Myoadenylate deaminase deficiency and malignant hyperthermia susceptibility: is there a relationship?
Muscle biopsies from 35 patients referred for possible malignant hyperthermia were subjected to contracture testing with halothane, caffeine, and the combined agents, histopathological and fiber-type-distribution analysis, and quantitative assay of three major muscle enzymes: adenylate deaminase, adenylate kinase, and creatine kinase. Adenylate kinase and creatine kinase were in the normal range in all biopsies and each averaged 92% of expected normal value when corrected for their fiber-type distribution. Of the 14 cases with a positive halothane test, 2 had primary myoadenylate deaminase deficiency, and 5 others had low levels of this enzyme (less than one-third normal). In contrast, only 3 of 21 cases negative to halothane testing had low adenylate deaminase levels, and none were deficient. This association was significant by several statistical tests, although it would not be highly predictive for an individual case. A positive halothane test also correlated with a high type 2 fiber contribution, but this was probably secondary, since cases with low enzyme levels had significantly higher type 2 fiber areas. Caffeine contractures did not correlate with either low enzyme levels or with fiber-type distribution. Sixty percent of the biopsies were entirely normal histologically, and showed a significant correlation with a negative combined contracture test. Data on the one family included in this study suggest separate inheritance of the trait for myoadenylate deaminase deficiency and the trait for positive contracture tests. The present findings suggest that patients with myoadenylate deaminase deficiency (and the carrier state as well) may be at increased risk of malignant hyperthermia when subjected to anesthesia.


Fundamental derivation of two Boris solvers and the Ge-Marsden theorem.
It has been known for some time that when one uses the Lorentz force law, rather than Hamilton's equation, one can derive two basic algorithms for solving trajectories in a magnetic field formally similar to the velocity-Verlet (VV) and position-Verlet (PV) symplectic integrators independent of any finite-difference approximation. Because the Lorentz force law uses the mechanical rather than the canonical momentum, the resulting magnetic field algorithms are exact energy conserving, rather than symplectic. In general, both types of algorithms can only yield the exact trajectory in the limit of vanishing small time steps. This work shows that, for a constant magnetic field, both magnetic algorithms can be further modified so that their trajectories are exactly on the gyrocircle at finite time steps. The magnetic form of the PV integrator then becomes the well-known Boris solver, while the VV form yields a second, previously unknown Boris-type algorithm, unrelated to any finite-difference scheme. Remarkably, the modification needed for the trajectory to be exact is a reparametrization of the time step, reminiscent of the Ge-Marsden theorem.


Characterization of endogenous G-CSF and the inverse correlation to chemotherapy-induced neutropenia in patients with breast cancer using population modeling.
Neutropenia is a severe adverse-event of chemotherapeutics. Neutrophils (ANC) are mainly regulated by granulocyte colony stimulating factor (G-CSF). The aim was to characterize the dynamics between endogenous G-CSF and ANC over time following chemotherapy. Endogenous G-CSF and ANC were monitored in forty-nine breast cancer patients treated with sequential adjuvant 5-fluorouracil-epirubicin-cyclophosphamide and docetaxel. During treatment courses ANC was transiently decreased and was reflected in an endogenous G-CSF increase, which was well described by a semi-mechanistic model including control mechanisms; when G-CSF concentrations increased the proliferation rate increased and the bone maturation time reduced for ANC. Subsequently, ANC in the circulation increased leading to increased elimination of G-CSF. Additionally, a non-specific elimination for G-CSF was quantified. The ANC-dependent elimination contributed to 97% at baseline and 49% at an ANC of 0.1 · 10(9)/L to the total G-CSF elimination. The integrated G-CSF-myelosuppression model captured the initial rise in endogenous G-CSF following chemotherapy-induced neutropenia and the return to baseline of G-CSF and ANC. The model supported the self-regulatory properties of the system and may be a useful tool for further characterization of the biological system and in optimization of chemotherapy treatment.


Feeding heat-treated colostrum to neonatal dairy heifers: effects on growth characteristics and blood parameters.
Newborn Holstein heifer calves were studied to compare absorption of immunoglobulin G (IgG(1) and IgG(2)), total serum protein concentration, lymphocyte counts, health scores, growth, and starter intake after receiving unheated or heat-treated colostrum. First-milking colostrum was collected from Holstein cows and frozen at -20 degrees C to accumulate a large batch. After thawing and mixing, half of the colostrum was transferred into 1.89-L plastic containers and frozen at -20 degrees C until needed for feeding. The remaining half was heated at 60 degrees C for 30 min, transferred into 1.89-L plastic containers, and then frozen at -20 degrees C until needed for feeding. Forty heifer calves weighing > or =32 kg at birth were enrolled into 1 of 2 treatment groups before suckling occurred. For the first feeding, 3.8 L of colostrum was bottle fed by 1.5 to 2 h of age. For the second and third feedings, pasteurized whole milk at 5% of birth body weight (BW) was fed. Subsequently, calves received milk replacer containing 20% crude protein and 20% fat at 10% of birth BW/d until wk 5. Milk replacer was reduced to 1 feeding of 5% birth BW until weaning at 6 wk of age. Blood samples and growth data were collected through wk 8. Batch heat-treatment of colostrum at 60 degrees C for 30 min lowered colostrum bacteria concentration while maintaining colostral IgG concentration and viscosity. Calves fed heat-treated colostrum had significantly greater IgG concentrations at 24 h and greater apparent efficiency of IgG absorption (IgG = 23.4 g/L; apparent efficiency of absorption = 33.2%) compared with calves fed unheated colostrum (IgG = 19.6 g/L; apparent efficiency of absorption = 27.7%). There was no difference between treatment groups in growth measurements, calf starter intake, lymphocyte counts, or health scores.


Effect of corn steep liquor on lettuce root rot (Fusarium oxysporum f.sp. lactucae) in hydroponic cultures.
Recent reports indicate that organic fertilisers have a suppressive effect on the pathogens of plants grown under hydroponic systems. Furthermore, microorganisms exhibiting antagonistic activity to diseases have been observed in organic hydroponic systems. This study evaluated the effect of corn steep liquor (CSL) on controlling lettuce root rot disease [Fusarium oxysporum f.sp. lactucae (FOL)] in a hydroponic system. The effect of CSL and Otsuka A (a chemical fertiliser) on the inhibition of FOL in terms of mycelial growth inhibition was tested in vivo. Addition of CSL suppressed FOL infection rates. CSL inhibited FOL infection by 26.3-42.5% from 2 days after starting incubation. In comparison, Otsuka A inhibited FOL growth by 5.5-19.4%. In addition, four of 10 bacteria isolated from the nutrient media containing CSL exhibited inhibition zones preventing FOL mycelial growth. We found that CSL suppressed FOL in lettuce via its antifungal and biostimulatory effects. We suggest that activation of beneficial microorganisms present in CSL may be used to decrease lettuce root rot disease and contribute to lettuce root growth.


Pressure transducer method for measuring gas production by microorganisms.
A simple method for measuring gas production by microorganisms by using a pressure transducer to sense pressure buildup was developed and tested with members of the coliform group. The test system consisted of a 5.0 lb/in(2) pressure transducer and a pressure equalizer valve attached to the metal cap of a test tube (20 by 150 mm); gas pressure was recorded on a strip-chart recorder. Gas pressure response curves consisted of (i) a lag period with no marked increase in pressure, (ii) a rapid pressure buildup period, and (iii) a leveling-off period. A linear relationship was established between inoculum size and length of the lag period. Cultures shaken at 200 oscillations/min showed a marked increase in rate of gas release over stationary cultures. Cell concentrations at the time of rapid buildup in pressure were 10(8)/ml. Mean maximum pressure recordings, lb/in(2) per 10 ml of broth, were: Enterobacter aerogenes, 3.70; Citrobacter intermedium, 2.70; and Escherichia coli, 2.10. Mean CO(2) concentrations, ppm of headspace gas, for E. coli were: (i) 2,000 at time of inoculation, (ii) 25,000 at time of rapid buildup in pressure, and (iii) 150,000 at maximum pressure. These results indicate the potential application of the pressure transducer method for rapidly detecting coliforms and other gas-producing microorganisms in clinical samples and in sterility testing of foods.


Changes in the number and causes of maternal deaths after the introduction of pregnancy checkbox on the death certificate in Taiwan.
To examine changes in the number and causes of maternal deaths after the introduction of pregnancy checkbox on the death certificate in January 2014 in Taiwan. We first used the cause-of-death (COD) mortality data for years 2010 through 2017 to examine the number of deaths by item of pregnancy checkbox. We then compared the distribution of the causes of maternal deaths before and after the introduction of pregnancy checkbox. Between 2014 and 2017, 111 women died, for whom the certifiers indicated the following in the pregnancy checkbox items: 2 (pregnant at the time of death; n = 10), 3 (died within 42 days after the termination of pregnancy; n = 64), and 4 (died between 43 days and 1 year after the termination of pregnancy; n = 37). However, in only 61 of the 111 deaths, the certifiers reported pregnancy or delivery-related diagnosis in the COD section of the death certificate-5 each for items 2 and 4 and 51 for item 3. The number of maternal deaths was 55 in 2010-2013; this number increased to 82 in 2014-2017. A decline in the percentage of maternal deaths from obstetric hemorrhage was noted from 38% (21/55) in 2010-2013 to 21% (17/82) in 2014-2017. The number of maternal deaths increased, and the distribution of causes of maternal deaths changed after the introduction of pregnancy checkbox. Additional studies are required to examine the possible misclassification of pregnancy-associated deaths indicated in the pregnancy checkbox.


Secondary tumors of the pancreas: an analysis of a surgical and autopsy database and review of the literature.
The vast majority of pancreatic carcinomas are primary, and, among these, more than 90% are of ductal origin. However, a variety of extrapancreatic tumors may involve the pancreas secondarily and may manifest different clinicopathological characteristics and outcomes. In this study, pathology material from 973 surgical specimens and 4955 adult autopsy cases was reviewed to identify the tumors metastatic to or secondarily involving the pancreas. Biliary and periampullary neoplasms and tumors confined to peripancreatic soft tissue were excluded. In the autopsy series, the pancreas was involved by tumor in 190 cases, and 81 of these were secondary tumors. These were predominantly of epithelial origin, most commonly from lung (34), followed by GI tract (20), kidney (4), breast (3), liver (2), ovary (1), and urinary bladder (1). In addition, there were six tumors of hematopoietic origin, two melanomas, two sarcomas, and two mesotheliomas. Among the 973 surgical specimens, 38 cases contained metastatic tumors to the pancreas. Of these, 11 were lymphomas, and the others were carcinomas of stomach (7), kidney (6), lung (2), liver, prostate, ovary, uterus (1 case of each), and a Merkel cell carcinoma. In addition, there were three malignant gastrointestinal stromal tumors and one retroperitoneal leiomyosarcoma. In conclusion, lung cancer is the most common source of metastasis to pancreas, followed by gastrointestinal carcinomas and lymphomas. These tumors are usually seen in patients with disseminated disease and are detected mainly in autopsies. Secondary tumors constitute about 4% of pancreatic specimens in the authors' surgical database. Approximately one-third of them are clinically mistaken as primary tumors of the pancreas. These are predominantly hematopoietic malignancies or carcinomas of renal or gastric origin. Secondary tumors should be entertained in both the clinical and pathological differential diagnosis of pancreatic neoplasia.


