Genome-wide association mapping of canopy wilting in diverse soybean genotypes.
Genome-wide association analysis identified 61 SNP markers for canopy wilting, which likely tagged 51 different loci. Based on the allelic effects of the significant SNPs, the slowest and fastest wilting genotypes were identified. Drought stress is a major global constraint for crop production, and slow canopy wilting is a promising trait for improving drought tolerance. The objective of this study was to identify genetic loci associated with canopy wilting and to confirm those loci with previously reported canopy wilting QTLs. A panel of 373 maturity group (MG) IV soybean genotypes was grown in four environments to evaluate canopy wilting. Statistical analysis of phenotype indicated wide variation for the trait, with significant effects of genotype (G), environment (E), and G × E interaction. Over 42,000 SNP markers were obtained from the Illumina Infinium SoySNP50K iSelect SNP Beadchip. After filtration for quality control, 31,260 SNPs with a minor allele frequency (MAF) ≥5% were used for association mapping using the Fixed and random model Circulating Probability Unification (FarmCPU) model. There were 61 environment-specific significant SNP-canopy wilting associations, and 21 SNPs that associated with canopy wilting in more than one environment. There were 34 significant SNPs associated with canopy wilting when averaged across environments. Together, these SNPs tagged 23 putative loci associated with canopy wilting. Six of the putative loci were located within previously reported chromosomal regions that were associated with canopy wilting through bi-parental mapping. Several significant SNPs were located within a gene or very close to genes that had a reported biological connection to transpiration or water transport. Favorable alleles from significant SNPs may be an important resource for pyramiding genes to improve drought tolerance and for identifying parental genotypes for use in breeding programs.


Paediatric deep brain stimulation: ethical considerations in malignant Tourette syndrome.
Gilles de la Tourette syndrome (TS) is a childhood neuropsychiatric disorder characterised by the presence of motor and vocal tics. Patients with malignant TS experience severe disease sequelae; risking morbidity and mortality due to tics, self-harm, psychiatric comorbidities and suicide. By definition, those cases termed 'malignant' are refractory to all conventional psychiatric and pharmacological regimens. In these instances, deep brain stimulation (DBS) may be efficacious. Current 2015 guidelines recommend a 6-month period absent of suicidal ideation before DBS is offered to patients with TS. We therefore wondered whether it may be ethically justifiable to offer DBS to a minor with malignant TS. We begin with a discussion of non-maleficence and beneficence. New evidence suggests that suicide risk in young patients with TS has been underestimated. In turn, DBS may represent an invaluable opportunity for children with malignant TS to secure future safety, independence and fulfilment. Postponing treatment is associated with additional risks. Ultimately, we assert this unique risk-benefit calculus justifies offering DBS to paediatric patients with malignant TS. A multidisciplinary team of clinicians must determine whether DBS is in the best interest of their individual patients. We conclude with a suggestion for future TS-DBS guidelines regarding suicidal ideation. The importance of informed consent and assent is underscored.


Histochemical studies on the male accessory gland of Oxya velox (Insecta: Orthoptera).
The male accessory gland of Oxya velox includes fourteen pair of tubules opening into the ejaculatory duct. Histochemically these tubules can be distinguished into six types (AG1--AG6). Their secretion is the mixture of polysaccharides (Glycogen, sialomucin and neutral mucopolysaccharides), proteins (-NH2 and SH groups, tyrosine, tryptophan, histidine and arginine) and lipids (neutral and phospholipids). The possible role of the accessory glands based on their histochemical analysis has been speculated.


Deficiency of transcription factor RelB perturbs myeloid and DC development by hematopoietic-extrinsic mechanisms.
RelB is an NF-κB family transcription factor activated in the noncanonical pathway downstream of NF-κB-inducing kinase (NIK) and TNF receptor family members including lymphotoxin-β receptor (LTβR) and CD40. Early analysis suggested that RelB is required for classical dendritic cell (cDC) development based on a severe reduction of cDCs in Relb-/- mice associated with profound myeloid expansion and perturbations in B and T cells. Subsequent analysis of radiation chimeras generated from wild-type and Relb-/- bone marrow showed that RelB exerts cell-extrinsic actions on some lineages, but it has remained unclear whether the impact of RelB on cDC development is cell-intrinsic or -extrinsic. Here, we reevaluated the role of RelB in cDC and myeloid development using a series of radiation chimeras. We found that there was no cell-intrinsic requirement for RelB for development of most cDC subsets, except for the Notch2- and LTβR-dependent subset of splenic CD4+ cDC2s. These results identify a relatively restricted role of RelB in DC development. Moreover, the myeloid expansion in Relb-/- mice resulted from hematopoietic-extrinsic actions of RelB. This result suggests that there is an unrecognized but critical role for RelB within the nonhematopoietic niche that controls normal myelopoiesis.


Discovery of Negative-Sense RNA Viruses in Trees Infected with Apple Rubbery Wood Disease by Next-Generation Sequencing.
Apple rubbery wood is a disease of apple found around the world, often associated with Apple flat limb disease, and regulated in many countries. Despite its long history in apple cultivation, the disease's causal agent has remained elusive. In this study, next-generation sequencing (NGS) was used to identify and characterize several related novel viral agents from apple rubbery wood-infected plants, which have been named Apple rubbery wood virus (ARWV) 1 and 2. Additional specimens with apple rubbery wood disease tested positive by polymerase chain reaction with primers designed to ARWV 1 and 2 genomic RNA segments. In an NGS-based screening of over 100 Malus and 100 Prunus specimens from a collection of virus-infected trees, only one Malus specimen was found to be infected with ARWV not known to be infected with the disease, which strongly suggests that ARWV is not commonly found in Malus spp. or other fruit trees. The two viruses are most closely related to members of the order Bunyavirales. Three RNA segments (large, medium, and small) were characterized and the viruses likely represent a new genus under the family Phenuiviridae, with a suggested name of Rubodvirus (Rubbery wood virus).


Association of IL4R gene polymorphisms with asthma in Chinese populations.
Cytokines, having central functions in immunological and inflammatory processes, are expected to play important roles in the pathogenesis of various diseases, such as asthma. Genetic polymorphisms of those cytokine and cytokine receptor genes are the focus of genetic association studies. In an effort to identify gene(s) whose variant(s) are associated with asthma, we screened all exons and their flanking regions, as well as the promoter region (1.5kb) of eight genes, including IL4, IL13, IL12B, IL5, IL3, IL9, CD14 and IL4R. We identified 42 single nucleotide polymorphisms, 15 of which were novel. Then, we examined the genetic effects of 30 single nucleotide polymorphisms in eight cytokine and cytokine receptor genes on asthma in a Chinese asthma cohort (n = 537). Genetic association analysis of polymorphisms revealed that six polymorphisms (c.899-2C>A, c.1199A>C, c.1242G>T, c.1291T>C, c.1299T>C, c.1507T>C) in the IL4R gene, three of which resulted in an amino-acid change, showed significant association with the risk of asthma (P = 0.00023). Further analysis indicates that these six polymorphisms segregated in strong linkage disequilibrium. The genetic association of IL4R with asthma might provide valuable insights into the pathogenesis of asthma.


The Application of Intravoxel Incoherent Motion Diffusion-Weighted Imaging in the Diagnosis of Hilar Obstructive Jaundice.
The aim of this study was to investigate the potential of intravoxel incoherent motion diffusion-weighted imaging in diagnosing hilar obstructive jaundice. Fifty-nine patients diagnosed with hilar obstructive jaundice were enrolled in our hospital form January 2017 to January 2018. All the patients received scanning by a 3.0-T nuclear magnetic resonance scanner. The values of apparent diffusion coefficient (ADC)slow, ADCfast, and f were obtained and analyzed by 2 experienced radiologists. The differences between patients with hilar biliary obstruction and healthy volunteers in ADCslow, ADCfast, and f values were analyzed. Moreover, the differences between benign and malignant obstructive jaundice in ADCslow, ADCfast, and f values were analyzed. According to the serum levels of total bilirubin, patients were divided into 3 groups: mild, moderate, and severe obstructive jaundice. The differences between the 3 groups in ADCslow, ADCfast, and f values were also analyzed. The ADCfast values were obviously lower in patients with hilar obstructive jaundice than in healthy controls, whereas no significant difference in the values of ADCslow and f was found between both groups. The optimal cutoff value for ADCfast was 0.0341. The ADCfast values were significantly different between patients with benign and malignant hilar obstructive jaundice. The ADCfast values were negatively associated with the severity of hilar obstructive jaundice. Intravoxel incoherent motion diffusion-weighted imaging was a promising method for diagnosing hilar biliary obstruction jaundice.


Comparative proteomic profiling of uric acid, ammonium acid urate, and calcium-based kidney stones.
Kidney stone matrix proteins may help explain cellular mechanisms of stone genesis. However, most existing proteomic studies have focused on calcium oxalate stones. Here, we present a comparative proteomic analysis of different kidney stone types. Proteins were extracted from the stones of patients undergoing percutaneous nephrolithotomy (PCNL). Approximately 20 μg of protein was digested into tryptic peptides using filter aided sample preparation, followed by liquid chromatography tandem-mass-spectrometry using an EASY-nLC 1200 and Orbitrap Fusion Lumos mass spectrometer. A standard false discovery rate cutoff of 1% was used for protein identification. Stone analysis was used to organize stone samples into similar groups. We selected the top 5% of proteins based on total ion intensities and used DAVID and Ingenuity Pathway Analysis to identify and compare significantly enriched gene ontologies and pathways between groups. Six specimens were included and organized into the following four groups: 1) mixed uric acid (UA) and calcium-based, 2) pure UA, 3) pure ammonium acid urate (AAU), and 4) pure calcium-based. We identified 2,426 unique proteins (1,310-1,699 per sample), with 11-16 significantly enriched KEGG pathways identified per group and compared via heatmap. Based on number of unique proteins identified, this is the deepest proteomic study of kidney stones to date and the first such study of an AAU stone. The results indicate that mixed UA and calcium-based kidney stones are more similar to pure UA stones than pure calcium-based stones. AAU stones appear more similar to pure calcium-based stones than UA containing stones and may be related to parasitic infections. Further research with larger cohorts and histopathologic correlation is warranted.


