Long-term effects on HEK-293 cell line after co-culture with porcine endogenous retrovirus.
Xenotransplantation of pig organs, tissues, and cells bears the risk of interspecies transmission of porcine endogenous retrovirus (PERV). To evaluate the long-term effect of PERV infection on human cells, human embryonic kidney cell line HEK-293 cells were co-cultured with PERV produced by the porcine kidney PK15 cell line for 24 hours and the infected HEK-293 cells were continually cultured for 6 months. PERV-gag, pol gene and gag protein were detected in infected HEK-293 cells by PCR and immunofluorescent staining. PERV from the supernatant of infected HEK-293 cells was same as that from PK15 in morphology. The concentration of reverse transcriptase in the supernatant of infected HEK-293 cells was almost 200 times lower than that of PK15 cells. Except that infected HEK-293 cells doubled a little earlier than the control and infected cells grew in serum-free medium poorly, further study for cell morphology and growth showed no significant difference between infected HEK-293 cells and uninfected control. These results suggested although PERV from PK15 could infect human cells in vitro, there was no significant acute effect attributable to PERV infection on the growth of HEK-293 cells by 6 months culture.


DEVELOPMENT AND VERIFICATION OF NEW SOLID DENTAL FILLING TEMPORARY MATERIALS CONTAINING ZINC. FORMULA DEVELOPMENT STAGE.
Caries is the most popular problem affecting teeth and this is the reason why so many temporary dental filling materials are being developed. An example of such filling is zinc oxide paste mixed with eugenol, Thymodentin and Coltosol F®. Zinc-oxide eugenol is used in dentistry because of its multiplied values: it improves heeling of the pulp by dentine bridge formation; has antiseptic properties; is hygroscopic. Because of these advantages compouds of zinc oxide are used as temporary fillings, especially in deep caries lesions when treatment is oriented on support of vital pulp. Temporary dental fillings based on zinc oxide are prepared ex tempone by simple mixing powder (Thymodentin) and eugenol liqiud together or a ready to use paste Coltosol F®. Quantitative composition depends mainly on experience of person who is preparing it, therefore, exact qualitative composition of dental fillings is not replicable. The main goal of the study was to develop appropriate dental fillings in solid form containing set amount of zinc oxide. Within the study, the influence of preparation method on solid dental fillings properties like mechanical properties and zinc ions release were examined.


National Health Insurance program and life satisfaction of the elderly.
To ensure people's fundamental right to adequate medical care, universal health insurance is given a high priority in contemporary public policy. This article investigates the effects of the introduction of Taiwan's National Health Insurance (NHI) on life satisfaction within the elderly segment of the population. A longitudinal data set including 610 males and 430 females aged 65 or above was constructed from the Survey of Health and Living Status of the Elderly in Taiwan. A difference-in-differences-in-differences model was employed and estimated by the random-effect regression method. The effects of NHI on life satisfaction are different by gender. Compared to the change in life satisfaction between the previously uninsured and insured elderly men, the introduction of NHI had a larger effect of 4.330 points on reducing the disparity in life satisfaction between previously uninsured and insured elderly women. Education, living arrangements, lifestyle, social activities, geographic location, and urbanization level are also important determinants for life satisfaction among the elderly. Although NHI is designed to ensure equality for accessing health care, the implementation of NHI has also improved the subjective well-being of the elderly, with a larger improvement for the elderly women. The post-NHI disparity reductions in life satisfaction between the previously uninsured and insured are significantly greater among elderly women. Our analysis of Taiwan's experience should provide a valuable lesson to countries that are in the initial stages of proposing a universal health insurance program.


Head circumference at birth and maternal factors related to cord blood total IgE.
A recent study reported an association between a large head circumference at birth and adult total IgE. However, no study has yet looked at the relation between head circumference and cord blood IgE. To assess the relationship between child's cord blood total IgE and head circumference at birth taking parental allergy and smoking habits as well as placental calcifications into account. Two samples of unselected newborns and their mothers with uncomplicated pregnancies were studied: 235 in study A with data on parental allergy and 99 in study B with data on placental calcifications. In both studies, cord blood IgE was significantly related to large head circumference at birth (0.07 vs 0.15 IU/mL for newborns < 37 cm vs >/= 37 cm, respectively, P = 0. 03 for study A and 0.09 vs 0.28 IU/mL, P = 0.04 for study B). Cord blood IgE was unrelated to parental smoking habits. Maternal IgE significantly increased in mothers exposed to both active and passive smoking during pregnancy compared with other pregnant women. High cord blood IgE were associated with high maternal IgE (r = 0. 38; P < 0.001). Multiple linear regression showed that large head circumference, maternal IgE and clinical manifestations of maternal, but not paternal, allergy were independently related to cord blood IgE (study A). Large head circumference and placental calcifications were independently related to a higher cord blood IgE level (study B). Besides the role of genetic factors, results on the preferential role of maternal vs paternal allergy and associations to large head circumference and placental calcifications support the hypothesis of the role of environmental factors during pregnancy on the level of cord blood IgE.


Effects of instability on fracture healing in the rat.
The effect of bending and rotational instability on the healing of a femoral osteotomy was studied in rats using intramedullary fixation with nails made of either steel or flexible polyacetal. All osteotomies were made rotationally unstable by reaming the medullary cavity to a diameter wider than the nails. At 16 weeks, four osteotomies had healed, and 17 had not healed. However, bending tests gave higher values for strength and energy absorption in non-unions with flexible as compared to Stiff nails. Rotational instability thus caused a high rate of non-union in the present model, which has given safe healing when the osteotomy has been stabilized for rotation. Flexible nailing increased strength and energy absorption in bones with non-union, but did not affect the incidence of healing.


Investigating the real-world emission characteristics of light-duty gasoline vehicles and their relationship to local socioeconomic conditions in three communities in Los Angeles, California.
This paper discusses results from a vehicular emissions research study of over 350 vehicles conducted in three communities in Los Angeles, CA, in 2010 using vehicle chase measurements. The study explores the real-world emission behavior of light-duty gasoline vehicles, characterizes real-world super-emitters in the different regions, and investigates the relationship of on-road vehicle emissions with the socioeconomic status (SES) of the region. The study found that in comparison to a 2007 earlier study in a neighboring community, vehicle emissions for all measured pollutants had experienced a significant reduction over the years, with oxides of nitrogen (NOX) and black carbon (BC) emissions showing the largest reductions. Mean emission factors of the sampled vehicles in low-SES communities were roughly 2-3 times higher for NOX, BC, carbon monoxide, and ultrafine particles, and 4-11 times greater for fine particulate matter (PM2.5) than for vehicles in the high-SES neighborhood. Further analysis indicated that the emission factors of vehicles within a technology group were also higher in low-SES communities compared to similar vehicles in the high-SES community, suggesting that vehicle age alone did not explain the higher vehicular emission in low-SES communities. Evaluation of the emission factor distribution found that emissions from 12% of the sampled vehicles were greater than five times the mean from all of the sampled fleet, and these vehicles were consequently categorized as "real-world super-emitters." Low-SES communities had approximately twice as many super-emitters for most of the pollutants as compared to the high-SES community. Vehicle emissions calculated using model-year-specific average fuel consumption assumptions suggested that approximately 5% of the sampled vehicles accounted for nearly half of the total CO, PM2.5, and UFP emissions, and 15% of the vehicles were responsible for more than half of the total NOX and BC emissions from the vehicles sampled during the study. This study evaluated the real-world emission behavior and super-emitter distribution of light-duty gasoline vehicles in California, and investigated the relationship of on-road vehicle emissions with local socioeconomic conditions. The study observed a significant reduction in vehicle emissions for all measured pollutants when compared to an earlier study in Wilmington, CA, and found a higher prevalence of high-emitting vehicles in low-socioeconomic-status communities. As overall fleet emissions decrease from stringent vehicle emission regulations, a small fraction of the fleet may contribute to a disproportionate share of the overall on-road vehicle emissions. Therefore, this work will have important implications for improving air quality and public health, especially in low-SES communities.


Biodiversity loss following the introduction of exotic competitors: does intraguild predation explain the decline of native lady beetles?
Exotic species are widely accepted as a leading cause of biodiversity decline. Lady beetles (Coccinellidae) provide an important model to study how competitor introductions impact native communities since several native coccinellids have experienced declines that coincide with the establishment and spread of exotic coccinellids. This study tested the central hypothesis that intraguild predation by exotic species has caused these declines. Using sentinel egg experiments, we quantified the extent of predation on previously-common (Hippodamia convergens) and common (Coleomegilla maculata) native coccinellid eggs versus exotic coccinellid (Harmonia axyridis) eggs in three habitats: semi-natural grassland, alfalfa, and soybean. Following the experiments quantifying egg predation, we used video surveillance to determine the composition of the predator community attacking the eggs. The extent of predation varied across habitats, and egg species. Native coccinellids often sustained greater egg predation than H. axyridis. We found no evidence that exotic coccinellids consumed coccinellid eggs in the field. Harvestmen and slugs were responsible for the greatest proportion of attacks. This research challenges the widely-accepted hypothesis that intraguild predation by exotic competitors explains the loss of native coccinellids. Although exotic coccinellids may not be a direct competitor, reduced egg predation could indirectly confer a competitive advantage to these species. A lower proportion of H. axyridis eggs removed by predators may have aided its expansion and population increase and could indirectly affect native species via exploitative or apparent competition. These results do not support the intraguild predation hypothesis for native coccinellid decline, but do bring to light the existence of complex interactions between coccinellids and the guild of generalist predators in coccinellid foraging habitats.


How to become a killer, or is it all accidental? Virulence strategies in oral streptococci.
Streptococci are a diverse group of Gram-positive microorganisms sharing common virulence traits and similar strategies to escape the oral niche and establish an infection in other parts of the host organism. Invasive infection with oral streptococci is "a perfect storm" that requires the concerted action of multiple biotic and abiotic factors. Our understanding of streptococcal pathogenicity and infectivity should probably be less mechanistic and driven not only by the identification of novel virulence factors. The observed diversity of the genus, including the range of virulence and pathogenicity mechanisms, is most likely the result of interspecies interactions, a massive horizontal gene transfer between streptococci within a shared oral niche, recombination events, selection of specialized clones, and modification of regulatory circuits. Selective pressure by the host and bacterial communities is a driving force for the selection of virulence traits and shaping the streptococcal genome. Global regulatory events driving niche adaptation and interactions with bacterial communities and the host steer research interests towards attempts to define the oral interactome on the transcriptional level and define signal cross-feeding and co-expression and co-regulation of virulence genes.


