Senior manager leadership competencies for quality residential aged care: an Australian industry perspective.
Documented poor quality and standards of care in Australia's residential aged care (RAC) sector have highlighted a need to better understand the role of and skills required by, RAC senior management personnel to address these concerns. This study examined which senior management leadership skills and personal qualities are necessary to deliver and strengthen the quality of RAC, with the aim of improving understanding of the professional development needs of leaders in the sector. We conducted 12 in-depth interviews with Australian aged care industry experts, including academics, and representatives from the primary health network, consumer, and provider advocate groups. Abductive, thematic analysis incorporated coding derived from existing leadership skills frameworks as well as inductively identified themes. Identified leadership skills were grouped into five domains including i) workforce development and retention, ii) governance and business acumen; iii) health systems knowledge; iv) stewardship and v) responding to regulatory and political contexts. Skills particularly emphasised by participants were those required to recruit and retain a skilled workforce, manage relationships, and promote a positive organisational culture and employee wellbeing. RAC senior managers require a complex mix of business, human resource management, and clinical skills to deliver quality care in Australia's complex RAC setting. The lack of any professional development framework to guide the acquisition or updating of those skills is a concern.


Investigation of the clinical effect of large volume leukocytapheresis on methotrexate-resistant rheumatoid arthritis.
Leukocytapheresis (LCAP) is already being used in a clinical setting for the treatment of autoimmune diseases such as inflammatory bowel disease and rheumatoid arthritis, and it has been reported to be effective. However, it is totally or partially ineffective in some patients, which has forced clinicians to rethink therapeutic strategies and concurrent treatment. With the aim of enhancing the therapeutic effect, we carried out large volume leukocytapheresis, with a throughput of 5000 mL instead of the 3000-mL throughput of conventional leukocytapheresis in nine patients with rheumatoid arthritis resistant to methotrexate treatment. Using Cellsorba, the column filled with the unwoven fabric made of the polyethylene phthalate, a leukocyte removal filter, large volume leukocytapheresis was carried out once a week for a total of five sessions. The observation period was the 12-week period following completion of treatment. The American College of Rheumatology (ACR) core set was used for assessment of efficacy. Eight weeks after completion of treatment, a 20% improvement in ACR was observed in 77.8% (7/9) of subjects, a 50% improvement in ACR was seen in 55.6% (5/9) of subjects, and a 70% improvement in ACR was observed in 22.2% (2/9) of subjects. C-reactive protein decreased gradually as treatment progressed, and a significant decrease was observed 4 weeks after completion of treatment. The fact that some subjects had an ACR70 response, few reports of which are observed in the case of conventional leukocytapheresis, and the fact that the effect continued up to 12 weeks after completion of treatment suggests that the degree and duration of the effect of large volume leukocytapheresis might be longer than those of conventional leukocytapheresis.


Leberagin-C, A disintegrin-like/cysteine-rich protein from Macrovipera lebetina transmediterranea venom, inhibits alphavbeta3 integrin-mediated cell adhesion.
Leberagin-C, a new member of the disintegrin-like/cysteine-rich (D/C) family, was purified to homogeneity from the venom of Tunisian snake Macrovipera lebetina transmediterranea. It is a monomeric protein with a molecular mass of 25,787 Da. Its complete sequence of 205 amino acid residues was established by cDNA cloning. The leberagin-C shows many conserved sequences with other known D/C proteins, like the SECD binding sites and a pattern of 28 cysteines. It is the first purified protein from M. lebetina transmediterranea with only two disintegrin-like/cysteine-rich domains. Leberagin-C is able to inhibit platelet aggregation induced by thrombin and arachidonic acid with IC(50) of 40 and 50 nM respectively. It was also able to inhibit the adhesion of melanoma tumour cells on fibrinogen and fibronectin, by interfering with the function of alphavbeta3 and, to a lesser extent, with alphavbeta6 and alpha5beta1 integrins. To our knowledge, leberagin-C is the sole described D/C protein that does not specifically interact with the alpha2beta1 integrin. Structure-activity relationship study of leberagin-C suggested that there are some important amino acid differences with jararhagin, the most studied PIII metalloprotease from Bothrops jararaca, notably around the SECD motif in its disintegrin-like domain. Other regions implicated in leberagin-C specificities could not be excluded.


A P-H Functionalized Al/P Frustrated Lewis Pair: Substrate Activation and Selective Hydrogen Transfer.
Hydroalumination of an alkynylphosphine gave an unprecedented P-H functionalized frustrated Lewis pair (FLP). The reactive P-H group does not influence the typical FLP properties, but the activation of substrates follows a new reaction pattern involving hydrogen transfer to yield unusual compounds with phosphaurea, iminophosphine, or phosphanyltriazene structural motifs.


Simultaneous determination of (+)-catechin and (-)-epicatechin in cacao and its products by high-performance liquid chromatography with electrochemical detection.
A fast single-step extraction procedure and HPLC with electrochemical detection (ECD) in the oxidative mode has been used for the simultaneous, quantitative determination of (+)-catechin (CA) and (-)-epicatechin (EC) in cacao and its products. A UV detector measuring at 280 nm was also used in-line for comparison purposes. The samples were extracted with methanol and applied directly to the reversed-phase column of the HPLC. The high sensitivity of the ECD allowed operation at a low voltage (+0.5 V), but with a high sensitivity for the readily oxidizable CA and EC, thus reducing baseline noise. As a result, ECD had a better sensitivity and resolution than UV detection for the simultaneous quantitative determination of CA and EC in cacao and its products.


Effect of dopamine transporter genotype on caudate volume in childhood ADHD and controls.
Polymorphism of the dopamine transporter genotype (DAT1) confers a small but significant susceptibility to attention deficit hyperactivity disorder (ADHD). We examined whether the volume of the head of caudate, a striatal structure with high DAT expression that is important for inhibitory function, differs by DAT1 in children diagnosed with the disorder relative to age and IQ matched controls. Volume of the head of caudate was delineated in the right and left hemisphere and compared between 7- and 13-year-old children with and without ADHD (combined type) who were carriers of two (10/10) or one (9/10) copy of the 10-repeat DAT1 allele. Caudate volumes were overall smaller in 10/10 than 9/10 children, particularly in the left than right hemisphere. While DAT1 effects did not vary by ADHD diagnosis, overall caudate volumes were smaller in ADHD relative to control children. Altered caudate development associated with 10-repeat homozygosity of DAT1 may contribute susceptibility to ADHD.


Niacin and progression of CKD.
Niacin is the oldest drug available for the treatment of dyslipidemia. It has been studied extensively and tested in clinical trials of atherosclerotic cardiovascular disease prevention and regression in the general population, but not specifically in patients with chronic kidney disease (CKD), who are at extremely high residual risk despite current therapy. Despite the current controversy about recent trials with niacin, including their limitations, there may be a place for this agent in select patients with CKD with dyslipidemia. Niacin has a favorable unique impact on factors affecting the rate of glomerular filtration rate decline, including high-density lipoprotein (HDL) particle number and function, triglyceride levels, oxidant stress, inflammation and endothelial function, and lowering of serum phosphorus levels by reducing dietary phosphorus absorption in the gastrointestinal tract. These effects may slow glomerular filtration rate decline and ultimately improve CKD outcomes and prevent cardiovascular risk. This review presents the clinically relevant concept that niacin holds significant potential as a renoprotective therapeutic agent. In addition, this review concludes that clinical investigations to assess the effect of niacin (in addition to aggressive low-density lipoprotein cholesterol lowering) on reduction of cardiovascular events in patients with CKD with very low HDL cholesterol (or those with identified dysfunctional HDL) and elevated triglyceride levels need to be considered seriously to address the high residual risk in this population.


Impact of oestradiol and progesterone on the glycosaminoglycans and their depolymerizing enzymes of the rat mammary gland.
The influence of oestradiol and progesterone either singly or in combination with each other on the levels of hyaluronic acid, heparan sulphate, chondroitin sulphate, and on the activity of hyaluronidase and chondroitinase were investigated in the mammary gland of ovary-intact and in ovariectomized rats, administered oestradiol and/or progesterone. Administration of oestradiol to ovary-intact rats elevated the levels of hyaluronic acid and decreased the levels of heparan sulphate while progesterone, when administered alone, could elevate only chondroitin sulphate when compared with controls. The steroids when administered in combination, however, increased the levels of all glycosaminoglycans studied. Ovariectomized animals showed a decrease in heparan sulphate alone as compared with controls while administration of oestradiol to these rats elevated the levels of both heparan sulphate and chondroitin sulphate as compared with ovariectomized rats. Also the administration of progesterone either singly or in combination increased the levels of heparan sulphate and also decreased the levels of hyaluronic acid with no impact on the levels of chondoritin sulphate. In ovary-intact animals administration of oestradiol alone had no effect on hyaluronidase activity. Progesterone either singly or in combination with oestradiol reduced the activity of hyaluronidase, whereas it had no influence on the activity of chondroitinase. The activities of both the enzymes were decreased in ovariectomized animals and administration of oestradiol and/or progesterone to the above groups resulted in an increase. This study demonstrates that oestradiol anzd progesterone play an important role in modulating glycosaminoglycans and their depolymerizing enzymes, thereby influencing the activities of the mammary epithelium.


Citrobacter freundii Foodborne Disease Outbreaks Related to Environmental Conditions in Yazd Province, Iran.
The aim of this study was to assess associations of Citrobacter freundii foodborne outbreaks with environmental factors in various regions of Yazd Province, Iran, 2012-2016. The public health surveillance data were used for one period of five years reported foodborne disease outbreaks in various regions of the Province. Multilevel regression statistical method was used to analyze associations of climatic and demographic variables with outbreaks. Significant associations were tested using likelihood ratio tests. Results showed a significant association between C. freundii outbreaks and air dust conditions, age groups and various regional cities. The current study revealed necessity of etiologic agent identification for use in foodborne disease outbreak guidance in future outbreaks. Systemic surveillance schemes can help prevent and control similar scenarios using reports of environmental effects on foodborne disease outbreaks.


