Surface Modification of Polysaccharide-Based Nanoparticles with PEG and Dextran and the Effects on Immune Cell Binding and Stimulatory Characteristics.
Surface modifications of nanoparticles can alter their physical and biological properties significantly. They effect particle aggregation, circulation times, and cellular uptake. This is particularly critical for the interaction with primary immune cells due to their important role in particle processing. We can show that the introduction of a hydrophilic PEG layer on the surface of the polysaccharide-based nanoparticles prevents unwanted aggregation under physiological conditions and decreases unspecific cell uptake in different primary immune cell types. The opposite effect can be observed with a parallel-performed introduction of a layer of low molecular weight dextran (3.5 and 5 kDa) on the particle surface (DEXylation) that encourages the nanoparticle uptake by antigen-presenting cells like macrophages and dendritic cells. Binding of DEXylated particles to these immune cells results in an upregulation of surface maturation markers and elevated production of proinflammatory cytokines, reflecting cell activation. Hence, DEXylated particles can potentially be used for passive targeting of antigen presenting cells with inherent adjuvant function for future immunotherapeutic applications.


Occupational therapy master-level students' evidence-based practice knowledge and skills before and after fieldwork.
ABSTRACT Evidence-based practice (EBP) has become a universal standard for practice among healthcare professions, but due to barriers to EBP, the most effective ways of teaching EBP are not well understood. The purpose of this study was to report students' EBP knowledge and skill gained from an entry-level Master's of Science in Occupational Therapy course in EBP. The Adapted Fresno Test of EBP was administered at the beginning and end of the course and after fieldwork experience. Results indicated that EBP knowledge and skills increased between the precourse and postcourse measurements (t = -7.98; p < 0.001), but declined between postcourse and postfieldwork measurements (t = 6.65; p < 0.001) indicating that the course improved basic EBP skills and knowledge, but was ineffective in giving the students the strategies to retain and use those skills beyond the classroom. Suggestions are made to strengthen the student retention and use of EBP skills and knowledge after graduation.


Complex trauma among psychiatrically impaired children: a cross-sectional, chart-review study.
To identify subgroups of severely psychiatrically impaired children on the basis of the complexity of their histories of exposure to abuse and other potential traumatic stressors, and to examine the relationship of complex trauma histories to DSM-IV-TR psychiatric diagnoses. In a sample of 397 consecutive inpatient child psychiatry admissions, cluster analysis was used to identify subgroups on the basis of measures of documented physical or sexual abuse, parental impairment (arrest, violence, and/or substance use), and disrupted attachment (ie, out-of-home placement). Data were collected for the years 1992 through 2002. Four subgroups were identified. Two "low trauma" subgroups had infrequent histories of abuse and out-of-home placement but were distinguished by low/moderate versus high levels of parental impairment. Two "complex trauma" subgroups were characterized by histories of either physical abuse or sexual abuse with multiple perpetrators, as well as extensive out-of-home placement and severe parental impairment. All subgroups had similar profiles of psychiatric diagnoses. Complex trauma status was associated with behavior problem severity and lower body mass index over and above the effects of psychiatric diagnoses, gender, and ethnicity. Although abuse history was a factor in subgroup membership, the multiple out-of-home placements variable was the most consistent correlate of externalizing and internalizing problems and psychosocial impairment. Childhood adversity that may constitute complex trauma was associated with externalizing behavior problems and psychosocial impairment among psychiatrically hospitalized children, and this association cannot be accounted for fully by existing psychiatric diagnoses, gender, or ethnicity.


An investigation of safety climate in OHSAS 18001-certified and non-certified organizations.
Many organizations worldwide have implemented Occupational Health and Safety Assessment Series (OHSAS) 18001 in their premises because of the assumed positive effects of this standard on safety. Few studies have analyzed the effect of the safety climate in OHSAS 18001-certified organizations. This case-control study used a new safety climate questionnaire to evaluate three OHSAS 18001-certified and three non-certified manufacturing companies in Iran. Hierarchical regression indicated that the safety climate was influenced by OHSAS implementation and by safety training. Employees who received safety training had better perceptions of the safety climate and its dimensions than other respondents within the certified companies. This study found that the implementation of OHSAS 18001 does not guarantee improvement of the safety climate. This study also emphasizes the need for high-quality safety training for employees of the certified companies to improve the safety climate.


The effect of the slope inclination of buccal polished surface of mandibular denture base on food retention.
The accumulation of food debris in the buccal vestibule can inhibit normal mastication and appears to be a factor that can cause patient discomfort. This study focused on the effect of the slope inclination of the buccal polished surface of the mandibular denture base on the ability to expel test-food particles from the buccal vestibule. It was revealed that an inclination of the slope steeper than 80 degrees markedly inhibits the normal ability to expel foods from the vestibule. It was revealed that the most appropriate inclination of the buccal slope is approximately 60 degrees or 70 degrees. These results could be utilized for constructing a denture prosthesis.


Polycompartment syndrome - intra-abdominal pressure measurement.
Intra-abdominal hypertension and the abdominal compartment syndrome are well-known, serious, life-threatening clinical entities in acute care surgery. A common characteristic of these syndromes is the permanent and irreversible damage that may affect the organs which can be found inside the given compartment if quick intervention cannot be provided. All factors which may and can lead to a sudden increase in the intra-abdominal pressure can be found among the triggering factors of abdominal compartment syndrome. Despite the modern and quick diagnostics, and the adequate surgical interventions performed in time, the mortality of this syndrome is extremely high (38-71%). It affects practically all vital organ systems: cardiovascular, respiratory, urinary and central nervous system. There are four major compartments in the human body: the head, the chest, the abdomen and the extremities. When two or more compartments have elevated pressures the name of the clinical entity is polycompartment syndrome, first described in 2007. The only possible way of establishing the diagnosis is to measure the intra-abdominal pressure, a widespread manner of which is the measurement through the bladder. Treatment of abdominal and polycompartment syndrome is nearly always surgical decompression with temporary abdominal wall closure or open abdominal treatment. Clinicians need to be aware of the real existence of polycompartment syndrome and the complex and constant interplay of raised pressure between compartments. This highlights the importance of research and development of new intra-abdominal pressure measurement techniques.


Extended field-of-view sonography: utility in clinical practice.
The purpose of this study was to evaluate the usefulness of real-time extended field-of view sonography in clinical practice (i.e., the frequency of use in various body systems, the frequency of use by different sonographers, and the benefits and drawbacks in comparison to conventional real-time sonography). The use of extended field-of-view sonography was monitored for a 6 month period. The pattern of usage among different sonographers and for different body systems was documented. Extended field-of-view sonography was utilized in 26.5% of patients. In comparison, color Doppler sonography was used in 23.2% of patients. Utilization of extended field-of-view sonography varied significantly among sonographers and among different body systems. Extended field-of-view sonography allowed measurement of large structures and revealed the anatomic context of abnormalities in circumstances under which conventional real-time scans could not provide this information.


Preferential T-cell receptor beta-chain variable gene use in myelin basic protein-reactive T-cell clones from patients with multiple sclerosis.
Multiple sclerosis is an autoimmune disease in which T lymphocytes reactive to myelin basic protein (BP) could play a central role. T cells specific for BP were cloned from the blood of multiple sclerosis patients and normal individuals, and expression of T-cell receptor variable region genes was analyzed. A remarkable bias for use of beta-chain variable region (V beta) 5.2 and, to a lesser extent, V beta 6.1 was seen among BP-specific clones from patients but not from controls. The preferential use of V beta 5.2 for BP recognition did not reflect altered expression of this V beta in the peripheral repertoire. Interestingly, shared V beta 5.2 usage was apparent for clones specific for different BP determinants, even when derived from the same individual. The concurrent demonstration by others (J. R. Oksenberg, M. A. Panzara, A. B. Begovich, H. Erlich, R. Murray, M. Sherritt, S. Stuart, C. C. Bernard, and L. Steinman, personal communication) that T cells within demyelinating areas of multiple sclerosis brains preferentially express V beta 5.2 and V beta 6.1 suggests that the BP-specific clones derived from blood may be relevant to disease pathogenesis. These findings may have important implications for the treatment of multiple sclerosis.


Synthesis and biological evaluation of novel benzothiazole clubbed fluoroquinolone derivatives.
In the present investigation, synthesis and anti-bacterial, analgesic and anthelmintic evaluation of a novel series of fluoroquinolone derivatives clubbed with benzothiazole moeity has been described. The synthesized compounds were characterised by spectral analysis (IR and (1)H NMR). Preliminary results indicated that the most of the synthesized compounds demonstrated good activities against gram negative and gram positive bacterial strains. Compounds 5a, 5b, 5f and 5k demonstrated potent anti-bacterial activities. Compound 5a exhibited most potent anti-bacterial activity with MIC values of 04, 03, 08 and 15 µg/ mL against B. subtilis, S. aureus, E. coli and P. aeruginosa. Analogs 5a, 5c, 5g and 5h showed promising anthelmintic activity against Eisemia foetida in a low concentration as compared to standard drug piperazine citrate with mean paralysis time ranging 22.60 ± 2.46 to 31.60 ± 3.07 min. All synthesized compounds depicted good in vivo analgesic activity with compound 5a exhibiting the most potent activity of 55.19% inhibition of writhing in comparison to the standard drug.


Biliary transport of serum IgA in sheep.
The existence of a hepato-biliary pump for IgA has been studied in sheep by measuring appearance of radioactivity in bile after simultaneous i.v. injection of IgG2 and homologous dimeric IgA each labelled with either 125I or 131I. These experiments confirm that in sheep, as in rodents, IgA is the predominant immunoglobulin in bile and is selectively transported into bile from serum relative to IgG2. In addition, there is evidence for local production of IgA in bile presumably by plasma cells within the liver and biliary tree.


