Liquiritin targeting Th17 cells differentiation and abnormal proliferation of keratinocytes alleviates psoriasis via NF-κB and AP-1 pathway.
Psoriasis is a common immune-mediated inflammatory skin disease, caused by disturbed interactions between keratinocytes and immune cells. Chinese medicine shows potential clinical application for its treatment. Liquiritin is a flavone compound extracted from licorice and shows potential antitussive, antioxidant and antiinflammatory effects, and therefore may have potential as a psoriasis therapeutic. The aim of this work was to examine the possible roles that liquiritin may have in treating psoriasis. HaCaT cells were stimulated by TNF-α with or without liquiritin, harvested for analysis by western blots and RT-qPCR, and the cellular supernatants were collected and analyzed by ELISA for cytokines. In addition, 4 groups of mice were examined: Normal, Vehicle, LQ-L and LQ-H. The mice were sacrificed after 6 days and analyzed using IHC, ELISA, RT-qPCR and flow cytometry. The results showed that liquiritin could significantly inhibit the progression of psoriasis both in vitro and in vivo. Liquiritin strongly suppressed the proliferation of HaCaT keratinocytes but did not affect cell viability. Moreover, liquiritin alleviated imiquimod-induced psoriasis-like skin inflammation and accumulation of Th17 cells and DCs in vivo. In TNF-α-induced HaCaT keratinocytes, both protein and mRNA expression levels of inflammatory cytokines were sharply decreased. In imiquimod-induced mice, the activation of NF-κB and AP-1 was reduced after treatment with liquiritin. Collectively, our results show that liquiritin might act as a pivotal regulator of psoriasis via modulating NF-κB and AP-1 signal pathways.


Seven-year follow-up of a smoking-prevention program for children.
Smoking-prevention programs, run by both teachers, and teachers and peers, have been introduced into school curricula in many parts of the world. This paper describes a long-term follow-up of a randomised controlled trial of a smoking education program for children conducted in Western Australia. Seven years after the first survey of 2,366 Year 7 students in 1981, 68 per cent of initial participants were traced through public records; 53 per cent of these responded to a new survey concerning smoking. Previous follow-up after one and two years had shown that both teacher-led and peer-led programs continued to reduce the taking up of smoking by girls to about the same degree, whereas in boys, the teacher-led program appeared to be effective after one year but neither program was effective after two years. In nonsmoking girls, both the intervention programs maintained their effects at the seven-year follow-up, with an almost 50 per cent reduction in smoking prevalence in the intervention group. Nonsmoking girls appeared to respond to cigarette advertisements. Mothers seemed to influence nonsmokers of both sexes and brothers seemed to influence smokers of both sexes. The seven-year follow-up confirmed the results seen at two years for boys, that the effects of the education program had dissipated. However, this study suggests that the smoking-prevention program had a lasting effect on preventing girls from taking up smoking.


Heteromodal conceptual processing in the angular gyrus.
Concepts bind together the features commonly associated with objects and events to form networks in long-term semantic memory. These conceptual networks are the basis of human knowledge and underlie perception, imagination, and the ability to communicate about experiences and the contents of the environment. Although it is often assumed that this distributed semantic information is integrated in higher-level heteromodal association cortices, open questions remain about the role and anatomic basis of heteromodal representations in semantic memory. Here we used combined neuroimaging evidence from functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to characterize the cortical networks underlying concept representation. Using a lexical decision task, we examined the processing of concepts in four semantic categories that varied on their sensory-motor feature associations (sight, sound, manipulation, and abstract). We found that the angular gyrus was activated across all categories regardless of their modality-specific feature associations, consistent with a heteromodal account for the angular gyrus. Exploratory analyses suggested that categories with weighted sensory-motor features additionally recruited modality-specific association cortices. Furthermore, DTI tractography identified white matter tracts connecting these regions of modality-specific functional activation with the angular gyrus. These findings are consistent with a distributed semantic network that includes a heteromodal, integrative component in the angular gyrus in combination with sensory-motor feature representations in modality-specific association cortices.


Mesendoderm cells induce oriented cell division and invagination in the marine shrimp Sicyonia ingentis.
The mesendoderm (ME) cells are the two most vegetal blastomeres in the early developing embryo of the marine shrimp Sicyonia ingentis. These two cells enter mitotic arrest for three cycles after the 5th cell cycle (32-cell stage) and ingress into the blastocoel at the 6th cycle (62-cell stage). Circumjacent to the ingressing ME cells are nine presumptive naupliar mesoderm (PNM) cells that exhibit a predictable pattern of spindle orientation into the blastopore, followed by invagination. We examined the role of ME cells and PNM cells in gastrulation using blastomere recombinations and confocal microscopy. Removal of ME progenitors prevented gastrulation. Removal of any other blastomeres, including PNM progenitors, did not interfere with normal invagination. Altered spindle orientations occurred in blastomeres that had direct contact with one of the ME cells; one spindle pole localized to the cytoplasmic region closest to ME cell contact. In recombined embryos, this resulted in an extension of the region of ME-embryo contact. Our results show that ME cells direct the spindle orientations of their adjacent cells and are consistent with a mechanism of oriented cell division being a responsible force for archenteron elongation.


Reply to Lilienfeld: why alcoholism is a disease.
Lilienfeld's attack on my conceptual examination of the disease concept of alcoholism suffers from erroneous interpretations, fallacious reasoning, and a lack of familiarity with relevant alcoholism research. He offers an alternative nominalist interpretation of the disease concept of alcoholism based on a fuzzy boundary between disease and wellness. He fails to recognize that the basic issue between nominalist and realist accounts of a lower-order concept such as alcoholism is the presence or absence of general principles that may account for the observed signs and symptoms characterizing a specific disease entity, not fuzzy boundaries between higher-order categories. Extensive evidence (which Lilienfeld ignores) of biological bases for the pathognomic signs and symptoms of alcoholism, particularly loss of control, demonstrates that the disease concept of alcoholism refers to a disease entity that has a biological basis. It is not a "mental construct."


Adjacent segment pathology of the cervical spine: A case report.
Adjacent segment pathology (ASP) refers to degenerative changes at segments immediately contiguous to previous spinal fusion. Its pathophysiology is hypothesized as being possibly due to altered biomechanical stresses on adjacent levels following spinal fusion or due to patient propensity to develop progressive degenerative change. This case report describes a 61-year-old female who presented with neck pain and cervical radiculopathy attributed to an anterior cervical discectomy and spinal fusion performed for degenerative disc disease 30 years earlier. ASP was seen on magnetic resonance imaging (MRI) and radiograph. Treatment consisted of cervical manipulation, soft-tissue mobilization, flexion-distraction decompression, and therapeutic ultrasound to release restriction and restore muscle strength. Following 34 sessions of chiropractic intervention, her symptoms were resolved. Patients with ASP will have ongoing shared care between general practitioners and secondary or tertiary care pain units. This report aims to build a shared understanding from the wider vision of ASP and help primary practitioners to manage ASP effectively.


Asymptomatic right atrial thrombus in a case of nephrotic syndrome.
Hypercoagulable state in nephrotic syndrome can be complicated by thrombosis in unusual sites. We describe the case of a steroid-responsive nephrotic syndrome in an adult patient complicated by isolated thrombus in the right atrium which was completely asymptomatic. The patient was treated with steroids, anticoagulation and excision of the intracardiac thrombus with complete resolution. The case is presented in view of its rarity and to highlight the importance of routine echocardiography in all cases of nephrotic syndrome.


Measurement of BCR-ABL1 by RT-qPCR in chronic myeloid leukaemia: findings from an International EQA Programme.
Sequential measurement of BCR-ABL1 mRNA levels by reverse transcription quantitative polymerase chain reaction (RT-qPCR) is embedded in the management of patients with chronic myeloid leukaemia (CML), and has played an important role in the remarkable improvement in patient outcomes seen in this disease. As a provider of external quality assessment (EQA) in this area, UK NEQAS for Leucocyte Immunophenotyping (UKNEQAS LI) has a unique perspective on the changing face of BCR-ABL1 testing in CML. To assess the impact of technical standardisation and the development of the International Scale (IS) upon the accuracy of BCR-ABL1 testing, we reviewed EQA trial data from 2007 to 2015. Comparison of participant results identified considerable variability at both high and low levels of disease, including therapeutically important decision points; however, results converted to the IS showed less variability compared to unconverted data sets. We also found that different methods of converting to the IS produce consistently different median results within UKNEQAS LI IS data sets. This data suggests that whilst the development of the IS has improved the comparability of results between centres, there is still the need for further improvement in the processes of converting raw results to the IS in order to fully realise the benefits of molecular monitoring of CML.


Catheter-related thrombosis diagnosed by computed tomography.
Catheter-related bloodstream infection can be detected with CT. Although it is not mandatory for its diagnosis, it is strong evidence as a cause of fever if detected incidentally.


Efficacy of peptide receptor radionuclide therapy with 177Lu-octreotate in metastatic pulmonary neuroendocrine tumors: a dual-centre analysis.
There is lack of data on the specific benefit of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET) of pulmonary origin. This dual- centre study aimed to assess outcome and toxicity of standardized PRRT with 177Lu-octreotate in a patient population of advanced pulmonary NET of grade 1-2. We retrospectively assessed 22 consecutively patients treated with 4 intended cycles at 3 monthly intervals (mean activity per cycle 7.8±0.68 GBq). In a median follow-up period of 54 months, no significant nephrotoxicity (≥ grade 3) was observed. Reversible hematotoxicity (grade 3) occurred in 3 patients (13.6%). Treatment response consisted of partial response in 6 (27.3%), stable disease in 9 (40.9%), and progressive disease in 7 (31.8%) patients. Median progression-free survival (PFS) and overall survival (OS) was 27 (95% CI, 9-45) and 42 months (95% CI, 25-59), respectively. High hepatic tumor load (> 50%) and high plasma chromogranin A (> 600 ng/mL) were negative baseline predictors for PFS and OS on univariate analysis, CgA remained significant on multivariate analysis (PFS, P=0.011; OS, P=0.026). Disease progression despite PRRT was associated with shorter survival (median OS 15 vs 53 mo, P<0.001). Despite a higher incidence of treatment failure compared to NET of other origins, the observed substantial and sustained disease stabilization (median PFS of 27 mo, disease control rate of > 2/3 of pts) indicates considerable efficacy of 177Lu-octreotate in pulmonary NET.