Consistency of Learning Styles of Undergraduate Athletic Training Students in the Traditional Classroom versus the Clinical Setting.
To examine the learning styles of undergraduate athletic training students to determine their consistency in traditional classroom versus clinical settings. Subjects completed the Learning Styles Inventory twice, once focusing on learning new information in the classroom and the other focusing on learning new information in the clinical setting. The order of focus regarding setting (classroom or clinical) was counterbalanced across subjects. A total of 26 undergraduate athletic training students from a Committee on the Accreditation of Allied Health Education Programs accredited athletic training education program (16 women and 10 men; mean age, 24.42 +/- 6.44 years) who were currently assigned to a clinical practicum as part of their academic program served as subjects. I performed 4 paired t tests, 1 for each learning mode, to determine if differences existed between the classroom and clinical settings. The percentage of respondents whose learning styles changed across settings was also calculated. The paired t tests revealed a significant difference between the Reflective Observation and Active Experimentation modes across settings. In addition, 58% of respondents' learning styles changed according to setting focus. It appears that learning styles do indeed shift, depending on the domain through which an individual is learning. Consequently, teaching strategies incorporated in 1 setting may not be equally effective in the other setting. Each learning setting should, therefore, be treated separately in order to accommodate individual learning styles and maximize learning achievement. Furthermore, if learning styles are to be considered when designing athletic training education, these findings indicate that in order to ensure the validity of the resulting learning style profile, it may be necessary to provide the respondent with a specific focus, either that of a classroom or clinical setting, before completing the Learning Styles Inventory.


Addressing Dual Patient and Staff Safety Through A Team-Based Standardized Patient Simulation for Agitation Management in the Emergency Department.
Emergency departments (EDs) have seen harm rise for both patients and health workers from an increasing rate of agitation events. Team effectiveness during care of this population is particularly challenging because fear of physical harm leads to competing interests. Simulation is frequently employed to improve teamwork in medical resuscitations but has not yet been reported to address team-based behavioral emergency care. As part of a larger investigation of agitated patient care, we designed this secondary study to examine the impact of an interprofessional standardized patient simulation for ED agitation management. We used a mixed-methods approach with emergency medicine resident and attending physicians, Physician Assistants (PAs) and Advanced Practice Registered Nurses (APRNs), ED nurses, technicians, and security officers at two hospital sites. After a simulated agitated patient encounter, we conducted uniprofessional and interprofessional focus groups. We undertook structured thematic analysis using a grounded theory approach. Quantitative data consisted of responses to the KidSIM Questionnaire addressing teamwork and simulation-based learning attitudes before and after each session. We reached data saturation with 57 participants. KidSIM scores revealed significant improvements in attitudes toward relevance of simulation, opportunities for interprofessional education, and situation awareness, as well as four of six questions for roles/responsibilities. Two broad themes emerged from the focus groups: (1) a team-based agitated patient simulation addressed dual safety of staff and patients simultaneously and (2) the experience fostered interprofessional discovery and cooperation in agitation management. A team-based simulated agitated patient encounter highlighted the need to consider the dual safety of staff and patients while facilitating interprofessional dialog and learning. Our findings suggest that simulation may be effective to enhance teamwork in behavioral emergency care.


ESCRT or endosomes?: Tales of the separation of two daughter cells.
The final abscission event of cytokinesis is necessary for daughter cells to part ways from one another. Failure to properly divide has been indicated as a potential cancer initiating event due to an increase in cellular aneuploidy. However, the exact mechanisms of abscission have remained obscured by our inability to properly discern the spatiotemporal regulation of the various proteins and organelles required for cytokinesis. Three recent publications have taken slightly varied high resolution imaging approaches to visualize cytokinesis and abscission. As a result of this work, two differing, but not necessarily mutually exclusive, models have emerged. One model is ESCRT-dependent and the other, recycling endosome-dependent, each describing the steps leading up to the final abscission event. Presently these models describe late cytokinesis events leading to abscission in greater detail than previously known.


Roles of Glycogen Synthase Kinase-3 (GSK-3) in Cardiac Development and Heart Disease.
Glycogen synthase kinase-3 (GSK-3) is a cytoplasmic serine/threonine protein kinase which is known to regulate a variety of cellular processes through a number of signaling pathways important for cell proliferation, stem cell renewal, apoptosis and development. Although GSK-3 exists in a variety of tissues, this kinase plays very important roles in the heart to control its development through the formation of heart and cardiomyocyte proliferation. GSK-3 is also recognized as one of the main molecules that control cardiac hypertrophy and fibrosis. Therefore, GSK-3 could be an attractive target for the development of new drugs to cure cardiac diseases. The present review summarizes the roles of GSK-3 in the signaling pathways and the heart, and discusses the possibility of new drug development targeting this kinase.


Raman scattering study of GaN nanostructures obtained by bottom-up and top-down approaches.
GaN nanocolumnar structures were grown by plasma-assisted molecular beam epitaxy (PAMBE) and also fabricated by electron cyclotron resonance reactive ion etching (ECR-RIE) of a compact GaN film parallel to the [111] direction of the Si(111) substrates. Scanning electron microscopy shows that the nanocolumns fabricated by PAMBE have a length of about 300-500 nm with diameters ranging from 20 to 150 nm while nanowhiskers formed by RIE have diameters of 40-80 nm and a height between 1.4 and 1.7 µm. A comparative study of the vibrational spectrum (including optical and interface phonons) of the nanostructures using conventional macro-Raman and micro-Raman scattering as well as surface-enhanced Raman scattering is presented.


[Analysis of 2,4-dibromophenol and 2,6-dibromophenol in phenolic-smelling flatfish].
A simple analytical method for dibromophenols (DBPs) in flatfiish was developed. 2,4-DBP and 2,6-DBP were extracted from a sample with acetone and n-hexane, cleaned up by treatment with conc. sulfuric acid and concentrated under a stream of nitrogen gas. The resulting extract was subjected to GC/MS. The recoveries of 2,4-DBP and 2,6-DBP were 89.4-96.5% and 81.4-86.2%, respectively, indicating that this method is useful for analysis of 2,4-DBP and 2,6-DBP. In the phenolic-smelling flatfish, 2,6-DBP was detected at the levels of 0.10 microg/g and 0.01 microg/g in skin and muscle, respectively, and 2,4-DBP was detected at the level of 0.02 microg/g in skin.


Compression with a pocket-sized ultrasound device to diagnose proximal deep vein thrombosis.
Compression ultrasonography (CUS) is a validated technique for the diagnosis of deep venous thrombosis (DVT), but has never been studied with pocket-sized ultrasound device (PUD). The main objective of this study was to assess the diagnostic performance of CUS made by emergency physicians (EPs) using a PUD. This was a prospective, diagnostic test assessment, single-center study. Patients underwent VCU performed by a trained EP with PUD (CUS-PUD) for searching proximal DVT (PDVT) and were then seen by an expert vascular physician who blindly performed a duplex venous ultrasound, which was the criterion standard. CUS-PUD's diagnostic performance was evaluated by sensitivity (Se), specificity (Sp), and positive and negative predictive values (PPV and NPV). The sample included 57 patients of whom 56 were analyzed. Eleven (20%) PDVT were diagnosed with CUS-PUD: 7 (64%) femoral and 4 (36%) popliteal. The CUS-PUD's Se was 100% [72%; 100%], Sp 100% [92%; 100%]. The PPV was 100% [74%; 100%], and the NPV was 100% [90%; 100%]. CUS-PUD performed with a pocket-sized ultrasound appears to be feasible in emergency practice for the diagnosis of proximal DVT. A study with a larger sample size will have to describe the accuracy.


Nutrients with immune-modulating effects: what role should they play in the intensive care unit?
This review will summarize recent clinical and experimental data on the use of immune-modulating nutrients in critical illness. It will present the concept of these nutrients as pharmacologic agents or 'nutraceuticals' administered in addition to protein, calorie, vitamin, and trace element sources. Studies have defined the physiologic roles of arginine in critical illness, such as its role as a precursor for the production of nitric oxide. Investigations have determined that, in critical illness, glutamine levels decrease and severe glutamine deficiency is associated with increased mortality. Experimental studies have revealed that glutamine attenuates proinflammatory cytokine responses, improves gut barrier and immune cell functions, increases the ability to mount a stress response, and decreases mortality. Clinical trials and meta-analyses of studies testing immune-modulating nutritional formulations have reported numerous benefits but also some conflicting results. Dose and route of administration are key factors that influence the benefit, or lack thereof, of these nutraceuticals. Cumulative studies of enteral immune-modulating nutritional formulations report benefits in surgical critically ill patients such as burn, trauma, or gastrointestinal surgery populations. Conflicting data in patients with sepsis warrant concern and further evaluation; in particular, controversy seems to stem around the use of arginine. Glutamine is beneficial when given in high doses or via the parenteral route (>0.20-0.30 g/kg per day or >or=30 g/day). Providing both omega-3 and omega-6 polyunsaturated fatty acids is important in immune modulation. The best doses and combinations of immune-modulating components remain unclear.


Proteomic Profile of Saliva in Parkinson's Disease Patients: A Proof of Concept Study.
Parkinson's disease (PD) is a progressive neurodegenerative disorder. It affects many organs. Lewy bodies-a histopathological "hallmark" of PD-are detected in about 75% of PD submandibular gland samples. We hypothesize that saliva can be a source of biomarkers of PD. The aim of the study was to evaluate and compare the salivary proteome of PD patients and healthy controls (HC). Salivary samples from 39 subjects (24 PD patients, mean age 61.6 ± 8.2; 15 HC, mean age 60.9 ± 6.7) were collected. Saliva was collected using RNA-Pro-Sal kits. Label-free LC-MS/MS mass spectrometry was performed to characterize the proteome of the saliva. IPA analysis of upstream inhibitors was performed. A total of 530 proteins and peptides were identified. We observed lower concentrations of S100-A16, ARP2/3, and VPS4B in PD group when compared to HC. We conclude that the salivary proteome composition of PD patients is different than that of healthy controls. We observed a lower concentration of proteins involved in inflammatory processes, exosome formation, and adipose tissue formation. The variability of expression of proteins between the two groups needs to be considered.