Association of the Glu298Asp polymorphism in the endothelial nitric oxide synthase gene with essential hypertension resistant to conventional therapy.
Endothelial nitric oxide synthase (eNOS) produces nitric oxide (NO) which, after diffusing into vascular smooth muscle cells, activates guanylate cyclase leading to vasodilatation. A polymorphism (894G to T) in exon 7 of the eNOS gene causes the conversion of Glu to Asp in position 298. The recently described crystal structure of the heme domain of eNOS protein shows that Glu298 is fully solvent accessible and distant from regions integral to enzyme function. Searching for phenotypic expression of eNOS gene variants, we genotyped a group of patients with essential hypertension (H, n = 119) for the Glu298Asp polymorphism and compared them with age- and sex-matched healthy normals (N, n = 85). To specify phenotypic expression further, the hypertensive patients were subdivided into one group that responded well to regular antihypertensive therapy (CH, n = 45) and one group that was resistant to the therapy (RH, n = 74). Patients with BP higher than 140/90 mmHg when on adequate lifestyle modification and triple-combination therapy (including diuretics) were considered resistant. In RH and H groups, a significantly higher frequency of T alleles (P = 0.022 and P = 0.046, respectively) was found compared to normotonics (N). In well-controlled hypertonics, the same tendency was found, but did not reach statistical significance. The Glu298Asp polymorphism may contribute to the complex pathogenesis of essential hypertension and may be a factor in the resistance of these patients to conventional antihypertensive therapy. The presence of this allele may thus be predictive of the patients' therapeutic response.


Determination of the optimal pressure support level evaluated by measuring transdiaphragmatic pressure.
The purpose of this study was to determine the optimum pressure support (PS) in six patients with respiratory failure. Esophageal pressure (Pe), gastric pressure (Pg), airway pressure, and transdiaphragmatic pressure (Pdi), obtained by subtracting Pe from Pg, were measured using a newly developed multiluminal nasogastric catheter. For each patient, different PS levels were selected every 20 minutes, and measurements were made at each PS level. We defined the optimum PS level as the level that showed the minimum Pe value. Respiratory rate (RR) decreased and tidal volume (VT) increased with an increase in PS level. RR and VT at the optimum PS were 19.7 +/- 5.5 breaths per minute and 11.7 +/- 4.5 ml/kg, respectively. Pdi decreased linearly with increasing PS level in all patients. Mean Pdi at the optimum Ps was 4.2 +/- 1.2 cm H2O. Based on the relationship between Pdi and PS level, we constructed an equation to estimate the optimum PS level as follows: Optimum PS level = [( Pdi during T-piece mode] - 4)/0.8. We conclude that Pdi measurement is helpful for titrating the required PS level.


Effect of high-dose 290 nm UV-B on resveratrol content in grape skins.
UV-C irradiation increases resveratrol content in grape skins, but it reaches a maximum at a certain UV-C dose. In contrast, UV-B has a weak resveratrol-enhancing effect at low doses, but it has not been investigated at high doses. In this study, we investigated the effect of high-dose UV-B on resveratrol contents in grape skins. Irradiation of Muscat Bailey A with 290 nm UV-B LED at 22 500 and 225 000 µmol m-2 increased the resveratrol contents in the grape skins by 2.1- and 9.0-fold, respectively, without significant increases in other phenolic compounds. The effect was also confirmed for 2 other cultivars: Shine Muscat and Delaware. Transcriptome analysis of the grape skins of Muscat Bailey A immediately after irradiation with UV-B at 225 000 µmol m-2 showed that genes related to biotic and abiotic stresses were upregulated. Hence, it was suggested that high-dose UV-B irradiation induces a stress response and specifically activates resveratrol biosynthesis.


Mucinous colorectal carcinoma: clinical pathology and prognosis.
Mucinous carcinomas accounted for 37 (6.4%) of 540 cases of colorectal carcinoma. The clinical and pathological features of these mucinous carcinomas were compared with those of the 510 well or moderately differentiated adenocarcinomas. Mucinous carcinoma was more common in the patients 39 years of age or under (P less than 0.05) and was more frequent in the female patients. A large number of mucinous carcinomas were located in the rectum, followed by the right colon. However, the right colon showed a higher relative incidence (40.5% vs 12.5%, P less than 0.005). Mucinous carcinoma was characterized by infiltration of the surrounding tissues (24.3% vs 7.8%, P less than 0.005), positive lymph node involvement (75.7% vs 48.6%, P less than 0.005), and peritoneal implant (21.6% vs 4.1%, P less than 0.005). The cumulative five and ten year survival rates after resection of mucinous carcinoma were 45.5 per cent and 39.8 per cent, respectively, and those after curative resection, 72.4 per cent and 63.5 per cent, respectively. These survival rates were lower, without significant differences, than those for the well or moderately differentiated adenocarcinomas. The results suggest the need for aggressive lymph node dissection and wide excision of the surrounding tissues for mucinous carcinoma, with special attention paid to local recurrence.


Neurally adjusted ventilatory assist during weaning from respiratory support in a case of guillain-barré syndrome.
We report a case of Guillain-Barré syndrome complicated by respiratory failure requiring mechanical ventilation. Neurally adjusted ventilatory assist (NAVA) allowed proper patient-ventilator synchronization by pressure support proportional to the electrical activity of the diaphragm (Edi). Prolonged ventilation with NAVA seems feasible in patients with neuromuscular impairment, but the weaning process conducted by a continuous monitoring of Edi for pressure support titration needed to be assessed in a Guillain-Barré syndrome patient. Beginning on day 12 after hospital admission, the patient was ventilated with NAVA for 8 d. The NAVA level (pressure support per unit of Edi) was decreased from 1.2 cm H2O/μV to zero over the 8-d period. A simultaneous decrease in the tidal volume/Edi ratio was interpreted as a sign of recovery. A spontaneous breathing trial was successfully performed on day 20, followed by decannulation 4 d later. In conclusion, NAVA should be further investigated in patients with Guillain-Barré syndrome, particularly during the weaning period.


TERRA, CpG methylation and telomere heterochromatin: lessons from ICF syndrome cells.
Self-reinforcing negative feedback loops are commonly observed in biological systems. RNA-mediated negative feedback loops have been described in the formation of heterochromatin at centromeres in fission yeast and the inactive X chromosome in mammalian cells. The telomere repeat-containing RNA (TERRA) has also been implicated in the formation of telomeric heterochromatin through a self-reinforcing negative feedback loop. In cells derived from human ICF syndrome, TERRA levels are abnormally elevated and telomeres are abnormally shortened. We now show that telomere heterochromatin is also abnormal in ICF cells. We propose that ICF cells fail to reinforce the TERRA-dependent negative feedback loop as a result of the inability to establish heterochromatin at subtelomeres. This failure is likely due to the lack of DNMT3b and DNA methylation, which is a genetic lesion associated with ICF syndrome. Failure of this feedback mechanism leads to catastrophic telomere dysfunction and chromosome instability.


Combination of diffusion tensor and functional magnetic resonance imaging during recovery from the vegetative state.
The rate of recovery from the vegetative state (VS) is low. Currently, little is known of the mechanisms and cerebral changes that accompany those relatively rare cases of good recovery. Here, we combined functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to study the evolution of one VS patient at one month post-ictus and again twelve months later when he had recovered consciousness. fMRI was used to investigate cortical responses to passive language stimulation as well as task-induced deactivations related to the default-mode network. DTI was used to assess the integrity of the global white matter and the arcuate fasciculus. We also performed a neuropsychological assessment at the time of the second MRI examination in order to characterize the profile of cognitive deficits. fMRI analysis revealed anatomically appropriate activation to speech in both the first and the second scans but a reduced pattern of task-induced deactivations in the first scan. In the second scan, following the recovery of consciousness, this pattern became more similar to that classically described for the default-mode network. DTI analysis revealed relative preservation of the arcuate fasciculus and of the global normal-appearing white matter at both time points. The neuropsychological assessment revealed recovery of receptive linguistic functioning by 12-months post-ictus. These results suggest that the combination of different structural and functional imaging modalities may provide a powerful means for assessing the mechanisms involved in the recovery from the VS.


Matrix attachment regions and transcription units in a polygenic mammalian locus overlapping two isochores.
Eukaryotic chromosomes are ponctuated by specialized DNA sequences (MARs) characterized by their ability to bind the network of nonhistone proteins that form the nuclear matrix or scaffold. We previously described an amplifiable cluster of genes with different tissue-specific expression patterns, located on Chinese hamster chromosome 1q. This model is especially appropriate to study the relationships between MARs and transcription units. We show here that four attachment regions, with sequences exhibiting motifs specific to MARs, are present within the 100 kb of screened DNA. Three of them are relatively short sequences localized in intergenic regions. The last one extends over one of the transcription units and contains a region previously identified as a recombination hot spot. Moreover, the analysis of a DNA sequence extending over some 50 Kb of this region and spanning at least four genes, disclosed a strikingly sharp change in G + C content. This strongly suggests that the studied region contains the boundary of two isochores. We propose that the frequency and the size of MARs are correlated to their localization in G + C rich or poor domains.


[Evaluation of transrectal power-Doppler ultrasonography and effect of contrast-enhancement for detecting prostate cancer].
There are many reports about the usefulness of transrectal power-Doppler ultrasonography (PDUS) for detecting prostate cancer because of the high microvessel density in cancerous tissue in the prostate. The purpose of this study was to assess the role of PDUS and contrast-enhanced transrectal power-Doppler ultrasonography (enhanced PDUS) in the identification of prostate cancer. One hundred forty-two cases (90 cases without enhancement, 52 cases with enhancement) of suspected prostate cancer found with digital rectal examination (DRE), transrectal ultrasound (TRUS) abnormal or prostate specific antigen (PSA) elevation were evaluated by PDUS and enhanced PDUS. Forty-three (30.3%) cases of cancer were detected, and there was a significant difference (p < 0.05) between PDUS group (22 cases, 24.4%) and enhanced PDUS (21 cases, 40.0%). However, there were no significant statistical results about the usefulness of enhancement to detect prostate cancer although imaging was clear with contrast agent. The results of statistical analysis of PDUS use were almost the same as for PSA of more than 10.1 ng/ml. Combination with PDUS was very helpful to detect prostate cancers. The positive predictive value of the combination with DRE, TRUS and PSA improved from 68.0% to 81.0% with the addition of PDUS. In particular, cancer was revealed frequently (65.8%) in peripheral hypoechoic lesions on gray-scale TRUS with hypervascular areas on PDUS. We conclude that enhancement with contrast agent is not especially useful in the identification of prostate cancer although imaging was clear with contrast agent. However, PDUS is useful especially for hypoechoic peripheral areas. It is suggested that we should add PDUS to DRE, TRUS and PSA examinations.


