Nomogram Predicts Risk and Prognostic Factors for Bone Metastasis of Pancreatic Cancer: A Population-Based Analysis.
The overall survival (OS) of pancreatic cancer (PC) patients with bone metastasis (BM) is extremely low, and it is pretty hard to treat bone metastasis. However, there are currently no effective nomograms to predict the diagnosis and prognosis of pancreatic cancer with bone metastasis (PCBM). Therefore, it is of great significance to establish effective predictive models to guide clinical practice. We screened patients from Surveillance Epidemiology and End Results (SEER) database between 2010 and 2016. The independent risk factors of PCBM were identified from univariable and multivariable logistic regression analyses, and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors affecting the prognosis of PCBM. In addition, two nomograms were constructed to predict the risk and prognosis of PCBM. We used the area under the curve (AUC), C-index and calibration curve to determine the predictive accuracy and discriminability of nomograms. The decision curve analysis (DCA) and Kaplan-Meier(K-M) survival curves were employed to further confirm the clinical effectiveness of the nomogram. Multivariable logistic regression analyses revealed that risk factors of PCBM included age, primary site, histological subtype, N stage, radiotherapy, surgery, brain metastasis, lung metastasis, and liver metastasis. Using Cox regression analyses, we found that independent prognostic factors of PCBM were age, race, grade, histological subtype, surgery, chemotherapy, and lung metastasis. We utilized nomograms to visually express data analysis results. The C-index of training cohort was 0.795 (95%CI: 0.758-0.832), whereas that of internal validation cohort was 0.800 (95%CI: 0.739-0.862), and the external validation cohort was 0.787 (95%CI: 0.746-0.828). Based on AUC of receiver operating characteristic (ROC) analysis, calibration plots, and decision curve analysis (DCA), we concluded that the risk and prognosis model of PCBM exhibits excellent performance. Nomogram is sufficiently accurate to predict the risk and prognostic factors of PCBM, allowing for individualized clinical decisions for future clinical work.


Factors that influence persistence or recurrence of high-grade squamous intraepithelial lesion with positive margins after the loop electrosurgical excision procedure: a retrospective study.
In 5-20 % of patients with cervical high-grade squamous intraepithelial lesion (HSIL), a positive margin after the loop electrosurgical excision procedure (LEEP) is associated with persistence/recurrence, but the prognostic value of other clinico-pathological factors is less clear. Among 4336 patients with HSIL who underwent an initial LEEP, 275 (6 %) had HSIL-positive margins, 37 of whom were lost to follow-up. We evaluated the remaining 238 patients. Persistence/recurrence was defined as histopathological HSIL during follow-up. The age of the patients ranged from 21 to 69 years (median: 40). The median follow-up period was 25 months (range: 6-43). Of the 238 patients, 211 (88.7 %) patients remained free of persistence/recurrence, while 27 (11.3 %) experienced persistence/recurrence. According to a univariate analysis, age (P = 0.03) and maximum specimen diameter (P = 0.043) were associated with persistence/recurrence, but number/location of involved margin sections and the pathology of the endocervical curettage were not (P > 0.10). The relative risk of the subjects (greater than or equal to 35 years ages) was 4.6 times of the subject less than 35 years, the difference was statistically significant (14 % vs. 3 %, P < 0.05). A multivariate analysis indicated that an age of 35 years or older was the only independent risk factor (OR 4.97, 95 % CI 1.14-21.62, P = 0.03). In patients with HSIL and HSIL-involved margins after an initial LEEP, age is a strong independent predictor of persistence/recurrence. Follow-up with screening cytology and/or biopsy may be considered in younger patients, whereas a secondary LEEP/hysterectomy may be considered in older patients.


Adipokines as mediators of endothelial function and atherosclerosis.
For many decades, adipose tissue was considered as an inactive body compartment that was only used as an energy store. During the recent years, an increasing amount of data has revealed that adipose tissue is a major endocrine and paracrine organ producing numerous enzymes, hormones and growth factors which are collectively termed as adipokines. Several experimental and clinical studies showed that adipokines modulate insulin sensitivity and have an influence on glucose/fat metabolism and obesity. Apart from these properties, recent research revealed several direct actions of adipokines on endothelial function, vascular homeostasis and atherogenesis which are independent of their effects on glucose and fat metabolism. The present review focuses on the direct effects of adipokines on vascular/endothelial function and atherosclerosis and summarizes the experimental and clinical data which suggest a role for these molecules as potential diagnostic and prognostic cardiovascular markers as well as potential therapeutic target to reduce cardiovascular risk.


Streptomycylamines: difference in activity and mode of action between short-chain and long-chain derivatives.
A homologue series of aliphatic streptomycylamines (SM-amines) have been prepared and tested in vitro (binding to 70S ribosomes) and in vivo (MIC). The short-chain SM-amines act as streptomycin (SM) but are less active than SM. They are inactive towards a SM-resistant Escherichia coli, our strain 042. The long-chain SM-amines are active both towards our sensitive and resistant E. coli, our strains 079 and 042. Their activities are not pH-dependent in contrast to that of SM. However, the higher homologues of the aliphatic amines (C10 Congruent TO C10) are considerably active per se although two to four times less than the corresponding SM-amines. Further, the amines do not compete with the SM-amine for the binding to the ribosomal particles. The binding affinities of these long-chain SM-amines to ribosomes are considerably smaller than that of SM. The binding is however specific as a typical isotope dilution curve can be obtained. We conclude that the long-chain SM-amines have a mode of action different from that of SM.


Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey.
Postacute COVID-19 syndrome (PACS) is an emerging entity characterised by a large array of manifestations, including musculoskeletal complaints, fatigue and cognitive or sleep disturbances. Since similar symptoms are present also in patients with fibromyalgia (FM), we decided to perform a web-based cross-sectional survey aimed at investigating the prevalence and predictors of FM in patients who recovered from COVID-19. Data were anonymously collected between 5 and 18 April 2021. The collection form consisted of 28 questions gathering demographic information, features and duration of acute COVID-19, comorbid diseases, and other individual's attributes such as height and weight. The American College of Rheumatology (ACR) Survey Criteria and the Italian version of the Fibromyalgia Impact Questionnaire completed the survey. A final sample of 616 individuals (77.4% women) filled the form 6±3 months after the COVID-19 diagnosis. Of these, 189 (30.7%) satisfied the ACR survey criteria for FM (56.6% women). A multivariate logistic regression model including demographic and clinical factors showed that male gender (OR: 9.95, 95% CI 6.02 to 16.43, p<0.0001) and obesity (OR: 41.20, 95% CI 18.00 to 98.88, p<0.0001) were the strongest predictors of being classified as having post-COVID-19 FM. Hospital admission rate was significantly higher in men (15.8% vs 9.2%, p=0.001) and obese (19.2 vs 10.8%, p=0.016) respondents. Our data suggest that clinical features of FM are common in patients who recovered from COVID-19 and that obesity and male gender affect the risk of developing post-COVID-19 FM.


Observing an induced-fit mechanism during sequence-specific DNA methylation.
The characterization of conformational changes that drive induced-fit mechanisms and their quantitative importance to enzyme specificity are essential for a full understanding of enzyme function. Here, we report on M.HhaI, a sequence-specific DNA cytosine C(5) methyltransferase that reorganizes a flexible loop (residues 80-100) upon binding cognate DNA as part of an induced-fit mechanism. To directly observe this approximately 26A conformational rearrangement and provide a basis for understanding its importance to specificity, we replaced loop residues Lys-91 and Glu-94 with tryptophans. The double mutants W41F/K91W and W41F/E94W are relatively unperturbed in kinetic and thermodynamic properties. W41F/E94W shows DNA sequence-dependent changes in fluorescence: significant changes in equilibrium and transient state fluorescence that occur when the enzyme binds cognate DNA are absent with nonspecific DNA. These real-time, solution-based results provide direct evidence that binding to cognate DNA induces loop reorganization into the closed conformer, resulting in the correct assembly of the active site. We propose that M.HhaI scans nonspecific DNA in the loop-open conformer and rearranges to the closed form once the cognate site is recognized. The fluorescence data exclude mechanisms in which loop motion precedes base flipping, and we show loop rearrangements are directly coupled to base flipping, because the sequential removal of single hydrogen bonds within the target guanosine:cytosine base pair results in corresponding changes in loop motion.


[Hic-5/ARA55 inhibits the growth of Lovo cells by up-regulating the expression of P27].
To investigate the effects of Hic-5/ARA55 on the growth of the human colorectal cancer cells (Lovo cells) and its mechanism. Flow cytometry (FCM) was used to study the cell cycle of Lovo cells (Lovo group), Lovo cells stably transfected with empty vector (Lovo-Vector group) and the Lovo cells stably transfected with vector containing Hic-5/ARA55 (Lovo-Hic-5/ARA55 group). Western blot assay was used to detect the principal cyclins in the three groups, and Luciferase assay was used to study the mechanism between Hic-5/ARA55 and the only target cyclin. The cells from the three groups were inoculated subcutaneously into 7 nude mice (Balb/c nu/nu) respectively to observe the effects of Hic-5/ARA55 on the growth of the cells in vivo. Seven weeks later, the subcutaneous tumors were harvested and weighed. Then immunohistochemistry assay was used to detect Hic-5/ARA55 and the target cyclin in the tumors. The cell cycle was obviously delayed from G0/G1 to S stage in Lovo-Hic-5/ARA55 cells. A significantly higher expression of P27 was found in Lovo-Hic-5/ARA55 cells than in the other two groups. The weight of the subcutaneous tumors of Lovo-Hic-5/ARA55 cells, Lovo cells and Lovo-Vector cells were (0.33 +/- 0.23) g, (1.20 +/- 0.39) g and (1.30 +/- 0.49) g, respectively; the tumors of Lovo-Hic-5/ARA55 cells was significantly lighter than those of the other two groups (P<0.05). Hic-5/ARA55 and P27 were both over-expressed in implanted tumors of Lovo-Hic-5/ARA55 cells, while were both expressed lower or not expressed in the other two groups. And the expressions of Hic-5/ARA55 and P27 were highly positive correlated (r=0.816, P<0.05). Hic-5/ARA55 could inhibit the growth of Lovo cells both in vitro and in vivo by up-regulating the transcription of P27.