A Role for Oxytocin in the Etiology and Treatment of Schizophrenia.
Schizophrenia is a chronic debilitating neuropsychiatric disorder estimated to affect 51 million people worldwide. Several symptom domains characterize schizophrenia, including negative symptoms, such as social withdrawal and anhedonia, cognitive impairments, such as disorganized thinking and impaired memory, and positive symptoms, such as hallucinations and delusions. While schizophrenia is a complex neuropsychiatric disorder with no single "cause," there is evidence that the oxytocin (Oxt) system may be dysregulated in some individuals. Further, treatment with intranasal Oxt reduces some of the heterogeneous symptoms associated with schizophrenia. Since Oxt is known for its modulatory effects on a variety of social and non-social behaviors, it is perhaps not surprising that it may contribute to some aspects of schizophrenia and could also be a useful therapeutic agent. In this review, we highlight what is known about Oxt's contributions to schizophrenia and schizophrenia-related behaviors and discuss its potential as a therapeutic agent.


WHO Western Pacific Regional Action Plan for the Prevention and Control of NCDs (2014-2020).
This is an excerpt of the "Western Pacific Regional Action Plan for the Prevention and Control of Noncommunicable Diseases (2014-2020)" (RAP NCD) which has been endorsed by the Member States of the Western Pacific Region of World Health Organization (WHO) in October 2013. The Regional plan is fully harmonized with the Global Action Plan for the Prevention and Control of Noncommunicable Diseases (2013-2020). The regional plan calls for a systematic approach to NCD prevention and control. The plan provides a road map and a menu of very cost-effective interventions for all Member States and other stakeholders, to take coordinated and coherent action at all levels to attain the nine voluntary global target by 2025. The original version of RAP NCD is downloadable from the website (http://www.wpro.who.int/noncommunicable_diseases/ WHO_NCD_RAP.pdf?ua=1). In addition, there are NCD tools in the WHO homepage (http://www.who.int/nmh/ncd-tools/en/).


Overcoming confinement limited swelling in hydrogel thin films using supramolecular interactions.
The thin film behavior of poly(N-isopropylacrylamide-stat-2-(N-ethylperfluorooctane sulfonamido)ethyl acrylate) (NIPAAm-stat-FOSA) based hydrogels containing 5 mol% FOSA was elucidated using quartz crystal microbalance with dissipation (QCM-D) in combination with spectroscopic ellipsometry (SE) through examination of the lower critical solution temperature (LCST) and temperature dependent swelling for (dry) thicknesses ranging from 10 nm to 121 nm. For all thin films measured, the LCST was shown to slightly increase (>3 °C) in comparison to that of the bulk sample. However for these films, the increase in LCST was statistically identical, irrespective of thickness. Surprisingly, the volumetric swelling of the hydrogel in thin films, even at temperatures less than the LCST, was similar (within 20%) to the volumetric swelling of the bulk hydrogel, despite the expected significant decrease associated with the hydrogel being constrained by the substrate as predicted by one dimensional Flory-Rehner theory. We attribute this enhancement in swelling compared to theoretical expectations to the ability of the hydrophobic crosslinks to re-arrange under stress, which provides a mechanism to alleviate the decreased dimensionality imposed by the substrate; this mechanism is consistent with a large hysteresis in the swelling when cycling between 35 °C and 5 °C. Unlike the LCST, the swelling ratio increases with decreasing film thickness. At low temperatures (below the LCST), the volume swelling ratio increased from 3.9 to 4.9, while at temperatures above the LCST the swelling ratio increased from 1.5 to 2.5 when the film thickness decreased from 121 nm to 10 nm. The combination of facile processing through solution casting without the need for additional crosslinking chemistry and limited thickness dependent variation of swelling and LCST behavior in these physically crosslinked hydrogels makes these materials attractive for applications requiring thermoresponsive soft coatings.


Language Familiarity and Proficiency Leads to Differential Cortical Processing During Translation Between Distantly Related Languages.
In the midst of globalization, English is regarded as an international language, or Lingua Franca, but learning it as a second language (L2) remains still difficult to speakers of other languages. This is true especially for the speakers of languages distantly related to English such as Japanese. In this sense, exploring neural basis for translation between the first language (L1) and L2 is of great interest. There have been relatively many previous researches revealing brain activation patterns during translations between L1 and English as L2. These studies, which focused on language translation with close or moderate linguistic distance (LD), have suggested that the Broca area (BA 44/45) and the dorsolateral prefrontal cortex (DLPFC; BA 46) may play an important role on translation. However, the neural mechanism of language translation between Japanese and English, having large LD, has not been clarified. Thus, we used functional near infrared spectroscopy (fNIRS) to investigate the brain activation patterns during word translation between Japanese and English. We also assessed the effects of translation directions and word familiarity. All participants' first language was Japanese and they were learning English. Their English proficiency was advanced or elementary. We selected English and Japanese words as stimuli based on the familiarity for Japanese people. Our results showed that the brain activation patterns during word translation largely differed depending on their English proficiency. The advanced group elicited greater activation on the left prefrontal cortex around the Broca's area while translating words with low familiarity, but no activation was observed while translating words with high familiarity. On the other hand, the elementary group evoked greater activation on the left temporal area including the superior temporal gyrus (STG) irrespective of the word familiarity. These results suggested that different cognitive process could be involved in word translation corresponding to English proficiency in Japanese learners of English. These difference on the brain activation patterns between the advanced and elementary group may reflect the difference on the cognitive loads depending on the levels of automatization in one's language processing.


An aging workforce and injury in the construction industry.
The relatively large birth cohort between 1946 and 1964, combined with the economic recession in the first decade of the 21st century, have led to an increase in the proportion of older workers in the US workplace. Understanding the health and safety needs of an aging workforce will be critical, especially in the construction industry, where physical job demands are high. This paper reviews the epidemiologic literature on the impact of age on injury among workers in the construction industry in terms of cause, type, and cost. PubMed was searched by using the following terms: older workers, construction, construction industry, injury, and age. The available studies reported that, among the construction industry workforce, older age at injury was related to higher injury costs but not to number of injuries. The higher injury costs associated with worker age are likely due in part to the severity of the injuries sustained by older workers. Identification of injury trends and subsequent analytical research efforts designed to ascertain factors associated with injury among older construction workers are needed for employers to effectively manage a health and safety program that addresses the needs of the aging worker.


[Influencing factors of diabetic patients applying for specific disease health insurance and its treatment cost].
To compare the treatment costs on type 2 diabetes between patients with and without specific diseases health insurance, and to identify the influencing factors related to specific diseases health insurance application. A structured questionnaire was used to investigate basic information, diabetes-related pharmacy, outpatient and inpatient treatment costs. SAS9.1 software was used for statistical analysis. The enumeration data was analyzed by using Chi-square test, and variables of statistical difference were bought into Logistic regression model through stepwise method. Continuous variables were represented by median(inter-quartile range)[M(Q)], and were analyzed by using Wilcoxon test. Compared with patients without specific disease health insurance in outpatient group, patients with specific disease health insurance had higher annual per capita total cost [2160(3081) vs 1000(2100) yuan, P<0.01] and lower out-of-pocket expense ratio [54.04% vs 93.78%, P<0.01]. Patients with middle or high level income (OR=1.94 and 2.11), participated in urban employee basic medical insurance (OR=4.19) and duration of disease >5 years (OR=2.04) were more likely to succeed in specific diseases health insurance application. To reduce the financial burden of patients with type 2 diabetes, government should make huge efforts to promote specific disease health insurance policies, and encourage patients to apply for it. Meanwhile, medical insurance department and medical institutions should reinforce supervision and simplify the application process. To improve the availability of specific disease health insurance, the number and coverage of designated retail pharmacies should be increased. Besides, government should pay more attention to low-income patients and those with short duration diabetes, so as to enhance their ability to resist economic risks and reflect the fairness of specific disease health insurance.


Herpes simplex virus infection in pemphigus vulgaris: clinical and immunological considerations.
Different environmental factors have been implicated in the pathogenesis of pemphigus vulgaris (PV), including drugs, diet, burns, X-rays, ultraviolet radiation, neoplasms, and infections. Several reports described the manifestation or aggravation of PV due to herpes simplex virus (HSV), varicella-zoster virus, Epstein-Barr virus, cytomegalovirus and human herpesvirus-8 infections. In the present study, we correlated secondary HSV1 infection in 3 PV patients on immunosuppressive treatment with the titers of IgG autoantibodies against desmoglein 1 (DSG1) and 3 (DSG3) over a follow-up period of at least 18 months. In these patients, the detection of HSV1 and clinical flare-up of PV did not correlate with a significant increase of DSG-specific IgG. Thus, secondary cutaneous HSV infections should be considered in patients with chronic PV with atypical sudden relapses or resistance to sufficient immunosuppressive treatment who do not show an increase of DSG-specific IgG autoantibodies.


[Epidemiological aspects and diagnosis of 60 cases of leptospiroses in French Polynesia].
60 cases of leptospiroses were diagnosed in Polynesia by blood culture and immunological test. Fever and pains are prevailing signs. Among 3 patients, presence of leptospires is revealed on the 43th, 54th and 90th days. The following serogroups are found: Icterohaemorrhagiae 69.7%, Canicola 13%, Pomona 4%, Australis 2%. 85% of the patients come from Tahiti and 15% from "Sousle-Vent" Islands and Tuamotou. Walking bare foot on wet ground in areas where numerous rodents are found is a source of contamination. The procedure of blood cultures plays a prominent part.


