and sGAG production of BMSCs were determined by Alcian blue staining and Blyscan assay, the expression of cartilage-associated genes by qRT-PCR, and the levels of inflammatory factors by ELISA. As for mechanism investigation, the Smad and ERK/MAPK signaling pathways were detected by western blot. RADA-16 hydrogel exhibited a well-distributed and interconnected porous surface structure, with a loading rate of 91.9% for TGF-β1. The TGF-β1/RADA-16 hydrogel had good release and degradation properties, and had no negative effect on the survival and proliferation ability of BMSCs, L929, and C28/I2 cells. Importantly, TGF-β1/RADA-16 hydrogel significantly accelerated chondrogenic differentiation and sGAG generation in BMSCs, and decreased pro-inflammatory factor production. In addition, the hydrogel also significantly activated the Smad and ERK/MAPK pathways of BMSCs. RADA-16 loaded with TGF-β1 has good biological properties and can enhance the chondrogenic differentiation ability of BMSCs.


The Exocyst: Dynamic Machine or Static Tethering Complex?
The exocyst is a conserved octameric complex that physically tethers a vesicle to the plasma membrane, prior to membrane fusion. It is important not only for secretion and membrane delivery but also, in mammalian cells, for cytokinesis, ciliogenesis, autophagy, tumorigenesis, and host defense. The combination of genome editing and advanced light microscopy of exocyst subunits in living cells has recently shown the complex to be much more dynamic than previously appreciated, and exposed how little we still know about its function and regulation.


Neurotoxin treatments for urinary incontinence in subjects with spinal cord injury or multiple sclerosis: a systematic review of effectiveness and adverse effects.
The objective was to evaluate the effectiveness of neurotoxin treatments of urinary incontinence (UI) in individuals with spinal cord injury (SCI) or multiple sclerosis (MS). Studies were included if published in English, presented randomized adults with SCI or MS, and reported UI outcomes. Ten trials randomizing 288 subjects with SCI (43%), MS (52%), or other spinal conditions (5%) and UI refractory to oral antimuscarinics were included. The overall mean age was 41 years, and 46% were women. Study durations ranged from 1 to 18 months. Treatments included botulinum toxin-A (BTX-A, 2 trials) and 2 vanilloid compounds, capsaicin (6 trials) and resiniferatoxin (4 trials). BTX-A was superior to placebo and resiniferatoxin in reducing daily UI episodes, mainly in individuals with SCI, although significant reductions vs placebo were not evident throughout the study duration. There were 1.1 fewer daily UI episodes in the BTX-A 200 unit group vs 0.1 fewer for the placebo group at the final week 24 assessment. Capsaicin was generally superior to placebo. The weighted difference between capsaicin and placebo in a pooled analysis of 2 trials enrolling subjects with either paraplegia or tetraplegia (n = 32) was -3.8 daily UI episodes [95% Cl -4.7 to -2.9] after 30 days. Capsaicin was comparable to resiniferatoxin. Pelvic pain and facial flushing were associated with capsaicin. Neurotoxins may improve refractive UI in adults with SCI or MS, although trial results were inconsistent. Trials were small in size and relatively short in duration. Further studies are needed to determine the efficacy and tolerability of long-term application.


Cooperative jump motions of jammed particles in a one-dimensional periodic potential.
Cooperative jump motions are studied for mutually interacting particles in a one-dimensional periodic potential. The diffusion constant for the cooperative motion in systems including a small number of particles is numerically calculated and it is compared with theoretical estimates. We find that the size distribution of the cooperative jump motions obeys an exponential law in a large system.


[Chemical fluctuation of the constituents during the drying of Ginseng radix and Ginseng radix Rubra. Crude drug processing by far-infrared treatment].
In order to evaluate the utility of far-infrared drying method for crude drugs, the efficiency in the drying process of Ginseng Radix and Ginseng Radix Rubra was examined. Furthermore, chemical fluctuation of the constituents of Ginseng Radix and Ginseng Radix Rubra, which may occur during their drying process, has been investigated by means of HPLC quantitative analysis for ginsenosides and malonyl-ginsenosides, and TLC qualitative analysis for lipophylic constituents. It has been found that the far-infrared drying method (oven temperature 45 degrees C) dried Ginseng Radix faster without reducing both ginsenosides and malonyl-ginsenosides in comparison with the conventional drying methods such as an air drying and a hot-air drying.