Response Patterns in Health State Valuation Using Endogenous Attribute Attendance and Latent Class Analysis.
Not accounting for simplifying decision-making heuristics when modelling data from discrete choice experiments has been shown potentially to lead to biased inferences. This study considers two ways of exploring the presence of attribute non-attendance (that is, respondents considering only a subset of the attributes that define the choice options) in a health state valuation discrete choice experiment. The methods used include the latent class (LC) and endogenous attribute attendance (EAA) models, which both required adjustment to reflect the structure of the quality-adjusted life year (QALY) framework for valuing health outcomes. We find that explicit consideration of attendance patterns substantially improves model fit. The impact of allowing for non-attendance on the estimated QALY weights is dependent on the assumed source of non-attendance. If non-attendance is interpreted as a form of preference heterogeneity, then the inferences from the LC and EAA models are similar to those from standard models, while if respondents ignore attributes to simplify the choice task, the QALY weights differ from those using the standard approach. Because the cause of non-attendance is unknown in the absence of additional data, a policymaker may use the range of weights implied by the two approaches to conduct a sensitivity analysis.


Magnesium Transport and Magnesium Homeostasis.
This review reviews the properties and regulation of the Salmonella enterica serovar Typhimurium and Escherichia coli transporters that mediate Mg2+ influx: CorA and the Mgt P-type ATPases. In addition, potential Mg2+ regulation of transcription and translation, largely via the PhoPQ two component system, is discussed. CorA proteins are a unique class of transporters and are widespread in the Bacteria and Archaea, with rather distant but functional homologs in eukaryotes. The Mgt transporters are highly homologous to other P-type ATPases but are more closely related to the eukaryotic H+ and Ca2+ ATPases than to most prokaryotic ATPases. Hundreds of homologs of CorA are currently known from genomic sequencing. In contrast, only when extracellular and possibly intracellular Mg2+ levels fall significantly is the expression of mgtA and mgtB induced. Topology studies using blaM and lacZ fusions initially indicated that the Salmonella serovar Typhimurium CorA contained three transmembrane (TM) segments; however, subsequent data obtained using a variety of approaches showed that the CorA superfamily of proteins have only two TMs at the extreme C terminus. PhoP-PhoQ is a two-component system consisting of PhoQ, the sensor/receptor histidine kinase, and PhoP, the response regulator/transcriptional activator. The expression of both mgtA and mgtCB in either E. coli or Salmonella serovar Typhimurium is markedly induced in a PhoPQ-dependent manner by low concentrations of Mg2+ in the medium. phoP and phoQ form an operon with two promoters in both E. coli and Salmonella serovar Typhimurium.


The proximal origin of the hamstrings and surrounding anatomy encountered during repair. A cadaveric study.
Avulsion of the proximal origin of the hamstrings has become a more frequently recognized athletic injury. Most orthopaedic surgeons rarely operate in this anatomic area. The purpose of the present study was to define the anatomy of the proximal origin of the hamstrings and its relationship to neurovascular and muscular structures encountered during a repair of a complete avulsion. Fourteen fresh-frozen hip-to-foot human cadaveric specimens were dissected in the prone position. The proximal origin of the hamstrings and its relationship to the surrounding neurologic and muscular structures were documented and measured with use of digital calipers. Six of the fourteen specimens were from female donors. The average age of the donors at the time of death was 68 +/- 13 years. The average height of the donors was 66 +/- 3.5 in (167 +/- 8.9 cm), and the average weight was 142 +/- 39 lb (64 +/- 17.7 kg). The semitendinosus and biceps femoris have a common tendinous site of origin on the ischium. A number of measurements were obtained. The musculotendinous junctions of the semitendinosus and biceps femoris separated at an average of 9.9 +/- 1.5 cm from the most proximal origin site on the ischium. The average distance from the proximal border of the semitendinosus/biceps femoris origin to the inferior border of the gluteus maximus was 6.3 +/- 1.3 cm. At the lateral border of the ischium, the average distance from the inferior gluteal nerve and artery to the inferior border of the gluteus maximus was 5.0 +/- 0.8 cm. The sciatic nerve was an average of 1.2 +/- 0.2 cm from the most lateral aspect of the ischial tuberosity. The site of origin of the semitendinosus/biceps femoris was oval, with average measurements of 2.7 +/- 0.5 cm from proximal to distal and of 1.8 +/- 0.2 cm from medial to lateral. The site of origin of the semimembranosus was crescent-shaped, with average measurements of 3.1 +/- 0.3 cm from proximal to distal and of 1.1 +/- 0.5 cm from medial to lateral. The semitendinosus and biceps femoris have a common tendon of origin on the ischium, and the semimembranosus originates just laterally. The proximal origin of the hamstrings has intimate relationships with the inferior gluteal nerve and artery and the sciatic nerve, which may be at risk during surgical dissection and retraction.


Comparison of sustained-release and standard preparations of clonidine in essential hypertension.
The antihypertensive drug, clonidine, was administered to 18 patients, 8 females and 10 males, with WHO grade I-II essential hypertension in two forms, either as sustained-release depot capsule of 250 micrograms once daily or as standard clonidine preparation, 150 micrograms twice daily. The two drug forms were administered for 2 months each, in a double-blind, crossover outpatient study. Both preparations were equally effective in reducing blood pressure. The depot form of clonidine was preferred by the patients because of fewer side effects, which included sedation and dry mouth. The antihypertensive effect of clonidine was unrelated to pretreatment plasma renin activity. Depot forms of clonidine appear to offer the advantages of once-daily dosing and fewer side effects than standard clonidine preparations.


[Gastric surgery].
Clinical and experimental studies related to gastric surgery in the First Department of Surgery, Niigata University Hospital are reported in this paper. For the curative resection of cancer which is located in the upper one-third of the stomach and infiltrates into the esophagus, gastrectomy with distal pancreatectomy and splenectomy is necessary in order to remove the lymph nodes around the splenic artery and hilum completely, and sufficient resection of the thoracic esophagus and removal of lymph nodes around the thoracic esophagus and diaphragm are also important. Postoperative G cell hyperplasia of the antral mucosa and consequent increased gastrin release are probable causes of recurrent ulcer after selective proximal vagotomy for duodenal ulcer. It is known that selective vagotomy with antrectomy for duodenal ulcer has scarcely shown recurrent ulcer but frequently accompanies gastric stasis in the early postoperative period. However, frequency of postoperative gastric stasis can be reduced by the preservation of right gastro-epiploic vessels and nerves around them during operative procedure of antrectomy. In conclusion, it is emphasized that not only seeking after radicality of operation but also minimizing postoperative disturbances and preserving gastric function as much as possible are essential in gastric surgery.


The Relation of Psychosocial Distress With Myocardial Perfusion and Stress-Induced Myocardial Ischemia.
Mental stress-induced myocardial ischemia is a frequent phenomenon in patients with coronary artery disease (CAD). The link between an integrated measure of chronic psychosocial distress and mental stress-induced myocardial ischemia, and whether it differs by sex, has not been examined before. We used latent class analysis to derive a composite measure of psychosocial distress integrating scales of depression, posttraumatic stress, anxiety, anger, hostility, and perceived stress in 665 individuals with stable CAD. Participants underwent myocardial perfusion imaging with mental stress and perfusion defects were quantified at rest (summed rest score), with mental stress (summed stress score), and their difference (summed difference score), the latter being an index of inducible ischemia. The M (SD) age was 63 (9) years, and 185 (28%) were women. Latent class analysis characterized the study sample into four distinct classes of incremental psychosocial distress. In women, class 4 (highest distress) had an adjusted 4.0-point higher summed rest score (95% confidence interval = 0.2-7.7) as compared with class 1 (lowest distress), whereas no difference was observed in men (-0.87 points, 95% confidence interval = -3.74 to 1.99, p = .04 for interaction). There was no association between the psychosocial distress latent variable and summed difference score in either women or men. Among patients with CAD, a higher level of psychosocial distress is not associated with mental stress ischemia, but it is associated with more resting (fixed) perfusion abnormalities in women only, as well as with blunted hemodynamic response to mental stress in both men and women.


Partial lesion of dopamine neurons of rat substantia nigra impairs conditioned place aversion but spares conditioned place preference.
Midbrain dopamine neurons play critical roles in reward- and aversion-driven associative learning. However, it is not clear whether they do this by a common mechanism or by separate mechanisms that can be dissociated. In the present study we addressed this question by testing whether a partial lesion of the dopamine neurons of the rat SNc has comparable effects on conditioned place preference (CPP) learning and conditioned place aversion (CPA) learning. Partial lesions of dopamine neurons in the rat substantia nigra pars compacta (SNc) induced by bilateral intranigral infusion of 6-hydroxydopamine (6-OHDA, 3μg/side) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 200μg/side) impaired learning of conditioned place aversion (CPA) without affecting conditioned place preference (CPP) learning. Control experiments demonstrated that these lesions did not impair motor performance and did not alter the hedonic value of the sucrose and quinine. The number of dopamine neurons in the caudal part of the SNc positively correlated with the CPP scores of the 6-OHDA rats and negatively correlated with CPA scores of the SHAM rats. In addition, the CPA scores of the 6-OHDA rats positively correlated with the tissue content of striatal dopamine. Insomuch as reward-driven learning depends on an increase in dopamine release by nigral neurons, these findings show that this mechanism is functional even in rats with a partial lesion of the SNc. On the other hand, if aversion-driven learning depends on a reduction of extracellular dopamine in the striatum, the present study suggests that this mechanism is no longer functional after the partial SNc lesion.


Endoscopic full-thickness resection of early colorectal neoplasms using an endoscopic submucosal dissection knife: a retrospective multicenter study.
Background and study aims Endoscopic full-thickness resection allows resection of early gastrointestinal neoplasms not amenable to conventional endoscopic resection techniques, due to their location, presence of submucosal fibrosis, or suspected deep mural invasion. It is typically achieved using a dedicated over-the-scope device (full-thickness resection device or FTRD). The aim of our study was to evaluate the feasibility, safety, and clinical outcomes of endoscopic full-thickness resection using an endoscopic submucosal dissection (ESD) knife. Patients and methods Consecutive patients who underwent full-thickness endoscopic resection at six tertiary care centers from August 2010 to June 2017 were retrospectively included. We conducted a comparative analysis of patient characteristics, technical success, adverse events, and time to discharge between patients treated by a full-thickness resection using an ESD knife. Results Twenty-one procedures were performed using an ESD knife. En-bloc resection and R0 resection rates were 95.2 % and 65 %, respectively. Clinical symptoms of perforation occurred in 66.7 %. There was no need for surgery or additional endoscopic procedures. Conclusion Endoscopic full-thickness resection of early colorectal neoplasms using an ESD knife might be feasible and safe. It allows complete resection of lesions with no limitation in size. The technique may be preferable to an other-the-scope resection device in lesions larger than 20 mm, and to surgery in selected cases of low-risk T1 colorectal carcinomas, non-lifting adenomas, submucosal tumors, or technically challenging lesion locations.