Ovalbumin-specific induction of IL2 responsiveness in lymphocytes from patients with hen egg allergy and its regulation by the culture supernatant of normal lymphocytes.
Interleukin 2 (IL2) responsiveness of ovalbumin (OVA)-stimulated lymphocytes from patients with hen-egg allergy was studied. The number of viable cells of 5-day cultured lymphocytes stimulated with OVA was increased by an additional three days incubation with recombinant IL2. This phenomenon was not observed when the lymphocytes of patients allergic to OVA but not to Dermatophagoides farinae extract antigen (Df) were stimulated with Df. Normal lymphocytes stimulated with OVA expressed Tac antigen (low affinity IL2 receptor) but, in contrast to those from the allergic patients, did not absorb nor respond to IL2. The induction of OVA-specific IL2 responsiveness in patient lymphocytes was markedly suppressed on the addition of culture supernatant from OVA-stimulated normal T cells, but Df-specific IL2 responsiveness of the lymphocytes from Df-sensitized patients with bronchial asthma was not suppressed by the same supernatant. The supernatant of lymphocytes from allergic patients did not show such suppressive effect. The patient lymphocytes whose IL2 responsiveness was suppressed with the supernatant from normal lymphocytes still expressed Tac antigen. These observations suggest that the culture supernatant of normal T lymphocytes stimulated with OVA contained an antigen-specific factor suppressing the induction of IL2 responsiveness of OVA-stimulated patient lymphocytes. The production of such a suppressive factor was impaired in the patient, and further, the factor may have inhibited the triggering signal of IL2 receptors having absorbed IL2. The existence of some allogeneic barrier between the factor(s) and patient lymphocytes was suggested, since the supernatant from OVA-stimulated normal T cells did not necessarily suppress the response of all patients tested.


Foliar architecture differentially restrains metal sequestration capacity in wheat grains (Triticum aestivum L.) grown in hyper-chloride-contaminated soils.
Anthropogenic activities, such as industrial wastewater and use of water softeners, cause hyper-accumulation of Cl- in water sources and soils. Currently, industries have no sustainable method to remove these Cl- ions from wastewater. This study was conducted to evaluate the integrative responses of wheat cultivated in five industrial effluent-affected areas (S2-S6) by investigating soil characters and bioaccumulation of metals in wheat plants and grains. The S4 site (near the second chloride outlet) exhibited a higher concentration of CO2, SO2, NO2, Cl-, Cd, Mn, Ni, Cr, and Zn. Soil from S6 (sewage wastewater downstream getting mixed with chloride-contaminated water) had a minimum level of nutrients (Na, K, and Ca), maximum metals (Cd, Fe, Pb, Mn), and reduction in plant biomass. In site S2 (sewage wastewater upstream of the chloride factory), a higher level of minerals and metals was noted in the roots. Maximum metals in grains occurred in S6 with higher organic osmolytes. The sequestration capacity of metals in leaves was also increased by alterations in anatomical traits. Results indicated that metals and hyper-Cl- concentration employed a negative influence on the plants because of poor soil quality, extremely damaged microstructures leading to reduced yield, poor grain quality, and excessive translocation from roots to wheat grains. These findings revealed that contaminated plants used as either green forage or hay are noxious to animals and if used as grain for feed or humans can lead to serious health hazards.


Severe violations of independence in response inhibition tasks.
The stop-signal paradigm, a primary experimental paradigm for understanding cognitive control and response inhibition, rests upon the theoretical foundation of race models, which assume that a go process races independently against a stop process that occurs after a stop-signal delay (SSD). We show that severe violations of this independence assumption at short SSDs occur systematically across a wide range of conditions, including fast and slow reaction times, auditory and visual stop signals, manual and saccadic responses, and especially in selective stopping. We also reanalyze existing data and show that conclusions can change when short SSDs are excluded. Last, we suggest experimental and analysis techniques to address this violation, and propose adjustments to extant models to accommodate this finding.


Virus diseases in lettuce in the Mediterranean basin.
Lettuce is frequently attacked by several viruses causing disease epidemics and considerable yield losses along the Mediterranean basin. Aphids are key pests and the major vectors of plant viruses in lettuce fields. Lettuce mosaic virus (LMV) is probably the most important because it is seed-transmitted in addition to be transmissible by many aphid species that alight on the crop. Tomato spotted wilt virus (TSWV) is another virus that causes severe damage since the introduction of its major vector, the thrips Frankliniella occidentalis. In regions with heavy and humid soils, Lettuce Mirafiori big-vein virus (LMBVV) can also produce major yield losses.


1-year treatment with recombinant somatropin in prepubertal and pubertal growth hormone deficient patients: results from a French multicentre trial.
In this French study with recombinant somatropin, the stimulation of growth in 32 prepubertal (age 10.0 +/- 3.5 years; mean +/- SD) and 19 pubertal (age 14 +/- 1.5 years) GH deficient children was compared; the stimulation of growth was similarly good in the two groups. The height velocity SD scores increased from -2.5 +/- 1.7 and -0.9 +/- 1.5 to 2.2 +/- 1.9 and 1.6 +/- 1.6 in prepubertal and pubertal children, respectively. Expressed as cm/year, these correspond to increases from 3.2 +/- 1.3 cm/year and 4.1 +/- 1.2 cm/year to 8.1 +/- 1.5 cm/year and 8.6 +/- 1.9 cm/year in the prepubertal and pubertal patients, respectively. Safety and tolerance were good and the immunogenicity of Genotonorm was low.


A septin from the filamentous fungus A. nidulans induces atypical pseudohyphae in the budding yeast S. cerevisiae.
Septins, novel cytoskeletal proteins, form rings at the bases of emerging round buds in yeasts and at the bases of emerging elongated hyphal initials in filamentous fungi. When introduced into the yeast Saccharomyces cerevisiae, the septin AspC from the filamentous fungus Aspergillus nidulans induced highly elongated atypical pseudohyphae and spore-producing structures similar to those of hyphal fungi. AspC induced atypical pseudohyphae when S. cerevisiae pseudohyphal or haploid invasive genes were deleted, but not when the CDC10 septin gene was deleted. AspC also induced atypical pseudohyphae when S. cerevisiae genes encoding Cdc12-interacting proteins Bem4, Cla4, Gic1 and Gic2 were deleted, but not when BNI1, a Cdc12-interacting formin gene, was deleted. AspC localized to bud and pseudohypha necks, while its S. cerevisiae ortholog, Cdc12, localized only to bud necks. Our results suggest that AspC competes with Cdc12 for incorporation into the yeast septin scaffold and once there alters cell shape by altering interactions with the formin Bni1. That introduction of the A. nidulans septin AspC into S. cerevisiae induces a shift from formation of buds to formation of atypical pseudohyphae suggests that septins play an important role in the morphological plasticity of fungi.


Anaerobic digestion of waste activated sludge combined with ozone post-treatment and recycling.
The aim of the study was to determine the performances of a combined ozone/anaerobic digestion system for waste activated sludge reduction. The objective was the estimation of the process efficiency and stability when keeping constant influent flow while increasing recycled chemically treated flow. The ozonation step consisted in a partial oxidation (0.16 g O3/g SS) of the anaerobic mesophilic digested sludge. Chemical treatment of digested sludge resulted in a threefold COD solubilization and a decrease of SS of 22%. Some of the advantages of digested sludge ozonation were: deodorization, better settlement and a reduction in viscosity. However there were drawbacks: foaming during ozonation and, at high ozone doses, poorer filterability. The anaerobic digestion was carried out over 6 months with an increasing recycling of ozonated flow. Suspended solids removal rate and COD removal rate were compared with initial operating conditions for the biological reactor and the whole combined process. The optimum recycling rate was 25% with increases of SS removal and COD removal of 54% and 66% respectively when considering the combined process; corresponding to a decrease of the hydraulic retention time from 24 days to 19 days.


Oryza glumaepatula: A wild relative to improve drought tolerance in cultivated rice.
Developing drought-resistant rice (Oryza sativa, L.) is essential for improving field productivity, especially in rain-fed areas affected by climate change. Wild relatives of rice are potential sources for drought-resistant traits. Therefore, we compared root growth and drought response among 22 wild Oryza species, from which Oryza glumaepatula was selected as a promising source for further exploration. A geographically diverse panel of 69 O. glumaepatula accessions was then screened for drought stress-related traits, and 6 of these accessions showed lower shoot dry weight (SDW) reduction, greater percentage of deep roots, and lower stomatal density (STO) under drought than the drought tolerant O. sativa variety, Sahbhagi dhan. Based on whole-genome resequencing of all 69 O. glumaepatula accessions and variant calling to a high-quality O. glumaepatula reference genome, we detected multiple genomic loci colocating for SDW, root dry weight at 30 to 45 cm depth, and STO in consecutive drought trials. Geo-referencing indicated that the potential drought donors originated in flood-prone locations, corroborating previous hypotheses about the coexistence of flood and drought tolerance within individual Oryza genomes. These findings present potential donor accessions, traits, and genomic loci from an AA genome wild relative of rice that, together with the recently developed reference genome, may be useful for further introgression of drought tolerance into the O. sativa backgrounds.


Sexual dimorphism in immunity: improving our understanding of vaccine immune responses in men.
Weaker immune responses are often observed in males compared to females. Since female hormones have proinflammatory properties and androgens have potent immunomodulatory effects, this sexual dimorphism in the immune response seems to be hormone dependent. Despite our current knowledge about the effect of sex hormones on immune cells, definition of the factors driving the sex differences in immunoclinical outcomes, such as the diminished response to infection and vaccination observed in men or the higher rates of autoimmunity observed in females, remains elusive. Recently, systems approaches to immune function have started to suggest a way toward establishing this connection. Such studies promise to improve our understanding of the mechanisms underlying the sexual dimorphism observed in the human immune system.


Serum copper and ceruloplasmin activity at the early growing stage in foals.
Serum concentrations of copper (Cu), zinc (Zn), manganese (Mn), calcium (Ca) and inorganic phosphorus (P), as well as antigenic ceruloplasmin (Cp) and oxidase activity as a functional index for copper metabolism, were measured in 10 foals (5 males and 5 females) and their dams. Samples were harvested from the foals within 1 wk after birth and monthly from 1 to 17 mo of age. Samples were collected from their dams in the perinatal period (monthly from 2 mo before delivery to 5 mo postpartum). Serum oxidase activity, antigenic Cp and Cu in foals were extremely low at 1 wk. Serum Cp had the lowest value of 17.0 +/- 8.0 (mean +/- SD) mg/dL within the 1st wk, then increased rapidly up to 43.7 +/- 5.8 mg/dL at 1 mo, and maintained this level until the 17th mo. Serum Zn in foals had the highest value of 73.2 +/- 13.1 micrograms/dL within 1 wk, then decreased to 38.3 +/- 5.9 micrograms/dL by 17 mo. Serum Mn, Ca and P in mares were almost stable and within established reference ranges for our laboratory in the perinatal period, and these values in foals were also in the normal range. Even on appropriate feeding, serum Cu, Cp and oxidase activity were quite low a few weeks after birth, while a higher proportion of Cp-binding copper was found in the foals. This might be caused by the limited synthesis of ceruloplasmin in this period. These data suggest that newborn foals are in a critical situation of marginal copper status in the early stage of growth.