Hematologic and hemostatic changes with repetitive air diving.
In order to determine the effects of repetitive compression-decompression cycles on hematologic and hemostatic factors in humans, 14 subjects were exposed to 150 ft sea water gauge (fswg) for 30 min with standard U.S. Navy decompression on each of 12 consecutive days. Red blood cell number, volume, and size distribution; hemoglobin concentration; hematocrit; white blood cell number and differential counts; platelet number and volume; prothrombin and partial thromboplastin times; and fibrinogen and fibrin/fibrinogen degradation products were measured in venous blood samples collected before the first and after alternate dives. Subjects in the study had no symptoms other than pruritus and occasional fatigue following the exposures. More than 60% had venous gas emboli detectable by precordial doppler monitoring which generally persisted for 3-5 h after surfacing. Results show a small decrease in red cell mass, with an increase in size distribution and no change in mean corpuscular volume. No change in total white cell number was noted, but the basophilic granulocytes and atypical lymphocytes were elevated at the end of the series. A biphasic change was noted in monocyte number, and immature neutrophilic granulocytes were reduced. No change in platelet number or volume, or in the prothrombin/partial thromboplastine time, was apparent. Although fibrinogen concentration significantly decreased during the exposures, fibrin/fibrinogen degradation products remained undetectable. All changes remained in a clinically acceptable range.(ABSTRACT TRUNCATED AT 250 WORDS)


Structural changes of the sarcoplasmic reticulum Ca(II)-ATPase nucleotide binding domain by pH and La(III).
The Ca(2+)-ATPase from sarcoplasmic reticulum couples the hydrolysis of one molecule of ATP to the transport of two Ca2+ ions in skeletal muscle fibers. Here, we study the accessibility of the fluorescein covalently attached to the Lys515 at the nucleotide binding domain of the ATPase to the small collisional quencher iodide at pH 6 and 8, as well as the effect of ligand binding (La3+, La(3+)-nucleotide, and Ca2+). Our results indicate that bound fluorescein is significantly more accessible at pH 6 than at pH 8, suggesting that pH modulates the structure of the nucleotide binding domain of the ATPase. This notion was further substantiated by the finding that La(3+)-nucleotide only interacted with the catalytic center at acidic pH. Notably, the differential accessibility of the nucleotide binding domain at acidic and basic pH cannot be rationalized in terms of the ATPase E1/E2 conformational equilibrium since a shift of the ATPase toward the E1 (plus Ca2+) or E2 (plus EGTA) did not affect the accessibility of fluorescein-labeled ATPase to the quencher. Taken together, these findings show the presence of structural flexibility in the FITC binding site and suggest a structural modulation of the Ca(2+)-ATPase nucleotide binding domain by pH and La3+ binding through long-range link-age mechanisms.


TIGER Team: Rapid Response at the University of Missouri.
By the end of the 20th century, health care organizations worldwide were recognizing the benefits of a quick response when patients were experiencing a clinical decline and the difficulty in achieving that goal. The University of Missouri STAT Nurse program, developed in 1989, was an early innovation to deliver the "right care" at the "right time" every time. Over the years, the STAT Nurse program evolved and became the core component of a Rapid Response System. Today Rapid Response at University of Missouri Health Care is called the Targeted Interventional Group Emergency Response Team, also known as the TIGER Team after the much beloved University mascot.


Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study.
Chemotherapy side effects are often reported in clinical trials; however, there is little evidence about their incidence in routine clinical care. The objective of this study was to describe the frequency and severity of patient-reported chemotherapy side effects in routine care across treatment centres in Australia. We conducted a prospective cohort study of individuals with breast, lung or colorectal cancer undergoing chemotherapy. Side effects were identified by patient self-report. The frequency, prevalence and incidence rates of side effects were calculated by cancer type and grade, and cumulative incidence curves for each side effect computed. Frequencies of side effects were compared between demographic subgroups using chi-squared statistics. Side effect data were available for 449 eligible individuals, who had a median follow-up of 5.64 months. 86% of participants reported at least one side effect during the study period and 27% reported a grade IV side effect, most commonly fatigue or dyspnoea. Fatigue was the most common side effect overall (85%), followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence rates were similar across side effects and cancer types. Age was the only demographic factor associated with the incidence of side effects, with older people less likely to report side effects. This research has produced the first Australian estimates of self-reported incidence of chemotherapy side effects in routine clinical care. Chemotherapy side effects in routine care are common, continue throughout chemotherapy and can be serious. This work confirms the importance of observational data in providing clinical practice-relevant information to decision-makers.


Regulation of natural genetic transformation and acquisition of transforming DNA in Streptococcus pneumoniae.
The ability of pneumococci to take up naked DNA from the environment and permanently incorporate the DNA into their genome by recombination has been exploited as a valuable research tool for 80 years. From being viewed as a marginal phenomenon, it has become increasingly clear that horizontal gene transfer by natural transformation is a powerful mechanism for generating genetic diversity, and that it has the potential to cause severe problems for future treatment of pneumococcal disease. This process constitutes a highly efficient mechanism for spreading beta-lactam resistance determinants between streptococcal strains and species, and also threatens to undermine the effect of pneumococcal vaccines. Fortunately, great progress has been made during recent decades to elucidate the mechanism behind natural transformation at a molecular level. Increased insight into these matters will be important for future development of therapeutic strategies and countermeasures aimed at reducing the spread of hazardous traits. In this review, we focus on recent developments in our understanding of competence regulation, DNA acquisition and the role of natural transformation in the dissemination of virulence and beta-lactam resistance determinants.


Lipophorin-facilitated hydrocarbon uptake by oocytes in the German cockroach Blattella germanica (L.).
Large amounts of hydrocarbons accumulate during vitellogenesis in the developing basal oocytes of the German cockroach Blattella germanica (L.), and all ovarian hydrocarbons are deposited into an egg case (ootheca) during oviposition. Hydrocarbons are not synthesized by the ovaries, but are delivered by hemolymph lipoproteins and accumulate within the basal oocytes. A native B. germanica hydrocarbon, [(3)H]3,11-dimethylnonacosane, injected into adult females of various ages, was taken up by the ovaries in relation to oocyte growth. Ovarian uptake of the hydrocarbon was low in day 0-1 females, increased dramatically between days 3 and 6 and declined sharply through oviposition on day 8-9; ovarian uptake of the hydrocarbon was low during a 21-day pregnancy that followed. [1-(14)C]Propionate, which becomes incorporated into methyl-branched hydrocarbons, was injected into 5-day-old vitellogenic females to monitor the de novo biosynthesis of hydrocarbons and the time course of hydrocarbon deposition in the ovary. Propionate was rapidly incorporated into hydrocarbons within 4 h. Hydrocarbon uptake by the ovaries, however, was three times higher 24 h after injection than 4 h after injection, showing that hydrocarbons are slowly and continuously deposited in oocytes. This result was confirmed with topical application of [(3)H]3,11-dimethylnonacosane: ovarian uptake was three times higher after 24 h than after 4 h. In vitro incubations of sternites, which synthesize hydrocarbons, with [(14)C]propionate and ovaries, showed that both hemolymph and purified high-density lipophorin facilitated ovarian uptake of newly synthesized hydrocarbons; maximum uptake occurred with 10 % hemolymph or 1 mg ml(-1) high-density lipophorin. These results were confirmed with sternites treated with [(3)H]3,11-dimethylnonacosane and co-incubated with ovaries. This is the first report to show that copious amounts of maternal hydrocarbons are provisioned in oocytes and to demonstrate the existence of a hydrocarbon transport pathway involving hemolymph high-density lipophorin.


Atypical presentation of bilateral maxillary supplemental lateral incisors: A rare case report.
Hyperdontia presents as a unique dental condition which may or may not require immediate corrective therapy. Supplemental teeth in the permanent dentitian comprises only 4% of all the supernumeraries, and bilateral supplemental teeth are even rarer entities. We present a rare case report of non-syndromic bilateral supplemental maxillary lateral incisors.


Immune system and gut microbiota senescence in elderly IBD patients.
In inflammatory bowel disease (IBD), the loss of immune tolerance against gut microbiota causes chronic inflammation and the progressive accumulation of organ damage in genetically susceptible individuals. In the elderly, IBD is often characterized by a different disease behaviour when compared with paediatric and young adult disease. Besides disease behaviour, another aspect of the multifaceted impact of age on elderly IBD course is increased susceptibility to infections. In this context, age-of-onset-dependent IBD behaviour and clinical course are two major contributors to immune system senescence and change of gut microbiota in older subjects. Here, we review the available literature linking immunosenescence and age-dependent changes in the gut microbiota composition to IBD pathogenesis speculating on their possible implications in disease expression in this age class.


HDAC inhibitor, valproic acid, induces p53-dependent radiosensitization of colon cancer cells.
Agents that inhibit histone deacetylases (HDAC inhibitors) have been shown to enhance radiation response. The aim of this study was to evaluate the effects of low, minimally cytotoxic concentrations of the HDAC inhibitor, valproic acid (VPA), on radiation response of colorectal cancer cells. Cell lines LS174T and an isogenic pair of HCT116, which differed only for the presence of wild-type p53, were exposed to ionizing radiation (IR) alone, VPA alone, or the combination. Clonogenic survival, gamma-H2AX induction, apoptosis, changes in mitochondrial membrane potential, and mitochondrial levels of p53 and Bcl-2 family proteins were assessed. In vivo studies monitored tumor growth suppression after therapy in mice bearing HCT116/p53(+/+) and HCT116/p53(-/-) tumor xenografts. VPA led to radiosensitization, which was dependent on p53 status. A decrease in clonogenic survival, an increase in apoptosis, and an increase in levels of gamma-H2AX were observed after VPA+IR, compared to IR alone, in wild-type p53 cells (LS174T and HCT116/p53(+/+)), as opposed to p53 null cells (HCT116/p53(-/-)). Exposure to VPA resulted in enhancement of IR-induced mitochondrial localizations of Bax and Bcl-xL, mitochondrial membrane potential, and cytochrome c release only in wild-type p53 cell lines. VPA also enhanced tumor growth suppression after IR only in wild-type p53 xenografts. These data suggest that VPA may have an important role in enhancing radiotherapy response in colorectal cancer, particularly in tumors with the wild-type p53 genotype.