Acetylator phenotyping: the effect of ethanol on the dapsone test.
In twelve healthy drug-free subjects (six slow acetylators), administration of alcohol (to achieve an ethanol concentration between 650 and 1180 mg 1(-1) ) did not significantly affect the ratio of monoacetyl dapsone (MADS) to dapsone (DDS) 3 h after oral dapsone (100 mg). We conclude that moderate acute ethanol consumption is unlikely to alter the acetylator phenotype measured by the dapsone test.


A mutation causes MuSK reduced sensitivity to agrin and congenital myasthenia.
Congenital myasthenic syndromes (CMSs) are a heterogeneous group of genetic disorders affecting neuromuscular transmission. The agrin/muscle-specific kinase (MuSK) pathway is critical for proper development and maintenance of the neuromuscular junction (NMJ). We report here an Iranian patient in whom CMS was diagnosed since he presented with congenital and fluctuating bilateral symmetric ptosis, upward gaze palsy and slowly progressive muscle weakness leading to loss of ambulation. Genetic analysis of the patient revealed a homozygous missense mutation c.2503A>G in the coding sequence of MUSK leading to the p.Met835Val substitution. The mutation was inherited from the two parents who were heterozygous according to the notion of consanguinity. Immunocytochemical and electron microscopy studies of biopsied deltoid muscle showed dramatic changes in pre- and post-synaptic elements of the NMJs. These changes induced a process of denervation/reinnervation in native NMJs and the formation, by an adaptive mechanism, of newly formed and ectopic NMJs. Aberrant axonal outgrowth, decreased nerve terminal ramification and nodal axonal sprouting were also noted. In vivo electroporation of the mutated MuSK in a mouse model showed disorganized NMJs and aberrant axonal growth reproducing a phenotype similar to that observed in the patient's biopsy specimen. In vitro experiments showed that the mutation alters agrin-dependent acetylcholine receptor aggregation, causes a constitutive activation of MuSK and a decrease in its agrin- and Dok-7-dependent phosphorylation.


Markers of bone metabolism during 14 days of bed rest in young and older men.
We aimed at comparing markers of bone metabolism during unloading in young and older men, and to assess countermeasure effectiveness. 16 older (60±2 years) and 8 younger men (23±3 years) underwent bed rest (BR) for 14 days. A subgroup of the Older performed cognitive training during BR and supplemented protein and potassium bicarbonate afterwards. Biochemical markers of bone and calcium/phosphate metabolism were assessed. At baseline urinary NTX and CTX were greater in younger than in older subjects (P<0.001), but increased during BR (P<0.001) by a similar amount (P>0.17). P1NP was greater in young than in older subjects (P<0.001) and decreased during BR in the Young (P<0.001). Sclerostin increased during BR across groups (P=0.016). No systematic effects of the countermeasure were observed. In men, older age did not affect control of bone metabolism, but bone turnover was reduced. During BR formation markers were reduced only in younger men whereas resorption markers increased to a comparable extent. Thus, we assume that older men are not at an elevated, and possibly even at a reduced risk to lose bone when immobilized.


Nature of DNA-bound fatty acids in Pseudomonas aurantiaca.
The existence of Pseudomonas aurantiaca DNA-bound fatty acids and lipids is presented in this work. The isolation of DNA was carried out by two different procedures, namely, phenol and detergent-based phenol isolation in order to prove the presence of DNA-bound lipids. The lipid content of DNA is expressed in terms of fatty acid profile. A high level of 16:0, 18:0 and 18:1 is characteristic for tightly bound DNA lipids. On the other hand, the fatty acids such as 14:1, iso14:0 and iso16:0 are found in trace amounts only in DNA lipid fraction, but these fatty acids are not found in the whole-cell lipids. Absolutely no 3-hydroxy fatty acids were found in DNA lipids. However, both C16 and C18 species represent the main fatty acids of whole-cell and DNA-bound lipids. The presence of DNA-bound lipids even under tough treatment of DNA allows to conclude that these lipids represent a special pool among cellular lipids.


Leishmania donovani phosphofructokinase. Gene characterization, biochemical properties and structure-modeling studies.
The characterization of the gene encoding Leishmania donovani phosphofructokinase (PFK) and the biochemical properties of the expressed enzyme are reported. L. donovani has a single PFK gene copy per haploid genome that encodes a polypeptide with a deduced molecular mass of 53 988 and a pI of 9.26. The predicted amino acid sequence contains a C-terminal tripeptide that conforms to an established signal for glycosome targeting. L. donovani PFK showed most sequence similarity to inorganic pyrophosphate (PPi)-dependent PFKs, despite being ATP-dependent. It thereby resembles PFKs from other Kinetoplastida such as Trypanosoma brucei, Trypanoplasma borreli (characterized in this study), and a PFK found in Entamoeba histolytica. It exhibited hyperbolic kinetics with respect to ATP whereas the binding of the other substrate, fructose 6-phosphate, showed slight positive cooperativity. PPi, even at high concentrations, did not have any effect. AMP acted as an activator of PFK, shifting its kinetics for fructose 6-phosphate from slightly sigmoid to hyperbolic, and increasing considerably the affinity for this substrate, whereas GDP did not have any effect. Modelling studies and site-directed mutagenesis were employed to shed light on the structural basis for the AMP effector specificity and on ATP/PPi specificity among PFKs.


Detection of human taeniases in Tibetan endemic areas, China.
Detection of taeniasis carriers of Taenia solium is essential for control of cysticercosis in humans and pigs. In the current study, we assessed the positive detection rate of a self-detection tool, stool microscopy with direct smear and coproPCR for taeniasis carriers in endemic Tibetan areas of northwest Sichuan. The self-detection tool through questioning about a history of proglottid expulsion within the previous one year showed an overall positive detection rate of more than 80% for Taenia saginata, T. solium and T. asiatica. The positive detection rate was similar for T. saginata and T. solium. In 132 taeniid tapeworm carriers, 68 (51·5%) were detected by microscopy and 92 (69·7%) were diagnosed by coproPCR. A combination of microscopy and coproPCR increased the positive detection rate to 77·3%. There remained 10 cases (7·6%) coproPCR negative but microscopy positive. Due to the high cost and complicated process, coproPCR is required for the identification of Taenia species only when necessary, though it had a significant higher positive detection rate than microscopy. Combined use of self-detection and stool microscopy are recommended in community-based mass screening for taeniases in this Tibetan area or in other situation-similar endemic regions.


Recounts of elderly deaths: endorsements for the Patient Self-Determination Act.
Circumstances in the last 3 days of life were examined for a sample of 1,227 elderly decedents in Fairfield County, Connecticut, in 1985. Interviews were with a surviving next-of-kin or a nonrelative about 3 months after the event of death. Most decedents were in a hospital or a nursing home the night before death (45% and 24%, respectively). In the days preceding death, about 34% of the decedents knew that death was impending and about 40% had difficulty recognizing family members. These and other findings support the need for elderly people to complete advance directives.


Retrograde semi-retrieval technique for combined stentriever plus aspiration thrombectomy in acute ischemic stroke.
The endovascular treatment of acute ischemic stroke has become a standard procedure. The combination of multiple neuroendovascular devices provides more possibilities for the improvement of the thrombectomy technique. We describe a modified retrieval technique using a distal intracranial catheter (DIC) for the semi-retrieval of stentriever during the thrombectomy procedure. The retrograde semi-retrieval technique involves completely unfolding the stent retriever by pulling a Navien catheter and the partial re-sheath of a retrievable stent forming a tapered configuration by pushing the Navien catheter, which results in the thrombi being embedded into the strut, securing the clot within the stent and there being a shorter distance for the clot to travel. This technique may lessen the occurrence of thrombus fragmentation and injury to the vessel wall. The retrograde semi-retrieval technique is an optional thrombectomy technique that may improve the efficiency of this procedure in the treatment of acute ischemic stroke.


[Production of transgenic mice from in vitro fertilized eggs cryopreserved by ultrarapid freezing].
In vitro fertilized mouse eggs (C57BL/6N), followed by ultrarapid freezing were used for production of transgenic mice by microinjection of the chicken beta-actin promoter-driven the firefly luciferase cDNA (beta act-Luc). Following micromanipulation, the survival rates of the cryopreserved eggs and of the fresh in vitro fertilized eggs (control) were 70.8% (131/185) and 71.9% (159/221), respectively. After transferring them into oviducts of psudopregnant recipients on Day 1, 13.6% (17/125) of the cryopreserved eggs developed to live offspring and 14.1% (21/149) of fresh eggs did so. It was confirmed by Southern blotting analysis that each two transgenic mice were produced from the cryopreserved eggs (12%, 2/17) and the fresh eggs (10%, 2/21). All of transgenic mice produced from both eggs showed the expression of the luciferase gene. These results indicate that the in vitro fertilized eggs cryopreserved by ultrarapid freezing, can be, easily and conveniently, used for generation of transgenic mice.


A novel method for isolation of histones from serum and its implications in therapeutics and prognosis of solid tumours.
Dysregulation in post-translational modifications of histones and their modifiers are now well-recognized as a hallmark of cancer and can be used as biomarkers and potential therapeutic targets for disease progression and prognosis. In most solid tumours, a biopsy is challenging, costly, painful or potentially risky for the patient. Therefore, non-invasive methods like 'liquid biopsy' for analysis of histone modifications and their modifiers if possible will be helpful in the better clinical management of cancer patients. Here, we have developed a cost-effective and time-efficient protocol for isolation of circulating histones from serum of solid tumor, HCC, called Dual Acid Extraction (DAE) protocol and have confirmed by mass spectrometry. Also, we measured the activity of HDACs and HATs in serum samples. The serum purified histones were profiled for changes in histone PTMs and have shown a comparable pattern of modifications like acetylation (H4K16Ac), methylation (H4K20Me3, H3K27Me3, H3K9Me3) and phosphorylation (γ-H2AX and H3S10P) to paired cancer tissues. Profiling for the histone PTM changes in various other organs of normal and tumor bearing animal suggests that the changes in the histone PTMs observed in the tumor serum is indeed due to changes in the tumor tissue only. Further, we demonstrate that the observed hypo-acetylation of histone H4 in tissue and serum samples of tumor bearing animals corroborated with the elevated HDAC activity in both samples compared to normal. Interestingly, human normal and tumor serum samples also showed elevated HDAC activity with no significant changes in HAT activity. Our study provides the first evidence in the context of histone PTMs and modifiers that liquid biopsy is a valuable predictive tool for monitoring disease progression. Importantly, with the advent of drugs that target specific enzymes involved in the epigenetic regulation of gene expression, liquid biopsy-based 'real time' monitoring will be useful for subgrouping of the patients for epi-drug treatment, predicting response to therapy, early relapse and prognosis.