Quantitative measurement of the histological features of alpha-1 antitrypsin deficiency-associated liver disease in biopsy specimens.
Pathological mutations in Alpha-1 Antitrypsin (AAT) protein cause retention of toxic polymers in the hepatocyte endoplasmic reticulum. The risk for cirrhosis in AAT deficiency is likely directly related to retention of these polymers within the liver. Polymers are classically identified on liver biopsy as inclusion bodies by periodic acid schiff staining after diastase treatment and immunohistochemistry. However, characterization of the polymer burden within a biopsy sample is limited to a semi-quantitative scale as described by a pathologist. Better methods to quantify polymer are needed to advance our understanding of pathogenesis of disease. Therefore, we developed a method to quantify polymer aggregation from standard histologic specimens. In addition, we sought to understand the relationship of polymer burden and other histologic findings to the presence of liver fibrosis. Liver samples from a well-categorized AATD cohort were used to develop histo-morphometric tools to measure protein aggregation. Whole-slide morphometry reliably quantifies aggregates in AATD individuals. Despite very low levels of inclusions present (0-0.41%), accumulation of globules is not linear and is associated with higher fibrosis stages. Immunohistochemistry demonstrates that fibrosis is associated with polymer accumulation and not total AAT. A proportion of patients were found to be "heavy accumulators" with a polymer burden above the upper 25% of normal distribution. Males had significantly more liver inclusions and polymer than females. These measurements also highlight interrelated phenotypes of hepatocellular degeneration and autophagy in AATD liver disease. Quantitative inclusion analysis measures AAT accumulation in liver biopsy specimens. Quantification of polymer may identify individuals at risk for progressive disease and candidates for therapeutic interventions. Furthermore, these methods may be useful for evaluating efficacy of drugs targeting accumulation of AAT.


Ultrastructure of the cell wall of Erwinia amylovora.
Thin sectioned cells of Erwinia amylovora revealed two electron-dense layers in their walls when fixed at 24 to 27 C and three when fixed at 4 C.


Results of therapy for acute lymphoblastic leukemia in black and white children.
Treatment results for acute lymphoblastic leukemia (ALL) clearly have improved over the past decade, but black children have not fared as well as white children in large national trials. To compare the clinical outcomes of therapy for black and white children with ALL treated at a single institution. A retrospective analysis of 412 children and adolescents (68 black, 338 white, and 6 other race) with newly diagnosed ALL who were treated consecutively at a pediatric cancer center in Memphis, Tenn. Patients were enrolled from December 1991 to July 1998 in successive Total Therapy studies regardless of race, ethnicity, or ability to pay and received risk-directed therapy according to stringent criteria. All patients received the same intensive, remission-induction therapy followed by 120 weeks of risk-assigned postremission therapy that included reinduction treatment, pulses of high-dose methotrexate, and early intensification of intrathecal chemotherapy. Event-free and overall survival rates for black and white children were estimated by the method of Kaplan and Meier and compared with the Mantel-Haenszel test and by Cox proportional hazards regression analysis, adjusting for known prognostic factors. The 68 black children were significantly more likely than the 338 white children to have higher-risk prognostic features, including an initial leukocyte count greater than 100 x 10(3)/ microL, a T-cell immunophenotype, and the t(1;19) chromosomal translocation with E2A-PBX1 fusion, and were less likely to have hyperdiploid blast cells, a favorable prognostic factor in childhood ALL. However, the clinical outcomes for these 2 cohorts were not significantly different: 5-year event-free and overall survival rates were 80.7% (95% confidence interval [CI], 70.3%-91.1%) and 86.2% (95% CI, 77.2%-95.2%) for black children vs 79.4% (95% CI, 74.7%-84.1%) and 85.0% (95% CI, 80.9%-89.1%) for white children. Ten-year results also were comparable, but the CIs were wide because of the small numbers of patients who had been followed up for 10 years or more. The lack of a racial effect on the long-term outcome of therapy was still apparent in a multivariate Cox regression analysis, adjusting for sex, age, presenting leukocyte count, leukemic cell DNA index, immunophenotype, and central nervous system status. With equal access to effective antileukemic therapy, black and white children with ALL can expect the same high rate of cure.


Technique for differentiating particles that are cell-associated or ingested by macrophages.
Phagocytosis is a two-step process involving attachment and ingestion of particulate material. It is often difficult to determine under a light microscope whether the particles are actually ingested or are merely attached to the cell. A more accurate, easy to perform technique with the use of xylene has been developed for determining the difference between the attachment and ingestion of polystyrene latex spheres. The xylene treatment dissolves the extracellular spheres, leaving only the intracellular spheres to be counted by the experimenter to obtain a more accurate phagocytic index. This technique also allows an investigator to get an ingestion index, an attachment index, or both.


Conditions associated with leukocytosis in a tertiary care hospital, with particular attention to the role of infection caused by clostridium difficile.
Few modern studies have enumerated the conditions associated with leukocytosis. Our clinical experience has implicated Clostridium difficile infection in a substantial proportion of patients with leukocytosis. In a prospective, observational study of 400 inpatients with WBC counts of >/=15,000 cells/mm(3), we documented >/=1 infection in 207 patients (53%). Of these 207 patients, 97 (47%) had pneumonia, 60 (29%) had urinary tract infection, 34 (16%) had soft-tissue infection, and 34 (16%) had C. difficile infection. C. difficile infection was present in 25% of patients with WBC counts of >30,000 cells/mm(3) who did not have hematological malignancy. Other causes of leukocytosis in the 400 patients included physiological stress, in 152 patients (38%); medications or drugs, in 42 (11%); hematological disease, in 22 (6%); and necrosis or inflammation, in 22 (6%). C. difficile infection is a prominent cause of leukocytosis and this diagnosis should be considered for patients with WBC counts of >/=15,000 cells/mm(3), even in the absence of diarrheal symptoms.


A review of the biological effects of Myrtus communis.
The World Health Organization stated that 1.6 million deaths worldwide were caused by contact with chemicals and toxins in 2019. In the same year, the Centers for Disease Control and Prevention stated that natural toxins caused 3960 deaths. Myrtus communis, also known as common Myrtle, is a flowering plant native to the Mediterranean region. Myrtle has been traditionally used to treat diarrhea, inflammation, bleeding, headache, pulmonary and skin diseases. This review was performed to assess Myrtle's protective and therapeutic efficacy against various chemical, natural, and radiational noxious. Multiple databases such as PubMed, Web of Sciences, and Scopus were investigated without publication time limitation. Recent studies have demonstrated its potential as a protective agent against both natural and chemical toxins. One of Myrtle's most significant protective properties is its high antioxidant content. Studies have shown that the antioxidant properties of Myrtle can protect against harmful substances such as heavy metals, pesticides, and other environmental toxins. Additionally, Myrtle has anti-inflammatory properties that can help reduce the damage caused by long-term exposure to toxins. The anti-inflammatory and antimicrobial properties of Myrtle have also proven effective in alleviating gastrointestinal conditions such as gastric ulcers.


Transduction of a Neospora caninum antigen gene into mammalian cells using a modified Bombyx mori nucleopolyhedrovirus for antibody production.
Autographa californica multiple nucleopolyhedrovirus (AcMNPV) can easily enter and transduce foreign genes into mammalian cells, but these functions are difficult for Bombyx mori nucleopolyhedrovirus (BmNPV). In this study, we investigated the induction of antibody production in mice immunized with an engineered BmNPV. The GP64 of BmNPV (BmGP64) was replaced with the GP64 of AcMNPV (AcGP64); this construct, designated BmNPVΔbgp/AcGP64, displays AcGP64 on the surface of BmNPV. The Neospora caninum antigen (NcSRS2) expression cassette, consisting of the cytomegalovirus immediate-early promoter and NcSRS2 from N. caninum, was inserted into BmNPVΔbgp/AcGP64; this construct was designated BmNPVΔbgp/AcGP64/SRS2. For comparison, AcMNPV/SRS2, which contains the same NcSRS2 expression cassette as for BmNPVΔbgp/AcGP64, was also constructed. NcSRS2 was expressed in HEK293T cells when the engineered BmNPVs were transduced at a multiplicity of infection of 150. BmNPVΔbgp/AcGP64/SRS2 induced the production of NcSRS2-specific antibodies in mice, whereas AcMNPV/SRS2 and the control BmNPV did not. These results suggest that BmNPV prepared from silkworm hemolymph induces the production of antigen-specific antibodies in immunized mice and can be used for antibody production and vaccine development.


[Social security and labor absenteeism in a regional health service].
Absenteism can generate important economic costs. To analyze the determinants of the time off work for sick leaves granted to workers of a regional health service. Information about 2033 individuals, working at a health service, that were granted at least one sick leave during 2012, was analyzed. Personal identification was censored. Special emphasis was given to the type of health insurance system of the workers (public or private). Workers ascribed to the Chilean public health insurance system (FONASA) had 11 days more off work than their counterparts ascribed to private health insurance systems. A higher amount of time off work was observed among older subjects and women. Age, gender and the type of health insurance system influence the number of day off work due to sick leaves.


[Role of nuclear factor-κB activation in bilirubin-induced rat hippocampal neuronal apoptosis and the effect of TAT-NBD intervention].
To investigate the role of nuclear factor-κB (NF-κB) activation in bilirubin-induced apoptosis of rat hippocampal neurons and the effect of TAT-NBD intervention on bilirubin neurotoxicity. Primary-cultured rat hippocampal neurons were treated with TAT-NBD in the initial 6 or 24 h or in the latter 6 h during a 24-h bilirubin exposure of the cells (early, continuous and late intervention groups, respectively). Immunocytochemistry was performed to detect NF-κB p65 protein expression, and the cell survival and apoptosis were assessed with a modified MTT assay, Annexin V-FITC/PI and TUNEL assay. IL-1β concentration in the supernatant was determined with ELISA. Compared with the control cells, bilirubin-treated cells showed a significantly increased NF-κB p65 protein expression (P<0.01), which reached the peak level at 6 and 24 h (P<0.01). The cell survival rate in early TAT-NBD intervention group was (80.784∓9.767)%, significantly lower than that of the control group (P<0.01) but higher than that of bilirubin group (P<0.01); the apoptotic rate in early TAT-NBD intervention group was significantly higher than that of control group (P<0.01) but lower than that of bilirubin group (P<0.01). IL-1β concentration was significantly lower in early TAT-NBD intervention group (15.348∓0.812 pg/ml) than in bilirubin group (P<0.05). The continuous and late TAT-NBD intervention groups showed comparable cell survival rate, apoptotic rate and IL-1β concentration with bilirubin group (P>0.05). NF-κB bidirectionally regulates bilirubin-induced apoptosis of rat hippocampal neurons. Selective inhibition of the early peak of NF-κB by TAT-NBD offers neuroprotective effect. TAT-NBD can be potentially used for prophylaxis of bilirubin-induced brain injury.