From locus to cellular disturbances: positional cloning of the infantile neuronal ceroid lipofuscinosis gene.
Neuronal ceroid lipofuscinoses (NCL) represent a group of common progressive encephalopathies of children with a global incidence of 1 in 12,500. NCL are divided into three autosomal recessive subtypes, all assigned to different chromosomal loci. The infantile subtype of NCL (INCL) is characterized by early visual loss and mental deterioration, and leads to a vegetative state of the patients by 3 years of age. We pursued the identification of the gene defective in INCL, enriched in the Finnish population by a positional cloning approach and identified mutations in the palmitoyl-protein thioesterase (PPT) gene in INCL patients. We have further shown that PPT represents a novel lysosomal enzyme and is routed to the lysosomes via the mannose 6-phosphate receptor-mediated pathway. The worldwide most common mutation in the PPT gene, INCLFin, results in the deficient routing of the mutant PPT to lysosomes and undetectable enzyme activity in the brain tissue of patients. Our results suggest that INCL can be classified as a new member of lysosomal enzyme deficiencies.


[The dynamic expression changes of myocardium p-p38MAPK, NF-κB and COX-2 in rats after an exhausted exercise].
To observe the dynamic expression changes of p38 mitogen-activated protein kinase (p38MAPK), nucler facter kappa B (NF-κB) and cyclooxygenase-2 (COX-2) in myocardial tissue after an exhausted exercise and study the impact of p38MAPK, NF-κB and COX-2 on its myocardial damage. Sixty Wister male rats were randomly divided into the control group (n = 10) and the exhausted exercise group (n = 50). Then the exhausted exercise group was further divided into 5 subgroups, namely 0 h, 3 h, 6 h, 12 h, 24 h after an exhausted exercise (n = 10). The myocardial injury animal model was set up by using an exhausted swimming exercise and the expression of p-p38MAPK, NF-κB and COX-2 were examined by Western blot. Compared with the control group, the expression of p-p38MAPK were increased significantly (P < 0.01) in all the groups and the 3 h group was the highest( P < 0.01); The expression of NF-κB were increased significantly (P < 0.05) in all the groups but 0 h P > 0.05) and the 6h group was increased significantly compared with the other groups( P < 0.05); The expression of COX-2 were increased significantly( P < 0.05) in all the groups but 0 h and the 24 h groups was increased significantly compared with the other groups(P < 0.05). p38MAPK was activated in an acute exhausted exercise, p-p38MAPK may play an important role in modulating NF-κB and COX-2 expression and mediating the exhausted exercise induced myocardial damage.


Involvement of ASR genes in aluminium tolerance mechanisms in rice.
Among cereal crops, rice is considered the most tolerant to aluminium (Al). However, variability among rice genotypes leads to remarkable differences in the degree of Al tolerance for distinct cultivars. A number of studies have demonstrated that rice plants achieve Al tolerance through an unknown mechanism that is independent of root tip Al exclusion. We have analysed expression changes of the rice ASR gene family as a function of Al treatment. The gene ASR5 was differentially regulated in the Al-tolerant rice ssp. Japonica cv. Nipponbare. However, ASR5 expression did not respond to Al exposure in Indica cv. Taim rice roots, which are highly Al sensitive. Transgenic plants carrying RNAi constructs that targeted the ASR genes were obtained, and increased Al susceptibility was observed in T1 plants. Embryogenic calli of transgenic rice carrying an ASR5-green fluorescent protein fusion revealed that ASR5 was localized in both the nucleus and cytoplasm. Using a proteomic approach to compare non-transformed and ASR-RNAi plants, a total of 41 proteins with contrasting expression patterns were identified. We suggest that the ASR5 protein acts as a transcription factor to regulate the expression of different genes that collectively protect rice cells from Al-induced stress responses.


Improving motor and cognitive recovery following severe traumatic brain injury using advanced emotional audio-video stimulation: Lessons from a case report.
It is estimated that about 6 million people suffer from severe traumatic brain injury (TBI) each year (73 cases per 100,000 people). TBI may affect emotional, sensory-motor, cognitive, and psychological functions with a consequent worsening of both patient and his/her caregiver's quality of life. In recent years, technological innovations allowed the development of new, advanced sensory stimulation systems, such as Neurowave, to further stimulate residual cognitive abilities and, at the same time, evaluate residual cognition. An 69-year-old Italian man entered our neurorehabilitation unit with a diagnosis of minimally conscious state following severe TBI. He breathed spontaneously via tracheostomy and was fed via percutaneous gastrostomy. At the neurological examination, the patient showed severe tetraparesis as he showed fluctuating alertness and responsiveness to external stimuli and opened the eyes without stimulation. Patient was affected by subarachnoid hemorrhage and frontotemporal bilateral hematoma, which were surgically treated with decompressive craniotomy and subsequent cranioplasty about 6 months before. The patient underwent a neuropsychological and clinical evaluation before (T0) and after a conventional rehabilitation cycle (T1), and after a Neurowave emotional stimulation-supported rehabilitative cycle (T2). Following conventional rehabilitation (T1), the patient achieved a partial improvement in behavioral responsiveness; there was also a mild improvement in the caregiver's distress. Conversely, Neurowave emotional stimulation session determined (at T2) a significant improvement of the patient's behavioral responsiveness, cognition, and in the caregiver's distress. The P300 recording in response to the NES showed a significant change of P300 magnitude and latency. Our data suggest that emotional-integrated sensory stimulation using adequate visual stimuli represents a beneficial, complementary rehabilitative treatment for patients in minimally conscious state following a severe TBI. This may occur because stimuli with emotional salience can provide a reliable motivational resource to stimulate motor and cognitive recovery following severe TBI.