Morphological alterations of the degenerated lumbar disc following chemonucleolysis with chymopapain.
Lumbar disc tissue from 10 patients who had previously undergone chemonucleolysis without success was studied by light and scanning electron microscopy. Seven patients had a sequestrated disc; three had large protrusions. As a control, material from 10 patients subjected to disc surgery without previous chemonucleolysis was studied in the same way. The control discs revealed the characteristic signs of degeneration: alteration of the collagen, microcystic areas, and giant chondromas. Changes following chemonucleolysis were restricted exclusively to the ground substance and characterized by a marked loss of basophilia in the cartilage matrix. There was no involvement of the anulus fibrosus, cartilage plate, or bone. Following chymopapain administration, scanning electron microscopy showed a naked collagen network devoid of ground substance.


A new strategy to construct a FRET platform for ratiometric sensing of hydrogen sulfide.
We introduce a new FRET strategy to construct a ratiometric fluorescent H2S sensor. The ratio emission signal of the coumarin-naphthalimide dyad is modulated by the FRET process, which works in coordination with the ICT mechanism. The FRET process on/off is controlled through tuning the overlap level of the donor emission spectrum with the acceptor absorption via modulation of the acceptor fluorophore absorption wavelength. was applied to visualize both the intracellular exogenous and endogenous H2S through blue and green emission channels.


Natural Bioenhancers in Drug Delivery: An Overview.
When the bioavailability of a drug increases, a corresponding increase in the levels of that drug in the bloodstream occurs. With this, drug efficacy is augmented and the dosage required to yield a specific therapeutic effect diminishes comparably. Until recently, only a few methods have proven effective in enhancing drug bioavailability, among which are the disaggregation of micronized molecules, the use of timedrelease and topical preparations, mechanization, polymorph and crystal form selection, drug solubilisation, and the use of nanotechnology. (Though still at the experimental stage, nanotechnology promises to become a powerful pharmacological tool in the future.) Bioenhancers are agents not possessing any inherent therapeutic effects but that, when combined with active drugs, potentiate the pharmacological effects of those drugs. Hence the current article describes the enhancement of the bioavailability of drug molecules through the utilization of natural bioenhancers.


Surveillance of the major pathogenic arboviruses of public health concern in Gabon, Central Africa: increased risk of West Nile virus and dengue virus infections.
Increasing arbovirus infections have been a global burden in recent decades. Many countries have experienced the periodic emergence of arbovirus diseases. However, information on the prevalence of arboviruses is largely unknown or infrequently updated because of the lack of surveillance studies, especially in Africa. A surveillance study was conducted in Gabon, Central Africa, on arboviruses, which are a major public health concern in Africa, including: West Nile virus (WNV), dengue virus (DENV), Zika virus (ZIKV), yellow fever virus (YFV), chikungunya virus (CHIKV), and Rift Valley fever virus (RVFV). Serological and molecular assays were performed to investigate past infection history and the current status of infection, using serum samples collected from healthy individuals and febrile patients, respectively. The overall seroprevalence during 2014-2017 was estimated to be 25.3% for WNV, 20.4% for DENV, 40.3% for ZIKV, 60.7% for YFV, 61.2% for CHIKV, and 14.3% for RVFV. No significant differences were found in the seroprevalence of any of the viruses between the male and female populations. However, a focus on the mean age in each arbovirus-seropositive individual showed a significantly younger age in WNV- and DENV-seropositive individuals than in CHIKV-seropositive individuals, indicating that WNV and DENV caused a relatively recent epidemic in the region, whereas CHIKV had actively circulated before. Of note, this indication was supported by the detection of both WNV and DENV genomes in serum samples collected from febrile patients after 2016. This study revealed the recent re-emergence of WNV and DENV in Gabon as well as the latest seroprevalence state of the major arboviruses, which indicated the different potential risks of virus infections and virus-specific circulation patterns. This information will be helpful for public health organizations and will enable a rapid response towards these arbovirus infections, thereby preventing future spread in the country.


Identification of two promoters for human D-amino acid oxidase gene: implication for the differential promoter regulation mediated by PAX5/PAX2.
D-amino acid oxidase (DAO) is a flavoenzyme that metabolizes d-amino acids. Until now, the DAO expression mechanism is still unclear. Our assessment of human DAO (hDAO) promoter activity using luciferase reporter system indicated the proximal upstream region of exon1 (-237/+1) has promoter activity (P1). Interestingly, we identified an alternative promoter in the proximal upstream region of exon2 (+4,126/+4,929) (P2). This alternative promoter has stronger activity than that of P1. Our results also revealed a negative regulatory segment (+1,163/+1,940) in intron1; that would act in concert with P1 and P2. Bioinformatics analyses elucidated the conservation of transcription factor PAX5 family binding sites among species. These sites (-60/-31) and (+4,464/+4,493), locate in P1 and P2 of hDAO, respectively. Gel shift assays demonstrated P1 contains a site (-60/-31) for PAX5 binding while P2 has three sites for both paired box gene 2 (PAX2) and paired box gene 5 (PAX5) binding. The dual roles of PAX5 family in regulating hDAO transcription by modulating promoter activity of P1 and activating promoter activity of P2 were implicated based on the site-directed mutagenesis experiment. Altogether, our data suggested the differential regulation of hDAO expression by two promoters whose activities may be modulated by the binding of PAX2 and PAX5.


Preoperative ultrasound and intraoperative findings of inguinal hernias in children: A prospective study of 642 children.
Preoperative sonographic studies of the groins have become a routine evaluation of inguinal hernia in children. Its value is not only to confirm the clinical diagnosis, but also to accurately assess the opposite side and to prevent an unnecessary exploration or additional operation at a later stage. The purpose of this study is to report more definitive criteria of inguinal hernias (IH) and patent process vaginalis (PPV) established from 1,284 groin examinations. From January 1999 to October 2000 the authors compared prospectively the sonographic dimensions of the inguinal canal to the operative findings as reported by the surgeons (blinded to the results) for 642 pediatric patients (ages 1 to 176 months) undergoing inguinal hernia repairs. A normal inguinal canal was found at operation when a preoperative sonographic groin width of 3.6 +/- 0.8 mm, on average, was detected. A PPV was found when a groin width of 4.9 +/- 1.1 mm was detected. A full hernia was found when a groin width of 7.2 +/- 2.0 mm was detected. A large hernia was found when a groin width of 12.8 +/- 3.6 mm was detected, and a hydrocele was found along with a groin width of 4.8 +/- 2.2 mm. Establishing accurate sonographic criteria for inguinal hernia and patent processus vaginalis is an important tool for the pediatric surgeon to plan the approach before groin surgery.


2-pyridylimidazoles as inhibitors of xanthine oxidase.
A series of 28 4-substituted and 4,5-disubstituted 2-pyridylimidazoles was synthesized and evaluated in vitro for inhibition of xanthine oxidase. Included within this group are examples of 2-pyridylimidazopyridines and halo-substituted 2-pyridylbenzimidazoles. Five compounds exhibited inhibitory activity in the same range as the standards, 4-hydroxypyrazolo[3,4-d]pyrimidine and 2-(4-pyridyl)-4-trifluoromethylimidazole (22). Two examples, 2-(4-pyridyl)-4,5-dicyanoimidazole (16) and 2-(4-pyridyl)-4-nitroimidazole (3), were at least an order of magnitude more active than the standards and therefore rank among the most potent known inhibitors of the enzyme.


Neuroendocrine System Regulatory Mechanisms: Acute Coronary Syndrome and Stress Hyperglycaemia.
Neurohormonal systems are activated in the early phase of acute coronary syndromes to preserve circulatory homeostasis, but prolonged action of these stress hormones might be deleterious. Cortisol reaches its peak at 8 hours after the onset of symptoms, and individuals who have continued elevated levels present a worse prognosis. Catecholamines reach 100-1,000-fold their normal plasma concentration within 30 minutes of ischaemia, therefore inducing the propagation of myocardial damage. Stress hyperglycaemia induces inflammation and endothelial dysfunction, and also has procoagulant and prothrombotic effects. Patients with hyperglycaemia and no diabetes elevated in-hospital and 12-month mortality rates. Hyperglycaemia in patients without diabetes has been shown to be an appropriate independent mortality prognostic factor in this type of patient.


Z-ring force and cell shape during division in rod-like bacteria.
The life cycle of bacterial cells consists of repeated elongation, septum formation, and division. Before septum formation, a division ring called the Z-ring, which is made of a filamentous tubulin analog, FtsZ, is seen at the mid cell. Together with several other proteins, FtsZ is essential for cell division. Visualization of strains with GFP-labeled FtsZ shows that the Z-ring contracts before septum formation and pinches the cell into two equal halves. Thus, the Z-ring has been postulated to act as a force generator, although the magnitude of the contraction force is unknown. In this article, we develop a mathematical model to describe the process of growth and Z-ring contraction in rod-like bacteria. The elasticity and growth of the cell wall is incorporated in the model to predict the contraction speed, the cell shape, and the contraction force. With reasonable parameters, the model shows that a small force from the Z-ring (8 pN in Escherichia coli) is sufficient to accomplish division.


Malignant transformation of uterine leiomyomata.
The malignant transformation of a uterine leiomyoma is still debated and, if it occurs, it is very rare. The case of a patient affected by three small leiomyomas, monitored by the same gynecologist over the years is described. Two of these leiomyomas were transformed into leiomyosarcoma after menopause and the patient died despite receiving therapy. The case reported here is meant to underline the need to keep all uterine myomas in check since the transition into leiomyosarcomas may occur with an evolution over a time period which has not been established so far.


Purification and characterization of the N-terminal domain of ExeA: a novel ATPase involved in the type II secretion pathway of Aeromonas hydrophila.
Aeromonas hydrophila secretes a number of degradative enzymes and toxins into the external milieu via the type II secretory pathway or secreton. ExeA is an essential component of this system and is necessary for the localization and/or multimerization of the secretin ExeD. ExeA contains two sequence motifs characteristic of the Walker superfamily of ATPases. Previous examination of substitution derivatives altered in these motifs suggested that ATP binding or hydrolysis is required for ExeAB complex formation and subsequent secretion function. To directly examine ExeA function, the N-terminal cytoplasmic domain of ExeA with the addition of a C-terminal hexahistidine tag (cytExeA) was overproduced in Escherichia coli and purified by metal chelate affinity and anion-exchange chromatographic techniques. Purified preparations of cytExeA exhibited ATPase activity in the presence of several divalent cations, Mg2+ being the preferred cation, with an optimum reaction temperature of approximately 37 to 42 degrees C and an optimum pH of 7 to 8. cytExeA exhibited an apparent K(m) for Mg-ATP of 0.22 mM and a V(max) of 0.72 nmol min(-1) mg(-1) of protein. cytExeA displayed low specificity for nucleoside triphosphate substrates and was significantly inhibited by F-type ATPase inhibitors. Gel filtration analyses of cytExeA, ExeA, and ExeAB indicated that ExeA dimerizes and forms a very large complex with ExeB. These findings support a model whereby ExeAB utilizes energy derived from ATP hydrolysis to facilitate the correct localization and multimerization of the ExeD secretin.