Spore Heat Activation Requirements and Germination Responses Correlate with Sequences of Germinant Receptors and with the Presence of a Specific spoVA2mob Operon in Foodborne Strains of Bacillus subtilis.
Spore heat resistance, germination, and outgrowth are problematic bacterial properties compromising food safety and quality. Large interstrain variation in these properties makes prediction and control of spore behavior challenging. High-level heat resistance and slow germination of spores of some natural Bacillus subtilis isolates, encountered in foods, have been attributed to the occurrence of the spoVA2mob operon carried on the Tn1546 transposon. In this study, we further investigate the correlation between the presence of this operon in high-level-heat-resistant spores and their germination efficiencies before and after exposure to various sublethal heat treatments (heat activation, or HA), which are known to significantly improve spore responses to nutrient germinants. We show that high-level-heat-resistant spores harboring spoVA2mob required higher HA temperatures for efficient germination than spores lacking spoVA2mob The optimal spore HA requirements additionally depended on the nutrients used to trigger germination, l-alanine (l-Ala), or a mixture of l-asparagine, d-glucose, d-fructose, and K+ (AGFK). The distinct HA requirements of these two spore germination pathways are likely related to differences in properties of specific germinant receptors. Moreover, spores that germinated inefficiently in AGFK contained specific changes in sequences of the GerB and GerK germinant receptors, which are involved in this germination response. In contrast, no relation was found between transcription levels of main germination genes and spore germination phenotypes. The findings presented in this study have great implications for practices in the food industry, where heat treatments are commonly used to inactivate pathogenic and spoilage microbes, including bacterial spore formers.IMPORTANCE This study describes a strong variation in spore germination capacities and requirements for a heat activation treatment, i.e., an exposure to sublethal heat that increases spore responsiveness to nutrient germination triggers, among 17 strains of B. subtilis, including 9 isolates from spoiled food products. Spores of industrial foodborne isolates exhibited, on average, less efficient and slower germination responses and required more severe heat activation than spores from other sources. High heat activation requirements and inefficient, slow germination correlated with elevated resistance of spores to heat and with specific genetic features, indicating a common genetic basis of these three phenotypic traits. Clearly, interstrain variation and numerous factors that shape spore germination behavior challenge standardization of methods to recover highly heat-resistant spores from the environment and have an impact on the efficacy of preservation techniques used by the food industry to control spores.


Parathyroid hormone-related peptide and parathyroid hormone-related peptide receptor type 1 expression in human lung adenocarcinoma.
In many primary tumors, parathyroid hormone-related peptide (PTHrP) and PTHrP type 1 receptor (PTH1R) are coexpressed, supporting the possibility that PTHrP/PTH1R system can mediate important signals for tumor progression through paracrine/autocrine mechanisms. In non-small cell lung carcinoma the clinical relevance of the expression of PTH1R remains to be investigated. Fifty-four lung adenocarcinomas of mixed histologic type from patients with stage I and II cancer were assayed by quantitative immunohistochemistry for the expression of PTHrP and PTH1R. PTHrP and PTH1R were expressed in a wide range of intensity in the cytoplasm of tumor cells, and their values showed a positive correlation. PTH1R, but not PTHrP, was expressed by plasma cells infiltrating the tumor stroma. PTHrP and PTH1R were not associated with age, tumor diameter, or histopathologic grading, whereas they were directly associated with lymph node involvement at presentation. Cox regression analysis, using PTHrP and PTH1R as continuous covariates, showed that the covariate levels were directly associated with the risk of death and metastasis. Patients whose tumors coexpressed high levels of PTHrP and PTH1R showed the highest risk of metastasis (relative risk, 5.89; 95% CI, 2.1-16.6; P = .0003) and death (relative risk, 6.24; 95% CI, 1.6-23.9; P = .0033). The presence of PTH1R-positive plasma cells in the tumor stroma was associated with a more favorable survival rate independently from the PTHrP status of the tumor. The paracrine/autocrine signaling through PTHrP/PTH1R could be important in early-stage lung adenocarcinoma progression.


Dietary supplementation with eicosapentaenoic and docosahexaenoic acid inhibits growth of Morris hepatocarcinoma 3924A in rats: effects on proliferation and apoptosis.
The effect of individual administration of low doses of highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (1 g/kg body weight) on the growth of Morris hepatocarcinoma 3924A transplanted in ACI/T rats was investigated. Both EPA and DHA inhibited growth of the hepatocarcinoma (50% reduction of tumor weight or volume at the 19th day after transplantation for both of the n-3 PUFA groups). EPA treatment reduced the percentage of proliferating tumor cells labeled with BUdR (10-fold), whereas DHA did not. Conversely, DHA supplementation induced a doubling of the number of cells undergoing apoptosis (labeled by TUNEL), whereas EPA treatment was much less effective. Analysis of changes in phospholipid fatty acids in tumor-cell membranes after both treatments with EPA and DHA showed a significant reduction in arachidonic-acid levels. EPA and docosapentaenoic acid (DPA), its elongation product, were increased in the phospholipids from EPA-treated animals. DHA and EPA, but not DPA, were increased in the DHA-treated group. It is concluded from the results of the present study that the anti-tumoral effect of EPA is related mainly to its inhibition of cell proliferation, whereas that of DHA corresponds with its induction of apoptosis. The alterations in fatty-acid composition induced by EPA or DHA appear to be factors underlying their differential actions on cell proliferation and apoptosis.


Rhodothermus obamensis sp. nov., a modern lineage of extremely thermophilic marine bacteria.
A novel extremely thermophilic bacterium was isolated from a shallow marine hydrothermal vent environment (depth, 22 m) in Tachibana Bay, Nagasaki Prefecture, Japan. The cells of this organism were gram-negative rods. Growth occurred at temperatures between 50 and 85 degrees C (optimum temperature, 80 degrees C; doubling time at optimum temperature, 90 min), at pH 5.5 and 9.0 (optimum pH, 7.0), and in the presence of 1 and 5% NaCl (optimum NaCl concentration, 3%). The new isolate was an aerobic heterotroph which utilized the following compounds as sole energy and carbon sources: yeast extract, peptone, starch, casein, Casamino Acids, a variety of sugars, some carboxylic acids, and amino acids. As determined by a sequence analysis of the 16S rRNA, the new isolate belongs to the genus Rhodothermus and represents a modern lineage of extreme thermophiles within the domain Bacteria. On the basis of the physiological and molecular properties of the new isolate, we describe a new species, Rhodothermus obamensis. The type strain of R. obamensis is strain OKD7 (= JCM 9785).


Fertility and pregnancy after operation for a prolactinoma.
Pituitary exploration was performed in 40 women with hyperprolactinaemic infertility and a prolactinoma was found in 37. After operation 26 (65%) of the 40 patients had a normal serum prolactin concentration; 31 women have so far had 49 pregnancies; in seven of these patients bromocriptine therapy was used after surgery. Eight of the remaining nine women were shown to be ovulating, but four of these subsequently decided not to attempt a pregnancy. The course and outcome of the 49 pregnancies were similar to those in normal women and no visual or endocrine complications occurred. Surgical removal of a prolactinoma often restores fertility, and may secure a safer pregnancy.


Drug resistance in vectorborne parasites: multiple actors and scenarios for an evolutionary arms race.
Drug-resistant pathogens emerge faster than new drugs come out of drug discovery pipelines. Current and future drug options should therefore be better protected, requiring a clear understanding of the factors that contribute to the natural history of drug resistance. Although many of these factors are relatively well understood for most bacteria, this proves to be more complex for vectorborne parasites. In this review, we discuss considering three key models (Plasmodium, Leishmania and Schistosoma) how drug resistance can emerge, spread and persist. We demonstrate a multiplicity of scenarios, clearly resulting from the biological diversity of the different organisms, but also from the different modes of action of the drugs used, the specific within- and between-host ecology of the parasites, and environmental factors that may have direct or indirect effects. We conclude that integrated control of drug-resistant vectorborne parasites is not dependent upon chemotherapy only, but also requires a better insight into the ecology of these parasites and how their transmission can be impaired.


Honokiol suppresses formyl peptide-induced human neutrophil activation by blocking formyl peptide receptor 1.
Formyl peptide receptor 1 (FPR1) mediates bacterial and mitochondrial N-formyl peptides-induced neutrophil activation. Therefore, FPR1 is an important therapeutic target for drugs to treat septic or sterile inflammatory diseases. Honokiol, a major bioactive compound of Magnoliaceae plants, possesses several anti-inflammatory activities. Here, we show that honokiol exhibits an inhibitory effect on FPR1 binding in human neutrophils. Honokiol inhibited superoxide anion generation, reactive oxygen species formation, and elastase release in bacterial or mitochondrial N-formyl peptides (FPR1 agonists)-activated human neutrophils. Adhesion of FPR1-induced human neutrophils to cerebral endothelial cells was also reduced by honokiol. The receptor-binding results revealed that honokiol repressed FPR1-specific ligand N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein binding to FPR1 in human neutrophils, neutrophil-like THP-1 cells, and hFPR1-transfected HEK293 cells. However, honokiol did not inhibit FPR2-specific ligand binding to FPR2 in human neutrophils. Furthermore, honokiol inhibited FPR1 agonist-induced calcium mobilization as well as phosphorylation of p38 MAPK, ERK, and JNK in human neutrophils. In conclusion, our data demonstrate that honokiol may have therapeutic potential for treating FPR1-mediated inflammatory diseases.


TGF-beta and HGF transmit the signals through JNK-dependent Smad2/3 phosphorylation at the linker regions.
Although hepatocyte growth factor (HGF) can act synergistically or antagonistically with transforming growth factor-beta (TGF-beta) signaling, molecular mechanism of their crosstalk remains unknown. Using antibodies which selectively distinguished receptor-regulated Smads (R-Smads) phosphorylated at linker regions from those at C-terminal regions, we herein showed that either HGF or TGF-beta treatment of normal stomach-origin cells activated the JNK pathway, thereafter inducing endogenous R-Smads phosphorylation at linker regions. However, the phosphorylation at their C-terminal regions was not induced by HGF treatment. The activated JNK could directly phosphorylate R-Smads in vitro at the same sites that were phosphorylated in response to TGF-beta or HGF in vivo. Thus, the linker regions of R-Smads were the common phosphorylation sites for HGF and TGF-beta signaling pathways. The phosphorylation induced by simultaneous treatment with HGF and TGF-beta allowed R-Smads to associate with Smad4 and to translocate into the nucleus. JNK pathway involved HGF and TGF-beta-mediated infiltration potency since a JNK inhibitor SP600125 caused the reduction of invasive capacity induced by HGF and TGF-beta signals. Moreover, a combined treatment with HGF and TGF-beta led to a potent increase in plasminogen activator inhibitor type 1 transcriptional activity through Smad3 phosphorylation at the linker region. In contrast, HGF treatment reduced TGF-beta-dependent activation of p15INK4B promoter, in which Smad3 phosphorylation at the C-terminal region was involved. In conclusion, HGF and TGF-beta transmit the signals through JNK-mediated R-Smads phosphorylation at linker regions.


