Evidence for lateral transfer to Brucellae: characterization of a locus with a Tn-like element (Tn2020).
A genomic locus was discovered within Brucella abortus that contains a novel transposon-like element designated Tn2020. Tn2020 is bounded by a copy of an insertion sequence designated IS2020 and a truncated imperfect copy of IS2020 (tIS2020A). The truncated copy is immediately adjacent to a second copy of IS2020. These data are consistent with the locus having evolved by a complex rearrangement following the transposition of a second copy of Tn2020. Analysis of the organization, orientation, and open reading frames (ORFs) of IS2020 places it within the IS6 family. Four ORFs from Tn2020 were translated in vitro producing a potential transposase with an apparent molecular mass of 27.5 kDa, and three polypeptides with apparent molecular masses of 71 kDa, 22 kDa, and 14 kDa. The central region of Tn2020 encodes the 71 kDa and 14 kDa proteins, while the 22 kDa protein is likely an internal translation initiation product of the IS2020 transposase. The 71 kDa protein shares sequence similarity with several bacterial transcriptional regulatory proteins and may form a helix-turn-helix structure capable of binding DNA. No homologous protein sequences to the 14 kDa peptide were detected in available databases. The 27.5 kDa transposase and its 22 kDa internal translation product shared significant similarity to several transposases from diverse bacterial hosts. Immediately 5' of Tn2020 are genes encoding ribosomal proteins RplU and RpmA. This region also contains a 90 bp sequence that shares significant homology to a repetitive element with inverted repeats from the Sinorhizobium genome. Downstream from Tn2020 is an ORF encoding a protein having significant similarity to a hypothetical protein from Caulobacter. The locus is lower in G+C content from that of the genome. These data suggest that lateral transfer of genetic material has occurred.


Isolation, Purification and Characterization of Two Laccases from Carrot (Daucus carota L.) and Their Response to Abiotic and Metal Ions Stresses.
Laccases, which belong to the blue copper oxidase enzyme family, oxidize many organic and inorganic compounds. The laccase-encoding genes DcLac1 and DcLac2 were isolated from the economically important tuberous root carrot, and their proteins were successfully expressed and purified using the Escherichia coli expression system BL21(DE3). DcLac1 and DcLac2 had molecular masses of approximately 64 and 61.9 kDa, respectively. With 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate acid) as the substrate, DcLac1 and DcLac2 had K m values of 3.9043 and 1.255 mM, respectively, and V max values of 54.0832 and 81.7996 μM mg(-1) min(-1), respectively. Moreover, DcLac1 and DcLac2 had optimal pH values of 2.8 and 2.6, respectively, and optimal temperatures of 45 and 40 °C, respectively. The activities of the two enzymes were promoted by Ca(2+), Mg(2+), Cu(2+), and Na(+) but inhibited by Fe(2+), Zn(2+), Mn(2+), K(+), SDS, and EDTA. Expression profiles showed that the two DcLac genes had almost identical responses to high and low temperature stresses but different responses to salt, drought, and metal stresses. This study provided insights into the characteristics and tolerance response mechanisms of laccase in carrot.


Quantitative analysis of yeast gene function using competition experiments in continuous culture.
One possible route to the evaluation of gene function is a quantitative approach based on the concepts of metabolic control analysis (MCA). An important first step in such an analysis is to determine the effect of deleting individual genes on the growth rate (or fitness) of S. cerevisiae. Since the specific growth-rate effects of most genes are likely to be small, we employed competition experiments in chemostat culture to measure the proportion of deletion mutants relative to that of a standard strain by using a quantitative PCR method. In this paper, we show that both densitometry and GeneScan analysis can be used with similar accuracy and reproducibility to determine the proportions of (at least) two strains simultaneously, in the range 10-90% of the total cell population. Furthermore, we report on a model competition experiment between two diploid nuclear petite mutants, homozygous for deletions in the cox5a or pet191 genes, and the standard strain (ho::kanMX4/ho::kanMX4) in chemostat cultures under six different physiological conditions. The results indicate that competition experiments is continuous culture are a suitable method to distinguish quantitatively between deletion mutants that qualitatively exhibit the same phenotype.


Severe psychosis due to Cushing's syndrome in a patient with a carcinoid tumour in the lung: a case report and review of the current management.
Severe psychosis in patients with Cushing's syndrome is a rare occurrence and can be extremely resistant to medical therapy. We describe a case of a 51-year-old Afro-Caribbean female patient, with refractory severe hypertension (initially resistant to polypharmacy) and gradual development of severe psychosis secondary to ectopic Cushing's syndrome, who was subsequently diagnosed to have a carcinoid tumour in her lung. Her psychotic episodes - secondary to hypercortisolism and initially refractory to the medical therapy - subsided only after the resection of the carcinoid tumour in her right lower pulmonary lobe. Early localization and appropriate surgical resection of the ectopic ACTH-secreting tumour can be of immense value to the successful alleviation of the psychotic episodes of the patients with ectopic Cushing's syndrome.


Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease.
Neuronal expression of familial Alzheimer's disease-mutant human amyloid precursor protein (hAPP) and hAPP-derived amyloid-beta (Abeta) peptides causes synaptic dysfunction, inflammation and abnormal cerebrovascular tone in transgenic mice. Fatty acids may be involved in these processes, but their contribution to Alzheimer's disease pathogenesis is uncertain. We used a lipidomics approach to generate a broad profile of fatty acids in brain tissues of hAPP-expressing mice and found an increase in arachidonic acid and its metabolites, suggesting increased activity of the group IV isoform of phospholipase A(2) (GIVA-PLA(2)). The levels of activated GIVA-PLA(2) in the hippocampus were increased in individuals with Alzheimer's disease and in hAPP mice. Abeta caused a dose-dependent increase in GIVA-PLA(2) phosphorylation in neuronal cultures. Inhibition of GIVA-PLA(2) diminished Abeta-induced neurotoxicity. Genetic ablation or reduction of GIVA-PLA(2) protected hAPP mice against Abeta-dependent deficits in learning and memory, behavioral alterations and premature mortality. Inhibition of GIVA-PLA(2) may be beneficial in the treatment and prevention of Alzheimer's disease.


Lapses of attention as outcome measure of the on-the-road driving test.
Lapses are brief periods of inattention and reduced alertness which may be a risk factor for car crashes. The Dutch on-the-road driving test is applied to examine effects of CNS drugs on driving, using the standard deviation of lateral position (SDLP) as primary outcome measure. This paper examines the utility of an alternative outcome measure, lapses, to determine the degree to which CNS drugs impair driving. Data from two double-blind, placebo-controlled on-the-road driving studies that examined the residual effects of hypnotic drugs were reanalyzed. The treatments were zaleplon and zolpidem tested 4 h after middle-of-the-night administration, and ramelteon and zopiclone tested 8.5 h after bedtime administration. In addition to SDLP, outcome measures related to lapses (number, total duration, and maximum deviation) were computed. A lapse was defined as a continuous change in lateral position of greater than 100 cm, lasting for at least 4 s. Both SDLP and lapses were able to detect significant driving impairment after middle-of-the-night administration of zolpidem (10 and 20 mg) and bedtime administration of ramelteon (8 mg) and zopiclone (7.5 mg) relative to placebo. Both measures found no differences from placebo after middle-of-the-night administration of zaleplon (10 and 20 mg). The number of lapses was more sensitive in differentiating treatment from placebo than the maximum deviation of a lapse or their duration. After considering different lapse duration criteria, a lapse was redefined as a continuous change in lateral position of greater than 100 cm, lasting for at least 8 s. This change in definition did not significantly alter the outcome of the statistical analyses. In addition to SDLP, the number of lapses is a useful outcome measure to identify treatments that impair driving. Future research should determine the unique contributions of SDLP and lapses in defining the potential risk of CNS drugs on driving.


Glomerular hypertension and injury in desoxycorticosterone-salt rats on antihypertensive therapy.
Uninephrectomized male Munich-Wistar rats received either weekly subcutaneous injections of vehicle and water for drinking; injections of desoxycorticosterone (DOC) and 1% saline (SALT) for drinking; or DOC and SALT with hydrochlorthiazide, hydralazine, reserpine and KCl added. All studies were performed six weeks after UNX. At that time, rats receiving DOC and SALT alone were hypertensive and had significantly more proteinuria and morphologic evidence of glomerular injury than rats given vehicle and tap water which were normotensive. Antihypertensive therapy normalized mean arterial pressure in DOC-SALT rats, but failed to prevent proteinuria, mesangial expansion or focal segmental glomerular lesions. Micropuncture studies revealed that glomerular capillary pressure was elevated in both untreated and treated DOC-SALT animals. We conclude that drugs which successfully reduce systemic blood pressure may fail to correct glomerular capillary hypertension in DOC-SALT rats. As persistence of intrarenal hypertension is associated with significant glomerular injury, normalization of glomerular capillary pressure rather than systemic arterial pressure is crucial to the prevention of glomerular injury in this model.


Response of sorghum genotypes to water deficit stress under different CO2 and nitrogen levels.
An open-top chamber experiment was conducted in the present study to investigate the growth and biochemical responses of six sorghum genotypes under two irrigation regimes (based on 40% and 75% soil-water depletion) and two N fertilizer levels (0 and 105 kgN ha-1), at two atmospheric CO2 conditions (390 ± 50 and 700 ± 50 μmol mol-1). The results revealed that water limited stress decreased the plant dry weight by reducing the plant leaf area, SPAD value, Fv/Fm, leaf RWC and membrane stability index (MSI), while it increased the specific activity of APX, CAT and POX enzymes, DPPH, LPC, Phe, TSC, H2O2, MDA and EL. The lowest decrease of the plant dry weight due to limited water stress was observed in the GS5 genotype, which was followed by the lowest decrease in the leaf RWC and MSI; also, the highest increase was seen in APX, Phe and TSC, while the lowest one was recorded in EL. Elevated CO2 improved DPPH and Phe under both control and water limited conditions, resulting in the decrease of APX, POX, H2O2 and EL, while a more pronounced effect was observed in the stress conditions. Furthermore, with the application of nitrogen, the reduction in DPPH, H2O2 and MDA values was greater under water limited stress rather than control conditions. It could be, therefore, concluded that the responses of sorghum genotypes to water deficit stress had interaction with atmospheric CO2 concentrations and nitrogen levels; this could be considered in breeding programs as well as planting management of sorghum.


