The immune response of CBA/N mice and their F1 hybrids to 2,4,6-trinitrophenylated (TNP) antigens. I. Analysis of the response to TNP-coupled lipopolysaccharide in vivo and at the clonal level.
Plaque-forming cell (PFC) responses to 2,4,6-trinitrophenylated lipopolysaccharide (TNP-LPS) were studied in normal and immunodeficient mice. In vivo immunizations with TNP-LPS showed a 25--50% reduction in PFC responses in CBA/N mice and their (CBA/N X BALB/c)F1(NBF1) male hybrids with an X-linked immune defect of B lymphocyte differentiation. A detailed clonal analysis of the reduced responses to TNP-LPS revealed that CBA/N and NBF1 male mice with the X-linked genetic defect have fewer precursor B cells engaged in the response to TNP-LPS than the control mice. The reduction in precursor cell numbers affects selectively B cells secreting high avidity anti-TNP antibodies as determined by PFC inhibition studies.


Integrating external clinical information with the ten-step monitoring and evaluation process: from theory to practice.
Traditionally, Sisters of Mercy Health System (SMHS)-St Louis hospitals have had difficulty integrating quality information from external sources into their own monitoring and evaluation activities. This difficulty became apparent at the 14 hospitals of the SMHS when the system headquarters began providing its hospitals with comparative clinical outcome information. Although the hospitals found value in the comparative studies, the information was not fully used in individual hospitals' quality improvement efforts. As a result, SMHS developed a model for integrating external quality information into the local hospitals' ten-step monitoring and evaluation process. This article explains the integration model and shows how it has worked in several clinical scenarios.


A N-heterocyclic carbene gold hydroxide complex: a golden synthon.
The synthesis and complete characterisation of a well-defined N-heterocyclic carbene bearing gold hydroxide complex, [Au(OH)(IPr)], is reported. Its reaction chemistry appears rich and diverse.


Nation-wide survey of antibiotic resistance by means of a computer. Analysis of 200.000 strains of problem bacteria isolated in 1973.
Based on a pilot study performed in 5 District Public Health Laboratories (PHL) in the Slovakia in 1972 (1), the computer system for elaborating the informations concerning the resistance of "problem bacteria" to antibiotics has completely been introduced in 18 PHLs for all-year studies on the resistance to antibiotics in 1973. The results obtained in each PHL and also in total of about 200.000 bacterial strains belonging to 8 of the clinically most important bacterial species were passed on to the corresponding PHL and to the health authorities twice a year. Each PHL elaborated these data being useful and instructive for general practitioners and clinicians in the hospitals of their districts to a commented information on the actual state of effectiveness of individual antibacterial drugs. The multiple spectra of resistance to antibiotics indicating the occurrence of R plasmids in clinical isolates of bacteria and the dynamics for the development of resistance against certain specially monitored "reserved antibiotics" are elaborated at present and will be published in a subsequent communication...


Dissimilatory nitrate reduction to ammonium in four Pseudomonas spp. under aerobic conditions.
Dissimilatory nitrate reduction to ammonium (DNRA) has an important role in soil nitrogen retention and is considered to be constrained to anaerobic conditions. However, a recent study found that Pseudomonas putida Y-9 is capable of DNRA under aerobic conditions. In this study, four species of Pseudomonas spp. were found to produce ammonium during the nitrite reduction process under aerobic conditions, similar to the Y-9 strain. The detectable ammonium in the culture supernatant during the nitrite reduction process for each of the four strains originated intracellularly. A subsequent 15N isotope experiment showed that these four strains were able to transform 15NO2 - to 15NH4 + in 3 h under aerobic conditions. The NirBD sequence in each of the four strains showed high similarity with that in the Y-9 strain (approximately 94.61%). Moreover, the nirBD sequences in the four strains and the Y-9 strain were all similar to those of other Pseudomonas spp., while they were relatively distant in terms of their phylogenetic relationship from those of other genera. Overall, these results suggest that these four strains of Pseudomonas spp. are capable of DNRA under aerobic conditions, which might be attributed to the existence of nirBD.


Optimization of ultrasonic circulating extraction of polysaccharides from Asparagus officinalis using response surface methodology.
Polysaccharides were extracted from Asparagus officinalis. A novel ultrasonic circulating extraction (UCE) technology was applied for the polysaccharide extraction. Three-factor-three-level Box-Behnken design was employed to optimize ultrasonic power, extraction time and the liquid-solid ratio to obtain a high polysaccharide yield. The optimal extraction conditions were as follows: ultrasonic power was 600 W, extraction time was 46 min, the liquid-solid ratio was 35 mL/g. Under these conditions, the experimental yield of polysaccharides was 3.134%, which was agreed closely to the predicted value. The average molecular weight of A. officinalis polysaccharide was about 6.18×10(4) Da. The polysaccharides were composed of glucose, fucose, arabinose, galactose and rhamnose in a ratio of 2.18:1.86:1.50:0.98:1.53. Compared with hot water extraction (HWE), UCE showed time-saving, higher yield and no influence on the structure of asparagus polysaccharides. The results indicated that ultrasonic circulating extraction technology could be an effective and advisable technique for the large scale production of plant polysaccharides.


[Methodological challenges concerning the selection of diseases for a standardized multimorbidity index].
Multimorbidity is defined as the coexistence of two or more chronic diseases. However, this complex health status, which primarily affects elderly, is still insufficiently understood. One reason is the underrepresentation of older, multimorbid people in studies. Another reason is that there is no agreement on the number and type of diseases, which have to be considered in the assessment of multimorbidity. Therefore, this article provides an overview on the status quo of research on multimorbidity indices and describes in detail, what kind of methodological challenges have to be faced regarding the development of a standardized index. Finally, recommendations are made for criteria, which can be used for the selection of diseases relevant for multimorbidity.


Combined delivery of neurotrophin-3 and NMDA receptors 2D subunit strengthens synaptic transmission in contused and staggered double hemisected spinal cord of neonatal rat.
We investigated whether administration of neurotrophin-3 (NT-3) and NMDA-2D-expressing units, found previously to enhance transmission in neonatal rat spinal cord, strengthens synaptic connections in the injured neonatal cord. We employed electrophysiological methods to evaluate the strength of synaptic transmission to individual motoneurons in the contusion and staggered double hemisection spinal cord injury (SCI) models. SCI at caudal thoracic levels (T11-T12) was carried out at postnatal day 2 (P2). Plugs containing NT-3- secreting fibroblasts and NR2D-expressing HSV-1 amplicons (HSVnr2d) were implanted above the lesion. Control animals were treated with an amplicon-expressing beta-galactosidase (HSVlac). After 8-10 days of treatment, the rats were sacrificed and spinal cords were removed for intracellular recording. Untreated contused cords preserved a fraction of white matter and weak monosynaptic responses were observed through the injury region. However, no synaptic connections were observed in control cords receiving double hemisection injury. Combined treatment with NT-3 and HSVnr2d strengthened monosynaptic connections in contused cords and induced the appearance of weak but functional multisynaptic connections in double hemisected cords. In contrast, treatment with either NT-3 or HSVnr2d alone failed to induce appearance of synaptic responses through the hemisected region. These results suggest that chronic treatment with NT-3 secreting fibroblasts combined with facilitated function of NMDA receptors by HSVnr2d treatment strengthens connections that survive incomplete SCI and therefore that such combined treatment might facilitate recovery of function following SCI.


[The Value of Using SCAI Cardiogenic Shock Stages in Predicting Mortality in CICU Patients].
To study the value of using the cardiogenic shock (CS) stages developed by the Society of Cardiovascular Imaging and Intervention (SCAI) in predicting the mortality of CS patients in cardiac intensive care unit (CICU). We retrospectively collected (Jan., 2011-Jan., 2018) the information of inpatients who were admitted to the CICU of West China Hospital of Sichuan University on consecutive days, and conducted analysis on those with CS. The patients were divided into groups C, D and E, according to the corresponding SCAI stages, and the primary outcome indicator was in-hospital mortality. Logistic regression was done to determine the association between SCAI staging and in-hospital mortality before and after multivariate adjustment. The receiver operating characteristic curve was used to assess the value of SCAI stages of CS in predicting in-hospital mortality. We studies 839 CS patients who met our inclusion criteria. The proportions of patients of SCAI stages C (Classic), D (Deteriorating), and E (Extremis) were 43.3% (363 cases), 38.7% (325 cases) and 18.0% (151 cases), respectively. The unadjusted in-hospital mortality rates were 22.9% (83 cases), 44.0% (143 cases) and 53.6% (81 cases), respectively ( P<0.001). The SCAI stages had an AUC (area under the curve) of 0.640 for predicting in-hospital mortality among CS patients in CICU. After multivariate adjustment, the AUC increased to 0.776 ( P<0.001). In patients with acute coronary syndrome, the Global Registry of Acute Coronary Events (GRACE) scores had an AUC of 0.644 for predicting in-hospital mortality, while a combination of the GRACE score with SCAI staging yielded an increased AUC of 0.702 ( P<0.001). In CICU patients with CS, the SCAI stages of CS can be used as a stratified method for rapid assessment of disease risks upon admission. In patients with acute coronary syndrome and CS, SCAI stages combined with GRACE scores improved the ability to predict risks of death.


Adrenal cortical responses to low- and high-dose ACTH(1-24) administration in major depressives vs. matched controls.
Increased hypothalamo-pituitary-adrenocortical (HPA) axis activity occurs in 30-50% of patients with major depression. This includes normal-to-increased adrenal cortical hormone (cortisol) secretion in spite of reduced corticotropin (ACTH) stimulation. A possible explanation is increased adrenal responsiveness to ACTH. Supporting this possibility is the finding of increased adrenal volume, which reverts to normal with successful treatment. Eight female and six male patients with major depression, and eight female and six male individually matched controls, underwent two test sessions 5-7 days apart. On the first day, a low ACTH(1-24) dose (0.014 microg/kg i.v.), equivalent to 1 microg in a 70-kg individual, was given. On the second day, a supramaximal stimulating dose (250 microg i.v.) was given. Serial blood samples were analyzed for immunoreactive (IR-)ACTH, ACTH(1-39), and cortisol. There were no significant sex or patient-control differences in IR-ACTH areas under the curve (AUCs) following low-dose ACTH(1-24), and the correlation between patient and matched control AUCs was +0.71, indicating good correspondence in the amount of circulating ACTH(1-24) available for adrenal stimulation. There were no significant sex or patient-control differences in cortisol response and no significant interaction between dose and subject group, indicating that patients did not differ from controls in their cortisol responses to either low- or high-dose ACTH(1-24). These findings do not indicate increased adrenal cortical responsiveness in patients with major depression. Neurochemical/neurohormonal and neural stimulatory factors other than ACTH might be responsible for the increased adrenal gland size and cortisol secretion, in spite of reduced pituitary ACTH secretion, that has been reported in this illness.