Implication of Extracellular Signal-Regulated Kinase in the Expression of Natural Reward: Evidence Not Found.
Many studies have implicated extracellular signal-regulated kinase (ERK) in drug-rewarding properties. Yet, only few investigated whether ERK also mediates the naturally rewarding stimuli. In this study, we compared ERK activation in the nucleus accumbens (NAc) after cocaine reward and after positive social interaction (SI) with a partner-reward in male rats. With our protocol, ERK phosphorylation in the NAc was not increased after cocaine reward. In addition, the interaction with a social partner did not alter ERK activation in the NAc. These results suggest that ERK in the NAc may not be involved in natural reward learning. SI in an alternative context to the one associated with drugs of abuse can abolish drug preference. Given that intra-NAc core ERK inhibition impaired the expression of cocaine preference, we wanted to investigate whether the protective effects of SI when an individual is allowed to interact with a social partner in an alternative context to the one associated with drugs during the learning phase are enhanced by ERK inhibition. For that, U0126 was bilaterally infused into the NAc core of rats conditioned with cocaine in one context and with SI in the opposite context before assessing the expression of reward-related learning. Intra-NAc core ERK inhibition was ineffective to impair the expression of drug reward as previously demonstrated, when a social partner was available in an alternative context. Thus, the effects of the pharmacological manipulations based on decreasing ERK activity are not cumulative to other treatments for drug addiction based on SI.


Ultrasonographic findings of renal dysplasia in cocker spaniels: eight cases.
A retrospective study of eight young Cocker Spaniels aged 9-24 months was performed to describe the ultrasonographic findings of histologically confirmed renal dysplasia. Ultrasonography revealed kidneys of significantly (p < 0.001) reduced volume in all dogs. During qualitative evaluation, two different types of sonographic alterations could be seen. In one type of the ultrasound alterations, corticomedullary demarcation was distinct and the renal cortex was remarkably thin, which was best seen in the dorsal (frontal) imaging plane. In the other type of the ultrasound appearance, overall increased echogenicity with poor corticomedullary demarcation was noticed, and the kidneys could hardly be separated from their surroundings. These features were best recognised in the sagittal (coronal) imaging plane. In one dog with secondary hypercalcaemia, a hyperechoic corticomedullary area was also seen. Post-mortem histological diagnosis revealed renal dysplasia and secondary fibrosis. Based on ultrasound findings alone, renal dysplasia (renal familial disease) can be suspected when small kidneys with thin echogenic cortex are present in young dogs. An ultrasound image, similar to that of fibrotic kidneys (increased overall echogenicity and reduced corticomedullary definition) cannot be differentiated from chronic inflammatory disease and from end-stage kidneys. Therefore, ultrasound-guided biopsy or post-mortem histology is necessary for the definitive diagnosis of renal dysplasia. This is the first study reporting on the ultrasound appearance of renal dysplasia in Cocker Spaniel dogs.


Whole-body imaging with PET/MRI.
Whole-body positron emission tomography (PET) scanning with the radiolabeled glucose analogue 2-[fluorine-18]-fluoro-2-deoxy-D-glucose ( superset 18 F-FDG) can identify areas of cancerous involvement and distinguish malignant from benign lesions and therefore, plays an important role in the diagnosis and management of patients with cancer. PET facilitates the evaluation of metabolic and molecular characteristics of a wide variety of cancers, but it is limited in its ability to visualize anatomical structures. Whole-body magnetic resonance imaging (MRI) is a promising diagnostic modality for the diagnosis and management of patients with cancer, because of its high anatomical resolution. Whole-body PET and whole-body MRI allow to evaluate both the primary tumor and for the presence of metastasis at the same time. The combination of these two excellent diagnostic imaging modalities into a single scanner offers several advantages in comparison to PET and MRI alone. A hybrid PET/MRI facilitates the accurate registration of metabolic and molecular aspects of the diseases with exact correlation to anatomical findings, improving the diagnostic value in identifying and characterizing of malignancies and tumor staging. Thus, hybrid PET/MRI could be a very important diagnostic imaging modality in oncological applications in the decades to come, and possibly for use in cancer screening and cardiac imaging.


Differential effects of cyclic uniaxial stretch on human mesenchymal stem cell into skeletal muscle cell.
Both fetal and adult skeletal muscle cells are continually being subjected to biomechanical forces. Biomechanical stimulation during cell growth affects proliferation, differentiation and maturation of skeletal muscle cells. Bone marrow-derived hMSCs [human MSCs (mesenchymal stem cells)] can differentiate into a variety of cell types, including skeletal muscle cells that are potentially a source for muscle regeneration. Our investigations involved a 10% cyclic uniaxial strain at 1 Hz being applied to hMSCs grown on collagen-coated silicon membranes with or without IGF-I (insulin-like growth factor-I) for 24 h. Results obtained from morphological studies confirmed the rearrangement of cells after loading. Comparison of MyoD and MyoG mRNA levels between test groups showed that mechanical loading alone can initiate myogenic differentiation. Furthermore, comparison of Myf5, MyoD, MyoG and Myf6 mRNA levels between test groups showed that a combination of mechanical loading and growth factor results in the highest expression of myogenic genes. These results indicate that cyclic strain may be useful in myogenic differentiation of stem cells, and can accelerate the differentiation of hMSCs into MSCs in the presence of growth factor.


ICS-II USA research locations: environmental, dental care delivery system, and population sociodemographic characteristics.
Secondary data sources are used to describe the ICS-II USA research locations in terms of external environment, dental care delivery system, and population sociodemographics. The Native American reservations located in Arizona, New Mexico, and South Dakota were rural, while the other research locations were primarily urban. Baltimore, Maryland, and the Native American communities had fluoridated water, but San Antonio did not. Dental services in Baltimore and San Antonio were predominantly financed by private sources, with a small public health component. Dental care services in Native American communities were largely Indian Health Services (IHS) financed by the US Government. Each geographical area exhibited diverse characteristics indicating unique challenges for the delivery of community and clinical dental services.


Poly(allylamine)-encapsulated water-soluble CdSe nanocrystals.
Water-soluble CdSe nanocrystal/poly(allylamine) clusters with sizes ranging between 50 and 200 nm were prepared using 3-amino-1-propanol as a compatibilizing agent. Photoluminescence (PL) quantum yields (QY) up to 20% were achieved in water without the need to clad these CdSe nanocrystals (NCs) with higher band gap inorganic layers. The polymer-to-nanocrystal ratio plays an important role in the internal structure and stability of these polymer/NC clusters, as determined by static and dynamic light scattering in conjunction with PL studies. These results were modeled by using an effective-mass approximation and perturbation theory on the change in dielectric constant of the immediate NC environment. The time evolution of the average cluster radius of gyration and hydrodynamic radius revealed that a higher polymer-to-NC ratio leads to increased PL stability and QY. This is a result of a denser cluster configuration, which affords improved NC passivation. Increasing the ionic strength results in greater nanocluster compaction and higher PL QYs. Decreasing the pH value below 12 resulted in dramatic reduction in PL brightness, despite cluster densification, due to partial ionization and dissolution of the amine-based NC surface-capping agents.


Suppression of fibroblast proliferation by oral spirochetes.
Soluble sonic extracts of several strains of Treponema denticola and Treponema vincentii were examined for their abilities to alter proliferation of both murine and human fibroblasts. We found that sonic extracts of all tested strains of T. denticola caused a dose-dependent inhibition of murine and human fibroblast proliferation when assessed by both DNA synthesis ([3H]thymidine incorporation) and direct cell counts. T. vincentii had only a minimal inhibitory effect at comparable doses. No inhibition was observed when sonic extracts were added simultaneously with [3H]thymidine, indicating that suppression was not due to the presence of excessive amounts of cold thymidine in the extract, nonspecific effects on thymidine utilization by the cells (transport and incorporation), or degradation of label. RNA ([3H]uridine incorporation) and protein ([3H]leucine incorporation) synthesis were similarly altered after exposure to the T. denticola sonic extracts. There was no effect on cell viability as measured by trypan blue exclusion. Inhibition could be reversed by extensive washing of the cells within the first few hours of exposure to sonic extracts. Preliminary characterization and purification indicated that the inhibitory factor(s) is not endotoxin since it is heat labile, and elutes in a single, well-defined peak on a Sephadex G-150 chromatography column corresponding to a molecular weight of approximately 50,000. Since oral spirochetes have been implicated in the pathogenesis of periodontal disorders, it is possible that they contribute to the disease process by inhibition of fibroblast growth and therefore may, at least in part, account for the loss of collagen seen in diseased tissue.


Enzyme induction: rifampin-disopyramide interaction.
A 62-year-old woman with a history of supraventricular tachycardia, paroxysmal atrial tachycardia, and premature ventricular contractions was admitted with palpitations and anxiety. Previous therapy with antiarrhythmics had resulted in intolerable adverse effects or no effect on the arrhythmia. She had been taking rifampin prior to admission for acid-fast bacilli. Disopyramide was started on admission for supraventricular tachycardia. Subtherapeutic disopyramide blood concentrations were noted with concomitant administration of rifampin and disopyramide at normal doses. This case report demonstrates a possible drug interaction between these two drugs and the importance of careful monitoring. It was found that it takes three to five days after rifampin is discontinued before the enzyme induction of disopyramide disappears and disopyramide concentrations return to normal.