Knowledge of Obstetric and Neonatal Danger Signs among Community Health Workers in the Rongo Sub-County of Migori County, Kenya: Results of a Community-based Cross-Sectional Survey.
In efforts to reduce maternal and neonatal mortality, it is recommended that all pregnant women be counseled on signs of pregnancy related complications and neonatal illness. In resource limited settings, such counselling may be task-shifted to lay health workers. We conducted a community-based cross-sectional survey of community health workers/volunteers in North and East Kamagambo of the Rongo Sub- County of Migori County, Kenya, between January-April 2018. A survey tool was administered through face-to-face interviews to investigate the level of knowledge of obstetric and neonatal danger signs among community health workers in North Kamagambo after one year of participation in the Lwala program, as well as to evaluate baseline knowledge of community health volunteers in East Kamagambo at the beginning of Lwala's expansion and prior to their receiving training from Lwala. The North Kamagambo group identified more danger signs in each category. The percentage of participants with adequate knowledge in the pregnancy, postpartum, and neonatal categories was significantly higher in North Kamagambo than in East Kamagambo. Sixty percent of participants in North Kamagambo knew 3 or more danger signs in 3 or more categories, compared to 24% of participants in East Kamagambo. Location in North Kamagambo (OR 2.526, p=0.03) and a shorter time since most recent training (OR 2.291, p=0.025) were associated with increased knowledge. Our study revealed varying levels of knowledge among two populations of lay health workers. This study highlights the benefit of frequent trainings and placing greater emphasis on identified gaps in knowledge of the labor and postpartum periods.


Epigenetic Changes of the ESR1 Gene in Breast Tissue of Healthy Women: A Missing Link with Breast Cancer Risk Factors?
Reproductive history and obesity are among the well-recognized risk factors in the development of breast cancer, which are partially mediated by the increased exposure of breast tissues to estrogens. However, only a few studies have investigated the link between these risk factors and the pattern of methylation signatures in the breast tissue of healthy women. The role of the estrogen receptor 1 (ESR1) gene hypermethylation is reportedly important in the development of breast cancer. Thus, it is speculated that such ESR1 epigenetic changes may be influenced or shaped by obesity and reproductive history-related factors before and during breast carcinogenesis. Breast samples were collected from 120 cancer-free women who had undergone cosmetic mammoplasty. DNA was extracted from the breast tissues and, then, the methylation levels at the promoter and exon 1 regions of the ESR1 gene CpG island were determined by using the methylated DNA immunoprecipitation-quantitative PCR assay. The methylation level of the ESR1 promoter observed in women with a body mass index (BMI) ≥30 kg/m2 (p ≤ 0.001) was higher than in the subgroups of women of BMI <25 kg/m2 (p < 0.001) and BMI 25-29 kg/m2 (p < 0.001) and was also higher in postmenopausal women compared with that in premenopausal women (p = 0.046). Pearson correlation coefficient analyses also showed that the high methylation of the ESR1 promoter was correlated with increasing age (r = -0.246, p = 0.007) and BMI (r = -0.331, p ≤ 0.001). Finally, linear multivariate regression revealed a significant association between high methylation rates in the ESR1 gene promoter and increased BMI (β = -0.285, 95% CI = -0.457 to -0.113, p = 0.001). Furthermore, a higher methylation level at the ESR1 gene exon 1 was found in the BMI ≥ 30 kg/m2 subgroup compared to the BMI 25-29 kg/m2 subgroup (p = 0.023). These findings provide new hints about the relationship between epigenetic changes within the ESR1 gene CpG island and postmenopausal obesity and aging in cancer-free women. In terms of lifestyle intervention opportunities, this study also highlights the significance and feasibility of such interventions for BMI as a modifiable risk factor.


Immunotherapeutic Approaches to Head and Neck Cancer.
Head and neck squamous cell carcinoma (HNSCC) is an immunosuppressive disease with multiple mechanisms to impair immune-mediated recognition and control of tumor cell proliferation and metastasis. Based on successes experienced with cancer immunotherapy in the treatment of other solid tumors, considerable efforts are underway to develop immunotherapeutics that can enhance the host antitumor response to HNSCC. Promising results in preclinical studies and early clinical trials have been reported, prompting the FDA to approve the use of the immune checkpoint PD-1 receptor antagonist pembrolizumab for the treatment of platinum-refractory recurrent or metastatic HNSCC in 2016. Ongoing clinical trials are investigating the use of various immunotherapies, such as vaccines, adoptive T-cell transfer, and immune modulating antibodies alone or in conjunction with traditional treatment modalities, to achieve more efficacious, more durable, and less toxic treatments. In this article, we provide a basic review of the role of the immune system in developing malignancy, and we discuss some notable mechanisms of immune evasion in HNSCC. We highlight current approaches and published clinical results of immunotherapy in the treatment of HNSCC.


Diagnosis of Dementia by Machine learning methods in Epidemiological studies: a pilot exploratory study from south India.
There are limited data on the use of artificial intelligence methods for the diagnosis of dementia in epidemiological studies in low- and middle-income country (LMIC) settings. A culture and education fair battery of cognitive tests was developed and validated for population based studies in low- and middle-income countries including India by the 10/66 Dementia Research Group. We explored the machine learning methods based on the 10/66 battery of cognitive tests for the diagnosis of dementia based in a birth cohort study in South India. The data sets for 466 men and women for this study were obtained from the on-going Mysore Studies of Natal effect of Health and Ageing (MYNAH), in south India. The data sets included: demographics, performance on the 10/66 cognitive function tests, the 10/66 diagnosis of mental disorders and population based normative data for the 10/66 battery of cognitive function tests. Diagnosis of dementia from the rule based approach was compared against the 10/66 diagnosis of dementia. We have applied machine learning techniques to identify minimal number of the 10/66 cognitive function tests required for diagnosing dementia and derived an algorithm to improve the accuracy of dementia diagnosis. Of 466 subjects, 27 had 10/66 diagnosis of dementia, 19 of whom were correctly identified as having dementia by Jrip classification with 100% accuracy. This pilot exploratory study indicates that machine learning methods can help identify community dwelling older adults with 10/66 criterion diagnosis of dementia with good accuracy in a LMIC setting such as India. This should reduce the duration of the diagnostic assessment and make the process easier and quicker for clinicians, patients and will be useful for 'case' ascertainment in population based epidemiological studies.


Bose-Einstein condensation in chains with power-law hoppings: Exact mapping on the critical behavior in d-dimensional regular lattices.
Recent experimental progress on the realization of quantum systems with highly controllable long-range interactions has impelled the study of quantum phase transitions in low-dimensional systems with power-law couplings. Long-range couplings mimic higher-dimensional effects in several physical contexts. Here, we provide the exact relation between the spectral dimension d at the band bottom and the exponent α that tunes the range of power-law hoppings of a one-dimensional ideal lattice Bose gas. We also develop a finite-size scaling analysis to obtain some relevant critical exponents and the critical temperature of the BEC transition. In particular, an irrelevant dangerous scaling field has to be taken into account when the hopping range is sufficiently large to make the effective dimensionality d>4.


High-Speed Rail Tunnel Panoramic Inspection Image Recognition Technology Based on Improved YOLOv5.
In order to meet the fast and accurate automatic detection requirements of equipment maintenance in railway tunnels in the era of high-speed railways, as well as adapting to the high dynamic, low-illumination imaging environment formed by strong light at the tunnel exit, we propose an automatic inspection solution based on panoramic imaging and object recognition with deep learning. We installed a hyperboloid catadioptric panoramic imaging system on an inspection vehicle to obtain a large field of view as well as to shield the high dynamic phenomena at the tunnel exit, and proposed a YOLOv5-CCFE object detection model based on railway equipment recognition. The experimental results show that the email@example.com value of the YOLOv5-CCFE model reaches 98.6%, and firstname.lastname@example.com:0.95 reaches 68.9%. The FPS value is 158, which can meet the automatic inspection requirements of railway tunnel equipment along the line and has high practical application value.


The effects of payments for pharmaceuticals: a systematic literature review.
The existence of different forms of out-of-pocket payments (OOPs) for pharmaceuticals across the globe provokes the question whether they can achieve more negative or positive consequences. A systematic literature review was conducted to assess the association between drug cost sharing and health care services utilization, health care costs as well as health outcomes. Studies published in The Cochrane Library, PubMed, Embase were searched with such keywords as: drug, pharmaceutical, cost sharing, out of pocket, co-payments paired with the following: impact, health outcomes, health care costs and utilization. The final review included 18 articles. A total of 11 publications reported the association between drug cost sharing and health care utilization patterns, of which nine found a statistically significant direct relationship. In all 10 publications concerned the association between drug copayments and health care costs. Majority were limited to the impact on the drug budget. Seven studies looked into the link between drug cost sharing and health outcomes, of which five reported statistically significant inverse relationship. There is some evidence for the association between drug copayments, health outcomes and health care services consumption. The optimal system of OOPs' payments for pharmaceuticals needs to prevent drugs' overconsumption and mitigate the risks of excessive cost sharing's burden.


Calsequestrin is a major binding protein of myotoxin alpha and an endogenous Ca2+ releaser in sarcoplasmic reticulum.
Myotoxin alpha from prairie rattlesnakes induced Ca2+ release from the heavy fraction of sarcoplasmic reticulum at submicromolar concentrations. 125I-Labeled myotoxin alpha (125I-myotoxin alpha) specifically bound to the heavy fraction. Fractionation of the solubilized heavy fraction with a spermine-agarose column gave purified calsequestrin as a major binding protein of 125I-myotoxin alpha. We have first indicated that calsequestrin is a target protein for Ca(2+)-releasing action of myotoxin alpha. Calsequestrin probably plays a key role in physiological Ca2+ release from sarcoplasmic reticulum.


Enhancing midwives' scope of practice: an innovative educational program for delivery suite operating rooms.
This retrospective study examined the enhancement of practice, knowledge, and skill of delivery suite midwives undertaking the circulating and instrument roles during emergent caesarean sections following a tailored educational program implemented to the benchmark standard. All midwives who attended the educational program were invited to participate (N = 48); a total of 20 responses were received. Descriptive data analysis of the bivariate nominal data was performed. Clinically significant outcomes were noted across all theme areas: knowledge of the Australian College of Operating Room Nurses standards, competence and knowledge of the main roles during a caesarean section, knowledge of policies and procedures, and patient safety. An improved working relationship between the perioperative and delivery ward staff also was identified. An educational program for midwives on the instrument and circulating roles for caesarean sections provides the knowledge and skill development required for clinically safe practice.