Epigenome data release: a participant-centered approach to privacy protection.
Large-scale epigenome mapping by the NIH Roadmap Epigenomics Project, the ENCODE Consortium and the International Human Epigenome Consortium (IHEC) produces genome-wide DNA methylation data at one base-pair resolution. We examine how such data can be made open-access while balancing appropriate interpretation and genomic privacy. We propose guidelines for data release that both reduce ambiguity in the interpretation of open-access data and limit immediate access to genetic variation data that are made available through controlled access.


[The immunity characteristics of men with gastric and duodenal peptic ulcer associated with Helicobacter pylori].
In males with peptic ulcer of the stomach and the duodenum, associated with H. pylori, the population and subpopulation spectrum of peripheral blood lymphocytes was studied by the method of CD typing with the use of monoclonal antibodies manufactured by the Research Institute "Preparat" (Nizhny Novgorod, Russia). The study revealed the development of disturbances in the amount of populations and subpopulations of peripheral blood lymphocytes, accompanied by a decrease in the absolute number of T lymphocytes (CD3, CD7), T helpers (CD4), T cytotoxic lymphocytes (CD8), B lymphocytes (CD22) and the ratio of CD4/CD8 cells. A decrease in the amount of IgA, IgG, the key complement components C1, C3, C5 was established. In peptic ulcer the immunological characteristics of gastric juice were found to essentially differ from those of saliva by a lower content of mucin, IgA and a higher content of SIgA and IgM in gastric secretions, which may form prerequisites for the colonization of the gastric mucosa by H. pylori.


Phenobarbital prior to preterm birth for preventing neonatal periventricular haemorrhage.
Preterm infants are at risk of periventricular haemorrhage. This can damage the brain and lead to neurodevelopmental abnormalities, including cerebral palsy. Phenobarbital might prevent ischaemic injury or reduce fluctuations in blood pressure and blood flow in the brain. The objective of this review was to assess the benefits and harms of giving phenobarbital to women at risk of imminent very preterm birth with the primary aim of preventing periventricular haemorrhage in the infant. We searched the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and bibliographies. Date of last search: December 1998. Randomised trials with reported data which compare outcomes, such as neonatal mortality, neonatal neurological and other morbidity, longterm neurodevelopment and maternal morbidity, following prenatal exposure to phenobarbital, with outcomes in controls with or without placebo. Assessments of trial eligibility, quality and data extractions were done by the two authors independently. Eligible trials were included in the initial analysis and prespecified sensitivity analyses done to evaluate the effect of trial quality. Over 1600 women were entered into the eight trials included. Analyses showed a significant reduction in the rates of all grades of periventricular haemorrhage (PVH) (relative risk 0.75, 95% confidence interval 0.65 to 0.88) and severe grades PVH (3 and 4) (relative risk 0.49, 95% confidence interval 0.32 to 0.74) in infants whose mothers had been given prenatal phenobarbital. These results were influenced by the earlier trials which were of poorer quality and contributed excessive weight in the analysis due to their higher rates of severe PVH. Over time, and with improved trial quality, these beneficial effects disappeared. No difference was found in the incidence of neurodevelopmental abnormalities at paediatric follow-up assessed between 18-36 months of age. Maternal sedation was more likely in women receiving phenobarbital. Phenobarbital administration to women prior to preterm birth cannot be recommended for routine clinical practice. Any future trials should examine the effects of phenobarbital prior to preterm birth at gestational ages with a high risk of PVH, stratify for gestational age and ensure minimal exclusions after randomisation. Neurodevelopmental status at follow-up should be measured as the most important outcome.


Fishery resource utilization of a restored estuarine borrow pit: a beneficial use of dredged material case study.
Numerous pits in coastal waters are subject to degraded water quality and benthic habitat conditions, resulting in degraded fish habitat. A pit in Barnegat Bay, New Jersey (USA) was partially filled with dredged sediment to increase flushing, alleviate hypoxia, and enhance benthic assemblages. Restoration objectives were assessed in terms of benthic community parameters and fishery resource occupation. Restoration resulted in increased benthic diversity (bottom samples) and the absence of water column stratification. Fisheries resources occupied the entire water column, unlike pre-restoration conditions where finfish tended to avoid the lower water column. The partial restoration option effectively reproduced an existing borrow pit configuration (Hole #5, control), by decreasing total depth from -11 m to -5.5 m, thereby creating a habitat less susceptible to hypoxic/anoxic conditions, while retaining sufficient vertical relief to maintain associations with juvenile weakfish and other forage fishes. Partially filling pits using dredged material represents a viable restoration alternative.


Is Obesity Associated With Increased Risk of Deep Vein Thrombosis or Pulmonary Embolism After Hip and Knee Arthroplasty? A Large Database Study.
Deep venous thrombosis (DVT) and pulmonary embolus (PE) remain an important cause of morbidity and mortality after THA and TKA. Prior recommendations have advocated for more aggressive prophylaxis for patients with obesity, whereas the evidence supporting these recommendations is conflicting and often based on underpowered studies. (1) What is the association between obesity and DVT and PE after primary and revision THA and TKA? (2) Is there a body mass index (BMI) threshold beyond which DVT and PE risk is elevated? We reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2008 to 2016 to evaluate the reported 30-day rates of DVT, PE, and combined venous thromboembolism (VTE) after primary THA, primary TKA, revision THA, and revision TKA according to BMI as a continuous variable and a categorical variable as defined by the World Health Organization cutoffs for underweight, normal weight, overweight, and obesity. This database is risk-adjusted and designed to capture complications after surgery, thus making it ideal for this study. The diagnosis of DVT and PE is included in the ACS-NSQIP database for any DVT or PE requiring treatment. Proximal versus distal DVT is not specified within the database. Multivariate logistic regression was performed to determine if obesity was independently associated with DVT and PE risk by controlling for age, sex, race, American Society of Anesthesiologists score, diabetes, hypertension, smoking status, general anesthesia, and hypoalbuminemia. After controlling for potential confounding variables such as medical comorbidities and procedure type, patients undergoing primary and revision THA and TKA with World Health Organization classification as underweight (BMI < 18.5 kg/m), overweight (BMI 25-29.9 kg/m), Class I obese (BMI 30-34.9 kg/m), Class II obese (BMI 35-39.9 kg/m), or Class III obese (BMI ≥ 40 kg/m) did not demonstrate an association with increased risk of DVT compared with patients classified as normal weight (BMI 18.5-25 kg/m). Compared with patients undergoing primary THA classified as normal weight, the risk of PE was elevated in patients with Class II obesity (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.23-4.50; p = 0.009) and all heavier categories. Compared with patients undergoing TKA classified as normal weight, the risk of PE was elevated in patients classified as overweight (OR, 1.56; 95% CI, 1.03-2.36; p = 0.035) and all heavier categories. This large administrative database study suggests that patient classification as overweight or obese is associated with increased risk of development of PE but not DVT after primary THA or TKA. Because aggressive pharmacologic anticoagulation regimens can decrease the DVT rate but have not been shown to affect the rate of PE or death, the data do not currently support increased anticoagulation in patients with obesity without other risk factors for VTE undergoing THA or TKA. Additional studies are required to refine VTE prophylaxis protocols to reduce PE risk while maintaining acceptable postoperative bleeding risk. Level III, therapeutic study.


LEF-1 drives aberrant β-catenin nuclear localization in myeloid leukemia cells.
Canonical Wnt/β-catenin signaling is frequently dysregulated in myeloid leukemias and is implicated in leukemogenesis. Nuclear-localized β-catenin is indicative of active Wnt signaling and is frequently observed in acute myeloid leukemia (AML) patients; however, some patients exhibit little or no nuclear β-catenin even where cytosolic β-catenin is abundant. Control of the subcellular localization of β-catenin therefore represents an additional mechanism regulating Wnt signaling in hematopoietic cells. To investigate the factors mediating the nuclear-localization of β-catenin, we carried out the first nuclear/cytoplasmic proteomic analysis of the β-catenin interactome in myeloid leukemia cells and identified putative novel β-catenin interactors. Comparison of interacting factors between Wnt-responsive cells (high nuclear β-catenin) versus Wnt-unresponsive cells (low nuclear β-catenin) suggested the transcriptional partner, LEF-1, could direct the nuclear-localization of β-catenin. The relative levels of nuclear LEF-1 and β-catenin were tightly correlated in both cell lines and in primary AML blasts. Furthermore, LEF-1 knockdown perturbed β-catenin nuclear-localization and transcriptional activation in Wnt-responsive cells. Conversely, LEF-1 overexpression was able to promote both nuclear-localization and β-catenin-dependent transcriptional responses in previously Wnt-unresponsive cells. This is the first β-catenin interactome study in hematopoietic cells and reveals LEF-1 as a mediator of nuclear β- catenin level in human myeloid leukemia.


Assessing the robustness of muscle strength and physical performance measures in women older than 40 years: a test-retest reliability study.
This study investigated the test-retest reliability and minimal detectable change (MDC) of muscle strength and physical performance tests in women older than 40 years. A total of 113 women, aged 58 ± 11 years (82% postmenopausal women), with a body mass index of 28.5 ± 5.8 kg/m2, participated in this study. One-repetition maximum (1RM) tests were conducted for seven strength exercises: 45° leg press, bench press, leg extension, pec deck, wide-grip lateral pull-down, leg curl, and seated cable row, with a retest after 48 hours. Timed Up and Go (TUG), 6-minute walk, and 30-second sit-to-stand tests were performed on the same day and retested after 72 hours. The tests and retests were administered by the same evaluators. Relative reliability (consistency of participant rank between test-retest) was assessed using the intraclass correlation coefficient for consistency and agreement, and absolute reliability (precision of score) was assessed using the MDC based on the standard error of prediction. The 1RM and performance tests exhibited excellent reliability: 45° leg press (consistency, 0.99; agreement, 0.98), bench press (consistency, 0.96; agreement, 0.96), leg extension (consistency, 0.93; agreement, 0.91), pec deck (consistency, 0.90; agreement, 0.88), wide-grip lateral pull-down (consistency, 0.91; agreement, 0.89), leg curl (consistency, 0.84; agreement, 0.83), seated cable row (consistency, 0.92; agreement, 0.94), TUG (consistency, 0.87; agreement, 0.87), 6-minute walk (consistency, 0.96; agreement, 0.95), and 30-second sit to stand (consistency, 0.85; agreement, 0.80). These tests showed meaningful MDC values, particularly for the 1RM test performed on the machine and the 30-second sit-to-stand test: 45° leg press, 22.2 kg (15%); bench press, 4.9 kg (19%); leg extension, 9.2 kg (35%); pec deck, 8.8 kg (44%); wide-grip lateral pull-down, 9.4 kg (31%); leg curl, 9.2 kg (51%); seated cable row, 11.4 kg (29%); TUG, 1.4 seconds (20%); 6-minute walk, 50.9 m (10%); and 30-second sit to stand, 4.6 reps (30%). Although the muscle strength and physical performance tests demonstrate excellent relative reliability in women older than 40 years, they exhibit low absolute reliability, particularly the 1RM test performed on the machine and the 30-second sit-to-stand test. Therefore, although these tests show good consistency in the positioning of women within the group after repeated measures, their precision measure is relatively low (high fluctuation). Changes in these tests that are smaller than the MDC may not indicate real changes in women at middle age and older.