Coronary artery calcification and aortic valve calcification in patients with kidney failure: a sex-disaggregated study.
Chronic kidney disease (CKD) is linked to an increased cardiovascular disease (CVD) burden. Albeit underappreciated, sex differences are evident in CKD with females being more prone to CKD development, but males progressing more rapidly to kidney failure (KF). Cardiovascular remodelling is a hallmark of CKD with increased arterial and valvular calcification contributing to CKD. However, little is known regarding sex differences in calcific cardiovascular remodelling in KF patients. Thus, we hypothesise that sex differences are present in coronary artery calcification (CAC) and aortic valve calcification (AVC) in patients with KF. KF patients, males (n = 214) and females (n = 107), that had undergone computer tomography (CT) assessment for CAC and AVC were selected from three CKD cohorts. All patients underwent non-contrast multi-detector cardiac CT scanning, with CAC and AVC scoring based on the Agatston method. Baseline biochemical measurements were retrieved from cohort databases, including plasma analyses for inflammation markers (IL-6, TNF, hsCRP) and oxidative stress by skin autofluorescence measuring advanced glycation end-products (AGE), amongst other variables. Sex-disaggregated analyses revealed that CAC score was associated with age in both males and females (both p < 0.001). Age-adjusted analyses revealed that in males CAC was associated with diabetes mellitus (DM) (p = 0.018) and CVD (p = 0.011). Additionally, for females CAC associated with IL-6 (p = 0.005) and TNF (p = 0.004). In both females and males CAC associated with AGE (p = 0.042 and p = 0.05, respectively). CAC was associated with mortality for females (p = 0.015) independent of age. AVC in females was not reviewed due to low AVC-positive samples (n = 14). In males, in multivariable regression AVC was associated with age (p < 0.001) and inflammation, as measured by IL-6 (p = 0.010). In female KF patients inflammatory burden and oxidative stress were associated with CAC. Whereas in male KF patients oxidative stress and inflammation were associated with CAC and AVC, respectively. Our findings suggest a sex-specific biomarker signature for cardiovascular calcification that may affect the development of cardiovascular complications in males and females with KF.


"Don't bother about me." The grief and mental health of bereaved adolescents.
Death of a relative or friend is a potentially disruptive event in the lives of adolescents. To provide targeted help, it is crucial to understand their grief and mental health experiences. Thematic analysis of 39 semistructured telephone interviews yielded two themes: Grieving apart together and Personal growth. High self-reliance and selective sharing were common. Feelings of guilt and "why" questions seemed more pronounced among the suicide bereaved. There was strong evidence of personal growth, increased maturity, and capacity to deal with personal mental health/suicidality. Despite its devastating effects, experiencing a death can be a catalyst for positive mental health.


Studies of olfactory system neural plasticity: the contribution of the unilateral naris occlusion technique.
Unilateral naris occlusion has long been the method of choice for effecting stimulus deprivation in studies of olfactory plasticity. A significant body of literature speaks to the myriad consequences of this manipulation on the ipsilateral olfactory pathway. Early experiments emphasized naris occlusion's deleterious and age-critical effects. More recent studies have focused on life-long vulnerability, particularly on neurogenesis, and compensatory responses to deprivation. Despite the abundance of empirical data, a theoretical framework in which to understand the many sequelae of naris occlusion on olfaction has been elusive. This paper focuses on recent data, new theories, and underappreciated caveats related to the use of this technique in studies of olfactory plasticity.


Increased fucosylation has a pivotal role in invasive and metastatic properties of head and neck cancer stem cells.
Oral squamous cell carcinoma (OSCC) is an aggressive malignancy with high mortality rates. Major challenges for OSCC management include development of resistance to therapy and early formation of distant metastases. Cancer stem cells (CSCs) have emerged as important players in both pathologic mechanisms. Increased fucosylation activity and increased expression of fucosylated polysaccharides, such as Sialyl Lewis X (SLex), are associated with invasion and metastasis. However, the role of fucosylation in CSCs has not been elucidated yet. We used the spheroid culture technique to obtain a CSC-enriched population and compared orospheres with adherent cells. We found that orospheres expressed markers of CSCs and metastasis at higher levels, were more invasive and tumorigenic, and were more resistant to cisplatin/radiation than adherent counterparts. We found fucosyltransferases FUT3 and FUT6 highly up-regulated, increased SLex expression and increased adhesion by shear flow assays in orospheres. Inhibition of fucosylation negatively affected orospheres formation and invasion of oral CSCs. These results confirm that orospheres are enriched in CSCs and that fucosylation is of paramount importance for CSC invasion. In addition, SLex may play a key role in CSC metastasis. Thus, inhibition of fucosylation may be used to block CSCs and metastatic spread.


POPULATION GENETIC STRUCTURE AND GENE FLOW ACROSS ARID VERSUS MESIC ENVIRONMENTS: A COMPARATIVE STUDY OF TWO PARAPATRIC SENECIO SPECIES FROM THE NEAR EAST.
To shed light on the potential effects of xeric/arid versus mesic environments on plant population genetic structure and patterns of gene flow, we have compared allozyme and cpDNA haplotype variation in populations of two closely related, highly outcrossed, and largely wind-dispersed winter annuals of Senecio (Asteraceae). The species form a distinctive zone of parapatric distribution in the Near East by differing in their ecogeographical regimes. Senecio vernalis mainly thrives in the mesic Mediterranean life zone of Israel, whereas S. glaucus inhabits either xeric maritime or arid (semi-) desert sites. Significant differences in allozymic population subdivision among S. vernalis (θn = 0.04; Nmn = 5.85) and S. glaucus (θn = 0.12; Nmn = 1.85) largely resulted from topogeographical substructuring present within the latter species. Because of the similarity of within-region estimates of population structure for S. glaucus with those measured among populations of S. vernalis, it appears unlikely that ecological "aridity" factors per se are important in influencing levels of population differentiation in these species. Based on hierarchical F-statistics and tests of isolation by distance, we further conclude that geographical topologies influence the level and mode of nuclear gene flow (via pollen and/or seed) among and within subsets of S. glaucus populations, although without providing a complete barrier to interregional dispersal (dNmreg = 2.16) and without promoting allopatric differentiation via drift. The allozymic data further suggested that S. vernalis and S. glaucus form a zone of secondary contact in the Near East, accompanied by an almost complete interspecific barrier to nuclear gene flow (dnNmsp = 0.253). However, to account for the considerable sharing of cpDNA haplotypes, both at the intra- and interspecific level, it is necessary to invoke either (1) selection acting against alien nuclear but not cytoplasmic DNA; or (2) the sporadic immigration of cpDNA via seed with large homogenizing effects on cytoplasmic population structure over time.


Porcine circovirus type 2 detection in in vitro produced porcine blastocysts after virus sperm exposure.
This study was aimed at assessing the capability of semen experimentally infected with porcine circovirus type 2 (PCV2) to produce porcine blastocysts PCR positive for PCV2. Embryos were obtained from in vitro maturation (IVM) and in vitro fertilization (IVF) of porcine oocytes or by parthenogenesis. Sperm suspension was exposed to PCV2b and utilized for IVF. PCV2 spiked semen did not reveal any reduction in sperm viability or motility but its ability to produce infected blastocysts was irrelevant as only one out of 15 blastocysts obtained by IVF were PCV2b; however two blastocysts were PCV2a positive. Furthermore, the presence of PCV2 was demonstrated also in embryos obtained by parthenogenesis (one out of 17 was PCV2b and one PCV2a positive). Even if PCV2 firmly attaches to the surface of spermatozoa, experimentally spiked sperm were not effective in infecting oocytes during IVF and in producing PCR positive embryos. The infected blastocysts we obtained derived most probably from infected oocytes recovered at the abattoir.


DTI measures identify mild and moderate TBI cases among patients with complex health problems: A receiver operating characteristic analysis of U.S. veterans.
Standard MRI methods are often inadequate for identifying mild traumatic brain injury (TBI). Advances in diffusion tensor imaging now provide potential biomarkers of TBI among white matter fascicles (tracts). However, it is still unclear which tracts are most pertinent to TBI diagnosis. This study ranked fiber tracts on their ability to discriminate patients with and without TBI. We acquired diffusion tensor imaging data from military veterans admitted to a polytrauma clinic (Overall n = 109; Age: M = 47.2, SD = 11.3; Male: 88%; TBI: 67%). TBI diagnosis was based on self-report and neurological examination. Fiber tractography analysis produced 20 fiber tracts per patient. Each tract yielded four clinically relevant measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity). We applied receiver operating characteristic (ROC) analyses to identify the most diagnostic tract for each measure. The analyses produced an optimal cutpoint for each tract. We then used kappa coefficients to rate the agreement of each cutpoint with the neurologist's diagnosis. The tract with the highest kappa was most diagnostic. As a check on the ROC results, we performed a stepwise logistic regression on each measure using all 20 tracts as predictors. We also bootstrapped the ROC analyses to compute the 95% confidence intervals for sensitivity, specificity, and the highest kappa coefficients. The ROC analyses identified two fiber tracts as most diagnostic of TBI: the left cingulum (LCG) and the left inferior fronto-occipital fasciculus (LIF). Like ROC, logistic regression identified LCG as most predictive for the FA measure but identified the right anterior thalamic tract (RAT) for the MD, RD, and AD measures. These findings are potentially relevant to the development of TBI biomarkers. Our methods also demonstrate how ROC analysis may be used to identify clinically relevant variables in the TBI population.


[POR 8 (ornipressin). Local vasoconstrictive effect and hemodynamic activity during surgery in ENT clinics].
POR 8 (ornipressin) at a concentration of 5 IU in 10 ml of 1% lidocaine was used as a local vasoconstrictor in 262 ENT operations. Anaesthesia was carried out with either halothane or enflurane, or with diazepam and fentanyl. The doses of POR 8 lay between 2.7 IU and 3.5 IU. Under inhalational anaesthesia there was a good vasoconstriction in 85% to 90%, and anaesthesia with diazepam-fentanyl in 60% to 83% of cases, depending on the site of operation. There should be a 10-20 minute interval between infiltration and the beginning of surgery. Under inhalational anaesthesia the systolic blood pressure fell by 10% after infiltration of POR 8, when the diastolic blood pressure rose by 6%. During diazepam-fentanyl anaesthesia the systolic blood pressure increased by 23%, the diastolic by 27%. POR 8 was not found to have an antidiuretic effect. There was no difference between the osmolality, sodium and potassium levels of 30 patients measured before infiltration and 24 hours later. Because of the minimal side effects of POR 8 on the cardiovascular system during inhalational anaesthesia we recommend the use of these substance as a local vasoconstrictor instead of epinephrine.