Robotic surgery in hip and knee arthroplasty.
This article provides an overview of current use of robotics in hip and knee arthroplasty. Several studies have reported radiographic improvements in joint alignment using robotic-assisted arthroplasty surgery. The economic case made for introducing robotics in joint arthroplasty largely focuses on the hypothesis of reduced hospital stay and reduction in the rate of revisions. This awaits robust data from long-term studies along with the documentation of clinical benefits that will follow the larger implementation of robotic-assisted surgery. However, modern robotic systems offer an opportunity for reproducible implementation of a preoperative plan, with low complication rates. Growing clinical use may in future present robust data demonstrating an appreciable clinical benefit that justifies the large scale clinical use of robotic technology.


Addressing Current Criticism Regarding the Value of Self-Report Dietary Data.
Recent reports have asserted that, because of energy underreporting, dietary self-report data suffer from measurement error so great that findings that rely on them are of no value. This commentary considers the amassed evidence that shows that self-report dietary intake data can successfully be used to inform dietary guidance and public health policy. Topics discussed include what is known and what can be done about the measurement error inherent in data collected by using self-report dietary assessment instruments and the extent and magnitude of underreporting energy compared with other nutrients and food groups. Also discussed is the overall impact of energy underreporting on dietary surveillance and nutritional epidemiology. In conclusion, 7 specific recommendations for collecting, analyzing, and interpreting self-report dietary data are provided: (1) continue to collect self-report dietary intake data because they contain valuable, rich, and critical information about foods and beverages consumed by populations that can be used to inform nutrition policy and assess diet-disease associations; (2) do not use self-reported energy intake as a measure of true energy intake; (3) do use self-reported energy intake for energy adjustment of other self-reported dietary constituents to improve risk estimation in studies of diet-health associations; (4) acknowledge the limitations of self-report dietary data and analyze and interpret them appropriately; (5) design studies and conduct analyses that allow adjustment for measurement error; (6) design new epidemiologic studies to collect dietary data from both short-term (recalls or food records) and long-term (food-frequency questionnaires) instruments on the entire study population to allow for maximizing the strengths of each instrument; and (7) continue to develop, evaluate, and further expand methods of dietary assessment, including dietary biomarkers and methods using new technologies.


Affinity Induced Surface Functionalization of Liposomes Using Cu-Free Click Chemistry.
Functionalization of nanoparticles is a key element for improving specificity of drug delivery systems toward diseased tissue or cells. In the current study we report a highly efficient and chemoselective method for post-functionalization of liposomes with biomacromolecules, which equally well can be used for functionalization of other nanoparticles or solid surfaces. The method exploits a synergistic effect of having both affinity and covalent anchoring tags on the surface of the liposome. This was achieved by synthesizing a peptide linker system that uses Cu-free strain-promoted click chemistry in combination with histidine affinity tags. The investigation of post-functionalization of PEGylated liposomes was performed with a cyclic RGDfE peptide. By exploring both affinity and covalent tags a 98 ± 2.0% coupling efficiency was achieved, even a diluted system showed a coupling efficiency of 87 ± 0.2%. The reaction kinetics and overall yield were quantified by HPLC. The results presented here open new possibilities for constructing complex nanostructures and functionalized surfaces.


Clinicopathological Examination of Metaplastic Spindle Cell Carcinoma of the Breast: Case Series.
Spindle cell carcinoma (SpCC) of the breast is a rare histological type, a subtype of metaplastic carcinoma characterized by atypical spindle cell and epithelial carcinoma. The proportions of the spindle cell and epithelial components vary among tumours. Due to its rarity, biological characteristics of this disease have been poorly studied. In total, 10 patients with SpCC were surgically treated at our institution from January 2007 to December 2018. We retrospectively investigated these SpCC cases, focusing on the differences between spindle cell and epithelial components. Microsatellite status was also examined. Nine cases were triple-negative breast cancer (TNBC). The rates of high tumour grade were 70% in spindle cell components and 56% in epithelial components (P = .65), while the mean Ki67 labelling index were 63% and 58%, respectively (P = .71). Mean programmed death ligand 1 (PD-L1) expression in these components was 11% and 1%, respectively (P = .20). All 10 tumours were microsatellite stable. Patient outcomes of triple-negative SpCC did not differ from those of propensity-matched patients with conventional TNBC. Spindle cell components showed higher values in factors examined, although there was no statistically significant difference. Our data reveal that these 2 components of SpCC may be of different biological nature.