The nucleus locus coeruleus/subcoeruleus affects the defensive-like, immobile posture following an air-puff startle reaction in the rat.
The air-puff startle is an example of a simple behavior in mammals. Following the startle reaction, rats assume a defensive-like, immobile posture (DIP) of approximately 2-5 s in length. The aim of the present study was to examine the effect of bilateral lesions of the nucleus locus coeruleus/subcoeruleus (LC/SC) on the DIP. Using male Sprague-Dawley rats, the DIP period in the air-puff startle was measured with a digital stop watch. The DIP period was defined as the time between the application of the air-puff stimuli and the first motion after the startle reaction. For air-puff stimulation (14.4 psi in strength, 0.1 s in duration), compressed house air was presented as a transient through a vinyl tube suspended 2.5 cm above the rat's head. Two weeks before the experiment, the rats received bilateral injections of 6 microg of the neurotoxin 6-hydroxydopamine to specifically lesion noradrenaline-containing neurons of the LC/SC. In the sham-lesioned rats (n=8), the DIP period did not significantly alter compared with that before operation. In contrast, in the LC/SC-lesioned rats (n=9), the DIP period significantly reduced to 78% of the values before lesions. The results suggest that the LC/SC is involved in the development of the DIP. We speculate that the DIP period is an attentional state and vigilance condition because LC/SC neurons have been implicated in the regulation of the attentional state and vigilance.


Clinical Challenge: A Rare Testicular Tumor.
We present the case of a 22-year-old male that comes to the Urology clinic with the incidental finding of a testicular mass. Typical findings in echography will guide us towards the diagnosis of an epidermoid cyst.1,2 This type of infrequent benign tumor is responsible for only around 2% of all testicular tumors.1 Because of this low incidence literature regarding epidermoid cysts is scarce. Treatment has been susceptible to change throughout the years.6 In this clinical case we challenge readers to review a rare tumor and to choose the most appropriate treatment for our patient.


Chaperonin TRiC/CCT participates in replication of hepatitis C virus genome via interaction with the viral NS5B protein.
To identify the host factors implicated in the regulation of hepatitis C virus (HCV) genome replication, we performed comparative proteome analyses of HCV replication complex (RC)-rich membrane fractions prepared from cells harboring genome-length bicistronic HCV RNA at the exponential and stationary growth phases. We found that the eukaryotic chaperonin T-complex polypeptide 1 (TCP1)-ring complex/chaperonin-containing TCP1 (TRiC/CCT) plays a role in the replication possibly through an interaction between subunit CCT5 and the viral RNA polymerase NS5B. siRNA-mediated knockdown of CCT5 suppressed RNA replication and production of the infectious virus. Gain-of-function activity was shown following co-transfection with whole eight TRiC/CCT subunits. HCV RNA synthesis was inhibited by an anti-CCT5 antibody in a cell-free assay. These suggest that recruitment of the chaperonin by the viral nonstructural proteins to the RC, which potentially facilitate folding of the RC component(s) into the mature active form, may be important for efficient replication of the HCV genome.


Growth factor-enriched autologous plasma improves wound healing after surgical debridement in odontogenic necrotizing fasciitis: a case report.
Odontogenic necrotizing fasciitis of the neck is a fulminant infection of odontogenic origin that quickly spreads along the fascial planes and results in necrosis of the affected tissues. It is usually polymicrobial, occurs frequently in immunocompromised patients, and has a high mortality rate. A 69-year old Mexican male had a pain in the maxillar right-canine region and a swelling of the submental and submandibular regions. Our examination revealed local pain, tachycardia, hyperthermia (39°C), and the swelling of bilateral submental and submandibular regions, which also were erythematous, hyperthermic, crepitant, and with a positive Godet sign. Mobility and third-degree caries were seen in the right mandibular canine. Bacteriological cultures isolated streptococcus pyogenes and staphylococcus aureus. The histopathological diagnosis was odontogenic necrotizing fasciitis of the submental and submandibular regions. The initial treatment was surgical debridement and the administration of antibiotics. After cultures were negative, the surgical wound was treated with a growth factor-enriched autologous plasma eight times every third day until complete healing occurred. The treatment with a growth factor-enriched autologous plasma caused a rapid healing of an extensive surgical wound in a patient with odontogenic necrotizing fasciitis. The benefits were rapid tissue regeneration, an aesthetic and a functional scar, and the avoidance of further surgery and possible complications.


A protein disulfide-thiol interchange activity of HeLa plasma membranes inhibited by the antitumor sulfonylurea N-(4-methylphenylsulfonyl)-N'-(4-chlorophenyl) urea (LY181984)
Plasma membrane vesicles isolated from HeLa cells grown in suspension culture contain a protein disulfide-thiol interchange (protein disulfide-like) activity. The activity was estimated from the restoration of activity to inactive (scrambled) pancreatic RNAase. RNAase activity was measured either by hydrolysis of cCMP or by a decrease in acid precipitable yeast RNA. The ability of plasma membrane vesicles to restore activity to inactive (scrambled) pancreatic ribonuclease was inhibited by the antitumor sulfonylurea N-(4-methylphenylsulfonyl)-N'-(4-chlorophenyl)urea (LY181984). The activity correlated with that of a cyanide-resistant NADH oxidase also associated with the plasma membrane vesicles that exhibited a similar pattern of drug response. The activity was stimulated by reduced glutathione and inhibited by oxidized glutathione but did not depend on either for activity. The antitumor sulfonylurea-inhibited activity was greatest in the presence of reduced glutathione and least in the presence of oxidized glutathione. The antitumor sulfonylurea-inhibited activity was unaffected by a monoclonal antibody to protein disulfide isomerase. Also the antitumor sulfonylurea-inhibited activity was unaffected by peptide antisera to the consensus active site sequence of protein disulfide isomerase. Thus the antitumor sulfonylurea-inhibited activity appeared to reside with a novel cell surface protein capable of oxidation of both NADH and protein thiols and of carrying out a protein disulfide isomerase-like protein disulfide-thiol interchange activity in the absence of NADH or other external reductants.


Predictors of prolonged hypotension requiring vasopressor support after resection of pheochromocytoma and paraganglioma.
Prolonged hypotension is a common complication after resection of pheochromocytoma (PCC) or paraganglioma (PGL). The objective of our study was to identify preoperative or intraoperative clinical factors that can predict prolonged hypotension after PCC/PGL resection. A total of 414 patients who underwent resection of PCC or PGL at our institution between January 2013 and January 2020 were included. Patients were divided into two groups according to whether or not vasopressor support was required postoperatively. Associations between preoperative and intraoperative variables and prolonged hypotension were evaluated. Two hundred and one (48.6%) patients had postoperative hypotension that required vasopressor support with a median duration of 20 h. Multivariable analysis demonstrated that increased 24-h urinary norepinephrine (NE) levels (odds ratio [OR] = 1.091, 95% confidence interval [CI]: 1.052-1.132, p < .001), longer operative time (OR = 1.008, CI: 1.004-1.011, p < .001) and lower preoperative phenoxybenzamine dose (OR = 0.336, CI: 0.150-0.753, p = .008) were predictors of prolonged hypotension. Moreover, operative time, body mass index, 24-h urinary level of NE and preoperative phenoxybenzamine dose were significantly correlated with the duration of postoperative vasopressor support. Increased urine NE level, longer operative time and lower preoperative phenoxybenzamine dose were predictors of prolonged hypotension requiring vasopressor support. Clinicians can identify these factors to manage their patients better and prevent severe complications.


Apparent pre- and postmenopausal bone loss evaluated by DXA at different skeletal sites in women: the OFELY cohort.
We measured the bone mineral density (BMD) at various skeletal sites (total body, hip, anteroposterior [AP] and lateral [lat] spine, and forearm) in a large population-based cohort of women aged 31-89 years (the OFELY cohort), and results were analyzed according to age and postmenopausal years. A significant apparent bone loss was found before the menopause in cancellous bone, i.e., at the lat spine and Ward's triangle (-10%; p < 0.05-0.001). Cross-sectional analysis indicated that, after the menopause, apparent bone loss was accelerated within the 10 years following menopause, continued thereafter at all sites except the AP spine, and was again accelerated in elderly menopausal for more than 25 years. Between 30 and 80 years, BMD decreased by 15 to 44% (T score -1.6 to -3.4) according to the site. The amount of apparent bone loss was highest at the Ward's triangle when expressed in percentage (44%) and at the mid- and distal radius when expressed in number of standard deviations from the peak bone mass (-3.4). As a result, the percentage of women classified as osteoporotic according to the World Heath Organization, i.e., with a T score < or = -2.5, varied substantially from site to site and was highest at the radius (37% and 46%) and lateral spine (25-31%), intermediate at the Ward's triangle, AP spine, and whole body BMD, and lowest at the whole body bone mineral content, femoral neck, and trochanter (10-12%). In conclusion, this cross-sectional but large study suggests that there is a moderate apparent premenopausal bone loss that occurs only at cancellous bone sites and that apparent bone loss is accelerated at most skeletal sites after the age of 75 years. Because of the highly variable coefficient of variation of the peak bone mass at various skeletal sites, the percentage of postmenopausal women identified as being osteoporotic varies widely according to the site of measurement.