Myosin and Ca2+-sensitive streaming in the alga Chara: detection of two polypeptides reacting with a monoclonal anti-myosin and their localization in the streaming endoplasm.
A monoclonal antibody to the heavy chain of myosin from mouse 3T3 cells was used to detect and localize related proteins in the green alga Chara. Proteins of 200,000 and 110,000 Mr reacted on immunoblots of proteins precipitated rapidly with trichloroacetic acid to minimize proteolysis. Immunofluorescence of whole cells localized these proteins to organelles of the streaming endoplasm, to a system of endoplasmic strands and to the subcortical actin bundles. Except that fewer endoplasmic strands and organelles were found and the strands were tangled, the localization pattern was similar in cells rapidly perfused to remove the bulk of the streaming endoplasm. Actin was confined almost entirely to the system of subcortical actin bundles in both whole and perfused cells. Myosin that was associated with the tangled endoplasmic strands but not that associated with the organelles or actin bundles was removed by concentrations of Ca2+ inhibiting ATP-dependent streaming in perfused cells. ATP extracted both organelles and endoplasmic strands but left a continuous pattern of myosin immunostaining along the actin bundles. The findings are discussed in relation to the possible existence of two forms of myosin and of separate mechanisms moving the bulk endoplasm and individual organelles.


Regioselective Ni-Catalyzed Carboxylation of Allylic and Propargylic Alcohols with Carbon Dioxide.
An efficient Ni-catalyzed reductive carboxylation of allylic alcohols with CO2 has been successfully developed, providing linear β,γ-unsaturated carboxylic acids as the sole regioisomer with generally high E/Z stereoselectivity. In addition, the carboxylic acids can be generated from propargylic alcohols via hydrogenation to give allylic alcohol intermediates, followed by carboxylation. A preliminary mechanistic investigation suggests that the hydrogenation step is made possible by a Ni hydride intermediate produced by a hydrogen atom transfer from water.


Update on the pharmacologic treatment of hypertension in pediatrics.
J Clin Hypertens (Greenwich). 2012; 14:383-387. ©2012 Wiley Periodicals, Inc. The past decade of investigation into the pharmacologic treatment of hypertension in children has been rewarding. The studies have shown that blood pressure medications effectively reduce blood pressure in children with hypertension and that these agents are generally well tolerated with few treatment-related adverse effects. While we have advanced our capacity to make rational therapeutic decisions, future efforts must be directed towards comparing the effectiveness of the different classes of antihypertensive agents and studies evaluating the impact of antihypertensive agents on outcome.


A case of Sweet's syndrome associated with monoclonal immunoglobulin of IgG-lambada type and p-ANCA positivity.
We report a case of Sweet's syndrome associated with monoclonal gammopathy of uncertain significance (MGUS) and positivity for perinuclear antineutrophil cytoplasmic antibodies (p-ANCA). A 65-year-old man patient came to our hospital complaining of remittent-intermittent fever, weight loss, associated with papules affecting all his body and without mucosal or ocular involvement. Histology of biopsy specimens of papules allowed the diagnosis of Sweet's syndrome. This is the first case of this rare syndrome associated both with MGUS and p-ANCA positivity. The monoclonal immunoglobulin, possibly directed to neutrophils like an antibody, may cause both their fragmentation and release of antigens responsible of p-ANCA appearance.


Immunohistochemical detection of the human herpes virus 8 (HHV8) latent nuclear antigen-1 in Kaposi's sarcoma.
The molecular genetics of the human herpes virus 8 (HHV8) has now been characterised and the virus appears to be important in the pathogenesis of Kaposi's sarcoma (KS). This study attempts to determine the rate of HHV8 infection in KS in an Australian cohort. Routine streptavidin-biotin-peroxidase immunostaining with diaminobenzidine was performed on paraffin-embedded archival tissues of 37 KS cases using a murine monoclonal antibody directed against the C-terminus of the latent nuclear antigen-1 molecule of HHV8 (clone 13B10; Novocastra) at 1:50 dilution. Positive HHV8 nuclear staining was detected in the nuclei of the spindle cells and endothelial cells of the vascular channels in about 78% (29/37) of all cases. HHV8 staining was absent in the non-neoplastic vessels in the adjacent tissue (P=0.0001, chi(2)=44.46; chi(2)-test with continuity correction) and the negative control cases of Merkel cell carcinoma (P=0.02, chi(2)=5.07; chi(2)-test with continuity correction). HHV8 staining was detected in 80% (8/10 cases) of the patch stage, 88% (7/8 cases) of the plaque stage and 74% (14/19 cases) of the late stage. No significant difference was found between HHV8 positivity and HIV status, age, gender, tumour recurrence, multiplicity or site of the lesions. The latent nuclear antigen-1 of HHV8 can be detected by immunohistochemistry in the majority of human KS lesions, raising the possibility of its future potential use as an adjunct for the diagnosis of KS in problematic cases.


One-Shot Manipulation of Dynamical Quantum Resources.
We develop a unified framework to characterize one-shot transformations of dynamical quantum resources in terms of resource quantifiers, establishing universal conditions for exact and approximate transformations in general resource theories. Our framework encompasses all dynamical resources represented as quantum channels, including those with a specific structure-such as boxes, assemblages, and measurements-thus immediately applying in a vast range of physical settings. For the particularly important manipulation tasks of distillation and dilution, we show that our conditions become necessary and sufficient for broad classes of important theories, enabling an exact characterization of these tasks and establishing a precise connection between operational problems and resource monotones based on entropic divergences. We exemplify our results by considering explicit applications to quantum communication, where we obtain exact expressions for one-shot quantum capacity and simulation cost assisted by no-signaling, separability-preserving, and positive partial transpose-preserving codes; as well as to nonlocality, contextuality, and measurement incompatibility, where we present operational applications of a number of relevant resource measures.


On-line fluorescence-monitoring of the methanogenic fermentation.
On-line in situ fluorescence measurements of the methanogenic fermentation were conducted with reactors receiving either glucose or a mixture of volatile fatty acids as the substrate. The reactors were perturbed from steady-state conditions in order to assess the response of fluorescence-monitoring probes. Two fluorescence-monitoring probes were evaluated over a period of 8 months; they performed in a consistent manner, and their response was not significantly affected by the changes in pH and redox potential encountered during routine reactor operation. A commercially available probe, designed to measure NAD(P)H, demonstrated particular promise for detecting imbalance caused by the entry of air, inhibitor addition and was capable of distinguishing between different substrates. This fluorescence-monitoring probe detected imbalance more rapidly than other on-line measurements such as pH, Eh, or gas production, or off-line measurements such as volatile fatty acid concentration or gas composition. An experimental fluorescence-monitoring probe, designed to measure coenzyme F(420), also showed some promise in this regard. The response of the fluorescence-monitoring probes also revealed details of the metabolic routes in the reactors and the probes represent a useful research tool. For example, a failure to observe the characteristic response of the NAD(P)H-monitoring probe to formate addition during the metabolism of acetate, propionate, or glucose strongly suggests that any formate liberated during their catabolism is degraded via a different route to exogenously added formate.


Health-related millennium development goals: policy challenges for Pakistan.
There are two objectives: (a) to clearly articulate the Millennium Development Goals (MDGs) adopted by the United Nations in 2000 and their implications for developing countries like Pakistan; and (b) to critically review the challenges faced by Pakistan in achieving the health-related MDGs. A critical review of secondary data and information generated primarily by multilateral agencies and United Nations organizations. The MDGs represent a global consensus on the broad goals of development to be achieved by 2015. Of the eight Millennium Development Goals, three are specifically health related--reducing infant (under-5) and maternal mortality; and combating HIV/AIDS, tuberculosis, malaria and other significant communicable diseases. According to various studies, many developing countries will not achieve the MDGs without concerted efforts and commitment of additional resources. Like many other developing countries, Pakistan is also faced with an enormous challenge in reaching the Millennium Development Goals and targets set by the United Nations. For Pakistan, perhaps the most challenging MDG is that of reducing "by three-quarters the maternal mortality ratio." Maternal mortality is so intertwined with other "social" factors--including the status of women--that a comprehensive holistic approach is required. In order to achieve the MDGs, Pakistan would require a fundamental shift in its policy and strategic directions. Along with allocation of significant additional resources for health, it needs to review and reprioritize the use of existing resources, focusing more on primary health care. Pakistan must also adopt a holistic integrated approach that views health, education, and other social sector development as intrinsically interrelated and interwoven. Without such an integrated approach, achieving the health-related MDGs is likely to remain illusive for Pakistan. There is a critical need to foster a healthy debate on the health-related Millennium Development Goals in Pakistan so as to inform and, hopefully influence, public policy.


Effect of vitamin B12 supplementation on retinal lesions in diabetic rats.
Diabetic retinopathy (DR) is the most common complication of diabetes involving microvasculature and neuronal alterations in the retina. Previously, we reported that vitamin B12 deficiency could be an independent risk factor for DR in humans. However, the effect of vitamin B12 supplementation in experimental DR is unknown. Thus, in this study, we investigated the impact of dietary supplementation of vitamin B12 on retinal changes in diabetic rats. Diabetes was induced in 2-month-old Sprague-Dawley rats and maintained for 4 months. One group of diabetic rats were fed normal levels of vitamin B12, and one group double the quantity of vitamin B12 (50 µg/kg diet). Vitamin B12 and homocysteine levels in the plasma were analyzed with radioimmunoassay (RIA) and high-performance liquid chromatography (HPLC), respectively. At the end of 4 months of experimentation, the eyeballs were collected. Retinal changes were analyzed with hematoxylin and eosin (H&E) staining, immunoblotting, and immunofluorescence methods. Dietary supplementation of vitamin B12 had no effect on food intake, bodyweight, fasting blood glucose, and plasma homocysteine levels in the diabetic rats. However, vitamin B12 supplementation prevented loss of rhodopsin, and overexpression of VEGF, and completely prevented overexpression of HIF1α, GFAP, and endoplasmic reticulum (ER) stress markers (GRP78, ATF6α, XBP1, CHOP, and caspase 12) in the diabetic rat retina. Further, vitamin B12 ameliorated apoptosis in the retina as shown with terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and prevented retinal thinning. Vitamin B12 supplementation of diabetic rats appeared to be beneficial by circumventing retinal hypoxia, VEGF overexpression, and ER stress-mediated cell death in the retina. The present study adds another potential therapeutic strategy of vitamin B12 in diabetes.


