A qualitative study of community home-based care and antiretroviral adherence in Swaziland.
Antiretroviral therapy (ART) has rendered HIV and AIDS a chronic condition for individuals in many parts of the world. Adherence, however, is integral to achieving chronicity. Studies have shown both relatively high ART adherence rates in sub-Saharan Africa and the importance of community home-based care (CHBC) to facilitating this process. In light of diminished HIV and AIDS funding globally and increased reliance on CHBC throughout Africa, a better understanding of how CHBC may strengthen ART adherence is essential to improving patients' quality of life, tending to the needs of care supporters and achieving healthier populations. This article reports findings from a qualitative study of a CHBC organiztion serving an estimated 2500 clients in rural Swaziland. Semi-structured questionnaires with 79 HIV-positive clients [people living with HIV and AIDS (PLWHA)] yielded data on diverse aspects of being HIV positive, including insights on whether and how PLWHA perceived care supporters to facilitate ART adherence in a high stigma and structurally impoverished setting. Ninety-two percent of participants said their health had improved since care supporters came into their lives. A major finding was that an estimated 53% of participants said they would have died, a few from suicide had the care supporter never intervened. More than one in four participants (27.9%) sought HIV testing after a care supporter began visiting them. Nearly a third (31%) commenced ART after and largely as a consequence of care supporter intervention. Approximately one in four (23%) reported that their care supporter had helped them to disclose their HIV-positive status to family members. Twenty-seven percent said they had felt discouraged or had been discouraged from taking ART by members of their family or community. General inductive analysis of participant reports suggested two social mechanisms of CHBC impact on ART adherence: (i) cultivating client-care supporter "talk" to enhance treatment uptake and literacy, reduce felt stigma and challenge social pressures to desist from ART and (ii) real-time interactions between clients and care supporters whereby the care "relationship" was itself the "intervention," providing lay counsel, material and financial assistance, and encouragement when clients suffered stigma, side effects and other obstacles to adherence. These social dynamics of adherence generally fall outside the purview of conventional clinical and public health research. PLWHA reports of care supporter practices that enabled ART adherence demonstrated the pivotal role that CHBC plays in many PLWHA lives, especially in hard to reach areas. Relative to clinic personnel, care supporters are often intensely engaged in clients' experiences of sickness, stigma and poverty, rendering them influential in individuals' decision-making. This influence must be matched with on-going training and support of care supporters, as well as a clear articulation with the formal and informal health sectors, to ensure that PLWHA are correctly counselled and care supporters themselves supported. Overall, findings showed that PLWHA experiences of CHBC should be captured and incorporated into any programme aimed at successfully implementing the Joint United Nations Programme on HIV and AIDS (UNAIDS) Treatment 2.0 agenda Pillar 4 (increasing HIV testing uptake and care linkages) and Pillar 5 (strengthening community mobilization).


Spectrum-Diverse Neuroevolution With Unified Neural Models.
Learning algorithms are being increasingly adopted in various applications. However, further expansion will require methods that work more automatically. To enable this level of automation, a more powerful solution representation is needed. However, by increasing the representation complexity, a second problem arises. The search space becomes huge, and therefore, an associated scalable and efficient searching algorithm is also required. To solve both the problems, first a powerful representation is proposed that unifies most of the neural networks features from the literature into one representation. Second, a new diversity preserving method called spectrum diversity is created based on the new concept of chromosome spectrum that creates a spectrum out of the characteristics and frequency of alleles in a chromosome. The combination of spectrum diversity with a unified neuron representation enables the algorithm to either surpass or equal NeuroEvolution of Augmenting Topologies on all of the five classes of problems tested. Ablation tests justify the good results, showing the importance of added new features in the unified neuron representation. Part of the success is attributed to the novelty-focused evolution and good scalability with a chromosome size provided by spectrum diversity. Thus, this paper sheds light on a new representation and diversity preserving mechanism that should impact algorithms and applications to come.


Acceptability of screening for pregnancy intention in general practice: a population survey of people of reproductive age.
Optimal parental preconception health benefits reproductive outcomes. However, preconception health promotion is not routinely offered in primary health care settings to people of reproductive age. The aim was to gauge the planned preconception health behaviours and attitudes towards being asked about pregnancy intention by a general practitioner (GP) among people of reproductive age in Australia. The research was conducted on a single wave of Australia's first and only probability-based online panel, Life in Australia™. Members of the Life in Australia™ panel are Australian residents aged 18 years or over. All active members between the ages of 18 and 45 years were eligible to participate. Eligible panel members were invited to complete a survey about fertility and childbearing. Data were collected from 18 February to 4 March 2019. In all 965 female and male members of Life in Australia™ aged between 18 and 45 years were invited to complete the survey. Of these, 716 (74.2%) agreed. Most respondents indicated that if they were planning to have a child they would try to optimise their preconception health by adopting a healthier diet (80%), seeing a GP for a health check-up (78%), reducing alcohol consumption (78% of those consuming alcohol), getting fitter (73%), and stopping smoking (70% of smokers). Three in four (74%) stated that they would not mind if their GP asked them about their pregnancy intentions. Findings suggests that routinely asking people of reproductive age about their pregnancy intentions and advising those who are planning pregnancy about what they can do to ensure optimal preconception health would be acceptable to most people and may improve reproductive outcomes.


[The immunometabolic status in persons exposed to technogenous factors of industrial production].
The immune system and lymphocyte activity of HADP-dependent dehydrogenases were studied in the patients living in the high incidence areas of Krasnoyarsk. The enhanced activity of cellular immunity was found to show up in the presence of considerable impaired lymphocyte metabolic processes, the change of the rate of which depended on the type of environmental pollution.


Decrease of serum ascorbic acid concentrations in patients with diabetic macroangiopathy.
The relationship between serum ascorbic acid (AA) and diabetic macroangiopathy was studied. Fifty-six patients with noninsulin-dependent diabetes mellitus were examined, together with 20 healthy controls matched for age against the diabetes patients. Aortic pulse wave velocity (PWV) was taken as an index of the severity of atherosclerosis. The level of serum AA in diabetic patients was significantly lower than that of the controls. Among the diabetic groups, those with elevated PWV levels by age demonstrated a significant drop in AA. No significant differences were seen in the level of serum dehydroascorbic acid (DHAA) between patients and controls, nor were there any significant differences among patient groups. The concentration of serum AA was inversely related to the risk factors of atherosclerosis, such as body mass index, Apo B/ Apo A-I ratio, thiobarbituric acid-reactive substances (TBARS), and microalbumin in urine. It was inferred from these findings that the depletion of serum AA was apparent in diabetics with advanced atherosclerosis.


Childhood trauma and distress tolerance in a trauma-exposed acute-care psychiatric inpatient sample.
Distress tolerance (DT; the perceived or actual ability to withstand negative internal states) has emerged as a promising transdiagnostic risk factor in clinically severe populations. However, little is known about etiological factors associated with the development of DT. We hypothesized that greater levels of childhood trauma would be associated with lower perceived and behavioral DT, beyond theoretically relevant covariates. The current investigation evaluated several childhood trauma types (i.e., physical abuse, sexual abuse, emotional abuse, physical neglect, and emotional neglect) in relation to perceived (i.e., self-report) and behavioral DT in a sample of 87 trauma-exposed adults in acute-care psychiatric inpatient treatment. Results of hierarchical linear regression models indicated that greater childhood physical abuse and emotional neglect were significantly associated with higher perceived DT. Greater levels of emotional abuse were associated with lower perceived DT, and greater physical neglect was associated with lower behavioral DT. DT may be differentially influenced by different forms of childhood trauma. (PsycINFO Database Record


Morphological and crystal chemical characteristic of panсreatic lithiasis.
Introduction: Information on chemical and phase composition of pancreoliths is limited and discrepant. There are reports, that pancreoliths are composed by calcium, phosphate, calcium carbonate or combination of calcium with fatty acids The aim of the work is studying of structural characteristics of pancreatoliths in 5 clinical cases. Materials and methods: Morphological and crystal-chemical study of five cases of pathological biomineralization in the pancreas were conducted in the work. Results: Two stones were located in the pancreatic duct, in other cases - in the ductal system of pancreas. Concretion sizes ranged from 0.5 to 1.5 cm in diameter. Pancreatic lithiasis' form depended on the location: in the duct of Wirsung single concretions were found (they were relatively large, oval stones with smooth, regular edges); multiple, small concretions with irregular edges, coral-like stones dominated in the ductal system of pancreas. Histological study of pancreas showed the signs of chronic pancreatitis, tissue fibrosis, atrophy and edema of glandular component, system distension of ducts, nidal mix-cell inflammatory infiltrates, vessels' plethora. Structural phase and chemical analysis of pathological biominerals responded calcite in all studied cases. Conclusion: The presence of pancreatic lithiasis was found to be accompanied by significant morphological changes of the pancreas. The pancreatolith crystal phase was established to be calcium carbonate in the form of calcite.


Retrotransposon-adenovirus hybrid vectors: efficient delivery and stable integration of transgenes via a two-stage mechanism.
It has long been recognized that the mechanisms mediating retrotransposition might be adapted for genomic integration and long-term expression of foreign genes. In particular, long interspersed nuclear elements (LINEs), an abundant class of retrotransposons that are the most active mobile genetic elements in the human genome, have been largely ignored as candidates for development as an integrating vector system because there has been no suitable method for efficiently introducing them into target cells. We have recently developed a LINE-based retrotransposon-adenovirus hybrid vector, in which a helper-dependent adenovirus (HDAd) is utilized as the platform for delivery of a human L1 element and its linked heterologous transgene cassette into the host cell nuclei. While a major drawback to the use of HDAd vectors has been their lack of specific mechanisms to achieve permanent integration into the host genome, the inserted retrotransposon sequences overcome this limitation. The L1-HDAd hybrid thus represents a single vector capable of mediating long-term gene expression by a two-stage mechanism: in the first (adenovirus) stage, the helper-dependent adenovirus serves as a carrier for efficient delivery and transient expression of its encoded L1/transgene cassette, and in the second (retrotransposon) stage, the L1 retro-element and its associated transgene then permanently integrate into the genome of the adenovirus-transduced cells. We propose that this novel retrotransposon-adenovirus hybrid vector system will be useful both as a vehicle for efficient delivery and long-term stable transduction of therapeutic genes, as well as a tool to elucidate aspects of retrotransposon biology that have previously been difficult to study.