[18F]FDOPA positron emission tomography in manganese-exposed workers.
Occupational manganese (Mn) exposure is associated with the development of parkinsonism; however, the mechanism of neurotoxicity is unknown. Brain positron emission tomography (PET) imaging provides a non-invasive method of assessing dopamineric neuronal function. 6-[18F]fluoro-L-DOPA (FDOPA) PET reflects in-vivo nigrostriatal function, but results in Mn exposure are conflicting. The objective of this study was to investigate the association between Mn exposure secondary to occupational welding, FDOPA striatal uptake, and clinical parkinsonism as measured by Unified Parkinson Disease Rating Scale motor subscore 3 (UPDRS3) scores. FDOPA PET scans were acquired on 72 subjects (27 Mn-exposed welders, 14 other Mn-exposed workers, and 31 non-exposed subjects). We estimated cumulative welding exposure from detailed work histories, and a movement disorders specialist examined all subjects. Striatal volumes of interest were identified on aligned magnetic resonance imaging (MRI) for each subject. Specific striatal FDOPA uptake was calculated with a graphical analysis method. We used linear regression while adjusting for age to assess the association between welding exposure and FDOPA uptake in the caudate, anterior putamen, and posterior putamen. Compared to the non-exposed subjects, mean caudate FDOPA uptake was 0.0014min-1 (95% confidence interval [CI] 0.0008, 0.0020) lower in Mn-exposed welders and 0.0012min-1 (95% CI 0.0005, 0.0019) lower in other Mn-exposed workers (both p≤0.001). There was no clear dose-response association between caudate FDOPA uptake and Mn exposure or UPDRS3 scores. Mn-exposed welders and workers demonstrated lower caudate FDOPA uptake, indicating pre-synaptic dopaminergic dysfunction in Mn-exposed subjects that was not associated with clinical parkinsonism.


Ultrasound for the Diagnosis of Carotidynia.
The purpose of this work is to draw attention to the characteristic sonographic features of carotidynia, which, in the context of a typical clinical picture support its diagnosis. Six patients presented with primary symptoms of neck pain and focal tenderness. In all patients, focal wall thickening of the distal end of the common carotid artery was found exactly in the region of tenderness, leading to mild lumen narrowing. Treatment with nonsteroidal anti-inflammatory drugs or glucocorticoids led to full symptom resolution. Carotidynia will often be encountered first on sonography performed for evaluation of neck pain and has a characteristic sonographic appearance.


Amelioration of type 1 diabetes following treatment of non-obese diabetic mice with INGAP and lisofylline.
Type 1 diabetes mellitus results from the autoimmune and inflammatory destruction of insulin-producing islet β cells, rendering individuals devoid of insulin production. Recent studies suggest that combination therapies consisting of anti-inflammatory agents and islet growth-promoting factors have the potential to cause sustained recovery of β cell mass, leading to amelioration or reversal of type 1 diabetes in mouse models. In this study, we hypothesized that the combination of the anti-inflammatory agent lisofylline (LSF) with an active peptide fragment of islet neogenesis associated protein (INGAP peptide) would lead to remission of type 1 diabetes in the non-obese diabetic (NOD) mouse. We treated groups of spontaneously diabetic NOD mice with combinations of LSF, INGAP peptide, or control saline parenterally for up to 6 weeks. Our results demonstrate that the mice receiving combined treatment with LSF and INGAP peptide exhibited partial remission of diabetes with increased plasma insulin levels. Histologic assessment of pancreata in mice receiving combined therapy revealed the presence of islet insulin staining, increased β cell replication, and evidence of Pdx1-positivity in ductal cells. By contrast, diabetic animals showed severe insulitis with no detectible insulin or Pdx1 staining. We conclude that the novel combination treatment with LSF and INGAP peptide has the potential to ameliorate hyperglycemia in the setting of established type 1 diabetes via the recovery of endogenous β cells and warrant further studies.


HPLC analysis of generic antiretroviral drugs purchased in Rwanda.
A reversed phase HPLC method using photo diode array detection for the simultaneous quantification of lamivudine, stavudine, nevirapine, zidovudine, methyl paraben and propyl paraben in solid and liquid drug formulations was developed and validated. The separation was achieved using a Waters Symmetry C8 column, using a mobile phase gradient comprising 50 mM NaH2PO4 (pH 3.8) and acetonitrile (95:5 to 45:55, v/v) and a flow gradient (0.5 to 1.0 ml/min). The limits of detection and quantification were below 19 ng/ml and 55 ng/ml respectively. The intra- and inter-day assay precisions were within 4.4% relative standard deviations. The developed method was applied to 12 different generic antiretroviral medications, consisting of tablets, capsules and solutions, produced by two Indian manufacturers and purchased by the Central Agency of Essential Drug Procurement of Rwanda for the ESTHER project in Rwanda. The average content of the antiretroviral agent(s) compared to the labeled amount(s) was 101.4%. Methyl paraben and propyl paraben, added to solutions as preservatives, were within the FDA recommended limits.


IgG4-Related Disease Presented as a Mural Mass in the Stomach.
Isolated gastric IgG4-related disease (IgG4-RD) is a very rare tumefactive inflammatory condition, with only a few cases reported to date. A 48-year-old woman was incidentally found to have a subepithelial tumor in the stomach. Given a presumptive diagnosis of gastrointestinal stromal tumor or neuroendocrine tumor, she underwent wedge resection. The lesion was vaguely nodular and mainly involved the submucosa and proper muscle layer. Microscopically, all classical features of type I autoimmune pancreatitis including lymphoplasmacytic infiltration, storiform fibrosis, obliterative phlebitis, and numerous IgG4-positive plasma cells were seen. She had no evidence of IgG4-RD in other organs. Although very rare, IgG4-RD should be considered one of the differential diagnoses in the setting of gastric wall thickening or subepithelial mass-like lesion. Deep biopsy with awareness of this entity might avoid unnecessary surgical intervention.


AJS1669, a novel small-molecule muscle glycogen synthase activator, improves glucose metabolism and reduces body fat mass in mice.
Impaired glycogen synthesis and turnover are common in insulin resistance and type 2 diabetes. As glycogen synthase (GS) is a key enzyme involved in the synthetic process, it presents a promising therapeutic target for the treatment of type 2 diabetes. In the present study, we identified a novel, potent and orally available GS activator AJS1669 {sodium 2-[[5-[[4-(4,5-difluoro-2-methylsulfanyl-phenyl)phenoxy] methyl]furan-2-carbonyl]-(2-furylmethyl)amino] acetate}. In vitro, we performed a glycogen synthase 1 (GYS1) activation assay for screening GS activators and identified that the activity of AJS1669 was further potentiated in the presence of glucose-6-phosphate (G6P). In vivo, we used ob/ob mice to evaluate the novel anti-diabetic effects of AJS1669 by measuring basal blood glucose levels, glucose tolerance and body fat mass index. Repeated administration of AJS1669 over 4 weeks reduced blood glucose and hemoglobin A1c (HbA1c) levels in ob/ob mice. AJS1669 also improved glucose tolerance in a dose-dependent manner, and decreased body fat mass. The mRNA levels of genes involved in mitochondrial fatty acid oxidation and mitochondrial biogenesis were elevated in skeletal muscle tissue following AJS1669 treatment. Hepatic tissue of treated mice also exhibited elevated expression of genes associated with fatty acid oxidation. In contrast to ob/ob mice, in C57Bl/6 mice AJS1669 administration did not alter body weight or reduce glucose levels. These results demonstrate that pharmacological agents that activate GYS1, the main GS subtype found in skeletal muscle, have potential for use as novel treatments for diabetes that improve glucose metabolism in skeletal muscle.


Stable Organic (Bi)Radicals by Delocalization of Spin Density into the Electron-Poor Chromophore Core of Isoindigo.
The first isoindigo (bi)radicals were obtained by proton coupled oxidation of their 4-hydroxyaryl substituted precursors. Optical and magnetic spectroscopic studies revealed a singlet open-shell biradicaloid electronic ground state for the bisphenoxyl-isoindigo (<s2 >=1.20) with a small singlet-triplet energy gap of 0.065 eV and a large biradical character of y=0.79 that was corroborated by temperature-dependent EPR spectroscopy and quantum chemical calculations. The concept of kinetic blocking of the radical centers and delocalization of spin density into the electron-withdrawing chromophore core of isoindigo offers an entry into a new class of exceptionally stable open-shell functional materials based on organic colorants.


The State of Parent Training: Program Offerings and Empirical Support.
Parent training programs, with a range of empirical support, are available to improve parenting skills and reduce child behavior problems. Yet, little is known about programs provided in typical communities. This pilot study's purpose was to identify and describe parent programs-and the agencies that provide them-in one midsized midwestern city. The sample included 21 program directors and 25 practitioners employed by 19 agencies. data were gathered using structured phone interviews. of the 35 programs represented, 37.1% were developed by the agency, while close to two thirds were previously developed interventions. only a small number of the parent programs identified were classified into the category of strong empirical support; however, several included hallmarks often associated with empirically supported parent programs.


Haematological and biochemical reference intervals for wild green turtles (Chelonia mydas): a Bayesian approach for small sample sizes.
Animal health is directly linked to population viability, which may be impacted by anthropogenic disturbances and diseases. Reference intervals (RIs) for haematology and blood biochemistry are essential tools for the assessment of animal health. However, establishing and interpreting robust RIs for threatened species is often challenged by small sample sizes. Bayesian predictive modelling is well suited to sample size limitations, accounting for individual variation and interactions between influencing variables. We aimed to derive baseline RIs for green turtles (Chelonia mydas) across two foraging aggregations in North Queensland, Australia, using Bayesian generalized linear mixed-effects models (n = 97). The predicted RIs were contained within previously published values and had narrower credible intervals. Most analytes did not vary significantly with foraging ground (76%, 22/29), body mass (86%, 25/29) or curved carapace length (83%, 24/29). Length and body mass effects were found for eosinophils, heterophil:lymphocyte ratio, alkaline phosphatase, aspartate transaminase and urea. Significant differences between foraging grounds were found for albumin, cholesterol, potassium, total protein, triglycerides, uric acid and calcium:phosphorus ratio. We provide derived RIs for foraging green turtles, which will be helpful in future population health assessments and conservation efforts. Future RI studies on threatened species would benefit from adapting established veterinary and biomedical standards.