Galectin-mediated immune recognition: Opsonic roles with contrasting outcomes in selected shrimp and bivalve mollusk species.
Galectins are a structurally conserved family of ß-galactoside-binding lectins characterized by a unique sequence motif in the carbohydrate recognition domain, and of wide taxonomic distribution, from fungi to mammals. Their biological functions, initially described as key to embryogenesis and early development via recognition of endogenous ("self") carbohydrate moieties, are currently understood as also encompassing tissue repair, cancer metastasis, angiogenesis, adipogenesis, and regulation of immune homeostasis. More recently, however, numerous studies have contributed to establish a new paradigm by revealing that galectins can also bind to exogenous ("non-self") glycans on the surface of potentially pathogenic virus, bacteria, and eukaryotic parasites, and function both as pathogen recognition receptors (PRRs) and effector factors in innate immunity. Our studies on a galectin from the kuruma shrimp Marsupenaeus japonicus (MjGal), revealed that it functions as a typical PRR. Expression of MjGal is upregulated by infectious challenge, and can recognize both Gram (+) and Gram (-) bacteria. MjGal also recognizes carbohydrates on the shrimp hemocyte surface, and can cross-link microbial pathogens to the hemocytes, promoting their phagocytosis and clearance from circulation. Therefore, MjGal contributes to the shrimp's immune defense against infectious challenge both as a PRR and effector factor. Our studies on galectins from the bivalve mollusks, however, have shown that although they can function in immune defense as MjGal, protistan parasites take advantage of the recognition roles of the host galectins, for successful attachment and host infection. We identified in the eastern oyster Crassostrea virginica two galectins (CvGal1 and CvGal2) that not only recognize a large variety of bacterial species, but also the protozoan parasite Perkinsus marinus. Like the shrimp MjGal, both oyster galectins function as opsonins, and promote parasite adhesion and phagocytosis. However, P. marinus survives intrahemocytic oxidative killing and proliferates, eventually causing systemic infection and death of the oyster host. In the softshell clam Mya arenaria we identified a galectin (MaGal1) that displays carbohydrate specificity and recognition properties for sympatric Perkinsus species (P. marinus and P. chesapeaki), that are different from CvGal1 and CvGal2. Our results suggest that although galectins from bivalves can function as PRRs, Perkinsus parasites have co-evolved with their hosts to subvert the galectins' immune functions for host infection by acquisition of carbohydrate-based mimicry.


Pethidine, metoclopramide and the gastro-oesophageal sphincter. A study in healthy volunteers.
The effects of intramuscular pethidine (1.0--3.0 mg/kg) followed by metoclopramide 10 mg intravenously, and those of a combination of pethidine 1.5 mg/kg and metoclopramide 10 mg given intramuscularly, on the lower oesophageal sphinct pressure have been studied manometrically in human volunteers. In the former group, the mean effect of all the doses of pethidine was a reduction of the lower oesophageal barrier pressure by 6.8 cmH2O from control values (p less than 0.0002), while the intravenous administration of metoclopramide resulted in a mean increase in barrier pressure of 8.75 cmH2O above the depressed level (p less than 0.0001). Following the combination of pethidine and metoclopramide given intramuscularly depression of the sphincter pressure was not totally prevented, but there was a reduction in its incidence and severity. It is suggested that pethidine is likely to increase the possibility of gastro-oesophageal reflux, and that metoclopramide is a useful adjunct in the prevention of reflux in preparation for, and after, surgery in patients who have been given pethidine for pain relief.


Trends in small organic fluorescent scaffolds for detection of oxidoreductase.
Oxidoreductases are diverse class of enzymes engaged in modulating the redox homeostasis and cellular signaling cascades. Abnormal expression of oxidoreductases including thioredoxin reductase, azoreductase, cytochrome oxidoreductase, tyrosinase and monoamine oxidase leads to the initiation of numerous disorders. Thus, enzymes are the promising biomarkers of the diseased cells and their accurate detection has utmost significance for clinical diagnosis. The detection method must be extremely selective, sensitive easy to use, long self-life, mass manufacturable and disposable. Fluorescence assay approach has been developed potential substitute to conventional techniques used in enzyme's quantification. The fluorescent probes possess excellent stability, high spatiotemporal ratio and reproducibility represent applications in real sample analysis. Therefore, the enzymatic transformations have been monitored by small activatable organic fluorescent probes. These probes are generally integrated with enzyme's substrate/inhibitors to improve their binding affinity toward the enzyme's catalytic site. As the recognition unit bio catalyzed, the signaling unit produces the readout signals and provides novel insights to understand the biochemical reactions for diagnosis and development of point of care devices. Several structural modifications are required in fluorogenic scaffolds to tune the selectivity for a particular enzyme. Hence, the fluorescent probes with their structural features and enzymatic reaction mechanism of oxidoreductase are the key points discussed in this review. The basic strategies to detect each enzyme are discussed. The selectivity, sensitivity and real-time applications are critically compared. The kinetic parameters and futuristic opportunities are present, which would be enormous benefits for chemists and biologists to understand the facts to design and develop unique fluorophore molecules for clinical applications.


Excitation function and yield for the 103Rh(d,2n)103Pd nuclear reaction: Optimization of the production of palladium-103.
Deuteron-induced nuclear reactions for the generation of 103Pd were investigated using the stacked-foil activation technique on rhodium targets at deuteron energies up to Ed=33MeV. The excitation functions of the reactions 103Rh(d,xn)101,103Pd, 103Rh(d,x)100g,cum,101m,g,102m,gRh and 103Rh(d,2p)103Ru have been measured, and the Thick-Target Yield for 103Pd has been calculated.


Investigation and treatment of asymptomatic bacteriuria in older patients with delirium: a cross-sectional survey of Canadian physicians.
Current guidelines suggest assessing non-infectious causes and careful observation before giving antibiotics to delirious patients with asymptomatic bacteriuria. Our study aims to describe the current practice of Canadian physicians regarding the investigation and treatment of asymptomatic bacteriuria in delirious older patients (aged ≥ 65 years). Our team of medical experts designed and reviewed a cross-sectional online survey. Study participants were physicians who conduct their clinical practice in Canada and care for older patients with delirium in their current practice. Potential study participants were reached through Canadian associations: Canadian Geriatrics Society, the Canadian Association of Emergency Physicians, the Association des Médecins d'Urgence du Québec and members of Choosing Wisely Canada. 297 physicians were included. The main results show 79.4% of our participants request a urine dipstick or urinalysis in delirious patients and 52.4% immediately order a urine culture with the urinalysis. If bacteriuria is found in delirious but afebrile patients without urinary symptoms, 38% of physicians immediately treat with antibiotics, 33.8% wait for culture before initiating treatment, 14.4% treat if no other cause is found for delirium and only 13.7% would refrain from giving antibiotics. Results from respondents were similar for delirious patients with known cognitive impairment. Participants were almost unanimous (92.5%) in saying they need clear guidelines regarding the treatment of bacteriuria in older delirious patients. This survey highlights the heterogeneous clinical management of asymptomatic bacteriuria in delirious patients and the need for clear guidelines for patients.


Hormone levels in women after hysterectomy.
The serum levels of FSH, LH and estradiol-17 beta (E2) were determined in 110 women aged between 38-48 years who had been hysterectomized 2-10 years previously and were compared with a control group (n = 112). In hysterectomized women both FSH and LH levels were higher than in controls during the whole 12 year period. These differences were significant up to 43 years of age. The hypergonadotropism in hysterectomized women correlates with the higher incidence of climacteric symptoms reported in the literature.


Association between sexual orientation acceptance and suicidal ideation, substance use, and internalised homophobia amongst the pink carpet Y cohort study of young gay, bisexual, and queer men in Singapore.
Gay, bisexual and queer (GBQ) men are frequently subjected to minority stressors that have negative impacts on their health. Milestones that include the acceptance and disclosure of sexual identity amongst GBQ men are hence key instruments in understanding the prevalence of internalised homophobia and predicting health outcomes. As such, this work takes a novel approach to deduce the correlates of delayed acceptance of sexual orientation in young GBQ men as a measure of internalised homophobia through retrospective self-reporting and age-based analysis. Participants were recruited as part of a cohort study exploring the syndemic risks associated with HIV acquisition among young GBQ men in Singapore. We examined their levels of internalised, perceived, experienced homophobia, as well as their health behaviours and suicidal tendencies. Two separate variables were also self-reported by the participants - the age of questioning of sexual orientation and the age of acceptance of sexual orientation. We subsequently recoded a new variable, delayed acceptance of sexual orientation, by taking the difference between these two variables, regressing it as an independent and dependent variable to deduce its psychosocial correlates, as well as its association with other measured instruments of health. As a dependent variable, delayed acceptance of sexual orientation is positively associated with an increase of age and internalised homophobia, while being negatively associated with reporting as being gay, compared to being bisexual or queer. As an independent variable, delayed acceptance of sexual orientation was associated with a delayed age of coming out to siblings and parents, suicide ideation, historical use of substances including smoking tobacco cigarettes and consuming marijuana, as well as reporting higher levels of experienced, internalised and perceived homophobia. Greater levels of early intervention and efforts are required to reduce the heightened experience of minority stress resulting from communal and institutional hostilities. Areas of improvement may include community-based counselling and psychological support for GBQ men, while not forsaking greater education of the social and healthcare sectors. Most importantly, disrupting the stigma narrative of a GBQ 'lifestyle' is paramount in establishing an accepting social environment that reduces the health disparity faced by GBQ men.


Effects of organic carbon sources on growth and oil accumulation by Desmodesmus subspicatus LC172266 under mixotrophic condition.
Energy crisis and environmental sustainability have attracted global attention to microalgal biofuels. The present study investigated the impact of organic carbon sources on growth and bio-oil accumulation by an oleaginous microalga Desmodesmus subspicatus LC172266 under mixotrophic culture condition. Glucose and glycerol supported higher growth rates and lipid productivities than sucrose, fructose, mannitol and acetate. Each of the organic carbon source tested supported significantly (P < 0.05) higher growth rates and lipid productivities than the photoautotrophic culture (without organic carbon source). The lipid productivity obtained with a mixture of optima concentrations of glucose and glycerol (5.0 gL-1 glycerol + 10.0 gL-1glucose) (0.14875 ± 0.002 g/L/day) was about 25% and 66% higher than the values obtained with only 10.0 gL-1glucose and 5.0 gL-1glycerol, respectively. When a batch culture with 5gL-1glycerol was fed with 0.5 gL-1glucose daily the cell growth and lipid productivity were lower than the values obtained in a batch culture with a mixture of glucose and glycerol. The lipid productivity obtained in a 4-L photobioreactor was 94% (0.217 gL-1 day-1), higher than the value obtained in a flask culture with 10.0 g/Lglucose (0.112 gL-1 day-1) and 46% higher than the value obtained in a flask culture with 5.0 gL-1glycerol (0.086 gL-1 day-1).