Visible-Light-Induced Desaturative β-Alkoxyoxalylation of N-Aryl Cyclic Amines with Difluoromethyl Bromides and H2O Via a Triple Cleavage Process.
A visible-light-driven desaturative β-alkoxyoxalyation of N-aryl cyclic amines with difluoromethyl bromides and H2O has been reported. This tandem reaction is triggered by homolysis of the C-Br bond to produce the difuoroalkyl radical, which undergoes the subsequent defluorinated β-alkoxyoxalylation cascades to afford a wide range of β-ketoester/ketoamides substituted enamines. The prominent feature of this reaction contains photocatalyst-free, transition-metal free, and mild conditions. The 18O labeling experiment disclosed that H2O is the oxygen source of the carbonyl unit.


Tissue loss, early primary graft occlusion, female gender, and a prohibitive failure rate of secondary infrainguinal arterial reconstruction.
This study tested the hypothesis that a subset of secondary infrainguinal arterial reconstructions show prohibitive failure rates. Records of 79 consecutive patients, 44 men and 35 women, with a mean age of 60 years, who underwent secondary infrainguinal bypass from 1992 to 2000 at the University of Michigan Hospital, were reviewed. Data were analyzed with life-table analysis, logistic regression, and descriptive statistics. Secondary infrainguinal reconstructions were performed in patients who had undergone earlier ipsilateral bypasses once (n = 35) or twice (n = 44). Among the prior procedures, 68% (n = 54) were done at an institution other than the authors'. Comorbidities included coronary artery disease (72%), tobacco use (77%), and diabetes mellitus (34%), but no patient had hemodialysis-dependent renal failure. Disabling claudication, with average ankle brachial index of 0.48, had been the indication for the primary operation in 77% of cases. Femoral-popliteal bypass was the primary procedure in 67%, with a prosthetic graft used in 62%. The mean patency duration of these earlier bypasses was 25 months. The indication for the final bypass was rest pain or tissue loss in 51% of patients, with an average ankle brachial index of 0.37. The most common procedure was a femoral-distal bypass with autologous vein (63%). Mean patency duration of the secondary bypasses was 30 months. Graft failure within 30 days of operation occurred in 22 patients (28%), and amputation was necessitated in 86% of these patients. The presence of rest pain or tissue loss, when accompanied with a history of early prior graft thrombosis in female patients, correlated with worse mean patency rates, recurrent graft failure (P </=.05), and a 94% amputation rate. Men in a similar setting incurred a 57% amputation rate. No association of final patency existed with regard to age, number of prior bypasses, conduit types, tobacco use, or diabetes. Secondary infrainguinal bypasses are associated with an increased rate of graft failure and significant limb loss, particularly in those with a history of rest pain or tissue loss, female gender, and early prior graft failure. More appropriate initial operations in carefully selected patients and aggressive postoperative graft surveillance is speculated to improve these outcomes.


[The concentration of viruses in water using the tangential flow ultrafiltration. Recovery effectiveness in experimental conditions].
Poliovirus 1 concentration tests were carried out in artificially contaminated water by tangential flow ultrafiltration with Polisulfone filters 100000 MWCO. The tests were performed in 1 and in 20 liters of waters. The filters were conditioned and eluted respectively with Beef extract 3% and with glicina 1% at pH 7 and pH 9. The recovery mean using Beef extract resulted properly good, about the 83% and comparable to percentages we obtained in previous works with filters in cellulose nitrate and Virosorb filters. The viral recovery was low using the glicina for conditioning and eluting the filters.


Protein kinase Cα downregulation via siRNA-PKCα released from foldable capsular vitreous body in cultured human retinal pigment epithelium cells.
We previously found that downregulation of protein kinase Cα (PKCα) can inhibit retinal pigment epithelium (RPE) cell proliferation involved in the development of proliferative vitreoretinopathy (PVR). In this study, we tested whether PKCα could be downregulated via small interfering RNA (siRNA)-PKCα released from foldable capsular vitreous body (FCVB) in cultured human RPE cells. SiRNA-PKCα content, determined by ultraviolet (UV) spectrophotometer, was released from FCVB containing 200, 300, 400, 500, and 600 nm siRNA-PKCα in a time-dependent manner from 1 to 96 hours and a dose-dependent manner at five concentrations. The content (y) had a good linear relationship with time (x), especially in the 600 nm siRNA-PKCα group (y = 16.214x, R(2) = 0.9809). After treatment with siRNA-PKCα released from FCVBs, the PKCα was significantly decreased by RT-PCR, Western blot, and immunofluorescence analysis in RPE cells. These results indicate that PKCα was significantly downregulated by siRNA-PKCα released from FCVB in human RPE cells and provide us with a new avenue to prevent PVR.


Homeostatic Response of Mouse renin Gene Transcription in a Hypertensive Environment Is Mediated by a Novel 5' Enhancer.
The renin-angiotensin system plays an essential role in blood pressure homeostasis. Because renin activity is reflected as a blood pressure phenotype, its gene expression in the kidney is tightly regulated by a feedback mechanism; i.e., renin gene transcription is suppressed in a hypertensive state. To address the molecular mechanisms controlling hypertension-responsive mouse renin (mRen) gene regulation, we deleted either 5' (17-kb) or 3' (78-kb) regions of the endogenous mRen gene and placed the animals in a hypertensive environment. While the mRen gene bearing the 3' deletion was appropriately downregulated, the one bearing the 5' deletion lost this hypertension responsiveness. Because the 17-kb sequence exhibited enhancer activity in vivo and in vitro, we narrowed down the enhancer to a 2.3-kb core using luciferase assays in As4.1 cells. When this 2.3-kb sequence was removed from the endogenous mRen gene in the mouse, its basal expression was dramatically reduced, and the hypertension responsiveness was significantly attenuated. Furthermore, we demonstrated that the angiotensin II signal played an important role in mRen gene suppression. We propose that in a hypertensive environment, the activity of this novel enhancer is attenuated, and, as a consequence, mRen gene transcription is suppressed to maintain blood pressure.


[Clinical and ergometric studies on the effectiveness of lidoflazine in the treatment of chronic ischemic heart disease].
During 6 months lidoflazine was applied ambulatorily in a dosage of 240 mg/a day orally in 21 patients after finished infarction. After 2 to 3 weeks one patient each was excluded due to incompatibility or reinfarction, respectively. In the remaining 19 patients consumption of nitrangin, mechanocardiogram, ECG and blood pressure were controlled in regular intervals during and after ergometric load as well as clinico-chemical examinations performed. The consumption of nitrangin clearly decreased in the course of the time of observation. The tolerance ofthe medicament was good. At the end of the treatment the unchanging load was tolerated with lower pulse rate, slightly decreased blood pressure and shortened period of isometric contraciton and period of the increase of blood pressure. The present results were discussed compared with literature.


Button battery as a foreign body in the nasal cavities. Special aspects.
Alkaline batteries as foreign bodies in the nasal cavities are dangerous because they can cause liquefaction necrosis with subsequent severe local tissue destruction. Batteries found in the nasal cavities should be removed immediately to prevent sequelae such as septal perforations or nasal meatus stenosis. Due to the common use of these batteries (e.g. watches, electronic toys and games, calculators) physicians and the general public should be more aware of this type of foreign body and the peculiarities in their management. We present five cases of button battery foreign bodies in the nasal cavities and review 12 cases described in the literature and discuss the special aspects of these foreign bodies.


Business of dialysis and the role of the medical director.
Since the inception of the Medicare End Stage Renal Disease Program in 1972, the medical director has been an important leader in the dialysis unit. The initial duties of the medical director were focused on quality and safety but were gradually expanded over the decades to include the development and oversight of protocols to manage metabolic bone disease and anemia. As the total cost of ESRD care has escalated, there have been progressive attempts to control costs through additional bundling and the creation of alternative payment schemes. While we await the financial and clinical outcomes of these initiatives, the medical director's role continues to expand in scope and now includes an enhanced role for not only clinical outcomes but financial outcomes as well.


Limitations of using dosimeters in impulse noise environments.
The National Institute for Occupational Safety and Health (NIOSH) investigated the capabilities of noise dosimeters to measure personal exposure to impulse noise. The two leading types of commercially available dosimeters were evaluated in terms of their ability to measure and integrate impulses generated from gunfire during live-fire exercises at a law enforcement indoor firing range. Sound measurements were conducted throughout the firing range using dosimeters, sound level meters, and a measurement configuration that consisted of a quarter-inch microphone and a digital audiotape recorder to capture the impulse waveforms. Personal dosimetry was conducted on eight shooters, an observer, and the range master. Peak levels from gunfire reached 163 decibels (dB), exceeding the nominal input limit of the dosimeters. The dosimeters "clipped" the impulses by acting as if the gunfire had a maximum level of 146 dB. In other cases, however, peak levels (e.g., 108 dB) were below the dosimeter input limits, but the dosimeters still showed a peak level of 146 dB. Although NIOSH recommends that sound levels from 80 to 140 dB (A-weighted) be integrated in the calculation of dose and the time-weighted average, our present data suggest this criterion may be inadequate. These results showed that some instruments are incapable of providing accurate measures of impulse sounds because of their electroacoustic limitations.


Quantitative analysis of triphenylboron in environmental water samples by liquid chromatography/mass spectrometry.
Liquid chromatography/mass spectrometry (LC/MS) has been applied to the analysis of triphenylboron, which has been produced as a substitute for organotin compounds, in water. Although commercial triphenylboron compounds are produced as pyridinyl complexes, the chemical form in water is supposed to be mainly triphenylboron after liberating pyridine. The triphenylborons were extracted from water with an Empore C18 extraction disk under acidic condition, and the extracts were introduced directly into a liquid chromatograph-mass spectrometer equipped with a negative ion electrospray ionization interface. Identification of the compounds was performed with specific ions produced from the triphenylboron, and a quantitative analysis was carried out using the peak areas. The average recoveries from distilled water, seawater and river water at 0.30 ng/ml were 92.3, 100 and 85.3%, respectively. A detection limit of 0.023 ng/ml for triphenylboron was achieved.


Robust and adhesive hydrogels from cross-linked poly(ethylene glycol) and silicate for biomedical use.
A systematic approach to develop robust and adhesive hydrogels by photopolymerizing poly(ethylene glycol) (PEG)-diacrylate and methoxy-PEG-acrylate in the presence of charged silicate nanoparticles (Laponite) is presented. PEG-diacrylate and silicate are used for covalent and physical cross-linking, thus providing the hydrogel with mechanical and adhesive strengths. Methoxy-PEG-acrylate is used as a softening agent. The resulting hydrogels can be extensively elongated and the hydrogels readily adhere to tissue even in the elongated state. These hydrogels may aid the development of adhesive tissue engineering matrixes, wound dressings, sealants, and the adhesive components of biomedical devices.