S-Palmitoylation of a Novel Site in the β2-Adrenergic Receptor Associated with a Novel Intracellular Itinerary.
We report here that a population of human β2-adrenergic receptors (β2AR), a canonical G protein-coupled receptor, traffics along a previously undescribed intracellular itinerary via the Golgi complex that is associated with the sequential S-palmitoylation and depalmitoylation of a previously undescribed site of modification, Cys-265 within the third intracellular loop. Basal S-palmitoylation of Cys-265 is negligible, but agonist-induced β2AR activation results in enhanced S-palmitoylation, which requires phosphorylation by the cAMP-dependent protein kinase of Ser-261/Ser-262. Agonist-induced turnover of palmitate occurs predominantly on Cys-265. Cys-265 S-palmitoylation is mediated by the Golgi-resident palmitoyl transferases zDHHC9/14/18 and is followed by depalmitoylation by the plasma membrane-localized acyl-protein thioesterase APT1. Inhibition of depalmitoylation reveals that S-palmitoylation of Cys-265 may stabilize the receptor at the plasma membrane. In addition, β2AR S-palmitoylated at Cys-265 are selectively preserved under a sustained adrenergic stimulation, which results in the down-regulation and degradation of βAR. Cys-265 is not conserved in β1AR, and S-palmitoylation of Cys-265 may thus be associated with functional differences between β2AR and β1AR, including relative resistance of β2AR to down-regulation in multiple pathophysiologies. Trafficking via the Golgi complex may underlie new roles in G protein-coupled receptor biology.


Hypoglycemic effect of insulin-like growth factor-1 in mice lacking insulin receptors.
We have investigated the metabolic actions of recombinant human IGF-1 in mice genetically deficient of insulin receptors (IR-/-). After intraperitoneal administration, IGF-1 caused a prompt and sustained decrease of plasma glucose levels in IR-/- mice. Plasma free fatty acid concentrations were unaffected. Interestingly, the effects of IGF-1 were identical in normal mice (IR+/+) and in IR-/- mice. Despite decreased glucose levels, IR-/- mice treated with IGF-1 died within 2-3 d of birth, like sham-treated IR-/- controls. In skeletal muscle, IGF-1 treatment caused phosphorylation of IGF-1 receptors and increased the levels of the phosphatidylinositol-3-kinase p85 subunit detected in antiphosphotyrosine immunoprecipitates, consistent with the possibility that IGF-1 stimulates glucose uptake in a phosphatidylinositol-3-kinase-dependent manner. IGF-1 receptor phosphorylation and coimmunoprecipitation of phosphatidylinositol3-kinase by antiphosphotyrosine antibodies was also observed in liver, and was associated with a decrease in mRNA levels of the key gluconeogenetic enzyme phosphoenolpyruvate carboxykinase. Thus, the effect of IGF-1 on plasma glucose levels may be accounted for by increased peripheral glucose use and by inhibition of hepatic gluconeogenesis. These data indicate that IGF-1 can mimic insulin's effects on glucose metabolism by acting through its own receptor. The failure of IGF-1 to rescue the lethal phenotype due to lack of insulin receptors suggests that IGF-1 receptors cannot effectively mediate all the metabolic actions of insulin receptors.


Nigella damascena L. Essential Oil-A Valuable Source of β-Elemene for Antimicrobial Testing.
The most commonly used plant source of β-elemene is Curcuma wenyujin Y. H. Chen & C. Ling (syn. of Curcuma aromatic Salisb.) with its content in supercritical CO₂ extract up to 27.83%. However, the other rich source of this compound is Nigella damascena L. essential oil, in which β-elemene accounts for 47%. In this work, the effective protocol for preparative isolation of β-elemene from a new source-N. damascena essential oil-using high performance counter-current chromatography HPCCC was elaborated. Furthermore, since sesquiterpens are known as potent antimicrobials, the need for finding new agents designed to combat multi-drug resistant strains was addressed and the purified target compound and the essential oil were tested for its activity against a panel of Gram-positive and Gram-negative bacteria, fungi, and mycobacterial strains. The application of the mixture of petroleum ether, acetonitrile, and acetone in the ratio 2:1.5:0.5 (v/v) in the reversed phase mode yielded β-elemene with high purity in 70 min. The results obtained for antimicrobial assay clearly indicated that N. damascena essential oil and isolated β-elemene exert action against Mycobacterium tuberculosis strain H37Ra.


Reduced thyroxine production in young household contacts of tuberculosis patients increases active tuberculosis disease risk.
In the current study, we followed 839 household contacts (HHCs) of tuberculosis (TB) patients for 2 years and identified the factors that enhanced the development of TB. Fourteen of the 17 HHCs who progressed to TB were in the 15- to 30-year-old age group. At baseline (the "0" time point, when all the individuals were healthy), the concentration of the thyroid hormone thyroxine (T4) was lower, and there were increased numbers of Tregs in PBMCs of TB progressors. At baseline, PBMCs from TB progressors stimulated with early secretory antigenic target 6 (ESAT-6) and 10 kDa culture filtrate antigen (CFP-10) produced less IL-1α. Thyroid hormones inhibited Mycobacterium tuberculosis (Mtb) growth in macrophages in an IL-1α-dependent manner. Mtb-infected Thra1PV/+ (mutant thyroid hormone receptor) mice had increased mortality and reduced IL-1α production. Our findings suggest that young HHCs who exhibit decreased production of thyroid hormones are at high risk of developing active TB disease.


Does quetiapine have mood altering properties?
We present a series of three cases who developed manic symptoms on introduction of quetiapine to their medication regime. All were male, with long-standing psychotic illnesses (schizophrenia/schizoaffective disorder), relatively well maintained on medication until their deterioration which prompted a review of their medication. The dose range of prescribed quetiapine was 300-800 mg daily. Two patients had previously received antidepressants without displaying manic symptoms. The mania subsided on withdrawal of quetiapine in two patients. The third patient continued on quetiapine but with the addition of zuclopenthixol depot. Sodium valproate was prescribed to the other two patients, and quetiapine was discontinued. These cases indicate that a side-effect of quetiapine may be mood elevation. An ability to elevate mood while controlling psychoses would be helpful in the treatment of post-psychotic and bipolar depression. Its clinical importance in the control of manic episodes, for which atypical antipsychotics are used increasingly, is uncertain.


In Vivo nonlinear optical imaging of immune responses: tissue injury and infection.
In this study, we demonstrate a noninvasive imaging approach based on multimodal nonlinear optical microscopy to in vivo image the responses of immune cells (neutrophils) to the tissue injury and bacterial infection in a zebrafish model. Specifically, the second harmonic generation from myosin thick filaments in sarcomere enabled a clear visualization of the muscle injury and infection. Two-photon excited fluorescence was used to track the behavior of the neutrophils that were transgenically labeled by red fluorescent protein. The corresponding reduced nicotinamide adenine dinucleotide (NADH) two-photon excited fluorescence images revealed a detailed morphological transformation process of individual neutrophils during muscle tissue injury and bacterial infection. The analysis of time-resolved NADH signals from the neutrophils provided important biological insights of the cellular energy metabolism during the immune responses. We found a significant increase of free/protein-bound NADH ratios in activated neutrophils in bacterial-infected tissue. In this study, we also discovered that, under 720 nm excitation, two wild-type strains (DH5? and BL21) of bacteria Escherichia coli emitted distinct endogenous fluorescence of double-peak at ?450 and ?520 nm, respectively. We demonstrated that the double-peak fluorescence signal could be used to differentiate the E. coli from surrounding tissues of dominant NADH signals, and to achieve label-free tracking of E. coli bacteria in vivo.


Chain length heterogeneity of lipopolysaccharide released from Salmonella typhimurium by ethylenediaminetetraacetic acid or polycations.
Cells of two smooth Salmonella typhimurium strains (SL696 and SH4247) were treated with ethylenediaminetetraacetic acid (EDTA) and the polycations poly(L-lysine) and protamine to monitor both quantitatively and qualitatively the release of [14C] galactose-labelled lipopolysaccharide into the medium to find out whether these effector substances caused selective release of certain fractions from the initially heterogenous lipopolysaccharide population. Each one of the substances released considerable amounts of lipopolysaccharide into the medium. Analysis by sodium dodecyl sulphate/polyacrylamide gel electrophoresis followed by autoradiography showed that the total lipopolysaccharide (from isolated membranes) and the released materials produced coincident banding patterns, each with a high degree of O side-chain length heterogeneity. Densitometric scans of the autoradiograms were analyzed for possible differences in the distribution and relative abundance of lipopolysaccharide molecules with different O chain lengths. It was found that in SL696 the released materials were identical to the total lipopolysaccharide; in SH4247 subtle deviations from the total lipopolysaccharide were seen. We conclude from these results that lipopolysaccharide molecules with short and long O side chains are linked to and stabilized in the outer membrane by similar mechanisms equally susceptible to the effects of EDTA and polycations.


[The prevalence of C. trachomatis genitourinary tract infection in 1986-1993].
The study comprised 7224 patients from Lower Silesia District, 3576 women and 3648 men, at age 18-69 yrs. Urethral and endocervical specimens were tested for Chlamydia trachomatis using culture method (on McCoy cells treated with cycloheximid), immunofluorescent technique (Chlamyset-Orion Diagnostica) or immunoenzymatic assay (Chlamydiazyme-Abbott). In the examined population chlamydial infection was found in prevalence among 20-40 yrs old patients. Symptomatic infection was observed in 97.3%, asymptomatic in 2.7%. Basing on the laboratory tests results chlamydiosis was diagnosed in 1393 (19.2%) patients, 658 (47.2%) women and 735 (52.7%) men. The highest percentage (25.7%) of the infected people was noticed in 1986, the lowest in 1991 (10.6%). Despite the general declining trend, every second year a small rising in number of C. trachomatis infection was regularly observed.


[Effects of light intensity on growth and photosynthetic characteristics of Tulipa edulis].
Present study was conducted to explore the growth and photosynthetic characteristics of Tulipa edulis under different light conditions (23%, 45%, 63%, 78%, 100% of full sunlight) and to determine the optimum light intensity for growth of T. edulis. The leaf area and biomass indicators as well as reproductive characteristics were measured. The photosynthetic basic parameters and light response curve were determined by a LI-6400XT portable photosynthesis system, and the light response curve characteristic parameters was determined. Additionally, chlorophyll fluorescence parameters were determined by assorted fluorescence leaf chamber of LI-6400XT. The lowest biomass yield was observed in the 23% and 100% of full sunlight treatments while the highest value was found under the 78% of full sunlight conditions. With the reduction of light availability, the success rate of sexual reproduction, light saturation point (LSP) and light compensation point (LCP) reduced, while apparent quantum yield (AQY) increased. 23% and 45% of full sunlight treatments led to lower photosynthesis rate (Pn) and higher apparent quantum yield (AQY) in comparison with other treatents. The highest photosynthesis rate was observed in the 78% and 100% of full sunlight treatments. In addition, 78% of full sunlight treatments led to highest Fv/Fm, Fv'/Fm', PhiPS II, ETR, and qP. T. edulis was able to adapt in a wide range of light intensity, and 78% of full sunlinght was the most suitable light condition for growth of T. edulis.