Increasing podiatry referrals for patients with inflammatory arthritis at a tertiary hospital in Singapore: A quality improvement project.
Foot disease is highly prevalent in people with inflammatory arthritis and is often under-recognized. Podiatry intervention can significantly reduce foot pain and disability, with timely access being the key factor. The aim of this study was to plan and implement a quality improvement project to identify the barriers to, and improve, uptake of podiatry services among patients with inflammatory arthritis-related foot problems seen at a tertiary hospital in Singapore. A 6-month quality improvement program was conducted by a team of key stakeholders using quality improvement tools to identify, implement and test several interventions designed to improve uptake of podiatry services. The number of patients referred for podiatry assessment was recorded on a weekly basis by an experienced podiatrist. The criterion for appropriate referral to podiatry was those patients with current or previous foot problems such as foot pain, swelling and deformity. Interventions included education initiatives, revised workflow, development of national guidelines for inflammatory arthritis, local podiatry guidelines for the management of foot and ankle problems, routine use of outcome measures, and introduction of a fully integrated rheumatology-podiatry service with reduced cost package. Referral rates increased from 8% to 11%, and were sustained beyond the study period. Complete incorporation of podiatry into the rheumatology consultation as part of the multidisciplinary team package further increased referrals to achieve the target of full uptake of the podiatry service. Through a structured quality improvement program, referrals to podiatry increased and improved the uptake and acceptance of rheumatology-podiatry services.


Understanding variability in algal solid-liquid separation process outcomes by manipulating extracellular protein-carbohydrate interactions.
Coagulation-flocculation followed by sedimentation or dissolved air flotation (DAF) are processes routinely used for separating microalgae from water; however, during algae separation then can exhibit inconsistent separation, high coagulant demand, and high operating cost. To circumvent these problems, previous studies reported the development of a novel DAF process in which bubbles were modified instead of particles. While this process was shown to be sustainable and inexpensive, the problem of inconsistent algal separation across species remained. Recent research has suggested that this could be due to the varying concentration and character of algal-derived proteins and carbohydrates within the extracellular organic matter (EOM) and their associated interactions. This hypothesis is tested in the current study using the novel modified-bubble DAF process, which has been highly susceptible to EOM protein and carbohydrate concentrations and character. Biomolecular additives (commercially available proteins and carbohydrates, and algal-extracted proteins) of widely differing molecular weight (MW) and charge were dosed in varying proportions into samples containing either Chlorella vulgaris CS-42/7, Microcystis aeruginosa CS-564/01, or Microcystis aeruginosa CS-555/1 after removing the intrinsic EOM. These cell-rich suspensions were then subject to flotation using cationic bubbles modified with poly(diallyldimethylammonium chloride) (PDADMAC). When additives were dosed independently, separation increased from <5% to up to 62%. The maximum separation was obtained when the dose was double the respective biopolymer concentration measured in the intrinsic EOM for the equivalent species, and, in the case of protein additives, when MW and charge were >50 kDa, and >0.5 meq·g-1, respectively, irrespective of the species tested. When evaluating steric- and charge-based protein-carbohydrate interactions on cell separation by simultaneously dosing high MW and high charge protein- and carbohydrate-additives, enhanced separation of up to 79% was achieved. It is suggested that enhanced cell separation is achieved due to proteins and carbohydrates bridging with cells and forming protein-carbohydrate-cell suprastructures in the presence of a flocculant, e.g. PDADMAC, and this only occurs when the intrinsic EOM comprises proteins and carbohydrates that have high MW (>25 kDa) and charge (>0.2 meq·g-1), and interactions with each other and with the cell surface.


Pain Relief During Childbirth in the Context of 50 Years of Social and Technological Change.
Pain relief during childbirth continues to stimulate controversy as new treatments emerge and continuing interventions in the birth process invoke concerns about safety, technologic imperatives, and informed consent. In this historical commentary, I identify a complex dissonance between scientific advances and women's needs and expectations regarding childbirth. Evidence-based practice became the standard during the last 50 years and has reinforced a more conservative and parsimonious use of technology to respond to women's needs for pain relief. In reviewing this history, it is apparent that pain relief during labor is inextricably linked to interventions. Nurses can advance evidence-based practice and facilitate robust informed consent as they support women during childbirth.


[Diagnosis and treatment of trauma-induced coagulopathy].
Trauma-induced coagulopathy is frequent and complex, and is responsible for an impairment of trauma outcome. Diagnosis of trauma coagulopathy is usually done with standard biology but recently new technics arose and gave us the opportunity to have faster information on coagulopathy with quick INR measure or clot formation study with thrombelastometry. Treatment of the coagulopathy should be done earlier in the course of trauma. Two strategies are possible that include either the association of RBC, platelet and FFP in a predefined ratio, or the use of factor concentrates guided with thrombelastometry. Treatment of favouring factors such as hypothermia, acidosis and hypocalcemia is also mandatory.


Increased interleukin-1 and modulation of interleukin-2 production by murine macrophages and lymphocytes treated with LF 1695.
Previous results have demonstrated that lectin-induced T cell proliferation was potentiated or suppressed by LF 1695, a synthetic immunomodulator, depending on the dose used. Therefore the activity of this compound was investigated on murine IL-1 and IL-2 production. Adherent peritoneal cells, incubated with LF 1695, could secrete high levels of IL-1 with only a slight elevation in intracellular IL-1. This effect apparent at 5 and 10 micrograms/ml was linked to a transient state of activation. At low doses, LF 1695 increased IL-2 production by Con A-stimulated spleen cells. A decrease was found at higher doses only when cells were preincubated 20 h with the compound. In murine macrophages stimulated either by A 23187 or LPS PGE2 synthesis was inhibited by LF 1695 even at low doses. However, supernatant LTB4 level was increased in LF 1695-treated culture with a time-dependent effect. Therefore modulation of lectin-induced T cell proliferation by LF 1695 may be IL-2 production-mediated. Inhibition of the cyclooxygenase and stimulation of the lipoxygenase pathway of arachidonic acid metabolism may be responsible for this pattern of activity.


Guidelines for apheresis personnel--an overview.
The Guidelines for Apheresis Specialists were prepared by the Standards Committee of the Society of Hemopheresis Specialists (SHS) in response to a need to safeguard donors and patients undergoing apheresis from the viewpoint of the technical staff performing the procedures. The Guidelines address technical and administrative topics not covered by instrument manufacturer's training sessions and manuals. The Guidelines contain the following objectives: To assure that apheresis procedures are performed and supervised by qualified personnel, thereby safeguarding the donors, patients and recipients of the components harvested. To assure that apheresis procedures are carried out in a safe, efficient and appropriate manner with minimum risk and maximum benefit. To assure donor/patient safety and high quality component preparation through an effective quality control program. The Guidelines are flexible, adaptable to various physical settings, applicable to different types of instruments, and useful for both therapeutic and donor hemopheresis procedures. They avoid references to issues that may be considered to interfere with internal or external policymaking bodies. In addition, they provide a base from which policies and procedures can be formulated and amended to account for advances in technology and expertise.


Parent-Child Discrepancies in Reports of Parental Monitoring and Their Relationship to Adolescent Alcohol-Related Behaviors.
Discrepancies between parents and adolescents regarding parenting behaviors have been hypothesized to represent a deficit in the parent-child relationship and may represent unique risk factors for poor developmental outcomes. The current study examined the predictive utility of multiple methods for characterizing discrepancies in parents' and adolescents' reports of parental monitoring on youth alcohol use behaviors in order to inform future study design and predictive modeling. Data for the current study came from a prospective investigation of alcohol initiation and progression. The analyzed sample consisted of 606 adolescents (6th-8th grade; 54 % female) and their parents were surveyed at baseline, with youth followed up 12 months later. A series of hierarchical logistic regressions were performed for each monitoring-related construct examined (parental knowledge, parental control, parental solicitation, and child disclosure). The results showed that adolescents' reports were more closely related to outcomes than parents' reports, while greater discrepancies were frequently found to be uniquely associated with greater likelihood of alcohol use behaviors. Implications for future work incorporating parents' and adolescents' reports are discussed.


Increased household financial strain, the Great Recession and child health-findings from the UK Millennium Cohort Study.
There is a growing body of evidence associating financial strain (FS) with poor health but most of this research has been cross-sectional and adult-focused. During the 'Great Recession' many UK households experienced increased FS. The primary aim of this study was to determine the impact of increased FS on child health. We analysed the Millennium Cohort Study, a longitudinal study of children born in the UK between 2000 and 2002. Surveys at 7 years (T1, 2008) and 11 years (T2, 2012) spanned the 'Great Recession'. Three measures of increased FS were defined; 'became income poor' (self-reported household income dropped below the 'poverty line' between T1 and T2); 'developed difficulty managing' (parental report of being 'financially comfortable' at T1 and finding it 'difficult to manage' at T2); 'felt worse off' (parental report of feeling financially 'worse off' at T2 compared with T1). Poisson regression was used to estimate risk ratios (RR), adjusted risk ratios (aRR) and 95% CIs for six child health outcomes: measured overweight/obesity, problematic behaviour as scored by parents and teachers, and parental reports of fair/poor general health, long-standing illness and bedwetting at T2 (N=13 112). In subanalyses we limited our sample to those who were above the poverty line at T2. Compared with those who were not financially strained at both time points, children in households which experienced increased FS were at an increased risk of all unhealthy outcomes examined. In most cases, these increased risks persisted after adjustment for confounding and when limiting the sample to those above the poverty line. FS is associated with a range of new or continued poor child health outcomes. During times of widespread economic hardship, such as the 'Great Recession', measures should be taken to buffer children and their families from the impact of FS, and these should not be limited to those who are income poor.


Body composition, muscle strength, functional capacity, and physical disability risk in liver transplanted familial amyloidotic polyneuropathy patients.
Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disease leading to sensory and motor polyneuropathies, and functional limitations. Liver transplantation is the only treatment for FAP, requiring medication that negatively affects bone and muscle metabolism. The aim of this study was to compare body composition, levels of specific strength, level of physical disability risk, and functional capacity of transplanted FAP patients (FAPTx) with a group of healthy individuals (CON). A group of patients with 48 FAPTx (28 men, 20 women) was compared with 24 CON individuals (14 men, 10 women). Body composition was assessed by dual-energy X-ray absorptiometry, and total skeletal muscle mass (TBSMM) and skeletal muscle index (SMI) were calculated. Handgrip strength was measured for both hands as was isometric strength of quadriceps. Muscle quality (MQ) was ascertained by the ratio of strength to muscle mass. Functional capacity was assessed by the six-minute walk test. Patients with FAPTx had significantly lower functional capacity, weight, body mass index, total fat mass, TBSMM, SMI, lean mass, muscle strength, MQ, and bone mineral density. Patients with FAPTx appear to be at particularly high risk of functional disability, suggesting an important role for an early and appropriately designed rehabilitation program.