Pyridinium-Based Strategy for a Bioorthogonal Conjugation-Assisted Purification Method for Profiling Cell Surface Proteome.
Cell surface proteins (CSPs) are valuable targets for therapeutic agents, but achieving highly selective CSP enrichment in cellular physiology remains a technical challenge. To address this challenge, we propose a newly developed sulfo-pyridinium ester (SPE) cross-linking probe, followed by two-step imaging and enrichment. The SPE probe showed higher efficiency in labeling proteins than similar NHS esters at the level of cell lysates and demonstrated specificity for Lys in competitive experiments. More importantly, this probe could selectively label the cell membranes in cell imaging with only negligible labeling of the intracellular compartment. Moreover, we successfully performed this strategy on MCF-7 live cells to label 425 unique CSPs from 1162 labeled proteins. Finally, we employed our probe to label the CSPs of insulin-cultured MCF-7, revealing several cell surface targets of key functional biomarkers and insulin-associated pathogenesis. The above results demonstrate that the SPE method provides a promising tool for the selective labeling of cell surface proteins and monitoring transient cell surface events.


Dietary fat consumption and health.
Dietary Guidelines have emerged over the past 30 years recommending that Americans limit their consumption of total fat and saturated fat as one way to reduce the risk of a range of chronic diseases. However, a low-fat diet is not a no-fat diet. Dietary fat clearly serves a number of essential functions. For example, maternal energy deficiency, possible exacerbated by very low-fat intakes (< 15% of energy), is one key determinant in the etiology of low birth weight. The debate continues over recommendations for limiting total fat and saturated fatty acid intake in children. Recent evidence indicates that diets with adequate energy providing less than 30% of energy from fat are sufficient to promote normal growth and normal sexual maturation. More attention needs to be devoted to the effect of dietary fat reduction on the nutrient density of children's diets. The association between dietary fat and CHD has been extensively studied. Diets high in saturated fatty acids and trans fatty acids increase LDL cholesterol levels, and in turn, the risk of heart disease. The relationship between high-carbohydrate/low-fat diets and CHD is more ambiguous because high-carbohydrate diets induce dyslipidemia in certain individuals. Obesity among adults and children is now of epidemic proportions in the United States. High-fat diets leading to excessive energy intakes are strongly linked to the increasing obesity in the United States. However, the prevalence of obesity has increased during the same time period that dietary fat intake (both in absolute terms and as a percentage of total dietary energy) has decreased. These trends suggest that a concomitant decrease in total dietary energy and modifications of other lifestyle factors, such as physical activity, also need to be emphasized. Obesity is also an independent risk factor for the development of diabetes. The current availability of fat-modified foods offers the potential for dietary fat reduction and treatment of the comorbidities associated with diabetes. However, to date, few studies have documented the effectiveness of fat-modified foods as part of a weight loss regimen or in reduction in CHD risks among individuals with diabetes mellitus. The association between total dietary fat and cancer is still under debate. While there is some evidence demonstrating associations between dietary fat intake and cancers of the breast, prostate, and colon, there are serious methodologic issues, including the difficulty in differentiating the effects of dietary fat independent of total energy intake. Reported total fat and saturated fatty acid intakes as a percentage of total energy have been declining over the past 30 years in the United States. Despite this encouraging trend, the majority of individuals--regardless of age--do not report consuming a diet that meets the levels of fat and saturated fatty acids recommended by the Dietary Guidelines for Americans. On a relative basis, saturated fat intake has gone down less than has total fat intake. Individuals of all ages who report consuming a diet with < or = 30% of energy from fat consistently have lower energy intakes. Given the increasing rates of obesity in the United States at an earlier and earlier age, dietary fat reduction may be an effective part of an overall strategy to balance energy consumption with energy needs. In each of the age/gender groups reporting consumption of < or = 30% of energy from fat and less than 10% of energy from saturated fatty acids, fat-modified foods play a more important role in their diets than for people who are consuming higher levels of fat and saturated fat. The data are clear than fat-modified foods make a more significant contribution to diets of consumers with low-fat intakes. While one cannot argue cause and effect from the results presented, the patterns of fat-modified foods/low-fat intakes are consistent. The focus on overall diet quality is often lost in the national obsession with lowering fat inta


Partial characterization of bacteriocins produced by two Lactobacilus strains with probiotic properties.
The probiotic characteristics of Lactobacillus brevis BG18 and Lb. plantarum BG33, isolated from traditional Turkish Tulum cheese were assessed. These two bacteriocinproducer strains exhibited good probiotic characteristics such as resistance in media containing 0.3% bile salt, pepsin (3 mg mL⁻¹), and pancreatine (1 mg mL⁻¹) as well as acid resistance at pH 2. They were also adhered to Caco-2 epithelial cells in a manner comparable to Escherichia coli LMG3083 (ETEC) and Salmonella Typhimurium SL1344. The strains produced a heat-stable antimicrobial compound that was shown to be proteinaceous in nature, and therefore, referred to as bacteriocins. The bacteriocins were able to inhibit growth of a number grampositive bacteria such as Listeria monocytogenes, Clostridium botulinum, Staphylococcus aureus and Bacillus cereus. Tricine-SDS-PAGE of the active fraction resulted in single bands with estimated molecular masses of 2.5 kDA and 2.7 kDA for Lb. brevis BG18 and Lb. plantarum BG33 bacteriocins, respectively.


Molecular detection of bacterial contamination in gnotobiotic rodent units.
Gnotobiotic rodents provide an important technique to study the functional roles of commensal bacteria in host physiology and pathophysiology. To ensure sterility, these animals must be screened frequently for contamination. The traditional screening approaches of culturing and Gram staining feces have inherent limitations, as many bacteria are uncultivable and fecal Gram stains are difficult to interpret. Thus, we developed and validated molecular methods to definitively detect and identify contamination in germ-free (GF) and selectively colonized animals. Fresh fecal pellets were collected from rodents housed in GF isolators, spontaneously contaminated ex-GF isolators, selectively colonized isolators and specific pathogen-free (SPF) conditions. DNA isolated from mouse and rat fecal samples was amplified by polymerase chain reaction (PCR) and subjected to quantitative PCR (qPCR) using universal primers that amplify the 16S rRNA gene from all bacterial groups. PCR products were sequenced to identify contaminating bacterial species. Random amplification of polymorphic DNA (RAPD) PCR profiles verified bacterial inoculation of selectively colonized animals. These PCR techniques more accurately detected and identified GF isolator contamination than current standard approaches. These molecular techniques can be utilized to more definitively screen GF and selectively colonized animals for bacterial contamination when Gram stain and/or culture results are un-interpretable or inconsistent.


Effects of dehulling, steam-cooking and microwave-irradiation on digestive value of white lupin (Lupinus albus) seed meal for rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar).
A digestibility trial was conducted to assess the effect of dehulling, steam-cooking and microwave-irradiation on the apparent digestibility of nutrients in white lupin (Lupinus albus) seed meal when fed to rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar). Six ingredients, whole lupin seed meal (LSM), dehulled LSM, dehulled LSM steam-cooked for 15 or 45 min (SC15 and SC45, respectively) and LSM microwave-irradiated at 375 or 750 W (MW375 and MW750, respectively), were evaluated for digestibility of dry matter, crude protein (CP), lipids, nitrogen-free extractives (NFE) and gross energy (GE). The diet-substitution approach was used (70% reference diet + 30% test ingredient). Faeces from each tank were collected using a settlement column. Dehulled LSM showed higher levels of proximate components (except for NFE and crude fibre), GE and phosphorus in comparison to whole LSM. Furthermore, SC15, SC45, MW375 and MW750 showed slight variations of chemical composition in comparison to dehulled LSM. Results from the digestibility trial indicated that dehulled LSM, SC15, SC45 and MW375 are suitable processing methods for the improvement of nutrients' apparent digestibility coefficient (ADC) in whole LSM. MW750 showed a lower ADC of nutrients (except for CP and lipids for rainbow trout) in comparison with MW350 for rainbow trout and Atlantic salmon, suggesting a heat damage of the ingredient when microwave-irradiation exceeded 350 W.


Macroscopic modeling of the growth and substrate consumption of wild type and genetically modified Pichia pastoris.
Pichia pastoris is a popular yeast platform to generate several industrially relevant products which have applications in a wide range of sectors. The complexities in the processes due to the addition of a foreign gene are not widely explored. Since these complexities can be dependent on the strain characteristics, promoter, and type of protein produced, it is vital to investigate the growth and substrate consumption patterns of the host to facilitate customized process optimization. In this study, the growth rates of P. pastoris GS115 wild type (WT) and genetically modified (GM) strains grown on glycerol and methanol in batch cultivation mode were estimated and the model providing the best representation of the true growth kinetics based on substrate consumption was identified. It was observed that the growth of P. pastoris exhibits Haldane kinetics on glycerol rather than the most commonly used Monod kinetics due to the inability of the latter to describe growth inhibition at high concentrations of glycerol. Whereas, the cardinal parameter model, a newly proposed model for this application, was found to be the best fitting to describe the growth of P. pastoris on methanol due to its ability to describe methanol toxicity. Interestingly, the findings from this study concluded that in both substrates, the genetically engineered strain exhibited a higher growth rate compared to the WT strain. Such an observation has not been established yet in other published works, indicating an opportunity to further optimize the carbon source feeding strategies when the host is grown in fed-batch mode.


[SIRT1 deficiency in CD4+T cells induces acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation].
To study the relationship between acute graft-versus-host disease (aGVHD) and the SIRT1 expression in peripheral blood CD4+T cells from patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: We collected 40 patients who underwent allo-HSCT from human leukocyte antigen (HLA)-identical sibling donors. SIRT1 expression level in CD4+T cells was measured by real-time PCR and Western blot. Acetylation and phosphorylation of STAT3 in CD4+T cells were detected by Western blot. The binding level between SIRT1 and STAT3 in CD4+T cells was analyzed by co-immunoprecipitation and Western blot. Over-expression of SIRT1 in aGVHD CD4+T cells, as well as STAT3 acetylation and phosphorylation were measured by Western blot. The mRNA levels of RORγt, IL-17A, IL-17F related to Th17 were detected by real-time PCR. Results: SIRT1 expression was significantly down-regulated, while STAT3 expression, acetylation and phosphorylation levels were significantly up-regulated in patients with aGVHD compared with patients without aGVHD. The STAT3 acetylation was positively correlated with STAT3 phosphorylation (r=0.69, P<0.01). Less SIRT1-STAT3 complexes were found in CD4+T cells from patients with aGVHD compared with patients without aGVHD. After SIRT1 over-expression in aGVHD CD4+T cells, the STAT3 acetylation and phosphorylation, and the expression of RORγt, IL-17A, and IL-17F related to Th17 were significantly down-regulated (P<0.05). Conclusion: SIRT1 deficiency in CD4+T cells plays a crucial role in up-regulation of STAT3 acetylation and phosphorylation, the increase of Th17 related gene expression, and induction of aGVHD after allogeneic hematopoietic stem cell transplantation.