Confirmatory reinforcement learning changes with age during adolescence.
Understanding how learning changes during human development has been one of the long-standing objectives of developmental science. Recently, advances in computational biology have demonstrated that humans display a bias when learning to navigate novel environments through rewards and punishments: they learn more from outcomes that confirm their expectations than from outcomes that disconfirm them. Here, we ask whether confirmatory learning is stable across development, or whether it might be attenuated in developmental stages in which exploration is beneficial, such as in adolescence. In a reinforcement learning (RL) task, 77 participants aged 11-32 years (four men, mean age = 16.26) attempted to maximize monetary rewards by repeatedly sampling different pairs of novel options, which varied in their reward/punishment probabilities. Mixed-effect models showed an age-related increase in accuracy as long as learning contingencies remained stable across trials, but less so when they reversed halfway through the trials. Age was also associated with a greater tendency to stay with an option that had just delivered a reward, more than to switch away from an option that had just delivered a punishment. At the computational level, a confirmation model provided increasingly better fit with age. This model showed that age differences are captured by decreases in noise or exploration, rather than in the magnitude of the confirmation bias. These findings provide new insights into how learning changes during development and could help better tailor learning environments to people of different ages. RESEARCH HIGHLIGHTS: Reinforcement learning shows age-related improvement during adolescence, but more in stable learning environments compared with volatile learning environments. People tend to stay with an option after a win more than they shift from an option after a loss, and this asymmetry increases with age during adolescence. Computationally, these changes are captured by a developing confirmatory learning style, in which people learn more from outcomes that confirm rather than disconfirm their choices. Age-related differences in confirmatory learning are explained by decreases in stochasticity, rather than changes in the magnitude of the confirmation bias.


Repeatability estimates for milk coagulation traits and non-coagulation of milk in Finnish Ayrshire cows.
Effects of systematic environmental factors and milk production and quality traits on milk coagulation properties (MCP), and on repeatability of those traits were estimated from 979 milk samples collected once a month over a period of 2 years from 83 Finnish Ayrshire cows. Estimation was based on a multitrait animal model and REML methodology. In addition, persistence of non-coagulation of milk in individual cows, and factors associated with it were established from a sub sample of 24 cows producing non-coagulating (NC) milk at least once. MCP were at their best during the first lactation, at the beginning and at the end of lactation, and during grazing seasons. Variation in MCP with systematic environmental factors was partly due to variation in composition and quality of milk, especially in pH and ln (somatic cell count, SCC). Coefficients of repeatability for milk coagulation time and curd firmness were 0.65 and 0.68. These estimates were of the same magnitude as those for protein content, but were higher than those for daily milk yield, fat content, pH, and SCC. Based on the repeatability estimates for the milk coagulation traits and effects of the environmental factors, cows should be sampled at least three times during a lactation to estimate reliably breeding values for the milk coagulation traits. A total of 10% of the milk samples did not coagulate in 30 min after addition of rennet. Cows that produced NC milk at least once (30% of the cows) could be classified into those that produced NC milk only a few times during a lactation and those that produced NC milk at almost every sampling. Based on logistic regression analyses, peak and mid-lactation, high milk yield, low protein and fat content and high pH increased the risk of non-coagulation of milk.


Rearrangement of immunoglobulin gamma 1-chain gene and mechanism for heavy-chain class switch.
Cloning and nucleotide sequence determination suggest that the rearranged gamma 1-chain gene in a gamma 1-chain-producing myeloma a-pears to be formed by the recombination between the 5' flanking regions of the gamma 1- and mu-chain genes of undifferentiated cells. The recombination site is distinct from the putative J region and is a novel region that we call the S region. We have extended our previous model that explains the heavy-chain class switching by two or more successive recombination events.


Arabidopsis thaliana class-II TGA transcription factors are essential activators of jasmonic acid/ethylene-induced defense responses.
The three closely related Arabidopsis basic leucine zipper (bZIP) transcription factors TGA2, TGA5 and TGA6 are required for the establishment of the salicylic acid (SA)-dependent plant defense response systemic acquired resistance, which is effective against biotrophic pathogens. Here we show that the same transcription factors are essential for the activation of jasmonic acid (JA)- and ethylene (ET)-dependent defense mechanisms that counteract necrotrophic pathogens: the tga256 triple mutant is impaired in JA/ET-induced PDF1.2 and b-CHI expression, which correlates with a higher susceptibility against the necrotroph Botrytis cinerea. JA/ET induction of the trans-activators ERF1 and ORA59, which act upstream of PDF1.2, was slightly increased (ERF1) or unaffected (ORA59). PDF1.2 expression can be restored in the tga256 mutant by increased expression of ORA59, as observed in the tga256 jin1 quadruple mutant, which lacks the transcription factor JIN1/AtMYC2 that functions as a negative regulator of the JA/ET-dependent anti-fungal defense program. Whereas JA/ET-induced PDF1.2 expression is strongly suppressed by SA in wild-type plants, no negative effect of SA on PDF1.2 expression was observed in the tga256 jin1 quadruple mutant. These results imply that the antagonistic effects of TGA factors and JIN1/AtMYC2 on the JA/ET pathway are necessary to evoke the SA-mediated suppression of JA/ET-induced defense responses.


Enumeration of free-living aerobic n(2)-fixing h(2)-oxidizing bacteria by using a heterotrophic semisolid medium and most-probable-number technique.
A heterotrophic semisolid medium was used with two sensitive assay methods, C(2)H(2) reduction and O(2)-dependent tritium uptake, to determine nitrogenase and hydrogenase activities, respectively. Organisms known to be positive for both activities showed hydrogenase activity in both the presence and absence of 1% C(2)H(2), and thus, it was possible to test a single culture for both activities. Hydrogen uptake activity was detected for the first time in N(2)-fixing strains of Pseudomonas stutzeri. The method was then applied to the most-probable-number method of counting N(2)-fixing and H(2)-oxidizing bacteria in some natural systems. The numbers of H(2)-oxidizing diazotrophs were considerably higher in soil surrounding nodules of white beans than they were in the other systems tested. This observation is consistent with reports that the rhizosphere may be an important ecological niche for H(2) transformation.


Fatal Case of Giant Chondrosarcoma of Rib with Paraplegia: A Case Report.
Chondrosarcoma of rib encroaching spine and subsequently leading to paraplegia has never been reported in the literature. Association of paraplegia can often lead to misdiagnosis with a common disease like breast cancer or Potts spine causing a significant delay in treatment. We describe a case of a 45-year-old male with chondrosarcoma of rib with paraplegia who was misdiagnosed initially as Pott's spine and was started empirically on anti-tubercular treatment for paraplegia and chest wall mass. Further work up at tertiary care center including detailed imaging and biopsy revealed features of chondrosarcoma. However, before any definitive treatment could be done; the patient passed away. Empirical treatment of paraplegia with chest wall mass for more common diseases like tuberculosis are often initiated without obtaining appropriate radiological and tissue diagnosis. This can lead to a delay in diagnosis and initiation of treatment.


Lipid profile of population of central region of Nepal.
This study was conducted to know the status of Lipid profile in people of central region of Nepal. This study was conducted in College of Medical Sciences & Teaching Hospital, Bharatpur, Nepal from February 2009 to March 2010 which is situated in central region of Nepal. A total of 870 cases, out of which 512(58.85%) male and 358(41.14%) female were included and study was carried out using data retrieved from the register maintained in the Department of Biochemistry. The variables collected were age, sex, lipid profile which includes total cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C) & low density lipoprotein-cholesterol (LDL-C). The data was analyzed using excel 2007 and Statistical Package for the Social Sciences (SPSS) 16.0. The total mean±SD of TC, TG, HDL-C, LDL-C were found to be 164.87±49.49, 157.56±79.78, 33.59±11.10, 97.79±40.68 respectively. Total Cholesterol, HDL-C & LDL-C were found to be statistically significant whereas TG was statistically insignificant between male and female. In both male and female, TG & LDL-C were higher in the age group of 21-40 years whereas HDL-C was higher in the age group of >61 years in both the group. Total cholesterol (TC) level was higher in the age group of 21-40 years in male while in female in the age group of 41-60 years. Desirable level of TC was observed in 78.50% of the total subjects while the normal TG, LDL-C were observed in 56.55%, 81.49%, respectively. Very high levels of TC, TG, LDL-C were observed in 4.94%, 0.34% & 1.6% of the total population studied, respectively. More percentage of female (27.65%) had higher HDL-C level than in male (15.62%). High triglycerides (TG) level is the commonest lipid abnormality in our study. HDL-C level was increase with increasing in age. Clinical evaluation can be made according to this study.


Lipoprotein (a) in familial hypercholesterolaemia.
The role of lipoprotein (a) in atherogenesis has been the subject of argument for many years. Evidence that it is raised in familial hypercholesterolaemia has been disputed not least because a mechanism related to low density lipoprotein (LDL) receptor mediated catabolism has been lacking. Whether lipoprotein (a) increases the already raised atherosclerotic cardiovascular disease (ASCVD) risk in familial hypercholesterolaemia is also more dubious than is often stated. We review the evidence in an attempt to provide greater clarity. Lipoprotein (a) levels are raised as a consequence of inheriting familial hypercholesterolaemia. The mechanism for this is likely to involve increased hepatic production, probably mediated by PCSK9 augmented by apolipoprotein E. The extent to which raised lipoprotein (a) contributes to the increased ASCVD risk in familial hypercholesterolaemia remains controversial.Unlike, for example, statins which are effective across the whole spectrum of LDL concentrations, drugs in development to specifically lower lipoprotein (a) are likely to be most effective in people with the highest levels of lipoprotein (a). People with familial hypercholesterolaemia may therefore be in the vanguard of those in whom theses agents should be exhibited. Inheritance of familial hypercholesterolaemia undoubtedly increases the likelihood that lipoprotein (a) will be raised. However, in familial hypercholesterolaemia when ASCVD incidence is already greatly increased due to high LDL cholesterol, whether lipoprotein (a) contributes further to this risk cogently needs to be tested with drugs designed to specifically lower lipoprotein (a).


[Psychological profile of the spa user. Preliminary study of motivations for spa treatment].
The main psychological and possible psychopathological traits of the spa user are identified and classified in order to clarify motivational aspects. Two different self-assessment tests, the Middlesex Hospital Questionnaire (MHQ) and the Minnesota Multiphasic Personality Inventory (MMPI) were given, the first to 500 subjects who had undergone spa treatment cycles lasting at least 10 days and the second to a control group of 50. MHQ data showed a significant incidence of certain neurotic traits, especially phobia, obsession and somatisation in the first group. Despite their different areas of competence and survey methods, both questionnaires produced results to support the hypothesis that a particular form of neurosis may play a significant part in motivating recourse to spa treatment.