Reversed left internal mammary artery graft for coronary bypass. Evaluation of function with digital subtraction angiography and radionuclide imaging.
Reversed left internal mammary artery grafting with retrograde flow to the left anterior descending coronary branch was used in five of 500 consecutive bypass operations. The indications were significant stenosis in the left subclavian artery (3 patients) or the proximal left internal mammary artery (1) and proximal damage to the left internal mammary artery during dissection from the thoracic wall (1). The postoperative clinical course was smooth in all five patients, with no evidence of myocardial ischemia. In follow-up averaging 14 months four patients were asymptomatic. The reversed internal mammary artery graft was visualized with digital subtraction angiography in four cases. Radionuclide imaging during exercise confirmed graft patency in all but the symptomatic patient, who was found to have an area of reversible ischemia anteriorly in the left ventricle.


Comparative analysis of cholinergic innervation in the dorsal hippocampus of adult mouse and rat: a quantitative immunocytochemical study.
To obtain quantitative data on the distribution of the acetylcholine (ACh) innervation in the dorsal hippocampus of adult mouse (C57/B6) and rat (Sprague-Dawley), a semicomputerized method was used to measure the length of immunostained axons in hippocampal sections processed for light microscopic immunocytochemistry with a highly sensitive antibody against choline acetyltransferase (ChAT). The results could be expressed in density of axons (meters per mm3) for the different layers and regions of dorsal hippocampus (CA1, CA3, DG), and also in density of axon varicosities (millions per mm3), after having determined the average number of varicosities per unit length of ChAT-immunostained axon (4 varicosities/10 microm). In mouse, the mean regional densities of ACh innervation were thus measured at 13.9, 16.1, and 15.8 m of axons, for 5.6, 6.4, and 6.3 million varicosities per mm3 of tissue, in CA1, CA3, and DG, respectively. The values were comparable in rat, except for CA1, in which the densities were lower than in mouse by 40% in the stratum lacunosum, and 20% in the stratum radiatum. Otherwise, the laminar patterns of innervation were similar in the two species, the highest densities being found in the stratum lacunosum moleculare of CA3, pyramidale of both CA1 and CA3, and moleculare of DG. These quantitative data will be of particular interest to evaluate changes in mutant mice, or mice and rats subjected to experimental conditions affecting the cholinergic phenotype.


Protein and energy requirements of pre-weaned West African dwarf goats fed soyabean diet as a replacement for milk in a tropical environment.
Twenty-one early-weaned West African dwarf goats weighing between 1.0 and 1.5 kg at birth were used to assess the protein and energy requirement of pre-weaned West African Dwarf (WAD) goats fed soyabean diet. Three isonitrogenous diets (24%) were prepared such that dried whole-milk protein was replaced by corn starch and soyabean concentrate protein at 0.0%, 25.0% and 50.0% levels such that a 14.5% total solid solution was obtained for each diet. Results indicated that a daily digestible energy (expressed as kcal/day/W0.75 kg) intake of 58.2, 63.7, 98.5 and 114.6 kcal was required for maintenance, while a corresponding value of 7.37, 4.50, 2.18 and 1.91 kcal was required per day per gram live weight gain by the kids at 4, 6, 9 and 13weeks old, respectively. Similarly, a digestible crude protein (DCP) intake of 3.59 g/day/W0.75 kg) appeared to be adequate for maintenance of the kids between 0 and 13 weeks, while 0.34 g/day/W0.75 kg of DCP intake was required per day per gram live weight.


The Sustainable Development Goals cannot be achieved without improving maternal and child nutrition.
Poor nutrition is a global pandemic with social, economic, and environmental causes and consequences. Of the 17 Sustainable Development Goals (SDGs), only SDG2 explicitly mentions nutrition. Turning the aspirations of the SDGs into reality will require recognition that good nutrition ensured through sustainable agriculture, is simultaneously an absolutely fundamental input and output. Because all of the other SDGs are directly or indirectly linked to improving nutrition, funding to improve nutrition is essential to success for many SDGs. Greater focus on cooperation across disciplines to advance the science of program delivery and to understand the full contribution of nutrition to many desirable outcomes as part of development are surely the ways forward. Missing today's opportunities to advance thinking and program implementation for more effectively improving nutrition for all, especially for women and children, will lead to a wider failure to meet the SDGs.


Radium-223 in the therapeutic sequence of metastatic castration-resistant prostate cancer.
Radium-223 is an □ -particle transmitter with specific action on bone metastases. The Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) study showed that radium-223 extended overall survival and delayed the onset of bone events in patients with symptomatic castration-resistant prostate cancer with bone metastases (mCRPC) and without visceral metastases, with a good safety profile. To review the new scientific evidence on radium-223 based on prespecified and post-hoc analyses of the ALSYMPCA study and on early-access programs after the publication of the ALSYMPCA study, thereby providing new data on the management of patients with mCRPC. We searched for evidence on PubMed and in the abstracts of international urology and oncology congresses, as well as ongoing clinical trials (ClinicalTrials.gov). The results of the reviewed studies offer promising results that will broaden the therapeutic benefits of radium-223 to patients with mild symptoms and those with no symptoms. The results also provide preliminary evidence on the benefit of radium-223 treatment after the failure of docetaxel, enzalutamide or abiraterone or the combination of radium-223 with these agents or other therapeutic agents such as bone-targeted agents and immunotherapy. Radium-223 can be a treatment option for patients with mild symptoms and can provide a therapeutic benefit after failure of currently available treatments or in combination with these treatments. This evidence should be corroborated in clinical trials before being added to clinical practice.


Enhanced Systemic Anti-Angiogenic siVEGF Delivery Using PEGylated Oligo-d-arginine.
Angiogenesis mainly mediated by upregulation of vascular endothelial growth factor (VEGF) provides a hallmark of rapidly proliferating tumor cells and an essential component of the tumor growth and microenvironment, making it a targetable process for antitumor therapy. RNA interference (RNAi) provides a very effective tool for developing antitumor therapies; however, its application to date has been hampered due to the lack of efficient small interfering RNA (siRNA) delivery systems in vivo. Here, we report a polymeric gene carrier system based on PEGylation of a cationic cysteine-ended 9-mer arginine oligopeptide (CR9C), which provides effective siRNA systemic delivery and specifically suppresses VEGF (siVEGF). The PEG500-CR9C/siVEGF oligopeptoplex provided improved blood circulation, enhanced protection from serum proteases, reduced uptake in the liver and kidneys, enhanced tumor targeting, and down-regulated intratumoral VEGF level, which comprehensively resulted in improved antitumor efficacy without significant toxicity in vivo. PEG500-CR9C has a great potential for safe and efficient siRNA delivery with diverse applications.


Catecholamines and cognition after traumatic brain injury.
Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person's catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain 'networks' that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner.


Surgical and short-term outcomes in robotic and laparoscopic distal gastrectomy for gastric cancer with enhanced recovery after surgery protocol: A propensity score matching analysis.
This study aims to evaluate the short-term surgical outcomes of laparoscopy-assisted distal gastrectomy (LADG) and robot-assisted distal gastrectomy (RADG) for gastric cancer (GC) with enhanced recovery after surgery (ERAS) protocols. We reviewed the medical records of 202 patients undergoing radical distal gastrectomy; among them, 67 cases were assisted through RADG, while 135 cases were assisted through LADG along with ERAS. We retrospectively collected the medical records in succession from a database (January 2016-March 2019). We adopted propensity score matching to compare surgical and short-term outcomes of both groups. After the successful examination of 134 cases, including 67 receiving RADG and 67 undergoing LADG, the operative times were noted as 5.78 ± 0.96 h for the RADG group and 4.47 ± 1.01 h for the LADG group (P < 0.001). The blood loss was noted as 125.52 ± 101.18 ml in the RADG group and 164.93 ± 109.32 ml in the LADG group (P < 0.05). The shorter time to first flatus was 38.82 ± 10.56 h in the RADG group and 42.88 ± 11.25 h in the LADG group (P < 0.05). In contrast, shorter days of postoperative hospital stay were 5.94 ± 1.89 days in the RADG group and 6.64 ± 1.92 days in the LADG group (P < 0.05). Also, the RADG group (84483.03 ± 9487.37) was much more costly than the LADG group (65258.13 ± 8928.33) (P < 0.001). The postoperative overall complication rates, numbers of dissected lymph nodes, visual analogue scale (VAS), and time to start a liquid diet for the RADG group and the LADG group were similar. In this research, we concluded that RADG provides surgical benefits and short-term outcomes compared to LADG for GC with ERAS.


Glucose/insulin infusions in the treatment of subarachnoid haemorrhage: a feasibility study.
Hyperglycaemia following subarachnoid haemorrhage (SAH) is well recognized and has been shown to be associated with a worse prognosis. It is currently unclear whether this is a secondary phenomenon reflecting the magnitude of the stress response or whether it contributes directly to the pathophysiological disturbances within the brain. There is significant experimental work on ischaemic stroke to suggest that hyperglycaemia increases infarct volume. The authors propose that controlling blood glucose following SAH is safe and that it might improve outcome. All patients admitted with SAH were treated with insulin to control plasma glucose with a target range of 5.0-7.0 mmol/l. Episodes of hypoglycaemia were recorded. Outcome was assessed at 3 months using the Glasgow Outcome Scale. Fifty-five patients were recruited. 32/3389 (0.94%) of glucose readings fell below 3.5 mmol/l. All were treated with i.v. glucose without evidence of clinical deterioration. Insulin treatment for hyperglycaemia following SAH is feasible and safe. A randomised trial is required to assess any effect on outcome.