Status epilepticus management and mortality risk factors: a retrospective study.
Status epilepticus (SE) is a neurological emergency with relatively high mortality rates. In this study, we analysed the management of SE and identified mortality risk factors that may be addressed with educational interventions or modifications to hospital protocols. In this retrospective study, we analysed demographic, treatment, and outcome data from 65 patients (mean age, 59 years [range, 44.5-77]; 53.8% women) who were admitted to our tertiary hospital during an 18-month period and met the 2015 International League Against Epilepsy criteria for SE. Thirty patients (46.2%) had history of epilepsy. The most frequent causes of SE were cerebrovascular disease (27.7%) and systemic infection (16.9%). The following deviations were observed in the administration of the antiepileptic drugs: benzodiazepines were used as first option in only 33 (50.8%) patients; the combination of 2 benzodiazepines was recorded in 7 cases (10.8%); and lacosamide was used as an off-label drug in 5 patients (7.7%). Electroencephalography studies were performed in only 26 patients (40%); and only 5 studies (7.7% of patients) were performed within 12 hours of seizure onset. The mortality rate was 21.5%. Acute stroke and cerebrovascular complications were associated with higher mortality rates, while previous history of epilepsy and admission to intensive care were related to better prognosis (P < .05). To improve SE management and reduce mortality rates, training activities targeting emergency department physicians should be implemented, together with elective intensive care admission for patients with multiple mortality risk factors (eg, absence of history of epilepsy, acute stroke, or cardiovascular complications).


Awareness and attitudes of a rural Ethiopian community toward suicidal behaviour. A key informant study in Butajira, Ethiopia.
One hundred key informants were interviewed regarding their awareness and attitudes toward suicidal behaviour. Eighty-eight informants were male, 58 were Muslim and 42 were Christian. Informants on average, claimed to know more persons who had completed suicide than those who had attempted suicide. Almost all informants mentioned more than one cause for suicide. Of these, frustration was the most frequently mentioned cause. Most informants believed that suicide attempters are cruel, feared and not trustworthy. Their attitude toward suicide completers was expressed as condemned sinners, do not deserve funeral ceremony, and should be buried separately from others. Christians gave importance to the funeral issue more than did the Muslims. Generally, the attitudes of informants were punitive and disapproving.


Recurrent oral squamous papilloma in a pediatric patient: Case report and review of the literature.
Squamous papillomas are common lesions of the oral mucosa. They are benign proliferating lesions often painless, slow growing and with a cauliflower appearance. However, its clinical appearance which sometimes mimics exophytic carcinoma, verrucous carcinoma or condyloma acuminatum raises concern when it occurs in the oral cavity. Squamous papilloma occurs predominantly in 30- to 50-year old's. However, they may be seen in children <10 years and accounted for 8% of all oral tumors in children. There is no sex predilection. It has a predilection for the tongue and soft palate, but may occur on any other surface of the oral cavity. Oral squamous papillomas have been associated with infection by the human papilloma virus (HPV). The present report is a case of a recurrent squamous papilloma of the hard palate in a 5-year-old patient with a review of the literature.


Endovascular closure of a hemiportocaval shunt after small-for-size adult-to-adult left lobe living donor liver transplantation.
Adult-to-adult living donor liver transplantation is an accepted treatment option for patients with end-stage liver disease. It is generally acknowledged that a graft weight to recipient body weight ratio > 0.8 is required in order to prevent the development of small-for-size syndrome. Size mismatch, however, is not the only factor responsible for the syndrome; instead, it results from a combination of factors, including the size, recipient status, and degree of portal hypertension. The ability to modulate the portal venous inflow has sparked renewed interest in the left lobe graft. We have used the hemiportocaval shunt, as described by Troisi et al. (Am J Transplant 2005;5:1397-1404), in left lobe living donor liver transplants in order to prevent small-for-size syndrome while enhancing the safety of the donor operation. In this report, we describe a novel technique for occluding a hemiportocaval shunt in a patient who developed hepatic encephalopathy after receiving a small-for-size left lobe liver allograft from a living donor.


Evidence for Anti-Aging South Korean Cosmeceuticals.

As the market for South Korean skin care products grows in the U.S. and worldwide, consumers will increasingly seek advice from dermatologists regarding their efficacy. In this paper, the evidence behind the anti-aging and skin whitening activity of ingredients in the most popular South Korean skin care products was reviewed and critically evaluated. Industry profit data from Euromonitor was obtained to identify the top cosmeceutical brands by retail value in South Korea. The top selling products and their ingredients were then identified from individual brand websites. A comprehensive literature search was conducted using Pubmed to identify and grade the anti-aging and whitening efficacy for nine popular ingredients: licorice, niacinamide, beta-glucan, snail mucus, ginkgo biloba, ginseng, green tea, pomegranate, and soy. Of the various ingredients reviewed, niacinamide, green tea, licorice, and soy have the most published data for anti-aging and whitening activity. Although the literature shows modest results, small sample sizes limit interpretation. High-level evidence to support the use of South Korean skin care products in anti-aging and skin whitening is lacking.

J Drugs Dermatol. 2017;16(4):358-364.
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Effect of in-office samples on dermatologists' prescribing habits: a retrospective review.
The relationship between physicians and pharmaceutical companies has caused the medical community to question the degree to which pharmaceutical interactions and incentives can influence physicians' prescribing habits. Our study aimed to analyze whether a change in institutional policy that restricted the availability of in-office samples for patients resulted in any measurable change in the prescribing habits of faculty physicians in the Department of Dermatology and Cutaneous Surgery at the University of South Florida (USF)(Tampa, Florida). Medical records were retrospectively reviewed for common dermatology diagnoses-acne vulgaris, atopic dermatitis, onychomycosis, psoriasis, and rosacea-before and after the pharmaceutical policy changes, and the prescribed medications were recorded. These medications were then categorized as brand name, generic, and over-the-counter (OTC). Statistical analysis using a mixed effects ordinal logistic regression model accounting for baseline patient characteristics was conducted to determine if a difference in prescribing habits occurred.


Catalase Hybrid Enzymes in Maize.
In maize endosperm there are two electrophoretic variants of catalase. The variations are under genetic control, and the heterozygote shows three hybrid enzymes with mobilities intermediate between the parental enzymes. Thus, maize catalase may exist as a tetramer, and the hybrid enzymes may be formed by random association of two different catalase monomers.


HDAC inhibition prevents white matter injury by modulating microglia/macrophage polarization through the GSK3β/PTEN/Akt axis.
Severe traumatic brain injury (TBI) elicits destruction of both gray and white matter, which is exacerbated by secondary proinflammatory responses. Although white matter injury (WMI) is strongly correlated with poor neurological status, the maintenance of white matter integrity is poorly understood, and no current therapies protect both gray and white matter. One candidate approach that may fulfill this role is inhibition of class I/II histone deacetylases (HDACs). Here we demonstrate that the HDAC inhibitor Scriptaid protects white matter up to 35 d after TBI, as shown by reductions in abnormally dephosphorylated neurofilament protein, increases in myelin basic protein, anatomic preservation of myelinated axons, and improved nerve conduction. Furthermore, Scriptaid shifted microglia/macrophage polarization toward the protective M2 phenotype and mitigated inflammation. In primary cocultures of microglia and oligodendrocytes, Scriptaid increased expression of microglial glycogen synthase kinase 3 beta (GSK3β), which phosphorylated and inactivated phosphatase and tensin homologue (PTEN), thereby enhancing phosphatidylinositide 3-kinases (PI3K)/Akt signaling and polarizing microglia toward M2. The increase in GSK3β in microglia and their phenotypic switch to M2 was associated with increased preservation of neighboring oligodendrocytes. These findings are consistent with recent findings that microglial phenotypic switching modulates white matter repair and axonal remyelination and highlight a previously unexplored role for HDAC activity in this process. Furthermore, the functions of GSK3β may be more subtle than previously thought, in that GSK3β can modulate microglial functions via the PTEN/PI3K/Akt signaling pathway and preserve white matter homeostasis. Thus, inhibition of HDACs in microglia is a potential future therapy in TBI and other neurological conditions with white matter destruction.


Moulds and Staphylococcus aureus enterotoxins are relevant allergens to affect Type 2 inflammation and clinical outcomes in chronic rhinosinusitis patients.
Sensitisation to moulds and Staphylococcus aureus enterotoxins (SEs) is associated with the pathophysiology of both asthma and chronic rhinosinusitis (CRS). The purpose of this study was to clarify the contribution of sensitisation to these allergens to Type 2 inflammation in the blood, nose and the lower airways, and clinical outcomes in CRS patients. We prospectively enrolled 56 CRS patients who underwent endoscopic sinus surgery (ESS) (20 with comorbid asthma) and 28 healthy controls between October 2015 and December 2017. CRS patients were followed up for 12 months after surgery. Type 2 inflammation-related biomarkers were analysed using blood, resected tissue samples and sputum. 10 allergens including Alternaria, Aspergillus and SEs were measured. Type 2 inflammation-related biomarkers and clinical outcomes were compared in the stratification with the presence or absence of allergen sensitisation. Sensitisation rate to moulds and SEs in asthmatic patients was increased when changing the cut-off value of specific IgE titre from 0.35 UA·mL-1 to 0.10 UA·mL-1 (1.7- and 4.5-fold, respectively). Moulds and SEs affected the prevalence of asthma and eosinophilic CRS by interacting with each other. All Type 2 inflammation-related biomarkers except for eosinophils in sinus tissue were significantly higher in patients with mould or SE (mould/SE) sensitisation (≥0.10 UA·mL-1) (n=19) than in those without (n=37) and healthy subjects (all p<0.05). Meanwhile, mould/SE sensitisation did not affect longitudinal changes in clinical outcomes after ESS. Changes in serum mould/SE-IgE levels after ESS remained unclear. Mould/SE sensitisation (≥0.10 UA·mL-1) may affect the development of Type 2 inflammation and clinical outcomes in CRS patients.