[Ultrasonic methods in the differential diagnosis of the "postcholecystectomy syndrome" (author's transl)].
The "postcholecystectomy syndrome" as a collective term for all upper abdominal complaints following cholecystectomy is a common clinical picture. For the purpose of clarification the easily practicable sonography offers itself in addition to conventional cholangiography and to endoscopic retrograde cholangiopancreaticography (ERCP). By means of echography, pathological changes in the upper abdominal organs can be detected or excluded. Chronologically, echography should be carried out at the beginning of diagnosis as an informative, harmless and rapid method. The most invasive investigations can then be omitted or performed specifically as required.


[Maternal eating disorders and their influence on eating behavior of the children: a review of the literature].
There is conclusive evidence about the influence of mothers with eating disorders (ED) on their children. To describe different aspects about mothers with ED and its implications in the feeding, growing and development in their children. A review of specialized textbooks and the available literature in PubMed was made. Mothers with previous or present ED show restrictive eating patterns, a deficient affective bond with their own mothers, exhibit more psychiatric comorbidities, mainly depression and anxiety; in addition, feelings of guilt and shame, early cessation of breastfeeding, high control of food consumption of their children, and/or pressure them to eat, irregular mealtimes, unbalanced and monotonous meals, proneness to slimness, a critical attitude about the body shape of their daughters. Breastfeeding implies a critical period for the irruption or relapse of an ED due to the adjustment to the characteristic body shape changes during pregnancy. There is a particular relationship between a maternal ED and its occurrence in their children, and it can be considered a risk factor for its development.


RELATIVE BIOAVAILABILITY OF RISEDRONATE SODIUM ADMINISTERED IN SUPERABSORBENT COPOLYMER PARTICLES VERSUS ORAL SOLUTION TO NORMAL HEALTHY RABBITS.
In this study, sustained release superabsorbent copolymer particles have been prepared and analyzed to increase bioavailability of orally administered risedronate sodium. Formulations were prepared by free radical polymerization of combination of 2-hydroxyethyl methacrylate (HEMA), itaconic acid (IA), polyvinyl pyrrolidone (PVP) / chitosan (CTS) by using ethylene glycol dimethacrylate (EGDMA) as crosslinker, potassium persulfate as initiator, and N,N,N,N-tetramethylethylene diamine as activator. Formulations were successfully loaded with risedronate sodium. Formulations as gel particles encapsulated in hard gelatin were analyzed to estimate drug content. The maximum plasma drug concentration (C.) and its corresponding time (Tmax.), area under the curve and relative bioavailability (with reference to oral solution of drug administered) were calculated. It was found a marked increase in Tmax. with lower Cmax. that confirmed the multiparticulte system to deliver drug at controlled rate. The results of relative bioavailability after oral administration of these formulations indicated a remarkable increase in the bioavailability.


Regulation of basal promoter activity of the human thiamine pyrophosphate transporter SLC44A4 in human intestinal epithelial cells.
Microbiota of the large intestine synthesize considerable amount of vitamin B1 in the form of thiamine pyrophosphate (TPP). There is a specific high-affinity regulated carrier-mediated uptake system for TPP in human colonocytes (product of the SLC44A4 gene). The mechanisms of regulation of SLC44A4 gene expression are currently unknown. In this study, we characterized the SLC44A4 minimal promoter region and identified transcription factors important for basal promoter activity in colonic epithelial cells. The 5'-regulatory region of the SLC44A4 gene (1,022 bp) was cloned and showed promoter activity upon transient transfection into human colonic epithelial NCM460 cells. With the use of a series of 5'- and 3'-deletion luciferase reporter constructs, the minimal genomic region that required basal transcription of the SLC44A4 gene expression was mapped between nucleotides -178 and +88 (using the distal transcriptional start site as +1). Mutational analysis performed on putative cis-regulatory elements established the involvement of ETS/ELF3 [E26 transformation-specific sequence (ETS) proteins], cAMP-responsive element (CRE), and SP1/GC-box sequence motifs in basal SLC44A4 promoter activity. By means of EMSA, binding of ELF3 and CRE-binding protein-1 (CREB-1) transcription factors to the SLC44A4 minimal promoter was shown. Contribution of CREB into SLC44A4 promoter activity was confirmed using NCM460 cells overexpressing CREB. We also found high expression of ELF3 and CREB-1 in colonic (NCM460) compared with noncolonic (ARPE19) cells, suggesting their possible contribution to colon-specific pattern of SLC44A4 expression. This study represents the first characterization of the SLC44A4 promoter and reports the importance of both ELF3 and CREB-1 transcription factors in the maintenance of basal promoter activity in colonic epithelial cells.


Translation, cultural adaptation and validation of the Arabic version of the king's Parkinson's disease pain scale.
Pain in Parkinson's disease (PD) is a highly prevalent non-motor symptom occurring in this population. The King's PD Pain Scale (KPPS) was developed to assess pain in people with PD. This study aimed to provide a cross-cultural adaptation and translation of the KPPS into the Arabic language (A-KPPS), and to investigate the construct and convergent validity, internal consistency, and reliability of the translated scale. The English KPPS was translated into Arabic and back-translated into English by an independent translation team. The Arabic version was tested in 103 native Arabic speaking PD patients. We assessed construct validity, convergent validity, and test-retest reliability of the A-KPPS using factor analysis method, comparison with other valid and reliable measures, and using intra-class correlations, respectively. The A-KPPS had three main factors "somatic pain", "visceral and burning pain" and "orofacial pain", rather than the original four factors scale. The A-KPPS correlated with measures of disease motor severity, depression, anxiety, quality of life and pain (p < 0.05). Furthermore, the A-KPPS total score had high test-retest reliability (ICC = 0.9). The A-KPPS demonstrated moderate to good validity and reliability. The A-KPPS can facilitate the assessment and treatment of pain in Arabic-speaking people with PD worldwide.


An Artificial Intelligence-based Support Tool for Automation and Standardisation of Gleason Grading in Prostate Biopsies.
Gleason grading is the standard diagnostic method for prostate cancer and is essential for determining prognosis and treatment. The dearth of expert pathologists, the inter- and intraobserver variability, as well as the labour intensity of Gleason grading all necessitate the development of a user-friendly tool for robust standardisation. To develop an artificial intelligence (AI) algorithm, based on machine learning and convolutional neural networks, as a tool for improved standardisation in Gleason grading in prostate cancer biopsies. A total of 698 prostate biopsy sections from 174 patients were used for training. The training sections were annotated by two senior consultant pathologists. The final algorithm was tested on 37 biopsy sections from 21 patients, with digitised slide images from two different scanners. Correlation, sensitivity, and specificity parameters were calculated. The algorithm shows high accuracy in detecting cancer areas (sensitivity: 100%, specificity: 68%). Compared with the pathologists, the algorithm also performed well in detecting cancer areas (intraclass correlation coefficient [ICC]: 0.99) and assigning the Gleason patterns correctly: Gleason patterns 3 and 4 (ICC: 0.96 and 0.94, respectively), and to a lesser extent, Gleason pattern 5 (ICC: 0.82). Similar results were obtained using two different scanners. Our AI-based algorithm can reliably detect prostate cancer and quantify the Gleason patterns in core needle biopsies, with similar accuracy as pathologists. The results are reproducible on images from different scanners with a proven low level of intraobserver variability. We believe that this AI tool could be regarded as an efficient and interactive tool for pathologists. We developed a sensitive artificial intelligence tool for prostate biopsies, which detects and grades cancer with similar accuracy to pathologists. This tool holds promise to improve the diagnosis of prostate cancer.


Simultaneous quantification of cardiolipin, bis(monoacylglycero)phosphate and their precursors by hydrophilic interaction LC-MS/MS including correction of isotopic overlap.
Cardiolipin (CL) and bis(monoacylglycero)phosphate (BMP) are unique lipid structures with important biological roles for mitochondrial integrity and endolysosomal degradation, respectively. They are synthesized from common precursors, phosphatidylglycerol (PG) and phosphatidic acid (PA). Here we present a rapid method for the simultaneous quantification of BMP, CL, PG, and PA using hydrophilic interaction chromatography coupled with electrospray ionization tandem mass spectrometry (HILIC-MS/MS). HILIC provides coelution of lipid species and their internal standards required for accurate quantification. Coelution leads to isotope overlap of lipid species which was successfully corrected. This assay was validated in mouse heart tissue and primary human skin fibroblasts. It shows reproducibility and limits of detection sufficient for biomarker studies contributing to basic research on BMP and CL metabolism.


Epigenetic focus on angioimmunoblastic T-cell lymphoma: pathogenesis and treatment.
Angioimmunoblastic T-cell lymphoma (AITL) is a frequent peripheral T-cell lymphoma affecting elderly patients with a poor outcome when treated with conventional chemotherapy. Molecular studies revealed a homogenous mutational landscape gathering anomalies in genes regulating the DNA methylation and hydroxymethylation and anomalies in T-cell signalling. Recent studies indicate that AITL emerges from a TET2 and/or DNMT3A mutated clonal haematopoiesis. This clonal haematopoiesis bearing mutations altering DNA hydroxymethylation can explain the observed coexistence of AITL with myeloid neoplasms. In addition, AITL development requires AITL-specific mutations, such as the RHOAG17V mutations. Combination of TET2 and RHOAG17V alterations results in the development of AITL-like disease in mouse models. The impact of the presence of these mutations on patient outcome seems limited and new biological factor predicting treatment response and survival remains to be determined. At the therapeutic level, therapies targeting epigenetic changes, such as histone deacetylase inhibitors and the hypomethylating 5-azacytidine agent, could have efficacy in this disease and gave promising results. Recent progress in mouse model development should allow development of new treatments. Epigenetic changes are frequent in AITL and could be a promising target.


SUMO-1 marks the nuclear inclusions in familial neuronal intranuclear inclusion disease.
Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder characterized by progressive ataxia and neuronal nuclear inclusions (NIs), similar to the inclusions found in expanded CAG repeat diseases. NIID may be familial or sporadic. The cause of familial NIID is poorly understood, as no CAG expansion has been detected. We examined three cases, from two unrelated families, who had autosomal dominant NIID but normal CAG repeats in genes involved in polyglutamine neurodegenerative diseases. We found that NIs in all three cases were intensely immunopositive for SUMO-1, a protein which covalently conjugates to other proteins and targets them to the nuclear regions (nuclear bodies) responsible for nuclear proteasomal degradation. Electron microscopy demonstrated that SUMO-1 was located on the 10-nm fibrils of NIs. In cultured PC12 cells, we found that inhibition of proteasome function by specific inhibitors resulted in the appearance of SUMO-1-immunopositive nuclear inclusions. Our study suggests that recruitment of SUMO-1 modified proteins into insoluble nuclear inclusions and proteasomal dysfunction may be involved in the pathogenesis of NIs in familial NIID cases.