One-year results of the SCORPIUS study: a German multicenter investigation on the effectiveness of sirolimus-eluting stents in diabetic patients.
This study sought to analyze the effectiveness of drug-eluting stents in a high-risk group of diabetic patients. Previously, this had been analyzed only in substudies of larger trials or in clinical investigations enrolling a small number of patients. Drug-eluting stents are highly effective in reducing the rate of in-stent restenosis. Two hundred patients with diabetes and de novo coronary artery lesions were enrolled in 16 centers: 98 were randomly assigned to sirolimus-eluting stents (SES) and 102 received bare-metal stents (BMS). The primary end point was in-segment late luminal loss. Major adverse cardiac events (MACE) rate was analyzed at 30 days and 8 and 12 months. The extent of in-segment late luminal loss in the SES group was 0.18 mm compared with 0.74 mm in the BMS group. In-segment restenosis was identified on follow-up angiography in 8.8% of the patients in SES and in 42.1% in BMS (p < 0.0001). Target lesion revascularization was performed in 5.3% of the patients in SES and in 21.1% of the patients in BMS (p = 0.002). The SES was effective in the treatment group with oral diabetic medication as well as in the insulin-dependent treatment group (3.6% SES vs. 38.8% BMS). There was no subacute stent thrombosis in the SES group up to 1 year. The MACE rate was not significantly different at 30 days. At 12 months, MACE rate was 14.7% in SES versus 35.8% in BMS. The SES is safe and highly effective in patients with diabetes mellitus and coronary artery disease and associated with a significant decrease in the extent of late luminal loss.


Corrosion of Q235 carbon steel induced by sulfate-reducing bacteria in groundwater: corrosion behavior, corrosion product, and microbial community structure.
Microbiologically influenced corrosion (MIC) is one of the reasons leading to the service failure of pipelines buried in the soil. In this work, the effect of sulfate-reducing bacteria (SRB) on the corrosion behavior of Q235 carbon steel in groundwater was investigated by electrochemical methods, surface analysis, and biological analysis. The results show that SRB utilizes iron as electron donor to sustain the vital activities of organic carbon-starved groundwater during the 14-day experimental period. The microbial community composition analysis at the genus level demonstrate that the diversity and richness decrease after corrosion, and the dominant SRB species has changed from Desulfovibrio to Desulfosporosinus. Moreover, the impedance of the carbon steel in the presence of biofilm was 1 order of magnitude higher than that of other periods in the electrochemical test, indicating that the biofilm and formed ferrous sulfide layer impeded the occurrence of corrosion. Although the 3D topography indicated that the surface of carbon steel was more uneven and pits were increased in the presence of SRB, the average weight loss (0.0396 ± 0.0050 g) was much higher than that without SRB (0.0139 ± 0.0007 g). These results implied that the growth of SRB makes the corrosion process of Q235 carbon steel more complicated.


Effects of perinatal asphyxia on cell proliferation and neuronal phenotype evaluated with organotypic hippocampal cultures.
The present report summarizes studies combining an in vivo and in vitro approach, where asphyxia is induced in vivo at delivery time of Wistar rats, and the long term effects on hippocampus neurocircuitry are investigated in vitro with organotypic cultures plated at postnatal day seven. The cultures preserved hippocampus layering and regional subdivisions shown in vivo, and only few dying cells were observed when assayed with a viability test at day in vitro 27. When properly fixed, cultures from asphyxia-exposed animals showed a decreased amount of microtubule-associated protein-2 immunocytochemically positive cells (approximately 30%), as compared with that from controls. The decrease in microtubule-associated protein-2 immunocytochemistry was particularly prominent in Ammon's horn 1 and dentate gyrus regions (approximately 40%). 5-Bromo-2'deoxyuridine labeling revealed a two-fold increase in cellular proliferation in cultures from asphyxia-exposed, compared with that from control animals. Furthermore, confocal microscopy and quantification using the optical disector technique demonstrated that in cultures from asphyxia-exposed animals approximately 30% of 5-bromo-2'deoxyuridine-positive cells were also positive to microtubule-associated protein-2, a marker for neuronal phenotype. That proportion was approximately 20% in cultures from control animals. Glial fibrillary acidic protein-immunocytochemistry and Fast Red nuclear staining revealed that the core of the hippocampus culture was surrounded by a well-developed network of glial fibrillary acidic protein-positive cells and glial fibrillary acidic protein-processes providing an apparent protective shield around the hippocampus. That shield was less developed in cultures from asphyxia-exposed animals. The increased mitotic activity observed in this study suggests a compensatory mechanism for the long-term impairment induced by perinatal asphyxia, although it is not clear yet if that mechanism leads to neurogenesis, astrogliogenesis, or to further apoptosis.


Striving to live a normal life: a review of children and young people's experience of feeling different when living with a long term condition.
This paper presents a review of findings from qualitative studies on children's experience of feeling different when living with the long term conditions; diabetes, epilepsy and asthma. Following electronic database and hand searches of reference lists of identified papers, eighteen studies were selected for inclusion in the review. These studies revealed three common themes; participation in everyday life-restrictions and adjustments; treatment regimens-constraining and enabling; and communication-disclosure, stigma and support. Across these themes it was evident that children felt different physically and socially and they grappled constantly with balancing the dilemma of feeling and acting normal or feeling, being and revealing difference.


Generation of recombinant antibodies by mammalian expression system for detecting S-metolachlor in environmental waters.
Current immunoassays for herbicide detection are usually based on polyclonal or monoclonal antibodies (MAbs) raised in animals. The mammalian expression system allows the procurement of specific and highly sensitive antibodies, avoiding animal immunization. In this study, S-metolachlor-specific IgG vectors bearing either Thosea asigna virus 2A or internal ribosome entry site (S-T2A or S-IRES) and single-chain variable fragment (scFv) vectors were designed and expressed. The recombinant antibodies (RAbs) were characterized by indirect competitive enzyme-linked immunosorbent assays (icELISA). The results showed that full-length RAbs exhibited significantly better performance than scFv, and both bicistronic vectors expressed antibodies of correct size, while RAb S-T2A elicited a higher yield than RAb S-IRES. Further analyses showed that RAb S-T2A and RAb S-IRES exhibited comparable reactivities and specificities to the parental MAb, with IC50 values of 3.44, 3.89 and 3.37 ng/mL, respectively. Finally, MAb- and RAb-based icELISAs were established for the determination of S-metolachlor in environmental waters. The recoveries were in the range of 73.0-128.1%, and the coefficients of variation were mostly below 10%. This article describes the production of RAbs for S-metolachlor from mammalian cells for the first time and paves the way to develop RAb-based immunoassays for monitoring herbicide residues in the environment.


Controlled release of thiamin in a glassy κ-carrageenan/glucose syrup matrix.
The work dealt with the diffusional mobility of thiamin embedded in a high-solid matrix of κ-carrageenan with glucose syrup. It utilized thermomechanical analysis in the form of modulated differential scanning calorimetry and small-deformation dynamic oscillation in shear, Fourier transform infrared spectroscopy, wide angle X-ray diffraction, scanning electron microscopy and UV-vis spectrophotometry. The structural properties of the matrix were assessed in a temperature induced rubber-to-glass transformation. A thiamin-dye binding assay was employed to monitor the diffusion process of the vitamin from the high-solid preparation to ethylene glycol. The relationship between mechanical properties of the carbohydrate matrix and vitamin mobility was assessed via the application of the combined framework of the free volume theory and the predictions of the reaction rate theory. Results argue that the transport of the micronutrient is governed by the structural relaxation of the high-solid matrix. These were further treated with the concept of Fickian diffusion coefficient to provide the rate of the bioactive compound mobility within the present experimental settings.


The influence of PAMAM-OH dendrimers on the activity of human erythrocytes ATPases.
Dendrimers are a relatively new and still not fully examined group of polybranched polymers. In this study polyamidoamine dendrimers with hydroxyl surface groups (PAMAM-OH) of third, fourth and fifth generation (G3, G4 and G5) were examined for their ability to influence the activity of human erythrocyte plasma membrane adenosinetriphosphatases (ATPases). Plasma membrane ATPases are a group of enzymes related, among others, to the maintenance of ionic balance inside the cell. An inhibition of their activity may result in a disturbance of cell functioning. Two of examined dendrimers (G4 and G5) were found to inhibit the activity of Na(+)/K(+) ATPase and Ca(2+) ATPase by 20-30%. The observed effect was diminished when higher concentrations of dendrimers were used. The experiment with the use of pyrene as fluorescent probe sensitive to the changes in microenvironment's polarity revealed that it was an effect of dendrimers' self-aggregation. Additional studies showed that PAMAM-OH dendrimers were able to decrease the fluidity of human erythrocytes plasma membrane. Obtained results suggest that change in plasma membrane fluidity was not caused by the dendrimer-lipid interaction, but dendrimer-protein interaction. Different pattern of influence of dendrimers on ATPases activity and erythrocyte membrane fluidity suggests that observed change in ATPases activity is not a result of dendrimer-lipid interaction, but may be related to direct interaction between dendrimers and ATPases.


A 50-picosiemens anion channel of the chloroplast envelope is involved in chloroplast protein import.
Single channel recordings were used to investigate the changes on the pea chloroplast envelope during protein import. In the inside-out patch configuration a 50-picosiemens (pS) anion channel of the chloroplast envelope membrane was identified. The open time probability of the channel was decreased by the addition of the wild type precursor protein of ferredoxin (wt-prefd) to the pipette-filling solution in the presence of 0.5 mM ATP. In the absence of ATP or in the presence of 50 microM ATP, wt-prefd did not affect the open time probability of the channel. A deletion mutant of prefd, Delta6-14-prefd, which is inactive in in vitro import, was also unable to affect the open time probability of the 50-pS anion channel. In the presence of 100 microM ATP, wt-prefd decreased the open time probability of the channel to a lesser extent, as did the transit peptide alone. It is concluded that the 50-pS anion channel could be part of the protein import machinery of the inner membrane. In addition the precursor protein under import conditions induced burst-like increases of the envelope conductivity. The implication of both responses for the chloroplast protein import process are discussed.


Noninvasive detection of coronary artery wall thickening with age in healthy subjects using high resolution MRI with beat-to-beat respiratory motion correction.
To demonstrate coronary artery wall thickening with age in a small healthy cohort using a highly efficient, reliable, and reproducible high-resolution MR technique. A 3D cross-sectional MR vessel wall images (0.7 × 0.7 × 3 mm resolution) with retrospective beat-to-beat respiratory motion correction (B2B-RMC) were obtained in the proximal right coronary artery of 21 healthy subjects (age, 22-62 years) with no known cardiovascular disease. Lumen and outer wall (lumen + vessel wall) areas were measured in one central slice from each subject and average wall thickness and wall area/outer wall area ratio (W/OW) calculated. Imaging was successful in 18 (86%) subjects with average respiratory efficiency 99.3 ± 1.7%. Coronary vessel wall thickness and W/OW significantly correlate with subject age, increasing by 0.088 mm and 0.031 per decade respectively (R = 0.53, P = 0.024 and R = 0.48, P = 0.046). No relationship was found between lumen area and vessel wall thickness (P = NS), but outer wall area increased significantly with vessel wall thickness at 19 mm(2) per mm (P = 0.046). This is consistent with outward vessel wall remodeling. Despite the small size of our healthy cohort, using high-resolution MR imaging and B2B-RMC, we have demonstrated increasing coronary vessel wall thickness and W/OW with age. The results obtained are consistent with outward vessel wall remodeling.