Congenital candidiasis.
Congenital candidiasis (CC) is a rare disease with less than 100 cases being reported in the literature. It presents within six days of life with manifestations ranging from localized skin disease to systemic involvement in the form of respiratory distress, sepsis, and death. We report a neonate who presented with diffuse pustular eruption on erythematous background involving face, trunk, and palms within 24 h after birth. Candida albicans was identified in 10% potassium hydroxide (KOH) smear and culture from the pustules. Intravenous fluconazole and topical ketoconazole were given and the condition improved completely in two weeks. CC is rare and needs to be differentiated from other conditions presenting with pustular lesions at birth in order to avoid complications. Early diagnosis and prompt treatment of this condition is important as untreated cases carry a mortality rate of 8-40%.


Management of raised blood pressure in New Zealand: a discussion document.
A report to the National Advisory Committee on Core Health and Disability Support Services, New Zealand, on the management of raised blood pressure recommends that decisions to treat raised blood pressure should be based primarily on the estimated absolute risk of cardiovascular disease rather than on blood pressure alone. In general, patients with a blood pressure of 150-170 mm Hg systolic or 90-100 mm Hg diastolic, or both, should be given treatment to lower blood pressure if the risk of a major cardiovascular disease event in 10 years is more than about 20%. The results of clinical trials indicate that, at this level of absolute risk, 150 people would require treatment to reduce the annual number of cardiovascular events by about one. Implementation of these recommendations may result in a smaller proportion of people aged under 60, particularly women, receiving treatment but an increased proportion of older people treated. In the absence of specific contraindications, low dose diuretics and low dose beta blockers should be considered for first line treatment, since for only these drug groups is there direct evidence of reduced risk of stroke and coronary disease in people with raised blood pressure.


Therapeutic potential of bone marrow-derived mesenchymal stem cells producing pigment epithelium-derived factor in lung carcinoma.
Specific and efficient gene delivery to target cells and the subsequent expression of the RNA and protein is crucial to the success of gene-based therapy for cancer. Mesenchymal stem cells (MSCs) represent novel and efficient tools for delivery of therapeutic agents to tumor cells. In this study, we evaluated the potential of bone marrow-derived mesenchymal stem cells, genetically modified to express pigment epithelium-derived factor (PEDF) for the treatment of Lewis lung carcinoma (LLC). MSCs derived from murine bone marrow were efficiently engineered to express human PEDF by adenoviral transduction, and the expression and bioactivity of the transgenic protein from engineered MSCs were confirmed in vitro. Animal experiments showed that the systemic administration of MSCs treated with PEDF dramatically reduced the growth of LLC tumors and significantly prolonged survival. Immunohistochemistry analysis of the tumors from MSC-PEDF-treated animals indicated an increase in apoptosis and a decrease in microvessel density. ELISA showed that the group of MSCs treated with PEDF had relatively higher expression levels of PEDF in tumor tissue and lower levels in serum compared with the free Ad-PEDF group. These results suggest that MSCs have potential use as effective delivery of vehicles for therapeutic genes in the treatment of LLC.


An Introduction and Brief Overview of Psychoanalysis.
The field of psychology has been shaped by the views and perspectives of Sigmund Freud and his former students: Carl Jung, Alfred Adler, Erik Erikson, and Karen Horney. These psychologists and their respective schools of thought provide distinct views on psychology and influences on personality and psychosocial development. The foundation for psychoanalysis was laid by Freud, his work on the unconscious mind, and his emphasis on early childhood experiences. His students also made substantial contributions that expanded, sharpened, and challenged his theories. This review will begin by highlighting the work of Sigmund Freud; it will then compare his theories with the theories of his students. This review will introduce and bring attention to the most important figures of psychoanalysis and give a brief overview of their theories.


Influence of maternal obesity on the skeletal muscle of offspring.
Maternal obesity has been described as a clinical entity associated with an increased incidence of metabolic diseases in the offspring, indicating a fetal programming phenomenon during this critical development period. Fetal exposure to an obesogenic environment affects multiple organs and tissues, including skeletal muscle, which is particularly susceptible to stressors from the external environment. Several studies have described alterations in the morphology and composition of skeletal muscle tissue secondary to obesogenic exposure in utero. In addition, modifications in signaling pathways related to the metabolism of energy substrates have been found in children born to mothers with obesity during pregnancy. This review addresses the current evidence describing the consequences of fetal exposure to an obesogenic maternal diet on skeletal muscle tissue, focusing on changes in tissue composition, alterations in signaling pathways related to glucose and fatty acid metabolism, mitochondrial biogenesis, and oxidative phosphorylation.


The influence of emotional valence on age differences in early processing and memory.
This study examined older and younger adults' attentional biases and subsequent incidental recognition memory for distracting positive, negative, and neutral words. Younger adults were more distracted by negative stimuli than by positive or neutral stimuli, and they correctly recognized more negative than positive words. Older adults, however, attended equally to all stimuli yet showed reliable recognition only for positive words. Thus, although an attentional bias toward negative words carried over into recognition performance for younger adults, older adults' bias appeared to be limited to remembering positive information.


Development of a simple genotyping method for the HLA-A*31:01-tagging SNP in Japanese.
To construct a simple, low-cost typing method for the surrogate marker of HLA-A*31:01, a risk factor for carbamazepine (CBZ) related Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). DNAs from Japanese SJS/TEN patients were used for genotyping and developing the assay. HLA-A*31:01 was confirmed to be significantly associated with definite/probable cases of CBZ-related SJS/TEN (p = 0.0040). Three single nucleotide polymorphisms, rs1150738, rs3869066 and rs259945, were in absolute linkage disequilibrium with HLA-A*31:01 in 210 Japanese SJS/TEN patients. Robust genotyping of rs3869066 in ZNRD1-AS1 was developed using polymerase chain reaction-restriction fragment length polymorphism assays. Single nucleotide polymorphism genotyping is less time consuming and cheaper than conventional HLA typing, and would be useful for identifying Japanese patients at risk of CBZ-related SJS/TEN.


Preparation and Characterization of Four Stereoisomers of Monatin.
Monatin is a naturally occurring, sweet amino acid comprising four stereoisomers due to its two asymmetric centers at C2 and C4. However, the characteristics of each stereoisomer have not yet been fully investigated. To obtain a sufficient amount of racemic monatin for optical resolution, a synthetic method was developed by modifying a possible biosynthetic pathway, i.e., a cross-aldol reaction and subsequent transamination. The key intermediate, 4-hydroxy-4-(3-indolylmethyl)-2-ketoglutaric acid, was obtained via the cross-aldol reaction of pyruvic acid and indole-3-pyruvic acid. Subsequently, the carbonyl group was converted to a hydroxyimino group through reaction with hydroxylamine and then to an amino group via hydrogenation to produce monatin. Next, the racemic monatin was divided into mixtures of two pairs of enantiomers through recrystallization. Finally, both enantiomers of the N-carbobenzoxy-γ-lactone derivatives of monatin were separated by preparative HPLC and deprotected. It was found that all optically pure stereoisomers exhibited a sweet taste. The isomer that displayed the most intense sweetness was the (2R,4R)-isomer, as determined by single crystal X-ray structure analysis of the monatin potassium salt, whereas the least sweet isomer was the (2S,4S)-isomer, which demonstrated a far lower sweetness than was previously reported.


Dynamic analysis of irreversible adsorption of protein on porous polymer resins as studied by pulse injection method.
Irreversible adsorption of bovine serum albumin onto porous polymer resins is examined by a pulse injection method. The experimental results are theoretically analyzed by a model based on the assumption that there exist three kinds of binding sites with different binding rates, which are considered to exist in the vicinity of the outer periphery surface, the inner surface of macropore, and the micropore, or center part, of particles. The three kinds of adsorption rates are also evaluated by a batch method and are nearly equal to the corresponding kinetic parameters by this method. The amount of BSA bound irreversibly to the resins is independent of the protein concentration and the flow rate examined, which suggests that protein molecules penetrate into pores of resins and occupy almost all the effective binding sites in the resins. The total amount of bound BSA shows a pH dependence with a maximum near the isoelectric point of BSA, and the amount of BSA bound at the slowest rate is most largely influenced by pH.


Synthesis of 1,2,4-triazole and 1,3,4-oxadiazole derivatives as inhibitors for STAT3 enzymes of breast cancer.
Disubstituted five-membered heterocycles (1,2,4-triazole and 1,3,4 oxadiazole) were synthesized and investigated as inhibitors for signal transducer and activator of transcription 3 (STAT3) enzyme of breast cancer. 3-(Benzylthio)-5-(4-chlorobenzyl)-4H-1,2,4-triazol-4-amine (12d) was found to be the most active among the synthesized compounds with a half-maximal inhibitory concentration (IC50 ) value of 1.5 µM on MCF7 cells and was found to show a great inhibitory effect on the STAT3 enzyme. Compounds 9a,b,d,e,f, 11, and 12a,b,f,e show IC50 values in the range of 3-12 µM for the MCF7 cell line. Molecular modeling was used to investigate the biological results of the synthesized compounds.


Systemic lupus erythematosus diagnosis impacts clinical outcomes of arteriovenous fistulas in comparison to other end-stage renal disease etiologies.
Arteriovenous fistulas primary patency at one-year occurs in 43-85% of the patients with end-stage renal disease. The diagnosis attributable to end-stage renal disease has been suggested to impact arteriovenous fistulas outcomes. The objective was to compare primary patency at one week, 1, 3, 6, and 12 months of follow-ups, among systemic lupus erythematosus patients and two control groups; additionally, we evaluated the impact of systemic lupus erythematosus to predict early patency loss. A retrospective review of charts from arteriovenous fistulas created between 2008 and 2017 was performed. One-hundred thirty-four patients were identified and classified according to end-stage renal disease attributable diagnosis as: systemic lupus erythematosus cases (N = 14), control-group-1 (91 patients with primarily diabetes and hypertension), and control-group-2 (29 patients with idiopathic end-stage renal disease). A case-control matched design (1:2:1) was proposed. Logistic regression analysis and Kaplan-Meier curves were used. Institutional Review Board approval was obtained. More systemic lupus erythematosus patients lost primary patency at 3 (28.6%) and 12 months (71.4%) than patients from control-groups-1 (vs. 3.6% and 35.7%, respectively) and -2 (vs. 0% and 14.3%, respectively), (p ≤ 0.011 for both). Days of primary patency survival were shorter in systemic lupus erythematosus patients (p = 0.003). Systemic lupus erythematosus diagnosis was the only factor associated with early patency loss, HR: 3.141, 95%CI: 1.161-8.493 (systemic lupus erythematosus diagnosis vs. control-group-1) and HR: 12.582, 95%CI: 1.582-100.035 (systemic lupus erythematosus diagnosis vs. control-group-2). Diagnosis attributable to end-stage renal disease has a major impact on arteriovenous fistula outcomes in patients. Systemic lupus erythematosus patients have an increased risk of arteriovenous fistulas patency loss within the first six months of follow-up. Patients with idiopathic end-stage renal disease had an excellent one year arteriovenous fistula patency survival.