Spatiotemporal patterns of clinical bovine dermatophilosis in Zimbabwe 1995-2014.
A retrospective study of clinical bovine dermatophilosis outbreaks and cases for the period 1995-2014 was conducted, using data obtained from the Division of Veterinary Services (DVS). A total of 3856 outbreaks and 26 659 cases of dermatophilosis were reported countrywide during this period. The post rainy season accounted for 37.9% of the outbreaks followed by the rainy season (26.7%), cold dry season (22.1%) and the hot dry season (13.2%). A retrospective space-time scan statistic in SaTScanTM was used to detect clusters. From this study, it was evident that dermatophilosis was spreading from the north-west of Zimbabwe through the central to the north-east during the period 2010-2014. Five clusters were identified mainly in the central and north-western regions of Zimbabwe. The primary cluster was centred at Ungwe, Gokwe district in Midlands; the second, third, fourth and fifth likely clusters were centred at Bonga (Mashonaland Central), ARDA (Mashonaland West), Nsenga (Matabeleland North) and Zanda in Gokwe, respectively. The findings of this study suggest the continued spread of dermatophilosis across the country; as such the Department of Livestock and Veterinary Services are advised to develop measures aimed at managing this spread such as dipping, quarantine, movement control and raising farmer awareness.


[Expression of CCAAT/enhancer binding protein beta in human gastric carcinoma and its clinical significance].
To explore the expression of CCAAT/enhancer binding protein beta (CEBPB) in gastric carcinoma tissues and its association with clinicopathological features and prognosis. CEBPB protein expression level was detected by immunohistochemistry method in resected gastric carcinomas and adjacent gastric mucosa tissues (n=81), and its association with clinicopathological features and prognosis was analyzed. The immunohistochemical staining of CEBPB was predominantly in the nucleus with some cytoplasmic staining. As a result, 16% (13/81) of the gastric carcinomas were stained positively, whereas there was hardly positive expression in adjacent gastric mucosa tissues. There was a significant association between the expression of CEBPB and distant metastasis on univariate analysis (P<0.05). The median survival time in patients with positive CEBPB expression was significantly lower than those with negative CEBPB expression (19.4 months vs. 45.2 months, P=0.024). Multivariable analysis showed that CEBPB was independently associated with prognosis (HR=2.544, 95%CI:1.154-5.610, P=0.021). Up-regulation of CEBPB suggests poor prognosis in patients with gastric cancer.


Occupational burnout among clinical research associates in China.
Clinical research associates (CRAs) play an important role in pharmaceutical research and development. Despite growing concern about occupational burnout among CRAs in China, little is known about this topic. We evaluated the factors associated with occupational burnout among CRAs in China and assessed the extent and nature of this syndrome in order to develop effective countermeasures. In October 2020, we collected data from a convenience sample of 438 CRAs from 26 major cities across China using a custom-designed questionnaire. We evaluated their psychopathological status and degree of occupational burnout based on the Maslach Burnout Inventory. Factors associated with burnout were identified using the Wilcoxon rank test, Kruskal-Wallis test, Spearman's rank correlation and multivariable ordinal logistic regression. Of the 438 CRAs analyzed, 82% showed signs of occupational burnout, with a large proportion experiencing moderate burnout (50%). Burnout in Chinese CRAs manifested as emotional exhaustion (77%), depersonalization (66%) and low sense of accomplishment (15%). The severity of burnout was significantly affected by mode of working (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.04-2.34), average number of working hours per week (OR 1.68, 95% CI 1.14-2.46), support provided by the hospital (OR 3.13, 95% CI 1.40-6.99) and likelihood of receiving a promotion (OR 4.05, 95% CI 1.34-12.22) (all P < 0.05). The incidence of occupational burnout among CRAs in China is high. Companies and hospitals must take effective measures to establish support systems for CRAs in order to alleviate this situation and thereby ensure the quality of clinical trials.


Half of older Americans seen in emergency department in last month of life; most admitted to hospital, and many die there.
Emergency department use contributes to high end-of-life costs and is potentially burdensome for patients and family members. We examined emergency department use in the last months of life for patients age sixty-five or older who died while enrolled in a longitudinal study of older adults in the period 1992-2006. We found that 51 percent of the 4,158 [corrected] decedents visited the emergency department in the last month of life, and 75 percent in the last six months of life. Repeat visits were common. A total of 77 percent of the patients seen in the emergency department in the last month of life were admitted to the hospital, and 68 percent of those who were admitted died there. In contrast, patients who enrolled in hospice at least one month before death rarely visited the emergency department in the last month of life. Policies that encourage the preparation of patients and families for death and early enrollment in hospice may prevent emergency department visits at the end of life.


Inflammatory Pseudotumor of the Lung Associated with Anemia: A Case Report and Review of the Literature.
Inflammatory pseudotumor of the lung is a benign tumor which is rarely seen. A mass in the left lung was observed in the chest roentgenogram of an 8 year-old boy while investigating for anemia. Preoperative investigations could not render the exact diagnosis. Pneumonectomy was required in exploratris thoracotomy. Histopathologic diagnosis was fibrohistiocytic type of inflammatory pseudotumor. Four months after the operation, anemia was cured without any further treatment.


[Tenofovir rescue therapy for chronic hepatitis B patients after suboptimal response to treatment with lamivudine plus adefovir dipivoxil].
To evaluate the efficacy of tenofovir (TDF) 300 mg/d, comparing with entecavir (ETV), in adults with chronic HBV infection who had previously virologic failure with lamivudine(LAM) and failed with rescue treatment of LAM combined adefovir(ADV). Fifty-seven patients of chronic hepatitis B on rescue treatment with TDF were analyzed retrospectively. The serum HBV DNA levels, HBeAg, ALT and serum creatinine (Cr) were detected after treatment for 12, 24 and 48 weeks respectively. In addition, data of 40 cases treated with ETV 1 mg per day as a control group were also collected. The baseline characteristics including HBV viral loads, median age, serum levels of ALT and Cr were compatible between TDF group and ETV group. At the time point of 24 weeks, there was only one patient (2.5%) in ETV group with HBV DNA<100 IU/ml, which means negative viral replication, while 49 patients in TDF group reached HBV negativity (86.0% vs 2.5%, χ(2) = 22.26, P < 0.001). At the time point of 48 weeks, the proportion of patients with HBV DNA<100 IU/ml in TDF group was significantly higher than that in ETV group (87.7% vs 12.5%,χ(2) = 24.17, P < 0.001). The ratios of ALT normalization (84.2% vs 77.5%, P = 0.431) and HBeAg seroconversion were similar in both groups. Elevated Cr was not found in both cohorts at the end of treatment. Tenofovir (300 mg/d) is an effective and safe rescue therapy in chronic hepatitis B patients who failed initial treatment with LAM and secondary treatment of LAM plus ADV.


The efficiency of the EmERGE pathway of care for people living with HIV in England.
This study estimated the efficiency of implementing the EmERGE Pathway of Care for people living with medically stable HIV in Brighton, UK; an App enables individuals to communicate with caregivers via their smart-phone. Individual data on the use of HIV outpatient services were collected one-year pre- and post-implementation of EmERGE. Unit costs of HIV outpatient services were calculated and linked with mean use of services per patient year. Primary outcomes were CD4 count and viral load; patient activation and quality-of-life measures were secondary outcomes. 565 participants were followed up April 2017 - October 2018: 93% men, mean age at recruitment 47.0 years (95%CI:46.2-47.8). Outpatient visits decreased by 9% from 5.6 (95%CI:5.4-5.8) to 5.1 (95%CI:4.9-5.3). Face-to-face visits decreased and virtual visits increased. Annual costs decreased by 9% from £751 (95%CI: £722-£780) to £678 (95%CI: £653-£705). Including anti-retroviral drugs, total annual cost decreased from £7,343 (95%CI: £7,314-7,372) to £7,270 (95%CI: £7,245-7,297): ARVs costs comprised 90%. EmERGE was a cost-saving intervention, patients remained engaged and clinically stable. Annual costs were reduced, but ARVs continue to dominate costs. Extension of EmERGE to other people with chronic conditions, could produce greater efficiencies but these needs to be evaluated and monitored over time.


Overexpression of a NAC-domain protein promotes shoot branching in rice.
For a better understanding of shoot branching in rice (Oryza sativa), a rice activation-tagging library was screened for mutations in tiller development. Here, an activation-tagging mutant Ostil1 (Oryza sativa tillering1) was characterized, which showed increased tillers, enlarged tiller angle and semidwarf phenotype. Flanking sequence was obtained by plasmid rescue. RNA-interfering and overexpression transgenic rice plants were produced using Agrobacterium-mediated transformation. The mutant phenotype was cosegregated with the reallocation of Ds element, and the flanking region of the reallocated Ds element was identified as part of the OsNAC2 gene. Northern analysis showed that expression of OsNAC2 was greatly induced in the mutant plants. Transgenic rice overexpressing the OsNAC2 resulted in recapture of the mutant phenotype, while downregulation of OsNAC2 in the Ostil1 mutant through RNA interfering (RNAi) complemented the mutant phenotype, confirming that the Ostil1 was caused by overexpression of OsNAC2. Overexpression of OsNAC2 regulates shoot branching in rice. Overexpression of OsNAC2 contributes tiller bud outgrowth, but does not affect tiller bud initiation. This suggests that OsNAC2 has potential utility for improving plant structure for higher light-use efficiency and higher yield potential in rice.


Propofol infusion syndrome: a case of increasing morbidity with traumatic brain injury.
A previously healthy 16-year-old boy with a closed, severe traumatic brain injury was admitted to a surgical and trauma intensive care unit. He was given a continuous infusion of propofol for sedation and to control intracranial pressure. About 3 days after the propofol infusion was started, metabolic acidosis and rhabdomyolysis developed. Acute renal failure ensued as a result of the rhabdomyolysis. Tachycardia with wide QRS complexes developed without hyperkalemia. The patient died of refractory cardiac dysrhythmia and circulatory collapse approximately 36 hours after the first signs of propofol infusion syndrome appeared. Propofol infusion syndrome is a rare but frequently fatal complication in critically ill children who are given prolonged high-dose infusions of the drug. The syndrome is characterized by severe metabolic acidosis, rhabdomyolysis, acute renal failure, refractory myocardial failure, and hyperlipidemia. Despite several publications on the subject in the past decade, most cases still seem to remain undetectable.