Metabolic complications associated with antiretroviral therapy in HIV-infected and HIV-exposed uninfected paediatric patients.
HIV-infection has become a chronic disease in paediatric patients with the potential for long-term survival and exposure to antiretroviral (ARV) therapies for 2 decades longer than HIV-infected adults. On the other hand, the administration of ARV to HIV-infected pregnant women has greatly increased both treatment of HIV infection and prevention of perinatal HIV transmission. Therefore, researches aiming to evaluate the safety of ARV therapies in HIV-infected children as well as in HIV-uninfected infants born to HIV-infected mothers are emerging as a new challenge and urgent priority. The purpose of this review is to describe some of the more concerning metabolic complications associated with ARV in paediatric population: hyperlactataemia (HLA) syndromes, body shape abnormalities, disorders of glucose homeostasis and dyslipidaemia in HIV-infected children and adolescents. Frequency, risk factors, clinical findings, prevention and intervention strategies of the previously described abnormalities are discussed in depth. This review covers our current understanding of HLA syndromes in ARV-exposed uninfected infants born to HIV-infected mothers. Prevention of these metabolic complications should assume prominence and future researches should address several of the existing treatment gaps.


Conical Intersections in Solution with Polarizable Embedding: Integral-Exact Direct Reaction Field.
A common strategy to exploring the properties and reactivity of complex systems is to use quantum mechanics/molecular mechanics (QM/MM) embedding, wherein a QM region is defined and treated with electronic structure theory, and the remainder of the system is treated with a force field. Important to the description of electronic excited states, especially those of charge-transfer character, is the treatment of the coupling between the QM and MM subsystems. The state of the art is to use a polarizable force field for the MM region and mutually couple the QM wavefunction and MM induced dipoles, in addition to the usual electrostatic embedding, yielding a polarizable embedding (QM/MM-Pol) approach. However, we showed previously that current popular QM/MM-Pol approaches exhibit issues of root flipping and/or incorrect descriptions of electronic crossings in multistate calculations [J. Chem. Theory Comput. 14, 2137 (2018)]. Here, we demonstrate a solution to these problems with an integral-exact reformulation of the direct reaction field approach of Thole and Van Duijnen (QM/MM-IEDRF). The resulting embedding potential includes one- and two-electron operators and many-body dipole-induced dipole interactions and thus includes a natural description of the screening of electron-electron interactions by the MM induced dipoles. Pauli repulsion from the environment is mimicked by effective core potentials on the MM atoms. Inherent to the DRF approach is the assumption that MM dipoles respond instantaneously to the positions of the QM electrons; therefore, dispersion interactions are captured approximately. All electronic states are eigenfunctions of the same Hamiltonian, while the polarization induced in the environment and the associated energetic stabilization are unique to each state. This allows for a consistent definition of transition properties and state crossings. We demonstrate QM/MM-IEDRF by exploring the influence of a (polarizable) inert xenon matrix environment on the conical intersection underlying the photoisomerization of ethylene.


[Characteristics of the cellular cooperation in the connective tissue base of the gingiva in periodontitis].
The features of clinical course of chronic generalized periodontitis were studied from the viewpoint of analysis of cellular cooperative connective tissue basis. This allowed to single out 2 groups of patients. In the 1st group, a potent lymphoid (seldom lymphoplasmocytic) infiltration was detected within the gingival connective tissue basis, and sIgA preserved or even increased in the mixed saliva. In the 2nd group, the oral cavity physiological neutralization of antigenic substances was impaired and neutrophilic leucocytes were dominating in the gingival connective tissue framework with considerably increased levels of serum IgG. The gingival tissue basophils population was investigated in these groups of patients and their variants given the histochemical characterization. Prognostic criteria of treatment effectiveness are derived from studies of biopsied gingival tissues.


Childhood visceral leishmaniasis.
Visceral leishmaniasis (VL) is caused by the protozoan parasite Leishmania donovani and transmitted by the bite of infected sandfly Phlebotomus argentipes. Nearly half of the VL cases occur in children (childhood or paediatric VL). The clinical manifestations of childhood VL are more or less same as in the adults. Prolonged fever with anorexia and loss of appetite are the major presenting features. Marked enlargement of the spleen and liver (spleen larger than liver) with moderate to severe anaemia and changes in hair take place. Bacterial infection is a common coinfection and intestinal parasitic infestations are very common in children with VL. Liver function tests, blood, urine and stool may show abnormalities. Confirmation of diagnosis is made by demonstration of parasite by microscopic examination and culture of materials obtained by bone marrow aspiration or splenic puncture. Sodium antimony gluconate (stibogluconate) has been the drug of choice for over past 50 yr. Pentamidine isothionate, though effective is relatively toxic. Amphotericin B is the most effective drug for the treatment of VL. Miltefosine is the first-ever oral drug, is highly effective. Post kala-azar dermal leishmaniasis (PKDL) in children poses a therapeutic challenge. In the absence of an ideal vaccine for VL, control measures would essentially include prevention of transmission through vector control and community awareness.


Repeatability of Quantitative Autofluorescence Imaging in a Multicenter Study Involving Patients With Recessive Stargardt Disease 1.
This study assesses the repeatability of quantitative autofluorescence (qAF) in a multicenter setting and evaluates qAF as the end point for clinical trials in recessive Stargardt disease 1 (STGD1). A total of 102 patients with STGD1 underwent qAF imaging as part of the Stargardt Remofuscin Treatment Trial (STARTT; EudraCT No. 2018-001496-20). For 166 eyes, we obtained qAF imaging at 2 visits, with 2 recordings per visit. The qAF8 values were independently determined by the study site and a central reading center. Intra- and inter-visit reproducibility, as well as interobserver (study site versus reading center) reproducibility were obtained using intraclass correlation (ICC), one-sample t-test, and Bland-Altman coefficient of repeatability. The qAF repeatability was ± 26.1% for intra-visit, ± 40.5% for inter-visit, and ± 20.2% for the interobserver reproducibility measures. Intra-visit repeatability was good to excellent for all sites (ICC of 0.88-0.96). Variability between visits was higher with an overall ICC of 0.76 (0.69-0.81). We observed no significant difference in qAF values across sites between visits (7.06 ± 93.33, P = 0.238). Real-life test-retest variability of qAF is higher in this set of data than previously reported in single center settings. With improved operator training and by selecting the better of two recordings for evaluation, qAF serves as a useful method for assessing changes in autofluorescence signal. The qAF can be adopted as a clinical trial end point, but steps to counterbalance variability should be considered.


Generation of induced pluripotent stem cell lines from helper and cytotoxic T cells of healthy individuals.
T lymphocytes are the most abundant mononuclear blood cells and can serve as a source for generating induced pluripotent stem cells (iPSCs) for disease modeling or drug development. Here, we report the derivation of two iPSC lines from CD4+ helper T cells and CD8+ cytolytic T cells, respectively. The reprogramming was performed using Sendai virus encoding Klf-4, c-Myc, Oct-4 and Sox-2. Both iPSC lines displayed typical embryonic stem cell-like morphology and normal karyotype. Pluripotency was confirmed using immunocytochemistry methods and teratoma formation assay.


Effects of different management regimes on microbial biodiversity in vineyard soils.
An active and diverse soil biota is important for maintaining crop productivity and quality, and preservation of these traits is a major goal of sustainable farming. This study aimed at unravelling the impact of different management practices on soil fungal and bacterial biodiversity in vineyards as a model for permanent crops. Species diversity was assessed using an amplicon sequencing approach in a long-term field experiment in the Rheingau wine region of Germany where integrated, organic and biodynamic management practices had been in place for 10 years. Fungal community composition under integrated management differed significantly from organic and biodynamic management, whereas fungal species richness remained unaffected. Soil under integrated management had a significantly reduced bacterial species richness compared to organic, but community composition was similar to organically and biodynamically managed soils. Highest fungal richness was obtained under cover crop between rows in topsoil, arising from cover cropping and organic carbon supply.


Ligand coordination and spin crossover in a nickel porphyrin anchored to mesoporous TiO2 thin films.
The coordination and spin equilibrium of a Ni(II) meso-tetra(4-carboxyphenyl)porphyrin compound, NiP, was quantified both in fluid solution and when anchored to mesoporous, nanocrystalline TiO2 thin films. This comparison provides insights into the relative rate constants for excited-state injection and ligand field population. In the presence of pyridine, the spectroscopic data were consistent with the presence of equilibrium concentrations of a 4-coordinate low-spin S = 0 ((1)A1g) Ni(II) compound and a high-spin S = 1 ((3)B1g) 6-coordinate compound. Temperature-dependent equilibrium constants were consistently smaller for the surface-anchored NiP/TiO2, as were the absolute values of ΔH and ΔS. In the presence of diethylamine (DEA), the ground-state 6-coordinate compound was absent, but evidence for it was present after pulsed light excitation of NiP. Arrhenius analysis of data, measured from -40 to -10 °C, revealed activation energies for ligand dissociation that were the same for the compound in fluid solution and anchored to TiO2, Ea = 6.6 kcal/mol, within experimental error. At higher temperatures, a significantly smaller activation energy of 3.5 kcal/mol was found for NiP(DEA)2/TiO2. A model is proposed wherein the TiO2 surface sterically hinders ligand coordination to NiP. The lack of excited-state electron transfer from Ni(II)P*/TiO2 indicates that internal conversion to ligand field states was at least 10 times greater than that of excited-state injection into TiO2.


Demethylmenaquinol is a substrate of Escherichia coli nitrate reductase A (NarGHI) and forms a stable semiquinone intermediate at the NarGHI quinol oxidation site.
Quinones are essential building blocks of respiration, a universal process dedicated to efficient harvesting of environmental energy and its conversion into a transmembrane chemiosmotic potential. Quinones differentiate mostly by their midpoint redox potential. As such, γ-proteobacteria such as Escherichia coli are characterized by the presence of demethylmenaquinone (DMK) with an intermediate redox potential between low-potential (menaquinone) and high-potential (ubiquinone) quinones. In this study, we show that demethylmenaquinol (DMKH2) is a good substrate for nitrate reductase A (NarGHI) in nitrate respiration in E. coli. Kinetic studies performed with quinol analogs on NarGHI show that removal of the methyl group on the naphthoquinol ring impacts modestly the catalytic constant but not the KM. EPR-monitored redox titrations of NarGHI-enriched membrane vesicles reveal that endogeneous demethylmenasemiquinone (DMSK) intermediates are stabilized in the enzyme. The measured midpoint potential of the DMK/DMKH2 redox couple in NarGHI (E'm,7.5 (DMK/DMKH2) ~-70mV) is significantly lower than that previously measured for unbound species. High resolution pulsed EPR experiments demonstrate that DMSK are formed within the NarGHI quinol oxidation site. Overall, our results provide the first characterization of a protein-bound DMSK and allows for comparison for distinct use of three quinones at a single Q-site in NarGHI.