Melatonin Attenuates Cardiac Ischemia-Reperfusion Injury through Modulation of IP3R-Mediated Mitochondria-ER Contact.
Although the interplay between mitochondria and ER has been identified as a crucial regulator of cellular homeostasis, the pathogenic impact of alterations in mitochondria-ER contact sites (MERCS) during myocardial postischemic reperfusion (I/R) injury remains incompletely understood. Therefore, in our study, we explored the beneficial role played by melatonin in protecting cardiomyocytes against reperfusion injury via stabilizing mitochondria-ER interaction. In vitro exposure of H9C2 rat cardiomyocytes to hypoxia/reoxygenation (H/R) augmented mitochondrial ROS synthesis, suppressed both mitochondrial potential and ATP generation, and increased the mitochondrial permeability transition pore (mPTP) opening rate. Furthermore, H/R exposure upregulated the protein content of CHOP and caspase-12, two markers of ER stress, and enhanced the transcription of main MERCS tethering proteins, namely, Fis1, BAP31, Mfn2, and IP3R. Interestingly, all the above changes could be attenuated or reversed by melatonin treatment. Suggesting that melatonin-induced cardioprotection works through normalization of mitochondria-ER interaction, overexpression of IP3R abolished the protective actions offered by melatonin on mitochondria-ER fitness. These results expand our knowledge on the cardioprotective actions of melatonin during myocardial postischemic reperfusion damage and suggest that novel, more effective treatments for acute myocardial reperfusion injury might be achieved through modulation of mitochondria-ER interaction in cardiac cells.


Antibody Response to SARS-CoV-2 Membrane Protein in Patients of the Acute and Convalescent Phase of COVID-19.
Understanding the course of the antibody response directed to individual epitopes of SARS-CoV-2 proteins is crucial for serological assays and establishment of vaccines. Twenty-one synthetic peptides were synthesized that have ten amino acids overlap and cover the complete membrane (M) protein. Plasma samples from 32 patients having acute disease and 30 patients from the convalescent phase were studied. Only peptide M01 (aa 1-20) and to a lesser extent peptide M21 (aa 201-222) showed specific reactivity as compared to historical control plasma samples. Peptide M01 was recognized by IgM- (71.9%) and IgG-specific antibodies (43.8%) during the acute phase as early as day 8 PIO. In a longitudinal analysis, a higher reactivity was observed for the IgM response directed to peptide M01 following day 20 PIO as compared to earlier time points of the acute phase. In the convalescent phase, antibody reactivity to the two M-specific peptides was significantly lower (<30% seropositivity). A fusion protein encoding major parts of RBD also showed higher rates of recognition during acute (50.0%) and lower rates in the convalescent phase (23.3%). Taken together, our results suggest that during the acute phase of COVID-19 antibodies are raised to two linear epitopes of the SARS-CoV-2 M protein, located at the very N- and C-termini, showing almost similar levels of reactivity as immunodominant linear epitopes derived from the spike and nucleocapsid protein. Anti-M is also present in the convalescent phase of COVID-19 patients, however at lower levels, with the N-terminus of the M protein as a preferred target.


Neonatal nutrition: a focus on parenteral nutrition and early enteral nutrition.
No population has benefited more from the development and advancement of specialized nutrition support than pediatric patients. Today, neonates comprise the largest group of pediatric patients receiving parenteral nutrition (PN). Nutrient needs of neonates differ substantially from other populations, presenting unique challenges in optimizing nutrition care. Neonates are highly susceptible to catabolic stress because of reduced energy stores and markedly increased energy needs. Immature organ systems and metabolic pathways further complicate the delivery of adequate nutrition in the preterm neonate. Early nutrition support is essential to improve survival, reduce catabolism, promote growth, and limit developmental complications. This article discusses feeding strategies for PN and early enteral nutrition in neonates, particularly the preterm neonate.


[Contact surface and pressure load at implant-bone interface in press-fit cups compared to natural hip joints].
The implantation of an endoprosthetic socket into the acetabulum alters the mechanical stresses in the periacetabular region in a significant manner compared with the natural hip joint. In this way, a remodelling process is initiated. Primary stability to achieve osseointegration and a loading of the acetabulum owing to the biomechanical interaction between cup and bone that is similar to the natural joint, are important prerequisites for a long-term bony integration of the implant. Therefore, the intra-articular pressure distribution in eight hip joints of fresh-frozen human pelvic cadavers and in the bone/implant interface of two press-fit cups was investigated using pressure-sensitive Prescale films. A modular cup with a pure hemispherical shape (PCA cup) and a monoblock cup with a biradial surface and flattening of the pole (press-fit cup) were tested. Loads of up to twice body weight were introduced into the sacrum, simulating a single-leg stance with the hip in neutral flexion. The results were extracted from the pressure prints applying digital image processing methods. It was demonstrated that intra-articular contact occurs over the whole articular surface of the joint, with contact areas between 39.0% and 56.9% of the hemisphere, showing zones of higher pressures where the acetabulum is supported by the iliac, ischial and pubic bone. The biradial press-fit cup showed mean contact areas of 44.7% of its surface when inserted under press-fit only. This area was enlarged to 53.0% and to 64.2% with increasing load. The corresponding figures for the PCA cup are 45.1%, 48.9% and 57.1%. The low-profile PCA cup produces a small band of high pressure near the periphery, and with increasing load its pole area comes into contact with the acetabular fossa. Occasionally, irregular gaps do occur. The press-fit cup enlarges the contact area from the periphery to the pole within its optimised biradial contact zone until the lunar surface is loaded. The acetabular fossa remains unloaded owing to the flattening of the pole. This load distribution is close to that of the natural hip joint. The pressure distribution of both cups is also characterised by three zones at the iliac, ischial and pubic bones showing a higher load transmission.


A novel RHCE*02 allele, containing the single-nucleotide change c.460A>G, encodes weakened expression of C and e antigens.
We report a novel RHCE*02 allele in a Swedish blood donor that is characterized by the change c.460A>G (Arg154Gly). The blood donor's red blood cells showed variable reactivity with different monoclonal anti-C and anti-e and antigen strength was markedly weakened. We believe that these changes represent both a quantitative and qualitative alteration of the antigens encoded by this allele.


First branchial cleft syndromes and associated congenital hearing loss.
We have recently encountered three cases of first branchial cleft syndromes, two of which had prominent hearing losses. The cases are described, and the literature pertaining to first branchial cleft syndrome is reviewed. Because of the frequent coexistence of various congenital anomalies, we feel that the prevalence of congenital otologic problems associated with a first branchial cleft syndrome may be greater than has previously been suspected.


Spray-Processed Composites with High Conductivity and Elasticity.
Highly conductive elastic composites were constructed using multistep solution-based fabrication methods that included the deposition of a nonwoven polymer fiber mat through solution blow spinning and nanoparticle nucleation. High nanoparticle loading was achieved by introducing silver nanoparticles into the fiber spinning solution. The presence of the silver nanoparticles facilitates improved uptake of silver nanoparticle precursor in subsequent processing steps. The precursor is used to generate a second nanoparticle population, leading to high loading and conductivity. Establishing high nanoparticle loading in a microfibrous block copolymer network generated deformable composites that can sustain electrical conductivities reaching 9000 S/cm under 100% tensile strain. These conductive elastic fabrics can retain at least 70% of their initial electrical conductivity after being stretched to 100% strain and released for 500 cycles. This composite material system has the potential to be implemented in wearable electronics and robotic systems.


3-D microstructure of olivine in complex geological materials reconstructed by correlative X-ray μ-CT and EBSD analyses.
We reconstruct the 3-D microstructure of centimetre-sized olivine crystals in rocks from the Almirez ultramafic massif (SE Spain) using combined X-ray micro computed tomography (μ-CT) and electron backscatter diffraction (EBSD). The semidestructive sample treatment involves geographically oriented drill pressing of rocks and preparation of oriented thin sections for EBSD from the μ-CT scanned cores. The μ-CT results show that the mean intercept length (MIL) analyses provide reliable information on the shape preferred orientation (SPO) of texturally different olivine groups. We show that statistical interpretation of crystal preferred orientation (CPO) and SPO of olivine becomes feasible because the highest densities of the distribution of main olivine crystal axes from EBSD are aligned with the three axes of the 3-D ellipsoid calculated from the MIL analyses from μ-CT. From EBSD data we distinguish multiple CPO groups and by locating the thin sections within the μ-CT volume, we assign SPO to the corresponding olivine crystal aggregates, which confirm the results of statistical comparison. We demonstrate that the limitations of both methods (i.e. no crystal orientation data in μ-CT and no spatial information in EBSD) can be overcome, and the 3-D orientation of the crystallographic axes of olivines from different orientation groups can be successfully correlated with the crystal shapes of representative olivine grains. Through this approach one can establish the link among geological structures, macrostructure, fabric and 3-D SPO-CPO relationship at the hand specimen scale even in complex, coarse-grained geomaterials.


The unstable patella after total knee arthroplasty: etiology, prevention, and management.
In total knee arthroplasty, most complications related to the extensor mechanism are caused by patellar maltracking or instability. Patellar maltracking may result from component malpositioning and limb malalignment, prosthetic design, improper patellar preparation, or soft-tissue imbalance. Patellofemoral instability likely results most frequently from internal malrotation of the femoral or tibial components. Although a patellofemoral radiograph may display the lateral subluxation of the patella, only computed tomography can quantify rotational malalignment of the femoral or tibial component. Nonsurgical treatment is generally unsuccessful; major malposition of components is best managed by implant revision. In the absence of component malposition, proximal realignments (lateral patellar retinacular release with lateral advancement of the vastus medialis obliquus muscle) or tibial tubercle transfers have been used. Surgical procedures on the patellar tendon itself may risk rupture of the extensor mechanism.