Rbf1-independent termination of E2f1-target gene expression during early Drosophila embryogenesis.
The initiation and maintenance of G1 cell cycle arrest is a key feature of animal development. In the Drosophila ectoderm, G1 arrest first appears during the seventeenth embryonic cell cycle. The initiation of G1(17) arrest requires the developmentally-induced expression of Dacapo, a p27-like Cyclin E-Cdk2 inhibitor. The maintenance of G1(17) arrest requires Rbf1-dependent repression of E2f1-regulated replication factor genes, which are expressed continuously during cycles 1-16 when S phase immediately follows mitosis. The mechanisms that trigger Rbf1 repressor function and mediate G1(17) maintenance are unknown. Here we show that the initial downregulation of expression of the E2f1-target gene RnrS, which occurs during cycles 15 and 16 prior to entry into G1(17), does not require Rbf1 or p27(Dap). This suggests a mechanism for Rbf1-independent control of E2f1 during early development. We show that E2f1 protein is destroyed in a cell cycle-dependent manner during S phase of cycles 15 and 16. E2f1 is destroyed during early S phase, and requires ongoing DNA replication. E2f1 protein reaccumulates in epidermal cells arrested in G1(17), and in these cells the induction of p27(Dap) activates Rbf1 to repress E2f1-target genes to maintain a stable G1 arrest.


Angiotensin II induces carbon monoxide production in the perfused kidney: relationship to protein kinase C activation.
Heme oxygenase (HO)-derived carbon monoxide (CO) attenuates vascular reactivity to constrictor stimuli. ANG II produces vasoconstriction and induces HO-1 isoform expression. However, direct evidence that ANG II promotes HO product generation is lacking. Therefore, we examined the effects of ANG II on CO release and HO isoform expression in isolated rat kidneys. Kidneys were perfused with oxygenated Krebs buffer. ANG II (1 micromol/l) increased (P < 0.05) perfusion pressure from 97 +/- 9 to 150 +/- 14 mmHg; it also increased (P < 0.05) the concentration of CO in the venous effluent (from 27.1 +/- 11.9 to 45.6 +/- 11.7, 62.5 +/- 16.7, 94.8 +/- 20.7, and 101.9 +/- 13.1 nmol/l after 30, 60, 90, and 120 min, respectively). The pressor effect of ANG II was blunted (P < 0.05) in kidneys perfused with buffer containing losartan (10 micromol/l) or PKC inhibitors staurosporine (0.1 micromol/l) or calphostin C (1 micromol/l). Kidneys perfused with buffer containing ANG II for 120 min also displayed increased (P < 0.05) HO-1 expression. Stannous mesoporphyrin (30 micromol/l) decreased CO release (P < 0.05) in preparations perfused with and without ANG II; the HO inhibitor also increased (P < 0.05) perfusion pressure, more so in kidneys perfused with that without ANG II. We conclude that ANG II stimulates CO production and release in isolated, perfused rat kidneys. This action of ANG II is linked to the activation of AT(1) receptors and involves PKC activation and upregulation of renal HO-1 but not of HO-2 protein expression. The study suggests upregulation of renal HO-1 and CO release are protagonic events in a counterregulatory mechanism that attenuates ANG II-induced renal vasoconstriction.


The impact of angiotensin II receptor blockade and the DASH diet on markers of endogenous fibrinolysis.
Hypertension is associated with impaired fibrinolysis. Both angiotensin receptor blockers (ARB) and the DASH (Dietary Approaches to Stop Hypertension) diet effectively lower blood pressure in hypertensive patients. Some evidence suggests that treatment with ARBs could increase fibrinolysis, however, data is conflicting. The impact of the DASH diet on fibrinolytic parameters is not known. Fifty-five hypertensive participants (35 African-American, 20 white) were randomly assigned to receive 8 weeks of either a control diet or the DASH diet. The diets did not differ in sodium content (approximately 3 g/day). Within each diet, individuals were randomly assigned to receive losartan or placebo for 4 weeks in double-blind, cross-over fashion. Tissue plasminogen activator (t-PA) antigen, t-PA activity, plasminogen activator inhibitor-1 (PAI-1) activity and plasma renin activity (PRA) were measured at the end of a 2-week run-in period on the control diet and after each treatment period. The DASH diet did not affect markers of fibrinolysis. Losartan significantly lowered t-PA antigen levels (-1.8 ng/mL, P = 0.045), but had no effect on t-PA or PAI-1 activities. This effect was more pronounced in whites (-4.1 ng/mL (P = 0.003)) compared with African-Americans (-0.3 ng/mL (P = 0.7), P-interaction = 0.03). Results were not materially affected by adjustment for basline values or changes in blood pressure. This study demonstrates that losartan reduces t-PA antigen levels in white, but not African-American hypertensive individuals. In contrast, the DASH diet had no significant effect on markers of fibrinolysis in whites or African-Americans.


Development of a Shortened Version of the Spatial Hearing Questionnaire (SHQ-S) for Screening Spatial-Hearing Ability.
The Spatial Hearing Questionnaire (SHQ) was developed to address how to measure spatial-hearing ability in complex listening situations (Tyler, Perreau, & Ji, 2009). It has been translated and validated into various languages, including Chinese, Dutch, French, and Persian. Although the SHQ contains only 24 items, it could be time-consuming in a busy clinic to administer. The purposes of this study were to develop and validate a shortened version of the SHQ (SHQ-S) and to compare self-perceived spatial-hearing ability across adults with normal hearing (NH), hearing loss (HL), and cochlear implants (CIs). This was a retrospective study. The full version of the SHQ was administered to measure self-perceived spatial-hearing ability for 51 adults with NH at Augustana College, 47 adults with essentially mild to moderately severe sensorineural HL at Illinois State University, and 72 adult CI users at the University of Iowa. Exploratory factor analysis was performed for the full version for the data collected from adults with NH and HL. Appropriate items were chosen to develop the SHQ-S from the results of the exploratory factor analysis. Confirmatory factor analysis was then applied to test the factor structure of the SHQ-S for all participants. One-way analysis of variance was used to compare the self-perceived spatial-hearing performance scores between the 3 groups. The exploratory factor analysis revealed scores loaded on 2 factors. Six items from the full version were chosen accordingly. The results of the confirmatory factor analysis indicated that that a shortened version of 6 items is sufficient to measure spatial-hearing ability. The internal consistency reliability of the SHQ-S was high. The main effect of the one-way analysis of variance was significant for the groups, F(2, 167) = 36.0, p < .0001. The comparisons with the Tukey adjustment indicated that the NH group reported significantly better spatial-hearing ability than either the HL or the CI group (both adjusted p values < .05). There was no significant difference between the participants with HL and CI users. The psychometric characteristics of the 6-item SHQ-S were similar to those of the full version of the SHQ. We conclude that the SHQ-S is a reliable and valid tool for measuring spatial-hearing ability and screening for spatial-hearing difficulties. Participants with NH reported better spatial-hearing ability than those with HL or with CIs, whereas the CI users and participants with HL perceived similar spatial-hearing ability in the present study.


VirB4- and VirD4-Like ATPases, Components of a Putative Type 4C Secretion System in Clostridioides difficile.
The type 4 secretion system (T4SS) represents a bacterial nanomachine capable of trans-cell wall transportation of proteins and DNA and has attracted intense interest due to its roles in the pathogenesis of infectious diseases. In the current investigation, we uncovered three distinct gene clusters in Clostridioides difficile strain 630 encoding proteins structurally related to components of the VirB4/D4 type 4C secretion system from Streptococcus suis strain 05ZYH33 and located within sequences of conjugative transposons (CTn). Phylogenic analysis revealed that VirB4- and VirD4-like proteins of the CTn4 locus, on the one hand, and those of the CTn2 and CTn5 loci, on the other hand, fit into separate clades, suggesting specific roles of identified secretion system variants in the physiology of C. difficile. Our further study on VirB4- and VirD4-like products encoded by CTn4 revealed that both proteins possess Mg2+-dependent ATPase activity, form oligomers (most likely hexamers) in aqueous solutions, and rely on potassium but not sodium ions for the highest catalytic rate. VirD4 binds nonspecifically to DNA and RNA. The DNA-binding activity of VirD4 strongly decreased with the W241A variant. Mutations in the nucleotide sequences encoding presumable Walker A and Walker B motifs decreased the stability of the oligomers and significantly but not completely attenuated the enzymatic activity of VirB4. In VirD4, substitutions of amino acid residues in the peptides reminiscent of Walker structural motifs neither attenuated the enzymatic activity of the protein nor influenced the oligomerization state of the ATPase. IMPORTANCE C. difficile is a Gram-positive, anaerobic, spore-forming bacterium that causes life-threatening colitis in humans. Major virulence factors of the microorganism include the toxins TcdA, TcdB, and CDT. However, other bacterial products, including a type 4C secretion system, have been hypothesized to contribute to the pathogenesis of the infection and are considered possible virulence factors of C. difficile. In the current paper, we describe the structural organization of putative T4SS machinery in C. difficile and characterize its VirB4- and VirD4-like components. Our studies, in addition to its significance for basic science, can potentially aid the development of antivirulence drugs suitable for the treatment of C. difficile infection.


The use of double staining techniques for investigating bacterial attachment to mucopolysaccharide-coated epithelial cells.
Double staining techniques were devised to study Escherichia coli attachment to mucopolysaccharide-coated urinary tract epithelial cells. In addition, vital stains were used to distinguish between viable and nonviable epithelial cells. Alcian blue was used to confirm the presence of glycosaminoglycans and periodic acid Schiff was used to distinguish a further group of polysaccharides, proteoglycans, neutral mucosubstances and glycolipids. The staining methods enabled investigations to be carried out concerning the possible importance of mucopolysaccharides in the attachment of bacteria to mucosal surfaces. Staining techniques were also used to investigate whether the presence of a mucopolysaccharide coat is related to epithelial cell viability. The combinations of vital and mucopolysaccharide stains were found to give reproducible results when cell preparations were evaluated by three individuals. Both in vivo and in vitro certain populations of epithelial cells have been found with a large number of bacteria preferentially attached. The double staining techniques described here may help to reveal the nature of these target cells.