Gestational diabetes mellitus: a qualitative study of lived experiences of South Asian immigrant women and perspectives of their health care providers in Melbourne, Australia.
South Asian women are at a high risk of developing gestational diabetes mellitus than other women in Australia. Gestational diabetes affects up to 14-19% of all pregnancies among South Asian, South East Asian, and Arabic populations placing women at risk of adverse pregnancy outcomes. Although, gestational diabetes resolves after childbirth, women with gestational diabetes are up to seven times more likely to develop type 2 diabetes within five to ten years of the index pregnancy. Increasingly, South Asian women are being diagnosed with gestational diabetes in Australia. Therefore, we aimed to gain a better understanding of the lived experiences of South Asian women and their experiences of self-management and their health care providers' perspectives of treatment strategies. Using an ethnographic qualitative research methodology, semi-structured one-on-one, face-to-face interviews were conducted with 21 health care providers involved in gestational diabetes management and treatment from the three largest tertiary level maternity hospitals in Melbourne, Victoria, Australia. In-depth interviews were conducted with 23 South Asian women post diagnosis between 24-28 weeks gestation in pregnancy. Health care providers had challenges in providing care to South Asian women. The main challenge was to get women to self-manage their blood glucose levels with lifestyle modification. Whilst, women felt self-management information provided were inadequate and inappropriate to their needs. Women felt 'losing control over their pregnancy', because of being preoccupied with diet and exercise to control their blood glucose level. The gestational diabetes clinical practice at the study hospitals were unable to meet consumer expectations. Health care providers need to be familiar of diverse patient cultures, rather than applying the current 'one size fits all' approach that failed to engage and meet the needs of immigrant and ethnic women. Future enabling strategies should aim to co-design and develop low Glycaemic Index diet plans of staple South Asian foods and lifestyle modification messages.


Revisiting the mitogenetic effect of ultra-weak photon emission.
This paper reviews the 90 years long controversial history of the so-called "mitogenetic radiation," the first case of non-chemical distant interactions, reported by Gurwitsch (1923). It was soon described as ultraweak UV, emitted by a number of biological systems, and stimulating mitosis in "competent" (in this sense) cells. In the following 20 years this phenomenon attracted enormous interest of the scientific community, and gave rise to more than 700 publications around the world. Yet, this wave of research vanished after several ostensibly disproving works in late 1930-s, and was not resumed later, regardless of quite serious grounds for that. The authors discuss separately two aspects of the problem: (1) do living organisms emit ultraweak radiation in the UV range (irrespective of whether it has any biological role), and (2) are there any real effects of this ultraweak photon emission (UPE) upon cell division and/or other biological functions? Analysis of the available data permits to conclude, that UV fraction of UPE should be regarded real, while its biological effects are difficult to reproduce. This causes a paradox. A number of presently known qualities of UPE were initially discovered (predicted?) by the "early workers" on the basis of biological effects. Yet the qualities they discovered were proved later (the UV component of UPE, the sources of UPE among biological systems, etc…), while the biological effect they used for UPE "detection" remains questionable. Importance of this area for basic biology and medicine, and potential usefulness of UPE as a non-invasive research method, invite scientists to attack this problem again, applying powerful research facilities of modern science. Yet, because of complexity and uncertainty of the problem, further progress in this area demands comprehensive examination of both positive and negative works, with particular attention to their methodical details.


Claspin: timing the cell cycle arrest when the genome is damaged.
DNA damage checkpoints maintain genomic integrity by delaying cell cycle progression in response to genotoxic stress and stalled replication forks. One central pathway in the checkpoint response is the ATR-Chk1 pathway, in which, upon DNA damage, ATR phosphorylates and activates the effector kinase Chk1. This process depends on the adaptor protein Claspin that bridges ATR and Chk1. Once the damage is repaired, this pathway must somehow be switched off to allow the cell to continue the cell division process, an event known as checkpoint recovery. Polo-like kinase 1 (Plk1) plays a central role during checkpoint recovery. Interestingly, the Xenopus homologue of Plk1, Plx1, is able to bind and phosphorylate Claspin, releasing it from DNA and thereby contributing to Chk1 inactivation. Moreover, it was recently demonstrated that Claspin levels are controlled by proteasomal degradation, and this is regulated by Plk1. Importantly, Plk1-mediated proteosomal degradation of Claspin appears to be essential for check-point recovery. Here we review these recent findings and discuss the mechanisms of checkpoint regulation by Claspin.