Spatiotemporal patterns and dynamics of species richness and abundance of woody plant functional groups in a tropical forest landscape of Hainan Island, South China.
Tropical forests are among the most species-diverse ecosystems on Earth. Their structures and ecological functions are complex to understand. Functional group is defined as a group of species that play similar roles in an ecosystem. The functional group approach has been regarded as an effective way of linking the compositions of complex ecosystems with their ecological functions. To understand the variation of functional groups in species-rich ecosystems after disturbance, the present study investigated the spatial pattern and temporal dynamics of woody plants in a typically fragmented natural forest landscape of Hainan Island in South China. The study area was classified into eight landscape types based on vegetation type, disturbance manner and the time of recovery. The woody plant species were aggregated into seven functional groups based on the growth form, successional status and plant size. The results gained from the present study showed that all functional groups, except for the emergent and canopy tree species, were present in all eight landscape types. Each landscape type had different numbers of dominant functional groups. There are similar species richness and stem abundance structure among functional groups between mid-successional clear cut lowland rainforest and old growth tropical coniferous forest. This similarity exists in selective logged lowland rainforest and old-growth lowland rainforest, as well as among landscape types of montane rainforest. The functional groups with the same successional status had similar patterns of species richness and stem abundance ratios among different landscape types. The variation patterns of functional groups along the successional stages in terms of species richness and stem abundance among the tropical lowland rainforest landscape types were more similar to each other than those in the tropical montane rainforest landscape types. This study provides further support for the competition-colonization tradeoff and successional niche theory as opposed to models of neutrality and ecological equivalence.


An African swine fever virus virulence-associated gene NL-S with similarity to the herpes simplex virus ICP34.5 gene.
We described previously an African swine fever virus (ASFV) open reading frame, 23-NL, in the African isolate Malawi Lil 20/1 whose product shared significant similarity in a carboxyl-terminal domain with those of a mouse myeloid differentiation primary response gene, MyD116, and the herpes simplex virus neurovirulence-associated gene, ICP34.5 (M. D. Sussman, Z. Lu, G. Kutish, C. L. Afonso, P. Roberts, and D. L. Rock, J. Virol. 66:5586-5589, 1992). The similarity of 23-NL to these genes suggested that this gene may function in some aspect of ASFV virulence and/or host range. Sequence analysis of additional pathogenic viral isolates demonstrates that this gene is highly conserved among diverse ASFV isolates and that the gene product exists in either a long (184 amino acids as in 23-NL) or a short form (70 to 72 amino acids in other examined ASFV isolates). The short form of the gene, NL-S, encodes the complete highly conserved, hydrophilic, carboxyl-terminal domain of 56 amino acids common to 23-NL, MyD116, and ICP34.5. Recombinant NL-S gene deletion mutants and their revertants were constructed from the pathogenic ASFV isolate E70 and an E70 monkey cell culture-adapted virus, MS44, to study gene function. Although deletion of NL-S did not affect viral growth in primary swine macrophages or Vero cell cultures in vitro, the null mutant, E70/43, exhibited a marked reduction in pig virulence. In contrast to revertant or parental E70 where mortality was 100%, all E70/43-infected animals survived infection. With the exception of a transient fever response, E70/43-infected animals remained clinically normal and exhibited a 1,000-fold reduction in both mean and maximum viremia titers. All convalescent E70/43-infected animals survived infection when challenged with parental E70 at 30 days postinfection. These data indicate that the highly conserved NL-S gene of ASFV, while nonessential for growth in swine macrophages in vitro, is a significant viral virulence factor and may function as a host range gene.


Osteoporosis knowledge and health beliefs among middle-aged men and women in the Southern United States.
The most common skeletal disease, osteoporosis, causes bone fragility due to decreased bone mass and bone microarchitecture destruction. The health belief model is often applied to asymptomatic, prevention-related diseases such as osteoporosis. Steps to mitigate the insidious nature of osteoporosis, including education, motivation, and monitoring of bone mineral density, must begin at an earlier age. This study evaluates the knowledge and health beliefs surrounding osteoporosis in a population of males and females 35-50 years old to determine sex-based differences in osteoporosis knowledge and beliefs and to assess the correlation between perceptions and health motivation. Participants (81 males, 92 females) completed two questionnaires: the Osteoporosis Knowledge Test and the Osteoporosis Health Belief Scale. Descriptive statistics were performed along with Pearson product-moment correlation analysis to determine the relationships between the variables. Sex-based differences were calculated utilizing independent t-tests. We discovered a statistically significant negative correlation between the barriers to exercise and health motivation (-0.434, p < 0.001) and a statistically significant positive correlation between the benefits of exercise and health motivation (0.385, p < 0.001). However, there was not a statistically significant correlation between health motivation with the following: the benefits of calcium, susceptibility, and the seriousness of osteoporosis. Between males and females, there was a statistically significant difference in exercise and calcium knowledge, susceptibility, and the benefits of both exercise and calcium (p < 0.05). Males and females 35-50 years old perceive themselves to have a low susceptibility to osteoporosis. They do not consider osteoporosis a serious disease and have little motivation to mitigate its inception or progression. Their perceptions show that barriers to exercise impact health motivation more than the perceived benefits of exercise.


Chemotherapy-induced nausea and vomiting in patients with breast cancer: a prospective cohort study.
To explore the actual status of chemotherapy-induced nausea and vomiting (CINV) through a multicenter prospective cohort study. Patients with breast cancer treated with moderately emetogenic (MEC) or highly emetogenic (HEC) chemotherapy were eligible. A 7-day diary was provided for all patients. Acute and delayed CINV were defined as nausea and vomiting that developed ≤ 24 or > 24 h after the start of chemotherapy, respectively. The severity of nausea was evaluated with a visual analog scale (VAS). We also assessed the accuracy of estimations of CINV by medical staff. In total, 426 patients were included; 352 patients (82.6%) received HEC, and 74 (17.3%) received MEC. In the acute phase, 44.9% of patients receiving HEC and 5.4% receiving MEC experienced nausea, and 12.8% receiving HEC and none receiving MEC experienced vomiting. More patients experienced nausea in both groups and vomiting in MEC during the delayed phase (nausea: 59.4% in HEC and 44.6% in MEC group; vomiting: 11.1% in HEC; and 13.5% in MEC group) than during the acute phase. Estimations of CINV by medical staff were not accurate, with a kappa coefficient of 0.10 and 0.08 for acute nausea and vomiting and 0.02 and 0.01 for delayed. The VAS scores showed that in the HEC group, the degree of nausea was worst on the first day. The degree of nausea was worst in the acute phase, although delayed nausea was more in proportion in HEC. Estimation by medical staff is not accurate.


Post-transcriptional regulation of breast cancer resistance protein after intestinal ischemia-reperfusion.
Breast cancer resistance protein (BCRP), the product of the ABCG2 gene, is a recently identified ATP binding cassette half-transporter. BCRP is expressed in a variety of tumor cells and many normal human tissues. In the small intestine, BCRP can limit the influx and facilitate the efflux to prevent intracellular accumulation of BCRP substrates. Ischemia-reperfusion (I/R) induces the release of reactive oxygen species, and organs are severely damaged by I/R. It has been shown that the expression of transporters was altered in the organ after I/R. The present study was undertaken to clarify the expression of BCRP after intestinal I/R. We showed that the expression level of Bcrp was significantly decreased at 1 h after I/R. Bcrp mRNA level was not altered at 1 h after I/R. These results suggest that Bcrp expression was regulated by a post-transcriptional regulation mechanism after intestinal I/R. Bcrp mRNA level was increased at 24 h after I/R, and the expression level of Bcrp protein was of the same level or slightly increased compared with sham operated-rats. Bcrp was slightly located at the intestinal membrane at 24 h after intestinal I/R. These results suggested that Bcrp was not translocated to the intestinal membrane after intestinal I/R. There is little information on post-transcriptional regulation compared with information on transcriptional regulation. In this study, it was shown that Bcrp expression is regulated by post-transcriptional regulation after intestinal I/R. These results of this study may provide important information for further studies aimed at revealing the biological function of Bcrp.


Control and elimination of rabies in Croatia.
Despite the implementation of control measures (preventive dog vaccination), rabies has become endemic in Croatia, with red foxes being the main reservoir species. Oral rabies vaccination (ORV) campaigns supported by the European Commission have been conducted twice a year since the spring of 2011. The first campaigns were limited to the northern and eastern parts of the country, and from the autumn of 2012, the program was extended to the entire country. The Lysvulpen vaccine containing the SAD Bern strain was used for ORV. Following the vaccination campaigns, the number of rabies cases decreased, and the last positive case was recorded in February 2014. The bait uptake ranged from 24.86% to 84.62% and the immunisation rate from 11.24% to 35.64%.


Subcellular localization and interactions among rubber particle proteins from Hevea brasiliensis.
Natural rubber (polyisoprene) from the rubber tree Hevea brasiliensis is synthesized by specialized cells called laticifers. It is not clear how rubber particles arise, although one hypothesis is that they derive from the endoplasmic reticulum (ER) membrane. Here we cloned the genes encoding four key proteins found in association with rubber particles and studied their intracellular localization by transient expression in Nicotiana benthamiana leaves. We show that, while the cis-prenyltransferase (CPT), responsible for the synthesis of long polyisoprene chains, is a soluble, cytosolic protein, other rubber particle proteins such as rubber elongation factor (REF), small rubber particle protein (SRPP) and Hevea rubber transferase 1-REF bridging protein (HRBP) are associated with the endoplasmic reticulum (ER). We also show that SRPP can recruit CPT to the ER and that interaction of CPT with HRBP leads to both proteins relocating to the plasma membrane. We discuss these results in the context of the biogenesis of rubber particles.