Autografting satellite cells to repair damaged muscle induced by repeated compression: an animal model.
Repeated elevation of intramuscular pressure (IMP) causes skeletal-muscles damage. The purpose of this paper was to investigate the regenerative effect of satellite cells autografted to the damaged muscle in a rabbit model. Twenty-four adult rabbits were randomized into three groups: 1) experimental group, 2) non-graft group, and 3) control group. The model of limb interval compression for 2 hours twice a day for 14 days was established in the experimental and non-graft group. Transplantation was performed in the experimental group and control group. Satellite cells from a half of soleus muscles in the experimental group and control group were isolated and then expanded in vitro. DAPI-tag satellite cells were transplanted back to the remaining half of the soleus muscle. The number of satellite cells with DAPI-tag was determined by fluorescence after grafts. The histological changes were compared at the time of the last compression and at the end of the 28th day after grafting. At the time period of 28 days following grafting of satellite cells into the soleus muscle, the satellite cells from the compressed soleus muscle increased significantly predominantly experimental group (p = 0.013), whereas those in the control group remained the same (p = 0.076). In HE staining, a large cluster of myofibers and interstitial fibers was present in compressed muscle in both the experimental group and non-graft group, while the skeletal muscle fibers and interstitial fibers were in continuity in the control group. After grafting, the muscle showed a great repair but the non-graft muscle exhibited dominant fibrosis. Autografting satellite cells by means of a small amount of expansion in vitro could improve the regenerative efficiency to repair large clusters of the damaged myofibers induced by repeated compression. This technique may be applicable in human compartment syndrome.


Oral manifestations of Albright hereditary osteodystrophy: a case report.
Albright hereditary osteodystrophy is a hereditary metabolic disorder of dominant autosomal etiology that is commonly characterized by short stature, round face, small metacarpus and metatarsus, mental retardation, osteoporosis, subcutaneous calcification, variable hypocalcemia, and hyperphosphatemia. In this study, we report a clinical case of a 17-year-old woman with Albright hereditary osteodystrophy, and we discuss her clinical, radiographic, and laboratory test characteristics together with the oral manifestations, and we correlate them with the characteristics found in the literature. We also discuss the odontological management of treatment of related periodontal disease and planning for corrections of related malocclusions.


Forensic Engineering of Advanced Polymeric Materials-Part V: Prediction Studies of Aliphatic⁻Aromatic Copolyester and Polylactide Commercial Blends in View of Potential Applications as Compostable Cosmetic Packages.
The main aim of the present study was to determine the behavior of the specimens from Ecovio, in the form of dumbbell-shaped samples and films, during degradation in selected cosmetic ingredients such as water and paraffin. The (bio)degradation test of the prototype cosmetic package (sachet) made from a PBAT (poly[(1,4-butylene adipate)-co-(1,4-butylene terephthalate)]) and PLA (polylactide) blend was investigated under industrial composting conditions, and compared with the sample behavior during incubation in cosmetic media at 70 °C. During the degradation tests, the changes of the samples were evaluated using optical microscopy, ¹H NMR (proton nuclear magnetic resonance) and GPC (gel permeation chromatography) techniques. The structures of the degradation products were investigated using ESI-MSn (mass spectrometry with electrospray ionization on positive and negative ions) analysis. The thermal properties of selected materials were determined by DSC (differential scanning calorimetry) and TGA (thermogravimetric analysis) analysis. It was concluded that the PBAT and PLA blend studied had a good stability during aging in cosmetic media, and could be recommended for long-shelf-life compostable packaging of cosmetics, especially with oily ingredients.


Graphene Nanoplatelet-Polymer Chemiresistive Sensor Arrays for the Detection and Discrimination of Chemical Warfare Agent Simulants.
A cross-reactive array of semiselective chemiresistive sensors made of polymer-graphene nanoplatelet (GNP) composite coated electrodes was examined for detection and discrimination of chemical warfare agents (CWA). The arrays employ a set of chemically diverse polymers to generate a unique response signature for multiple CWA simulants and background interferents. The developed sensors' signal remains consistent after repeated exposures to multiple analytes for up to 5 days with a similar signal magnitude across different replicate sensors with the same polymer-GNP coating. An array of 12 sensors each coated with a different polymer-GNP mixture was exposed 100 times to a cycle of single analyte vapors consisting of 5 chemically similar CWA simulants and 8 common background interferents. The collected data was vector normalized to reduce concentration dependency, z-scored to account for baseline drift and signal-to-noise ratio, and Kalman filtered to reduce noise. The processed data was dimensionally reduced with principal component analysis and analyzed with four different machine learning algorithms to evaluate discrimination capabilities. For 5 similarly structured CWA simulants alone 100% classification accuracy was achieved. For all analytes tested 99% classification accuracy was achieved demonstrating the CWA discrimination capabilities of the developed system. The novel sensor fabrication methods and data processing techniques are attractive for development of sensor platforms for discrimination of CWA and other classes of chemical vapors.


[Potential role of gravity in computerized tomography in neoplasms].
The possible evolution of the usual CT signs in oncology makes the logical premise of our experience. Our goal was to transform instrumental findings in information richer in clinical yield, in compliance with the guidelines of the National Cancer Institute (Bethesda, Md, USA). Our study was developed over a 3-year period and involved 432 selected patients with primary neoplasms. The lesions were in pulmonary, gastroenteric and genitourinary sites and stages differed (T2/T3, N0/N3, M0/M1); the Karnofsky score ranged 60-90. We integrated the tumor staging obtained with CT with gravitational tests by means of simple changes in the position of forced decubitus resulting in procubitus and triclinium-like positions (right and left lateral decubitus). We restudied only the cT class of each lesion, looking for a better depiction of the lesion-adjacent, fat, and compared the results the examinations in the standard versus the modified decubitus. Judgements were relative to the technical quality of the modified examination and to the potential impact of these findings on the following pTNM staging. In our 432 patients and only relative to the cT parameter, CT with standard decubitus correctly staged 312 lesions (mean accuracy: 72.2%) versus 352 for CT with modified decubitus (mean accuracy: 81.5%). Improvements were more marked in gastric (22.9% of 48 cases), vesical (23% of 26 cases) and colic (22.3% of 76 cases) lesions, and less marked in pulmonary (10.6% of 132 cases), ovarian (14% of 71 cases) and endometrial (17.1% of 70 cases) lesions. The routine application of pTNM verifications to CT staging helped show the most frequent causes of cTNM mistaging in solid lesions which, in most of the T2/T3 classes, involve the direct spread to an adjacent organ and the depth of invasion of adjacent structures. The combination and comparison of cTNM with pTNM are useful not only for final tumor staging but also to assess the pretreatment diagnostic accuracy of CT studies. Introducing gravitational tests and reading examinations in pairs improved lesion location, which is the most important technical information for subsequent prognosis and treatment and can help decrease pre-/post-treatment management costs.


Lean Yet Unhealthy: Asian American Adults Had Higher Risks for Metabolic Syndrome than Non-Hispanic White Adults with the Same Body Mass Index: Evidence from NHANES 2011-2016.
(1) Background: Despite having consistently lower rates of obesity than other ethnic groups, Asian Americans (AAs) are more likely to be identified as metabolically obese, suggesting an ethnic-specific association between BMI and cardiometabolic outcomes. The goal of this study was to provide an estimate of metabolic syndrome (MetS) prevalence among AAs using national survey data and to compare this rate to that of non-Hispanic Whites (NHWs) over the BMI continuum. (2) Methods: Using the NHANES 2011-2016 data, we computed age-adjusted, gender-specific prevalence of MetS and its individual components for three BMI categories. Furthermore, we conducted multivariate binary logistic regression to examine the risk of MetS in AAs compared to NHWs, controlling for sociodemographic and lifestyle factors. The analysis sample consisted of 2121 AAs and 6318 NHWs. (3) Results: Among AAs, the prevalence of MetS and its components increased with higher BMI levels, with overall prevalence being 5.23% for BMI < 23, 38.23% for BMI of 23-27.4, and 77.68% for BMI ≥ 27.5 in men; and 18.61% for BMI < 23, 47.82% for BMI of 23-27.4, and 67.73% for BMI ≥ 27.5 in women. We also found that for those with a BMI > 23, AAs had a higher predicted risk of MetS than their NHW counterparts of the same BMI level, in both men and women. (4) Conclusions: Our findings support the use of lower BMI ranges for defining overweight and obesity in Asian populations, which would allow for earlier and more appropriate screening for MetS and may better facilitate prevention efforts.


Optical path clearing and enhanced transmission through colloidal suspensions.
We utilize advanced laser fields to clear a path through a dynamic turbid medium, a concept termed "Optical path clearing (OPC)." Particles are evacuated from a volume of the medium using the gradient and/or scattering forces due to an applied laser field with a suitably tailored spatial profile. Our studies encompass both an analytical model and proof-of-principle experiments where paths are cleared in dense bulk colloidal suspensions. Based on our results we suggest that high-performance and high efficiency OPC will be achieved by multiple-step clearing using dynamic laser fields based on Airy or inverted axicon beams.


Net transport due to noise-induced internal reciprocating motion.
We consider a system of two coupled Brownian particles fluctuating between two states. The fluctuations are produced by both equilibrium thermal and external nonthermal noise, the transition rates depending on the interparticle distance. An externally induced modulation of the transition rates acts on the internal degree of freedom (the interparticle distance) and generates reciprocating motion along this coordinate. The system moves unidirectionally due to rectification of the internal motion by asymmetric friction fluctuations and thus operates as a dimeric motor that converts input energy into net movement. The properties of the motor are primarily determined by the properties of the reciprocating engine, represented by the interparticle distance dynamics. Two main mechanisms are recognized by which the engine operates: energetic and informational. In the physically important cases where only one of the motion-inducing mechanisms is operative, exact solutions can be found for the model with linearly coupled particles. We focus on the informational mechanism, in which thermal noise is involved as a vital component and the reciprocating velocity exhibits a rich behavior as a function of the model parameters. An efficient rectification method for the reciprocating motion is also discussed.