Intestinal parasitic infections among human immunodeficiency virus-infected and -uninfected children hospitalized with diarrhea in Bangkok, Thailand.
A prospective observational study was conducted to determine the prevalence and the clinical impact of intestinal parasitic infections in diarrheal illness among HIV-infected and HIV-uninfected children hospitalized with diarrhea in Bangkok, Thailand. Stool samples were examined for intestinal parasites using a simple smear method, a formalin-ether concentration method, a modified acid-fast stain and a modified trichrome stain. Intestinal parasites (IP) were identified in the stool specimens of 27 of 82 (33%) HIV-infected and 12 of 80 (15%) HIV-uninfected children (p=0.01). Microsporidia and Cryptosporidium were the most common IP found. Eighty-two percent of HIV-infected and 97% of HIV-uninfected groups presented with acute diarrhea and 76% of each group had watery diarrhea. Pneumonia was the most common concurrent illness, found in 22%. Clinical findings were unable to differentiate children infected with IP. Sixty-three percent of HIV-infected and 83% of HIV-uninfected children who had IP made a satisfactory recovery without specific anti-parasitic therapy. However, 9 children (7 HIV-infected and 2 HIV-uninfected) with persistent diarrhea who also had cryptosporidiosis and/or microsporidiosis did not respond to azithromycin and/or albendazole respectively. HIV-infected children with cryptosporidiosis were older and had more advanced HIV infection than those with microsporidiosis. Routine stool examination for IP should be considered due to the absence of clinical markers. The lack of effective therapy for the major IP found underscores the importance of preventive measures.


Validity assessment of self-reported construction tasks.
This study assessed agreement between workers' and observers' daily estimates of exposure to construction work tasks. The ultimate aim was to develop a valid method and instrument for the collection of self-reported data on duration of exposure to a priori identified work tasks for use in characterizing exposure in settings with substantial task variability. Forty-nine shop workers and 52 construction site sheet metal workers were observed for up to 3 full workdays. Observers sampled approximately 25% of each worker's day, recording the work performed from a prespecified list of tasks. Each participant completed a daily questionnaire, indicating the tasks he or she performed that day and time spent on each task. Shop workers tended to specialize in particular tasks, while at the construction site, the workers' tasks reflected substantial day-to-day variability. Agreement between worker and observer estimates was generally better for major shop tasks (with intraclass correlation coefficients [ICCs] ranging from 0.52 to 0.85), than for major construction site tasks (with ICCs ranging from 0.36 to 0.64). Workers tended to overestimate the amount of time spent at tasks of longer duration and to underestimate time spent at short-duration tasks. Rank order analysis of time spent on task revealed fairly high agreement. Agreement was acceptable for shop-based work, which has less day-to-day variability than construction site work. Overall, however, the data suggest that, for highly variable work, the use of task as the unit of exposure does not improve recall over assessment approaches focusing on questions about posture and material handling.


Identification of Tibicen cicada species by a Principal Components Analysis of their songs.
Specific identification of three Tibicen cicadas, T. japonicus, T. flammatus and T. bihamatus, by their chirping sounds was carried out using Principal Components Analysis (PCA). High quality recordings of each species were used as the standards. The peak and mean frequencies and the pulse rate were used as the variables. Out of 12 samples recorded in the fields one fell in the vicinity of T. japonicus and all other were positioned near T. bihamatus. Then the cluster analysis of the PCA scores clearly separated each species and allocated the samples in the same way.


Thorax disease diagnosis using deep convolutional neural network.
Computer aided diagnosis (CAD) is an important issue, which can significantly improve the efficiency of doctors. In this paper, we propose a deep convolutional neural network (CNN) based method for thorax disease diagnosis. We firstly align the images by matching the interest points between the images, and then enlarge the dataset by using Gaussian scale space theory. After that we use the enlarged dataset to train a deep CNN model and apply the obtained model for the diagnosis of new test data. Our experimental results show our method achieves very promising results.


"If We Build It, Will They Come?" A Cohort Study of Family Utilization of a Pediatric-Specific Hospice Home.
Objective: To determine whether families would make use of a pediatric-specific inpatient hospice facility for end-of-life care for children. Background: Location of end-of-life care and death are important considerations when treating children with life-limiting conditions. There is very limited research on utilization of an inpatient hospice facility for end-of-life care if a pediatric-specific facility is available. We examined changes in family utilization of inpatient hospice services with the availability of an inpatient pediatric hospice facility (PHF). Methods: We conducted a retrospective cohort study with data collected on location of end-of-life care and death five years prior to and five years following the opening of a PHF that receives referrals from a large children s hospital in United States. Two data sources from the hospice organization were used: (1) a dataset on origins and outcomes of referrals to pediatric inpatient hospice care and (2) a dataset on location of death for all pediatric patients who had any contact with the hospice system. Chi-square analyses were conducted to assess the associations between the PHF opening and referral outcomes and location of death. Results: Significant results were found with respect to both referral outcomes and location of death. Engagement in inpatient hospice care increased between 2- and 10-fold following the opening of the inpatient PHF. The percent of patients who died in an inpatient hospice unit also increased significantly with the opening of the pediatric facility. Discussion: Results of this study show that providers are more likely to refer, and families are more likely to use inpatient hospice services when pediatric facilities are available. These results are important for establishing an evidence base in support for increasing access to PHFs.