A mathematical model for the peristaltic flow of chyme movement in small intestine.
A mathematical model based on viscoelastic fluid (fractional Oldroyd-B model) flow is considered for the peristaltic flow of chyme in small intestine, which is assumed to be in the form of an inclined cylindrical tube. The peristaltic flow of chyme is modeled more realistically by assuming that the peristaltic rush wave is a sinusoidal wave, which propagates along the tube. The governing equations are simplified by making the assumptions of long wavelength and low Reynolds number. Analytical approximate solutions of problem are obtained by using homotopy analysis method and convergence of the obtained series solution is properly checked. For the realistic values of the emerging parameters such as fractional parameters, relaxation time, retardation time, Reynolds number, Froude number and inclination of tube, the numerical results for the pressure difference and the frictional force across one wavelength are computed and discussed the roles played by these parameters during the peristaltic flow. On the basis of this study, it is found that the first fractional parameter, relaxation time and Froude number resist the movement of chyme, while, the second fractional parameter, retardation time, Reynolds number and inclination of tube favour the movement of chyme through the small intestine during pumping. It is further revealed that size of trapped bolus reduces with increasing the amplitude ratio whereas it is unaltered with other parameters.


O-acetylation and de-O-acetylation of sialic acids. O-acetylation of sialic acids in the rat liver Golgi apparatus involves an acetyl intermediate and essential histidine and lysine residues--a transmembrane reaction?
Isolated intact rat liver Golgi vesicles utilize [acetyl-3H]coenzyme A to add 3H-O-acetyl esters to sialic acids of internally facing endogenous glycoproteins. During this reaction, [3H]acetate also accumulates in the vesicles, even though the vesicles are impermeant to free acetate. On the other hand, entry of intact AcCoA into the lumen of the vesicles could not be demonstrated, and permeabilization of the vesicles did not alter the reaction substantially (Diaz, S., Higa, H. H., Hayes, B. K., and Varki, A. (1989) J. Biol. Chem. 264, 19416-19426). When vesicles prelabeled with [acetyl-3H] coenzyme A are permeabilized with saponin, we can demonstrate a [3H]acetyl intermediate in the membrane that can transfer label to the 7- and 9-positions of exogenously added free N-acetylneuraminic acid but not to glucuronic acid or CMP-N-acetylneuraminic acid. This labeled acetyl intermediate represents a significant portion of the radioactivity incorporated into the membranes during the initial incubation and cannot be accounted for by nonspecifically "trapped" acetyl-CoA in the permeabilized vesicles. There was no evidence for involvement of acetylcarnitine or acetyl phosphate as an intermediate. The overall acetylation reaction appears to involve two steps. The first step (utilization of exogenous acetyl-CoA to form the acetyl intermediate) is inhibited by coenzyme A-SH (apparent Ki = 24-29 microM), whereas the second (transfer from the acetyl intermediate to sialic acid) is not affected by millimolar concentrations of the nucleotide. Studies with amino acid-modifying reagents indicate that 1 or more histidine residues are involved in the first step of the acetylation reaction. Diethylpyrocarbonate (which can react with both nonsubstituted and singly acetylated histidine residues) also blocks the second reaction, indicating that the acetyl intermediate on both sides of the membrane involves histidine residue(s). Taken together with data presented in the preceding paper, these results indicate that the acetylation of sialic acids in Golgi vesicles may occur by a transmembrane reaction, similar to that described for the acetylation of glucosamine in lysosomes (Bame, K. J., and Rome, L. H. (1985) J. Biol. Chem. 260, 11293-11299). However, several features of this Golgi reaction distinguish it from the lysosomal one, including the nature and kinetics of the reaction and the additional involvement of an essential lysine residue. The accumulation of free acetate in the lumen of the vesicles during the reaction may occur by abortive acetylation (viz. transfer of label from the acetyl intermediate to water). It is not clear if this is an artifact that occurs only in the in vitro reaction.


A contribution towards checklist of fungus gnats (Diptera, Diadocidiidae, Ditomyiidae, Bolitophilidae, Keroplatidae, Mycetophilidae) in Georgia, Transcaucasia.
The fungus gnats of Georgia are studied based on 2682 specimens collected from 57 localities during 2011-2019. Altogether, 245 species are recorded including four species of Bolitophilidae, three species of Diadocidiidae, two species of Ditomyiidae, 34 species of Keroplatidae and 202 species of Mycetophilidae. 230 and 188 species are recorded from Georgia and the whole of Transcaucasia for the first time, respectively. Three new species - Sciophila georgei sp. nov., Leia katae sp. nov. and Anatella metae sp. nov. - are described including detailed illustrations of the male terminalia. Photographs are provided for an additional 38 species to highlight a variability of their general facies. Combined with earlier published data, the number of fungus gnat species in Georgia is set at 246. The estimated diversity of fungus gnats in Georgia is calculated using non-parametric methods and discussed with respect to other Western Palaearctic regions.


Cell cycle transcription factor E2F2 mediates non-stress temperature response of AtHSP70-4 in Arabidopsis.
AtHSP70 expression exhibits both stress and non-stress temperature response, however, the molecular mechanisms underlying these temperature signaling pathways remain elusive. Here we performed truncation and deletion assay to investigate the cis-elements within the promoter region of AtHSP70-4 (AT3G12580). And found the region between -1000 and -1100 bp from the translation initiation site (TIS) was indispensable for the non-stress temperature response of AtHSP70. Further deletion assay of several candidate motifs within this region suggested that one 'GCGCCAAA' sequence played the critical role. This motif was found as the reverse DNA-binding motif of cell cycle transcription factor E2F family. EMSA assay verified one number of Arabidopsis E2F family-E2F2 could bind to AtHSP70-4 promoter via this motif. These results indicated the temperature regulated expression of AtHSP70-4 may be mediated by cell cycle transcription factors and participate in plant acclimations to non-stress temperature changes.


Sleep Duration and Daytime Napping and Risk of Type 2 Diabetes Among Japanese Men and Women: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk.
Little is known about the impacts of sleep duration and daytime napping on the risk of type 2 diabetes mellitus (T2DM). In this study, 20,318 participants (7,597 men, 12,721 women) aged 40-79 years without a history of T2DM, stroke, coronary heart disease, or cancer at baseline (1988-1990), completed the baseline survey and the 5-year follow-up questionnaires, which included average sleep duration, napping habits, and self-reports of physician-diagnosed diabetes. The multivariable odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a logistic regression model. During the 5-year follow-up, 531 new cases of T2DM (266 men and 265 women) were documented. Sleep duration ≥10 hours was associated with higher risk of T2DM compared to sleep duration of 7 hours (OR 1.99; 95% CI, 1.28-3.08). The excess risk was observed for both sexes and primarily found among the non-overweight; the multivariable ORs of sleeping ≥10 hours compared to 7 hours were 2.05 (95% CI, 1.26-3.35) for the non-overweight (BMI <25 kg/m2) and 1.38 (95% CI, 0.49-3.83) for the overweight (BMI ≥25 kg/m2). The respective ORs of nappers versus non-nappers were 1.30 (95% CI, 1.03-1.63) and 0.92 (95% CI, 0.65-1.29). Among the non-overweight, nappers who slept ≥10 hours had the highest risk of T2DM (OR 2.84; 95% CI, 1.57-5.14), non-nappers who slept ≥10 hours (OR 2.27; 95% CI, 1.27-4.06), and nappers who slept <10 hours (OR 1.30; 95% CI, 1.03-1.64), compared with non-nappers who slept <10 hours. Long sleep duration was associated with the risk of T2DM in both sexes, which was confined to the non-overweight.


Activation of GPR55 attenuates cognitive impairment and neurotoxicity in a mouse model of Alzheimer's disease induced by Aβ1-42 through inhibiting RhoA/ROCK2 pathway.
The accumulation of amyloid-β (Aβ) peptides in the brain is considered to be the initial event in the Alzheimer's disease (AD). Neurotoxicity mediated by Aβ has been demonstrated to damage the cognitive function. In the present study, we sought to determine the effects of O-1602, a specific G-protein coupled receptor 55 (GPR55) agonist, on the impairment of learning and memory induced by intracerebroventricular (i.c.v.) of Aβ1-42 (400 pmol/mouse) in mice. Our results showed that i.c.v. injection of aggregated Aβ1-42 into the brain of mice resulted in cognitive impairment and neurotoxicity. In contrast, O-1602 (2.0 or 4.0 μg/mouse, i.c.v.) can improve memory impairment induced by Aβ1-42 in the Morris water maze (MWM), and novel object recognition (NOR) tests. Besides, we found that O-1602 reduced the activity of β-secretase 1 (BACE1) and the level of soluble Aβ1-42 in the hippocampus and frontal cortex. Importantly, O-1602 treatment reversed Aβ1-42-induced GPR55 down-regulation, decreased pro-inflammatory cytokines, and the level of malondialdehyde (MDA), increased the levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT), as well as suppressed apoptosis as indicated by decreased TUNEL-positive cells, and increased the ratio of Bcl-2/Bax. O-1602 treatment also pronouncedly ameliorated synaptic dysfunction by promoting the upregulation of PSD-95 and synaptophysin (SYN) proteins. Moreover, O-1602 concurrently down regulated the protein levels of RhoA, and ROCK2, the critical proteins in the RhoA/ROCK2 pathway. This study indicates that O-1602 may reverse Aβ1-42-induced cognitive impairment and neurotoxicity in mice by inhibiting RhoA/ROCK2 pathway. Taken together, these findings suggest that GPR55 could be a novel and promising target for the treatment of AD.