High-risk fertility behaviours among women in sub-Saharan Africa.
High-risk fertility behaviours such as too early or advanced age at delivery, shorter birth interval, birth order and a higher number of live births to a woman often lead to adverse maternal and child health outcomes. We assessed high-risk fertility behaviours and their associated factors among women in sub-Saharan Africa (SSA). Data on 200 716 women pooled from the demographic and health surveys of 27 countries conducted between 2010 and 2020 in SSA were analysed. High-risk fertility behaviour from four indicators, mother aged <18 years at the time of delivery; mother aged >34 years at the time of delivery; mother of a child born after a short birth interval (<24 months) and mother of high parity (>3 children), was derived. Multi-level multi-variable logistic regression analyses were carried out and the results were presented as adjusted odds ratios at 95% confidence interval. Women who were in polygamous marriages had higher odds of single and multiple high-risk fertility behaviour compared with their counterparts who were in monogamous marriages. Women with middle or high maternal decision-making power had higher odds of single and multiple high-risk fertility behaviours compared with those with low decision-making power. Single and multiple high-risk fertility behaviours were lower among women with access to family planning, those with at least primary education and those whose partners had at least primary education compared with their counterparts who had no access to family planning, those with no formal education and those whose partners had no formal education. Family structure, women's decision-making power, access to family planning, women's level of education and partners' level of education were identified as predictors of high-risk fertility behaviours in SSA. These findings are crucial in addressing maternal health and fertility challenges. Policy makers, maternal health and fertility stakeholders in countries with high prevalence of high parity and short birth intervals should organize programs that will help to reduce the prevalence of these high-risk factors, taking into consideration the factors that predispose women to high-risk fertility behaviours.


The bioavailability and postprandial utilisation of sweet lupin (Lupinus albus)-flour protein is similar to that of purified soyabean protein in human subjects: a study using intrinsically 15N-labelled proteins.
Sweet lupin (Lupinus albus), a protein-rich legume devoid of anti-nutritional factors, is considered to have a high potential for protein nutrition in man. Results concerning the nutritional value of lupin protein are, however, conflicting in animals and very scarce in human subjects. Furthermore, where fibre-rich protein sources are concerned, the long-term nutritional results are often obscured, particularly since fibre-promoted colonic fermentation may bias the energy supply and redistribute N flux. We therefore studied, during the postprandial phase, the bioavailability and utilisation of lupin-flour protein in nine healthy men who had ingested a mixed meal containing intrinsically 15N-labelled lupin flour as the protein source (Expt 1). The real ileal digestibility (RID) and ileal endogenous N losses (IENL) were assessed using a perfusion technique at the terminal ileum, and the N content and 15N enrichment of ileal samples. Lupin flour exhibited a high RID of 91 (SD 3)% and low IENL (5-4 (SD 1.3) mmol N/h). Postprandial dietary deamination was also assessed from body dietary urea and urinary dietary N excretion, and compared with results in nine healthy men following an iso-energetic meal containing a 15N-soyabean-protein isolate with a similar RID, as a control (Expt 2). Postprandial dietary deamination was similar after lupin and soyabean meals (17 (SD 2) and 18 (SD 4)% ingested N respectively). We therefore conclude that lupin protein is highly bioavailable, even if included in fibre-rich flour, and that it can be used with the same efficiency as soyabean protein to achieve postprandial protein gain in healthy human subjects.


A miniature chip for protein detection based on magnetic relaxation switches.
A miniature multi-sample chip for protein detection with a bench-top magnetic resonance imager was created on the basis of magnetic relaxation switches. The chip was assessed with two protein systems. Both qualitative and quantitative results for the target proteins were obtained by image analysis and relaxation time measurement, respectively. The detection of prostate specific antigen, the serum marker of human prostate cancer, showed a linear concentration range of 17.3-43.2 ng mL(-1) and a detection limit of 13.7 ng mL(-1). As proof of concept, the analysis of 18 samples with a volume of 6.37 μL each was completed in 26 min by this chip. This technique may become an easy and efficient approach for rapid and high-throughput protein assay and protein-protein interaction screening.


2,7-Dihydrodichlorofluorescein diacetate as a fluorescent marker for peroxynitrite formation.
Reactive oxygen species (ROS) have been implicated as an important causative factor in cell damage, including apoptosis and necrosis. Their proposed actions comprise lipid peroxidation, DNA damage, destruction of the mitochondrial respiratory chain and protein modifications. Recent experiments underline the importance of peroxynitrite, the reaction product of the two potent reactive species nitric oxide and superoxide. Several fluorogenic compounds have been used in order to determine ROS formation in living cells. Besides dihydrorhodamine-123 (DHR-123), at present mostly applied to monitor peroxynitrite, 2,7-dihydrodichlorofluorescein (DCF-H) is used for detection of hydrogen peroxide and nitric oxide. We employed a cell free approach to evaluate the specificity and sensitivity of DCF-H to various oxidizing compounds. Our studies imply that DCF-H is much more sensitive to peroxynitrite oxidation than any other compound tested. In order to study peroxynitrite generation within individual cells, primary glial cultures loaded with DCF-H were monitored with a laser scanning microscope. Microglia, stimulated to simultaneously produce the peroxynitrite precursors nitric oxide and superoxide, displayed the greatest increase in DCF fluorescence, whereas microglia producing either nitric oxide or superoxide alone showed a relatively small increase in DCF fluorescence. In conclusion, DCF-H was demonstrated to be an excellent peroxynitrite marker with the potential to detect peroxynitrite formation in living cells.


Protein and gene expression characteristics of heterogeneous nuclear ribonucleoprotein H1 in esophageal squamous cell carcinoma.
To investigate the expression characteristics of heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) mRNA and protein in cell lines and tissues of esophageal squamous cell carcinoma (ESCC). Western blotting was used to assess the expression of HNRNPH1 protein in seven ESCC cell lines and 30 paired fresh tissue specimens. The subcellular localization of HNRNPH1 was determined by immunofluorescence in ESCC cells. The RNA sequencing data from 87 patients with ESCC were obtained from the cancer genome atlas (TCGA), and the expression and clinical characteristics analysis of different transcript variants of HNRNPH1 were evaluated in this dataset. In addition, immunohistochemistry was carried out to detect the expression of HNRNPH1 protein in 125 patients. The expression of HNRNPH1 protein varied across different ESCC cell lines. It was exclusively restricted to the nucleus of the ESCC cells. There are two transcript variants of the HNRNPH1 gene. Variant 1 was constitutively expressed, and its expression did not change during tumorigenesis. In contrast, levels of variant 2 were low in non-tumorous tissues and were dramatically increased in ESCC (P = 0.0026). The high levels of variant 2 were associated with poorer differentiated tumors (P = 0.0287). Furthermore, in paired fresh tissue specimens, HNRNPH1 protein was overexpressed in 73.3% (22/30) of neoplastic tissues. HNRNPH1 was significantly upregulated in ESCC, with strong staining in 43.2% (54/125) of tumor tissues and 22.4% (28/125) of matched non-cancerous tissues (P = 0.0005). Positive HNRNPH1 expression was significantly associated with poor tumor differentiation degree (P = 0.0337). The different alternative transcript variants of HNRNPH1 exhibited different expression changes during tumorigenesis. Its mRNA and protein were overexpressed in ESCC and associated with poorer differentiation of tumor cells. These findings highlight the potential of HNRNPH1 in the therapy and diagnosis of ESCC.


Performance evaluation of the Biocartis Idylla EGFR Mutation Test using pre-extracted DNA from a cohort of highly characterised mutation positive samples.
Targeted therapies for non-small cell lung carcinoma (NSCLC) rely on the detection of specific genomic lesions, such as mutations within the epidermal growth factor receptor (EGFR) gene. The Biocartis Idylla platform and single-use EGFR mutation test cartridge is CE-IVD for use with formalin-fixed paraffin embedded (FFPE) tumour material, but can also function off-scope using extracted DNA as input material. This can expand the utility of the platform and potentially conserve valuable tissue. We sought to evaluate the performance of this system to detect known EGFR mutations using extracted DNA at different input levels. 130 next generation sequencing-characterised NSCLC cases possessing EGFR mutations that were theoretically detectable by the Idylla system were selected. Replicate analyses were performed using the Idylla EGFR test with up to three different DNA input levels (20 ng, 50 ng and 250 ng). Considering only variants within the test manufacturer's specified scope, the Idylla EGFR test generated concordant findings for 90.77% of cases at 20 ng DNA input, 98.46% at 50 ng input and 100% at 250 ng input. Analyses with discordant findings all generated control quantification cycle (CQ) values greater than 23. Very low CQ values were associated with EGFR gene amplification. The Idylla EGFR Mutation Test can be used at least as well with pre-extracted DNA than with direct FFPE input. In cases with control CQ >23, reanalysis with an increased DNA input should ideally be undertaken. If this is not possible, the risk of false negative calls may be mitigated by manual review of the quantitative PCR data and/or by reflexing to alternative analysis options.


Renal cyclooxygenase and lipoxygenase products are altered in polycystic kidneys and by dietary soy protein and fish oil treatment in the Han:SPRD-Cy rat.
Dietary fish oil (FO) and soy protein (SP) are two interventions that slow disease progression in the Han:SPRD-Cy rat model of polycystic kidney disease (PKD). Inhibition of cyclooxygenase (COX)-derived eicosanoids also reduces disease progression, but the role of lipoxygenase (LOX) products in this disease is not known. Since dietary FO and SP have been shown to alter eicosanoid formation via differing mechanisms, Han:SPRD-Cy rats were given diets containing either casein protein (CP) or SP, and soy oil (SO) or FO. Analysis of eicosanoids revealed that renal COX products were higher and LOX products were lower in diseased kidneys. SP feeding resulted in lower COX products, activity and COX1 protein and higher LOX products in the diseased kidneys in parallel with reduced renal cyst growth and fibrosis. By comparison, FO reduced both COX and LOX products produced from n-6 fatty acids and increased 3-series prostanoids in both normal and diseased cortex and medulla, but these differences did not parallel effects on disease. Renal COX-derived eicosanoids are elevated and LOX products are reduced in this model of kidney disease. The effects of dietary SP, but not FO, on renal eicosanoids parallel the effects on disease.