Antimony isotopic composition in river waters affected by ancient mining activity.
In this study, antimony (Sb) isotopic composition was determined in natural water samples collected along two hydrosystems impacted by historical mining activities: the upper Orb River and the Gardon River watershed (SE, France). Antimony isotope ratio was measured by HG-MC-ICP-MS (Hydride Generation Multi-Collector Inductively Coupled Plasma Mass Spectrometer) after a preconcentration and purification step using a new thiol-cellulose powder (TCP) procedure. The external reproducibility obtained for δ(123)Sb measurements of our in-house Sb isotopic standard solution and a certified reference freshwater was 0.06‰ (2σ). Significant isotopic variations were evident in surface waters from the upper Orb River (-0.06‰≤δ(123)Sb≤+0.11‰) and from the Gardon River watershed (+0.27‰≤δ(123)Sb≤+0.83‰). In particular, streams that drained different former mining sites exploited for Sb or Pb-Zn exhibited contrasted Sb isotopic signature, that may be related to various biogeochemical processes occurring during Sb transfer from rocks, mine wastes and sediments to the water compartment. Nevertheless, Sb isotopic composition appeared to be stable along the Gardon River, which might be attributed to the conservative transport of Sb at distance from mine-impacted streams, due to the relative mobile behavior of Sb(V) in natural oxic waters. This study suggests that Sb isotopic composition could be a useful tool to track pollution sources and/or biogeochemical processes in hydrologic systems.


The Vanguard of Community-based Integrated Care in Japan: The Effect of a Rural Town on National Policy.
Japan has the largest percentage of elderly people in the world. In 2012 the government implemented a community-based integrated care system which provides seamless community healthcare resources for elderly people with chronic diseases and disabilities. This paper describes the challenges of establishing a community-based integrated care system in 1974 in Mitsugi, a rural town of Japan. This system has influenced the government and become the model for the nationwide system. In the 1970s, Mitsugi's aging population was growing faster than Japan's, but elder care was fragmented among a variety of service sections. A community-based integrated care system evolved because of the small but aging population size and the initiative of some local leaders of medical care and politics. After the system took effect, the proportion of bedridden people and medical care costs for the elderly dropped in Mitsugi while it continued to rise everywhere else in Japan. Mitsugi's community-based integrated care system is now shaping national policy. Mitsugi is in the vanguard of Japan's community-based integrated care system. The case showed the community-based integrated care system can diffuse from rural to urban areas.


Improving the cytotoxicity of immunotoxins by reducing the affinity of the antibody in acidic pH.
Immunotoxins are antibody-toxin conjugates that bind to surface antigens and exert effective cytotoxic activity after internalization into tumor cells. Immunotoxins exhibit effective cytotoxicity and have been approved by the FDA to treat multiple hematological malignancies, such as hairy cell leukemia and cutaneous T-cell lymphoma. However, most of the internalized immunotoxin is degraded in lysosomes, and only approximately 5% of free toxin escapes into the cytosol to exert cytotoxicity. Many studies have improved immunotoxins by engineering the toxin fragment to reduce immunogenicity or increase stability, but how the antibody fragment contributes to the activity of immunotoxins has not been well demonstrated. In the current study, we used 32A9 and 42A1, two anti-GPC3 antibodies with similar antigen-binding capabilities and internalization rates, to construct scFv-mPE24 immunotoxins and evaluated their in vitro and in vivo antitumor activities. Next, the antigen-binding capacity, trafficking, intracellular protein stability and release of free toxin of 32A9 scFv-mPE24 and 42A1 scFv-mPE24 were compared to elucidate their different antitumor activities. Furthermore, we used a lysosome inhibitor to evaluate the degradation behavior of 32A9 scFv-mPE24 and 42A1 scFv-mPE24. Finally, the antigen-binding patterns of 32A9 and 42A1 were compared under neutral and acidic pH conditions. Although 32A9 and 42A1 had similar antigen binding capacities and internalization rates, 32A9 scFv-mPE24 had superior antitumor activity compared to 42A1 scFv-mPE24. We found that 32A9 scFv-mPE24 exhibited faster degradation and drove efficient free toxin release compared to 42A1 scFv-mPE24. These phenomena were determined by the different degradation behaviors of 32A9 scFv-mPE24 and 42A1 scFv-mPE24 in lysosomes. Moreover, 32A9 was sensitive to the low-pH environment, which made the 32A9 conjugate easily lose antigen binding and undergo degradation in lysosomes, and the free toxin was then efficiently produced to exert cytotoxicity, whereas 42A1 was resistant to the acidic environment, which kept the 42A1 conjugate relatively stable in lysosomes and delayed the release of free toxin. These results showed that a low pH-sensitive antibody-based immunotoxin degraded faster in lysosomes, caused effective free toxin release, and led to improved cytotoxicity compared to an immunotoxin based on a normal antibody. Our findings suggested that a low pH-sensitive antibody might have an advantage in the design of immunotoxins and other lysosomal degradation-dependent antibody conjugate drugs.


Ayurveda management of cystocele, uterine prolapse and weak pelvic floor strength-A case report.
Pelvic organ prolapse (POP) is the downward displacement of pelvic organs. The condition is very common in women and negatively affects their quality of life. The aging process reflects in the form of structural and functional weakness of the pelvic floor which leads to pelvic floor dysfunction (PFD). The strength and endurance of the Pelvic floor muscles (PFM) decrease significantly by these dysfunctions. In the present study, Pelvic floor strength (PFS) and endurance were assessed with the help of a perineometer. The patient was diagnosed with cystocele, uterine prolapse and weak PFS was assessed with the Perineometer. Patient was treated with Ayurvedicsthanika chikitsa (local treatment)- Yoni abhyanga (vaginal massage) and improvement in PFS was assessed after treatment. The present article aims to assess the pre and post-outcome results of PFM by using the objective tool perineometer. Seven days of yoni abhyanga along with oral medication were given and on follow-up after three months, the patient showed increased strength and endurance on the perineometer. Early diagnosis and management of the PFD will help to improve the QoL (Quality of Life) and prevent further deterioration of PFS.


A novel Y/13 familial translocation.
A novel Y/13 translocation was discovered in a female fetus during amniocentesis. The familial translocation is present in a phenotypically normal female sibling and in the father who also possesses a pericentric inversion. Karyotype of the father is 46,XY,-13,+der(13)t(Y;13)(q12;p12),inv(22)(p13q12.1).


Quantification of aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase activity in human placentae: development of a protocol suitable for studying effects of environmental exposures on human metabolism.
Several issues regarding measurement of placental AHH and 7ECD activity were studied, and standardized procedures that appeared more suitable than previous assay procedures for measurement of MFO induction in epidemiological studies were adopted. In the AHH assay, deletion of the rat-liver supernatant eliminated a possible extraneous contribution to measurement of low levels of AHH activity and did not substantially affect measurement of higher levels of activity. Increasing the protein concentration of placentae homogenate from 2 to 6 mg, and the length of the incubation time from 20 to 60 min, allowed for accumulation of more BaP products, potentially maximizing the detection of low levels of AHH activity. Use of tissue homogenates made the procedure more convenient and did not appear to interfere with interindividual comparisons of activity. Assay of homogenates of fresh and frozen tissue from the same placenta gave similar results, so that frozen tissue was adopted for convenience and replicability. Although a potential problem for specimens with high AHH activity, degradation of product(s) was modest in AHH assays of human placenta. The efficiency of extraction of fluorescent products declined with increasing protein concentrations in the reaction mixture of AHH assays, but it was stable for a range of product concentrations, and could be controlled by the use of a constant amount of protein per assay. Recovery of product for the 7ECD assay was more complete and was not affected by protein concentration. Additionally, the 7ECD activity was easily detected in every placenta, regardless of smoking exposure. However, in this study the AHH assay appeared to be better at discriminating between non-smokers and smokers. These observations, and the potential differences in the spectrum of agents causing induction of mixed-function oxidases, suggest that both assays are potentially useful measures of human MFO induction in clinical or epidemiological studies.


Synthesis and characterization of barbarin, a possible source of unexplained aminorex identifications in forensic science.
Aminorex is a US DEA Schedule 1 controlled substance occasionally detected in racing horses. A number of aminorex identifications in sport horses were thought to have been caused by exposure to plant sources of aminorex. Glucobarbarin, found in plants of the Brassicaceae family, has been suggested as a potential proximate chemical source by being metabolized in the plant or the horse to aminorex. In Brassicaceae, glucobarbarin is hydrolyzed by myrosinase to yield barbarin, which serves as an insect repellant and/or attractant and is structurally related to aminorex. The synthesis, purification, and characterization of barbarin is now reported for use as a reference standard in aminorex related research concerning equine urinary identifications of aminorex and also for possible use in equine administration experiments. Synthesis of barbarin was performed via ring closure between phenylethanolamine and carbon disulfide in tetrahydrofuran with the catalyst pyridine under reflux. The reaction yielded a white crystalline substance that was purified and chemically characterized as barbarin for use as a Certified Reference Standard or for studies related to equine aminorex identification.


Liquid chromatographic determination of barbiturates using a hollow-fibre membrane for postcolumn pH modification.
A sensitive, high-performance liquid chromatographic method is described for the determination of barbiturates by postcolumn pH modification. The barbiturates (barbital, phenobarbital, hexobarbital and amobarbital) were separated on a C18 column using a mixture of methanol and water as an eluent. Then the pH of the eluent was raised to 10 by introducing ammonia or ammonium ion through a sulphonated hollow-fibre membrane inserted between the column and the detector. The detection was based on the primary ionized barbiturates at 240 nm. At barbiturate concentrations of 2.0 micrograms/ml, the within- and between-experiment precision (relative standard deviation) was 0.65-3.28 and 0.76-1.90%, respectively. The limits of detection were about 0.5-2.5 ng at a signal-to-noise ratio of 3. The method was applied to the determination of amobarbital in saliva.


Development of an ulcer in the side-to-side anastomosis of a jejunal pouch after proximal gastrectomy reconstructed by jejunal interposition: report of a case.
We present herein the first reported case of a deep ulceration developing in the pouch of a jejunal side-to-side anastomosis following the interposition of a jejunal U-shaped pouch (jejunal pouch), performed as reconstruction. A 47-year-old woman underwent a proximal gastrectomy and interposition of a jejunal pouch for early gastric cancer, 4 months after which she began to develop a fever. Esophagogastroscopy revealed a deep ulceration in the side-to-side anastomosis of the jejunal pouch. Her serum gastrin level was much higher than the normal range, and 24-h monitoring of the intraremnant stomach pH revealed that it was below 7.0 at night. A peptic ulcer was thought to be one of the causes of the pouchitis. Due to the drug-resistant ulceration and fever, a reoperation was performed, in which the jejunal pouch and remnant stomach were removed and Roux-en-Y reconstruction was done. There were no postoperative complications, and the fever resolved after surgery. Reconstruction of the jejunal pouch after proximal gastrectomy is recommended from the standpoint of quality of life (QOL); however, further studies on the size of the remnant stomach and the length of the interposed jejunal pouch are necessary.