Rhinovirus C15 Induces Airway Hyperresponsiveness via Calcium Mobilization in Airway Smooth Muscle.
Rhinovirus (RV) exposure evokes exacerbations of asthma that markedly impact morbidity and mortality worldwide. The mechanisms by which RV induces airway hyperresponsiveness (AHR) or by which specific RV serotypes differentially evoke AHR remain unknown. We posit that RV infection evokes AHR and inflammatory mediator release, which correlate with degrees of RV infection. Furthermore, we posit that rhinovirus C-induced AHR requires paracrine or autocrine mediator release from epithelium that modulates agonist-induced calcium mobilization in human airway smooth muscle. In these studies, we used an ex vivo model to measure bronchoconstriction and mediator release from infected airways in human precision cut lung slices to understand how RV exposure alters airway constriction. We found that rhinovirus C15 (RV-C15) infection augmented carbachol-induced airway narrowing and significantly increased release of IP-10 (IFN-γ-induced protein 10) and MIP-1β (macrophage inflammatory protein-1β) but not IL-6. RV-C15 infection of human airway epithelial cells augmented agonist-induced intracellular calcium flux and phosphorylation of myosin light chain in co-cultured human airway smooth muscle to carbachol, but not after histamine stimulation. Our data suggest that RV-C15-induced structural cell inflammatory responses are associated with viral load but that inflammatory responses and alterations in agonist-mediated constriction of human small airways are uncoupled from viral load of the tissue.


5-Lipoxygenase (ALOX5) and FLAP (ALOX5AP) gene polymorphisms as factors in vascular pathology and Alzheimer's disease.
We first hypothesized in 2000 that a polymorphism of the human gene encoding the enzyme 5-lipoxygenase (5-LOX) might be associated with Alzheimer's disease. Only a little progress has been made in directly testing our proposal. However, additional important new data lead us to hypothesize that genetic variability not only in the 5-LOX gene, i.e., ALOX5, but also in polymorphism of the five-lipoxygenase activating protein (FLAP) gene, i.e., ALOX5AP, may be associated with Alzheimer's pathology. Studies in mice followed by several extensive clinical studies have identified ALOX5 and ALOX5AP polymorphisms as strong risk factors for atherosclerosis and cerebrovascular pathologies. New data point to a significant aggregation of vascular risk factors and risk of Alzheimer's disease. Preliminary findings in postmortem brain of Alzheimer's patients identified elevated 5-LOX immunostaining in this disease. We suggest that our hypothesis of a link between the ALOX5 and ALOX5AP gene polymorphisms and Alzheimer's disease could be tested in a clinical setting and in animal models, i.e., transgenic mice could be produced by crossing the available 5-LOX-deficient mice with the available transgenic mice models of Alzheimer's disease.


A network of Notch-dependent and -independent her genes controls neural stem and progenitor cells in the zebrafish thalamic proliferation zone.
Neural proliferation zones mediate brain growth and employ Delta/Notch signaling and HES/Her transcription factors to balance neural stem cell (NSC) maintenance with the generation of progenitors and neurons. We investigated Notch-dependency and function of her genes in the thalamic proliferation zone of zebrafish larvae. Nine Notch-dependent genes, her2, her4.1-4.5, her12, her15.1-15.2, and two Notch-independent genes, her6 and her9, are differentially expressed and define distinct NSC and progenitor populations. her6 prominently executes patterning information to maintain NSCs and the zona limitans intrathalamica Shh signaling activity. Surprisingly, simultaneous deletion of nine Notch-dependent her genes does not affect NSCs or progenitor formation, and her4 overexpression only caused reduction of ascl1b progenitors. Combined genetic manipulations of Notch-dependent and -independent her genes suggest that her6 in the thalamic proliferation zone prominently maintains NSCs and inhibits NSC-to-progenitor lineage transitions. The her gene network is characterized by redundant gene functions, with Notch-independent her genes better substituting for loss of Notch-dependent her genes than vice versa. Together, her gene regulatory feedback loops and cross-regulation contribute to the observed robustness of NSC maintenance.


Radiation-Induced Cardiovascular Disease: Mechanisms, Prevention, and Treatment.
Despite the advancements of modern radiotherapy, radiation-induced cardiovascular disease (RICVD) remains a common cause of morbidity and mortality among cancer survivors. Proposed pathogenetic mechanisms of RICVD include endothelial cell damage with accelerated atherosclerosis, pro-thrombotic alterations in the coagulation pathway as well as inflammation and fibrosis of the myocardial, pericardial, valvular, and conduction tissues. Prevention of RICVD can be achieved by minimizing the exposure of the cardiovascular system to radiation, by treatment of underlying cardiovascular risk factors and cardiovascular disease, and possibly by prophylactic pharmacotherapy post exposure. Herein we summarize current knowledge on the mechanisms underlying the pathogenesis of RICVD and propose prevention and treatment strategies.


Spinal metastases 2021: a review of the current state of the art and future directions.
Spinal metastases are an increasing societal health burden secondary to improvements in systemic therapy. Estimates indicate that 100,000 or more people have symptomatic spine metastases requiring management. While open surgery and external beam radiotherapy have been the pillars of treatment, there is growing interest in more minimally invasive technologies (eg separation surgery) and non-operative interventions (eg percutaneous cementoplasty, stereotactic radiosurgery). The great expansion of these alternatives to open surgery and the prevalence of adjuvant therapeutic options means that treatment decision making is now complex and reliant upon multidisciplinary collaboration. To help facilitate construction of care plans that meet patient goals and expectations, clinical decision aids and prognostic scores have been developed. These have been shown to have superior predictive value relative to more classic prediction models and may become an increasingly important aspect of the clinical practice of spinal oncology. Here we overview current therapeutic advances in the management of spine metastases and highlight emerging areas for research. Given the rapid advancements in surgical technologies and adjuvants, the field is likely to undergo further transformative changes in the coming decade.


[The orthoMIT project. Gentle surgery using innovative technology].
The main objective of orthoMIT is to develop an integrated platform for "gentle" surgery in orthopedics and traumatology with particular emphasis on hip, knee and spinal column surgery. The goal of the 24 partners of the orthoMIT consortium and further associated industrial partners is an integrated approach to reduce the cost of orthopedic interventions: full workflow integration in the operating room, full treatment integration extending through to rehabilitation, and full integration of the typical value chain of medical product development, from the laboratory to production and commercialization by the firms and industrial partners involved in the project including education and training. Development, therefore, focuses on new strategies in minimally invasive surgery and improved, knowledge-based planning and navigation systems. Other topics include the development of improved methods of interventional imaging using ultrasound and computed tomography (flat panel detectors) and new, miniaturized instruments with integrated sensors and a modular integration of various applications and components into an integrated surgical workstation.


RANKL employs distinct binding modes to engage RANK and the osteoprotegerin decoy receptor.
Osteoprotegerin (OPG) and receptor activator of nuclear factor κB (RANK) are members of the tumor necrosis factor receptor (TNFR) superfamily that regulate osteoclast formation and function by competing for RANK ligand (RANKL). RANKL promotes osteoclast development through RANK activation, while OPG inhibits this process by sequestering RANKL. For comparison, we solved crystal structures of RANKL with RANK and RANKL with OPG. Complementary biochemical and functional studies reveal that the monomeric cytokine-binding region of OPG binds RANKL with ∼500-fold higher affinity than RANK and inhibits RANKL-stimulated osteoclastogenesis ∼150 times more effectively, in part because the binding cleft of RANKL makes unique contacts with OPG. Several side chains as well as the C-D and D-E loops of RANKL occupy different orientations when bound to OPG versus RANK. High affinity OPG binding requires a 90s loop Phe residue that is mutated in juvenile Paget's disease. These results suggest cytokine plasticity may help to fine-tune specific tumor necrosis factor (TNF)-family cytokine/receptor pair selectivity.


Socio-economic inequality of utilization of cancer testing in Europe: A cross-sectional study.
There are currently screening programmes for breast, cervical and colorectal cancer in many European countries. However, the uptake of cancer screening in general may vary within and between countries. The aim of this study is to assess the inequalities in testing utilization by socio-economic status and whether the amount of inequality varies across European regions. We conducted an analysis based on cross-sectional data from the second wave of the European Health Interview Survey from 2013 to 2015. We analysed the use of breast, cervical, and colorectal cancer testing by socio-economic position (household income, educational level and employment status), socio-demographic factors, self-perceived health and smoking behaviour, by using multinomial logistic models, and inequality measurement based on the Slope index of inequality (SII) and Relative index of inequality (RII). The results show that the utilization of mammography (Odds Ratio (OR) = 0.55, 95% confidence interval (95%CI):0.50-0.61), cervical smear tests (OR = 0.60, 95%CI:0.56-0.65) and colorectal testing (OR = 0.82, 95%CI:0.78-0.86) was overall less likely among individuals within a low household income compared to a high household income. Also, individuals with a non-EU country of birth, low educational level and being unemployed (or retired) were overall less likely to be tested. The income-based inequality in breast (SII = 0.191;RII = 1.260) and colorectal testing utilization (SII = 0.161;RII = 1.487) was the greatest in Southern Europe. For cervical smears, this inequality was greatest in Eastern Europe (SII = 0.122;RII = 1.195). We concluded that there is considerable inequality in the use of cancer tests in Europe, with inequalities associated with household income, educational level, employment status, and country of birth.


[Comparison of DRG revenues between fast and slow-track procedures for a two-stage replacement of prostheses for periprosthetic hip infections in the aG-DRG system 2020].
The treatment of periprosthetic hip infections is usually cost intensive, so it is generally not cost effective for hospitals. In chronic infections, a two-stage procedure is often indicated, which can be done as a fast-track procedure with a short prosthetic-free interim interval (2-4 weeks) or as a slow-track procedure with a long prosthetic-free interim interval (over 4 weeks). The aim of this study was to elucidate the revenue situation of both forms of treatment in the aG-DRG-System 2020, taking into account revenue-relevant influencing factors. For fast-track and slow-track procedures with two-stage revision and detection of a staphylococcus aureus (MSSA), treatment cases were simulated using a grouper software (3M KODIP Suite) based on the diagnoses (ICD-10-GM) and procedures (OPS) and then grouped into DRGs. Revenue-relevant parameters, such as length of stay and secondary diagnoses (SD), were taken into account. In addition, two real treatment cases with fast-track and slow-track procedures were compared to each other. The total revenues for the slow-track procedure with a length of stay of 25 days (without SD) were 27,551 € and for a length of stay of 42 days (with SD) even 40,699 €, compared to 23,965 € with the fast-track procedure with a length of stay of 25 days (without SD) and 27,283 € for a length of stay of 42 days (with SD). The real treatment cases also showed a big difference in the total revenues of 12,244 € in favor of the slow-track procedure. Even in the aG-DRG-System 2020, the two-stage revision procedure with a long interim interval seems to be more interesting from a financial point of view and the hospital perspective compared to the fast-track procedure, especially with multimorbid patients. This creates a financial barrier to the treatment of such patients with a short interim interval.