Squamous Cell Carcinoma Scalp With Intracranial Extension: Challenging Case of Multidisciplinary Care.
Squamous cell carcinoma (SCC) of the scalp is the second most common non-melanoma cancer of the skin. The incidence of squamous cell carcinoma on the scalp is on the rise, but the intracranial extension is rare. Cranial invasion is rare in SCC of the scalp, but when present, it is associated with a poor prognosis. A 62-year-old female presented with complaints of swelling over the back of her scalp for three months, which rapidly increased in size. She also had a throbbing headache, alopecia in that area, and multiple episodes of pustules in that area. On examination, she had an ulceroproliferative lesion measuring 5*5*3 cm with an irregular surface and varying consistency over the occipital area in the midline surrounded by ulcerations and crusted discharge and fixed to the bone. Contrast-enhanced magnetic resonance imaging (MRI) showed an irregular lesion with the destruction of the right parietal and occipital bones involving both inner and outer tables with intracranial and extracranial components, and the lesion was abutting the superior sagittal sinus. The treatment is surgical resection of the tumor with margin clearance. The treatment plan was designed using a multidisciplinary approach with the collaboration of oncosurgery, neurosurgery, and plastic surgery. The patient underwent wide local excision of the tumor with adequate skin and cranial bone clearance. The tumor was found to have infiltrated the dura mater overlying the superior sagittal sinus. The defect was then closed using a vault prosthetic cover and a scalp transposition flap from the left parietal area. This case report intends to highlight the need for a multidisciplinary approach to the proper management of advanced squamous cell carcinoma to decrease the morbidity and mortality in patients.


[X-ray microanalysis of the activity of immobilized glucose oxidase on enzyme electrode].
The localization of activity of glucose oxidase (GOD) on the pussian blue modified electrode by SiO2 sol-gel was studied by X-ray microanalysis. Glucose and Ce(NO3)3 served as substrate and capture respectively. Substrate was catalysed by immobilized GOD toproduce H2O2, and the H2O2 was captured by Ce(NO3)3 to form precipitate. The precipitation deposited the active site of immobilized GOD on the enzyme electrode. The X-ray microanalysis showed that the distribution of active enzyme on the surface of the enzyme electrode was uniform, and the GOD immobilized maintained high activity. The X-ray analysis exhibited that the properties of the enzyme electrode depended on the distribution of enzyme activity on its surface from the view of microstructure, and the developed GOD electrode was of high sensitivity and excellent stability. The results agreed with the results of the electrochemical study.


Singlet versus Triplet Excited State Mediated Photoinduced Dehalogenation Reactions of Itraconazole in Acetonitrile and Aqueous Solutions.
Photoinduced dehalogenation of the antifungal drug itraconazole (ITR) in acetonitrile (ACN) and ACN/water mixed solutions was investigated using femtosecond and nanosecond time-resolved transient absorption (fs-TA and ns-TA, respectively) and nanosecond time-resolved resonance Raman spectroscopy (ns-TR3) experiments. An excited resonance energy transfer is found to take place from the 4-phenyl-4,5-dihydro-3H-1,2,4-triazol-3-one part of the molecule to the 1,3-dichlorobenzene part of the molecule when ITR is excited by ultraviolet light. This photoexcitation is followed by a fast carbon-halogen bond cleavage that leads to the generation of radical intermediates via either triplet and/or singlet excited states. It is found that the singlet excited state-mediated carbon-halogen cleavage is the predominant dehalogenation process in ACN solvent, whereas a triplet state-mediated carbon-halogen cleavage prefers to occur in the ACN/water mixed solutions. The singlet-to-triplet energy gap is decreased in the ACN/water mixed solvents and this helps facilitate an intersystem crossing process, and thus, the carbon-halogen bond cleavage happens mostly through an excited triplet state in the aqueous solutions examined. The ns-TA and ns-TR3 results also provide some evidence that radical intermediates are generated through a homolytic carbon-halogen bond cleavage via predominantly the singlet excited state pathway in ACN but via mainly the triplet state pathway in the aqueous solutions. In strong acidic solutions, protonation at the oxygen and/or nitrogen atoms of the 1,2,4-triazole-3-one group appears to hinder the dehalogenation reactions. This may offer the possibility that the phototoxicity of ITR due to the generation of aryl or halogen radicals can be reduced by protonation of certain moieties in suitably designed ITR halogen-containing derivatives.


Microbiological contamination with moulds in work environment in libraries and archive storage facilities.
Microbiological contamination with fungi, including moulds, can pose a significant health hazard to those working in archives or museums. The species involved include Aspergillus, Penicillium, Geotrichum, Alternaria, Cladosporium, Mucor, Rhizopus, Trichoderma, Fusarium which are associated mostly with allergic response of different types. The aim of the study was to analyse, both in quantitative and qualitative terms, workplace air samples collected in a library and archive storage facilities. Occupational exposure and the related health hazard from microbiological contamination with moulds were assessed in three archive storage buildings and one library. Air samples (total 60) were collected via impact method before work and at hourly intervals during work performance. Surface samples from the artifacts were collected by pressing a counting (RODAC) plate filled with malt extract agar against the surface of the artifacts. The air sample and surface sample analyses yielded 36 different mould species, classified into 19 genera, of which Cladosporium and Penicillium were the most prevalent. Twelve species were regarded as potentially pathogenic for humans: 8 had allergic and 11 toxic properties, the latter including Aspergillus fumigatus. Quantitative analysis revealed air microbiological contamination with moulds at the level ranging from 1.8 x 10(2)-2.3 x 10(3) cfu/m(3). In surface samples from library and archive artifacts, 11 fungal species were distinguished; the number of species per artifact varying from 1-6 and colony count ranging from 4 x 10(1) to 8-10(1) cfu/100 cm(2). Higher contamination levels were found only for Cladosporium cladosporioides (1.48 x 10(3) cfu/100 cm(2)) and Paecillomyces varioti (1.2 x 10(2) cfu/100 cm(2)). At the workposts examined, although no clearly visible signs of mould contamination could be found, the study revealed abundant micromycetes, with the predominant species of Cladosporium and Penicillium. The detected species included also potentially pathogenic microorganisms which can cause allergic and toxic effects, such as Aspergillus fumigatus, that could be hazardous to workers' health. For some species, the concentration levels exceeded the values considered the proposed hygienic standards for total microscopical fungi in occupational settings. The findings of the study point to unsatisfactory hygienic conditions at the worksites examined, resulting in microbiological contamination with moulds, as well as the necessity for prompt remedial activities on the part of the employers.


Complementation of an RNase P RNA (rnpB) gene deletion in Escherichia coli by homologous genes from distantly related eubacteria.
We report the construction of a strain of Escherichia coli in which the only functional gene for the RNA moiety of RNase P (rnpB) resides on a plasmid that is temperature sensitive for replication. The chromosomal RNase P RNA gene was replaced with a chloramphenicol acetyltransferase gene. The conditionally lethal phenotype of this strain was suppressed by plasmids that carry RNase P RNA genes from some distantly related eubacteria, including Alcaligenes eutrophus, Bacillus subtilis, and Chromatium vinosum. Thus, the rnpB genes from these organisms are capable of functioning as the sole source of RNase P RNA in E. coli. The rnpB genes of some other organisms (Agrobacterium tumefaciens, Pseudomonas fluorescens, Bacillus brevis, Bacillus megaterium, and Bacillus stearothermophilus) could not replace the E. coli gene. The significance of these findings as they relate to RNase P RNA structure and function and the utility of the described strain for genetic studies are discussed.


Systemic Platelet-Activating Factor-Receptor Agonism Enhances Non-Melanoma Skin Cancer Growth.
Platelet-activating factor-receptor (PAF-R) agonists are pleiotropic lipid factors that influence multiple biological processes, including the induction and resolution of inflammation as well as immunosuppression. PAF-R agonists have been shown to modulate tumorigenesis and/or tumor growth in various skin cancer models by suppressing either cutaneous inflammation and/or anti-tumoral adaptive immunity. We have previously shown that a chronic systemic PAF-R agonist administration of mice enhances the growth of subcutaneously implanted melanoma tumors. Conversely, chronic topical applications of a PAF-R agonist suppressed non-melanoma skin cancer (NMSC) in a topical chemical carcinogenesis model (dimethylbenz[a]anthracene/phorbol 12-myristate 13-acetate (DMBA/PMA)) in-part via anti-inflammatory effects. These results indicate that the context of PAF-R agonist exposure via either chronic cutaneous or systemic administration, result in seemingly disparate effects on tumor promotion. To further dissect the contextual role of PAF-R agonism on tumorigenesis, we chronically administered systemic PAF-R agonist, carbamoyl-PAF (CPAF) to mice under a cutaneous chemical carcinogenesis protocol, recently characterized to initiate both NMSC and melanocytic nevus formation that can progress to malignant melanoma. Our results showed that while systemic CPAF did not modulate melanocytic nevus formation, it enhanced the growth of NMSC tumors.


Developing effective and caring nurse-patient relationships.
Establishing positive and trusting therapeutic relationships with patients has long been recognised as an essential component of nursing practice and is important for effective care. There are various challenges in clinical practice that make it increasingly difficult to deliver effective care centred on such relationships. Understanding and addressing these challenges is crucial to ensure a positive experience of care for patients, families, carers and nurses. This article outlines how nurses can use a framework to develop therapeutic relationships with patients and use the best available evidence to deliver effective care. It also explores the challenges in developing effective therapeutic relationships with patients at the healthcare system level, and considers how these challenges can be addressed.


Challenges and strategies for commercialization and widespread practical applications of superhydrophobic surfaces.
Superhydrophobic (SH) surfaces have progressed rapidly in fundamental research over the past 20 years, but their practical applications lag far behind. In this perspective, we first present the findings of a survey on the current state of SH surfaces including fundamental research, patenting, and commercialization. On the basis of the survey and our experience, this perspective explores the challenges and strategies for commercialization and widespread practical applications of SH surfaces. The comprehensive performances, preparation methods, and application scenarios of SH surfaces are the major constraints. These challenges should be addressed simultaneously, and the actionable strategies are provided. We then highlight the standard test methods of the comprehensive performances including mechanical stability, impalement resistance, and weather resistance. Last, the prospects of SH surfaces in the future are discussed. We anticipate that SH surfaces may be widely commercialized and used in practical applications around the year 2035 through combination of the suggested strategies and input from both academia and industry.