Feasibility of a virtually delivered eating disorder prevention program for young females with type 1 diabetes.
This study aimed to develop a virtual diabetes-specific version of the eating disorder (ED) prevention program the Body Project, and to assess feasibility and preliminary efficacy of this program for young females with type 1 diabetes. Young females with type 1 diabetes aged 16-35 years were invited to participate in the study. A total of 35 participants were allocated to five Diabetes Body Project groups (six meetings over 6 weeks) and completed pretest assessments; 26 participants completed all sessions and posttest assessments (<7 days after last meeting). Primary measures included ED risk factors and symptoms, and secondary outcomes included diabetes-specific constructs previously found to be associated with ED psychopathology (e.g., diabetes distress and illness perceptions). The ease of recruitment, timely conduct of five groups, moderate drop-out rate and appreciation of the intervention by participants indicated that the Diabetes Body Project is feasible. Meaningful reductions occurred on the primary outcomes (i.e., ED psychopathology, body dissatisfaction, and thin ideal internalization) and on internalization of appearance ideals and appearance pressures at posttest (Cohen's d ranging from .63 to .83, which are medium to large effects). Small to medium effect sizes were found for diabetes illness perceptions and distress (.41 and .48, respectively). The virtual Diabetes Body Project is a promising and much-needed intervention, worthy of more rigorous evaluation. A randomized controlled trial is warranted to determine its effectiveness compared with a control condition.


Target sites for chemical regulation of strigolactone signaling.
Demands for plant growth regulators (PGRs; chemicals that control plant growth) are increasing globally, especially in developing countries. Both positive and negative PGRs are widely used to enhance crop production and to suppress unwanted shoot growth, respectively. Strigolactones (SLs) are multifunctional molecules that function as phytohormones, inhibiting shoot branching and also functioning in the rhizospheric communication with symbiotic fungi and parasitic weeds. Therefore, it is anticipated that chemicals that regulate the functions of SLs will be widely used in agricultural applications. Although the SL biosynthetic pathway is not fully understood, it has been demonstrated that β-carotene isomerases, carotenoid cleavage dioxygenases (CCDs), and a cytochrome P450 monooxygenase are involved in strigolactone biosynthesis. A CCD inhibitor, abamine, which is also an inhibitor of abscisic acid biosynthesis, reduces the levels of SL in several plant species and reduces the germination rate of Orobanche minor seeds grown with tobacco. On the basis of the structure of abamine, several chemicals have been designed to specifically inhibit CCDs during SL synthesis. Cytochrome P450 monooxygenase is another target enzyme in the development of SL biosynthesis inhibitors, and the triazole-derived TIS series of chemicals is known to include SL biosynthesis inhibitors, although their target enzyme has not been identified. Recently, DWARF14 (D14) has been shown to be a receptor for SLs, and the D-ring moiety of SL is essential for its recognition by D14. A variety of SL agonists are currently under development and most agonists commonly contain the D-ring or a D-ring-like moiety. Several research groups have also resolved the crystal structure of D14 in the last two years. It is expected that this information on the D14 structure will be invaluable not only for developing SL agonists with novel structures but also in the design of inhibitors of SL receptors.


Evolutionary genetic consequences of facultative sex and outcrossing.
Explaining the selective forces that underlie different reproductive modes forms a major part of evolution research. Many organisms are facultative sexuals, with the ability to reproduce both sexually and asexually. Reduced sequencing costs means it is now possible to start investigating genome sequences of a wider number of these organisms in depth, but teasing apart the genetic forces underlying the maintenance of facultative sexual reproduction remains a challenge. An analogous problem exists when determining the genetic consequences of a degree of outcrossing (and recombination) in otherwise self-fertilizing organisms. Here, I provide an overview of existing research on the evolutionary basis behind different reproductive modes, with a focus on explaining the population genetic effects favouring low outcrossing rates in either partially selfing or asexual species. I review the outcomes that both self-fertilization and asexuality have on either purging deleterious mutations or fixing beneficial alleles, and what empirical data exist to support these theories. In particular, a greater application of mathematical models to genomic data has provided insight into the numerous effects that transitions to self-fertilization from outcrossing have on genetic architecture. Similar modelling approaches could be used to determine the forces shaping genetic diversity of facultative sexual species. Hence, a further unification of mathematical models with next-generation sequence data will prove important in exploring the genetic influences on reproductive system evolution.