Evolving Role for Pharmacotherapy in NAFLD/NASH.
Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent, dynamic disease that occurs across the age spectrum and can lead to cirrhosis and hepatocellular carcinoma. There are currently no US Food and Drug Administration (FDA) approved treatments for NAFLD; however, this is a field of active research. This review summarizes emerging pharmacotherapies for the treatment of adult and pediatric NAFLD. Investigated pharmacotherapies predominantly target bile acid signaling, insulin resistance, and lipid handling within the liver. Three drugs have gone on to phase III trials for which results are available. Of those, obeticholic acid is the single agent that demonstrates promise according to the interim analyses of the REGENERATE trial. Obeticholic acid showed reduction of fibrosis in adults with nonalcoholic steatohepatitis (NASH) taking 25 mg daily for 18 months (n = 931, reduction in fibrosis in 25% vs. 12% placebo, P < 0.01). Ongoing phase III trials include REGENERATE and MAESTRO-NASH, which investigates thyroid hormone receptor-β agonist MGL-3196. Outcomes of promising phase II trials in adults with NASH are also available and those have investigated agents, including the fibroblast growth factor (FGF)19 analogue NGM282, the GLP1 agonist liraglutide, the FGF21 analogue Pegbelfermin, the sodium glucose co-transporter 2 inhibitor Empagliflozin, the ketohexokinase inhibitor PF-06835919, the acetyl-coenzyme A carboxylase inhibitor GS-0976, and the chemokine receptor antagonist Cenicriviroc. Completed and ongoing clinical trials emphasize the need for a more nuanced understanding of the phenotypes of subgroups within NAFLD that may respond to an individualized approach to pharmacotherapy.


Tannins and Tannin-Related Derivatives Enhance the (Pseudo-)Halogenating Activity of Lactoperoxidase.
Several hydrolyzable tannins, proanthocyanidins, tannin derivatives, and a tannin-rich plant extract of tormentil rhizome were tested for their potential to regenerate the (pseudo-)halogenating activity, i.e., the oxidation of SCN- to hypothiocyanite -OSCN, of lactoperoxidase (LPO) after hydrogen peroxide-mediated enzyme inactivation. Measurements were performed using 5-thio-2-nitrobenzoic acid in the presence of tannins and related substances in order to determine kinetic parameters and to trace the LPO-mediated -OSCN formation. The results were combined with docking studies and molecular orbital analysis. The -OSCN-regenerating effect of tannin derivatives relates well with their binding properties toward LPO as well as their occupied molecular orbitals. Especially simple compounds like ellagic acid or methyl gallate and the complex plant extract were found as potent enzyme-regenerating compounds. As the (pseudo-)halogenating activity of LPO contributes to the maintenance of oral bacterial homeostasis, the results provide new insights into the antibacterial mode of action of tannins and related compounds. Furthermore, chemical properties of the tested compounds that are important for efficient enzyme-substrate interaction and regeneration of the -OSCN formation by LPO were identified.


Experimental study of combination of extraaortic balloon counterpulsation and ventricular assist cup to acute heart failure in dogs.
The goal of this study is to evaluate the applicability and effectiveness of combination support of the extraaortic balloon (EAB) and the ventricular assist cup (VAC) to the acute heart failure model. Under general anesthesia, 10 adult dogs were used. Through the median sternotomy, EAB was placed around the ascending aorta and VAC in the pericardial cavity. After heart failure was induced by administration of propranolol, the on-off tests of devices were done as follows. Only EAB was used, and only VAC was used and both devices were used. Regional blood flows (RBFs) of both ventricles, liver kidneys, and brain were measured by colored microsphere technique. Hemodynamic parameters were also measured. In heart failure model, cardiac output (CO) decreased to 66% of control value. In the group assisted by EAB, aortic peak-diastolic pressure and RBFs of both ventricle and brain increased significantly. In the group assisted by VAC, CO and RBFs of all but the left ventricle significantly increased. In the group assisted by EAB and VAC, aortic peak-diastolic pressure, CO, and all five RBFs significantly increased. These results suggest the combination of EAB and VAC is applicable and effective and would be a promising implantable device for the chronic heart failure.


The mandate project: institutionalizing a system of patient care quality assurance.
In 1970, prior to present-day requirements for quality assurance programs, a project was undertaken to institute such a program voluntarily in ten hospitals. Five hospitals succeeded in fully implementing the program which was based on the "Bi-Cycle Process" and each documented improvements in desired patient care behaviors. Two hospitals partially implemented the process and demonstrated no significant changes in desired patient care behaviors. Two hospitals failed to provide the data upon which assessments could be made and one hospital never got beyond preliminary efforts at instituting the process. The project demonstrates that a voluntary quality assurance program is feasible and has important implications for PSROs and continuing medical education. It also provides evidence that attention to psychosocial factors is essential in the institutionalization of programs designed to produce desired changes in patient care behaviors.


Risk factors for urethrocutaneous fistula following hypospadias repair surgery in Indonesia.
Hypospadias is one of the most common congenital malformations with a worldwide increasing trend over the years. Despite advancements in hypospadias repair, complications still occur. One of the most common complications of hypospadias repair surgery is Urethrocutaneous fistula. Studies attempting to analyze the association between the complication and risk factors are always beneficial, especially for studies performed in different areas of the world. We hypothesize that several evaluated risk factors among Indonesian hypospadias patients could be associated with the occurrence of urethrocutaneous fistula after the repair procedure. To determine the risk factors associated with urethrocutaneous fistula after hypospadias repair surgery by collecting and analyzing data obtained from multiple centers in Indonesia. A nationwide, retrospective study with 12 hospitals in Indonesia of children with a diagnosis of hypospadias was conducted. The collected data, taken from patients admitted in 2018, from each center's medical records consisted of patient identity, repair technique used, neourethra length, percutaneous cystostomy, and splint size as independent variables speculated to be possible risk factors correlated to the presence of urethrocutaneous fistulae. Binomial logistic regression analysis was performed using SPSS 21.0 to determine the relationship between urethrocutaneous fistulae as a post-repair complication and possible risk factors. We collected 591 hypospadias cases from 12 centers in 9 cities in Indonesia. Most patients came when they were already at the age of more than four years old (60.4%). The chordee-only and failed urethroplasty groups are excluded from the analysis as they are not classified as true hypospadias. Most repairs were performed by using the Tubular Incised Plate (TIP) with Thiersch-Duplay technique (44.16%). Most of the reconstructed neourethra are 2-3 cm in length (32.13%). The 8 Fr urethral splint (46.41%) was mostly used during the operation. Most surgeons decided not to perform cystostomy throughout the procedure (61.03%) based on personal preferences. Urethrocutaneous fistula was found in 80 patients (15.27%) out of the total patients who underwent the surgery. The binomial logistic regression analysis shows that age (OR = 1.398, p = 0.015), the decision to not perform cystostomy (OR = 2.963, p = 0.014), and splint size (OR = 1.243, p = 0.023) are significantly associated (p < 0.05) with the development of urethrocutaneous fistula. Age and splint size are significant risk factors for urethrocutaneous fistula after hypospadias repair in Indonesia, whereas performing percutaneous cystostomy during the repair decreases the risk for urethrocutaneous fistula occurrence.


Width of the normal ankle joint.
An investigation of the talocrural joint was performed in 160 normal adults, 80 males and 80 females. The joint space was measured on films at six locations, three in the antero-posterior and three in the lateral view of the ankle. The average joint space in men was 3.4 mm and in women 2.9 mm, which is a significant difference (p less than 0.001). The joint space was wider in the medial part when evaluating the antero-posterior view, but did not change with age.


Quercetin-Crosslinked Chitosan Films for Controlled Release of Antimicrobial Drugs.
Natural polymer-based films, due to their favorable biological and mechanical properties, have demonstrated great potential as coatings for biomedical applications. Among them, chitosan films have been widely studied both as coating materials and as controlled drug release systems. Crosslinkers are often used to tune chitosan's crosslinking degree and thus to control the drug release kinetics. For this purpose, quercetin, a plant-derived natural polyphenol, has gained attention as a crosslinker, mainly for its intrinsic anti-inflammatory, antioxidant, and antibacterial features. In this study, chitosan films crosslinked with three different concentrations of quercetin (10, 20, and 30% w/w) have been used as controlled release systems for the delivery of the antibacterial drug trimethoprim (TMP, 10% w/w). Physicochemical and antimicrobial properties were investigated. Surface wettability and composition of the films were assessed by contact angle measurements, X-ray photoelectron spectroscopy (XPS), and Fourier-transform infrared spectroscopy (FTIR), respectively. The release kinetic of TMP in phosphate-buffered saline (PBS) and 2-(N-morpholino) ethanesulfonic acid (MES) was studied over time. Finally, antibacterial properties were assessed on E. coli and S. aureus through Kirby-Bauer disc diffusion and micro-dilution broth assays. Results show that quercetin, at the tested concentrations, clearly increases the crosslinking degree in a dose-dependent manner, thus influencing the release kinetic of the loaded TMP while maintaining its bactericidal effects. In conclusion, this work demonstrates that quercetin-crosslinked chitosan films represent a promising strategy for the design of antibiotic-releasing coatings for biomedical applications.


Conditions for young infants' perception of object trajectories.
When an object moves behind an occluder and re-emerges, 4-month-old infants perceive trajectory continuity only when the occluder is narrow, raising the question of whether time or distance out of sight is the important constraining variable. One hundred and forty 4-month-olds were tested in five experiments aimed to disambiguate time and distance out of sight. Manipulating the object's visible speed had no effect on infants' responses, but reducing occlusion time by increasing object speed while occluded induced perception of trajectory continuity. In contrast, slowing the ball while it was behind a narrow or intermediate screen did not modify performance. It is concluded that 4-month-olds perceive trajectory continuity when time or distance out of sight is short.


In vitro assay for the quantitative measurement of apoptotic lymphocytes phagocytosis by peripheral blood monocytes.
Currently used assays for the quantification of apoptotic cells uptake by phagocytes have several methodological problems. Our assay overcomes some of these problems. As a source of apoptotic cells we used peripheral blood lymphocytes obtained from the patients with chronic lymphoblast leukaemia. Apoptosis was induced by incubating cells with cycloheximide for up to 24 h. The assay was performed in suspension of peripheral blood mononuclear cells. For the visualisation of the phagocytes and phagocyted cells and discrimination of phagocyted from bound apoptotic cells we used Acridine orange/Ethidium bromide double staining. Here we offer a simple test which enables reliable measurement and it can show the difference of phagocytic potential between different individuals.


[Carbon dioxide as an intra-arterial contrast agent in echography: a technic for its preparation and the preliminary results in assessing hepatocarcinoma vascularization].
This paper reports on an original method to prepare a contrast agent consisting of CO2 microbubbles to be injected i.a. during ultrasound examinations (ultrasound angiography-USA), whose value was investigated in the study of tumor neovascularity in HCC patients. Thirty-five HCC patients underwent USA. CO2 was drawn out from a gas container under pressure and, through a sublimation process, made available in predetermined quantities in test tubes. USA was performed during angiography in 9 cases and immediately before arterial chemoembolization in the other 26 cases. In 51 lesions vascularity was evaluated with conventional angiography, USA and lipiodol CT. USA demonstrated lesion hypervascularity in 91% of cases, as confirmed by lipiodol CT (88%), versus 72.4% of angiography. In 3 of 35 patients USA demonstrated 6 more lesions undetected by other modalities: two of them were proved to be HCC and adenomatous hyperplasia at percutaneous biopsy. USA is a cost-effective procedure, which is easy to perform during conventional angiography: it is more sensitive than conventional angiography in the study of lesion neovascularity and can help plan lesion management, anticipating the results of chemoembolization. The role of USA in the diagnosis and treatment of HCC is, however, still to be defined.