Co-Influence of Nanofiller Content and 3D Printing Parameters on Mechanical Properties of Thermoplastic Polyurethane (TPU)/Halloysite Nanotube (HNT) Nanocomposites.
Thermoplastic polyurethane (TPU) belongs to a polyurethane family that possesses an elongation much higher than 300%, despite having low mechanical strength, which can be overcome by incorporating clay-based halloysite nanotubes (HNTs) as additives to manufacture TPU/HNT nanocomposites. This paper focuses on the co-influence of HNT content and 3D printing parameters on the mechanical properties of 3D printed TPU/HNT nanocomposites in terms of tensile properties, hardness, and abrasion resistance via fused deposition modelling (FDM). The optimum factor-level combination for different responses was determined with the aid of robust statistical Taguchi design of experiments (DoEs). Material characterisation was also carried out to evaluate the surface morphology, nanofiller dispersion, chemical structure, thermal stability, and phase behaviour corresponding to the DoE results obtained. It is evidently shown that HNT level and infill density play a significant role in impacting mechanical properties of 3D-printed TPU/HNT nanocomposites.


Effects of erythropoietin on osteoblast in the tooth extraction socket in mice periodontitis model.
Periodontitis is an excessive inflammatory event in tooth-supporting tissues and can cause tooth loss. We used erythropoietin (EPO), which has been reported to play an important role in bone healing and modulation of angiogenesis, as a therapeutic agent in vivo and in vitro experimental models to analyze its effect on periodontitis. First, EPO was applied to in vitro MC3T3-E1 cells and human periodontal ligament fibroblast (hPDLF) cells to examine its function in altered cellular events and gene expression patterns. In vitro cultivation of MC3T3-E1 and hPDLF cells with 10 IU/ml EPO at 24 and 48 h showed an obvious increase in cell proliferation. Interestingly, EPO treatment altered the expression of osteogenesis-related molecules, including alkaline phosphatase (ALP), bone morphogenetic protein-2 (BMP-2), and osteocalcin (OC) in MC3T3-E1 cells but not in hPDLF cells. In particular, MC3T3-E1 cells showed increased expression of ALP, BMP-2, and OC on day 5, while hPDLF cells showed increased expression of BMP-2, and OC on day 14. Based on the in vitro examination, we evaluated the effect of EPO on bone formation using an experimentally-induced animal periodontitis model. After the induction of periodontitis in the maxillary left second M, 10 IU/ml of EPO was locally applied to the extraction tooth sockets. Histomorphological examination using Masson's trichrome (MTC) staining showed facilitated bone formation in the EPO-treated groups after 14 days. Similarly, stronger positive reactions against vascular endothelial growth factor (VEGF), cluster of differentiation 31 (CD31), runt-related transcription factor 2 (RUNX2), and osteocalcin (OC) were detected in the EPO-treated group compared to the control. Meanwhile, myeloperoxidase, an inflammatory marker, was decreased in the EPO-treated group on days 1 and 5. Overall, EPO facilitates bone healing and regeneration through altered signaling regulation and modulation of inflammation in the osteoblast cell lineage and to a lesser extent in hPDLF cells.


Postoperative acute kidney injury and renal replacement therapy after DCD lung transplantation.
Acute kidney injury (AKI) after lung transplantation (LTx) is a common complication. We aimed to assess whether donation after circulatory death (DCD) is associated with an increased risk of AKI and renal replacement therapy (RRT) in the early postoperative period compared to the donation after brain death (DBD). Retrospective data on a cohort (N = 95) of LTx patients (DCD n = 17, DBD n = 78) characterized by no use of ex-vivo lung perfusion were analyzed for the incidence of AKI within 30 postoperative days and incidence of RRT within 7 and 30 days. After optimal full matching, an imbalance remained between the DCD and DBD patients in respect to intraoperative use of cardiopulmonary bypass (CPB). Therefore, a further subset (n = 77) was defined that excluded CPB patients, and matching was repeated (DCD n = 13 vs. DBD n = 63) resulting in a fair balance on a range of preoperative characteristics and intraoperative use of ECMO. In both matched subsets, DCD was associated with around twice higher risk of AKI and RRT within 7 and 30 postoperative days. In conclusion, data suggest that DCD could be associated with worse early renal outcomes in a subset of LTx patients and justify further studies on the topic in order to refine further renal care pathways perioperatively.


[Phage typing and biotyping of salmonella typhi-murium (author's transl)].
1998 strains of Salmonella typhi-murium from two different regions of West-Germany were investigated according to their biotype and phagetype. 132 strains were isolated from sewage, 320 strains from animals and the others from human beings. 60 different phagetypes were found. The phagetype 49 occurred most often (11,9% resp. 10,3%). A correlation between biotype and phagetype could not be observed. Nearly every phagetype could be divided into several biotypes. However, only few biotypes prevaled. These comprised the biotypes 1, 10 and 17. The examination of the splitting of trehalose was useful in the biochemical differentiation. Concerning strains of animal origin it was remarkable that most strains from cattle resp. calves belonged to the phagetype 49. Among 145 strains from pigeons 95,9% could be classified as phagetype 2. With exception of 3 strains all the other strains from pigeons did not possess the O-antigen 5. The majority of the strains belonged to the biotype 8. All these strains could not split maltose.


[Initial experience with the PCDiary: software for physicians for documenting and evaluating individual learning].
A computer diary was developed for physicians to create a portfolio of their self-directed learning. Each item of learning is recorded in the form of a question along with the stimulus, the learning resources used and the outcome planned for the learning. The records of 123 physicians which volunteered to use the diary were analyzed. Their response to the software, elicited by survey, is described. Items of learning were most often stimulated by scanning the literature and while seeking information to manage a patient. The physicians recorded their intent to change their practice as the outcome to learning most often when the learning was stimulated while managing a patient. One-half of the physicians reported that keeping the diary made them think about their patient care.


Madurella mycetomatis is not susceptible to the echinocandin class of antifungal agents.
Eumycetoma caused by Madurella mycetomatis is treated surgically and with high doses of ketoconazole. Therapeutic responses are poor, and recurrent infections are common. In search of therapeutic alternatives in the treatment of mycetoma, we determined the in vitro susceptibilities of M. mycetomatis isolates against caspofungin, anidulafungin, and micafungin. As a comparator fungus, Aspergillus fumigatus was used. Minimal effective concentrations (MECs) and MICs were assessed and compared to those of ketoconazole. M. mycetomatis isolates were not susceptible to the echinocandins.


Hyperspectral NIR imaging for calibration and prediction: a comparison between image and spectrometer data for studying organic and biological samples.
A hyperspectral image in the near infrared contains thousands of position-referenced spectra. After imaging reference materials of known composition it is possible to build Partial Least Squares (PLS) regression models for predicting unknown compositions from new images or spectra. In this paper a comparison is made between spectra from a hyperspectral image and spectra from two spectrometers: a scanning grating instrument with rotating sample holders and an FT-NIR instrument utilizing a fiber-optic probe. The raw spectra and the quality of the PLS calibration models and predictions are compared. Two sample datasets consist of a set of 13 designed artificial mixtures of pure constituents and a selection of 13 sampled cheeses. The prediction error from the hyperspectral image spectra is between that of the two spectrometers. For a typical food sample, the average bias [and replicate standard deviation] was -0.6% [0.5%] for protein and -0.2% [1.3%] for fat. Comparable values for the best spectrometer were -0.2% bias for protein and -0.5% for fat. Some of the advantages of working with hyperspectral images are highlighted: the simultaneous exploration of representations of both spectral and spatial data, and the analysis of concentration profiles and concentration maps all contribute to better characterization of organic and biological materials.


Neutrophil, quo vadis?
Neutrophils were traditionally considered to be a homogeneous population of terminally differentiated cells with very defined roles in inflammation and fighting infections. However, recent advances in neutrophil research challenge this limited view and demonstrate that neutrophils are highly versatile, play different roles in various pathologic scenarios, and are heterogeneous. With this, it is becoming clear that one term-"neutrophil"-is too general, and more precise nomenclature is urgently required. In this mini review, we discuss the knowns and unknowns in neutrophil terminology and highlight the critical questions that should be addressed for the establishment of clear neutrophil nomenclature.


The challenge of grandmultiparity in obstetric practice.
Traditionally grandmultiparity has been considered to be an obstetric hazard both to the mother and foetus. Compounding factors are low socioeconomic status, poor female literacy and social deprivation. In developed populations with improved and optimal obstetric services, parity per se is no longer considered a significant risk for adverse obstetric and perinatal outcome. To compare the obstetric and perinatal outcome between grandmultiparas and second gravidas with previous one delivery as well as analyse certain socio demographic features in the two groups. Case records from Maternity Hospital, Kathmandu, an inner city tertiary care centre were retrospectively studied. 106 cases of grandmultiparous patients were compared with 110 cases of second gravidas who had previously delivered once which was taken as the control group. Biosocial features as well as obstetric and perinatal outcome were analyzed. Rural residents comprised 60.4% of the grandmultiparous group versus 27.7% of the control group. A predominance of early marriage as well as an older age profile was noted in the grandmultipara. ANC attendance was documented to be much lower among grandmultipara with 26.4% having absolutely no antenatal care. A higher frequency of hypertensive disorders in pregnancy, preterm birth, anaemia, malpresentations, multiple pregnancy and premature rupture of membranes, postpartum haemorrhage and retained placenta was noted in the grandmultipara which also had a slightly higher caesarean delivery rate. The salient adverse perinatal outcome was found to be intrauterine foetal death, preterm birth and neonatal sepsis. In our set up, grandmultiparity continues to challenge our obstetric practice with its associated increased likelihood of maternal and perinatal complications. Concerted effort should be directed to reducing high parity in the community through effective family planning initiatives and specialized antepartum and intrapartum supervision of this group should be available.