99m-Technetium sestamibi localized solitary parathyroid adenoma as an indication for limited unilateral surgical exploration.
Because of its successful localization of solitary adenomas, 99m-Technetium sestamibi (MIBI) may challenge the standard operation for primary hyperparathyroidism. Thirty-five consecutive patients underwent preoperative MIBI localization to optimize a surgical approach. Single-site localization in 21 patients directed a limited unilateral neck exploration (UNE) with adenomectomy and ipsilateral gland biopsy. Fourteen patients who did not localize underwent bilateral neck exploration (BNE). Conversion to a bilateral operation was required in 1 UNE patient because no adenoma was found on that side. There were no significant differences in preoperative and postoperative serological markers between the two groups. However, the total operative time for UNE (49 +/- 21 minutes) was significantly less than for BNE (103 +/- 45 minutes; P <0.001). Preoperative MIBI scan-directed limited unilateral neck operation may be used reliably for primary hyperparathyroidism due to a single adenoma, and thereby reduce operative time, extent of surgical dissection, and risk.


Testicular extramedullary myeloid cell tumor: report of a case with unique clinicopathologic features and a brief review of the literature.
We report a case of testicular extramedullary myeloid cell tumor in a 37-year-old man who presented with an acute testicular hemorrhage. A pathologic examination revealed no gross tumor mass. A well-differentiated extramedullary myeloid cell tumor infiltrate was seen histologically, localized largely to the seminiferous tubules. The patient had no evidence of any past or concurrent myeloid disorders. The lack of the usual clinical features of a testicular mass and the presence of an intratubular pattern of infiltration can further compound the challenges in diagnosing this entity.


Cortical activation patterns during long-term memory retrieval of visually or haptically encoded objects and locations.
The present study used functional magnetic resonance imaging to delineate cortical networks that are activated when objects or spatial locations encoded either visually (visual encoding group, n=10) or haptically (haptic encoding group, n=10) had to be retrieved from long-term memory. Participants learned associations between auditorily presented words and either meaningless objects or locations in a 3-D space. During the retrieval phase one day later, participants had to decide whether two auditorily presented words shared an association with a common object or location. Thus, perceptual stimulation during retrieval was always equivalent, whereas either visually or haptically encoded object or location associations had to be reactivated. Moreover, the number of associations fanning out from each word varied systematically, enabling a parametric increase of the number of reactivated representations. Recall of visual objects predominantly activated the left superior frontal gyrus and the intraparietal cortex, whereas visually learned locations activated the superior parietal cortex of both hemispheres. Retrieval of haptically encoded material activated the left medial frontal gyrus and the intraparietal cortex in the object condition, and the bilateral superior parietal cortex in the location condition. A direct test for modality-specific effects showed that visually encoded material activated more vision-related areas (BA 18/19) and haptically encoded material more motor and somatosensory-related areas. A conjunction analysis identified supramodal and material-unspecific activations within the medial and superior frontal gyrus and the superior parietal lobe including the intraparietal sulcus. These activation patterns strongly support the idea that code-specific representations are consolidated and reactivated within anatomically distributed cell assemblies that comprise sensory and motor processing systems.


Association of left ventricular abnormalities with incident cerebrovascular events and sources of thromboembolism in patients with chronic Chagas cardiomyopathy.
Although Chagas cardiomyopathy is related to thromboembolic stroke, data on risk factors for cerebrovascular events in Chagas disease is limited. Thus, we assessed the relationship between left ventricular (LV) impairment and cerebrovascular events and sources of thromboembolism in patients with Chagas cardiomyopathy. This retrospective cohort included patients with chronic Chagas cardiomyopathy who underwent cardiovascular magnetic resonance (CMR). CMR was performed with a 1.5 T scanner to provide LV volumes, mass, ejection fraction (LVEF), and myocardial fibrosis. The primary outcome was a composite of incident ischemic cerebrovascular events (stroke or transient ischemic attack-TIA) and potential thromboembolic sources (atrial fibrillation (AF), atrial flutter, or intracavitary thrombus) during the follow-up. A total of 113 patients were included. Median age was 56 years (IQR: 45-67), and 58 (51%) were women. The median LVEF was 53% (IQR: 41-62). LV aneurysms and LV fibrosis were present in 38 (34%) and 76 (67%) individuals, respectively. The median follow-up time was 6.9 years, with 29 events: 11 cerebrovascular events, 16 had AF or atrial flutter, and two had LV apical thrombosis. In the multivariable model, only lower LVEF remained significantly associated with the outcomes (HR: 0.96, 95% CI: 0.93-0.99). Patients with reduced LVEF lower than 40% had a much higher risk of cerebrovascular events and thromboembolic sources (HR: 3.16 95% CI: 1.38-7.25) than those with normal LVEF. The combined incidence rate of the combined events in chronic Chagas cardiomyopathy patients with reduced LVEF was 13.9 new cases per 100 persons-year. LV systolic dysfunction is an independent predictor of adverse cerebrovascular events and potential sources of thromboembolism in patients with chronic Chagas cardiomyopathy.


Human spleen cysteineproteinase inhibitor. Purification, fractionation into isoelectric variants and some properties of the variants.
The papain inhibitor from human spleen was purified by extraction in isotonic sucrose, acetone fractionation, papain-Sepharose affinity chromatography and gel filtration on Sephadex G-50. The purified inhibitor was fractionated by electrofocusing into four major isoelectric variants with pI values of 4.7, 5.0, 6.0 and 6.5. These variants can be classified into two groups: the acidic type, comprising the variants with pI 4.7 and 5.0, and the neutral type, comprising the variants with pI 6.0 and 6.5. The following properties distinguish the two types: 1. Immunological properties: antibodies raised against either of the neutral variants precipitated both of these, but not the acidic variants. The antiserum against the human epidermal cysteineproteinase inhibitor precipitated the acidic variants, but not the neutral variants. 2. Molecular size: two-dimensional electrophoresis of the purified inhibitor gave molecular weights of 11400 for the acidic variants and 12000 for the neutral variants. The pI 6.0 variant contained two compounds with molecular weights of 12000 and 12800. 3. Enzyme spectrum: human cathepsin B was inhibited by the acidic type, while the neutral type was a poor inhibitor. Both types inhibited cathepsin H, papain, ficin and bromelain, although the inhibition of bromelain did not exceed 70%. Human cathepsin D, bovine trypsin and chymotrypsin and porcine elastase were not inhibited by either type.


Analysis of Escherichia coli K1 Virulence Genes by Transposon-Directed Sequencing.
Transposon-directed insertion site sequencing (TraDIS) combines random transposon mutagenesis and massively parallel sequencing to shed light on bacterial gene function on a genome-wide scale and in a high-throughput manner. The technique has proven to be successful in the determination of the fitness contribution of every gene under specific conditions both in vitro and in vivo. In this contribution, we describe the procedure used for the identification of Escherichia coli K1 genes essential for in vitro growth, survival in pooled human serum and gastrointestinal colonisation in a rodent model of neonatal invasive infection. TraDIS has broad application for systems-level analysis of a wide range of pathogenic, commensular and saprophytic bacteria.


A Comparison of the Incidences of Venous Thromboembolism after Total Hip Arthroplasty between the Direct Anterior Approach and the Direct Lateral Approach, Especially in the Early Period after Introduction of the Direct Anterior Approach.
To compare the incidence of venous thromboembolism (VTE) after total hip arthroplasty (THA) using the direct anterior approach (DAA) with that using the direct lateral approach (DLA). In addition, patient background characteristics and the incidence of VTE were compared between the first half and the latter half of the period after introducing DAA and against DLA. This was a retrospective, multicenter study involving 109 patients (116 hips) who had undergone primary unilateral THA. Thirty-six hips underwent THA using DAA and 80 hips underwent THA using DLA. Patient information including sex, age, and preoperative diagnosis was collected. The incidence of VTE was compared between DAA and DLA. Moreover, the patients who underwent THA using DAA were divided into 2 groups (first half and latter half groups), and sex, age, body mass index (BMI), and surgical time were compared between the 2 groups. Moreover, the incidence of VTE was compared among the 3 groups (first half of DAA, latter half of DAA, and DLA). The incidence of VTE in the DAA group was significantly higher than that in the DLA group (p=0.014). The incidence of VTE in the first half group was significantly higher than in the latter half group and the DLA group (p=0.035 and p=0.001, respectively), and there was no difference in the incidence of VTE between the latter half group and the DLA group (p=0.923). Surgical time was significantly longer in the first half group than in the latter half group (p=0.046). In the first half of the period after introducing the DAA, more VTEs occurred than in the DLA. It may be important to shorten the surgical time in the early stage of introducing the DAA, and aggressive anticoagulation therapy may be required until the surgeon becomes familiar with the procedure.


Time-related factors in quantitative risk assessment.
In regulatory or decision-making contexts related to carcinogenic hazards, one would like to know the extra risks associated with various levels, durations, and ages of exposure to a carcinogen. To supply that information, quantitative risk assessments are required that make extrapolations on variables related to dose levels, timing of exposure, and age. Quantitative models that express age-specific mortality rates as functions of the exposure pattern and that allow such extrapolations to be made are presented. The uncertainty inherently associated with those extrapolations is discussed and is found to be exacerbated by small data sets and inadequate data availability. Specific examples are provided that involve asbestos-induced mesothelioma and leukemia caused by benzene exposure.


Staging of colorectal cancer: biology vs. morphology.
An accurate determination of the extent or staging of a disease is critical, because it provides the basis for making therapeutic decisions. Staging is a collaborative effort by the surgeon and the pathologist. Radioimmunoguided surgery has been evaluated for its ability to help surgeons determine the extent of disease during surgery, when management decisions have the most impact on patient care. This study was done to compare radioimmunoguided surgery "biostaging" with traditional pathologic staging (TNM) as predictors of survival in patients undergoing curative resections for colorectal cancer. Ninety-seven patients with colorectal cancer were prospectively enrolled in radioimmunoguided surgery protocols. Evaluation of follow-up survival data was performed. All patients underwent exploratory laparotomy and radioimmunoguided surgery with resection of their primary colorectal tumor. Survival data were analyzed with the Kaplan-Meier method with log-rank comparisons. Of 97 patients enrolled in the study, 59 were evaluable and completely resectable by radioimmunoguided surgery. Mean follow-up was 62 months, with a range of 34 to 89 months. By traditional staging 13 patients were pStage I, 18 patients were pStage II, and 28 patients were pStage III. By radioimmunoguided surgery biostaging, 24 patients were radioimmunoguided surgery-negative whereas 35 patients were radioimmunoguided surgery-positive. Survival rates by pathologic stage approached a significant difference, but did not, as of the conclusion of the study period, reach it (P = 0.12). Survival rates based on radioimmunoguided surgery status demonstrated a highly significant difference (P = 0.0002). Radioimmunoguided surgery biostaging provides new information intraoperatively on cancer staging that has not been available before. This may lead to new strategies for therapy that can be individualized and optimized for each patient with cancer.