[Variations in rectal capacity and compliance after abdominal rectopexy].
The aim of this study was to attempt to gain insight in to the pathophysiologic characteristics of rectal prolapse by evaluating rectal compliance in patients with complete or incomplete rectal prolapse, before and after rectopexy. 21 subjects with complete rectal prolapse and 10 subjects with internal procidentia of rectum were treated with one of two abdominal rectopexies, according to Wells or according to a modified Ripstein's technique. For comparison, measurements were also carried out in 17 age and sex control subjects who had no bowel disturbances or anal symptoms. On distension with 40 cm H2O rectal volume amounted to 218 (175-255) ml for controls, 225 (178-256) ml for complete prolapses and 200 (125-225) ml for invaginations. Compliance amounted respectively to 9.5 (5-11,4), 8.5 (5-12,6), 7.5 (4-10,6) ml/cm H2O in the pressure interval 0-10 cm H2O with a decrease in compliance at higher pressure intervals. There was no correlation between rectal volume and compliance and gas or faecal incontinence, evacuation difficulties, feeling of blockade upon defecation and constipation. The effect of rectopexy has been separately evaluated according to the diagnosis. In complete prolapse significant changes of rectal capacity were observed for lower distending pressures (from 10 to 30), but not for higher (40-50). The compliance was significantly different for even lower distending pressures (0-10 cm H2O). In internal rectal procidentia rectopexy did not significantly changed capacity compliance. This work confirms the observations that the rectal compliance in rectal prolapse, complete and incomplete, do not differ from healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS)


Lung Consolidation Locations for Optimal Lung Ultrasound Scanning in Diagnosing Pediatric Pneumonia.
Lung ultrasound (US) has been shown to be accurate in diagnosing pneumonia in children. Evidence to inform an optimal scanning protocol is limited. Our objective is to describe an optimized lung US scanning protocol for pediatric pneumonia based on the anatomic location and transducer orientation. We performed a secondary analysis of data and images from 2 prospective lung US studies for the emergency department diagnosis of pneumonia in children (0-21 years). The anatomic location of each lung consolidation was mapped to 1 or more of 6 anatomic zones on the chest, noting the transducer orientation (sagittal or transverse) in which it was identified. Seventy-eight patients were included; 51% were female, and the median age was 3 years (interquartile range, 1-7 years). Overall, 46.5% (95% CI confidence interval [CI], 37.9%-55.1%) of lung zones with a visible consolidation were posterior; 31.0% (95% CI, 23.0%-39.0%) were anterior; and 22.5% (95% CI, 15.3%-29.1%) were axillary. A total of 54.3% (95% CI, 45.7%-62.9%) of affected lung zones were in the lower lung compared to the upper lung (8.5%; 95% CI, 3.7%-13.3%) and middle lung (37.2%; 95% CI, 28.9%-45.5%). Most lung consolidations were seen in both transducer orientations: 96.2% (95% CI, 92.0%-100%) of patients had a visible consolidation on the transverse view, whereas 85.9% (95% CI, 78.2%-93.6% had a consolidation on the sagittal view. Efficient lung US scanning may start with the posterior, anterior, and then lateral chest zones if no pneumonia is identified. A transverse transducer orientation detects more pneumonia than a sagittal orientation. Omission of either orientation or any lung zone may miss pneumonia.


Extreme testing of undiluted e-cigarette aerosol in vitro using an Ames air-agar-interface technique.
There is a growing consensus that e-cigarettes hold the potential for reducing the harm associated with cigarette smoking. Recently published studies have reported in vitro testing of e-cigarettes, demonstrating reduced toxicological and biological effects. Few studies however have reported the use of e-cigarettes under extreme testing conditions. To assess the full mutagenic potential of a commercially available electronic-cigarette (Vype ePen), this study investigated the delivery of aerosol under extreme conditions, using a scaled-down 35 mm plate Ames bacterial reverse mutagenicity assay. S. typhimurium strains TA98, TA100, TA97, TA104 and E. coli WP2 uvrA pKM101 with or without metabolic activation (S9), were employed. Using a modified Vitrocell VC 10 exposure system 0, 180, 360, 540, 720 or 900 puffs of undiluted e-cigarette aerosol was generated and delivered to bacterial cultures aligned to reported human consumption data. The results demonstrate that no mutagenic activity was observed in any strain under any test condition even when exposed to 900 puffs of undiluted e-cigarette aerosols +/- S9. Positive control responses were observed in all strains +/- S9. Nicotine assessments demonstrated an increased and consistent aerosol delivery, with calculated maximum doses of ∼1 mg/mL delivery of nicotine. These data demonstrate the validity of this unique testing approach and adds further information to the growing weight of evidence that e-cigarettes offer substantially reduced exposure when compared to conventional cigarette smoke. For future in vitro assessments of next generation tobacco and nicotine products, the generation, delivery and testing of undiluted aerosols can now be considered.


Distribution of HIV-1 subtypes circulating in Slovakia (2009-2012).
Slovakia is one of the European countries reporting a low prevalence of human immunodeficiency virus 1 (HIV-1) infection. The HIV-1 subtype B was previously the most prevalent in Slovakia and mostly associated with men having sex with men (MSM) (Habekova et al., 2010). The aim of this study was to determine the distribution of individual HIV-1 subtypes among the virus-positive individuals diagnosed in 2009-2012 in Slovakia and to compare these data with those from 2004-2008. The HIV-1 subtype B exhibited the highest prevalence (86.1%) and was mostly associated with MSM as stated before. HIV-1 non-B subtypes were found in 13.9% of patients, led by CRF01_AE (6.3%) and followed by subtype C (2.8%), F1 (1.4%), CRF03_AB (1.4%), G (0.7%), CRF02_AG (0.7%), and CRF12_BF (0.7%). The incidence of non-B subtypes varied in 2009-2012, showing a maximum in 2012. MSM represented the main risk group for total HIV-1 (68.1%) as well as B subtype (63.9%) infections in Slovakia. In contrast, the heterosexual contact represented the main route of HIV-1 acquisition of the non-B subtype virus infection. Together with the increase in the number of patients infected with the viruses of non-B subtype also other changes were observed: infections with the viruses of non-B subtype became more common among MSM and not so strongly associated with heterosexual contact. All these findings may help to design the right strategy for retaining of HIV epidemic in Slovakia at low level.


Vaginal Lactobacillus Inhibits HIV-1 Replication in Human Tissues Ex Vivo.
Lactobacillus species, which dominate vaginal microbiota of healthy reproductive-age women, lower the risks of sexually transmitted infections, including the risk of human immunodeficiency virus (HIV) acquisition. The exact mechanisms of this protection remain to be understood. Here, we investigated these mechanisms in the context of human cervico-vaginal and lymphoid tissues ex vivo. We found that all six Lactobacillus strains tested in these systems significantly suppressed HIV type-1 (HIV-1) infection. We identified at least three factors that mediated this suppression: (i) Acidification of the medium. The pH of the undiluted medium conditioned by lactobacilli was between 3.8 and 4.6. Acidification of the culture medium with hydrochloric acid (HCl) to this pH in control experiments was sufficient to abrogate HIV-1 replication. However, the pH of the Lactobacillus-conditioned medium (CM) diluted fivefold, which reached ∼6.9, was also suppressive for HIV-1 infection, while in control experiments HIV-1 infection was not abrogated when the pH of the medium was brought to 6.9 through the use of HCl. This suggested the existence of other factors responsible for HIV-1 inhibition by lactobacilli. (ii) Lactic acid. There was a correlation between the concentration of lactic acid in the Lactobacillus-CM and its ability to suppress HIV-1 infection in human tissues ex vivo. Addition of lactic acid isomers D and L to tissue culture medium at the concentration that corresponded to their amount released by lactobacilli resulted in HIV-1 inhibition. Isomer L was produced in higher quantities than isomer D and was mostly responsible for HIV-1 inhibition. These results indicate that lactic acid, in particular its L-isomer, inhibits HIV-1 independently of lowering of the pH. (iii) Virucidal effect. Incubation of HIV-1 in Lactobacillus-CM significantly suppressed viral infectivity for human tissues ex vivo. Finally, lactobacilli adsorb HIV-1, serving as a sink decreasing the number of free virions. In summary, we found that lactobacilli inhibit HIV-1 replication in human tissue ex vivo by multiple mechanisms. Further studies are needed to evaluate the potential of altering the spectra of vaginal microbiota as an effective strategy to enhance vaginal health. Human tissues ex vivo may serve as a test system for these strategies.


Virulence of the Shiga toxin type 2-expressing Escherichia coli O104:H4 German outbreak isolate in two animal models.
In May 2011, a large food-borne outbreak was traced to an unusual O104:H4 enteroaggregative Escherichia coli (EAEC) strain that produced Shiga toxin (Stx) type 2 (Stx2). We developed a mouse model to study the pathogenesis and treatment for this strain and examined the virulence of the isolate for Dutch belted rabbits. O104:H4 strain C227-11 was gavaged into C57BL/6 mice at 10(9) to 10(11) CFU/animal. The infected animals were then given water with ampicillin (Amp; 5 g/liter) ad libitum. The C227-11-infected, Amp-treated C57BL/6 mice exhibited both morbidity and mortality. Kidneys from mice infected with C227-11 showed acute tubular necrosis, a finding seen in mice infected with typical Stx-producing E. coli. We provided anti-Stx2 antibody after infection and found that all of the antibody-treated mice gained more weight than untreated mice and, in another study, that all of the antibody-treated animals lived, whereas 3/8 phosphate-buffered saline-treated mice died. We further compared the pathogenesis of C227-11 with that of an Stx-negative (Stx(-)) O104:H4 isolate, C734-09, and an Stx2(-) phage-cured derivative of C227-11. Whereas C227-11-infected animals lost weight or gained less weight over the course of infection and died, mice infected with either of the Stx(-) isolates did not lose weight and only one mouse died. When the Stx-positive (Stx(+)) and Stx2(-) O104:H4 strains were compared in rabbits, greater morbidity and mortality were observed in rabbits infected with the Stx2(+) isolates than the Stx2(-) isolates. In conclusion, we describe two animal models for EAEC pathogenesis, and these studies show that Stx2 is responsible for most of the virulence observed in C227-11-infected mice and rabbits.


Sleep and respiration under acute hypobaric hypoxia.
The purpose of this study was to elucidate the effects of acute hypobaric hypoxia on nocturnal sleep architecture and respiratory responses in a hypobaric simulator. Five healthy young males (19-23 years old) were recruited to sleep for 8 h at sea level and at simulated altitudes of 1,500, 3,000, and 4,000 m in the simulator (61.2 m3, 20 degrees C, and 60% RH). Each experimental run was separated by at least 3 d. Standard polysomnograph, respiration, and arterial oxygen saturation (SaO2) during sleep were observed. 1) SaO2 decreased significantly with increasing altitude. At 4,000 m, SaO2 showed its lowest value during 1 to 3 h after sleep onset. 2) Sleep architecture below 3,000 m showed almost the same pattern. However, reduction in REM sleep and increased wakefulness were observed at 4,000 m, though such sleep disturbance was not observed in the first one-third of the night spent in bed. 3) Periodic breathing (PB) with apnea and/or hypopnea developed in all subjects above 3,000 m. PB tended to appear in light sleep, though sleep was not always disturbed by PB. It might be concluded that there was no sleep disturbance up to 3,000 m altitude. Nocturnal sleep at 4,000 m, however, was disturbed after a few hours from sleep onset by severe hypoxemia induced by multiplicative effects of hypoxia and hypoventilation during deep sleep. At high altitude, PB seems to not induce arousals consistently, which was different from sleep apnea syndrome at sea level.