Cutaneous phaeohyphomycosis in a hematopoietic stem cell transplant patient caused by Alternaria rosae: First case report.
Alternaria species have been reported as a rare cause of fungal infection in organ and stem cell transplant recipients, but to date, no reports have been published of infection in humans caused by Alternaria rosae. Here, we report cutaneous A. rosae infection in a 66-year-old farmer with a history of primary myelofibrosis who had undergone allogeneic unrelated donor hematopoietic stem cell transplantation. Forty-nine days post transplant, he presented with a nodule on the thumb with no findings suggestive of disseminated infection. Pathology, culture, and molecular speciation showed the nodule was caused by cutaneous A. rosae. He had been on voriconazole as antifungal prophylaxis, but was found to have a subtherapeutic voriconazole level. He was switched to posaconazole based on published in vitro data showing its superior efficacy in Alternaria treatment. Susceptibility testing showed that the A. rosae isolate was indeed susceptible to posaconazole. His cutaneous lesion remained stable, but he died from respiratory failure secondary to lobar pneumonia. At lung autopsy, A. rosae was not identified in the lungs. We believe this to be the first published report, to our knowledge, of A. rosae infection in humans.


Cord blood transplantation in Japan.
Cord blood transplantation (CBT) has increasingly been used in Japan and the annual number of CBT now exceeds 1,200. The cumulative number of CBT reached 12,853 in 2015, accounting for almost 1/3 of total CBT performed worldwide. It is true that smaller body size and lower costs, as compared to western countries, have been advantages for Japanese people in using CB as graft alternative. In addition, several novel findings regarding serious issues following CBT have been obtained, which further enhanced the use of CB. First, several mechanisms of engraftment failure following CBT other than cell dose have been reported, such as the presence of donor-specific anti-HLA antibodies or the development of hemophagocytic syndrome. Second, unique profiles of infectious complications following CBT have been reported, such as higher incidences of early bacterial infections and HHV-6 encephalitis, as compared to those following bone marrow (BM)/peripheral blood (PB) transplants. Third, the incidence of disease relapse was comparable to those following BM/PB transplants. Novel pre-transplant conditioning regimens using intravenous busulfan have been investigated with promising results being obtained to date. A recent analysis of Japanese transplant registry data revealed similar survival following CBT to HLA-matched unrelated BM/PB transplants.


Volatile constituents of uncooked rhubarb (Rheum rhabarbarum L.) stalks.
Volatiles of rhubarb (Rheum rhabarbarum L.) stalks were isolated by means of vacuum headspace method and analyzed by capillary gas chromatography-mass spectrometry. Fifty-nine components were reported for the first time in rhubarb. A striking feature of the extracts obtained is the preponderance (approximately 65%) of compounds with C(6) skeletons. In addition to unsaturated C(6) aldehydes and alcohols, substantial amounts of the less common (E)-2- and (E)-3-hexenoic acid were detected. Gas chromatography-olfactometry and determination of odor activity values revealed the sensory importance of the C(6) compounds to the aroma of rhubarb. Comparative experiments involving the inhibition of enzyme activities revealed that the initial spectrum of C(6) components is changed due to subsequent isomerization and reductions. Thus, contributions of (Z)-3-hexenal and the unsaturated acids decrease, and (E)-2-hexenal/(E)-2-hexenol play major sensory roles.


Depolarization of the intergeniculate leaflet neurons by serotonin - in vitro study.
The intergeniculate leaflet of the thalamus (IGL) is a part of the mammalian biological clock which integrates photic and non-photic information and conveys it to the master biological clock - suprachiasmatic nuclei (SCN). One of the non-photic cues is delivered by the serotoninergic projection from dorsal raphe nucleus. In vitro electrophysiological recordings were performed from single IGL neurons using whole-cell patch clamp technique. We investigated the influence of serotonin (serotonin creatinine sulfate complex, 5HT) on 'spontaneous' neuronal activity in this structure. In most of recorded cells, 5-HT caused significant increases in firing rate. In majority of cases the effect was presynaptic. However, in some cases we observed postsynaptic depolarization. To our knowledge, depolarizing influence of 5HT on the single neurons in the IGL has been shown here for the first time.


Recent advances in cardiopulmonary resuscitation.
Mechanical and pharmacologic measures intended to increase blood flow to vital organs are the mainstay of therapy for patients in cardiac arrest. Several new cardiopulmonary resuscitation (CPR) techniques as well as novel devices and pharmacologic agents have been developed and tested since the first report of manual closed chested CPR over three decades ago. These recent mechanical and pharmacologic advances in the treatment of cardiac arrest are described. Some of these new techniques, devices, and drug therapies are presently undergoing clinical evaluation in patients in cardiac arrest. While many of these new methods and techniques have shown promise in small clinical trials in humans, none have yet to be found to be conclusively superior to manual closed chested CPR and treatment with standard pharmacologic agents.


Extreme Metabolic Alkalosis and Acute Kidney Injury in a 38-Year-Old Male Patient.
Repeated vomiting may lead to profound loss of fluid and electrolytes. We describe a case with life-threatening acid-base disturbances due to vomiting. A 38-year-old man presented to an emergency department with weakness and decreased urine output after having vomited up to 20 times per day over a period of 7 days. Arterial blood gas analysis revealed a metabolic alkalosis with partial respiratory compensation. Initial management consisted of oxygen therapy and intravenous fluid therapy with normal saline and potassium chloride. To prevent further gastric losses of HCl, proton-pump inhibitors and metoclopramide were administered. The vomiting was caused most likely by a temporary duodenal stenosis due to portal hypertension of unknown etiology. In our opinion, this case demonstrates the successful management of a life-threatening condition by simple measures. Despite extensive diagnostic procedures, the effective treatment of the underlying condition consisted of watchful waiting.


Growth trends in body, fat, circumferential and physiological traits during adolescence among Rajput females of Theog, Shimla District (Himachal Pradesh), India.
Information on growth status of a population is essential to establish the health status of the population and administer any health intervention programmes. The study aimed to examine growth patterns in body, fat and physiological traits during adolescence in the light of various hypotheses and other studies. Cross-sectional data on a sample of 220 Rajput girls aged 11-17 years were collected from Theog tehsil, Shimla District in Himachal Pradesh. Mean body height and weight increased by 11% and 45.5%, respectively, from age 11 to 17 years. The first marked growth in height took place between 11 and 12 years, while the maximum annual increment was witnessed between 13 and 14 years. ANOVA revealed significant differences in anthropometric traits between various adolescent age groups. Waist-hip ratio (WHR) decreased from 0.77 at age 11 to 0.72 at age 17 years to attain gynoid pattern of body fat. Mean systolic and diastolic blood pressure increased from 106.92 and 66.48 mm Hg to 111.74 and 72.89 mm Hg, respectively. Although the girls in the present study did not suffer from any severe malnutrition, they had lower dimensions than their Western counterparts when they entered the adolescence phase and also later on. In contrast to height deficits, increase in weight deficits was greater. There is no indication of any compensatory or catch-up growth during adolescence. The present study does not support the hypothesis that lower nutritional stage during childhood affects the timing of adolescent take-off, age at peak height and weight velocity. The data lend support to the hypothesis of saltatory patterns with intervening periods of stasis. BMI, %fat and FM were significantly correlated with diastolic blood pressure but non-significantly correlated with systolic blood pressure.


Qualitative comparison of bremsstrahlung X-rays and 800 MeV protons for tomography of urania fuel pellets.
We present an assessment of x-rays and proton tomography as tools for studying the time dependence of the development of damage in fuel rods. We also show data taken with existing facilities at Los Alamos National Laboratory that support this assessment. Data on surrogate fuel rods have been taken using the 800 MeV proton radiography (pRad) facility at the Los Alamos Neutron Science Center (LANSCE), and with a 450 keV bremsstrahlung X-ray tomography facility. The proton radiography pRad facility at LANSCE can provide good position resolution (<70 μm has been demonstrate, 20 μm seems feasible with minor changes) for tomography on activated fuel rods. Bremsstrahlung x-rays may be able to provide better than 100 μm resolution but further development of sources, collimation, and detectors is necessary for x-rays to deal with the background radiation for tomography of activated fuel rods.


The differential expression of MC1R regulators in dorsal and ventral quail plumages during embryogenesis: Implications for plumage pattern formation.
Melanin pigmentation patterns are ubiquitous in animals and function in crypsis, physical protection, thermoregulation and signalling. In vertebrates, pigmentation patterns formed over large body regions as well as within appendages (hair/feathers) may be due to the differential distribution of pigment producing cells (melanocytes) and/or regulation of the melanin synthesis pathway. We took advantage of the pigmentation patterns of Japanese quail embryos (pale ventrum and patterned feathers dorsally) to explore the role of genes and their transcripts in regulating the function of the melanocortin-1-receptor (MC1R) via 1. activation: pro-opiomelanocortin (POMC), endoproteases prohormone convertase 1 (PC1) and 2 (PC2), and 2. inhibition-agouti signaling and agouti-related protein (ASIP and AGRP, respectively). Melanocytes are present in all feather follicles at both 8 and 12 days post-fertilisation (E8/E12), so differential deposition of melanocytes is not responsible for pigmentation patterns in embryonic quail. POMC transcripts expressed were a subset of those found in chicken and POMC expression within feather follicles was strong. PC1 was not expressed in feather follicles. PC2 was strongly expressed in all feather follicles at E12. ASIP transcript expression was variable and we report four novel ASIP transcripts. ASIP is strongly expressed in ventral feather follicles, but not dorsally. AGRP expression within feather follicles was weak. These results demonstrate that the pale-bellied quail phenotype probably involves inhibition of MC1R, as found previously. However, quail may require MC1R activation for eumelanogenesis in dorsal feathers which may have important implications for an understanding of colour pattern formation in vertebrates.


Gastric ischaemia following a fall.
A previously well 73-year-old gentleman presented 5 days after a fall from 6 feet from a ladder with abdominal pain and vomiting. X-rays demonstrated evidence of bowel perforation. On arrival, the patient was peritonitic and displayed a severely septic picture. He was subsequently taken for emergency laparotomy. A 5 mm perforation was found in the small bowel which was repaired but unusually a large segment in the fundus and greater curvature of the stomach was found to be necrotic. A partial gastrectomy was performed and histology confirmed ischaemia likely to be secondary to trauma. The patient has now been successfully discharged home.