Vitamin E prevents increase in oxidative damage to lipids and DNA in liver of ODS rats given total body X-ray irradiation.
We examined the effects of dietary vitamin E (VE) on oxidative damage to DNA and lipids in the liver a few days after total body irradiation (TBI). ODS rats, which lack vitamin C synthesis, were fed either a low VE diet (4.3 mg VE/kg) or a basal VE diet (75.6 mg VE/kg) for 5 weeks while vitamin C was supplied in the drinking water. The VE level in the liver of the low VE group was lower and the levels of lipid peroxides were higher compared to those of the basal VE group: the relative levels in the two groups were 1:30 for VE, 18:1 for 4-hydroxynonenal (HNE), and 10:1 for hexanal (HA). The level of 8-hydroxydeoxyguanosine (8OHdG), a marker of oxidative DNA damage, did not differ between the low VE and the basal VE groups. When the rats received TBI at the dose of 3 Gy and were killed on day 6, the levels of HNE, HA and 8OHdG increased by 2.2-, 2-, and 1.5-times, respectively, in the low VE group, but TBI did not cause such increases in the basal VE group. Changes in antioxidative enzymes (glutathione peroxidase, catalase, and Cu/Zn-SOD) in the liver could not explain the different responses of the two diet groups to TBI-induced oxidative damage. The concentrations of vitamin C and glutathione in the liver did not differ between the two groups. These results suggest that dietary VE can prevent the oxidative damage to DNA and lipids in the liver which appear a few days after TBI at dose of 3 Gy.


[HIV-related malignancies: state of art].
HIV infection is related to an increased risk of cancer compared with general population, both AIDS-defining cancers (Kaposi's sarcoma, non Hodgkin's lymphoma, invasive cervical cancer) and non-AIDS-defining cancers. Although the advent of the highly active antiretroviral therapy era has decreased the Kaposi's sarcoma and non-Hodgkin's lymphoma incidences, non-AIDS-defining malignancies, such as lung cancer, hepatocarcinoma, anal cancer and skin cancers, remain a major cause of morbidity and death in the HIV-infected population. The clinical presentation is often different between the infected and non-infected populations, often with a more advanced stage at diagnosis, a more aggressive pathology, and associated morbidities like immunosuppression, leading to poorer outcomes. Numerous studies have focused on HIV-related malignancies' treatment, however specific guidelines are still missing. Practitioners have to be careful with interactions between antiretroviral and antineoplastic drugs, particularly through the cytochrome P 450. Because of this, a national multidisciplinary approach, "Cancer and HIV, " was started in 2013 thanks to the National Institute of Cancer (INCa). The aim of this review is to present a scientific update about AIDS-and non-AIDS-defining malignancies, both in their clinical aspects and regarding their specific therapeutic management.


A Rare Cause of Primary Aortoenteric Fistula: Streptococcus parasanguinis Aortitis.
Primary aortoenteric fistula is a rare cause of upper gastrointestinal bleed but can lead to significant mortality if the diagnosis is delayed. Aortitis, characterized by inflammation of the aortic wall, is a rare cause of aortoenteric fistula. We present a case report of a 72-year-old male patient with infectious aortoenteric fistula secondary to Streptococcus parasanguinis, along with a review of the literature. This case demonstrates the importance of early diagnosis and aggressive surgical treatment of aortoenteric fistulae and recognizing infectious aortitis as a potential etiology.


Strokes in Patients With Injection Drug Use and Tricuspid Valve Endocarditis - A Case Series.
Research Design: In this study, we describe patients from a tertiary care safety-net hospital endocarditis registry with tricuspid valve infective endocarditis (TVIE), and concomitant acute or subacute ischemic stroke predominantly associated with injection drug use (IDU). We retrospectively obtained data pertinent to neurologic examinations, history of injection drug use (IDU), blood cultures, transthoracic/transesophageal echocardiography (TTE/TEE), neuroimaging, and Modified Rankin Scale (mRS) scores at discharge. Only those patients with bacteremia, tricuspid valve vegetations, and neuroimaging consistent with acute to subacute ischemic infarction and microhemorrhages in two cases were included in this series. Results: Of 188 patients in the registry, 66 patients had TVIE and 10 of these were complicated by ischemic stroke. Neurologic symptoms were largely non-specific, eight patients had altered mental status and only 3 had focal deficits. Nine cases were associated with IDU. Two patients had evidence of a patent foramen ovale on echocardiography. Blood cultures grew S. aureus species in 9 of the patients, all associated with IDU. Three patients died during hospitalization. The mRS score at discharge for survivors ranged 0-4. Conclusions: Patients with strokes from TVIE had heterogeneous presentations and putative mechanisms. We noted that robust neuroimaging is lacking for patients with TVIE from IDU and that such patients may benefit from neuroimaging as a screen for strokes to assist peri-operative management. Further inquiry is needed to elucidate stroke mechanisms in these patients.


Modulation of autonomic activity in neurological conditions: Epilepsy and Tourette Syndrome.
This manuscript considers the central but neglected role of the autonomic nervous system in the expression and control of seizures in epilepsy (small) and tics in Tourette Syndrome (TS). In epilepsy, consideration of autonomic involvement is typically confined to differential diagnoses (e.g., syncope), or in relation to Sudden Unexpected Death in Epilepsy (SUDEP). Investigation is more limited in Tourette Syndrome. The role of the autonomic nervous system in the generation and prevention of epileptic seizures is largely overlooked. Emotional stimuli such as anxiety and stress are potent causes of seizures and tic activity in epilepsy and TS, respectively. This manuscript will describe a possible neural mechanism by which afferent autonomic projections linked to cognition and behavior influence central thalamo-cortical regulation, which appears to be an important means for controlling both seizure and tic activity. It also summarizes the link between the integrity of the default mode network and autonomic regulation in patients with epilepsy as well as the link between impaired motor control and autonomic regulation in patients with TS. Two neurological conditions; epilepsy and TS were chosen, as seizures and tics represent parameters that can be easily measured to investigate influences of autonomic functions. The EDA biofeedback approach is anticipated to gain a strong position within the next generation of treatment for epilepsy, as a non-invasive technique with minimal side effects. This approach also takes advantage of the current practical opportunity to utilize growing digital health technology.


Epigenetic age acceleration is associated with cardiometabolic risk factors and clinical cardiovascular disease risk scores in African Americans.
Cardiovascular disease (CVD) is the leading cause of mortality among US adults. African Americans have higher burden of CVD morbidity and mortality compared to any other racial group. Identifying biomarkers for clinical risk prediction of CVD offers an opportunity for precision prevention and earlier intervention. Using linear mixed models, we investigated the cross-sectional association between four measures of epigenetic age acceleration (intrinsic (IEAA), extrinsic (EEAA), PhenoAge (PhenoAA), and GrimAge (GrimAA)) and ten cardiometabolic markers of hypertension, insulin resistance, and dyslipidemia in 1,100 primarily hypertensive African Americans from sibships in the Genetic Epidemiology Network of Arteriopathy (GENOA). We then assessed the association between epigenetic age acceleration and time to self-reported incident CVD using frailty hazard models and investigated CVD risk prediction improvement compared to models with clinical risk scores (Framingham risk score (FRS) and the atherosclerotic cardiovascular disease (ASCVD) risk equation). After adjusting for sex and chronological age, increased epigenetic age acceleration was associated with higher systolic blood pressure (IEAA), higher pulse pressure (EEAA and GrimAA), higher fasting glucose (PhenoAA and GrimAA), higher fasting insulin (EEAA), lower low density cholesterol (GrimAA), and higher triglycerides (GrimAA). A five-year increase in GrimAA was associated with CVD incidence with a hazard ratio of 1.54 (95% CI 1.22-2.01) and remained significant after adjusting for CVD risk factors. The addition of GrimAA to risk score models improved model fit using likelihood ratio tests (P = 0.013 for FRS and P = 0.008 for ASCVD), but did not improve C statistics (P > 0.05). Net reclassification index (NRI) showed small but significant improvement in reassignment of risk categories with the addition of GrimAA to FRS (NRI: 0.055, 95% CI 0.040-0.071) and the ASCVD equation (NRI: 0.029, 95% CI 0.006-0.064). Epigenetic age acceleration measures are associated with traditional CVD risk factors in an African-American cohort with a high prevalence of hypertension. GrimAA was associated with CVD incidence and slightly improved prediction of CVD events over clinical risk scores.


Monitoring ecstasy content in France: results from the National Surveillance System 1999-2004.
The French National Identification System for Drugs and Other Substances (SINTES) is an original scheme gathering analytical information for synthetic drugs, both through police and customs' seizures in the entire country and collection of samples and questionnaires directly from the users by social field workers. Between July 1999 and June 2004, 9543 samples were included. Tablets (7004) were mainly containing MDMA (82%) and caffeine was the most frequent blended psychoactive substance. Mean MDMA dosage of tablets decreased from 1999 to 2003 and dosage for tablets bearing the same logo appeared to be highly variable. Notwithstanding the difficulties for data collection due to the illicit nature of these drugs, this surveillance and early warning system, which combines the cooperative efforts of law enforcement laboratories and social workers, provided relevant and timely information. It is accurate regarding the follow-up of trends in drugs' composition, and the identification of new or potentially dangerous substances, to the professionals, the public, and the European partners.


Lymphatic filariasis in 2016 in American Samoa: Identifying clustering and hotspots using non-spatial and three spatial analytical methods.
American Samoa completed seven rounds of mass drug administration from 2000-2006 as part of the Global Programme to Eliminate Lymphatic Filariasis (LF). However, resurgence was confirmed in 2016 through WHO-recommended school-based transmission assessment survey and a community-based survey. This paper uses data from the 2016 community survey to compare different spatial and non-spatial methods to characterise clustering and hotspots of LF. Non-spatial clustering of infection markers (antigen [Ag], microfilaraemia [Mf], and antibodies (Ab [Wb123, Bm14, Bm33]) was assessed using intra-cluster correlation coefficients (ICC) at household and village levels. Spatial dependence, clustering and hotspots were examined using semivariograms, Kulldorf's scan statistic and Getis-Ord Gi* statistics based on locations of surveyed households. The survey included 2671 persons (750 households, 730 unique locations in 30 villages). ICCs were higher at household (0.20-0.69) than village levels (0.10-0.30) for all infection markers. Semivariograms identified significant spatial dependency for all markers (range 207-562 metres). Using Kulldorff's scan statistic, significant spatial clustering was observed in two previously known locations of ongoing transmission: for all markers in Fagali'i and all Abs in Vaitogi. Getis-Ord Gi* statistic identified hotspots of all markers in Fagali'i, Vaitogi, and Pago Pago-Anua areas. A hotspot of Ag and Wb123 Ab was identified around the villages of Nua-Seetaga-Asili. Bm14 and Bm33 Ab hotspots were seen in Maleimi and Vaitogi-Ili'ili-Tafuna. Our study demonstrated the utility of different non-spatial and spatial methods for investigating clustering and hotspots, the benefits of using multiple infection markers, and the value of triangulating results between methods.