Development of a Pantetheine Force Field Library for Molecular Modeling.
Pantetheine is ubiquitous in nature in various forms of pantetheine-containing ligands (PCLs), including coenzyme A and phosphopantetheine. Lack of scalable force field libraries for PCLs has hampered the computational studies of biological macromolecules containing PCLs. We describe here the development of the first generation Pantetheine Force Field (PFF) library that is compatible with Amber force fields; parameterized using Gasteiger, AM1-BCC, or RESP charging methods combined with gaff2 and ff14SB parameter sets. In addition, a "plug-and-play" strategy was employed to enable the systematic charging of computationally expensive molecules sharing common substructural motifs. The validation studies performed on the PFF library showed promising performance where molecular dynamics (MD) simulations results were compared with experimental data of three representative systems. The PFF library represents the first force field library capable of modeling systems containing PCLs in silico and will aid in various applications including protein engineering and drug discovery.


Comprehensive geriatric assessment in Korean elderly cancer patients receiving chemotherapy.
Growing evidence suggests that a comprehensive geriatric assessment (CGA) in older patients with cancer can detect unsuspected health problems, predict survival, and predict tolerance to chemotherapy. However, studies regarding CGA in cancer patients are scarce in Asia. We prospectively enrolled 65 elderly cancer patients who were candidates of systemic chemotherapy between July 2006 and March 2008. Baseline CGA data including demographic information, comorbidity, functional status by means of Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL), cognition, psychological state, nutritional status, and medication were collected and analyzed. Quality of life (QoL) was assessed by the EORTC questionnaire QLQ-C30. Of the 65 patients, the median age was 71 years (range, 65-80), 49 (75%) were males, and 58 (89%) had Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1. All patients had solid tumor, 74% received palliative chemotherapy, and 18% received adjuvant chemotherapy. Twenty-five percent of patients had Charlson's comorbidity index score of 2 or more, 23% were ADL dependent, and 14% were IADL dependent. Using Mini-Mental Status Exam (MMSE), it was found that 51% of patients had mild cognitive impairment (MMSE score 17-24), and 5% had cognitive impairment (≤ 16). Forty percent of patients had depression by Short form Geriatric Depression Scale (SGDS), 19% had malnutrition by Mini-Nutritional Assessment (MNA), and 23% had body mass index (BMI) less than 19.4 kg/m(2) (lowest 10%). Global health status/quality of life (QoL) was less than 50% in 39% of patients. Frail patients according to the Balducci classification had significantly poor ECOG PS and worse global health status/QoL. CGA was feasible and could detect multiple unsuspected health problems including functional impairment and malnutrition in Korean elderly cancer patients receiving chemotherapy.


Efficacy of a Methanolic Extract of Adansonia digitata Leaf in Alleviating Hyperglycemia, Hyperlipidemia, and Oxidative Stress of Diabetic Rats.
Traditionally, in many countries, various parts of the Adansonia digitata (A. digitata) tree have been used in the treatment of many clinical ailments including diarrhea and dysentery. The phytochemical screening has indicated that the leaf extract of A. digitata contains flavonoids, saponins, mucilage, steroids, and alkaloids. Thus, this paper aims to evaluate the hyperglycaemic and hypolipidaemic effects of methanolic extract of A. digitata leaves (200 mg/kg and 400 mg/kg) in diabetic rats. The extract was administered orally for six weeks in the streptozotocin (STZ)-induced diabetic rats. The treatment with the extract caused a significant reduction in the blood glucose, glycosylated hemoglobin, cholesterol, triglycerides, low-density lipoprotein (LDL), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and malondialdehyde (MDA) levels by 46.7%, 46.15%, 48.91%, 43%, 60%, 66%, 45.45%, and 30.4%, respectively, as compared to the diabetic group after the sixth week of treatment. The leaf extract also mitigated the decline of high-density lipoprotein (HDL) level, RBCs count, hemoglobin level, packed cell volume (PCV %), and erythropoietin concentration in diabetic rats by 31%, 33.25%, 24.72%, 51.42%, and 220.68% with respect to the diabetic group. Also, the extract maintained the level of antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD), and reduced glutathione (GSH) in the diabetic rats. It also reduced the elevation in the white blood corpuscles (WBC) count in the STZ-induced diabetic rats. Our study, therefore, indicates that methanolic extract of A. digitata leaf exerts strong antidiabetic and hypolipidaemic properties in a dose-dependent manner by improving the hematological properties and redox parameters in the experimental diabetic rats.


On human outmigration model.
"This paper provides a probability model for the total out-migration pattern from the rural areas [of India]. The suitability of [the] model [is] tested through observed data."


Native Americans: Where in Environmental Justice Research?
While the last two decades have seen important theoretical, empirical, and policy advancements in environmental justice generally, much remains to be done regarding Native Americans. Unique political and cultural dynamics shape the study and pursuit of environmental justice (EJ) in Native American communities. This review summarizes Native American EJ issues based on a cross-disciplinary search of over 60 publications. In so doing, we discuss the unique nature of Native American EJ in terms of conducting research and working toward reducing the continuation of historical trauma associated with environmental ills, the types of strategies used in Native American EJ research, and issues of Native American climate justice. We conclude with discussion of remaining knowledge gaps and future research needs.


Membrane-linked energy transductions. Bioenergetic functions of sodium: H+ is not unique as a coupling ion.
The concept is developed according to which Na+, like H+, can play the role of a coupling ion in energy-transducing biomembranes. This idea is based on observations that (i) Na+ can be extruded from the cell by primary pumps (Na-motive NADH-quinone reductase, decarboxylase or ATPase), and (ii) the downhill Na+ flux into the cell can be coupled with the performance of all the three types of membrane-linked work i.e. chemical (ATP synthesis), osmotic (accumulation of solutes) and mechanical (motility). Marine alkalotolerant Vibrio alginolyticus represents the first example of such a complete sodium cycle pattern. Simplified versions of the sodium cycle or some of its constituents are found in the cytoplasmic membrane of a great variety of taxa including anaerobic, aerobic and photosynthetic bacteria, cyanobacteria and animals; this fact indicates that Na+ energetics should be regarded as a common case, rather than a rare exception applied to some natural niches only.


"Bread and a pennyworth of treacle": excess female mortality in England in the 1840s.
The author analyzes excess female mortality in nineteenth-century England. She concludes that such mortality was affected by the economic environment and that "much literary evidence points to unequal access to food and a resulting susceptibility to epidemic and respiratory diseases as the transmission mechanism converting dependence and discrimination into relatively high death rates." Women were also adversely affected by harsh labor conditions, in addition to the heavy duties involved in motherhood and housework.


Rapid identification and quantitation for oral bacteria based on short-end capillary electrophoresis.
High-speed capillary electrophoresis (HSCE) is a promising technology applied in ultra-rapid and high-performance analysis of biomolecules (such as nucleic acids, protein). In present study, the short-end capillary electrophoresis coupled with one novel space domain internal standard method (SDIS) was employed for the rapid and simultaneous analysis of specific genes from three oral bacteria (Porphyromonas gingivalis (P.g), Treponema denticola (T.d) and Tannerela forsythia (T.f)). The reliability, reproducibility and accuracy properties of above mentioned SDIS method were investigated in detail. The results showed the target gene fragments of P.g, T.d and T.f could be precisely, fast identified and quantitated within 95s via present short-end CE system. The analyte concentration and the ratio of space domain signals (between target sample and internal standard sample) featured a well linear relationship calculated via SDIS method. And the correlation coefficients R(2) and detection limits for P.g, T.d, T.f genes were 0.9855, 0.9896, 0.9969 and 0.077, 0.114 and 0.098ng/μl, respectively.


Phylogenetic characterization of Polish isolates of infectious pancreatic necrosis virus in salmonid fish.
Infectious pancreatic necrosis virus belongs to the genus Aquabirnavirus and family Birnaviridae. By VP2 gene similarity, aquatic birnavirus is clustered into seven genogroups. The aim of this study was to genetically analyse IPN viruses occurring on Polish fish farms. Samples from freshwater fish mostly from 2012 to 2013 and from northern Poland were examined for the presence of IPN virus using isolation on cell cultures, real-time RT-PCR and RT-PCR. Fragments of 1,377 and 1,079 bp of the VP2 and VP5 genes, respectively, were sequenced, and the results were assembled into one consensus and analysed by Geneious software. The same VP2 gene region was compared and a phylogenetic tree generated by the neighbour-joining method and MEGA6 software. All tested Polish isolates belonged to genogroup 5, like other European Spajurup isolates. Our findings prove that there is only one IPN virus genogroup in Poland. Polish isolates show close relationships with each other. There is a close relationship between Polish isolates and isolates from Turkey, Spain and Iran. Isolate 57 is a separate branch related to isolates from the United States and Taiwan. This points to the likelihood of past virus introduction via import of stock from those countries.


Technological transfer to demonstrative scale of sequencing batch biofilter granular reactor (SBBGR) technology for municipal and industrial wastewater treatment.
The paper reports the results of an experimental investigation aimed at transferring to demonstrative scale an innovative technology (SBBGR-Sequencing Batch Biofilter Granular Reactor) for the treatment of municipal and industrial wastewater by financial support of the EU Life programme. When this technology was applied for treating municipal wastewater, the results showed that the system was able to remove 80-90% of COD, total suspended solids and ammonia independently of the hydraulic residence time investigated (i.e., from 12 to 4 h). In the case of tannery wastewater, chosen as representative of concentrated industrial wastewater, SBBGR technology was suitable for removing 80-90% of the COD, suspended solids and ammonia content up to organic loading values of 3.5 kg COD/m3.d. During both periods, the process was characterised by a very high sludge age value (theta(c) approximately 150 d) that led to a biomass concentration as high as 35 gTSS/L(bed) and a sludge production much lower (5-6 times lower) that than commonly reported for conventional treatment plants.


Differential submergence tolerance between juvenile and adult Arabidopsis plants involves the ANAC017 transcription factor.
Plants need to attune their stress responses to the ongoing developmental programmes to maximize their efficacy. For instance, successful submergence adaptation is often associated with a delicate balance between saving resources and their expenditure to activate measures that allow stress avoidance or attenuation. We observed a significant decrease in submergence tolerance associated with ageing in Arabidopsis thaliana, with a critical step between 2 and 3 weeks of post-germination development. This sensitization to flooding was concomitant with the transition from juvenility to adulthood. Transcriptomic analyses indicated that a group of genes related to abscisic acid and oxidative stress response was more highly expressed in juvenile plants than in adult ones. These genes are induced by the endomembrane tethered transcription factor ANAC017 that was in turn activated by submergence-associated oxidative stress. A combination of molecular, biochemical and genetic analyses showed that these genes are located in genomic regions that move towards a heterochromatic state with adulthood, as marked by lysine 4 trimethylation of histone H3. We concluded that, while the mechanisms of flooding stress perception and signal transduction were unaltered between juvenile and adult phases, the sensitivity that these mechanisms set into action is integrated, via epigenetic regulation, into the developmental programme of the plant.