Is sedation safe during dynamic sleep fluoroscopy of children with obstructive sleep apnea?
Airway compromise is considered a relative contraindication for pediatric sedation. This contraindication presents a paradoxical problem when patients require sedation in preparation for imaging performed to evaluate the cause of airway obstruction. We use dynamic sleep fluoroscopy in the evaluation of children who have obstructive sleep apnea. The purpose of this study was to evaluate the success and safety of a structured sedation program for dynamic sleep fluoroscopy. Eighty consecutive dynamic sleep fluoroscopic studies were evaluated. The type of sedation used, success rate, complications related to the sedation, and characteristics of the children studied were reviewed. Patients were sedated in accordance with our departmental sedation program guidelines. Findings on fluoroscopy were correlated with episodes of oxygen desaturation or noisy breathing. In all 80 cases, dynamic sleep fluoroscopy was successfully performed. Seventy-two studies were performed, with sedation supervised by the radiologist. Four patients fell asleep without sedation. In four patients, sedation was performed by an anesthesiologist (preprocedural decision). Sixty-four children (80%) had complex medical problems, and 39 (49%) had a history of previous airway surgery. All studies were considered successful. Specific diagnoses were identified in 66 children (83%). No children suffered complications or required tracheal intubation. Children with airway compromise who are being evaluated for obstructive sleep apnea can be successfully and safely sedated for dynamic sleep fluoroscopy when a structured sedation program is used.


Ocular manifestations in bidi industry workers: possible consequences of occupational exposure to tobacco dust.
Tobacco consumption is the leading preventable cause of disease, disability, and premature death but little is known about its deleterious effect on the ocular health of workers handling tobacco. The goal of this study was to identify probable effects of occupational tobacco exposure among south Indian bidi-industry workers. This study included 310 females (mean age, 34.8 +/- 10.9 years) actively involved in bidi-rolling presenting with eye symptoms to a tertiary eye care hospital. Results suggested that a wide spectrum of ocular complications exist among these workers. Common ocular symptoms were defective vision, dull-aching headache and eye irritation. The main ocular findings were papillary conjunctival hyperplasia, hyperpigmentation of ocular surface, punctate epithelial erosion or superficial punctate keratitis, cataract or pseudophakia and segmental optic atrophy. Abstaining from work, supplementation of Vitamin B complex rich in B 12 and appropriate surgical or medical management reversed visual loss due to corneal disease or cataract but was not effective in optic neuropathy.


Missense mutations in exon 6 of the survival motor neuron gene in patients with spinal muscular atrophy (SMA).
Spinal muscular atrophy (SMA) is a frequent autosomal recessive neurodegenerative disorder leading to weakness and atrophy of voluntary muscles. The survival motor neuron gene (SMN) is a strong candidate for SMA and present in two highly homologous copies (telSMN and cenSMN) within the SMA region (5q11.2-q13.3). More than 90% of SMA patients show homozygous deletions of at least exon 7 of telSMN, whereas absence of cenSMN seems to have no clinical consequences. In 23 non-deleted SMA patients, we searched for intragenic mutations of the SMN genes in exons 1-7 and the promotor region by single strand conformation analysis. We identified two different missense mutations, S2621 and T2741, in exon 6 of telSMN in three independent SMA families, providing further evidence for the telSMN gene as a SMA determining gene. Both mutations, as well as two previously described mutations (Y272C and G279V) are located within a highly conserved interval from codon 258 to codon 279 which seems to be an important functional domain of the telSMN protein. Recently, this region has been shown to contain a tyrosine/glycine-rich motif, which is also present in various RNA binding proteins, suggesting a potential role of SMN in RNA metabolism. Missense mutations might be useful for in vivo and transgenic experiments and further investigations on understanding the function of the telSMN protein.


Virion-independent transfer of replication-competent hepatitis C virus RNA between permissive cells.
In this study, we show that replication-competent subgenomic hepatitis C virus (HCV) RNA can be transferred to permissive Huh7 cells, leading to the establishment of viral RNA replication. Further, we show that these events are mediated by exosomes rather than infectious virus particles. If similar events occur in vivo, this could represent a novel, albeit inefficient, mechanism of viral spread and immune escape.


BB creatine kinase and myogenic differentiation. Immunocytochemical identification of a distinct precursor compartment in the chicken skeletal myogenic lineage.
Antisera specific for the B monomer of creatine kinase (B-CK), the M monomer of creatine kinase (M-CK), and muscle-specific myosin heavy chain (MHC) were used to investigate the biochemical characteristics of individual cells in primary myogenic cultures. Through the use of immunocytochemical techniques, in conjunction with 3H-thymidine autoradiography, it was determined that (1) all of the terminally differentiated myoblasts contained B-CK in addition to M-CK and MHC, (2) none of the cycling cells contained M-CK or MHC, (3) a fraction (7.5%) of the cycling cells contained B-CK, and (4) the cycling, B-CK positive cells divided once, and only once, and produced two terminally differentiated myoblasts. These results indicate that myogenic precursors in vitro are a phenotypically heterogeneous cell population and that the appearance of B-CK in cycling myogenic cells is a biochemical manifestation of a distinct precursor compartment in the chicken skeletal myogenic lineage.


Comparison between the direct capillary tube leucocyte migration technique (LMCT) and the direct agarose leucocyte migration technique (LMAT) as indicators of tumour-directed cell-mediated hypersensitivity (TCMH) in patients with renal carcinoma.
A comparison was made between the direct capillary tube leucocyte migration technique (LMCT) and the direct agarose leucocyte migration technique (LMAT) using crude homogenates of tumour tissue as antigen in patients with renal carcinoma. A state of specifically altered reactivity of leucocytes from patients with renal carcinoma as compared with normal control persons towards allogeneic hypernephroma extracts could be detected in the LMCT but not in the LMAT. The reactivity in the LMCT was manifest at protein concentrations of 300 and 400 mug/ml. The study indicates that in contrast to the LMCT, the LMAT cannot be used for detection of TCMH towards allogeneic hypernephroma tissue extracts in patients with renal carcinoma.


Diagnosis of childhood tuberculosis in Malawi: an audit of hospital practice.
All 44 non-private hospitals in Malawi that register and treat children with tuberculosis (TB). To determine 1) clinical features and diagnostic practices in children registered with TB, and 2) the use of the WHO score chart in diagnosis. A cross-sectional study of all children aged 14 years or below in hospital receiving anti-tuberculosis treatment, using reviews of treatment cards, case files and chest X-rays and performing a clinical assessment. There were 150 children, 98 with pulmonary TB (PTB) and 52 with extra-pulmonary TB (EPTB). The median duration of illness was 8 weeks. Most patients had fever, no response to anti-malarial treatment and antibiotics, and 40% had a family history of TB. Nearly 45% had weight for age <60%. Diagnosis was mainly based on clinical features and radiography, with less than 10% having tuberculin skin tests or HIV serology, and very few having other sophisticated investigations. A WHO diagnostic score chart was used in 13 (9%) patients by hospital staff. An independent assessment by the study team found that 61% of patients had a score of 7 or more; this was higher in EPTB than PTB patients. Diagnostic practices in children with TB in Malawi are poor, and improvements should be made.


Interaction between Na+ and H+ ions on Na-H exchange in sheep cardiac Purkinje fibers.
The interaction between Na+ and H+ ions upon Na-H exchange (NHE) was examined in sheep cardiac Purkinje fibers. Acid equivalent fluxes through NHE were examined using recordings of intracellular pH and Na+ in isolated preparations measured with ion selective microelectrodes. The extent of acid-extrusion by NHE was estimated from pH(i) recovery-rate, multiplied by beta(i) (intracellular buffering power) in response to an internal acid load induced by 20 mm NH4Cl removal (nominally HCO3- free media). A mixed inhibitory effect was found of extracellular H+ on external Na+-activation of NHE (i.e. an increase, at low pH(o), in the apparent Michaelis constant for external Na+ ions [K(Nao)(0.5)] and a decrease in the maximum transport rate [V(Nao)(max)]). In addition, we confirmed that the stoichiometry of Na(o) binding is unaffected by the pH(o) (between 7.5 and 6.5), showing a Hill coefficient close to one. The interaction between Na+ and H+ ions at the internal face of the cardiac NHE was also studied. Our evidence suggests that an increase in the intracellular Na+ ion concentration ([Na+]i) inhibits acid efflux and that this inhibition can be approximated by the decrease in thermodynamic driving force caused by reducing the transmembrane Na+ gradient. It appears, however, that small variations in [Na+]i from the normal resting level (intracellular sodium activity, a(i)Na = 7 to 13 mm) have little or no effect on acid efflux, suggesting that variation of a(i)Na is not a physiologically important controller of NHE activity in heart.


Cross-sectional neurotoxicology study of lead-exposed cohort.
Although the toxic effects of lead have been known for centuries, lead intoxication is still widespread in the United States. Without baseline tests of neuropsychological, neurobehavioral and neurophysiological testing it may be difficult to detect subtle changes in neurological function after lead exposure. This may be further confounded by partial chelation treatment and exposure to neurotoxic mixtures or inability to quantitate alcohol consumption. We undertook a cross-sectional study to address these problems in 24 exposed and 29 control subjects in a plant that manufactured electrical components using fritted leaded glass to coat capacitors and transistors. Potentially exposed workers had blood lead levels ranging between 3 micrograms/dL to 135 micrograms/dL. Industrial hygiene monitoring revealed the plant's air lead levels ranged from 61 micrograms/m3 to 1,700 micrograms/m3 in excess of OSHA permissible exposure limits of 40 micrograms/m3/10 hr day. Using a specially designed battery of neurophysiological, neurobehavioral and neuropsychological screening tests, we demonstrated a significant difference from controls in measures of psychomotor speed, motor strength and verbal memory. Although limited by the cross-sectional design, these findings support the hypothesis that the battery of neurophysiological, neuropsychological and neurobehavioral tests can detect a significant inter-group differences between lead-exposed and control subjects.


Whiter, brighter, and more stable cellulose paper coated with TiO2 /SiO2 core/shell nanoparticles using a layer-by-layer approach.
To inhibit the photocatalytic degradation of organic material supports induced by small titania (TiO2 ) nanoparticles, four kinds of TiO2 nanoparticles, that is, commercial P25-TiO2 , commercial rutile phase TiO2 , rutile TiO2 nanorods and rutile TiO2 spheres, prepared from TiCl4 , were coated with a thin, but dense, coating of silica (SiO2 ) using a conventional sol-gel technique to form TiO2 /SiO2 core/shell nanoparticles. These core/shell particles were deposited and fixed as a very thin coating onto the surface of cellulose paper samples by a wet-chemistry polyelectrolyte layer-by-layer approach. The TiO2 /SiO2 nanocoated paper samples exhibit higher whiteness and brightness and greater stability to UV-bleaching than comparable samples of blank paper. There are many potential applications for this green chemistry approach to protect cellulosic fibres from UV-bleaching in sunlight and to improve their whiteness and brightness.