Biochemical Characterization of Parsley Glycosyltransferases Involved in the Biosynthesis of a Flavonoid Glycoside, Apiin.
The flavonoid glycoside apiin (apigenin 7-O-[β-D-apiosyl-(1→2)-β-D-glucoside]) is abundant in apiaceous and asteraceous plants, including celery and parsley. Although several enzymes involved in apiin biosynthesis have been identified in celery, many of the enzymes in parsley (Petroselinum crispum) have not been identified. In this study, we identified parsley genes encoding the glucosyltransferase, PcGlcT, and the apiosyltransferase, PcApiT, that catalyze the glycosylation steps of apiin biosynthesis. Their substrate specificities showed that they were involved in the biosynthesis of some flavonoid 7-O-apiosylglucosides, including apiin. The expression profiles of PcGlcT and PcApiT were closely correlated with the accumulation of flavonoid 7-O-apiosylglucosides in parsley organs and developmental stages. These findings support the idea that PcGlcT and PcApiT are involved in the biosynthesis of flavonoid 7-O-apiosylglucosides in parsley. The identification of these genes will elucidate the physiological significance of apiin and the development of apiin production methods.


The New APGAR SCORE: A Checklist to Enhance Quality of Life in Geriatric Patients with Hip Fracture.
For geriatric patients with hip fractures, the broken bone is the reason for admission, but only part of the overall disease. Indeed, it may be more helpful to consider the patient having geriatric hip fracture syndrome or sustaining a hip attack, as there are many associated medical, social, psychological, and other problems to which attention must be paid. To that end, we have identified a series of 10 steps, collected into a checklist, that can be undertaken for all patients with geriatric hip fracture. In homage to the maxim "we come into the world under the brim of the pelvis and go out through the neck of the femur," we defined our checklist by the acronym APGAR SCORE, named after the classic checklist of the same name used to assess a newborn child. The 10 elements include attending to problems of Alimentation and nutrition, Polypharmacy, and Gait; initiating a discussion about Advance care planning; correcting any Reversible cognitive impairment; maximizing Social support; checking for and remediating Cataracts or other impairments of vision; assessing for and addressing Osteoporosis; and last, ensuring that Referrals are made and that the patient has a safe Environment after discharge. For the newborn, the Apgar score has been criticized as an imperfect tool, and likewise the problem of geriatric hip fracture will not be solved with this new Apgar score either. Nonetheless, a score of 10 here,1 point for each item, may help to optimize the outcome for this difficult disease.


Clinical analysis of fever of unknown origin in children: A 10-year experience in a northern Taiwan medical center.
Fever of unknown origin (FUO) was first described in 1961 as fever >38.3°C for at least 3 weeks with no apparent source after 1 week of investigations in the hospital. Infectious disease comprises the majority of cases (40-60%). There is no related research on FUO in children in Taiwan. The aim of this study is to determine the etiologies of FUO in children in Taiwan and to evaluate the relationship between the diagnosis and patient's demography and laboratory data. Children under 18 years old with fever >38.3°C for >2 weeks without apparent source after preliminary investigations at Taipei Veterans General Hospital during 2002-2012 were included. Fever duration, symptoms and signs, laboratory examinations, and final diagnosis were recorded. The distribution of etiologies and age, fever duration, laboratory examinations, and associated symptoms and signs were analyzed. A total of 126 children were enrolled; 60 were girls and 66 were boys. The mean age was 6.7 years old. Infection accounted for 27.0% of cases, followed by undiagnosed cases (23.8%), miscellaneous etiologies (19.8%), malignancies (16.6%), and autoimmune disorders (12.7%). Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were the most commonly found pathogens for infectious disease, and Kawasaki disease (KD) was the top cause of miscellaneous diagnosis. Infectious disease remains the most common etiology. Careful history taking and physical examination are most crucial for making the diagnosis. Conservative treatment may be enough for most children with FUO, except for those suffering from malignancies.


Laparoscopic virtual reality training: are 30 repetitions enough?
Current literature suggests that novices reach a plateau after two to seven trials when training on the MIST VR laparoscopic virtual reality system. We hypothesize that significant benefit may be gained through additional training. Second-year medical students (n = 12) voluntarily enrolled under an IRB-approved protocol for MIST VR training. All subjects completed pre- and posttraining questionnaires and performed 30 repetitions of 12 tasks. Performance data were automatically recorded for each trial. Learning curves for each task were generated by fitting spline curves to the mean overall scores for each repetition. Scores were assessed for plateaus by repeated measures, slope, and best score. On average, subjects completed training in 7.1 h. (range, 5.9-9.2). Two to seven performance plateaus were identified for each of the 12 MIST VR tasks. Initial plateaus were found for all tasks by the 8th repetition; however, ultimate plateaus were not reached until 21-29 repetitions. Overall best score was reached between 20 and 30 repetitions and occurred beyond the ultimate plateau for 9 tasks. These data indicate that a lengthy learning curve exists for novices and may be seen throughout 30 repetitions and possibly beyond. Performance plateaus may not reliably determine training endpoints. We conclude that a significant and variable amount of training may be required to achieve maximal benefit. Neither a predetermined training duration nor an arbitrary number of repetitions may be adequate to ensure laparoscopic proficiency following simulator training. Standards which define performance-based endpoints should be established.


Lisdexamfetamine and immediate release d-amfetamine - differences in pharmacokinetic/pharmacodynamic relationships revealed by striatal microdialysis in freely-moving rats with simultaneous determination of plasma drug concentrations and locomotor activity.
Lisdexamfetamine mesylate (Vyvanse(®)) is a novel prodrug approved for attention deficit hyperactivity disorder (ADHD). It is metabolised to d-amfetamine and l-lysine. In drug-experienced humans, lisdexamfetamine evoked lower "Drug liking" scores on Drug Rating Questionnaire (DRQ) scales than immediate-release (IR) d-amfetamine. This study investigated why lisdexamfetamine may have lower abuse potential and a better therapeutic window than d-amfetamine. We compared the pharmacokinetic/pharmacodynamic relationships of lisdexamfetamine and IR d-amfetamine in freely-moving rats by measuring simultaneously extracellular concentrations of striatal dopamine, plasma concentrations of d-amfetamine and lisdexamfetamine, and locomotor activity. At equivalent doses (1.5 mg/kg d-amfetamine base), lisdexamfetamine produced smaller, but more sustained, increases in striatal dopamine efflux than d-amfetamine and substantially less locomotor activation. Consistent with it being a prodrug, increased striatal dopamine and locomotion correlated with plasma concentration of its metabolite, d-amfetamine, but not the parent compound. Compared with IR d-amfetamine, lisdexamfetamine produced an identical AUC for plasma d-amfetamine, but a 50% lower C(max) and significantly delayed t(max). Where a hysteresis relationship did exist between plasma concentrations of d-amfetamine and striatal dopamine or locomotor activity, they were anticlockwise in direction for lisdexamfetamine and IR d-amfetamine. For extracellular striatal dopamine (neurochemical mediator) and locomotor activity (functional outcome), it was anticlockwise for lisdexamfetamine, but clockwise for IR d-amfetamine. This shows that lisdexamfetamine produced less pronounced behavioural activation as dopamine concentrations increased, but activity was maintained for longer when they declined. These findings help explain why the unusual pharmacokinetics of lisdexamfetamine evoked lower "Drug liking" scores than IR d-amfetamine and also suggest therapeutic window between efficacy and stimulant side-effects will be larger.


[Nomogram for the determination of arterial oxygen partial pressure of man in relation to high altitude and in dependence from age (author's transl)].
If somebody ascends from sea level to higher altitude within a short time, the change of the atmospheric conditions can be a danger for his life. Therefore, a nomogram was constructed which allows to read off the arterial oxygen partial pressures and the corresponding arterial oxygen saturation in relation to altitude. On the basis of the oxygen partial pressure of the atmosphere determined by steps of 500 m from sea level up to an antitude of 10,000 m, we calculated the decrease of the oxygen partial pressure from the inspired air to the arterial blood. When passing our airways, the inspired oxygen partial pressure is dimished by the adaptation to BTPS conditions and by the increasing CO2 partial pressure when approaching the alveolar gas exchanging zone. Another oxygen partial pressure gradient formed by inhomogeneities of ventilation to perfusion, diffusing capacity to perfusion and shunt perfusion is found at the alveolar-arterial barrier. The value of this alveolar-arterial oxygen partial pressure difference is closely correlated to age. With the values of the single steps, the nomogram was constructed. Seven abscissas show the oxygen partial pressure gradients from the inspired air at a distinct altitude to the arterial blood. In relation to a lot of CO2-depending oxygen dissociation curves, it is possible to read off additionally the corresponding arterial oxygen saturation for a person in rest up to an altitude of 10,000 m.


Detailed characterization of the mRNA mapping in the HindIII fragment K region of the herpes simplex virus type 1 genome.
We have isolated as recombinant DNA clones, in the plasmid pBR322, regions of the herpesvirus type 1 genome spanning the region between 0.53 and 0.6 on the prototypical arrangement. This 11,000-base-pair region corresponds to 10% of the large unique region and encodes five major and several minor mRNA species abundant at different times after infection, which range in length from 7 to 1 kilobase. In this report, we have used RNA transfer blots and S1 nuclease digestion of hybrids between viral DNA and polyribosomal RNA to precisely localize (+/- 0.1 kilobase) these mRNA's. Comparison of neutral and alkaline gels of S1 nuclease-digested hybrids indicates no internal introns in the coding sequences of these mRNA's, although noncontiguous leader sequences near (ca. 0.1 kilobase) the 5' ends of any or all mRNA's could not be excluded. The 5' ends of several late mRNA's that are encoded opposite DNA strands map very close to one another, and the 3' ends of a major late and a major early mRNA, which are partially colinear, terminate in the same region. In vitro translation of the viral mRNA's isolated by hybridization with DNA bound to cellulose and fractionation of mRNA species on denaturing agarose gels allowed us to assign specific polypeptide products to each of the mRNA's characterized. Among other results, it was demonstrated unequivocally that two major late mRNA's, which partially overlap, encode the same polypeptide.