LACHESIS-dependent egg-cell signaling regulates the development of female gametophytic cells.
In contrast to animals, plant germ cells are formed along with accessory cells in specialized haploid generations, termed gametophytes. The female gametophyte of flowering plants consists of four different cell types, which exert distinct functions in the reproductive process. For successful fertilization, the development of the four cell types has to be tightly coordinated; however, the underlying mechanisms are not yet understood. We have previously isolated the lachesis (lis) mutant, which forms supernumerary gametes at the expense of adjacent accessory cells. LIS codes for the Arabidopsis homolog of the pre-mRNA splicing factor PRP4 and shows a dynamic expression pattern in the maturing female gametophyte. Here, we used LIS as a molecular tool to study cell-cell communication in the female gametophyte. We show that reducing LIS transcript amounts specifically in the egg cell, affects the development of all female gametophytic cells, indicating that cell differentiation in the female gametophyte is orchestrated by the egg cell. Among the defects observed is the failure of homotypic nuclei fusion in the central cell and, as a consequence, a block in endosperm formation. LIS-mediated egg cell signaling, thus, provides a safeguard mechanism that prevents the formation of nurturing tissue in the absence of a functional egg cell.


Emerging contaminants in wastewater, stormwater runoff, and surface water: Application as chemical markers for diffuse sources.
Diffuse sources of pollution such as sewer leakages, sewer overflows, illicit discharges and stormwater runoff affect the urban surface water quality but often remain unknown. Therefore, the development of chemical markers for identifying and characterizing the origin of diffuse sources of pollution in urban surface waters is a requisite for protecting and managing urban water resources. In this study, the occurrence of 31 emerging contaminants (ECs) in untreated wastewater, treated wastewater, urban stormwater runoff, agricultural stormwater runoff, and freshwater bodies was investigated. Artificial sweeteners (ASs), pharmaceuticals and personal care products (PPCPs) were more frequently detected in the collected water samples. In raw wastewater, 21 target ECs were detected 100% in the collected samples with median concentrations ranging from 49.6 to 77,721 ng/L, while in freshwater bodies, only 13 compounds were found with detection frequency >50%. The median concentration of the majority of detected ECs in freshwater samples was below 100 ng/L. The suitability of ECs as chemical markers of diffuse sources in an urban watershed was assessed using a suite of criteria, including the detection frequency (DF), detection ratio (DR) (i.e. the ratio between median concentration and method quantification limit of a compound) and attenuation rates (i.e., biodegradation, sorption and abiotic degradation) in wastewater treatment processes. In addition, we propose a new key criterion, the concentration ratio (CR) of labile to conservative compounds, to evaluate the applicability of suitable chemical markers for source tracking. Using this new set of criteria (i.e. CR, DF, DR and attenuation rates), our analysis showed that among the investigated ECs, only acesulfame (ACE), acetaminophen (ACT), cyclamate (CYC), saccharin (SAC) were suitable as chemical markers of diffuse sources in surface waters. For caffeine (CF), N,N-diethyl-meta-toluamide (DEET), crotamiton (CTMT), triclocarban (TCC) and triclosan (TCS), their median concentration ratio to sucralose (SUC) in water bodies was consistently higher than that in raw wastewater, suggesting that these compounds might be unsuitable as chemical markers of sewage leakage in surface waters for this study area.


Understanding Barriers and Facilitators of Maternal Health Care Utilization in Central Myanmar.
The study objective was to examine barriers and facilitators of maternal health services utilization in Myanmar with the highest maternal mortality ratio in Southeast Asia. Data for 258 mothers with children under five were extracted from a community health survey administered between 2016 and 2017 in Mandalay, the largest city in central Myanmar, and analyzed for associations between determinants of maternal health care choices and related outcomes. The study showed that late antenatal care was underutilized (41.7%), and antenatal care attendance was significantly associated with geographical setting, household income, education, and access to transportation (p ≤ 0.05). Less than one-third of women gave birth at home and 18.5% of them did so without the assistance of traditional birth attendants. Household education level was a significant predictor for home delivery (p < 0.01). Utilization of postnatal care services was irregular (47.9%-70.9%) and strongly associated with women's places of delivery (p < 0.01). Efforts geared towards improving maternal health outcomes should focus on supporting traditional birth attendants in their role of facilitating high-quality care and helping women reach traditional health facilities, as well as on maternal health literacy based on culturally appropriate communication.


Plasma proteome responses in zebrafish following λ-carrageenan-Induced inflammation are mediated by PMN leukocytes and correlate highly with their human counterparts.
Regulation of inflammation is a critical process for maintaining physiological homeostasis. The λ-carrageenan (λ-CGN) is a mucopolysaccharide extracted from the cell wall of red algae (Chondrus crispus) capable of inducing acute intestinal inflammation, which is translated into the production of acute phase reactants secreted into the blood circulation. However, the associated mechanisms in vertebrates are not well understood. Here, we investigated the crucial factors behind the inflammatory milieu of λ-CGN-mediated inflammation administered at 0, 1.75, and 3.5% (v/w) by i.p. injection into the peritoneal cavity of adult zebrafish (ZF) (Danio rerio). We found that polymorphonuclear leukocytes (neutrophils) and lymphocytes infiltrating the ZF peritoneal cavity had short-term persistence. Nevertheless, they generate a strong pattern of inflammation that affects systemically and is enough to produce edema in the cavity. Consistent with these findings, cell infiltration, which causes notable tissue changes, resulted in the overexpression of several acute inflammatory markers at the protein level. Using reversed-phase high-performance liquid chromatography followed by a hybrid linear ion-trap mass spectrometry shotgun proteomic approach, we identified 2938 plasma proteins among the animals injected with PBS and 3.5% λ-CGN. First, the bioinformatic analysis revealed the composition of the plasma proteome. Interestingly, 72 commonly expressed proteins were recorded among the treated and control groups, but, surprisingly, 2830 novel proteins were differentially expressed exclusively in the λ-CGN-induced group. Furthermore, from the commonly expressed proteins, compared to the control group 62 proteins got a significant (p < 0.05) upregulation in the λ-CGN-treated group, while the remaining ten proteins were downregulated. Next, we obtained the major protein-protein interaction networks between hub protein clusters in the blood plasma of the λ-CGN induced group. Moreover, to understand the molecular underpinnings of these effects based on the unveiled protein sets, we performed a bioinformatic structural similarity analysis and generated overlapping 3D reconstructions between ZF and humans during acute inflammation. Biological pathway analysis pointed to the activation and abundance of diverse classical immune and acute phase reactants, several catalytic enzymes, and varied proteins supporting the immune response. Together, this information can be used for testing and finding novel pharmacological targets to treat human intestinal inflammatory diseases.


Impact of intensive lifestyle intervention on depression and health-related quality of life in type 2 diabetes: the Look AHEAD Trial.
We examined the effects of an intensive lifestyle intervention (ILI), compared with a diabetes support and education (DSE) control intervention, on long-term changes in depression symptoms, antidepressant medication (ADM) use, and health-related quality of life (HRQoL) in overweight/obese individuals with type 2 diabetes. Look AHEAD was a multisite randomized controlled trial of 5,145 overweight/obese participants assigned to ILI (designed to produce weight loss) or DSE and followed for a median of 9.6 years. The Beck Depression Inventory (BDI) was administered at baseline, annually at years 1-4, and again at year 8. Mean BDI scores and incidence of BDI scores ≥10, indicative of likely mild or greater depression, were examined. Annually through year 10, participants reported their ADM use and completed the Medical Outcomes Study Short Form 36 (SF-36) questionnaire, which yields physical component summary (PCS) and mental component summary (MCS) scores. ILI significantly reduced the incidence of mild or greater depression symptoms (BDI scores ≥10) compared with DSE (hazard ratio [HR] = 0.85; 95% CI 0.75-0.97; P = 0.0145). Although SF-36 PCS scores worsened over time in both groups, ILI participants reported better physical function than DSE throughout the first 8 years (all P values <0.01). There were no significant differences between treatment arms in the proportion of participants who used ADMs or in SF-36 MCS scores. ILI for overweight/obese patients with type 2 diabetes may reduce the risk of developing clinically significant symptoms of depression and preserve physical HRQoL. These findings should be considered when evaluating the potential benefits of ILIs.


[Changes in the physiological functions, the mechanisms of their recovery and the temperature limits for life under hypothermia].
On the basis of the newest literature and author's own investigations the variations of the main life ensuring functions (the minute volume of respiration, the oxygen transport functions of the blood, the tissue oxygen supply ect) are analyzed under the immersion hypothermia in homoisothermal animals and man. The mechanisms of these function variations under hypothermia of various degree are described. On the basis of the newest theories of cold action on a cell the main physiological mechanisms of oppressing these functions are described, which result in the loss of homoiothermy. The possibilities and regularities of the physiological function resuscitation after deep hypothermia are analyzed. The factors, influencing the level of the lower temperature limit of life in homoiothermal animals, are determined.


Effect of ultra-high pressure homogenization on the interaction between bovine casein micelles and ritonavir.
The aim of this work was to develop a milk-based powder formulation appropriate for pediatric delivery of ritonavir (RIT). Ultra-high pressure homogenization (UHPH) at 0.1, 300 and 500 MPa was used to process a dispersion of pasteurized skim milk (SM) and ritonavir. Loading efficiency was determined by RP-HPLC-UV; characterization of RIT:SM systems was carried out by apparent average hydrodynamic diameter and rheological measurements as well as different analytical techniques including Trp fluorescence, UV spectroscopy, DSC, FTIR and SEM; and delivery capacity of casein micelles was determined by in vitro experiments promoting ritonavir release. Ritonavir interacted efficiently with milk proteins, especially, casein micelles, regardless of the processing pressure; however, results suggest that, at 0.1 MPa, ritonavir interacts with caseins at the micellar surface, whilst, at 300 and 500 MPa, ritonavir is integrated to the protein matrix during UHPH treatment. Likewise, in vitro experiments showed that ritonavir release from micellar casein systems is pH dependent; with a high retention of ritonavir during simulated gastric digestion and a rapid delivery under conditions simulating the small intestine environment. Skim milk powder, especially, casein micelles are potentially suitable and efficient carrier systems to develop novel milk-based and low-ethanol powder formulations of ritonavir appropriate for pediatric applications.