SARS-CoV-2 Nsp1 regulates translation start site fidelity to promote infection.
A better mechanistic understanding of virus-host interactions can help reveal vulnerabilities and identify opportunities for therapeutic interventions. Of particular interest are essential interactions that enable production of viral proteins, as those could target an early step in the virus lifecycle. Here, we use subcellular proteomics, ribosome profiling analyses and reporter assays to detect changes in polysome composition and protein synthesis during SARS-CoV-2 (CoV2) infection. We identify specific translation factors and molecular chaperones whose inhibition impairs infectious particle production without major toxicity to the host. We find that CoV2 non-structural protein Nsp1 selectively enhances virus translation through functional interactions with initiation factor EIF1A. When EIF1A is depleted, more ribosomes initiate translation from an upstream CUG start codon, inhibiting translation of non-structural genes and reducing viral titers. Together, our work describes multiple dependencies of CoV2 on host biosynthetic networks and identifies druggable targets for potential antiviral development.


Practical stereoselective synthesis of an alpha-trifluoromethyl-alpha-alkyl epoxide via a diastereoselective trifluoromethylation reaction.
A practical stereoselective synthesis is reported for an alpha-trifluoromethyl-alpha-alkyl epoxide (1), which is an important pharmaceutical intermediate. The key step involves a chiral auxiliary-controlled asymmetric trifluoromethylation reaction for the introduction of the unique trifluoromethyl-substituted tertiary alcohol stereogenic center in the target molecule. The fluoride-initiated CF3 addition to chiral keto ester 6a proceeded with a diastereoselectivity up to 86:14. The major diastereomer was readily obtained with a >99.5:0.5 dr through a simple crystallization of the crude product mixture.


[Evaluation of the four simple methods in the diagnosis of diabetic peripheral neuropathy].
To evaluate the efficacy of neuropathy symptom score/neuropathy disability score (NSS/NDS), Michigan Neuropathy Screening Instrument (MNSI), vibration perception threshold (VPT) and 24010 g monofilament examination in the diagnosis of diabetic peripheral neuropathy (DPN). 240 patients with type 2 diabetes underwent the 4 simple tests: NSS/NDS, MNSI, VPT, and 10 g monofilament examination and nerve conduction velocity (NCV) examination. Using the results of NCV as golden criteria, the sensitivity, specificity, positive and negative predictive values, accuracy and kappa values of these tests were analyzed. The sensitivity, specificity, accuracy, and kappa value of MNSI score over 2 were 78.15%, 88.43%, 83.33%, and 0.67 respectively. The validity could be ranked in the following order with respect to the diagnosis of DPN: MNSI > VPT > NSS/NDS > 10 g monofilament examination. MNSI is a rapid, simple and reliable test for screening DPN in both diabetes clinics and epidemiological surveys.


[Comparative assessment of efficiency of the low-calorie diets modified by proteinaceous and vitamin cocktails].
The aim of the work is comparative assessment of efficiency of a hypocaloric diet with inclusion of proteinaceous and vitamin cocktails at obesity. 90 patients with obesity of the II–III degree at the age of 18–65 years by the principle of casual selection were divided into three groups. Control group (30 patients) received a standard low-calorie diet with an energy value of 1600 kcal/day. The diet of the 1st group (30 patients) was modified by the inclusion of protein-vitamin-mineral cocktail (16 g of dry mixture with the addition of 250 ml of yogurt 1.0% fat) twice a day, diet of the 2nd group (30 patients) – the inclusion of a protein cocktail (16 g of dry mixture with the addition of 250 ml of yogurt 1.0% fat), while excluding from the diet equivalent caloric meals. The 1st group of patients had a decrease in fat mass by 4.2±0.7 kg (p<0.02), in active lean mass by 1.1±0.1 kg, in total fluid volume by 2.2±0.3 kg (p<0.02). The 2nd group of patients had a decrease in fat mass by 3.8±0.9 kg (p<0.01), in lean mass by 1.4±0.3 kg and in the total fluid volume by 3.1±0.9 l (p<0.02). In the control group attention should be paid to a decrease in lean mass by 1.9±0.6 kg, while fat mass decreased by 3.0±0.4 kg (p<0.02) and the total fluid volume by 3.1±0.9 l (p<0.02). Evaluation of the changes of serum biochemical parameters after treatment demonstrated that the 1st group of patients had significant favorable dynamics of reduction of serum level of total cholesterol, uric acid and glucose (17.7, 28.2 and 18.3%, respectively), which was more pronounced compared with the dynamics in the control group (the decrease by 15, 19.2 and 8.2%, respectively). In the 2nd group of patients the decrease rate of the observed parameters was less pronounced (15, 19.2 and 8.2%, respectively). More appreciable favorable dynamics of biochemical parameters and reduction in body weight in the 1st and 2nd groups in relation to the control group allow to reasonably apply the protein-vitamin cocktails in a diet therapy at obesity.


Applicability of cardiogoniometry as a non-invasive screening tool for the detection of graft vasculopathy in heart transplant recipients.
Currently available diagnostic modalities for the detection of graft vasculopathy following orthotopic heart transplantation are subject to various restrictions. We hypothesized that cardiogoniometry, a novel non-invasive diagnostic tool for the detection of atherosclerotic coronary vessel disease, is applicable in the graft vasculopathy setting. Cardiogoniometric results were obtained during routine follow-up in 49 consecutive, unselected heart transplant recipients and then retrospectively correlated blindly by an independent reader to recent angiographic findings. Sensitivity of cardiogoniometry was 100%, specificity 62.3%, positive predictive value 68.75%, negative predictive value 100%, negative likelihood ratio 0 and positive likelihood ratio 2.888. Cardiogoniometry is potentially applicable as an easy-to-perform, non-invasive screening tool predominantly for the exclusion but also for the detection of graft vasculopathy in heart transplant recipients.


Immunocytochemical demonstration of human immunodeficiency virus infected cells in the cerebrospinal fluid.
Although involvement of the central nervous system represents one of the most common manifestations of the acquired immunodeficiency syndrome (AIDS), a standard diagnostic test for this condition has not yet been established. At necropsy human immunodeficiency virus (HIV) has been demonstrated in brain macrophages in such patients. HIV antigen was detected in CSF macrophages by immunocytochemistry in six out of 11 HIV infected patients. In addition to the detection of intrathecal synthesis of anti-HIV antibodies this method may be suitable for early diagnosis of CNS involvement in AIDS patients.


Ultrasensitive reporter DNA sensors built on nucleic acid amplification techniques: Application in the detection of trace amount of protein.
The detection of protein is of great significance for the study of biological physiological function, early diagnosis of diseases and drug research. However, the sensitivity of traditional protein detection methods for detecting trace amount of proteins was relatively low. By integrating sensitive nucleic acid amplification techniques (NAAT) with protein detection methods, the detection limit of protein detection methods can be substantially improved. The DNA that can specifically bind to protein targets and convert protein signals into DNA signals is collectively referred to reporter DNA. Various NAATs have been used to establish NAAT-based reporter DNA sensors. And according to whether enzymes are involved in the amplification process, the NAAT-based reporter DNA sensors can be divided into two types: enzyme-assisted NAAT-based reporter DNA sensors and enzyme-free NAAT-based reporter DNA sensors. In this review, we will introduce the principles and applications of two types of NAAT-based reporter DNA sensors for detecting protein targets. Finally, the main challenges and application prospects of NAAT-based reporter DNA sensors are discussed.


Use of a purified and functional recombinant calcium-channel beta4 subunit in surface-plasmon resonance studies.
Native high-voltage-gated calcium channels are multi-subunit complexes comprising a pore-forming subunit Ca(v) and at least two auxiliary subunits alpha(2)delta and beta. The beta subunit facilitates cell-surface expression of the channel and contributes significantly to its biophysical properties. In spite of its importance, detailed structural and functional studies are hampered by the limited availability of native beta subunit. Here, we report the purification of a recombinant calcium-channel beta(4) subunit from bacterial extracts by using a polyhistidine tag. The purified protein is fully functional since it binds on the alpha1 interaction domain, its main Ca(v)-binding site, and regulates the activity of P/Q calcium channel expressed in Xenopus oocytes in a similar way to the beta(4) subunit produced by cRNA injection. We took advantage of the functionality of the purified material to (i) develop an efficient surface-plasmon resonance assay of the interaction between two calcium channel subunits and (ii) measure, for the first time, the affinity of the recombinant His-beta(4) subunit for the full-length Ca(v)2.1 channel. The availability of this purified material and the development of a surface-plasmon resonance assay opens two immediate research perspectives: (i) drug screening programmes applied to the Ca(v)/beta interaction and (ii) crystallographic studies of the calcium-channel beta(4) subunit.


Emotional Recognition in Patients With Mesial Temporal Epilepsy Associated With Enlarged Amygdala.
Amygdalae play a central role in emotional processing by interconnecting frontal cortex and other brain structures. Unilateral amygdala enlargement (AE) is associated with mesial temporal lobe epilepsy (mTLE). In a relatively large sample of patients with mTLE and AE, we aimed to evaluate functional integration of AE in emotion processing and to determine possible associations between fMRI activation patterns in amygdala and deficits in emotion recognition as assessed by neuropsychological testing. Twenty-two patients with drug resistant unilateral mTLE due to ipsilateral AE were prospectively recruited in a large epilepsy unit and compared with 17 healthy control subjects in terms of amygdala volume, fMRI activation patterns and performance in emotion recognition as assessed by comprehensive affect testing system (CATS) and Ekman faces. All patients underwent structural and functional 1.5 Tesla MRI, electro-clinical assessment and neuropsychological testing. We observed BOLD signal ipsilateral to AE (n = 7; group PAT1); contralateral to AE (n = 6; group PAT2) and no activation (n = 9; group PAT3). In the region of interest (ROI) analysis, beta estimates for fearful face > landscape contrast in the left amygdala region did not differ significantly in patients with left TLE vs. patients with right TLE [T (16) = -1.481; p = 0.158]. However, beta estimates for fearful face > landscape contrast in the right amygdala region were significantly reduced in patients with right TLE vs. patients with left TLE [T (16) = -2,922; p = 0.010]. Patients showed significantly lower total scores in CATS and Ekman faces compared to healthy controls. In our cohort, patients with unilateral mesial TLE and ipsilateral AE, an amygdala could display either functional integration in emotion recognition or dysfunction as demonstrated by fMRI. Perception and recognition of emotions were impaired more in right-sided mTLE as compared to left-sided mTLE. Neuropsychological tests showed deficits in emotion recognition in patients as compared to healthy controls.