Radiation-induced changes in permeability in unilamellar phospholipid liposomes.
Gamma-radiation-induced oxidative damage in unilamellar dipalmitoylphosphatidylcholine liposomes was investigated using a fluorescence technique. Liposomal changes in permeability induced by gamma radiation were monitored by measuring the leakage of pre-encapsulated 6-carboxyfluorescein, and alterations in lipid bilayer fluidity were determined by 1,6-diphenyl-1,3,5-hexatriene fluorescence polarization. The changes in permeability and fluidity in the bilayer were found to be dependent on the radiation dose in a biphasic fashion. The results are interpreted in terms of lipid bilayer fluidization after exposure to doses up to 1 kGy, but rigidization of the bilayer at higher doses. These results indicate a relationship between alterations in permeability and fluidity in the lipid bilayer after irradiation. The vesicles were protected significantly against radiation-induced oxidative damage in the presence of alpha-tocopherol and ascorbic acid. Radiation-induced changes in the permeability of the liposomes after exposure to gamma radiation and their modification by antioxidants indicate the involvement of a free radical mechanism in the production of damage, which may offer new insights in to the modification of cellular radiosensitivity by modulation of membrane damage.


Positive association between progestins and the evolution of multiple fibroadenomas in 72 women.
Multiple fibroadenomas (MFA) of the breast is a rare benign disease, thus its natural history is poorly understood. The aim of our study was to describe the radiological evolution of MFA and to evaluate the influence of different factors on this evolution. This was a longitudinal cohort study. All patients included had two clinical and radiological assessments (breast ultrasound (US) and/or MRI) at least 5 years apart. Seventy-two women were followed for 7.6 ± 2.1 years. The radiological evolution showed a decrease or stability in the number of fibroadenomas (FA) in 26/44 cases on the MRI and in 38/64 cases on the US. There was a decrease of size in 35/44 cases on the MRI and in 53/64 cases on the US. An increase in the number of FAs was found in 18/44 cases in the MRI and 26/64 cases in the US with, for the majority, a decrease of size (19/26 by MRI and 16/18 by MRI). Older age at the first FA (P < 0.0001) and at the diagnosis of MFA (P < 0.0001), pregnancy (P = 0.003) and progestin use (P < 0.001), particularly lynestrenol (P < 0.0001), had a beneficial effect on the evolution of MFA. This is the first longitudinal study describing women with MFA. The radiological evolution of MFA seamed favorable and similar to that expected for a single FA. We identified factors influencing the evolution of the disease, including progestin treatments such as lynestrenol, which could have a beneficial effect. Our cohort should be followed further in order to expand our knowledge of MFA, especially concerning the risk of breast cancer.


Pediatric Vision Screener 2: pilot study in adults.
Amblyopia is a form of visual impairment caused by ocular misalignment (strabismus) or defocus in an otherwise healthy eye. If detected early, the condition can be fully treated, yet over half of all children with amblyopia under age 5 escape detection. We developed a Pediatric Vision Screener (PVS) to detect amblyopia risk factors. This instrument produces a binocularity score to indicate alignment and a focus score to indicate focus. The purpose of this study is to assess the performance of the PVS by testing adults who were fully cooperative for testing. The study group includes 40 subjects (20 controls, 20 patients) aged 22 to 79 years. 12 patients had constant strabismus (8 to 50Delta), and eight had variable strabismus (12 to 55Delta). All controls had binocularity scores >50%. Binocularity was <50% in 11/12 patients. The patient with binocularity >50% had a well-controlled intermittent exotropia and was not at risk for amblyopia. Focus scores were highly sensitive for good focus but not specific. The PVS shows high sensitivity and specificity for detection of strabismus in adults. Future studies will determine whether this performance can be achieved in preschool children, who are at greatest risk for vision loss.


PALEONTOLOGY: Homoplasy in the Mammalian Ear.
The separation of the middle ear bones from the mandible is considered a defining feature of all modern mammals. But did this event happen once in a primitive mammalian ancestor or independently in the monotreme lineage and therian (marsupial and placental) lineage? As Martin and Luo discuss in their Perspective, a new fossil-the dentary bone of an ancient toothed monotreme-suggests that the middle ear bones formed independently in these two mammalian lineages, providing a remarkable example of homoplastic evolution.


Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial.
Continuous veno-venous haemofiltration is increasingly used to treat acute renal failure in critically ill patients, but a clear definition of an adequate treatment dose has not been established. We undertook a prospective randomised study of the impact different ultrafiltration doses in continuous renal replacement therapy on survival. We enrolled 425 patients, with a mean age of 61 years, in intensive care who had acute renal failure. Patients were randomly assigned ultrafiltration at 20 mL h(-1) kg(-1) (group 1, n=146), 35 mL h(-1) kg(-1) (group 2, n=139), or 45 mL h(-1) kg(-1) (group 3, n=140). The primary endpoint was survival at 15 days after stopping haemofiltration. We also assessed recovery of renal function and frequency of complications during treatment. Analysis was by intention to treat. Survival in group 1 was significantly lower than in groups 2 (p=0.0007) and 3 (p=0.0013). Survival in groups 2 and 3 did not differ significantly (p=0.87). Adjustment for possible confounding factors did not change the pattern of differences among the groups. Survivors in all groups had lower concentrations of blood urea nitrogen before continuous haemofiltration was started than non-survivors. 95%, 92%, and 90% of survivors in groups 1, 2, and 3, respectively, had full recovery of renal function. The frequency of complications was similarly low in all groups. Mortality among these critically ill patients was high, but increase in the rate of ultrafiltration improved survival significantly. We recommend that ultrafiltration should be prescribed according to patient's bodyweight and should reach at least 35 mL h(-1) kg(-1).


Guided tissue regeneration with and without demineralized freeze-dried bone allografts for maxillary Class II furca invasions of rapidly progressive periodontitis.
Guided tissue regeneration (GTR) using an expanded polytetrafluorethylene (ePTFE) membrane is an established treatment modality for periodontal disease. This study was designed to compare the effects of ePTFE membranes with and without demineralized, freeze-dried bone allografts (DFDBA) for treating maxillary class II buccal furca invasions of rapidly progressive periodonitis. Seven patients with pairs of maxillary class II buccal furca invasions comprised the study group. The clinical parameters investigated were probing depth, probing attachment level and marginal tissue recession. One defect from each pair of teeth was randomly selected for the ePTFE membrane and DFDBA group and the other tooth defect received ePTFE membrane treatment only. During the operation, horizontal probing depths at the buccal furcation areas were measured. The membrane was removed 6 weeks after insertion. All measurements were repeated 1 year later at surgical re-entry of the buccal furcation. The Wilcoxon ranked sum test was used to test the significance of the difference between the groups 1 year after treatment. In the ePTFE membrane and DFDBA group, the mean probing depth reduction was 2.1 +/- 0.8 mm. The probing attachment gain was 2.6 +/- 1.0 mm and the bone fill was 3.1 +/- 1.7 mm. There was no statistically significant difference between the groups for these parameters. The marginal tissue recession was reduced 0.4 +/- 0.7 mm in ePTFE membrane and DFDBA group but increased 0.9 +/- 0.6 mm in ePTFE membrane only group. This difference was statistically significant (p = 0.016). There was no difference in probing depth reduction, probing attachment gain or bone fill between the two treatment modalities for treating maxillary class II buccal furca invasion of rapidly progressive periodontitis. Marginal tissue recession can be significantly reduced with the treatment of combined ePTFE membrane and DFDBA.


Determinants of vaccine-induced resistance in animal models of pulmonary tuberculosis.
A more effective vaccine will be essential if the global tuberculosis (TB) pandemic is ever to be controlled. A large number of new tuberculosis vaccines have been developed, representing the whole range of modern strategies for vaccine formulation and delivery. There is currently no alternative to testing these new vaccines in experimental animals challenged with virulent Mycobacteriurn tuberculosis in order to assess their protective efficacy. Although such testing is being carried out in several animal species (mice, guinea pigs, rabbits), all rational models include pulmonary challenge with a low dose of virulent mycobacteria. The quantitative measures for TB vaccines include increased survival, amelioration of clinical signs and symptoms (e.g. prevention of weight loss), decreased lesion size, reduction in bacillary loads in the lungs, and prevention of extrapulmonary dissemination and hematogenous reseeding of the lung. Although the ultimate objective of vaccination in humans is to prevent transmission to susceptible contacts, no such measurement is being used in animal studies of new vaccines. The validation of an immunological "correlate of protection" is urgently needed. Candidates for such a correlate include antigen-specific interferon-gamma production by T cells of the memory phenotype (CD45RB(high) or mycobacterial killing by macrophages co-cultured with immune T cells. Additional animal models must be developed for vaccines designed to prevent endogenous reactivation or exogenous reinfection, or to be used as a adjunct to chemotherapy.


Inhaled Bacteriophage Therapy for Multi-Drug Resistant Achromobacter.
The rise of antimicrobial resistant (AMR) bacteria is a global public health threat. AMR Achromobacter bacteria pose a challenging clinical problem, particularly for those with cystic fibrosis (CF) who are predisposed to chronic bacterial lung infections. Lytic bacteriophages (phages) offer a potential alternative to treat AMR infections, with the possible benefit that phage selection for resistance in target bacteria might coincide with reduced pathogenicity. The result is a genetic "trade-off," such as increased sensitivity to chemical antibiotics, and/or decreased virulence of surviving bacteria that are phage resistant. Here, we show that two newly discovered lytic phages against Achromobacter were associated with stabilization of respiratory status when deployed to treat a chronic pulmonary infection in a CF patient using inhaled (nebulized) phage therapy. The two phages demonstrate traits that could be generally useful in their development as therapeutics, especially the possibility that the phages can select for clinically useful trade-offs if bacteria evolve phage resistance following therapy. We discuss the limitations of the current study and suggest further work that should explore whether the phages could be generally useful in targeting pulmonary or other Achromobacter infections in CF patients.