Increase in CD4 cell counts between 2 and 3.5 years after initiation of antiretroviral therapy and determinants of CD4 progression in India.
Estimation of CD4 cell count remains the primary monitoring tool in assessing efficacy or failure of Anti Retroviral Therapy (ART) under national program conditions in India. To study the average trajectory of CD4 cell count after two years of initiation of potent ART and to find the determinants of CD4 progression over time. A prospective cohort study under program conditions. Materials and Methods : Adult ART naïve patients, receiving drug regimens consisting of two NRTIs and one NNRTI were studied for CD4 progression. Laboratory monitoring included the baseline and follow-up CD4 cell count, hemoglobin level and absolute lymphocyte count estimation. The change in CD4 cell count, hemoglobin and bodyweight was calculated from the baseline to the latest follow up measurements. Statistical Analysis : Survival curve using Life table methods was plotted. Comparison between survival curves was done using Tarone-Ware statistics. Generalized estimating equation with exchangeable correlation structure was done to find the risk factors for CD4 progression. Results : Among 7,934 HIV positive patients in the ART program, one-year cohort of 714 adult patients who had completed two consecutive follow-up CD4 values were assessed. Those with baseline CD4 < 100 had cumulative probability of survival 85%, 82%, 82% and 82% at 12, 24, 36 and 42 months respectively. Those who had baseline CD4 count between 100-199 had cumulative probability of survival 96%, 93%, 92% and 90% at 12, 24, 36 and 42 months respectively (P < 001). Lower the CD4 count ( 100) lower the hemoglobin values. Conclusions : CD4 progression continues two years after ART in patients who had base level > 100 cells. Early initiation of ART is necessary before CD4 crashing to < 100 cells for increasing the survival function.


Full-range public health leadership, part 1: quantitative analysis.
Workforce and leadership development are central to the future of public health. However, public health has been slow to translate and apply leadership models from other professions and to incorporate local perspectives in understanding public health leadership. This study utilized the full-range leadership model in order to examine public health leadership. Specifically, it sought to measure leadership styles among local health department directors and to understand the context of leadership in local health departments. Leadership styles among local health department directors (n = 13) were examined using survey methodology. Quantitative analysis methods included descriptive statistics, boxplots, and Pearson bivariate correlations using SPSS v18.0. Self-reported leadership styles were highly correlated to leadership outcomes at the organizational level. However, they were not related to county health rankings. Results suggest the preeminence of leader behaviors and providing individual consideration to staff as compared to idealized attributes of leaders, intellectual stimulation, or inspirational motivation. Holistic leadership assessment instruments such as the multifactor leadership questionnaire can be useful in assessing public health leaders' approaches and outcomes. Comprehensive, 360-degree reviews may be especially helpful. Further research is needed to examine the effectiveness of public health leadership development models, as well as the extent that public health leadership impacts public health outcomes.


Echocardiography improves detection of rejection after heterotopic mouse cardiac transplantation.
Current assessments of cardiac rejection in murine transplant models rely on subjective estimates of the force of the palpable heart beat that have limited sensitivity and precision. We used 2-dimensional echocardiography to evaluate changes in left ventricular posterior wall thickness (PWT) in a heterotopic cardiac mouse transplant model of rejection. Nine allografts and 6 isografts were imaged daily for 6 days and harvested. Thirteen allografts were imaged daily and harvested at day 3. Intraobserver variability on PWT was 0.003 +/- 0.09 mm, interobserver variability 0.09 +/- 0.11 mm. Allograft PWT increased after transplantation (0.74 +/- 0.02 mm to 1.28 +/- 0.05 mm at day 5, P <.0001). For isografts, PWT remained constant (0.73 +/- 0.03 mm to 0.85 +/- 0.01 mm) after an initial increase at day 1. Palpation failed to identify rejection at day 3 whereas PWT was already increased (1.15 +/- 0.02 mm in the allografts at day 3 vs 0.85 +/- 0.02 mm in the isografts, P <.0001). There was a relation between histologic score and PWT (P <.0001). Two-dimensional echocardiography allows the noninvasive detection and follow-up of cardiac rejection after transplantation. It eliminates the subjectivity of palpation and provides quantitative and reliable indices of rejection.


Context-dependent regulation of the GLI code in cancer by HEDGEHOG and non-HEDGEHOG signals.
A surprisingly large and unrelated number of human tumors depend on sustained HEDGEHOG-GLI (HH-GLI) signaling for growth. This includes cancers of the skin, brain, colon, lungs, prostate, blood and pancreas among others. The basis of such commonality is not obvious. HH-GLI signaling has also been shown to be active in and required for cancer stem cell survival and expansion in different cancer types, and its activity is essential not only for tumor growth but also for recurrence and metastatic growth, two key medical problems. Here we review recent data on the role of HH-GLI signaling in cancer focusing on the role of the GLI code, the regulated combinatorial and cooperative function of repressive and activating forms of all Gli transcription factors, as a signaling nexus that integrates not only HH signals but also those of multiple tumor suppressors and oncogenes. Recent data support the view that the context-dependent regulation of the GLI code by oncogenes and tumor suppressors constitutes a basis for the widespread involvement of GLI1 in human cancers, representing a perversion of its normal role in the control of stem cell lineages during normal development and homeostasis.


High spatial resolution phase-sensitive optical time domain reflectometer with a frequency-swept pulse.
A high spatial resolution phase-sensitive optical time domain reflectometer (ϕ-OTDR) with an optical frequency-swept pulse (FSP) is proposed, and the experimental results are presented in the Letter. The FSP ϕ-OTDR uses optical pulses with linear frequency modulation with higher pulse energy for longer sensing fiber and uses matched filter in the receiver to compress the processed pulse width. Thus, the contradiction between spatial resolution and the working distance in ordinary ϕ-OTDR is relaxed. A spatial resolution of 30 cm, a sensing distance of 19.8 km, and a signal-to-noise ratio of 10 dB for vibration sensing were obtained experimentally. To our best of our knowledge, this is the first time that a sub-meter spatial resolution over such a long sensing range has been reported in ϕ-OTDR sensors.


Association between sleep quality and quality of life among students: a cross sectional study.
Background Lack of sleep and on going sleep disorder can affect family health and interpersonal relationships. Objective The aim of study was to investigate the association between sleep quality and the probable determinants of quality of life among students of a public health faculty at Shahid Beheshti University of Medical Sciences (SBMU) in the 2015 academic year. Methods The data from a cross-sectional study of 275 students that randomly stratified sampling between different classes of college students of a public health faculty of Shahid Beheshti University of Medical Sciences were used in this study. The data were collected using a structured questionnaire consisted of modules on socio-demographic characteristics, the Petersburg Standardized Sleep Quality Questionnaire(PSQL) and the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF). Data analysis was done with descriptive and logistic regression. All analyses were carried out using SPSS software V.19. Results A total of 275 students participated in this study. The mean age ± standard deviation (SD) was 22.1 ± 3.6 years. In the univariable model, students that were living in their own homes had the odds of 2.18 times more than the others to have a higher quality of life level [95% confidence interval (CI): 1.07-4.45]. Moreover, sleep disorder was negatively associated with the quality of life [odds ratio (OR) = 0.23; 95% CI: 0.12-0.46]. Conclusion These results will help university administrators and policy makers to identify factors associated with poor sleep and provide approaches to enhance sleep hygiene and relevant knowledge in university students. Living in a dormitoy while also suffering from sleep problems could significantly reduce the quality of life.


Impact of the Russian-Ukrainian Conflict on Global Food Crops.
The Russian-Ukrainian conflict has been proven to cause significant losses of life and goods on both sides. This may have potentially impacted the agricultural sector. This study examines the impact of the conflict between Russia and Ukraine on the global food situation. We performed a descriptive analysis and literature review to answer this objective. Russia and Ukraine play essential roles in world food production and trade. However, the war has disrupted food production in Ukraine. Estimated Ukrainian wheat, soybean, and maize production in 2022-2023 fell precipitously. On the other hand, Russian production of these three food products shows positive growth during the same period. Furthermore, the global supply chain and food trade are hampered, causing an increase in the world's food prices. From March to May 2022, the average global price of wheat, soybeans, and maize increased dramatically compared to during and before the COVID-19 pandemic. Finally, this poses a danger to global food security, particularly for low-income countries that depend heavily on food imports from both countries. Therefore, all countries must be prepared for the possibility that the Sustainable Development Goals cannot be achieved.


Effect of Crack Defects on Magnetostriction and Magnetic Moment Evolution of Iron Thin Films.
Molecular dynamics simulations of body-centered cubic (bcc) iron thin films with crack defects were carried out by adopting methods of EAM (Embedded Atom Method) potential, spin/exchange potential and spin/neel potential. In this article, the effects of the variation of distance between two crack defects and their directions on the magnetostrictive properties of the thin films are studied, and the corresponding microscopic mechanism is also analyzed. The results show that the defects affect the atomic magnetic moment nearby, and the magnetostrictive properties of thin iron films vary with the direction and spacing of the crack defects. If the defect spacing is constant, the iron model with crack perpendicular to the magnetization direction has stronger magnetostriction than that of parallel to the magnetization direction. The variation of the defect spacing has a great influence on the magnetostrictive properties of the iron model with crack direction parallel to magnetization direction, but it has a small effect on another perpendicular situation. The atoms between the defects may move, but if the defect spacing increases to a certain value, then none of the atoms will move.