Stem cells for neuroprotection in glaucoma.
Stem cell transplantation is currently being explored as a therapy for many neurodegenerative diseases including glaucoma. Cellular therapies have the potential to provide chronic neuroprotection after a single treatment, and early results have been encouraging in models of spinal cord injury and Parkinson's disease. Stem cells may prove ideal for use in such treatments as they can accumulate at sites of injury in the central nervous system (CNS) and may also offer the possibility of targeted treatment delivery. Numerous stem cell sources exist, with embryonic and fetal stem cells liable to be superseded by adult-derived cells as techniques to modify the potency and differentiation of somatic cells improve. Possible neuroprotective mechanisms offered by stem cell transplantation include the supply of neurotrophic factors and the modulation of matrix metalloproteinases and other components of the CNS environment to facilitate endogenous repair. Though formidable challenges remain, stem cell transplantation remains a promising therapeutic approach in glaucoma. In addition, such studies may also provide important insights relevant to other neurodegenerative diseases.


Determining Diffusion Coefficients of Chemical Warfare Agents in Metal-Organic Frameworks.
Metal-organic frameworks (MOFs) have shown potential for selective capture of chemical warfare agents (CWAs). To determine characteristic adsorption times, the kinetics of CWA uptake in MOFs must be known. Here, we calculate diffusion coefficients of the CWA sarin and simulants in prototypical MOFs using classical molecular simulations. Sarin can diffuse throughout a one micrometer crystal in less than a second in MIL-47 and Cu-BTC, but this process takes more than 3 h in ZIF-8 and UiO-66. A simple estimate based on Knudsen diffusion is able to describe diffusion of sarin in MIL-47 but fails to do so in other MOFs. This work has implications in designing devices to detect and capture CWAs.


McIsaac Modification of Centor Score in Diagnosis of Streptococcal Pharyngitis and Antibiotic Sensitivity Pattern of Beta-hemolytic Streptococci in Chennai, India.
To assess the validity of modified Centor Score in predicting streptococcal pharyngitis, and describe the antibiotic sensitivity of streptococcal strains. A cross-sectional study of 120 children (age 1-18 y) with signs and symptoms of pharyngitis was undertaken in the pediatric department of a tertiary care teaching hospital in Chennai from July 2015 to April 2016. Modified Centor score was calculated for all children, and streptococcal sore throat was confirmed by throat swab culture. Predictive validity of Centor score was assessed by Receiver Operating Curve (ROC) analysis. Streptococcal culture positivity was 35%. The Area Under the Curve (AUC) value for modified Centor score was 0.589 (95% CI 0.481 to 0.697, P=0.11) in predicting streptococcal pharyngitis. Cough had the highest sensitivity (63.4%), but poor specificity (36.7%) for streptococcal pharyngitis confirmed by culture. The specificity was 100% for palatine petechiae, followed by palatine exudates (97.5%) and tender anterior cervical nodes (88.6%) to diagnose streptococcal pharyngitis. The proportion of antibiotic resistance was highest for cotrimoxazole (16.7%). Predictive validity of modified Centor score was not satisfactory, and resistance to cotrimoxazole, fluoroquinolones and macrolides was high among S. pyogenes strains.


Integration of SARS-CoV-2 RNA in infected human cells by retrotransposons: an unlikely hypothesis and old viral relationships.
Zhang et al. (Proc Natl Acad Sci 118:e2105968118, 2021) recently reported that SARS-CoV-2 RNA can be retrotranscribed and integrated into the DNA of human cells by the L1 retrotransposon machinery. This phenomenon could cause persistence of viral sequences in patients and may explain the prolonged PCR-positivity of SARS-CoV-2 infected patients, even long after the phase of active virus replication has ended. This commentary does critically review the available data on this topic and discusses them in the context of findings made for other exogenous viruses and ancestral endogenous retroviral elements.


Radiotherapy after mastectomy.
Classic randomized trials documented the benefit of postmastectomy radiotherapy in women with node-positive or locally advanced breast cancer. Modern advances in surgical therapy, systemic therapy, and radiotherapy, however, along with an improved understanding of cancer biology, have called into question previously assumed recurrence risks and treatment benefits. This article explores the impact of tumor biology and genomic medicine on utilization of postmastectomy radiotherapy and how treatment decision making is moving beyond TNM-based predictors.


Increased Age, Cardiovascular Comorbidities, COPD, and Diabetes mellitus Determine Excess Mortality in Trauma Patients with SSI or Chronic Wounds.
The constant aging of the German population leads, among other things, to an increase in the average age of hospitalised patients. In association with the reduced physiological reserve and the endogenous defence mechanism, this results in an increased susceptibility to infections and complications. Compared with that in trauma patients, the age distribution in patients with surgical site infections (SSI) has been poorly studied. Studies on the impact of age, diverse underlying diseases and influence of alcohol and nicotine consumption on the mortality risk in patients with SSI are limited. In 2014/15 (Exam 1), 345 patients with SSI were included in this study. The 3-year follow-up examination was performed in 2017/18 (Exam 2). The questionnaires (Exams 1 and 2) assessed demographic parameters, comorbidities, medication use, alcohol and nicotine consumption, and different risk factors related to morbidity. The mortality risk in patients with SSI was calculated as a function of various risk factors (age, comorbidities, medication intake, and noxious agents). Furthermore, the development of the patients' age in the trauma department, especially of those with SSI, were evaluated between 2010 and 2019. In 2014/15 (Exam 1), 345 patients were included in the study. Of these, 274 (79.4%) were contacted by telephone in 2017/18. Thirty-six (10.4%) declined to be questioned again. Twenty (8.4%) of the 238 remaining participants had already died, resulting in 218 patients (63.2%) re-participating. From 2010 (n = 492) to 2019 (n = 885), the number of patients with SSI increased by 79.9%, especially those aged < 65 years. After the age of 60 years, the mortality risk increased rapidly (60 years: 0.0377 vs 70 years: 0.1395); the mortality risk of a 60-year-old patient with SSI was equal to that of an 80-year-old in the general population. Nicotine (p = 0.93) and alcohol consumption (p = 0.344) had no significant effect on mortality, whereas history of cardiac disease (p = 0.01), chronic obstructive pulmonary disease (COPD) (p = 0.01), diabetes mellitus (p = 0.05) and peripheral artery disease (p = 0.01) were associated with a significant increase in the mortality risk. Age, pre-existing cardiac conditions, as well as COPD, diabetes mellitus and peripheral artery disease are associated with a significantly increased mortality risk in patients with SSI. Thus, an exponential increase in mortality risk was found between the ages of 50 and 60 years, with the mortality risk of a 60-year-old patient with SSI being equivalent to that of an 80-year-old in the general population.


Mental Disorder Diagnosis from EEG Signals Employing Automated Leaning Procedures Based on Radial Basis Functions.
In this paper, a new automated procedure based on deep learning methods for schizophrenia diagnosis is presented. To this aim, electroencephalogram signals obtained using a 32-channel helmet are prominently used to analyze high temporal resolution information from the brain. By these means, the data collected is employed to evaluate the class likelihoods using a neuronal network based on radial basis functions and a fuzzy means algorithm. The results obtained with real datasets validate the high accuracy of the proposed classification method. Thus, effectively characterizing the changes in EEG signals acquired from schizophrenia patients and healthy volunteers. More specifically, values of accuracy better than 93% has been obtained in the present research. Additionally, a comparative study with other approaches based on well-knows machine learning methods shows that the proposed method provides better results than recently proposed algorithms in schizophrenia detection. The proposed method can be used as a diagnostic tool in the detection of the schizophrenia, helping for early diagnosis and treatment.


[The effect of hepatotoxins on the activity of organelle-specific enzymes and metabolism of liver lipids].
Release of lysosomal hydrolases (including phospholipase A), increase in content of lysophosphatidyl choline and cardiolipin and decrease in content of phosphatidyl choline and phosphatidyl ethanolamine, activation of lipid peroxidation, inhibition of the cell antioxidant system, inhibition of tricarboxylic acid cycle enzymes and of beta-hydroxybutyrate dehydrogenase in mitochondria were detected in hepatocytes of rats after acute poisoning with necrosogenic toxins D-galactosamine, allyl alcohol and apamide. Hydrazine and ethanol caused an extensive steatosis of liver tissue parenchyma, decreased moderately the activity of mitochondrial enzymes, stimulated lipid peroxidation without impairment of antiradical activity of the lipids, contributed to accumulation of cardiolipin and to a decrease in phosphatidyl choline content.


Phospholipase C Beta 1: a Candidate Signature Gene for Proneural Subtype High-Grade Glioma.
Phospholipase C beta 1 (PLCβ1) expresses in gliomas and cultured glial cells, but its expression is barely detectable in normal glial cells. We analyzed data from Gene Expression Omnibus (GEO-GDSxxx), The Cancer Genome Atlas (TCGA), and the Repository for Molecular Brain Neoplasia Data (REMBRANDT) to explore the potential role of PLCβ1 as a biomarker in high-grade glioma (HGG). PLCβ1 expression is significantly higher in grade III gliomas than that in grade IV gliomas from GDS1815 (n = 24 vs. 76), GDS1962 (n = 19 vs. 81), and GDS1975 (n = 26 vs. 59). In GDS1815, PLCβ1 expression correlates with several known proneural (PN) signature genes; its expression from PN subtype (n = 15) is significantly higher than that from mesenchymal (Mes) subtype (n = 33) HGG. In GDS1962, PLCβ1 expression is the highest in nontumor brain tissue (n = 23) and is significantly higher than its expression in grade II gliomas [astrocytomas (n = 7) and oligodendrogliomas (n = 37)]. A Kaplan-Meier survival curve from a REMBRANDT cohort demonstrates that glioma patients with intermediate PLCβ1 expression (n = 103) survived significantly longer than PLCβ1 downregulated (2X) groups (n = 226). From TCGA data, PLCβ1 RNA-Seq signal inversely correlates with the pathological grades, and PLCβ1 expression in PN (n = 8) is of significantly higher levels than that in Mes (n = 8) subtypes of glioblastoma. The top 50 % of PLCβ1 expression subgroup (n = 294) of gliomas (grades II to IV merged) survived significantly longer than the low 50 percentile of the PLCβ1 expression subgroup (n = 293). p values are less than 0.05 for all these analyses. We conclude that PLCβ1 is a candidate signature gene for PN subtype HGG, and its expression inversely correlates with glioma pathological grade and is a potential prognostic factor.