Size-selective encapsulation of hydrophobic guests by self-assembled M4L6 cobalt and nickel cages.
Subtle differences in metal-ligand bond lengths between a series of [M(4)L(6)](4-) tetrahedral cages, where M = Fe(II), Co(II), or Ni(II), were observed to result in substantial differences in affinity for hydrophobic guests in water. Changing the metal ion from iron(II) to cobalt(II) or nickel(II) increases the size of the interior cavity of the cage and allows encapsulation of larger guest molecules. NMR spectroscopy was used to study the recognition properties of the iron(II) and cobalt(II) cages towards small hydrophobic guests in water, and single-crystal X-ray diffraction was used to study the solid-state complexes of the iron(II) and nickel(II) cages.


How the Beneficial Effects of Alvimopan Differ With Surgical Approach for Radical Cystectomy.
To assess whether the beneficial perioperative effects of alvimopan differ with surgical approach for patients who undergo open radical cystectomy (ORC) vs robot-assisted radical cystectomy (RARC). This retrospective study reviewed all patients who underwent cystectomy with urinary diversion at our institution between January 1, 2007, and January 1, 2018. Data were collected on demographic characteristics, comorbidities, surgical approach, alvimopan therapy, hospital length of stay (LOS), days until return of bowel function (ROBF), and complications. Outcomes and interactions were evaluated through regression analysis. Among 573 patients, 236 (41.2%) underwent RARC, 337 (58.8%) underwent ORC, and 205 (35.8%) received alvimopan. Comparison of 4 cohorts (ORC with alvimopan, ORC without alvimopan, RARC with alvimopan, and RARC without alvimopan) showed that patients who underwent ORC without alvimopan had the highest rate of postoperative ileus (25.6%, P = .02), longest median hospital LOS (7 days, P < .001), and longest time until ROBF (4 days, P < .001). On multivariable analysis, the interaction between surgical approach and alvimopan use was significant for the outcome of ROBF (estimate, 1.109; 95% confidence interval, 0.418-1.800; P = .002). In the RARC cohort, multivariable analysis showed no benefit of alvimopan with respect to ileus (P = .27), LOS (P = .09), or ROBF (P = .36). Regarding joint effects of robotic approach and alvimopan, RARC had no effect on gastrointestinal tract outcomes. We observed a diminished beneficial effect of alvimopan among patients undergoing RARC and a statistically significant benefit of alvimopan among patients undergoing ORC. The implications of these findings may permit more selective medication use for patients who would benefit the most from this drug.


Applied machine learning and artificial intelligence in rheumatology.
Machine learning as a field of artificial intelligence is increasingly applied in medicine to assist patients and physicians. Growing datasets provide a sound basis with which to apply machine learning methods that learn from previous experiences. This review explains the basics of machine learning and its subfields of supervised learning, unsupervised learning, reinforcement learning and deep learning. We provide an overview of current machine learning applications in rheumatology, mainly supervised learning methods for e-diagnosis, disease detection and medical image analysis. In the future, machine learning will be likely to assist rheumatologists in predicting the course of the disease and identifying important disease factors. Even more interestingly, machine learning will probably be able to make treatment propositions and estimate their expected benefit (e.g. by reinforcement learning). Thus, in future, shared decision-making will not only include the patient's opinion and the rheumatologist's empirical and evidence-based experience, but it will also be influenced by machine-learned evidence.


Evidence for a single rolling circle in the replication of potato spindle tuber viroid.
We analyzed in vivo-labeled RNA to determine which of the two proposed rolling-circle models is more likely to depict the replication cycle of potato spindle tuber viroid. A key feature distinguishing the two models is the presence of a circular monomeric minus strand in one and not the other. Chromatography on cellulose CF11 was used to purify a fraction containing the replication intermediates free from single-stranded progeny. Heat denaturation followed by gel electrophoresis was used to seek possible circular templates-species required for rolling-circle replication to take place. Upon heating, a (32)P-labeled RNA was released. Limited nuclease digestion ("nicking") revealed that this was a unitlength circular RNA. Fingerprinting identified it as a plus strand. No circular minus strands were detected in this population or in nuclease-treated samples containing RNase T1-resistant cores of the replication complex. Thus, potato spindle tuber viroid appears to use an asymmetric pathway in which minus strands are synthesized by rolling-circle copying, but plus strands are not. More details of the replication pathways used by various viroid-like RNAs are needed and will help to establish the evolutionary relationships among these infectious agents.


A guideline for atomistic design and understanding of ultrahard nanomagnets.
Magnetic nanoparticles are of immense current interest because of their possible use in biomedical and technological applications. Here we demonstrate that the large magnetic anisotropy of FePt nanoparticles can be significantly modified by surface design. We employ X-ray absorption spectroscopy offering an element-specific approach to magnetocrystalline anisotropy and the orbital magnetism. Experimental results on oxide-free FePt nanoparticles embedded in Al are compared with large-scale density functional theory calculations of the geometric- and spin-resolved electronic structure, which only recently have become possible on world-leading supercomputer architectures. The combination of both approaches yields a more detailed understanding that may open new ways for a microscopic design of magnetic nanoparticles and allows us to present three rules to achieve desired magnetic properties. In addition, concrete suggestions of capping materials for FePt nanoparticles are given for tailoring both magnetocrystalline anisotropy and magnetic moments.


Evaluation of Streptococcus thermophilus IFFI 6038 Microcapsules Prepared Using an Ultra-fine Particle Processing System.
Microencapsulation technology has the potential to protect probiotics and to deliver them to the gut, and extrusion is one of the most commonly used methods. However, the rather large diameters of 1~5 mm produced tend to cause oral grittiness and result in low compliance. In this article, Streptococcus thermophilus IFFI 6038 (IFFI 6038) microcapsules were prepared using an ultra-fine particle processing system (UPPS) previously developed by this research group. IFFI 6038 suspension was pumped by a peristaltic pump to the feeding inlet nozzle and then dispersed into micro-droplets by a rotating disk, followed by solidification. Trehalose (16%) was used as a cryoprotectant to protect IFFI 6038 from damage by lyophilization used in the process. Alginate (3%) resulted in IFFI 6038 microcapsules with a median particle diameter (d 50) of 29.32 ± 0.12 μm and a span value of 1.00 ± 0.02, indicating uniform particle size distribution. To evaluate the potential of microencapsulation in protecting IFFI 6038 from the gastric conditions, the viable counts of IFFI 6038 following incubation of IFFI 6038 microcapsules in simulated gastric juices for 120 min were determined and compared with those of free IFFI 6038. The stability of microencapsulated IFFI 6038 upon storage for 3 months at 4°C and 25°C, respectively, was also determined. The results showed that microcapsules prepared by UPPS protected IFFI 6038 from gastric conditions. The results from a rat diarrhea model showed that microcapsules prepared by the UPPS method were able to effectively improve the diarrhea conditions in rats.


Temporal dynamics of RSV shedding and genetic diversity in adults during the COVID-19 pandemic in a French hospital, early 2021.
Human respiratory syncytial virus (RSV) is responsible of lower respiratory tract infections which may be severe in infants, elderly and immunocompromised adults. Europe and North-American countries have observed a massive reduction of RSV incidence during the 2020-2021 winter season. Using a systematic RSV detection coupled to SARS-CoV-2 for all adult patients admitted at the Foch hospital (Suresnes, France) between January and March 2021 (n = 11,324), only eight RSV infections in patients with prolonged RNA shedding were diagnosed. RSV whole-genome sequencing revealed that six and two patients were infected by RSV groups A and B, respectively. RSV carriage lasted from 7 to at least 30 days disregarding of RSV lineage. The most prolonged RSV shedding was observed in an asymptomatic patient. We detected novel patient-specific non-synonymous mutations in the G glycoprotein gene, including a double identical mutation in the repeated region for one patient. No additional mutation occurred in the RSV genome over the course of infection in the four patients tested for. In conclusion, our results suggest that the temporal shift in the RSV epidemic is not likely to be explained by the emergence of a high frequency, unreported variant. Moreover, prolonged RSV carriages in asymptomatic patients could play a role in virus spread.


RGD-Modified Nanofibers Enhance Outcomes in Rats after Sciatic Nerve Injury.
Nerve injuries requiring surgery are a significant problem without good clinical alternatives to the autograft. Tissue engineering strategies are critically needed to provide an alternative. In this study, we utilized aligned nanofibers that were click-modified with the bioactive peptide RGD for rat sciatic nerve repair. Empty conduits or conduits filled with either non-functionalized aligned nanofibers or RGD-functionalized aligned nanofibers were used to repair a 13 mm gap in the rat sciatic nerve of animals for six weeks. The aligned nanofibers encouraged cell infiltration and nerve repair as shown by histological analysis. RGD-functionalized nanofibers reduced muscle atrophy. During the six weeks of recovery, the animals were subjected to motor and sensory tests. Sensory recovery was improved in the RGD-functionalized nanofiber group by week 4, while other groups needed six weeks to show improvement after injury. Thus, the use of functionalized nanofibers provides cues that aid in in vivo nerve repair and should be considered as a future repair strategy.


Nitrogen isotopomer site preference of N2O produced by Nitrosomonas europaea and Methylococcus capsulatus Bath.
The relative importance of individual microbial pathways in nitrous oxide (N(2)O) production is not well known. The intramolecular distribution of (15)N in N(2)O provides a basis for distinguishing biological pathways. Concentrated cell suspensions of Methylococcus capsulatus Bath and Nitrosomonas europaea were used to investigate the site preference of N(2)O by microbial processes during nitrification. The average site preference of N(2)O formed during hydroxylamine oxidation by M. capsulatus Bath (5.5 +/- 3.5 per thousand) and N. europaea (-2.3 +/- 1.9 per thousand) and nitrite reduction by N. europaea (-8.3 +/- 3.6 per thousand) differed significantly (ANOVA, f((2,35)) = 247.9, p = 0). These results demonstrate that the mechanisms for hydroxylamine oxidation are distinct in M. capsulatus Bath and N. europaea. The average delta(18)O-N(2)O values of N(2)O formed during hydroxylamine oxidation for M. capsulatus Bath (53.1 +/- 2.9 per thousand) and N. europaea (-23.4 +/- 7.2 per thousand) and nitrite reduction by N. europaea (4.6 +/- 1.4 per thousand) were significantly different (ANOVA, f((2,35)) = 279.98, p = 0). Although the nitrogen isotope value of the substrate, hydroxylamine, was similar in both cultures, the observed fractionation (delta(15)N) associated with N(2)O production via hydroxylamine oxidation by M. capsulatus Bath and N. europaea (-2.3 and 26.0 per thousand, respectively) provided evidence that differences in isotopic fractionation were associated with these two organisms. The site preferences in this study are the first measured values for isolated microbial processes. The differences in site preference are significant and indicate that isotopomers provide a basis for apportioning biological processes producing N(2)O.