Comparison of Sacral-Alar-Iliac and Iliac-Only Methods of Pelvic Fixation in Early-Onset Scoliosis at 5.8 Years' Mean Follow-up.
Retrospective. Compare clinical outcomes in early-onset scoliosis (EOS) patients treated with sacral-alar-iliac (SAI) versus iliac-only methods of pelvic fixation at two years' minimum follow-up. Pelvic fixation in EOS is challenged by poor bone, anchor migration, and displacement. The long-term outcomes of SAI fixation in EOS is unknown. We retrospectively reviewed EOS patients in a single center from 2000 to 2017. Inclusion criteria were posterior spinal instrumentation with pelvic fixation before age 10 and 2 years' minimum follow-up. Clinical and radiographic data were analyzed using chi-squared and Student t tests (significance defined as p <.05). Seven subjects were included in the iliac-only fixation group (Galveston technique = 2, iliac screws = 5) and 17 in the SAI group. For the iliac-only group (mean follow-up = 6.8 years), pelvic obliquity improved from a mean of 18° at initial presentation to 11° at first instrumentation (p = .096), to 9° at end follow-up (p = .060), whereas the major curve improved correspondingly from a mean of 84° to 50° (p = .002) to 39° (p = .006). For the SAI group (mean follow-up = 5.5 years) at the same time points, pelvic obliquity improved from a mean of 25° to 6° (p <.001) to 5° (p <.001), whereas the major curve improved from a mean of 83° to 38° (p <.001) to 29° (p <.001). SAI fixation was associated with fewer complications (11 complications in 17 patients) compared to iliac-only fixation (10 complications in 7 patients) (p = .04). Neither method was associated with pelvic growth disturbances or neurologic deficits. In EOS patients at 2 years' minimum (5.8 years' mean) follow-up, both SAI and iliac-only methods corrected major curve, only SAI fixation corrected pelvic obliquity, and neither was associated with pelvic growth disturbances. SAI fixation was also associated with fewer complications. These findings may be due to the length and direction of the SAI anchors and abutment on the iliac cortex. Level III.


[Survey on computerized immunization registries in Italy].
Computerized immunization registries are essential for conducting and monitoring vaccination programs. In fact, they enable to improve vaccine offering to target population, generating needed-immunization lists and assessing levels of vaccination coverage. In 2007, a national survey on immunization registries was conducted in Italy. In February 2007, all the 21 Regional Health Authorities (RHAs) completed and returned an ad hoc questionnaire. In June 2007, RHAs were further contacted by telephone in order to verify and update the information provided in questionnaires. In 9 Italian Regions (42.8%), vaccination registries are computerized in all Local Health Units (LHUs). In five of these Regions, all LHUs use the same software, while in the remaining four Regions, different softwares are in use. In six additional Regions (28.6%), only some LHUs use computerized immunization registries (range 61.5%-95%). In the remaining 6 Regions (28.6%), which are all in Southern Italy, there are no computerised immunization registries at all. In total, computerised immunization registries cover 126/180 Italian LHUs (70%); in 76/126 (60%) of these LUHs, immunization registries are linked with population registries. This survey shows the need to improve the implementation of computerised immunization registries in Italy, especially in Southern Regions.


Consider Myocarditis When Patients Treated with Immune Checkpoint Inhibitors Present with Ocular Symptoms.
Immune checkpoint inhibitors (ICIs) have been associated with neurological immune related adverse events (irAE-N) and patients with ICI toxicity may present with neurological or ocular symptoms. Furthermore, patients on ICI may initially present to oncology or neurology. We report a case series of 3 patients treated with ICIs presenting with diplopia or ptosis, found to have concurrent myocarditis in addition to immune-related myopathy (irMyopathy) or myasthenia gravis (irMG). None of the patients described cardiac symptoms, underscoring the importance of screening for myocarditis in patients presenting with diplopia and/or other neuromuscular symptoms which may suggest either irMyopathy or irMG.


Stereotactic brain biopsies: specimen preparation and evaluation.
Stereotactically directed needle biopsy of central nervous system lesions is a widely used diagnostic procedure with low morbidity and mortality. Diagnostic tissue is obtained in most instances. As a part of the College of American Pathologists Practical Topics in Neuropathology series, the following report summarizes the pathologist's role in the procurement, preparation, and interpretation of these important specimens.


Synchronous Occurrence of Chronic Myeloid Leukemia and Mantle Cell Lymphoma.
Chronic myeloid leukemia (CML) and mantle cell lymphoma (MCL) are hematologic malignancies that originate from different oligopotent progenitor stem cells, namely, common myeloid and lymphoid progenitor cells, respectively. Although blastic transformation of CML can occur in the lymphoid lineage and CML has been related to non-Hodgkin lymphoma on transformation, to our knowledge, de novo and synchronous occurrence of CML and MCL has not been reported. Herein, we report the first case of synchronous CML and MCL in an otherwise healthy 38-year-old man. Potential etiologies and pathological relationships between the two malignancies are explored, including the possibility that the downstream effects of BCR-ABL may link it to an overexpression of cyclin D1, which is inherent to the etiology of MCL.


Effect of different concentrations of benzyladenine and frequency of watering on growth and quality of Dracaena sanderiana and Codiaeum variegatum.
The effect of benzyladenine concentration and watering frequency on the growth and quality of Dracaena sanderiana and Codiaeum variegatum was evaluated. Plants were treated with different benzyladenine concentrations of (0, 75, 150, 225 or 300 mg l(-1)) and watering frequencies, daily, every 4, 7 or 10 days interval. Benzyladenine concentration and watering frequency interacted significantly for plant grade on both species. This interaction resulted in the highest grade at 225 mg l(-1) benzyladenine and daily watering for D. sanderiana and 150 mgl(-1) benzyladenine and daily watering for C. variegatum. No significant interactions between benzyladenine concentration and watering frequency were observed for photosynthesis rate, stomatal conductance, specific leaf area and fresh weight of either species. For D. sanderiana, the highest photosynthesis rate (5.70 mmolm(-2)s(-1)) occurred at 225 mg l(-1) and decreased with increasing watering frequency. For C. variegatum, the highest photosynthesis rate (4.49 mmolm(-2)s(-1)) was recorded with benzyladenine concentration of 150 mg l(-1), and photosynthesis rate was found independent of watering frequency. For both species, stomatal conductance was recorded highest at 225 mg l(-1), but watering frequency failed to influence stomatal conductance. For better quality, D. sanderiana should be sprayed with benzyladenine at 225 mg l(-1), and C. variegatum with benzyladenine at 150 mg l(-1) in combinations with watering at 4 days interval.


Pyrogallol structure in polyphenols is involved in apoptosis-induction on HEK293T and K562 cells.
As multiple mechanisms account for polyphenol-induced cytotoxicity, the development of structure-activity relationships (SARs) may facilitate research on cancer therapy. We studied SARs of representatives of 10 polyphenol structural types: (+)-catechin (1), (-)-epicatechin (2), (-)-epigallocatechin (3), (-)-epigallocatechin gallate (4), gallic acid (5), procyanidin B2 (6), procyanidin B3 (7), procyanidin B4 (8), procyanidin C1 (9), and procyanidin C2 (10). Amongst them, the polyphenols containing a pyrogallol moiety (3-5) showed the most potent cytotoxicic activity. These compounds evoked a typical DNA-laddering phenomenon in HEK293T, which indicated that the induction of apoptosis at least partly mediates their cytotoxic activity. Anti-oxidative capacity of compounds 3-5 were comparable to those of the trimers 9 and 10, which were not cytotoxic. Therefore, we suggest that pyrogallol moiety is important for fitting of polyphenols to their putative target molecule(s) in non-oxidative mechanism.


Two Cases of Advanced Hepatocellular Carcinoma Who Responded Well to the Combination of Durvalumab Plus Tremelimumab After Disease Progression During Atezolizumab Plus Bevacizumab Therapy Under Bevacizumab Withdrawal.
Many systemic chemotherapies, including immune checkpoint inhibitors (ICI), are now available for the treatment of advanced hepatocellular carcinoma. On the other hand, it is often difficult to continue administration of angiogenesis inhibitors in these patients due to various side effects. In the two cases described in this paper, following the introduction of combination therapy with atezolizumab plus bevacizumab (Atezo/Bev), it was difficult to continue bevacizumab treatment due to side effects, such as proteinuria and fluid retention, with disease control in the two patients being ultimately poor. However, both patients experienced treatment success after switching Atezo/Bev to a regimen that included durvalumab, an anti-programmed cell death ligand 1 antibody (anti-PD-L1 antibody) similar to atezolizumab, plus tremelimumab, an anti-cytotoxic T lymphocyte-associated antigen 4 antibody (anti-CTLA-4 antibody) in situations where the continuation of bevacizumab was difficult. The efficacy of subsequent drug sequencing from ICI to another ICI after atezolizumab plus bevacizumab, which is the standard first-line treatment in advanced hepatocellular carcinoma, has not yet been established. We consider that the two cases described in this paper provide valuable information worthy of the report.


[Unusual injuries of the intestinal tract and gynecologic laparotomy].
A case of a 61-year-old patient is reported who underwent laparotomy for presumptive torsion of an ovarian tumor. The acute abdominal symptoms were caused by a fish bone which had perforated the omentum. Bilateral ovarian cystadenofibromas were present, yet torsion had not occurred; they were exstirpated. In addition, a case of a 70-year-old patient is presented who underwent relaparotomy for a cervicosigmoidal fistula. The fistula contained a poultry rib. Complete healing was observed after removal of the bone and suturing of the cervical sigmoidal defects.


Mass Casualties and Disaster Implications for the Critical Care Team.
Preparing for disasters both natural and anthropogenic requires assessment of risk through hazard vulnerability analysis and formulation of facility and critical care-specific disaster plans. Disaster surge conditions often require movement from conventional to contingency or crisis-level operations to meet the needs of the many under our care. Predisaster planning for modification of critical care space, staffing, and supplies is essential to successful execution of operations during a surge. Expansion of intensive care unit beds to nonconventional units such as perioperative areas, general care units, and even external temporary units may be necessary. Creative, tiered staffing models as well as just-in-time education of noncritical care clinicians and support staff are important to multiply capable personnel under surge conditions. Finally, anticipation of demand for key equipment and supplies is essential to maintain stockpiles, establish supply chains, and sustain operations under prolonged disaster scenarios.