Lack of Neurosteroid Selectivity at δ vs. γ2-Containing GABAA Receptors in Dentate Granule Neurons.
GABAA receptors mediate a large fraction of inhibitory neurotransmission in the central nervous system. Two major classes of GABAA receptors are γ2-containing receptors and δ-containing receptors, which are largely located synaptically and extrasynaptically, respectively. Neuroactive steroids such as allopregnanolone (3α5αP) and allotetrahydrodeoxycorticosterone (THDOC) are hypothesized to selectively affect δ-containing receptors over γ2-containing receptors. However, the selectivity of neurosteroids on GABAA receptor classes is controversial. In this study, we re-examined this issue using mice with picrotoxin resistance associated with either the δ or γ2 subunit. Our results show that 3α5αP potentiated phasic inhibition of GABAA receptors, and this is mainly through γ2-containing receptors. 3α5αP, with or without exogenous GABA, potentiated tonic inhibition through GABAA receptors. Surprisingly, potentiation arose from both γ2- and δ-containing receptors, even when a δ selective agonist THIP was used to activate current. Although ethanol has been proposed to act through neurosteroids and to act selectively at δ receptors, we found no evidence for ethanol potentiation of GABAA receptor function at 50 mM under our experimental conditions. Finally, we found that the actions of pentobarbital exhibited very similar effects on tonic current as 3α5αP, emphasizing the broad spectrum nature of neurosteroid potentiation. Overall, using chemogenetic analysis, our evidence suggests that in a cell population enriched for δ-containing receptors, neurosteroids act through both δ-containing and non-δ-containing receptors.


Alpha-synuclein delays mitophagy and targeting Miro rescues neuron loss in Parkinson's models.
Alpha-synuclein is a component of Lewy bodies, the pathological hallmark of Parkinson's disease (PD), and is also mutated in familial PD. Here, by extensively analyzing PD patient brains and neurons, and fly models, we show that alpha-synuclein accumulation results in upregulation of Miro protein levels. Miro is a motor/adaptor on the outer mitochondrial membrane that mediates mitochondrial motility, and is removed from damaged mitochondria to facilitate mitochondrial clearance via mitophagy. PD patient neurons abnormally accumulate Miro on the mitochondrial surface leading to delayed mitophagy. Partial reduction of Miro rescues mitophagy phenotypes and neurodegeneration in human neurons and flies. Upregulation of Miro by alpha-synuclein requires an interaction via the N-terminus of alpha-synuclein. Our results highlight the importance of mitochondria-associated alpha-synuclein in human disease, and present Miro as a novel therapeutic target.


Przewalski's Horse (Equus ferus przewalskii) Re-introduction in the Great Gobi B Strictly Protected Area: from Species to Ecosystem Conservation.
The Przewalski's horse (Equus ferus przewalskii Poljakov, 1881), or "Takhi" in Mongolian, became extinct in the wild by the mid 1960's. The last recorded sightings of Przewalski's horses occurred in the Dzungarian Gobi desert in SW Mongolia, today's Great Gobi B Strictly Protected Area (SPA). A re-introduction program was initiated in 1992 and the first group of captive-born Przewalski's horses was airlifted to the SPA. Given the logistical challenges associated with such a venture, the initial project focus has been on transport logistics and the well-being of the re-introduced horses. Today, conservation efforts are spread over the entire protected area. Present day efforts include other mammals, vegetation and the local people. Due to its important symbolic value in Mongolian culture, the Przewalski's horse became an important flagship species for the protected area's conservation and management.


5-HT(3) receptor antagonists and anxiety; a preclinical and clinical review.
The present paper reviews the evidence for anxiolytic activity of 5-HT(3) receptor antagonists in animal models of anxiety and in clinical trials in humans. Compared to the established anxiolytics (benzodiazepine receptor agonists and, to a lesser extent, 5-HT(1A) receptor agonists) 5-HT(3) receptor antagonists display a different anxiolytic profile. They are anxiolytic in a limited number of animal anxiety models. If active, they often are very potent and display bell-shaped dose response curves, whereas the ratio between therapeutic activity and side effects appears remarkably large. 5-HT(3) receptor antagonists remain active after chronic dosing and no indications for tolerance, dependence or rebound effects were found, which seems to make these drugs an attractive alternative to the benzodiazepines. However, the large body of animal data indicating a complete lack of psychotropic activity of 5-HT(3) receptor antagonists weakens the prediction of anxiolytic activity in these drugs. Human data are also controversial; some investigators have reported positive effects in anxiety disorders (panic disorder, GAD), others did not. It can be concluded that 5-HT(3) receptor antagonists do not represent a breakthrough in the treatment of various anxiety disorders, as initially suggested.


Biopsy assessment of drug efficacy in the gastrointestinal tract.
When using biopsy pathology in clinical pharmacology to assess drug efficacy in the gastrointestinal tract, a number of questions must be answered: Is the biopsy necessary or more effective than macroscopic views by endoscopy? Can we extract maximal information from the specimen? Are there surrogate serum or other markers that give an overall measure of disease and/or improvement? Indeed, clinicopathological correlation is of paramount importance. If biopsy is to be used, it is important to utilize appropriate scoring systems. Many grading systems use continuous spectra, which are ordinal categorical variables and therefore a grading system of assigned 'numbers' which cannot be used in processes that require continuous variables such as linear regression. The use of grading vs a 'true' score with real numbers must be carefully considered, the site and number of biopsies must be precisely chosen and interobserver reproducibility of results evaluated before undertaking drug trials. Immunocytochemistry and in situ hybridization, however, can provide quantifiable molecular information related to mechanisms of drug action. The biopsy is of significant value as it is a true in vivo assessment if the above caveats are taken into account. However, further work is needed to determine sound histological criteria to assess the efficacy of drugs for use in gastrointestinal disease.


A new sesquiterpene, prosoterpene, from Prosopis africana (Guill. & Perr.) Taub.
A new sesquiterpene (Prosoterpene, 1) and eleven reported compounds (2-12) of several classes, such as flavonoids, alkaloids, phenolic acids, and long-chain alcohols, were isolated from the BuOH extract of Prosopis africana (Guill. & Perr.) Taub. Compounds 2-10 were reported for the first time from this plant. Isomers 11 and 12 were separated for the first time. Extensive spectroscopic techniques and literature comparisons were used to characterise their structures. Furthermore, compounds 3, 5-8, and 10-12 were performed for anti-glycation and cytotoxicity activities. Compound 3 (quercetin-3-O-α-L-rhamnoside) exhibited moderate anti-glycation activity. All tested compounds were non-cytotoxic against MCF-7 (breast cancer), NCI-H460 (lung cancer), Hela (cervical cancer), and BJ (normal human fibroblast) cell lines.


Prosthodontic Rehabilitation with Fixed Monolithic Translucent Zirconia Restorations: A Case History Report.
Recent attempts in the development of novel zirconia ceramics aim at improving its optical characteristics by increasing the yttria content to up to 5 mol% so that these ceramics can be used for the fabrication of stable and esthetic monolithic restorations. However, clinical evidence on the outcomes of such restorations is sparse. In this case report, monolithic inlays, partial crowns, tooth- and implant-supported single crowns, and fixed dental prostheses were fabricated out of a zirconia ceramic doped with 5 mol% yttria. The restorations in the present case history report showed a satisfying esthetic outcome and are in situ as inserted 18 months after insertion.


Infective larvae of Haemonchus contortus found from the base to the top of the grass sward.
The resistance of gastrointestinal nematodes (GIN) of sheep to anthelmintic treatment has motivated researchers to seek alternatives to reduce the use of these drugs in sheep farming and decontaminate pastureland based on knowledge about the survival dynamics of larvae. The aim of this work was to evaluate the migration of the infective larvae (L3) of Haemonchus contortus at different times of the day, strata, and sward heights, with and without shade after the deposition of contaminated sheep feces. The grass species used here was Cynodon dactylon cv. Tifton 85 in four treatments: low sward height shade; low sward height sunshine; high sward height shade; and high sward height sunshine. The number of L3 recovered from the pasture at different times of the day did not differ. The highest number of L3 recovered was in shade. The number of L3 at different times and strata occurred uniformly, confirming that L3 remain in the same place after migrating from dung at the hottest times of the day. Infective larvae of H. contortus were able to migrate across all the strata regardless of the time of day in the summer season in humid subtropical climate.


Thermal transport through fishbone silicon nanoribbons: unraveling the role of Sharvin resistance.
Heat conduction has been shown to be greatly suppressed in Si nanomeshes, which has attracted extensive attention for potential thermoelectric applications, yet the precise suppression mechanism remains to be fully understood. Attempting to further disclose the underlying mechanisms, we report on the thermal conductivity of the building block for nanomeshes, i.e., Si nanoribbons with fins attached to the two opposite sides. By expanding only the fin width while keeping both the period length and the backbone size constant, we observed an unexpected non-monotonic trend of the effective thermal conductivity normalized with the backbone cross-section. Further analysis showed that the corrected thermal conductivity extracted with appropriate consideration of the geometrical effect on diffusion followed a monotonically decreasing trend, reaching a maximum thermal conductivity reduction of 18% at 300 K for a ribbon with the maximum explored fin width of 430 nm, as compared to that of the straight ribbon of 66 nm backbone width. We attribute the thermal conductivity reduction to the thermal constriction resistance induced by the cross-section reduction between the fin and backbone sections. For ribbons with a larger fin width, the effective phonon mean free path is longer for phonons arriving at the constriction, which boosts the ballistic constriction resistance, i.e., Sharvin resistance, and leads to a lower thermal conductivity.


Eco-Friendly Incorporation of Crumb Rubber and Waste Bagasse Ash in Bituminous Concrete Mix.
The consumption of waste materials in the construction sector is a sustainable approach that helps in reducing the environmental pollution and decreases the construction cost. The present research work emphasizes the mechanical properties of bituminous concrete mix prepared with crumb rubber (CR) and waste sugarcane bagasse ash (SCBA). For the preparation of bituminous concrete mix specimens with CR and SCBA, the effective bitumen content was determined using the Marshall Mix design method. A total of 15 bituminous concrete mix specimens with 4%, 4.5%, 5%, 5.5% and 6% of bitumen content were prepared, and the effective bitumen content turned out to be 4.7%. The effect of five different CR samples of 2%, 4%, 6%, 8% and 10% by weight of total mix and SCBA samples of 25%, 50%, 75% and 100% by weight of filler were investigated on the performance of bituminous concrete. A total of 180 samples with different percentages of CR and SCBA were tested for indirect tensile strength (ITS) and Marshall Stability, and the results were compared with conventional bituminous concrete mix. It was observed that the stability values rose with an increase in CR percentage up to 6%, while the flow values rose as the percentage of SCBA increased in the mix. Maximum ITS results were observed at 4% CR and 25% SCBA replacement levels. However, a decrease in stability and ITS result was observed as the percentages of CR and SCBA increased beyond 4% and 25%, respectively. We concluded that the optimum CR and SCBA content of 4% and 25%, respectively, can be effectively used as a sustainable alternative in bituminous concrete mix.