Creutzfeldt-Jakob disease with a novel four extra-repeat insertional mutation in the PrP gene.
To investigate the role of a short insertional mutation in the prion protein (PrP) gene (PRNP) in prion disease pathogenesis. The genetic forms of Creutzfeldt-Jakob disease (CJD) are associated with point or insertional mutations in PRNP. Whereas patients with five, six, seven, eight, and nine extra octapeptide repeats show an autosomal dominant pattern of inheritance and features of CJD, Gerstmann-Sträussler-Scheinker disease, or atypical dementia, patients with one, two, or four extra repeats have typical CJD and lack a family history of neurologic disorder. A genetic, neuropathologic, and biochemical study was carried out in a 65-year-old patient with clinical features of sporadic CJD. A novel four extra-repeat insertional mutation of PRNP was found in the patient and in his 59-year-old healthy sister. The patient showed spongiosis, nerve cell loss, and gliosis associated with diffuse PrP immunoreactivity in the cerebral cortex, subcortical gray structures, and cerebellum. A peculiar aspect was the presence of focal PrP deposits in the basal ganglia and hypothalamus, superimposed to diffuse PrP immunoreactivity. The biochemical analysis revealed that both mutant and wild-type PrP participated in the pathologic process, and that the protease-resistant core of the altered PrP isoforms was distinct from that observed in sporadic, acquired, and other genetic forms of CJD. These findings support the view that the four extra-repeat insertion in PRNP is a pathogenic mutation with low penetrance rather than a benign polymorphism, and suggest that this mutation results in the formation of a distinct PrP conformer.


The evolution of the serotonergic nervous system.
The pattern of development of the serotonergic nervous system is described from the larvae of ctenophores, platyhelminths, nemerteans, entoprocts, ectoprocts (bryozoans), molluscs, polychaetes, brachiopods, phoronids, echinoderms, enteropneusts and lampreys. The larval brain (apical ganglion) of spiralian protostomes (except nermerteans) generally has three serotonergic neurons and the lateral pair always innervates the ciliary band of the prototroch. In contrast, brachiopods, phoronids, echinoderms and enteropneusts have numerous serotonergic neurons in the apical ganglion from which the ciliary band is innervated. This pattern of development is much like the pattern seen in lamprey embryos and larvae, which leads the author to conclude that the serotonergic raphe system found in vertebrates originated in the larval brain of deuterostome invertebrates. Further, the neural tube of chordates appears to be derived, at least in part, from the ciliary band of deuterostome invertebrate larvae. The evidence shows no sign of a shift in the dorsal ventral orientation within the line leading to the chordates.


Detection of serum anticerebellar antibodies in patients with Miller Fisher syndrome.
We performed Western blot analysis to detect anticerebellar antibodies in the serum of patients with Miller Fisher syndrome (MFS). We studied 7 MFS patients, 6 Guillain-Barré syndrome (GBS) patients and 10 normal healthy persons as controls. Six MFS patients (86%) had IgG antibodies against mouse cerebellar protein, whereas 3 GBS patients (50%) and 4 healthy controls (40%) had antibodies. The mean number of antibodies in the serum of patient with MFS was 2.43, which was significantly more than that of GBS patients (mean 0.67) and healthy control (mean 0.70). This finding suggests variability and complexity of target in nervous systems that suffer aberrant immunity in MFS, and may also reflect the variability and heterogeneity of the pathogenesis of this syndrome.


Dynamic conversion of cell sorting patterns in aggregates of embryonic stem cells with differential adhesive affinity.
Mammalian early development comprises the proliferation, differentiation, and self-assembly of the embryonic cells. The classic experiment undertaken by Townes and Holtfreter demonstrated the ability of dissociated embryonic cells to sort and self-organize spontaneously into the original tissue patterns. Here, we further explored the principles and mechanisms underlying the phenomenon of spontaneous tissue organization by studying aggregation and sorting of mouse embryonic stem (ES) cells with differential adhesive affinity in culture. As observed previously, in aggregates of wild-type and E-cadherin-deficient ES cells, the cell assemblies exhibited an initial sorting pattern showing wild-type cells engulfed by less adhesive E-cadherin-deficient ES cells, which fits the pattern predicted by the differential adhesive hypothesis proposed by Malcom Steinberg. However, in further study of more mature cell aggregates, the initial sorting pattern reversed, with the highly adhesive wild-type ES cells forming an outer shell enveloping the less adhesive E-cadherin-deficient cells, contradicting Steinberg's sorting principle. The outer wild-type cells of the more mature aggregates did not differentiate into endoderm, which is known to be able to sort to the exterior from previous studies. In contrast to the naive aggregates, the mature aggregates presented polarized, highly adhesive cells at the outer layer. The surface polarity was observed as an actin cap contiguously spanning across the apical surface of multiple adjacent cells, though independent of the formation of tight junctions. Our experimental findings suggest that the force of differential adhesive affinity can be overcome by even subtle polarity generated from strong bilateral ligation of highly adhesive cells in determining cell sorting patterns.


Military traumatic brain injury: a review.
Military mild traumatic brain injury (mTBI) differs from civilian injury in important ways. Although mTBI sustained in both military and civilian settings are likely to be underreported, the combat theater presents additional obstacles to reporting and accessing care. The impact of blast forces on the nervous system may differ from nonblast mechanisms, mTBI although studies comparing the neurologic and cognitive sequelae in mTBI survivors have not provided such evidence. However, emotional distress appears to figure prominently in symptoms following military mTBI. This review evaluates the extant literature with an eye towards future research directions.


Pulmonary tumor thrombotic microangiopathy: a systematic review.
Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal disease process in which pulmonary hypertension (PH) develops in the setting of malignancy. The purpose of this study is to present a detailed analysis of cases of PTTM reported in literature in the hopes of achieving more ante-mortem diagnoses. We conducted a systematic review of currently published and available cases of PTTM by searching the term "pulmonary tumor thrombotic microangiopathy" on the Pubmed.gov database. Seventy-nine publications were included consisting of 160 unique cases of PTTM. The most commonly reported malignancy was gastric adenocarcinoma (94 cases, 59%). Cough and dyspnea were reported in 61 (85%) and 102 (94%) cases, respectively. Hypoxemia was reported in 96 cases (95%). Elevation in D-dimer was noted in 36 cases (95%), presence of anemia in 32 cases (84%), and thrombocytopenia in 30 cases (77%). Common findings on chest computed tomography (CT) included ground-glass opacities (GGO) in 28 cases (82%) and nodules in 24 cases (86%). PH on echocardiography was noted in 59 cases (89%) with an average right ventricular systolic pressure of 71 mmHg. Common features of PTTM that are reported across the published literature include presence of dyspnea and cough, hypoxemia, with abnormal CT findings of GGO, nodules, and mediastinal/hilar lymphadenopathy, and PH. PTTM is a universally fatal disease process and this analysis provides a detailed examination of all the available published data that may help clinicians establish an earlier diagnosis of PTTM.


Metabolic indices of pulmonary damage. Changes in angiotensin converting enzyme and alpha 1 anti-trypsin activity after cardiopulmonary bypass.
The activity of angiotensin-converting enzyme was measured in patients undergoing cardiopulmonary bypass and in a control group requiring thoracotomy for pulmonary surgery. The activity of the enzyme was higher in patients with cardiac disease, fell during operations involving cardiopulmonary bypass, but did not change during thoracotomy for pulmonary surgery. Possible reasons for these differences are discussed. The activity of another enzyme, alpha 1 anti-trypsin, did not change during cardiopulmonary bypass and no arteriovenous difference could be detected during or after operation.


Attempting Well-Tempered Funnel Metadynamics Simulations for the Evaluation of the Binding Kinetics of Methionine Aminopeptidase-II Inhibitors.
Understanding the unbinding kinetics of protein-ligand complexes is considered a significant approach for the design of ligands with desired specificity and safety. In recent years, enhanced sampling methods have emerged as effective tools for studying the unbinding kinetics of protein-ligand complexes at the atomistic level. MetAP-II is a target for the treatment of cancer for which not a single effective drug is available yet. The identification of the dissociation rate of ligands from the complexes often serves as a better predictor for in vivo efficacy than the ligands' binding affinity. Here, funnel-based restraint well-tempered metadynamics simulations were applied to predict the residence time of two ligands bound to MetAP-II, along with the ligand association and dissociation mechanism involving the identification of the binding hotspot during ligand egress. The ligand-egressing route revealed by metadynamics simulations also correlated with the identified pathways from the CAVER analysis and by the enhanced sampling simulation using PLUMED. Ligand 1 formed a strong H-bond interaction with GLU364 estimating a higher residence time of 28.22 ± 5.29 ns in contrast to ligand 2 with a residence time of 19.05 ± 3.58 ns, which easily dissociated from the binding pocket of MetAP-II. The results obtained from the simulations were consistent to reveal ligand 1 being superior to ligand 2; however, the experimental data related to residence time were close for both ligands, and no kinetic data were available for ligand 2. The current study could be considered the first attempt to apply an enhanced sampling method for the evaluation of the binding kinetics and thermodynamics of two different classes of ligands to a binuclear metalloprotein.


Upstream reciprocity in heterogeneous networks.
Many mechanisms for the emergence and maintenance of altruistic behavior in social dilemma situations have been proposed. Indirect reciprocity is one such mechanism, where other-regarding actions of a player are eventually rewarded by other players with whom the original player has not interacted. The upstream reciprocity (also called generalized indirect reciprocity) is a type of indirect reciprocity and represents the concept that those helped by somebody will help other unspecified players. In spite of the evidence for the enhancement of helping behavior by upstream reciprocity in rats and humans, theoretical support for this mechanism is not strong. In the present study, we numerically investigate upstream reciprocity in heterogeneous contact networks, in which the players generally have different number of neighbors. We show that heterogeneous networks considerably enhance cooperation in a game of upstream reciprocity. In heterogeneous networks, the most generous strategy, by which a player helps a neighbor on being helped and in addition initiates helping behavior, first occupies hubs in a network and then disseminates to other players. The scenario to achieve enhanced altruism resembles that seen in the case of the Prisoner's Dilemma game in heterogeneous networks.