Spontaneous iliac vein rupture: case report and literature review.
Spontaneous rupture of the iliac vein is a rare cause of exsanguinating haemorrhage. A case is described of a 66 year old woman who required immediate resuscitation in Accident and Emergency following a 24 hour history of left leg and lower quadrant abdominal pain. Emergency laparotomy revealed a 2 cm tear in the left iliac vein. The previously reported cases are reviewed, together with discussion of the patterns of presentation and possible underlying causes.


Gold-Catalyzed Benzylic Azidation of Phthalans and Isochromans and Subsequent FeCl3-Catalyzed Nucleophilic Substitutions.
The benzylic positions of the phthalan and isochroman derivatives (1) as benzene-fused cyclic ethers effectively underwent gold-catalyzed direct azidation using trimethylsilylazide (TMSN3) to give the corresponding 1-azidated products (2) possessing the N,O-acetal partial structure. The azido group of the N,O-acetal behaved as a leaving group in the presence of catalytic iron(III) chloride, and 1-aryl or allyl phthalan and isochroman derivatives were obtained by nucleophilic arylation or allylation, respectively. Meanwhile, a double nucleophilic substitution toward the 1-azidated products (2) occurred at the 1-position using indole derivatives as a nucleophile accompanied by elimination of the azido group and subsequent ring opening of the cyclic ether nucleus produced the bisindolylarylmethane derivatives.


Splicing reprogramming of TRAIL/DISC-components sensitizes lung cancer cells to TRAIL-mediated apoptosis.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selective killing of cancer cells underlines its anticancer potential. However, poor tolerability and resistance underscores the need to identify cancer-selective TRAIL-sensitizing agents. Apigenin, a dietary flavonoid, sensitizes lung cancer cell lines to TRAIL. It remains unknown, however, whether apigenin sensitizes primary lung cancer cells to TRAIL and its underlying mechanisms. Here we show that apigenin reprograms alternative splicing of key TRAIL/death-inducing-signaling-complex (DISC) components: TRAIL Death Receptor 5 (DR5) and cellular-FLICE-inhibitory-protein (c-FLIP) by interacting with the RNA-binding proteins hnRNPA2 and MSI2, resulting in increased DR5 and decreased c-FLIPS protein levels, enhancing TRAIL-induced apoptosis of primary lung cancer cells. In addition, apigenin directly bound heat shock protein 70 (Hsp70), promoting TRAIL/DISC assembly and triggering apoptosis. Our findings reveal that apigenin directs alternative splicing and inhibits Hsp70 enhancing TRAIL anticancer activity. These findings underscore impactful synergies between diet and cancer treatments opening new avenues for improved cancer treatments.


[Tropical endemic limbal conjunctivitis in Cameroon patients. Apropos of 819 cases in Yaounde].
The authors report the epidemiological and clinical aspects of tropical endemic limbo-conjunctivitis in 819 cameroonian patients followed up from June 1989 to June 1990: Tropical endemic limbo-conjunctivitis constitutes about 4% of causes of consultation in our services. The population concerned with LCT is composed of 46.28% of girls and 53.72% of boys; 85% of patients presenting with tropical endemic limbo conjunctivitis are aged between 7 months and 15 years; Allergy and past family history of tropical endemic limbo conjunctivitis are rare and filariasis is an aggravating factor of the disease; The pure globus form is the most frequent (80%) and we did observe especially stages I and II of the disease; The disease does not seem to cause blindness in our area. Synonym: Vernal kerato conjunctivitis.


Biological variation of thromboelastrography variables in 10 clinically healthy horses.
To assess the utility of population-based reference intervals (PRIs) for interpreting thromboelastography (TEG) variables in horses using biological variation data. Prospective cohort biologic variation study conducted over a 5-week period. Veterinary teaching hospital and research facility. Ten clinically healthy horses randomly selected from a veterinary school research and teaching herd. Horse health was determined using physical examination, CBC, and biochemical and coagulation profiles prior to the start of the study. Subsequently, once weekly blood sampling for TEG testing was performed for 5 weeks. The 4 TEG variables reaction time (R), clot formation time (K), angle, and maximum amplitude (MA) were measured, and coefficient of variation representing within- and between-horse biological variation (CVi and CVg , respectively) and coefficient of variation representing analytical variation (CVa ) were calculated using a nested ANOVA after removing outlier data. The CVi , CVg , and CVa for R were 26.8%, 5.2%, and 5.9%; for K were 31.0%, 0.0%, and 5.9%; for angle were 9.4%, 6.2%, and 21.7%; and for MA were 3.4%, 4.1%, and 4.4%, respectively. Index of individuality (IOI) was then calculated for each variable using the formula {( CVi² + CVa²/CVg²)}¹/². IOI for R was 5.3, for angle was 3.8, and for MA was 1.4; IOI was not assessed for K. PRIs are appropriate for TEG variables, R, angle, and MA when interpreting results from individual horses based on calculated IOI values equal to or greater than 1.4. PRIs are likely appropriate when interpreting K, but IOI could not be calculated for this variable.