The standard problem.
This article proposes a framework to support the scientific research of standards so that they can be better measured, evaluated, and designed. Beginning with the notion of common models, the framework describes the general standard problem-the seeming impossibility of creating a singular, persistent, and definitive standard which is not subject to change over time in an open system. The standard problem arises from uncertainty driven by variations in operating context, standard quality, differences in implementation, and drift over time. As a result, fitting work using conformance services is needed to repair these gaps between a standard and what is required for real-world use. To guide standards design and repair, a framework for measuring performance in context is suggested, based on signal detection theory and technomarkers. Based on the type of common model in operation, different conformance strategies are identified: (1) Universal conformance (all agents access the same standard); (2) Mediated conformance (an interoperability layer supports heterogeneous agents); and (3) Localized conformance (autonomous adaptive agents manage their own needs). Conformance methods include incremental design, modular design, adaptors, and creating interactive and adaptive agents. Machine learning should have a major role in adaptive fitting. Research to guide the choice and design of conformance services may focus on the stability and homogeneity of shared tasks, and whether common models are shared ahead of time or adjusted at task time. This analysis conceptually decouples interoperability and standardization. While standards facilitate interoperability, interoperability is achievable without standardization.


Order-of-mutation effects on cancer progression: models for myeloproliferative neoplasm.
In some patients with myeloproliferative neoplasms (MPN), two genetic mutations are often found, JAK2 V617F and one in the TET2 gene. Whether or not one mutation is present will influence how the other subsequent mutation affects the regulation of gene expression. When both mutations are present, the order of their occurrence has been shown to influence disease progression and prognosis. We propose a nonlinear ordinary differential equation (ODE), Moran process, and Markov chain models to explain the non-additive and non-commutative mutation effects on recent clinical observations of gene expression patterns, proportions of cells with different mutations, and ages at diagnosis of MPN. These observations consistently shape our modeling framework. Our key proposal is that bistability in gene expression provides a natural explanation for many observed order-of-mutation effects. We also propose potential experimental measurements that can be used to confirm or refute predictions of our models.


Binuclear wirelike dimers based on ruthenium(II)-bipyridine units linked by ethynylene-oligothiophene-ethynylene bridges.
The syntheses, structural characteristics, electrochemical behavior, ground-state spectra, photophysical properties, and transient absorption (TA) spectra in CH(3)CN solvent are reported for binuclear [(bpy)(2)Ru(bpy-E(T)(n)()E-bpy)Ru(bpy)(2)](4+) complexes, Ru(bpyT(n)bpy)Ru, where the Ru-based units are connected by alternating 3,4-dibutylthiophene (DBT')/thiophene (T') fragments linked via ethynyl groups (E) to bpy ligands at the 5-position (bpy is 2,2'-bipyridine). The ligand bpyT(3)bpy represents a module containing DBT'/T'/DBT' subunits, and bpyT(5)bpy accounts for a DBT'/T'/DBT'/T'/DBT' pattern. The syntheses and electrochemical and spectroscopic (emission and TA) properties in CH(2)Cl(2) solvent of the bpyT(n)()bpy ligands are likewise reported. The behavior of the Ru(bpyT(n)bpy)Ru dimers has been compared to that of the bpyT(n)bpy ligands and to that of a related mononuclear complex, [(bpy)(2)Ru(bpy-E-DBT')](2+), Ru(bpyDBT'). For the dimeric complexes, the electrochemical results show that the first reduction step takes place at the bpy ligand(s) bearing an ethynylene group, the first oxidation step is thiophene-centered, and further oxidation involves the metal centers, which are only weakly interacting. The photophysical and TA results for the Ru(bpyT(n)bpy)Ru dimers account for the presence of low-lying oligothiophene-centered (3)pi,pi levels, while higher-lying metal-ligand charge transfer ((3)MLCT) levels are thermally accessible only for the case of Ru(bpyT(3)bpy)Ru; the possible role of charge separation (CS) levels (from oxidation at the thiophene bridge and reduction at one of the coordinated bpy's) is also discussed.


Influence of IL-10 on murine CFU-pre-B formation.
We have examined the ability of interleukin-10 (IL-10) to influence murine B cell development in vitro and in vivo. In vitro treatment of young adult mouse bone marrow cells with 0.5 to 10 ng/ml human IL-10 (hIL-10) produced a significant enhancement of IL-7-mediated colony-forming unit-pre-B (CFU-pre-B) formation, while IL-10 concentrations > 10 ng/ml had no net effect. IL-10 by itself was unable to stimulate pre-B cell colony formation, even at optimal concentrations. The increase in CFU-pre-B produced by IL-10 was specifically blocked by anti-hIL-10 antibody, but not by anti-stem cell factor (SCF) antibody, and was observed with both unfractionated and purified B220+ surface immunoglobulin (sIg-) bone marrow cells. CFU-pre-B from the IL-10 treatment group contained a higher percentage of CD43+B220+ blast-like cells than colonies exposed to IL-7 only. In vivo administration of 0.1 microgram hIL-10 per day to mice treated with a single sublethal dose of cyclophosphamide (CY) resulted in a dramatic and accelerated recovery of CFU-pre-B numbers as compared to vehicle-administered mice. This enhancement was seen as early as day 11 post-CY, and the number of CFU-pre-B was comparable to normal age-matched control mice by day 16. In contrast, the number of CFU-pre-B in vehicle-treated mice remained significantly lower than age-matched and IL-10-treated animals as long as day 22 post-CY. No differences in the number of pre-B and mature B cells in bone marrow or in the number of mature B cells in peripheral lymphoid organs were detected in IL-10-treated mice. Myeloid cell recovery, assessed by the CFU-granulocyte/macrophage (CFU-GM) assay and the number of marrow Mac-1+ cells, was unaffected by IL-10 treatment of CY-dosed animals. These results indicate that IL-10 enhanced IL-7-stimulated murine pre-B cell colony formation and imply a role for IL-10 in normal B lymphopoiesis.


The risk for cutaneous malignant melanoma, melanoma in situ and intraocular malignant melanoma in relation to tobacco use and body mass index.
The incidence of cutaneous malignant melanoma (CMM) and melanoma in situ (MIS) has been increasing during the last 50 years. Malignant melanoma (MM) is also the most common intraocular malignancy (IMM). Besides ultraviolet radiation, the cause of these tumours is largely unknown. We designed a study to examine the effect of body mass index (BMI) and tobacco use on the risk for MM and MIS. Analyses were performed on a nationwide cohort of 339 802 Swedish construction workers. Exposure information was collected prospectively by questionnaires combined with personal interviews. Follow up yielded a total of 7 663 400 person-years during which 1639 workers developed MM/MIS. The risk for MM/MIS was reduced in current or previous smokers compared with those who had never smoked, both when analysing all smoking tobacco products combined and when analysing cigarette and pipe smokers separately. The risk was further diminished with longer duration of smoking and greater quantity of tobacco smoked. The effect was more evident in CMM/MIS than in IMM. Snuff taking conferred a decreased risk for CMM/MIS, and a BMI over normal weight range conferred an increased risk for CMM. Tobacco smoking was found to be inversely associated with the risk for CMM and MIS. The mechanism of action is unknown but it has been suggested to be due to the immune suppressive effect that tobacco exerts which would be protective against deleterious immune reactions caused by, for example, the sun. Neither is the mechanism behind the higher risk for CMM due to being overweight known. One hypothesis is that it is an effect of a hormonal imbalance. Further studies are required to elucidate these mechanisms.


Marmoset Flavin-Containing Monooxygenase 3 in the Liver Is a Major Benzydamine and Sulindac Sulfide Oxygenase.
Common marmosets (Callithrix jacchus) are potentially primate models for preclinical drug metabolism studies because there are similarities in the molecular characteristics of cytochrome P450 enzymes between this species and humans. However, characterization of non-cytochrome P450 enzymes has not been clarified in marmosets. Here, we report characterization of flavin-containing monooxygenases FMO1-FMO5 identified in marmoset tissues. Marmoset FMO forms shared high amino acid sequence identities (93%-95%) and phylogenetic closeness with human homologous FMO forms. FMO1 and FMO3 mRNA were abundantly expressed in the liver and kidneys among five marmoset tissues examined, where FMO3 protein was detected by immunoblotting. FMO inhibition assays using preheated tissue microsomes indicated that benzydamine N-oxygenation and sulindac sulfide S-oxygenation in the marmoset liver was mainly catalyzed by FMO3, the major hepatic FMO. Marmoset FMO3 protein heterologously expressed in Escherichia coli effectively catalyzed benzydamine N-oxygenation and sulindac sulfide S-oxygenation comparable to marmoset liver microsomes. These results indicate that the FMO3 enzyme expressed in marmoset livers mainly metabolizes benzydamine and sulindac sulfide (typical human FMO substrates), suggesting its importance for FMO-dependent drug metabolism in marmosets.


Coroners' recommendations following fatal heavy vehicle crash investigations.
This paper quantifies and describes the nature of coroners' recommendations and comments on fatal heavy vehicle crashes in Victoria, Australia. A retrospective, descriptive study was performed using coroners' findings. Fatal heavy vehicle crashes between January 2001 and December 2007 were identified through coronial databases. Individual findings were examined by incident type. Identified recommendations or preventative comments were reviewed and compared with national heavy vehicle safety objectives. Of 330 fatal crashes, which resulted in 376 deaths, recommendations were made in 21 incidents (6%). From these 21 incidents, 45 separate recommendations or comments were made by coroners. Ten (22%) called for specific remedial action, predominantly targeting road environment changes; the remainder had a broader application for prevention. Of the 21 incidents from which these recommendations arose, 11 (52%) were from a public inquest. No recommendation was made following any of the 45 single heavy vehicle crashes. The frequency of coroners' recommendations varied by crash nature including vehicle type involved and number of resulting fatalities. Multiple factors are likely to influence their development, including the holding of a public inquest and the perceived level of preventability. Coroners' investigations serve an important public health and safety role. Recognition of the significance of recommendations for reducing the extent of injury from heavy vehicle crashes and monitoring of their uptake is vital.


Recurrence of pediatric intussusception: A nationwide population-based descriptive study in Taiwan.
Intussusception is frequently observed pediatric emergency that is often followed by recurrent intussusception after initial treatment. This study investigated the risk factors associated with recurrent intussusception in children aged ≤ 3 years. Between January 2007 and December 2015, a cohort study was conducted by linking the Taiwan Maternal and Child Health Database to the Birth Certificate Application database and the National Health Insurance Research Database in Taiwan. Patients aged ≤ 3 years with intussusception diagnosis and related treatment were included in our study. Multivariable logistic regression was used to analyze the risk factors associated with recurrent intussusception. In total, 5341 children with intussusception aged ≤ 3 years were enrolled in our cohort. The adjusted odds ratio (aOR) for recurrent intussusception in children aged 2 to 3 years was 0.62 (95% confidence interval [CI]: 0.47-0.82) compared with children aged < 1 year, and surgery decreased the risk of recurrent intussusception (aOR = 0.64, 95% CI: 0.46-0.88). Male patients had higher risk of recurrent intussusception than female patients had (aOR = 1.41, 95% CI: 1.13-1.75). Higher birth weight may increase the risk of recurrent intussusception, but this association was not statistically significant. Furthermore, gestational age did not seem to affect the risk of recurrent intussusception. Surgical treatment and delayed onset of intussusception are associated with a reduced risk of recurrent intussusception; males are associated with increased risk of recurrent intussusception. In addition, we suggest that in early infancy, patients who received non-surgical treatment as the initial treatment for intussusception should be closely followed up for potential recurrence of intussusception.