A real-time programming system.
The paper describes a Basic Operating and Scheduling System (BOSS) designed for a small computer. User programs are organised as self-contained modular 'processes' and the way in which the scheduler divides the time of the computer equally between them, while arranging for any process which has to respond to an interrupt from a peripheral device to be given the necessary priority, is described in detail. Next the procedures provided by the operating system to organise communication between processes are described, and how they are used to construct dynamically self-modifying real-time systems. Finally, the general philosophy of BOSS and applications to a multi-processor assembly are discussed.


Neoadjuvant Immune Checkpoint Inhibitor Therapy in Melanoma: Efficacy, Safety and Timing.
The introduction of effective systemic therapies has significantly changed the treatment of stage III and IV melanoma. Both immune checkpoint inhibitors and targeted therapies have improved recurrence-free survival in the adjuvant setting. Recent interest has sparked for neoadjuvant systemic therapy with immune checkpoint inhibitors. The intended benefit of pre-operative treatment with immunotherapy is amongst others to enable tailoring of the surgery and adjuvant systemic therapy according to the treatment response. Most importantly, recurrence-free survival might be improved by neoadjuvant systemic therapy over the current standard of care of surgery followed by adjuvant systemic therapy. The first phase I and II trials investigating anti-PD1 inhibitors, both as a single agent and in combination with anti-CTLA-4 inhibitors or other therapeutic agents, have shown promising results. Pathological complete response on neoadjuvant systemic therapy seems a valid surrogate endpoint for relapse-free and overall survival. Pathological complete response rates in these trials vary between 30 and 70%. The optimal dose with respect to efficacy and toxicity and the interval between systemic and surgical treatment remain important issues to address. Accumulating follow-up data and ongoing phase III studies must prove if neoadjuvant systemic therapy is superior to surgery followed by standard-of-care adjuvant therapy.


The p53-Mdm2 feedback loop protects against DNA damage by inhibiting p53 activity but is dispensable for p53 stability, development, and longevity.
The p53-Mdm2 feedback loop is perceived to be critical for regulating stress-induced p53 activity and levels. However, this has never been tested in vivo. Using a genetically engineered mouse with mutated p53 response elements in the Mdm2 P2 promoter, we show that feedback loop-deficient Mdm2(P2/P2) mice are viable and aphenotypic and age normally. p53 degradation kinetics after DNA damage in radiosensitive tissues remains similar to wild-type controls. Nonetheless, DNA damage response is elevated in Mdm2(P2/P2) mice. Enhanced p53-dependent apoptosis sensitizes hematopoietic stem cells (HSCs), causing drastic myeloablation and lethality. These results suggest that while basal Mdm2 levels are sufficient to regulate p53 in most tissues under homeostatic conditions, the p53-Mdm2 feedback loop is critical for regulating p53 activity and sustaining HSC function after DNA damage. Therefore, transient disruption of p53-Mdm2 interaction could be explored as a potential adjuvant/therapeutic strategy for targeting stem cells in hematological malignancies.


Effectiveness of a video lesson for the correct use in an emergency of the automated external defibrillator (AED).
Every year around 275 thousand people in Europe and 420 thousand in the United States are affected by sudden cardiac arrest. Early electrical defibrillation before the arrival of emergency services can improve survival. Training the population to use the AED is essential. The training method currently in use is the BLSD course, which limits training to a population cohort and may not be enough to meet the requirements of the proposed Law no. 1839/2019. This study aims to verify the effectiveness of an online course that illustrates the practical use of the AED to a population of laypeople. An observational study was conducted to compare a lay population undergoing the view of a video spot and a cohort of people who had participated in BLSD Category A courses. The performances of the two groups were measured immediately after the course and 6 months later. Overall, the video lesson reported positive results. Six months later the skills were partially retained. The cohort that followed the video lesson showed significant deterioration in the ability to correctly position the pads and in safety. Although improved through significant reinforcements, the video spot represents a valid alternative training method for spreading defibrillation with public access and could facilitate the culture of defibrillation as required by the new Italian law proposal.


The development of Graves' disease following radiation therapy in Hodgkin's disease.
Radiation-related thyroid dysfunction is a common occurrence in patients with Hodgkin's disease treated with mantle field radiation. Although chemical and clinical hypothyroidism are most commonly seen, Graves' disease has also been described. We have examined the records of 437 surgically staged patients who received mantle field irradiation between April 1969 and December 1980 to ascertain the frequency of manifestations of Graves' disease. Within this group, seven patients developed hyperthyroidism accompanied by ophthalmic findings typical of those seen in Graves' disease. The actuarial risk of developing Graves' disease at 10 years following mantle irradiation for Hodgkin's disease was 3.3% in female patients and 1% in male patients in this study. The observed/expected ratios were 5.9 and 5.1 for female and male patients, respectively. This observed risk significantly exceeded that seen in the general population.


Micafungin in the treatment of candiduria: A case series.
Echinocandin antifungal agents are not routinely recommended for the treatment of candiduria due to low urine concentrations and a paucity of clinical data supporting this indication. This report presents five cases describing the use of micafungin for the treatment of candiduria. Each patient received parenteral micafungin for a minimum of 6 days and had resolution of baseline fungal within 30 days of treatment completion.


Purification and properties of the membrane-bound hydrogenase from Proteus mirabilis.
The cytoplasmic membrane-bound hydrogenase of the facultative anaerobe, Proteus mirabilis, has been solubilized and purified to homogeneity. The purified enzyme exhibited a maximal specific activity of about 780 mumol H2 oxidized/min per mg protein (benzyl viologen reduction). The hydrogenase has a molecular weight of 205 000 and is composed of two subunits with a molecular weight of 63 000 and two of 33 000. The absorption spectrum of the enzyme was characteristic of non-heme iron proteins. The millimolar extinction coefficients at 400 and 280 nm are 106 and 390, respectively. The hydrogenase has about 24 iron atoms and 24 acid-labile sulfide atoms/molecule. Amino acid analyses revealed the presence of 39 half-cystine residues/molecule and a preponderance of acidic amino acids. The hydrogenase in its oxidized form exhibits an EPR signal of the HiPIP-type with g values at 2.025 and 2.018. Upon reduction with either dithionite or H2 the signal disappears; no other signals were detectable.


The versatile relationships between eIF4E and eIF4E-interacting proteins.
RNA metabolism and gene expression lie at the core of cellular life. eIF4E has emerged as a central interface in both processes as it plays critical roles in mRNA processing, transport, translation, and storage. Crucially, eIF4E depends on its association with a universe of proteins to form biologically meaningful complexes.


New insights into FeS/persulfate system for tetracycline elimination: Iron valence, homogeneous-heterogeneous reactions and degradation pathways.
In this study, complete tetracycline (TTC) and above 50% of total organic carbon (TOC) were removed by FeS/PS after 30 min under optimized conditions. Although free radicals and high-valent iron ions were identified to generate in the process, the apparent similarity between intermediate products of FeS/PS, Fe/PS, and UV/PS systems demonstrated that the degradation of TTC was due to sulfate radicals (SO4⋅-) and hydroxyl radicals (⋅OH). Based on the reaction between free radicals and organic matter, we speculated that TTC in the FeS/PS system was decomposed and mineralized by dehydration, dehydrogenation, hydroxyl addition, demethylation, substitution, E-transfer, and ring-opening. Furthermore, a new understanding of FeS-mediated PS activation based on stoichiometry and kinetic analysis showed that there were both homogeneous and heterogeneous reactions that occurred in the entire progress. However, due to the effect of pH on the dissolution of iron ions, the homogeneous reaction became the principal process with iron ions concentration exceeding 1.35 mg/L. This work provides a theoretical basis for the study of the degradation of TTC-containing wastewater by the iron-based advanced oxidation process.


Failure of an ACE inhibitor to improve exercise tolerance. A randomized study of trandolapril. Trandolapril study group.
There has been conflicting evidence of the effect of angiotensin-converting enzyme (ACE) inhibitors on exercise tolerance. Meta-analysis of published results has suggested that a beneficial effect of ACE inhibitors is demonstrated if a trial design is adequate. Multicentre International Trial. In a double-blind, randomized, multicentre trial, 292 patients with moderate (New York Heart Association Grades II and III) heart failure were treated with trandolapril or placebo in addition to diuretics, and followed for 16 weeks. Exercise tolerance on a treadmill was assessed at baseline and after 4, 8, 12 and 16 weeks of treatment. Both a modified Bruce and a modified Naughton protocol were used. Exercise tolerance improved in both treatment groups, with no significant benefit from trandolapril treatment. Trandolapril does not improve exercise tolerance as measured by treadmill testing.


Performing gender: Social workers' roles during the COVID-19 pandemic in China.
Women social workers' roles during COVID-19 have been under-researched. We contribute to filling this gap by examining patriarchal inequalities in the pay and status of women social workers in Wuhan, China to determine whether change occurred when they replaced men in first-tier responder or protector roles when the government replaced men in frontline social work with women social workers. We conducted a qualitative investigation into these practitioners' work during the COVID-19 pandemic lockdown in Wuhan from 23 January to April 7, 2020 through 30 in-depth interviews of women social workers (11 working in Residents' Committees, 12 in NGOs from Wuhan and six other cities; and 7 in other local organizations). The findings highlight how women social workers' roles shifted during the pandemic from being second-tier responders to assuming the first-tier responder or 'protector' roles previously held by men while they continued their second-tier responders' and traditional caring roles. Despite this shift, the data show that women's demands for higher pay and status and involvement in decision-making structures remained unmet. Although women resisted unequal gender relations, doing men's roles as protectors loaded them with a 'triple' burden as protectors, second-tier responders and carers. The lack of gender equality for these women social workers highlights an urgency for policymakers and practitioners to promote gender equality by implementing women social workers' entitlements to pay parity, engagement in decision-making, and assumption of leadership roles, i.e., as men's equals.


Prevalence of hyperinsulinemia and clinical correlates in overweight children referred for lifestyle intervention.
Although not well documented in the literature, there is growing evidence that overweight children may develop hyperinsulinemia. Children (n=171) with a body mass index greater than the 85th percentile for age using the Centers for Disease Control and Prevention growth charts for children were recruited through primary care physician offices for a lifestyle change intervention. Laboratory measurements were obtained. About 30% of these children were identified as hyperinsulinemic, using an insulin-to-glucose ratio of > or =33% or a serum insulin > or =25 microU/mL. When compared with non-hyperinsulinemic children, there were significant differences in cardiovascular risk factors. Dietetics professionals providing medical nutrition therapy to overweight children need to be aware of dietary and physical activity recommendations for individuals with marked hyperinsulinemia.