Enantioselective recognitions of chiral molecular tweezers containing imidazoliums for amino acids.
Two kinds of novel chiral molecular tweezers containing imidazoliums were synthesized from L-alanine, L-phenylalanine, and L-glutamic acid. They are constructed by the chiral imidazolium pincers and two different spacers which are 1,3-bis (bromomethyl)benzene and 2,6-bis(bromomethyl)pyridine, respectively. The enantioselective recognition of L- and D-amino acid derivatives by these molecular tweezers was investigated by UV spectroscopic titration experiments and good enantioselectivities were obtained, which are highly sensitive to whether the spacer has the binding site and the pincers has the other aromatic rings besides imidazolium ring. The host molecular 3b.2PF6- showed remarkable enantioselectivity for N-Boc protected histidine methyl ester, affording K(L)/K(D) of 5.10.


Vitamin D status in patients with systemic lupus erythematosus (SLE): A systematic review and meta-analysis.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease where chronic inflammation and tissue or organ damage is observed. Due to various suspected causes, inadequate levels of vitamin D (a steroid hormone with immunomodulatory effects) has been reported in patients with SLE, however, contradictory. The aim of this systematic review and meta-analysis was to evaluate the serum levels of vitamin D in patients with SLE in compared to healthy controls. PubMed, SCOPUS, ScienceDirect and Google Scholar electronic databases were searched systematically without restricting the languages and year (up to March 2, 2019) and studies were selected based on the inclusion criteria. Mean difference (MD) along with 95% confidence intervals (CI) were used and the analyses were carried out by using a random-effects model. Different subgroup and sensitivity analyses were conducted. Study quality was assessed by the modified Newcastle-Ottawa Scale (NOS) and publication bias was evaluated by a contour-enhanced funnel plot, Begg's and Egger's tests. We included 34 case-control studies (2265 SLE patients and 1846 healthy controls) based on the inclusion criteria. Serum levels of vitamin D was detected significantly lower in the SLE patients than that in the healthy controls (MD: -10.44, 95% CI: -13.85 to -7.03; p < .00001). SLE patients from Asia (MD: -13.75, 95% CI: -21.45 to -6.05; p = .0005), South America (MD: -3.16, 95% CI: -4.62 to -1.70; p < .0001) and Africa (MD: -16.15, 95% CI: -23.73 to -8.56; p < .0001); patients residing below 37° latitude (MD: -11.75, 95% CI: -15.79 to -7.70; p < .00001); serum vitamin D during summer season (MD: -7.89, 95% CI: -11.70 to -4.09; p < .0001), patients without vitamin D supplementation (MD: -15.57, 95% CI: -19.99 to -11.14; p < .00001) or on medications like hydroxychloroquine, corticosteroids or immunosuppressants without vitamin D supplementation (MD: -16.46, 95% CI: -23.86 to -9.05; p < .0001) are in higher risk in presenting inadequate serum levels of vitamin D. The results remained statistically significant from different sensitivity analyses which represented the robustness of this meta-analysis. According to the NOS, 91.2% of the studies were considered as of high methodological quality (low risk of bias). No significant publication bias was detected from contour-enhanced and trim and fill funnel plots or Begg's test. Inadequate levels of serum vitamin D is significantly high in patients with SLE compared to healthy subjects, therefore, vitamin D supplementation with regular monitoring should be considered as part of their health management plans.


CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response.
Aprataxin, defective in the neurodegenerative disorder ataxia oculomotor apraxia type 1, resolves abortive DNA ligation intermediates during DNA repair. Here, we demonstrate that aprataxin localizes at sites of DNA damage induced by high LET radiation and binds to mediator of DNA-damage checkpoint protein 1 (MDC1/NFBD1) through a phosphorylation-dependent interaction. This interaction is mediated via the aprataxin FHA domain and multiple casein kinase 2 di-phosphorylated S-D-T-D motifs in MDC1. X-ray structural and mutagenic analysis of aprataxin FHA domain, combined with modelling of the pSDpTD peptide interaction suggest an unusual FHA binding mechanism mediated by a cluster of basic residues at and around the canonical pT-docking site. Mutation of aprataxin FHA Arg29 prevented its interaction with MDC1 and recruitment to sites of DNA damage. These results indicate that aprataxin is involved not only in single strand break repair but also in the processing of a subset of double strand breaks presumably through its interaction with MDC1.


Multiscale modeling of composite materials: a roadmap towards virtual testing.
A bottom-up, multiscale modeling approach is presented to carry out high-fidelity virtual mechanical tests of composite materials and structures. The strategy begins with the in situ measurement of the matrix and interface mechanical properties at the nanometer-micrometer range to build up a ladder of the numerical simulations, which take into account the relevant deformation and failure mechanisms at different length scales relevant to individual plies, laminates and components. The main features of each simulation step and the information transferred between length scales are described in detail as well as the current limitations and the areas for further development. Finally, the roadmap for the extension of the current strategy to include functional properties and processing into the simulation scheme is delineated.


Comparison of hip fracture and osteoporosis medication prescription rates across Canadian provinces.
The study explores osteoporosis medication prescribing across Canadian provinces and any impact on hip fracture rates. Despite a marked variation in the prescribing of such medication, there is no effect on the hip fracture rate in either gender or any age group, suggesting either poor targeting or lack of efficacy. Hip fractures are the most disabling and costly of osteoporotic fractures, and a reduction in the risk of hip fracture is an expectation of osteoporosis medications. In this study, we have compared the use of osteoporosis medication across Canadian provinces with the rate of hip fractures in the same regions. Three years of hip fracture data (2007-2009 inclusive) were obtained from the Canadian Institute for Health Information for all Canadian provinces excluding Quebec. Population information was obtained from Statistics Canada and medication information from the Brogan Inc. database. Because osteoporosis medication is available daily, weekly, monthly, and yearly, medication prescriptions were converted to "units" of prescribing, so that a once a year infusion represented 365 units, a monthly prescription 30 units, and so forth. There is a fourfold difference in prescribing across provinces but no corresponding variation in hip fracture rate. No significant correlation exists between prescribing load and hip fracture rate. This was true for all age groups, both genders, and for both intertrochanteric and subcapital hip fracture. We find no association between osteoporosis medication prescribing and hip fracture rate. Possible explanations include insufficient numbers of at-risk patients on treatment, inappropriate targeting, and either lack of efficacy or efficacy limited to only certain subgroups of patients such as those with demonstrable trabecular osteoporosis.


Roles of Testosterone and Estradiol in Mediation of Acute Neuroendocrine and Electroencephalographic Effects of Sevoflurane During the Sensitive Period in Rats.
Testosterone (T), predominantly acting through its derivative 17β-estradiol (E2), regulates the brain's sexual differentiation in rodents during the perinatal sensitive period, which mirrors the window of vulnerability to the adverse effects of general anesthetics. The mechanisms of anesthesia's adverse effects are poorly understood. We investigated whether sevoflurane alters T and E2 levels and whether they contribute to sevoflurane's acute adverse effects in postnatal day 5 Sprague-Dawley rats. The rats underwent electroencephalography recordings for 2 h of baseline activity or for 1 h before and another hour during 2.1% sevoflurane exposure, followed by collection of trunk blood and brain tissue. Pharmacological agents, including the GABA type A receptor inhibitor bicuculline and the aromatase inhibitor formestane, were administered 30 min before sevoflurane anesthesia. Sevoflurane increased serum T levels in males only. All other effects of sevoflurane were similar in both sexes, including increases in serum levels of E2, hypothalamic mRNA levels of aromatase, estrogen receptor α (Erα) [not estrogen receptor β (Erβ)], Na+-K+-Cl- cotransporter (Nkcc1)/K+-Cl- cotransporter (Kcc2) mRNA ratio, electroencephalography-detectable seizures, and stress-like corticosterone secretion. Bicuculline and formestane alleviated these effects, except the T level increases. The ERα antagonist MPP, but not the ERβ antagonist PHTPP, reduced electroencephalography-detectable seizures and normalized the Nkcc1/Kcc2 mRNA ratio. Collectively, sevoflurane exacerbates levels of T in males and E2 in both sexes during the period of their organizational effects in rodents. Sevoflurane acts through GABAAR-mediated, systemic T-independent elevation of E2 to cause electroencephalography-detectable seizures, stress-like corticosterone secretion, and changes in the expression of genes critical for brain development.


The mode of biofilm formation on smooth surfaces by Campylobacter jejuni.
Many microorganisms produce extracellular polymers referred to collectively as "slime" or glycocalyx, and form biofilms on solid surfaces in natural ecosystems. Campylobacter jejuni, one of the most important foodborne pathogens, also has the ability to form biofilm on stainless steel, glass, or polyvinyl chloride in vitro. However, the issue of biofilm formation by Campylobacter species has not been extensively examined. The present study was performed to examine the mode of adhesion of C. jejuni to a smooth surface. When bacterial suspensions in Brucella broth were incubated in microplate wells with a glass coverslip, microcolonies 0.5~2 mm in diameter were formed on the coverslip within 2 hr from the start of incubation. These microcolonies gradually grew and formed a biofilm of net-like connections within 6 hr. Transmission electron microscopy indicated that massive amounts of extracellular material masked the cell surface, and this material bound ruthenium red, suggesting the presence of a polysaccharide moiety. Scanning electron microscopy indicated that the flagella acted as bridges, forming net-like connections between the organisms. To determine the genes associated with biofilm formation, aflagellate (flaA(-)) and flagellate but non-motile (motA(-)) mutants were constructed from strain 81-176 by natural transformation-mediated allelic exchange. The flaA(-) and motA(-) mutants did not form the biofilm exhibited by the wild-type strain. These findings suggest that flagella-mediated motility as well as flagella is required for biofilm formation in vitro.


Children and homicide.
Child homicide is as old as human history. It can be classified into intra- and extra familial child homicide. Different forms of homicide are discussed, and research findings show that in the age group 0-3 years the majority of cases were within the family. After age 12 years, it is primarily extra familial. With increased age of the child the phenomenon of child perpetrators is seen to be manifested in school homicide and juvenile crime. Risk factors are mentioned and pediatricians and family physicians should be aware of these in order to try preventive measures.