[Goodpasture Syndrome: a Rare Cause of Acute Anuric Renal Failure].
We report a case of a 68 year old male who presented with an acute onset of anuric renal failure. Investigations revealed a histologically confirmed "double-positive" anti-GBM disease with initially undetectably high antibody values. An induction therapy with plasma exchange, cyclophosphamide and initially high dose steroids and further maintenance therapy for three months was initiated. The patient remained dialysis-dependent despite partial recovering of renal function. Without pulmonary involvement there were no clues for Goodpasture's disease. Renal prognosis is unfavourable.


Effective connectivity during successful and unsuccessful recollection in young and old adults.
Aging effects on regional brain activation have been studied extensively to explain the gradual recollection failure that occurs with advancing age. However, little is known about the consequence of aging on the interaction among brain regions that support recollection. The purpose of this study was to examine effective connectivity at encoding and retrieval during successful and unsuccessful recollection in young and old adults. In particular, we analyzed a recollection network that is characterized by its susceptibility to aging effects by middle age or later, which is comprised of the occipital cortex, hippocampus and orbitofrontal cortex. Participants' brains were scanned using functional magnetic resonance imaging while they performed a spatial source memory task. Dynamic causal modeling and Bayesian model selection revealed that subsequent recollection during encoding and recollection during retrieval modulated the influence of the orbitofrontal cortex on the hippocampus in both age groups; this particular connectivity was not modulated by unsuccessful encoding in either group. Successful encoding and retrieval of item-source associations modulated all connections within the network in old adults. The findings revealed that the orbitofrontal cortex influences processes in the hippocampus to ensure successful recollection, and aging alters the recollection network by engaging non-specialized connections.


Constitutive expression and phenobarbital modulation of drug metabolizing enzymes and related nuclear receptors in cattle liver and extra-hepatic tissues.
In humans and rodents, phenobarbital (PB) induces hepatic and extra-hepatic drug metabolizing enzymes (DMEs) through the activation of specific nuclear receptors (NRs). In contrast, few data about PB transcriptional effects in veterinary species are available. The constitutive expression and modulation of PB-responsive NR and DME genes, following an oral PB challenge, were investigated in cattle liver and extra-hepatic tissues (duodenum, kidney, lung, testis, adrenal and muscle). Likewise to humans and rodents, target genes were expressed to a lower extent compared to the liver with few exceptions. Phenobarbital significantly affected hepatic CYP2B22, 2C31, 2C87, 3A and UDP-glucuronosyltransferase 1A1-like, glutathione S-transferase A1-like and sulfotransferase 1A1-like (SULT1A1-like) mRNAs and apoprotein amounts; in extra-hepatic tissues, only duodenum showed a significant down-regulation of SULT1A1-like gene and apoprotein. Nuclear receptor mRNAs were never affected by PB. Presented data are the first evidence about the constitutive expression of foremost DME and NR genes in cattle extra-hepatic tissues, and the data obtained following a PB challenge are suggestive of species-differences in drug metabolism; altogether, these information are of value for the extrapolation of pharmacotoxicological data among species, the characterization of drug-drug interactions as well as the animal and consumer's risk caused by harmful residues formation.


An ultrasonographic method to study reproductive seasonality in ewes isolated from rams.
In studies concerning the seasonality in sheep, the effect of the teaser-ram, which can by itself induce oestrus as well as the development of ovary function bodies, has not been considered. In this study, a method is developed to determine ovarian activity during the year while excluding a possible influence of the ram. The study was carried out on 10 German Blackhead Mutton ewes (GBM) and 10 German Mutton Merino ewes (GMM) and lasted for 14 months. The ewes were kept without contact with any ram, and once a week a transrectal ultrasonography was conducted to determine ovary function bodies (corpora lutea, follicles) and a blood sample was taken to analyse progesterone (P4) concentration. In both breeds, the number of ovulating ewes, the ovulation rate (OR), the size of the corpora lutea (CL) and P4-concentrations showed significant seasonal fluctuations. During the main breeding period (September-February), the OR was higher (2.0 +/- 0.4) than during the rest of the year (1.6 +/- 0.5). Outside the main breeding season (March-August), approximately 40% GBM ewes and only approximately 15% GMM ewes produced CL. The cycle and the related seasonal changes in the P4-concentration coincide with different ultrasonically diagnosed CL (developing or regressing, insufficient, no CL). Between the volume of fully developed CL and P4-concentration, correlations of 0.57 (GMM) and 0.45 (GBM), respectively, were found. On average, P4-concentration in September to February was by approximately 1.60-1.66 nmol/l in the GMM and by approximately 1.80-1.86 nmol/l in the GBM higher than in spring and summer. Considering the OR, the P4-values corresponded with the CL volumes, i.e. in the months from August to February the CL values were significantly larger than in the months March to August. The ultrasonic ovarian diagnosis is a useful method to determine the ram-uninfluenced seasonality of reproduction in sheep.


Intraoperative Topical Antibiotics for Infection Prophylaxis in Pelvic and Acetabular Surgery.
To determine if topical vancomycin and tobramycin powder reduces the incidence of surgical site infection after pelvic ring and acetabulum fracture surgery. Retrospective cohort study. University of Alabama at Birmingham, Academic Level I Trauma Center. Two hundred nineteen patients (140 meeting inclusion criteria) with pelvic and acetabular fractures who underwent open reduction and internal fixation from March 2012 to November 2013. One gram vancomycin and 1.2 g tobramycin powder applied deep in the surgical wound of the treatment group. Postoperative infection rate. One hundred forty patients were included. Control group (n = 69) and treatment group (n = 71) were similar for sex, age, ethnicity, and body mass index. There was no difference between groups with regards to renal function postoperative day 2 (P = 0.24). The risk of infection was 14.5% and 4.2% (P = 0.04) for the control and treatment groups, respectively. No significant effect of antibiotic treatment was observed overall after adjusting for EBL (odds ratio 0.20, 95% confidence interval, 0.02-1.06). Of note, a nonsignificant 71% increase was observed among those with ≥1 L EBL (odds ratio 1.71, 95% confidence interval, 0.02-147.02). Topical antibiotics possibly reduce the incidence of surgical site infection after open pelvic and acetabulum fixation without increasing risk of renal impairment. The protective effect of topical antibiotics may be limited to patients with minimal intraoperative blood loss. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Plant dnaj homologue: molecular cloning, bacterial expression, and expression analysis in tissues of cucumber seedlings.
Proteins homologous to the bacterial dnaJ protein have been implicated as molecular chaperones in different compartments of eukaryotes. A plant equivalent is now described in various cucumber tissues. Using a cDNA library constructed from poly(A)-rich RNA of cotyledons of etiolated seedlings and dnaJ-specific probes, we isolated clones encoding full-length cDNAs: clone CSDNAJ-1 contained a 1.7-kb insert with a single open reading frame of 413 amino acid residues encoding a protein of M(r) 46, 012; pCSDNAJ-2 differed from pCSDNAJ-1 by an additional nucleotide and predicted a protein of M(r) 26, 104. Peptides of similar sizes were observed when the cDNA information was expressed by in vitro transcription and translation or expressed in vivo in bacteria. Using mRNA isolated by hybrid selection for in vitro translation we observed the formation of CSDNAJ-1 protein. Comparisons revealed that the similarity in primary structure between CSDNAJ-1 protein and dnaJ homologues in eukaryotes is most pronounced in the N-terminal region. The high degree of identity (39%) of CSDNAJ-1 protein with the yeast dnaJ homologue YDJ1 protein suggests that csdnaJ proteins assist intracellular protein transfer. The predicted CSDNAJ-1 protein is characterized by a fourfold repetition of the motif CXXCXGX(G) and by a C-terminus -QCAQQ. Analysis of gene expression at the level of mRNA showed that the putative dnaJ protein is expressed in cucumber seedlings in all tissues, but exceedingly high in hypocotyledons and roots. The level of dnaJ mRNA was transiently increased by a factor of 1.5-2.0 when heat shock was applied to the seedlings.


Generation of Hydrofluoronickelacycles from Trifluoroethylene and Ni(0): Ligand Effects on Regio-/Stereoselectivity and Reactivity.
Treatment of Ni(0) complexes 1a-e with sub-atmospheric pressures of trifluoroethylene (TrFE) affords hydrofluoronickelacyclopentanes L2Ni(C4F6H2) 2a-e (L = PPh3, P(O-o-tol)3, PPh2Me, PPhMe2, PMe3). Fluorine NMR analysis of 2a-e demonstrates predominant formation of three (of the possible six) isomers upon oxidative cycloaddition of TrFE: the cis and trans head-tail isomers and the trans head-head isomer, where the CHF group is defined as the TrFE "head". The respective ratios of L2Ni(C4F6H2) isomers are influenced by the nature of L, with smaller phosphines favoring the thermodynamically preferred (from DFT calculations) trans head-head isomer (cf. 50% with PMe3) and the largest affording small amounts of the tail-tail isomers. Lewis and Brønsted acids induce a surprising double C-F bond activation in 2c-d, affording small functionalized hydrofluoroalkenes. Interestingly, varying the acid employed dictates the organic product obtained from the head-tail isomers: BF3·OEt2 is selective for 1,1,2,3-tetrafluorocyclobutene, whereas Me3SiOTf and N,N-dimethylanilinium bromide yield (Z,E)-1,1,3,4-tetrafluorobutadiene as the major fluorinated product. Reaction intermediates were isolated, and possible pathways are discussed.


[Polyarteritis nodosa with hepatitis and pancreatitis].
A 39-year-old man, known as a heavy drinker, presented with general malaise, abdominal pain, a history of icterus and progressive weight loss. He was found to have an acute hepatitis B infection and pancreatitis with pancreatic pseudocysts. A diagnosis of polyarteritis nodosa was made on clinical grounds, and confirmed pathologically. The patient was treated with high-dose corticosteroids, cyclophosphamide, antibiotics and drainage. However, the disease was progressive and the patient died. Pancreatitis in relation to polyarteritis nodosa, the association with hepatitis B infection, and new therapeutic possibilities are discussed.