Homogeneity and synchronous dynamics of microbial communities in particulate biofilms: from major populations to minor groups.
Natural or engineered microbial populations often show variations over time. These variations may be due to environmental fluctuations or intrinsic factors. Thus, studying the dynamics of microbial diversity for different communities living in a spatially homogeneous landscape is of interest. As a model ecosystem, nitrifying biofilm communities were grown in a two litre inverse turbulent bed reactor (ITBR) containing an estimated 200 million small particles (about 150 µm in diameter). Each particulate biofilm is considered as a distinct community growing in the neighborhood of other similar particles, in a homogeneous and well-controlled environmental context. A molecular approach was adopted to test how microbial community structures might evolve: either in synchrony, converging or diverging. The shape of biofilm was observed by microscopy for each particle. The biomass content was evaluated by quantitative PCR and showed similar values for each particle. The microbial community structure was evaluated by Capillary Electrophoresis-Single Strand Conformation Polymorphism (CE-SSCP) fingerprinting and showed extraordinary homogeneity between particles, even though transitory community structures were observed when reactor operating conditions were modified. This homogeneity was observed for the Bacteria primer set but, more interestingly, was also observed when minor non-nitrifying bacteria making up the biofilm, representing about 5% and 10% of total cells, were targeted.


Comparison of recipient outcomes following transplant from local versus imported pancreas donors.
The shortage of deceased donor organs for solid organ transplantation continues to be an ongoing dilemma. One approach to increase the number of pancreas transplants is to share organs between procurement regions. To assess for the effects of organ importation, we reviewed the outcomes of 1014 patients undergoing deceased donor pancreas transplant at a single center. We performed univariate and multivariate analyses of the association of donor, recipient and surgical characteristics with patient outcomes. Organ importation had no effect on graft or recipient survival for recipients of solitary pancreas transplants. Similarly, there was no effect on technical failure rate, graft survival or long-term patient survival for simultaneous kidney-pancreas (SPK) recipients. In contrast, there was a significant and independent increased risk of death in the first year in SPK recipients of imported organs. SPK recipients had longer hospitalizations and increased hospital costs. This increased medical complexity may make these patients more susceptible to short-term complications resulting from the longer preservation times of import transplants. These findings support the continued use of organ sharing to reduce transplant wait times but highlight the importance of strategies to reduce organ preservation times.


A review of ovary torsion.
Ovarian torsion is a rare but emergency condition in women. Early diagnosis is necessary to preserve the function of the ovaries and tubes and prevent severe morbidity. Ovarian torsion refers to complete or partial rotation of the adnexal supporting organ with ischemia. It can affect females of all ages. Ovarian torsion occurs in around 2%-15% of patients who have surgical treatment of adnexal masses. The main risk in ovarian torsion is an ovarian mass. The most common symptom of ovarian torsion is acute onset of pelvic pain, followed by nausea and vomiting. Pelvic ultrasonography can provide information on ovarian cysts. Once ovarian torsion is suspected, surgery or detorsion is the mainstay of diagnosis and treatment.


COVID-19- related work, managerial factors and exhaustion among general practitioners in Sweden: a cross-sectional study.
A significant number of international studies show that general practitioners (GPs) suffered from burnout when working during the COVID-19 pandemic. A Swedish study found that more than 16% of GPs had exhaustion in spring 2021. Exhaustion can be regarded as an initial stage of burnout. A knowledge gap remains on GPs´ working conditions, the impact of management during the pandemic and how it was associated with exhaustion. This study aims to explore the association between severe symptoms of exhaustion and COVID-19 pandemic-related work and managerial factors among Swedish GPs and whether managerial factors have an impact on the association between exhaustion and COVID-19-related work factors. Cross-sectional data was drawn from the Longitudinal Occupational Health survey in Health Care Sweden (LOHHCS), which included a representative sample of practicing doctors in Sweden. The sample consisted of 6699 doctors with a response rate of 41.2%. This study constitutes a sample of doctors who reported working in primary care facilities at the time of data collection, i.e. 1013 GPs. The Burnout Assessment Tool (BAT) was used to assess severe symptoms of exhaustion. Questions were also asked about pandemic-related work and managerial factors. The data was analysed using descriptive statistics and multivariate logistic regression to identify the association between exhaustion, work and managerial factors. The multivariate analysis showed that GPs who managed COVID-19 patients were about twice as likely to report severe symptoms of exhaustion. Further, GPs who reported that management was unsupportive, provided unsatisfactory working conditions and unsatisfactory policies for patient prioritisation were between two and four times more likely to report severe symptoms of exhaustion. COVID-19-related work and managerial factors had a significant impact on the mental health of GPs. Furthermore, the potentially protective effect that satisfactory management actions had on mental health was limited. In the aftermath of the COVID-19 pandemic and in preparation for future major crises that have a high impact on healthcare, there is a need to investigate the measures that can be taken to enable GPs to carry out their work, while maintaining their wellbeing.


A standardised diagnostic approach to pituitary neuroendocrine tumours (PitNETs): a European Pituitary Pathology Group (EPPG) proposal.
The 2017 World Health Organization (WHO) classification proposes to type and subtype primary adenohypophyseal tumours according to their cell lineages with the aim to establish more uniform tumour groups. The definition of atypical adenoma was removed in favour of high-risk adenoma, and the assessment of proliferative activity and invasion was recommended to diagnose aggressive tumours. Recently, the International Pituitary Pathology Club proposed to replace adenoma with the term of pituitary neuroendocrine tumour (PitNET) to better reflect the similarities between adenohypophyseal and neuroendocrine tumours of other organs. The European Pituitary Pathology Group (EPPG) endorses this terminology and develops practical recommendations for standardised reports of PitNETs that are addressed to histo- and neuropathologists. This brief report presents the results of EPPG's consensus for the reporting of PitNETs and proposes a diagnostic algorithm.


Quantitation of an alpha subunit splicing intermediate: evidence for transcriptional activation in the control of acetylcholine receptor expression in denervated chick skeletal muscle.
We have investigated the mechanisms responsible for the increase in acetylcholine receptor subunit mRNAs during the induction of denervation supersensitivity in skeletal muscle. Using a cRNA probe specific for exon 7 (224 nucleotides; with flanking intron sequences of 105 nucleotides on the 3' end, and of 70 nucleotides on the 5' end) of the alpha subunit of the chicken muscle acetylcholine receptor gene, we were able to quantitate the concentration of mature alpha subunit mRNA and its precursor. In 3-wk-old chicks, the concentration of alpha subunit message in leg muscle was found to be 4.0 attomoles per microgram total RNA, and to increase 40-fold within 1 wk after section of the sciatic nerve. The molar ratio of precursor/mature mRNA, which was approximately 0.023 in innervated as well as denervated muscle, transiently rose to 0.047 at the beginning of the second postoperative day when mature message content increased 20-fold; the rise in precursor level preceded the increase in mature message content. These findings suggest that an accelerated rate of transcription of the message coding for the alpha subunit causes increased message content and the stimulation of receptor synthesis characteristic of denervated muscle.


ACC2 is expressed at high levels in human white adipose and has an isoform with a novel N-terminus [corrected].
Acetyl-CoA carboxylases ACC1 and ACC2 catalyze the carboxylation of acetyl-CoA to malonyl-CoA, regulating fatty-acid synthesis and oxidation, and are potential targets for treatment of metabolic syndrome. Expression of ACC1 in rodent lipogenic tissues and ACC2 in rodent oxidative tissues, coupled with the predicted localization of ACC2 to the mitochondrial membrane, have suggested separate functional roles for ACC1 in lipogenesis and ACC2 in fatty acid oxidation. We find, however, that human adipose tissue, unlike rodent adipose, expresses more ACC2 mRNA relative to the oxidative tissues muscle and heart. Human adipose, along with human liver, expresses more ACC2 than ACC1. Using RT-PCR, real-time PCR, and immunoprecipitation we report a novel isoform of ACC2 (ACC2.v2) that is expressed at significant levels in human adipose. The protein generated by this isoform has enzymatic activity, is endogenously expressed in adipose, and lacks the N-terminal sequence. Both ACC2 isoforms are capable of de novo lipogenesis, suggesting that ACC2, in addition to ACC1, may play a role in lipogenesis. The results demonstrate a significant difference in ACC expression between human and rodents, which may introduce difficulties for the use of rodent models for development of ACC inhibitors.


Statistical approaches to the monitoring and surveillance of infectious diseases for veterinary public health.
This paper covers the aspect of using statistical methodology for the monitoring and surveillance of routinely collected data in veterinary public health. An account of the Farrington algorithm and Poisson cumulative sum schemes for the prospective detection of aberrations is given with special attention devoted to the occurrence of seasonality and spatial aggregation of the time series. Modelling approaches for retrospective analysis of surveillance counts are also described. To illustrate the applicability of the methodology in veterinary public health, data from the monitoring of rabies among fox in Hesse, Germany, are analysed.


Stenosis in gastric bypass: Endoscopic management.
Gastric bypass is a treatment option for morbid obesity. Stenosis of the gastrojejunal anastomosis is a recognized complication. The pathophysiological mechanisms involved in the formation of stenosis are not well known. Gastrojejunal strictures can be classified based on time of onset, mechanism of formation, and endoscopic aspect. Diagnosis is usually obtained by endoscopy. The two main treatment alternatives for stomal stricture are: endoscopic dilatation (balloon or bouginage) and surgical revision (open or laparoscopic). Both techniques of dilation [through-the-scope (TTS) balloon dilators, Bougienage dilators] are considered safe, effective, and do not require hospitalization. The optimal technique for dilation of stomal strictures remains to be determined, but many authors prefer the use of TTS balloon catheters. Most patients can be successfully treated with 1 or 2 sessions. The need for reconstructive surgery of a stomal stricture is extremely rare.


Isolation and geographic distribution of Mycobacterium other than M. tuberculosis in British Columbia, 1972-81.
It has been suggested that the incidence of infection with mycobacteria other than typical tubercle (MOTT) bacilli is increasing. Laboratory and epidemiologic information relating to MOTT infection in British Columbia between 1972 and 1981 was analysed. Patient records for 1960-81 were also analysed. Of the 313 661 laboratory specimens 13 474 yielded Mycobacterium tuberculosis isolates and 3172, MOTT isolates. Over the 10 years the number of M. tuberculosis isolates declined, whereas the absolute and relative numbers of MOTT isolates increased. Members of the highly drug-resistant MAIS complex (M. avium-intracellulare, M. scrofulaceum and M. simiae) accounted for 73.3% of the 1778 potentially pathogenic MOTT isolates. MAIS isolation rates varied geographically. Analysis of patient records revealed 217 MOTT infections, of which 152 (70%) were due to MAIS organisms. Further studies are needed to determine the source of MAIS organisms in order that the infection and the disease may be more clearly understood.