Improving autism and developmental screening and referral in US primary care practices serving Latinos.
Latino children experience delays in access to diagnosis and treatment of autism spectrum disorder. Primary care-based screening of all children for autism spectrum disorder and referring them for services may reduce racial/ethnic differences and improve care. REAL-START, a yearlong screening intervention, was effective in increasing screening for autism spectrum disorder and general developmental delays, increasing therapy referrals, and shortening time for developmental assessment in primary care clinics with Latino patients.


Novel α-1,3/α-1,4-Glucosidase from Aspergillus niger Exhibits Unique Transglucosylation to Generate High Levels of Nigerose and Kojibiose.
α-Glucosidase from Aspergillus niger (AgdA; typical α-1,4-glucosidase) is known to industrially produce α-(1→6)-glucooligosaccharides. This fungus also has another α-glucosidase-like protein, AgdB. To learn its function, wild-type AgdB was expressed in Pichia pastoris. However, the enzyme displayed two electrophoretic forms due to heterogeneity of N-glycosylation at Asn354. The deglycosylation mutant N354D shared the same properties with wild-type AgdB. N354D demonstrated hydrolytic specificity toward α-(1→3)- and α-(1→4)-glucosidic linkages, indicating that AgdB is an α-1,3-/α-1,4-glucosidase. N354D-catalyzed transglucosylation from maltose was analyzed in short- and long-term reactions, enabling us to learn the transglucosylation specificity and product accumulation, respectively. A short-term reaction (<15 min) synthesized 3II- O-α-glucosyl-maltose and maltotriose, indicating α-1,3-/α-1,4-transferring specificity. A long-term reaction (<24 h) accumulated kojibiose and nigerose using formed glucose as an acceptor substrate. AgdA and AgdB are distinct α-glucosidases. At a high concentration of glucose added exogenously, AgdB largely generated the rare sugars kojibiose and nigerose (exhibiting beneficial physiological functions) with 19% and 24% yields from maltose, respectively.


Neuropeptide W as a stress mediator in the hypothalamus.
Neuropeptide W (NPW) was isolated and found to be an endogenous peptide ligand for the orphan receptors GPR7 and GPR8. Centrally administered NPW caused a dose-dependent increase in corticosterone levels in rats. This observation indicates that NPW may play an important role in the hypothalamic organization of the endocrine response to stress. We examined the effects of immobilization stress and cold exposure on NPW-containing neurons in the hypothalamus of the rat, using dual immunostaining for NPW and Fos. In addition, to analyze the function of NPW, we studied the effect of intracerebroventricular (icv) NPW administration on Fos protein accumulation in the brain. Double immunohistochemistry for NPW and Fos showed that the percentage of Fos expression in the NPW-immunoreactive cells of the perifornical nucleus was significantly increased by immobilization stress compared with that in nonstressed rats. Similarly, the results indicated that cold exposure activates NPW-immunoreactive neurons in the perifornical nucleus. An icv administration of NPW resulted in significant Fos expression in the paraventricular nucleus, as compared with saline-infused controls. These results suggest that NPW is related to stress-responsive signal transduction, and that NPW may modulate the hypothalamus-pituitary-adrenal axis.


Discovery of three novel lipase ( lipA1 , lipA2 , and lipA3) and lipase-specific chaperone ( lipB) genes present in Acinetobacter sp. DYL129.
A microbe isolated from a soil sample obtained on Deog-yu Mountain in Korea, was found to produce an extracellular lipase. This microbe, which was designated as DYL129, was identified as an Acinetobacter sp. based on phylogenetic analysis of its 16S rDNA. A genomic library was constructed by using DYL129 fragment digested with HindIII and a recombinant plasmid, pLip-1, was selected for further analysis by colony polymerase chain reaction (PCR). Sequencing of a 3.8-kb insert in the pLip-1 clone revealed the presence of one incomplete and three complete open reading frames (ORFs). The ORFs were predicted to encode a partial lipase, two putative lipases and a 50S ribosomal protein. Genome-walking PCR also identified transcripts encoding a complete lipase chaperone and three lipaseA proteins. The lipase structural gene present in Acinetobacter sp. DYL129 was similar to the lipase structural gene found in Acinetobacter calcoaceticus BD413 (lipBA). However, the three lipase genes were located downstream of the chaperone gene in Acinetobacter sp. DYL129 (lipBA (1) A (2) A (3)), which differs from the location of these genes in A. calcoaceticus BD413. Although the amino acid sequences of these lipases (LipA(1), LipA(2), and LipA(3)) differed, both strains had a common "GHSHG" consensus motif, which is the conserved active-site pentapeptide of lipaseA. Moreover, all three lipases were found to share a conserved domain, the so-called alpha/beta hydrolase fold.


Relationship between gut microbiome diversity and hepatitis B viral load in patients with chronic hepatitis B.
Hepatitis B virus (HBV) infection is associated with a reduced risk of developing dyslipidemia and non-alcoholic fatty liver diseases. Given that the gut microbiota plays a significant role in cholesterol metabolism, we compared the differences in gut microbial diversity and composition between HBV-infected and uninfected subjects. A prospective case-control study was designed comprising healthy controls (group A) and HBV-infected individuals (group B) in a 1:1 ratio (57 participants each; total = 114). The patients in group B were divided into two subgroups according to their HBV DNA loads: B1 < 2000 IU/mL (N = 40) and B2 ≥ 2000 IU/mL (N = 17). In a pairwise comparison of HBV-infected individuals and controls, higher alpha diversity was noted in group B, and the difference was significant only in patients in group B1. Alloprevotella and Eubacterium coprostanoligenes were predominant in group B1 compared to the control, whereas the abundance of Bacteroides fragilis and Prevotella 2 was lower. The gut microbiome in HBV-infected individuals with a low viral load is highly diverse and is dominated by specific taxa involved in fatty acid and lipid metabolism. To our knowledge, this is the first demonstration of a correlation between the presence of certain bacterial taxa and chronic HBV infection depending on the load of HBV DNA.


Rainbow's end: the quest for multiplexed fluorescence quantitative analysis in proteomics.
During the past two years, the performance of fluorescence-based protein detection methods has demonstrably eclipsed conventional technologies such as colloidal Coomassie Blue and silver staining with respect to detection sensitivity, quantitative accuracy and compatibility with modern protein identification and characterization procedures. At this point, fluorescence-based methods are poised to offer unprecedented new capabilities in proteomics investigations through the performance of multi-parameter quantitative measurements. The feasibility of such measurements has already been demonstrated through the specific detection of antibiotic-binding proteins, drug-metabolizing enzymes or post-translationally glycosylated proteins, along with the total protein expression profile from electrophoretically separated, complex biological specimens.


Risk factors for HIV and syphilis infection among male sex workers who have sex with men: a cross-sectional study in Hangzhou, China, 2011.
To investigate the prevalence and risk factors of HIV and syphilis infection among men who have sex with men (MSM) in male sex workers (MSW). Cross-sectional survey. Hangzhou, China. 259 MSW in MSM were recruited by respondent-driven sampling from May 2011 to December 2011.The inclusion criteria were: (1) age ≥18 years; (2) engaging in sex with men in the previous year and (3) willing to cooperate in the implementation of the study. HIV-related knowledge, high-risk behaviour and condom use. Among these MSW in MSM, 23.2% were infected with HIV and/or syphilis, 8.9% were infected only with HIV, 12.7% only with syphilis and 1.5% with HIV/syphilis co-infection; 96.6% sold sex to males, 8.9% bought sex from males and 15.4% sold sex to females; 49.0% had non-commercial sex behaviours with males and 24.3% with females. The rate of condom use while having commercial sex with clients was 86.9% and 53.3% (selling anal and oral sex to males, respectively), 95.5% (buying sex from males) and 77.5% (selling sex to females), respectively. Regarding their non-commercial sex behaviour, the rate of condom use was 77.2% (with males) and 49.2% (with females), respectively. Multivariate analysis showed that age >30 years (OR 1.055; 95% CIs 1.015 to 1.095) and having ≥10 non-commercial male sex partners (OR, 1.573; 95% CI 1.018 to 2.452) were significantly associated with HIV/syphilis infection, while heterosexuality (OR, 0.238; 95% CI 0.066 to 0.855) was significantly associated with a low HIV/syphilis infection rate. The MSW in MSM population in Hangzhou has a high prevalence of HIV/syphilis infection, poor perceived risks of HIV and more engagement in unsafe sex with its clients and partners, in addition to a low rate of condom use. These risk factors may account for their relatively high infection rate of HIV/syphilis.


First Draft Genome Sequence of Staphylococcus condimenti F-2T.
This report describes the draft genome sequence of S. condimenti strain F-2(T) (DSM 11674), a potential starter culture. The genome assembly comprised 2,616,174 bp with 34.6% GC content. To the best of our knowledge, this is the first documentation that reports the whole-genome sequence of S. condimenti.


Influence of aFusarium culmorum inoculation of wheat onin sacco dry matter degradation of wheat straw and wheat chaff.
The aim of this study was to investigate the effect of aFusarium culmorum inoculation of wheat on thein sacco dry matter degradation (DG) of wheat straw and wheat chaff in dairy cows. The ruminal disappearance of dry matter was measured with thein situ nylon bag technique. Samples of wheat straw and wheat chaff from non-inoculated andFusarium-inoculated wheat were used to examine the ruminal dry matter degradability. Samples were subjected to ruminal incubation in two dairy cous fitted with a permanent rumen fistula and incubated for 4, 8, 16, 24, 48, 72, 96 and 120 h. To describe the degradation kinetics, the equation by Ørskov and McDonald (1979) was used. DG rates obtained for contaminates straw and chaff were higher compared to the corresponding rates of the non-contaminated samples, which is assumed to be due to the activity of fungal enzymes. It can be concluded that an infection of wheat withF. culmorum may have an influence on the dry matter degradation of straw and chaff.