Measurement of evoked diaphragm twitch strength during anaesthesia. Adaptation and evaluation of an existing technique.
The technique of recording the mechanical response of the diaphragm after the transcutaneous stimulation of the phrenic nerve, during anaesthesia and surgery, is described in patients undergoing non-abdominal surgery. The pressure difference generated across the diaphragm after phrenic nerve stimulation was derived from the simultaneous recording of gastric and oesophageal pressures with air-filled balloon catheter systems. This was recorded as the diaphragm "twitch" in a manner similar to that of peripheral muscles. Special problems encountered in the use and the validation of the technique in the anaesthetized patient are considered.


Biologic studies of chimeras of highly and moderately virulent molecular clones of simian immunodeficiency virus SIVsmPBj suggest a critical role for envelope in acute AIDS virus pathogenesis.
Previous studies identified three molecular clones of the acutely pathogenic SIVsmPBj strain that varied in terms of relative in vivo pathogenicity. One clone, SIVsmPBj6.6, reproducibly induced a rapidly fatal disease in pigtailed macaques. In contrast, a highly related clone (SIVsmPBj6.9) was only minimally pathogenic in macaques. PBj6.6 and PBj6.9 shared a tyrosine substitution at position 17 in the Nef protein that is a major determinant of virulence but differed at one residue in Vpx (C89R), three residues within the envelope (D119G, R871G, G872R), and a single residue in Nef (F252L). SIVsmPBj6.9 was less efficient in inducing proliferation of resting macaque peripheral blood mononuclear cells in vitro than SIVsmPBj6.6 and exhibited a marked reduction in infectivity relative to SIVsmPBj6.6. Chimeric viruses for each of these variable residues were constructed, and their biologic properties were compared to those of the parental strains. Differences in Vpx and Nef did not alter the basic biologic phenotype of the chimeras. However, the D119G substitution in the envelope of SIVsmPBj6.9 was associated with a marked reduction in the infectivity of this virus relative to SIVsmPBj6.6. An associated processing defect in gp160 of SIVsmPBj6.9 and chimeras expressing the D119G substitution suggests that a reduction in virion envelope incorporation is the mechanistic basis for reduced virion infectivity. In vivo studies revealed that substitution of the PBj6.9 amino acid into PBj6.6 (D119) abrogated the pathogenicity of this previously pathogenic virus. Introduction of the PBj6.9 G119, however, did not confer full virulence to the parental PBj6.9 virus, implicating one or all of the other four substitutions in the virulence of SIVsmPBj6.6.


Evidences of the inflammasome pathway in chronic prostatitis and chronic pelvic pain syndrome in an animal model.
The mechanism of non-bacterial chronic prostatitis (CP/CPPS) has long been investigated but remains unclear. Under the hypothesis that abnormal response of innate immunity may be a cause of CP/CPPS, this study evaluated inflammasome, as part of innate immunity, and its effects on persist inflammation and CP/CPPS. Carrageenan was used to induce CP/CPPS in a rat animal model. After confirming tactile hyper-algesia in the rats, their local prostate inflammation status, and inflammasome expression were determined. The amount of inflammasome and its downstream protein was checked, along with prostate localization. Chlorogenic acid (CHA), an active ingredient of Chinese herbal remedy for CP/CPPS treatment, was used as treatment. The rats had CP/CPPS once scrotal static tactile allodynia developed and CHA treatment relieved the scrotal hypersensitivity. Downstream inflammasome proteins like IL-1β and caspase 1 increased within the prostate and decreased with CHA treatment. Inflammasome, NALP1 but not NALP3, was significantly increased in the prostate glandular endothelial cells. Treatment with CHA also changed the distribution pattern of NALP1 in the prostate. There is a close relationship between activation of inflammasome and patho-physiologic changes of CP/CPSS in rats. Increased inflammasome may be a possible mechanism of CP/CPPS and clinically active regimen may inhibit the inflammasome-related pathway. This provides a new therapeutic rationale and approach for CP/CPPS treatment.


Semmes-weinstein monofilaments: influence of temperature, humidity, and age.
To determine whether the buckling force of Semmes-Weinstein monofilaments is influenced by changes in temperature, humidity, and aging. We tested 16 Semmes-Weinstein monofilaments from North Coast Medical, varying in age from new to 12 years old. From each kit, we used the 2.83/0.07 g, 3.61/0.4 g, 4.31/2g, and 4.56/4 g filaments. Four observers tested the filaments under temperature/humidity conditions of 26°C/33%, 26°C/80%, 37°C/33%, and 37°C/80%. Air temperature and humidity both significantly influence buckling force. At 26°C/33% the buckling force varies by an average of 2% from the standard data supplied by the manufacturer, whereas in the other 3 conditions (26°C/80%, 37°C/33%, and 37°C/80%), the buckling force can decrease by as much as 39%. Effect of age was small and not clinically relevant. The significant changes in buckling force of the Semmes-Weinstein monofilaments in different temperature and humidity conditions might lead to a potential misinterpretation by the examiner regarding the level of peripheral nerve function loss. This could lead to incorrect diagnosis and treatment. Examiners should be aware when using Semmes-Weinstein monofilaments that the environmental effects of temperature and humidity can affect the accuracy of measurement.


Perceptions of the parent-adolescent relationship: a longitudinal investigation.
A self-report measure of conflict and aspects of warmth in the parent-child relationship was completed by 1,330 11-year-old twins, 1,176 of whom completed the inventory again 3 years later. On average, adolescents' perceptions of the quality of the parent-child relationship declined consistently and moderately between age 11 and age 14. Conflict with parents increased, whereas all aspects of warmth decreased; changes were significantly greater for girls than boys. Variances increased with age, primarily because of increases in the magnitude of genetic effects. Heritability estimates ranged from .09 to .31 at intake and .35 to .45 at follow-up and tended to be higher for boys than girls. Changes in the parent-child relationship are interpreted as reflecting genotype-environment correlation processes whereby adolescents increasingly influence their relationships with their parents.


Pseudomonas aeruginosa utilizes the host-derived polyamine spermidine to facilitate antimicrobial tolerance.
Pseudomonas aeruginosa undergoes diversification during infection of the cystic fibrosis (CF) lung. Understanding these changes requires model systems that capture the complexity of the CF lung environment. We previously identified loss-of-function mutations in the 2-component regulatory system sensor kinase gene pmrB in P. aeruginosa from CF lung infections and from experimental infection of mice. Here, we demonstrate that, while such mutations lowered in vitro minimum inhibitory concentrations for multiple antimicrobial classes, this was not reflected in increased antibiotic susceptibility in vivo. Loss of PmrB impaired aminoarabinose modification of LPS, increasing the negative charge of the outer membrane and promoting uptake of cationic antimicrobials. However, in vivo, this could be offset by increased membrane binding of other positively charged molecules present in lungs. The polyamine spermidine readily coated the surface of PmrB-deficient P. aeruginosa, reducing susceptibility to antibiotics that rely on charge differences to bind the outer membrane and increasing biofilm formation. Spermidine was elevated in lungs during P. aeruginosa infection in mice and during episodes of antimicrobial treatment in people with CF. These findings highlight the need to study antimicrobial resistance under clinically relevant environmental conditions. Microbial mutations carrying fitness costs in vitro may be advantageous during infection, where host resources can be utilized.


[Effects of different kinds of organic fertilizer on fruit yield, quality and nutrient uptake of watermelon in gravel-mulched field].
The effects of different kinds of organic fertilizer on the growth, yield, quality, and nutrient absorption and utlization of watermelon were examined to provide theoretical basis for adequate fertilization and efficient production of watermelon in gravel-mulched field in the Loess Pla-teau of Northwest China. The growth index and nutrient absorption at main stages of growth and development, yield and quality of watermelon were compared among treatments of applying chemical fertilizer (CK), cattle dung, chicken manure, sheep manure and pig manure which contained the equal amount of nitrogen, phosphorus and potassium. The results showed that vegetative growth index, nitrogen and potassium transportation were promoted, yield and nutrient accumulation were improved in treatments of cattle dung, chicken manure and pig manure. Compared to chemical fertilizer, the fruit yield increased by 27.4%, 31.6% and 30.2%, respectively, nitrogen accumulation improved by 26.3%, 39.8% and 47.4%, phosphorus accumulation increased by 49.3%, 48.3% and 55.9%, potassium accumulation improved by 35.8%, 41.6% and 51.9%, respectively, under cattle dung, chicken manure and pig manure treatments. The quality of watermelon was better in pig manure treatment among all the treatments. The central and edge sugar content of watermelon increased by 5.5% and 11.6%, respectively, and Vc content increased by 19.9%, compared with the chemical fertilizer treatment. There was no significant difference between sheep manure and chemical fertilizer treatments. In conclusion, chicken manure and pig manure were optimal organic fertilizers for watermelon planting in gravel-mulched field. The application of sheep manure should be avoided or reduced.


Recent Advances and Future Perspectives in Polymer-Based Nanovaccines.
Vaccination is the most valuable and cost-effective health measure to prevent and control the spread of infectious diseases. A significant number of infectious diseases and chronic disorders are still not preventable by existing vaccination schemes; therefore, new-generation vaccines are needed. Novel technologies such as nanoparticulate systems and adjuvants can enable safe and effective vaccines for difficult target populations such as newborns, elderly, and the immune-compromised. More recently, polymer-based particles have found application as vaccine platforms and vaccine adjuvants due to their ability to prevent antigen degradation and clearance, coupled with enhanced uptake by professional antigen-presenting cells (APCs). Polymeric nanoparticles have been applied in vaccine delivery, showing significant adjuvant effects as they can easily be taken up by APCs. In other words, polymer-based systems offer a lot of advantages, including versatility and flexibility in the design process, the ability to incorporate a range of immunomodulators/antigens, mimicking infection in different ways, and acting as a depot, thereby persisting long enough to generate adaptive immune responses. The aim of this review is to summarize the properties, the characteristics, the added value, and the limitations of the polymer-based nanovaccines, as well as the process of their development by the pharmaceutical industry.