Differential Regulation of Mas-Related G Protein-Coupled Receptor X2-Mediated Mast Cell Degranulation by Antimicrobial Host Defense Peptides and Porphyromonas gingivalis Lipopolysaccharide.
Porphyromonas gingivalis is a keystone pathogen that contributes to periodontal pathogenesis by disrupting host-microbe homeostasis and promoting dysbiosis. The virulence of P. gingivalis likely reflects an alteration in the lipid A composition of its lipopolysaccharide (LPS) from the penta-acylated (PgLPS1690) to the tetra-acylated (PgLPS1435/1449) form. Mast cells play an important role in periodontitis, but the mechanisms of their activation and regulation remain unknown. The expression of epithelium- and neutrophil-derived host defense peptides (HDPs) (LL-37 and human β-defensin-3), which activate mast cells via Mas-related G protein-coupled receptor X2 (MRGPRX2), is increased in periodontitis. We found that MRGPRX2-expressing mast cells are present in normal gingiva and that their numbers are elevated in patients with chronic periodontitis. Furthermore, HDPs stimulated degranulation in a human mast cell line (LAD2) and in RBL-2H3 cells stably expressing MRGPRX2 (RBL-MRGPRX2). PgLPS1690 caused substantial inhibition of HDP-induced mast cell degranulation, but PgLPS1435/1449 had no effect. A fluorescently labeled HDP (FAM-LL-37) bound to RBL-MRGPRX2 cells, and PgLPS1690 inhibited this binding, but PgLPS1435/1449 had no effect. These findings suggest that low-level inflammation induced by HDP/MRGPRX2-mediated mast cell degranulation contributes to gingival homeostasis but that sustained inflammation due to elevated levels of both HDPs and MRGPRX2-expressing mast cells promotes periodontal disease. Furthermore, differential regulation of HDP-induced mast cell degranulation by PgLPS1690 and PgLPS1435/1449 may contribute to the modulation of disease progression.


The oral motor capacity and feeding performance of preterm newborns at the time of transition to oral feeding.
The objective of the present study was to determine the oral motor capacity and the feeding performance of preterm newborn infants when they were permitted to start oral feeding. This was an observational and prospective study conducted on 43 preterm newborns admitted to the Neonatal Intensive Care Unit of UFSM, RS, Brazil. Exclusion criteria were the presence of head and neck malformations, genetic disease, neonatal asphyxia, intracranial hemorrhage, and kernicterus. When the infants were permitted to start oral feeding, non-nutritive sucking was evaluated by a speech therapist regarding force (strong vs weak), rhythm (rapid vs slow), presence of adaptive oral reflexes (searching, sucking and swallowing) and coordination between sucking, swallowing and respiration. Feeding performance was evaluated on the basis of competence (defined by rate of milk intake, mL/min) and overall transfer (percent ingested volume/total volume ordered). The speech therapist's evaluation showed that 33% of the newborns presented weak sucking, 23% slow rhythm, 30% absence of at least one adaptive oral reflex, and 14% with no coordination between sucking, swallowing and respiration. Mean feeding competence was greater in infants with strong sucking fast rhythm. The presence of sucking-swallowing-respiration coordination decreased the days for an overall transfer of 100%. Evaluation by a speech therapist proved to be a useful tool for the safe indication of the beginning of oral feeding for premature infants.


Calcification of MC3T3-E1 cells on titanium and zirconium.
To confirm similarity of hard tissue compatibility between titanium and zirconium, calcification of MC3T3-E1 cells on titanium and zirconium was evaluated in this study. Mirror-polished titanium (Ti) and zirconium (Zr) disks and zirconium-sputter deposited titanium (Zr/Ti) were employed in this study. The surface of specimens were characterized using scanning electron microscopy and X-ray diffraction. Then, the cellular proliferation, differentiation and calcification of MC3T3-E1 cells on specimens were investigated. The surface of Zr/Ti was much smoother and cleaner than those of Ti and Zr. The proliferation of the cell was the same among three specimens, while the differentiation and calcification on Zr/Ti were faster than those on Ti and Zr. Therefore, Ti and Zr showed the identical hard tissue compatibility according to the evaluation with MC3T3-E1 cells. Sputter deposition may improve cytocompatibility.