Development of a Patient-Derived 3D Immuno-Oncology Platform to Potentiate Immunotherapy Responses in Ascites-Derived Circulating Tumor Cells.
High-grade serous ovarian cancer (HGSOC) is responsible for the majority of gynecology cancer-related deaths. Patients in remission often relapse with more aggressive forms of disease within 2 years post-treatment. Alternative immuno-oncology (IO) strategies, such as immune checkpoint blockade (ICB) targeting the PD-(L)1 signaling axis, have proven inefficient so far. Our aim is to utilize epigenetic modulators to maximize the benefit of personalized IO combinations in ex vivo 3D patient-derived platforms and in vivo syngeneic models. Using patient-derived tumor ascites, we optimized an ex vivo 3D screening platform (PDOTS), which employs autologous immune cells and circulating ascites-derived tumor cells, to rapidly test personalized IO combinations. Most importantly, patient responses to platinum chemotherapy and poly-ADP ribose polymerase inhibitors in 3D platforms recapitulate clinical responses. Furthermore, similar to clinical trial results, responses to ICB in PDOTS tend to be low and positively correlated with the frequency of CD3+ immune cells and EPCAM+/PD-L1+ tumor cells. Thus, the greatest response observed with anti-PD-1/anti-PD-L1 immunotherapy alone is seen in patient-derived HGSOC ascites, which present with high levels of systemic CD3+ and PD-L1+ expression in immune and tumor cells, respectively. In addition, priming with epigenetic adjuvants greatly potentiates ICB in ex vivo 3D testing platforms and in vivo tumor models. We further find that epigenetic priming induces increased tumor secretion of several key cytokines known to augment T and NK cell activation and cytotoxicity, including IL-6, IP-10 (CXCL10), KC (CXCL1), and RANTES (CCL5). Moreover, epigenetic priming alone and in combination with ICB immunotherapy in patient-derived PDOTS induces rapid upregulation of CD69, a reliable early activation of immune markers in both CD4+ and CD8+ T cells. Consequently, this functional precision medicine approach could rapidly identify personalized therapeutic combinations able to potentiate ICB, which is a great advantage, especially given the current clinical difficulty of testing a high number of potential combinations in patients.


Neural dependence and independence of myotube production in chicken hindlimb muscles.
Chicken embryos were paralyzed by repeated injections of the neuromuscular blocking agent d-tubocurarine, from the fourth day in ovo until sacrificed. This treatment affected the late but not early stages of myogenesis. The production of the initial generation(primary) of myotubes was unaffected whereas, in contrast, the acquisition of subsequent generations (secondary) of myotubes was totally inhibited. The elongation and growth of primary myotubes proceeded normally although their differentiation was retarded. An atrophy of these myotubes was not observed even in Day 17 embryos. It is concluded that the factors regulating myogenesis change as the muscle matures.


Effect of lipid composition on hydrophobic properties of liposomes.
Partition behavior of liposomes of different composition in the aqueous Ficoll-Dextran biphasic system was examined. The relative hydrophobicity of the liposomes was estimated. The effect of cholesterol on the solvent interactions of lecithin and sphingomyelin liposomes was studied. It is found that the effect of phosphatidylethanolamine on the hydrophobic character of lecithin liposomes exceeds that produced by cholesterol. The relative hydrophobicity of all the liposomes examined was found to be independent of the ionic composition of the system containing varied amounts of NaCl and Na-phosphate buffer, pH 7.4. The hydrophobic character of the liposomes under study is shown to increase in the following order: phosphatidylserine less than phosphatidylethanolamine less than phosphatidylcholine less than sphingomyelin. Hydrophobic properties of the liposomes are compared to those of human red cells. It is suggested that the dependence of the hydrophobic character of membrane particles on the ionic composition of an aqueous environment can be of fundamental importance for the selective distribution of the particles in vivo.


["And zebras do exist after all"! : Pulmonary nocardiosis: case series and overview].
Nocardiosis is a rare disease that occurs primarily in patients with predisposing factors (immunosuppression/chronic lung disease). It is caused by aerobic, Gram-positive bacteria that are ubiquitous in soil. Cutaneous and pulmonary manifestations are most common, but disseminated forms also occur. In terms of treatment, long-term antibiotic therapy is usually necessary. The prognosis for the cutaneous or pulmonary form is generally good.


Network Localization of Unconscious Visual Perception in Blindsight.
Blindsight is a disorder where brain injury causes loss of conscious but not unconscious visual perception. Prior studies have produced conflicting results regarding the neuroanatomical pathways involved in this unconscious perception. We performed a systematic literature search to identify lesion locations causing visual field loss in patients with blindsight (n = 34) and patients without blindsight (n = 35). Resting state functional connectivity between each lesion location and all other brain voxels was computed using a large connectome database (n = 1,000). Connections significantly associated with blindsight (vs no blindsight) were identified. Functional connectivity between lesion locations and the ipsilesional medial pulvinar was significantly associated with blindsight (family wise error p = 0.029). No significant connectivity differences were found to other brain regions previously implicated in blindsight. This finding was independent of methods (eg, flipping lesions to the left or right) and stimulus type (moving vs static). Connectivity to the ipsilesional medial pulvinar best differentiates lesion locations associated with blindsight versus those without blindsight. Our results align with recent data from animal models and provide insight into the neuroanatomical substrate of unconscious visual abilities in patients. ANN NEUROL 2022;91:217-224.


Ultrasound-assisted pH-shifting to construct a stable aqueous solution of paprika oleoresin using egg yolk low-density lipoprotein as a natural liposome-like nano-emulsifier.
In this study, a stable aqueous solution of paprika oleoresin (PO, the natural colorant extracted from the fruit peel of Capsicum annuum L) was constructed. The solubility of PO in an alkline aqueous solution (pH 10.95-11.10) increased rapidly. However, the aqueous solution of PO (pH 12.00) was unstable, obvious stratification was observed, and the color retention rate was only 52.99% after 28 days of storage. Chicken egg yolk low-density lipoprotein (LDL) was added combined with ultrasonic treatment to improve the stability of LDL-PO solution. The method could decrease the turbidity by 17.5 %, reduce the average particle size of the LDL-PO solution (13.9%), and enhance the interaction and combination of LDL and PO. The prepared PO aqueous solution was used in yogurt, egg white gel, fish balls and soymilk, and it could significantly improve the color of products and provided potential health benefits.


Intranasal therapeutic vaccine containing HBsAg and HBcAg for patients with chronic hepatitis B; 18 months follow-up results of phase IIa clinical study.
HBsAg loss with anti-HBs acquisition is considered a functional cure and ideal treatment goal for patients with CHB. Our group have reported the efficacy of therapeutic vaccine with HBsAg and HBcAg (NASVAC) by intranasal and subcutaneous injection. In this study, we investigated the safety and efficacy of newly developed CVP-NASVAC, which contained NASVAC with mucoadhesive carboxyl vinyl polymer (CVP) in the dedicated device. A single dose, open-label, phase IIa clinical trial of CVP-NASVAC was conducted. Patients with CHB treated with nucleoside/nucleotide analogs (NAs) and HBV carriers not undergoing anti-HBV treatment were enrolled. CVP-NASVAC was injected through the nose for, in total, 10 times. Participants were followed-up for 18 months, and their HBsAg reduction and anti-HBs induction assessed as endpoints. Among the patients with CHB treated with NAs (n = 27) and HBV carriers without NAs (n = 36), 74.1% and 75.0% exhibited reductions in their baseline HBsAg, and the mean reductions were -0.1454 log10 IU/ml (p < 0.05) and -0.2677 log10 IU/ml (p < 0.05), respectively. Anti-HBs antibody was detected in 40.7% and 58.3% of patients treated with and without NAs, respectively. Six of 71 (9.5%) patients were functionally cured after the CVP-NASVAC treatment. Anti-HBs induction and HBsAg reduction was observed after CVP-NASVAC treatment in some patients with CHB. The CVP-NASVAC is a safe treatment, which might expect to achieve functional cure for patients with CHB.


Temporary parental separation at birth and substance use disorder in adulthood. A long-term follow-up of the Finnish Christmas Seal Home Children.
Adversities in the early mother-infant relation pose a hypothetical risk for addiction. We studied the association between very early separation and later development of substance use disorder. A follow-up study was performed of subjects temporarily isolated from their family immediately after birth to adequate nursing homes in order to protect them against morbidity and mortality for tuberculosis. The average separation time was 7 months. The index cohort consisted of 3,020 subjects born in 1945-1965. For every index subject, two reference subjects were matched for sex, year of birth and place of birth. We were able to obtain the SES of the family of origin as recorded in 1971 from Statistics Finland. Finnish Hospital Discharge Register was used to identify subjects with substance use disorder arising from childhood to middle age, between January 1,1971 and December 31, 1998. The 28-year cumulative incidence of alcohol use disorders was 4.2% in the index cohort and 3.1% in the reference cohort (rate ratio, RR 1.4, 95% CI 1.1-1.8). The incidences of hospital-treated drug abuse or dependence were 0.6% and 0.2% (RR 2.5, 95% CI 1.2-5.1), respectively. The differences in socioeconomic status of the family of origin did not explain the differences found. Substance use disorders were more prevalent among subjects temporarily separated at birth from their mothers because of tuberculosis in the family than in the reference cohort. While risks experienced during pregnancy, delivery and childhood are alternative explanations, this result suggests that very early temporal separation from the mother at birth may have had unfavourable but modest effects on later psychological development, including vulnerability to addiction.


Increase in SARS-CoV-2 RBD-Specific IgA and IgG Antibodies in Human Milk From Lactating Women Following the COVID-19 Booster Vaccination.
The United States Centers for Disease Control and Prevention recommended a third dose or booster of the Pfizer-BioNTech Comirnaty (BNT162b2) COVID-19 mRNA vaccine in September 2021 for high-risk individuals. Pregnant and high-risk lactating women were encouraged to receive the booster to obtain potential prolonged protection for themselves and their infants. To investigate the ability of the booster vaccine to increase IgA and IgG antibodies specific to the receptor-binding domain of the SARS-CoV-2 spike protein in human milk compared to levels pre-booster. This was a prospective one-group study with a pretest-posttest design. Six of 12 participants were recruited prospectively. Participants were instructed to collect ≥ 2 ounces of milk in the morning at 30 days and 1-day pre-booster, and 7, 14, 21, 30, 45, and 60 days post-booster. Levels of IgA and IgG antibodies specific to the receptor-binding domain of the SARS-CoV-2 spike protein were quantified in human milk via an ELISA assay. We found a significant increase in anti-receptor-binding domain-specific IgA and IgG antibodies in human milk 1-2 weeks after the Pfizer-BioNTech booster and at the study endpoint (45- and 60-days post-booster). This suggests that the booster vaccination enhances SARS-CoV-2 specific immunity in human milk, which may be protective for infants.