Atmospheric black carbon in urban and traffic areas in Shanghai: Temporal variations, source characteristics, and population exposure.
Black carbon (BC) measurements were performed at Pudong (PD) urban supersite and Gonghexin (GH) roadside station from December 1, 2017 to August 10, 2020 to investigate the variations, source characteristics, and population exposure levels of BC in traffic and urban areas in Shanghai, China. The BC median concentration at GH was more than two-fold that at PD. Absorption Ångström exponent (AAE) values were 1.27 ± 0.17 and 1.31 ± 0.17 at PD and GH, respectively, suggesting the dominance of liquid fossil fuel combustion sources (i.e., traffic exhaust) at these stations. The higher BC and AAE values in winter at PD indicated the relatively increasing contribution of solid fuels (i.e., biomass burning) to BC concentration in urban Shanghai. The diurnal variation in BC showed similar twin-peak patterns at PD and GH, implying that traffic emission mainly contributed to ambient BC concentration in urban Shanghai. The estimated daily intakes (EDIs) of BC were generally higher in males than in females at both PD and GH. The highest BC EDIs at PD were found in age subgroups 1-<2 and 2-<3 years. In contrast, the BC EDIs at GH were observed in age subgroups 6-<9, 12-<15, and 15-<18 years, which were higher than those determined at PD, indicating that more attention must be paid to BC exposure of the population in these age subgroups. These results provide scientific insights into variations, source characteristics, and population exposure levels of BC in urban and traffic areas and could help in the development of BC control strategies in Shanghai.


Placental 13C-DHA metabolism and relationship with maternal BMI, glycemia and birthweight.
Fetal docosahexaenoic acid (DHA) supply relies on preferential transplacental transfer, which is regulated by placental DHA lipid metabolism. Maternal hyperglycemia and obesity associate with higher birthweight and fetal DHA insufficiency but the role of placental DHA metabolism is unclear. Explants from 17 term placenta were incubated with 13C-labeled DHA for 48 h, at 5 or 10 mmol/L glucose treatment, and the production of 17 individual newly synthesized 13C-DHA labeled lipids quantified by liquid chromatography mass spectrometry. Maternal BMI positively associated with 13C-DHA-labeled diacylglycerols, triacylglycerols, lysophospholipids, phosphatidylcholine and phosphatidylethanolamine plasmalogens, while maternal fasting glycemia positively associated with five 13C-DHA triacylglycerols. In turn, 13C-DHA-labeled phospholipids and triacylglycerols positively associated with birthweight centile. In-vitro glucose treatment increased most 13C-DHA-lipids, but decreased 13C-DHA phosphatidylethanolamine plasmalogens. However, with increasing maternal BMI, the magnitude of the glucose treatment induced increase in 13C-DHA phosphatidylcholine and 13C-DHA lysophospholipids was curtailed, with further decline in 13C-DHA phosphatidylethanolamine plasmalogens. Conversely, with increasing birthweight centile glucose treatment induced increases in 13C-DHA triacylglycerols were exaggerated, while glucose treatment induced decreases in 13C-DHA phosphatidylethanolamine plasmalogens were diminished. Maternal BMI and glycemia increased the production of different placental DHA lipids implying impact on different metabolic pathways. Glucose-induced elevation in placental DHA metabolism is moderated with higher maternal BMI. In turn, findings of associations between many DHA lipids with birthweight suggest that BMI and glycemia promote fetal growth partly through changes in placental DHA metabolism.


Evaluation of the Effect of Fungatol and Gamma-T-ol on the Emergence and Adult Parasitoid Survival of Mummies of Cotton Aphids Parasitized by Aphidius colemani.
Beneficial insects play a major role in controlling pest populations. In sustainable agricultural production systems, control methods compatible with integrated pest management (IPM) are preferred over broad-spectrum pesticides. EOs from aromatic plants may provide a new and safe alternative to synthetic chemicals. In this research, the efficacy of Fungatol, Gamma-T-ol, Fungatol plus neem, and Gamma-T-ol plus neem was evaluated against Aphidius colemani Viereck (Hymenoptera: Braconidae; Aphidiidae), the parasitoid of the cotton aphid, Aphis gossypii Glover (Hemiptera: Aphididae). Under laboratory and greenhouse conditions, five different concentrations of each formulation were applied to parasitized mummies and adult parasitoids. Results for parasitoid emergence from aphid mummies sprayed with different concentrations of Fungatol, Gamma-T-ol, Fungatol plus neem, and Gamma-T-ol plus neem in the laboratory and glasshouse showed that the formulations did not adversely affect adult emergence as rates above 60% were observed. For residual toxicity tests done by exposing adult parasitoids to a fresh, dry biopesticide film sprayed on glass plates, less than 20% mortality was observed after 48 h of exposure. Adult longevity tests revealed that the highest concentrations of some of the formulations evaluated were slightly toxic to A. colemani. According to the IOBC rating, our results indicated that most of the tested concentrations for each formulation were harmless to A. colemani. Based on the above results, it may be proposed that the formulations evaluated in this study are potential botanical pesticide candidates for incorporation into an IPM program.


Differential effects of asymptomatic Ascaris lumbricoides, Schistosoma mansoni or hook worm infection on the frequency and TGF-beta-producing capacity of regulatory T cells during active tuberculosis.
Helminth induced expansion of regulatory T cells (Tregs) may take part in suppressing protective host responses during tuberculosis (TB), although Tregs functionality and link to TB disease severity remains unexplored. We investigated the species-specific effect of helminths on frequency and TGF-β producing capacity of Tregs, and possible connection to TB disease severity. 89 pulmonary TB patients (PTB) and 69 community controls (CCs) from Gondar, Ethiopia, were included. Clinical disease severity was graded by TB score, and flow cytometry used to characterize Treg frequency and functionality measured as their TGF-β-producing capacity. In helminth positive PTB patients (Helminth+PTB+) compared to helminth negative PTB or CCs, TGF-β+ Tregs were significantly increased mainly in hookworm coinfection whereas S. mansoni increased TGF-β+ Tregs in CCs. Treatment of TB and helminths decreased TGF-β+ Tregs in Helminth+PTB+ at 2 months follow-up. There were no overall differences in the frequency of Tregs in CCs or PTB unless stratification on TB disease severity was performed. At inclusion Helminth+PTB+ had increased frequency of Tregs already at low disease severity, and TGF-β+ Tregs correlated to intermediate-to-high disease severity. In conclusion, helminth specific increase of TGF-β+ Tregs in PTB patients was correlated to TB disease severity and was restored following anti-helminth treatment.


Cytogenetic analysis of nuclear abnormalities in the erythrocytes of gecko lizards (Phyllopezus periosus) collected in a semi-arid region of northeast Brazil: Possible effects of natural background radioactivity.
High natural-background radioactivity levels occur in the semi-arid region of the State of Rio Grande do Norte, northeastern Brazil. We have studied the lizard Phyllopezus periosus, an endemic species of the Brazilian caatinga with saxicolous habitat, as a bioindicator of environmental quality. Specimens were collected in three areas, an environmental protection area and two areas recognized as having high natural background radiation, one of these being a mining area. Level of metals and gamma radiation emitters present in the water sources potentially used by the lizards were measured. The biological endpoints assessed were micronuclei and nuclear abnormalities in blood samples. Significant differences in background radioactivity levels were found among the assessed areas. Statistically significant differences in micronuclei and nuclear abnormality frequencies were seen, among the study areas and a relationship between radioactivity level and genetic damage was observed.


Programmed Cell Death in Health and Disease.
Programmed cell death is a conserved evolutionary process of cell suicide that is central to the development and integrity of eukaryotic organisms [...].


PPARs: regulators of metabolism and as therapeutic targets in cardiovascular disease. Part I: PPAR-α.
This article provides a comprehensive review about the molecular and metabolic actions of PPAR-α. It describes its structural features, ligand specificity, gene transcription mechanisms, functional characteristics and target genes. In addition, recent progress with the use of loss of function and gain of function mouse models in the discovery of diverse biological functions of PPAR-α, particularly in the vascular system and the status of the development of new single, dual, pan and partial PPAR agonists (PPAR modulators) in the clinical management of metabolic diseases are presented. This review also summarizes the clinical outcomes from a large number of clinical trials aimed at evaluating the atheroprotective actions of current clinically used PPAR-α agonists, fibrates and statin-fibrate combination therapy.


Does Public Reporting of Staffing Ratios and Nursing Home Compare Ratings Matter?
Public reporting is a policy to improve quality and increase data transparency. The objective was to examine the association between publicly available staffing ratios and the Five-Star Quality Ratings from Nursing Home Compare over time. Panel data analysis. About 146 nursing homes with complete quarterly data in New Jersey between January 1, 2012, and December 31, 2019. Using data from the State of New Jersey Department of Health and Nursing Home Compare, staff-to-resident ratios were trended for registered nurses, licensed practical nurses, and certified nursing assistants by shift and over time. Panel data analysis was used to test the association between the ratios and the ratings. Compared to 2012, staffing ratios improved slightly for licensed practical nurses but not for registered nurses or certified nursing assistants in 2019 (P < .001). The number of residents assigned doubled at night for all personnel. During the day and evening shifts, registered nurse staffing was significantly associated with the Nursing Home Compare staffing rating (P < .01) but not the overall rating. Decreasing the number of residents assigned to a registered nurse in NHs results in an increase in staffing ratings. Mandatory public reporting holds nursing homes accountable for quality outcomes but does not improve staffing ratios. Quality resident care is the cumulative result of multiple measures inclusive of staffing; therefore, administrators should continue to focus on improving quality in NHs, which may improve staffing ratios across shifts.


Determination of the mass of viruses by quantitative electron microscopy.
The photometric method of quantitative determination of dry mass by electron microscopy has been applied to the study of various types of viruses: animal, plant, insect, and bacterial. The method is applicable to all viruses having a mass of 1 x 10-18g or greater. The molecular weight of viruses can be calculated from the mass value by multiplying it by Avogadro's number. In comparison to other methods of determining the molecular weight of viruses, sedimentation and diffusion, sedimentation equilibrium, light scattering, and electron microscopy counting, the method of quantitative electron microscopy is competitive. In some ways quantitative electron microscopy is superior to other methods for the determination of molecular weight: There is no limitation to the size of the virus, no experimental time involved and no concentration and purity of virus preparations required, and finally it is independent of the geometry of the virion. In one important aspect it is unique when compared to other methods; namely, it affords one the capacity to analyse individual virus particles.