A novel combination therapy of arginine deiminase and an arginase inhibitor targeting arginine metabolism in the tumor and immune microenvironment.
Tumor progression is dependent on tumor cells and their microenvironment. It is important to identify therapies that inhibit cancer cells and activate immune cells. Arginine modulation plays a dual role in cancer therapy. Arginase inhibition induced an anti-tumor effect via T-cell activation through an increase in arginine in the tumor environment. In contrast, arginine depletion by arginine deiminase pegylated with 20,000-molecular-weight polyethylene glycol (ADI-PEG 20) induced an anti-tumor response in argininosuccinate synthase 1 (ASS1)-deficient tumor cells. ADI-PEG 20 did not cause toxicity to normal immune cells, which can recycle the ADI-degraded product citrulline back to arginine. To target tumor cells and their neighboring immune cells, we hypothesized that the combination of an arginase inhibitor (L-Norvaline) and ADI-PEG 20 may trigger a stronger anticancer response. In this study, we found that L-Norvaline inhibits tumor growth in vivo. Pathway analysis based on RNA-seq data indicated that the differentially expressed genes (DEGs) were significantly enriched in some immune-related pathways. Significantly, L-Norvaline did not inhibit tumor growth in immunodeficient mice. In addition, combination treatment with L-Norvaline and ADI-PEG 20 induced a more robust anti-tumor response against B16F10 melanoma. Furthermore, single-cell RNA-seq data demonstrated that the combination therapy increased tumor-infiltrating CD8+ T cells and CCR7+ dendritic cells. The increase in infiltrated dendritic cells may enhance the anti-tumor response of CD8+ cytotoxic T cells, indicating a potential mechanism for the observed anti-tumor effect of the combination treatment. In addition, populations of immunosuppressive-like immune cells, such as S100a8+ S100a9+ monocytes and Retnla+ Retnlg+ TAMs, in tumors were dramatically decreased. Importantly, mechanistic analysis indicated that the processes of the cell cycle, ribonucleoprotein complex biogenesis, and ribosome biogenesis were upregulated after combination treatment. This study implied the possibility of L-Norvaline as a modulator of the immune response in cancer and provided a new potential therapy combined with ADI-PEG 20.


Prognostic factors in 1,038 women with metastatic breast cancer.
Treatment of metastatic breast cancer (MBC) remains palliative. Patients with MBC represent a heterogeneous group whose prognosis and outcome may be dependent on host factors. The purpose of the present study was dual: first, to draw up a list of factors easily available in everyday clinical practice requiring no sophisticated or costly methods and second, to provide results from a large cohort of women who underwent diagnostic and treatment at a single institution. From 1975 to 2005, a total of 1,038 women with MBC during their follow-up were included in this retrospective analysis. Patients were subsequently assigned to five groups according to the period of metastatic diagnosis. It is shown that age at initial diagnosis, hormonal receptor status and site of metastasis are the most relevant prognostic factors for predicting survival from the time of metastastic occurrence. It is also shown that a metastasis-free interval is an easily and immediately available multifactorial prognostic index reflecting the multiparametric variability of the disease. These fundamental observations may assist physicians in evaluating the survival potential of patients and in directing them toward the appropriate therapeutic decision.


Unmasking inhibition prolongs neuronal function in retinal degeneration mouse model.
All neurodegenerative diseases involve a relatively long period of timeframe from the onset of the disease to complete loss of functions. Extending this timeframe, even at a reduced level of function, would improve the quality of life of patients with these devastating diseases. The retina, as the part of the central nervous system and a frequent site of many distressing neurodegenerative disease, provides an ideal model to investigate the feasibility of extending the functional timeframe through pharmacologic intervention. Retinitis Pigmentosa (RP) is a group of blinding diseases. Although the rate of progression and degree of visual loss varies, there is usually a prolonged time before patients totally lose their photoreceptors and vision. It is believed that inhibitory mechanisms are still intact and may become relatively strong after the gradual loss of photoreceptors in RP patients. Therefore, it is possible that light-evoked responses of retinal ganglion cells and visual information processes in retinal circuits could be "unmasked" by blocking these inhibitory mechanisms restoring some level of visual function. Our results indicate that if the inhibition in the inner retina was unmasked in the retina of the rd10 mouse (the well-characterized RP mimicking, clinically relevant mouse model), the light-evoked responses of many retinal ganglion cells can be induced and restore their normal light sensitivity. GABA A receptor plays a major role in this masking inhibition. ERG b-wave and behavioral tests of spatial vision partly recovered after the application of PTX. Hence, removing retinal inhibition unmasks signalling mediated by surviving cones, thereby restoring some degree of visual function. These results may offer a novel strategy to restore the visual function with the surviving cones in RP patients and other gradual and progressive neurodegenerative diseases.


Therapy and Prevention of Noise Fears in Dogs-A Review of the Current Evidence for Practitioners.
Noise fears represent the most common behavioural problem in dogs. This manuscript provides an overview of diverse approaches for alleviating fear of noises in dogs and the supporting evidence. In the treatment of noise fears, both short-term solutions to prevent trauma or the deterioration of fear during unavoidable noise events and longer-term training need to be considered. Environmental management, the provision of incentives (food/play) during noise exposure, and, when indicated, anxiolytic medication, can safeguard dogs' welfare during noise events. Most "alternative" products (such as nutraceuticals, herbal remedies, pheromones, homeopathy, Bach flowers, and essential oils) are unlikely to be sufficient as monotherapy for noise fears, whereas there is good evidence for the efficacy of several anxiolytic medications. In the longer term, counterconditioning to real-life noises, relaxation training, and desensitisation/counterconditioning using noise recordings have been shown to improve fear of noises in dogs. Preventative training appears to be highly effective in preventing the development of noise fears in puppies and adult dogs.


Pericytopathy: oxidative stress and impaired cellular longevity in the pancreas and skeletal muscle in metabolic syndrome and type 2 diabetes.
The pericyte's role has been extensively studied in retinal tissues of diabetic retinopathy; however, little is known regarding its role in such tissues as the pancreas and skeletal muscle. This supportive microvascular mural cell, plays an important and novel role in cellular and extracellular matrix remodeling in the pancreas and skeletal muscle of young rodent models representing the metabolic syndrome and type 2 diabetes mellitus (T2DM). Transmission electron microscopy can be used to evaluate these tissues from young rodent models of insulin resistance and T2DM, including the transgenic Ren2 rat, db/db obese insulin resistant - T2DM mouse, and human islet amyloid polypeptide (HIP) rat model of T2DM. With this method, the earliest pancreatic remodeling change was widening of the islet exocrine interface and pericyte hypercellularity, followed by pericyte differentiation into islet and pancreatic stellate cells with early fibrosis involving the islet exocrine interface and interlobular interstitium. In skeletal muscle there was a unique endothelial capillary connectivity via elongated longitudinal pericyte processes in addition to pericyte to pericyte and pericyte to myocyte cell-cell connections allowing for paracrine communication. Initial pericyte activation due to moderate oxidative stress signaling may be followed by hyperplasia, migration, and differentiation into adult mesenchymal cells. Continued robust oxidative stress may induce pericyte apoptosis and impaired cellular longevity. Circulating antipericyte autoantibodies have recently been characterized, and may provide a screening method to detect those patients who are developing pericyte loss and are at greater risk for the development of complications of T2DM due to pericytopathy and rarefaction. Once detected, these patients may be offered more aggressive treatment strategies such as early pharmacotherapy in addition to life style changes targeted to maintaining pericyte integrity. In conclusion, we have provided a review of current knowledge regarding the pericyte and novel ultrastructural findings regarding its role in metabolic syndrome and T2DM.


Local INR correction: justification for a simplified approach.
Errors in reporting International Normalised Ratios (INR) may be corrected by assignment of a System International Sensitivity Index (System ISI). This 57 centre study tests the validity of several procedures for INR correction. Prothrombin times of eight lyophilised coumarin calibrants, a lyophilised normal pool calibrant, and eight frozen coumarin plasmas were determined at each centre. The calibrants were calibrated using international reference preparations. The eight frozen coumarin plasmas were calibrated in a four centre international exercise. The relations tested were: (a) the logarithm of local prothrombin time against the logarithm of reference prothrombin time; (b) reference INR against local prothrombin time; and (c) logarithm of reference INR against logarithm of local prothrombin time. These methods were analysed by both linear and orthogonal regression. All system groups required correction, the mean percentage deviation of the uncorrected data from the calibrated values was 19.0%. There was also considerable variation in INR, with the coefficient of variance (CV) ranging from 11.30 to 17.29%. Correction of INR was possible with all methods (CV reduced to < 7%). However, only when a plot of the logarithm of local prothrombin time against the logarithm of reference prothrombin time was fitted by orthogonal regression, or a plot of logarithm of reference INR against logarithm of local prothrombin time was fitted by either type of regression analysis, did the best fit line through the calibrant plasmas also pass close to the local mean normal prothrombin time. While INR correction may be achieved by all the above methods, that relating log reference INR to log local prothrombin time by linear regression analysis is the simplest to perform.


Functionalized carbon nanotubes as transporters for antisense oligodeoxynucleotides.
The use of DNA-based therapeutics requires efficient delivery systems to transport the DNA to their place of action within the cell. To accomplish this, we investigated multiwalled carbon nanotubes (pristine MWCNT, p-MWCNT) functionalized with hydroxyl groups via 1,3-dipolar cycloaddition. In this way, we have obtained MWCNT-f-OH with improved stability in aqueous dispersions which is an advantageous property for their use in cellular environments. Afterwards, a carrier strand oligodeoxynucleotide (CS-ODN) was adsorbed to MWCNT-f-OH followed by hybridization with a therapeutic antisense oligodeoxynucleotide (AS-ODN). The amount of adsorbed CS-ODN, as well as the complementary AS-ODN and a non-complementary oligodeoxynucleotide (NS-ODN) as reference, was directly measured by radionuclide labeling of ODNs. We show that subsequent release of AS-ODNs and NS-ODNs was possible for MWCNT-f-OH above the melting temperature of AS-ODNs at 80 °C and under physiological conditions at different pH values at 37 °C. We also show a very low influence of p-MWCNT and MWCNT-f-OH on the cell viability of the bladder carcinoma (BCa) cell line EJ28 and that both MWCNT types were internalized by EJ28. Therefore, MWCNT-f-OH represents a promising carrier able to transport and release AS-ODNs inside cells.