International Validation of the EORTC QLQ-ANL27, a Field Study to Test the Anal Cancer-Specific Health-Related Quality-of-Life Questionnaire.
The European Organisation for Research and Treatment of Cancer (EORTC) health-related quality of life questionnaire for anal cancer (QLQ-ANL27) supplements the EORTC cancer generic measure (QLQ-C30) to measure concerns specific to people with anal cancer treated with chemoradiotherapy. This study tested the psychometric properties and acceptability of the QLQ-ANL27. People with anal cancer were recruited from 15 countries to complete the QLQ-C30 and QLQ-ANL27 and provide feedback on the QLQ-ANL27. Item responses, scale structure (multitrait scaling, factor analysis), reliability (internal consistency and reproducibility) and sensitivity (known group comparisons and responsiveness to change) of the QLQ-ANL27 were evaluated. Data from 382 people were included in the analyses. The EORTC QLQ-ANL27 was acceptable, comprehensive, and easy to complete, taking an average 8 minutes to complete. Psychometric analyses supported the EORTC QLQ-ANL27 items and reliability (Cronbach's α ranging from 0.71-0.93 and test-retest coefficients above 0.7) and validity of the scales (particularly nonstoma bowel symptoms and pain/discomfort). Most scales distinguished people according to treatment phase and performance status. Bowel (nonstoma), pain/discomfort, and vaginal symptoms were sensitive to deteriorations over time. The stoma-related scales remained untested because of low numbers of people with a stoma. Revisions to the scoring and question ordering of the sexual items were proposed. The QLQ-ANL27 has good psychometric properties and is available in 16 languages for people treated with chemoradiotherapy for anal cancer. It is used in clinical trials and has a potential role in clinical practice.


Strategies to preventing pressure injuries among intensive care unit patients mechanically ventilated in prone position: a systematic review and a Delphi study.
Although the incidence of pressure injury in the prone position is high for the mechanically ventilated patients in the intensive care unit, evidence-based strategies are still lacking. To conduct a systematic review of current evidence, and to propose a series of strategies to prevent pressure injuries among mechanically ventilated patients with prone position in the intensive care unit. The study was guided by the Medical Research Council framework. After a systematic review of current evidence of original articles, guidelines, expert consensus and theories, a strategy draft was developed. Then we invited 20 experts to modify and refine these strategies through two rounds of Delphi consensus method. After two rounds of Delphi process, the importance of coefficient of variation (Cv) and Kendall's coefficient of concordance in the strategies repository were 0.067 and 0.311, respectively. And the operability of Cv and Kendall's coefficient of concordance in the strategy draft was 0.055 and 0.294, respectively. Ultimately, we established 31 strategies for including 7 themes (assess risk factors, assess skin and tissue, body position management, skin care, nutrition, preventing medical device-related pressure injuries, education and supervision). In addition, we also developed a strategy framework to clarify our strategies. According to the Medical Research Council framework, we developed 7 themes and 31 strategies to prevention prone-position pressure injuries among the intensive care unit mechanically ventilated patients. This study was considered to improve the clinical management of pressure injuries among prone position patients in the intensive care unit settings.


Triterpenoids from the stems and leaves of Schisandra incarnata.
Six undescribed triterpenoids, schincarins A‒F, categorized as the preschisanartane (schincarin A), 3,4-secocycloartane (schincarins B‒D), 3,4; 9,10-disecocycloartane (schincarin E), and 3,4-secolanostane (schincarin F) classes, along with twelve known analogues, were obtained from the stems and leaves of Schisandra incarnata Stapf. Their structures were elucidated on the basis of extensive spectroscopic analyses. The absolute configuration of schincarin A was corroborated by analysis of the experimental ECD spectrum, and single-crystal X-ray diffraction with Mo Kα irradiation. Schincarin A represented the first example of preschisanartane-type triterpenoid with two oxa-bridged hemiketals. Among the selected compounds which were evaluated for immunosuppressive activities, schincarin C and kadsudilactone A showed potential inhibition against ConA-induced T-cell proliferation with IC50 values of 5.83 and 6.32 μM, and LPS-induced B cell proliferation with IC50 values of 10.21 and 11.49 μM, respectively.


Selenoprotein S attenuates high glucose and/or ox-LDL-induced endothelium injury by regulating Akt/mTOR signaling and autophagy.
Glucolipid metabolism disorder in diabetes mellitus (DM) causes human endothelial injury and autophagy dysfunction is an important cause of endothelial dysfunction (ED). Selenoprotein S (SelS) could protect endothelium from oxidative stress, inflammatory responses, and apoptosis. This study assessed the effect of SelS on autophagy in glucolipid metabolic disorders and protection of the resulted vascular endothelial injury. The results showed that high glucose (HG), high oxidized low-density lipoprotein (HL), and HG combined with HL (HGL) could reduce viability of human aortic endothelial cells (HAECs), induce HAECs injury and increase SelS expression in a time-dependent manner. HG, HL, and HGL also initially induced autophagy but later reduced it in HAECs, while activity of the Akt/mTOR signaling was inhibited, especially in HGL culture of HAECs. SelS overexpression reduced the endothelial injury and autophagy and activated the Akt/mTOR signaling in HG, HL and HGL-cultured HAECs, compared to the control. Conversely, knockdown of SelS expression had the opposite effects on HAECs. In conclusion, SelS demonstrated a protective effect on endothelial injury induced by high glucose and/or ox-LDL and the underlying molecular events might be related to its regulation of HAECs autophagy by activating the Akt/mTOR signaling. SelS could be a potential intervention target in prevention and treatment of diabetic vascular complications.


miRNA expression profile in chicken ovarian follicles throughout development and miRNA-mediated MMP expression.
Accumulating evidence has demonstrated the role of microRNAs (miRs) in the avian ovary. In this study, high-throughput transcriptome analyses were employed to study the differential miR expression profiles in the chicken ovary, aiming to reveal miR-targeting matrix metalloproteinase (MMP) expression during follicular growth, maturation, and atresia. Using tissues of chicken ovarian follicles at key steps of development (slow growing - white, the most recently recruited - small yellow, and preovulatory - F2) and regression (the third postovulatory), 14 small RNA (sRNA) libraries were constructed. The 25 most highly expressed known miRs were identified along with eight significantly differentially expressed (DE) miRs (gga-miR-let-7d, gga-miR-31-3p, gga-miR-138-1-3p, gga-miR-1552-5p, gga-miR-92-3p, gga-miR-31-5p, gga-miR-202-3p, and gga-miR-6648-3p) which were further examined by quantitative real time-PCR (qRT-PCR) in white, yellowish, small yellow, and atretic follicles as well as in the granulosa and theca layer of yellow preovulatory F3-F1 follicles (n = 6 hens). These miRs were mainly associated with four pathways: inhibition of MMPs, axonal guidance signaling, HIF1α signaling, and GP6 signaling. Four predicted target genes (i.e. MMP-16, ADAM10, COL4A2, and COL4A5) were examined by qRT-PCR and negatively correlated with DE miRs. The identified candidate miR:mRNA target pairs include gga-miR-31-5p or gga-miR-92-3p:MMP-16, gga-miR-31-5p or gga-miR-92-3p:ADAM10, let-7d:COL4A2, and gga-miR-138-1-3p:COL4A5 are potentially associated with MMP modulation in the hen ovary, mostly in the granulosa and theca cells of the largest preovulatory follicles. These results provide a novel insight to the role of miRs in follicle development by identifying a miR target network that is putatively engaged in remodeling of the extracellular matrix during ovarian follicle development in chickens.


Voluma: A Systematic Review of Clinical Experience.
Dermal fillers are important for facial aesthetic enhancement as patients are favoring non-surgical procedures with minimal recovery time. Voluma is a volumizing hyaluronic acid filler, 20 mg/ml HA dermal filler, which was FDA-approved in 2013 as the first dermal filler for treatment of age-related volume loss in the midface. We sought to systematically review clinical studies and expert opinions of this 20 mg/ml HA dermal filler and to provide evidence-based recommendations and expert opinions. A search of the computerized bibliographic databases Medline, Embase, Embal, Biosis, SciSearch, Pascal, HCAPlus, IPA, and Dissertation Abstracts was performed on August 18th 2014. Thirteen articles met inclusion and were included in our review: clinical trials with this 20 mg/ml HA dermal filler (10) and expert opinions and questionnaire survey studies of experts (3). This 20 mg/ml HA dermal filler has shown consistent, favorable results for treatment of age-related facial volume loss, aesthetic enhancement, and HIV facial lipoatrophy. HA fillers are safe and effective with minimal recovery time and complications. Future studies with longer follow-up period and use of this 20 mg/ml HA dermal filler on areas other than midface may provide additional efficacy and safety outcomes.


Allelic MHC class I chain related B (MICB) molecules affect the binding to the human cytomegalovirus (HCMV) unique long 16 (UL16) protein: implications for immune surveillance.
Unique long 16 (UL16) is a viral glycoprotein produced in a host cell infected with human cytomegalovirus (HCMV). It down regulates surface expression of MICB, one of the NKG2D ligands, by forming stable intracellular complexes and retained in the endoplasmic reticulum. Down expression of MICB renders cells less susceptible to NK cell lysis via the NKG2D receptor. Diverse UL16 sequences were identified from different strains of HCMV. MICB is known to be polymorphic. It is not known whether these polymorphisms affect the interactions between these molecules leading to alteration of the immune surveillance of HCMV. The soluble Fc fusion variant UL16 proteins from four laboratory and clinical isolates (AD169, Toledo, PH, and TR) were produced. Four allelic MICB alleles (008, 003, 004, and 00502) were cloned and stable cell lines expressing these MICB alleles were produced. The binding activities of variant UL16 to allelic MICB proteins were determined by flow cytometry. The variants of UL16 proteins did not affect the binding activities to allelic MICB proteins. However, diverse MICB alleles differentially bound UL16. We found that MICB*008 which contains methionine and asparagine at the amino acid positions 98 and 113, respectively, in the alpha 2 domain showed decreased binding activities to UL16 when compared to MICB*003, 004, and MICB*00502 containing isoleucine and aspartic acid, respectively. This finding may imply that MICB*008 is a protective allele and involved in the immune surveillance of HCMV infected patients.


[Patients with craniocerebral injuries and their reintegration into vocational life. The effect of parameters independent of the accident on expert assessment].
A prospective study of 60 patients with head injuries who received both primary care and an assessment at our Department, the influence of various parameters on the assessment was investigated. Catamnestically, the insurance-relevant results actually achieved are shown. It can be seen that at a 40 per cent incapacitation, reintegration into the work-a-day world is hardly possible.


The relationship between changes in REM sleep and clinical improvement in depressed patients treated with amitriptyline.
EEG sleep recordings were obtained on consecutive nights from six hospitalized depressed patients before, during, and after treatment with amitriptyline for a total of 370 nights of data, about 85% of all nights of the study. Amitriptyline significantly reduced time spent in rapid eye movement (REM) sleep and prolonged the REM latency throughout the treatment period. Three patients who improved during treatment showed a REM rebound when amitriptyline was discontinued, whereas three patients who did not improve showed no REM rebound.