Molecular basis of LMAN1 in coordinating LMAN1-MCFD2 cargo receptor formation and ER-to-Golgi transport of FV/FVIII.
The LMAN1-MCFD2 (lectin, mannose binding 1/multiple coagulation factor deficiency protein 2) cargo receptor complex transports coagulation factors V (FV) and VIII (FVIII) from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment (ERGIC). LMAN1 (ERGIC-53) is a hexameric transmembrane protein with a carbohydrate recognition domain (CRD) on the ER luminal side. Here, we show that mutations in the first beta sheet of the CRD abolish MCFD2 binding without affecting the mannose binding, suggesting that LMAN1 interacts with MCFD2 through its N-terminal beta sheet, consistent with recently reported crystal structures of the CRD-MCFD2 complex. Mutations in the Ca(2+)- and sugar-binding sites of the CRD disrupt FV and FVIII interactions, without affecting MCFD2 binding. This interaction is independent of MCFD2, as LMAN1 mutants defective in MCFD2 binding can still interact with FVIII. Thus, the CRD of LMAN1 contains distinct, separable binding sites for both its partner protein (MCFD2) and the cargo proteins (FV/FVIII). Monomeric LMAN1 mutants are defective in ER exit and unable to interact with MCFD2, suggesting that the oligomerization of LMAN1 is necessary for its cargo receptor function. These results point to a central role of LMAN1 in regulating the binding in the ER and the subsequent release in the ERGIC of FV and FVIII.


Polymer surfaces with reversibly switchable ordered morphology.
Honeycomb macroporous films fabricated by the "breath figures" method were composed of poly2-vinylpyridine (P2VP) distributed in the holes of polystyrene (PS). The porous films exhibited reversible behavior responding to water and different solvent vapors. When the porous film was treated with water, the honeycomb pattern would change to the hexagonal islandlike pattern. Once heated to remove the water, the honeycomb pattern emerged again. When the porous film was exposed to different solvent vapors, the same reversible process appeared. Carbon disulfide (CS(2)), toluene (TOL), and tetrahydrofuran (THF) solvent vapors induced the honeycomb pattern into the ordered islandlike pattern, and ethanol, chloroform, methyl ethyl ketone (MEK), and dimethylformamide (DMF) solvent vapors made the islandlike pattern come back to the honeycomb pattern. The hygroscopic property of P2VP and the polymer-solvent interaction are the driving force for the reversibly switchable morphology. The appropriate control of the hole depth is very crucial in determining the reversible changes.


Endothelial Heme Dynamics Drive Cancer Cell Metabolism by Shaping the Tumor Microenvironment.
The crosstalk among cancer cells (CCs) and stromal cells within the tumor microenvironment (TME) has a prominent role in cancer progression. The significance of endothelial cells (ECs) in this scenario relies on multiple vascular functions. By forming new blood vessels, ECs support tumor growth. In addition to their angiogenic properties, tumor-associated ECs (TECs) establish a unique vascular niche that actively modulates cancer development by shuttling a selected pattern of factors and metabolites to the CC. The profile of secreted metabolites is strictly dependent on the metabolic status of the cell, which is markedly perturbed in TECs. Recent evidence highlights the involvement of heme metabolism in the regulation of energy metabolism in TECs. The present study shows that interfering with endothelial heme metabolism by targeting the cell membrane heme exporter Feline Leukemia Virus subgroup C Receptor 1a (FLVCR1a) in TECs, resulted in enhanced fatty acid oxidation (FAO). Moreover, FAO-derived acetyl-CoA was partly consumed through ketogenesis, resulting in ketone bodies (KBs) accumulation in FLVCR1a-deficient TECs. Finally, the results from this study also demonstrate that TECs-derived KBs can be secreted in the extracellular environment, inducing a metabolic rewiring in the CC. Taken together, these data may contribute to finding new metabolic vulnerabilities for cancer therapy.


Quantum dot-based nanosensors for diagnosis via enzyme activity measurement.
Enzymes are essential in the human body, and the disorder of enzymatic activities has been associated with many different diseases and stages of disease. Luminescent semiconductor nanocrystals, also known as quantum dots (QDs), have garnered great attention in molecular diagnostics. Owing to their superior optical properties, tunable and narrow emissions, stable brightness and long lifetime, QD-based enzyme activity measurement has demonstrated improved detection sensitivity, which is considered particularly valuable for early disease diagnosis. Recent studies have also shown that QD-based nanosensors are capable of probing multiple enzyme activities simultaneously. This review highlights the current development of QD-based nanosensors for enzyme detection. The enzyme-QD hybrid system, equipped with unique electronic, optical and catalytic properties, is envisioned as a potential solution in addressing challenges in diagnostics and therapeutics.


Does school social capital modify socioeconomic inequality in mental health? A multi-level analysis in Danish schools.
It seems that social capital in the neighbourhood has the potential to reduce socioeconomic differences in mental health among adolescents. Whether school social capital is a buffer in the association between socioeconomic position and mental health among adolescents remains uncertain. The aim of this study is therefore to examine if the association between socioeconomic position and emotional symptoms among adolescents is modified by school social capital. The Health Behaviour in School-aged Children Methodology Development Study 2012 provided data on 3549 adolescents aged 11-15 in two municipalities in Denmark. Trust in the school class was used as an indicator of school social capital. Prevalence of daily emotional symptoms in each socioeconomic group measured by parents' occupational class was calculated for each of the three categories of school classes: school classes with high trust, moderate trust and low trust. Multilevel logistic regression analyses with parents' occupational class as the independent variable and daily emotional symptoms as the dependent variable were conducted stratified by level of trust in the school class. The prevalence of emotional symptoms was higher among students in school classes with low trust (12.9%) compared to school classes with high trust (7.2%) (p < 0.01). In school classes with low level of trust, the odds ratio for daily emotional symptoms was 1.89 (95% CI 1.25-2.86) in the low socioeconomic group compared to the high socioeconomic group. In school classes characterised by high and moderate trust, there were no statistically significant differences in emotional symptoms between high and low socioeconomic groups. Although further studies are needed, this cross-sectional study suggests that school social capital may reduce mental health problems and diminish socioeconomic inequality in mental health among adolescents.


Reclassification of Xylanibacter oryzae Ueki et al. 2006 as Prevotella oryzae comb. nov., with an emended description of the genus Prevotella.
16S rRNA gene sequence information has indicated that Xylanibacter oryzae has a close relationship with the genus Prevotella. To clarify the taxonomic position of X. oryzae, we determined the sequence of hsp60 as it represents an alternative phylogenetic marker for identification and classification of Gram-negative anaerobic rods. On the basis of hsp60 sequences, X. oryzae was located within the genus Prevotella, indicating that the species does not represent a distinct taxon at the genus level. Statistical tests (the Shimodaira-Hasegawa test and the approximately unbiased test) supported the finding that X. oryzae is monophyletic with members of the genus Prevotella and thus belongs to the genus. On the basis of the phylogenetic findings, we propose that X. oryzae should be reclassified as Prevotella oryzae comb. nov.; the type strain is KB3(T) (=JCM 13648(T) =DSM 17970(T)). An emended description of the genus Prevotella is also provided.


Parapoxviruses: from the lesion to the viral genome.
Viruses of the genus parapoxvirus from the family poxviridae cause widespread but localized diseases of small and large ruminants. The economically most important disease is contagious pustular dermatitis or contagious ecthyma among sheep and goats, often simply called orf. The parapoxviruses (PPV) can be transmitted to man leading to localized lesions that are named pseudocowpox or milkers' node as being mostly restricted to the hands and fingers. In cattle two forms of PPV manifestation are commonly observed, the bovine papular stomatitis in young calves and the occurrence of lesions at the udder of cows. We here report about the recent efforts in molecular characterization of orf viruses and the state of the art about the generation of orf virus recombinants. In addition the current knowledge on immune responses against orf viruses and some new data on the behaviour of orf virus recombinants under non-permissive conditions are reported.


Topochemical transformation route to atomically thick Co3O4 nanosheets realizing enhanced lithium storage performance.
We first demonstrate the rational design and fabrication of novel atomically thick Co3O4 nanosheets (ATCNs) with a specific facet exposed by topochemical transformation from layered intermediate precursors to optimize energy storage. The eminently enhanced lithium storage performance can be attributed not only to the synergistic advantages of inorganic graphene analogues but also the increase of Co(2+) atoms and charge redistribution for ATCNs, which were first revealed by means of synchrotron radiation X-ray absorption near-edge spectroscopy. This work opens the window for the preparation of non-layered atomically thick nanosheets, which will significantly enrich the species of inorganic graphene analogues and optimize energy storage by reasonable materials design and fabrication.


Aspiration and the elderly.
Aspiration is prevalent in the elderly but its association with impairment of oral intake and gastroesophageal reflux is often misunderstood. This paper describes the causes, pathophysiology, and consequences of aspiration and their unique features in aged persons. It also explains how videofluoroscopic evaluation can assess current function while limiting factors that result in misinformation. The management of aspiration is discussed, emphasizing the importance and difficulties in maintaining functional well-being and possible complications of therapy.


Lipids of human lens fiber cell membranes.
A study of the membranes of human lens fiber cells revealed a very high protein to lipid ratio, which tended to increase with aging and in brunescent cataract. Phospholipids were more abundant than cholesterol, cholesterol esters, and other neutral lipids. With aging and cataract formation, a marked decrease in membranes phospholipid content occurred. Sphingomyelin was present in highest amount. Phosphatidylethanolamine, phosphatidylcholine, lysophosphatidyl-ethanolamine, phosphatidylserine, and phosphatidylglycerol were also present. Cholesterol represented approximately 40% of the total lipids. Saturated and unsaturated fatty acids having 16 to 24 carbons were present. The lipid composition varied according to the portion of the lens examined and the state of the lens. The results do not support a conclusion that lipid peroxidation represents a major mechanism of membrane damage that contributes to cataract formation, since there is no decrease in unsaturated fatty acids with age or in cataractous lenses. We suggest that the aggregation of soluble proteins, and their association with lens membranes, and altered membrane function due to the loss of phospholipids are important processes leading to loss of transparency.