The effects of electronic cigarette aerosol exposure on inflammation and lung function in mice.
Electronic cigarette usage is increasing worldwide, yet there is a paucity of information on the respiratory health effects of electronic cigarette aerosol exposure. This study aimed to assess whether exposure to electronic cigarette (e-cigarette) aerosol would alter lung function and pulmonary inflammation in mice and to compare the severity of any alterations with mice exposed to mainstream tobacco smoke. Female BALB/c mice were exposed for 8 wk to tobacco smoke, medical air (control), or one of four different types of e-cigarette aerosol. E-cigarette aerosols varied depending on nicotine content (0 or 12 mg/ml) and the main excipient (propylene glycol or glycerin). Twenty-four hours after the final exposure, we measured pulmonary inflammation, lung volume, lung mechanics, and responsiveness to methacholine. Mice exposed to tobacco cigarette smoke had increased pulmonary inflammation and responsiveness to methacholine compared with air controls. Mice exposed to e-cigarette aerosol did not have increased inflammation but did display decrements in parenchymal lung function at both functional residual capacity and high transrespiratory pressures. Mice exposed to glycerin-based e-cigarette aerosols were also hyperresponsive to methacholine regardless of the presence or absence of nicotine. This study shows, for the first time, that exposure to e-cigarette aerosol during adolescence and early adulthood is not harmless to the lungs and can result in significant impairments in lung function.


Longitudinal trajectories of sleep duration in the general population.
Sleep duration has been associated with overall health status, health behaviours, and mortality. Little is known about habitual longitudinal patterns of sleep in the general population. Furthermore, evidence about whether sleep duration has declined in recent years is contradictory. The study was based on 8,673 adults aged 18 or older in 2002/2003 (cycle 5 of the National Population Health Survey) and used five self-reported biennial measurements of sleep duration spanning eight years. Multiple distinct trajectories of sleep duration were estimated using latent class growth modeling. Four modelled trajectories of sleep duration were identified: short (11.1% of the population); low-normal (49.4%); high-normal (37.0%); and long (2.4%). The short, low-normal and high-normal sleep trajectories each exhibited a slight linear decline in hours of sleep over the eight years of follow-up. Poor sleep quality was predictive of trajectory group membership and associated with a decrease in sleep duration for three of the four groups. Age and sex were also significant predictors of trajectory group membership. Trajectory analysis is a useful descriptive tool in the investigation of sleep duration over time.


Evaluation of finger strength and spasticity in hemiplegic patients using hand-finger robotic device: A validity and reliability study.
We aimed to investigate the validity, reliability, and clinical relevance of Amadeo hand-finger robotic rehabilitation system measurements for evaluating spasticity and strength in hemiplegic patients. In total, 161 participants (107 hemiplegic patients and 54 sex- and age-matched healthy controls) were included in this study. Spasticity was evaluated using the Modified Ashworth Scale, hand motor functions were evaluated using the Fugl-Meyer Assessment Hand Subscale, and hand grip and pinch strength were evaluated using the Jamar hand grip and pinch dynamometer. The Amadeo (Tyromotion) hand-finger robotic rehabilitation system was used to evaluate finger spasticity and strength of the participants. A statistically significant difference was found between the median values of the Modified Ashworth Scale (both clinical and robotic evaluation results) and the mean values of hand flexor and extensor strength measured with the robotic device in patients compared to healthy subjects (P < .01). Statistically, excellent agreement was obtained between the clinical and robotic test-retest results of the scale (P < .01) (intra-class correlation coefficient, ICC = .98-.99; ICC = .98-.99, respectively). There was a statistically significant positive correlation between the clinical and robotic device results of the Modified Ashworth Scale (r = .72; P < .01). There was a statistically significant positive correlation between the hand strength values measured with the robotic device, Jamar grip, pinch, and Fugl-Meyer Assessment Hand Subscale scores (P < .01) in the patient group. Hand finger spasticity and strength measurements of the Amadeo hand-finger robotic rehabilitation system were valid, reliable, and clinically correlated in stroke patients.


Biopolymer as an additive for effective biochar-based rhizobial inoculant.
Biochar is an efficient and inexpensive carrier for bacteria that stimulate plant development and growth. In this study, different biopolymer additives (cellulose, xanthan gum, chitin and tryptone) were tested with different addition ratios (1:0.1, 1:0.5 and 1:1) on further enhancing biochar capacity for supporting the growth and activity of Bradyrhizobium japonicum (CB1809). We utilized pine wood biochar (PWBC) pyrolyzed at 400 °C as the base inoculum carrier. The shelf life and survival rate of CB1809 were counted using the colony-forming unit (CFU) method for up to 120 days. Peat served as a standard reference material against which all treatments were compared. Subsequent experiments evaluated the ability of carrier inoculants to promote Glycine max L. (soybean) plant growth and nodulation under different watering regimes, i.e., 55 % water holding capacity (WHC) (D0), 30 % WHC (D1) and, 15 % WHC (D2) using sandy loam soil. Results revealed that among different additives; xanthan gum with 1:0.5 to PWBC [PWBC-xanthan gum(1:0.5)] was observed as a superior formulation in supporting rhizobial shelf life and survival rate of CB1809. In pot experiments, plants with PWBC-xanthan gum(1:0.5) formulation showed significant increase in various physiological characteristics (nitrogenase activity, chlorophyll pigments, membrane stability index, and relative water content), root architecture (root surface area, root average diameter, root volume, root tips, root forks and root crossings), and plant growth attributes (shoot/root dry biomass, shoot/root length, and number of nodules). Additionally, a reduced enrichment of isotopic signatures (δ13C, δ15N) was observed in plants treated with PWBC-xanthan gum(1:0.5), less enrichment of δ15N indicates an inverse link to nodulation and nitrogenase activity, while lower δ13C values indicates effective water use efficiency by plants during drought stress. These results suggest that biopolymers supplementation of the PWBC is useful in promoting shelf life or survival rate of CB1809.


Gene expression during formation of earlywood and latewood in loblolly pine: expression profiles of 350 genes.
The natural variability of wood formation in trees affords opportunities to correlate transcript profiles with the resulting wood properties. We have used cDNA microarrays to study transcript abundance in developing secondary xylem of loblolly pine (Pinus taeda) over a growing season. The cDNAs were selected from a collection of 75 000 ESTs that have been sequenced and annotated (http://web.ahc.umn.edu/biodata/nsfpine/). Cell wall thickness and climatic data were related to earlywood and latewood formation at different time points during the growing season. Seventy-one ESTs showed preferential expression in earlywood or latewood, including 23 genes with no significant similarity to genes in GenBank. Seven genes involved in lignin synthesis were preferentially expressed in latewood. The studies have provided initial insights into the variation of expression patterns of some of the genes related to the wood formation process.


Correlation of plasma coagulation tests and fibrinogenClauss with rotational thromboelastometry parameters and prediction of bleeding in dogs.
Correlation of plasma fibrinogen concentration (fibrinogenClauss ) with rotational thromboelastometry (ROTEM) parameters has not been investigated in dogs. To determine the correlation between plasma coagulation tests and fibrinogenClauss with ROTEM parameters and to evaluate their ability to predict bleeding in dogs. Ninety-seven dogs with concurrent determination of fibrinogenClauss and fibrin polymerization test (FIBTEM) analysis. Signalment, pretreatment, clinical signs of bleeding, fibrinogenClauss , plasma coagulation test results, hematocrit, platelet count, FIBTEM, extrinsic (EXTEM) and intrinsic (INTEM) activated ROTEM assays were retrieved retrospectively. Correlations between fibrinogenClauss and FIBTEM maximum clot firmness (MCFFIBTEM ) and between prothrombin time (PT) or activated partial thromboplastin time (aPTT) and ROTEM parameters were determined. Dogs were further assigned to groups with or without clinical signs of bleeding. The prognostic significance of significantly different parameters to predict bleeding was evaluated. FibrinogenClauss showed strong correlation with MCFFIBTEM (r = 0.860, n = 97, P < .001). PT showed strong correlation with EXTEM clotting time (CTEXTEM ) (r = 0.839, n = 53, P < .001), and aPTT was strongly correlated with INTEM CT (CTINTEM ) (r = 0.664, n = 31, P < .001). Platelet count, PT/aPTT, EXTEM clot formation time (CFTEXTEM ), MCFEXTEM , EXTEM maximum clot elasticity (MCEEXTEM ), and CTINTEM were significantly different between groups. A CTINTEM >149 seconds was 100% sensitive to detect bleeding. The MCFFIBTEM can be used to evaluate the effect of fibrinogen on hemostasis as an alternative to determination of fibrinogenClauss . In addition, CTEXTEM and CTINTEM are strongly correlated with PT and aPTT, respectively.


Next-Generation Sequencing Analysis of the Tineola bisselliella Larval Gut Transcriptome Reveals Candidate Enzymes for Keratin Digestion.
The clothes moth Tineola bisselliella is one of a few insects that can digest keratin, leading to the destruction of clothing, textiles and artwork. The mechanism of keratin digestion is not yet fully understood, partly reflecting the lack of publicly available genomic and transcriptomic data. Here we present a high-quality gut transcriptome of T. bisselliella generated from larvae reared on keratin-rich and keratin-free diets. The overall transcriptome consists of 428,221 contigs that were functionally annotated and screened for candidate enzymes involved in keratin utilization. As a mechanism for keratin digestion, we identified cysteine synthases, cystathionine β-synthases and cystathionine γ-lyases. These enzymes release hydrogen sulfite, which may reduce the disulfide bonds in keratin. The dataset also included 27 differentially expressed contigs with trypsin domains, among which 20 were associated with keratin feeding. Finally, we identified seven collagenases that were upregulated on the keratin-rich diet. In addition to this enzymatic repertoire potentially involved in breaking down keratin, our analysis of poly(A)-enriched and poly(A)-depleted transcripts suggested that T. bisselliella larvae possess an unstable intestinal microbiome that may nevertheless contribute to keratin digestion.