Persistence in patients with breast cancer treated with tamoxifen or aromatase inhibitors: a retrospective database analysis.
Compliance and persistence are often underestimated in breast cancer (BC) treatment. The aim of our study was to analyze the persistence with tamoxifen (TAM) and aromatase inhibitors (AI) in postmenopausal women with hormone-receptor-positive BC and to identify determinants of non-persistence. We used data of the Disease Analyzer database (IMS HEALTH, Germany) including 2,067 general practices and 397 gynecological practices. Out of a dataset of 15 million patients, we identified BC patients with a first-time TAM or AI prescriptions from October 2001 to December 2010. For persistence analyses, 12,412 women on tamoxifen, 2,796 on anastrozole, 647 on exemestane, and 1,657 on letrozole met the inclusion/exclusion criteria. Within 3 years of follow-up, the discontinuation rates increased to 52.2 % for tamoxifen, 47 % for anastrozole, 55.1 % for exemestane, and 44.3 % for letrozole treated women. A minor proportion of patients switched to a different endocrine treatment; 33 % tamoxifen, 20 % anastrozole, 22.9 % exemestane, and 23 % letrozole. The multivariate hazard ratios of the cox regression models showed that patients younger than 50 were most likely to discontinue initial therapy when compared with the reference group of women over 70 (p < 0.001). In contrast, patients treated in gynecologist practice had significantly longer persistence than patients who obtained their prescriptions in general practitioner practice (p < 0.001). In addition, the presence of the co morbidities like diabetes (p < 0.001) or depression (p < 0.002) was also associated with decreased risk of treatment discontinuation. Persistence with all endocrine treatments in women with hormone-receptor-positive BC is low and needs to be significantly increased to improved outcome in clinical practice. Further research is required to understand this complex issue.


[Retroperitoneal laparoscopic unroofing of renal cyst: use of close method].
To study the close method of retroperitoneal laparoscopic unroofing of renal cyst. A close method retroperitoneal laparoscopic unroofing of renal cyst was attempted in 35 cases between May 1995 and December 1996. The age of the patients ranged from 30 to 72 and the cyst size from 4.0 to 9.3 cm. The operative procedure took around 50 minutes. After a 1 - 18 month follow up, we observed the disappearance of all renal cysts. The laparoscopic procedure renders less trauma and discomfort to the patients and may be better indicated for symptomatic, simple renal cysts.


[Primary cancer of the stump of the stomach resected for peptic ulcer].
According to the author's data initial carcinoma of the stomach stump occurs more often after the resection for peptic ulcer, than after the duodenal ulcer surgery. In this case the character of surgical intervention depends upon the degree of the propagation of the tumor and on the patient's general condition.


Immunochemical estimations of allergenic activities from outdoor aero-allergens, collected by a high-volume air sampler.
To quantify airborne allergens in amorphus and morphological particles, a survey with collection of aero-allergens on glass fibre filters by means of a high-volume air-sampler (HIVOL) was conducted. In preliminary laboratory experiments we compared various filter elution techniques, and the pulverizing elution technique was found to be optimal with regard to yield and convenience. When a surfactant, Tween 20 (0.5% v/v), was added to the elution buffer, a recovery of 80% could be obtained. Allergens in eluates were analysed by means of an IgG-subclass RAST inhibition assay. This immunochemical method for quantification of airborne allergens was validated, as a high recovery of timothy grass pollen allergens was eluted from air filters, and eluates were shown specific by RAST inhibition. The amount of immunochemically measured airborne timothy and birch allergens collected by means of the HIVOL sampler was highly correlated with pollen counts obtained with a Burkard sampler (pollen trap) situated in the same place.


A sequence related to 4.5 S RNA and the B1 family of repeated DNA in the 5' flanking region of the mouse beta-globin gene.
A beta-globin gene probe containing 5' flanking DNA hybridizes to a small nuclear RNA from Friend erythroleukemia cells, which was subsequently identified as 4.5 S RNA. This hybridization is shown to reflect complementarity between the Alu consensus region of 4.5 S RNA and the DNA sequence between nucleotides -33 and -48 from the beta-globin gene transcription initiation site.


Relationship between kalemia and intensive care unit admission or death in hospitalized COVID-19 patients: A cohort study.
SARS-CoV-2 uses Angiotensin-Converting Enzyme 2 as a viral gateway to the cell and could interact with the renin-angiotensin-aldosterone system. Other studies have shown kalemia abnormalities in patients with severe forms of coronavirus disease 2019. Our goal was to assess the prognosis value of kalemia within ten days of symptom offset in the COVID-19 hospitalized population. We analyzed data from a prospective cohort that included 65 patients with COVID-19, admitted between March 15, 2020, and March 21, 2020. The study aimed at determining the relationship between baseline kalemia and the admission to an intensive care unit (ICU) or death. The median age of the patients was 65 [54-79] years old, and 66.2% of the patients were men. Baseline kalemia under 3.8mmol/l occurred in 31 patients (48%), including 11 patients (35.5%) who were admitted to an ICU and one patient (3.2%) who died before ICU admission. In the primary end-point analysis, the adjusted hazard ratios for admission to an ICU or death were 3.52 [95% confidence interval (CI), 1.12 to 11.04] among patients with low baseline kalemia. Our study suggests that low kalemia levels within ten days of the first symptom onset might be associated with an increased risk of intensive care unit admission or death. The future perspective should be to better understand this relationship.


Interactive behavior of Saccharomyces cerevisiae, Bacillus pumilus and Propionibacterium freudenreichii subsp. shermanii.
Prevention of ropy bread caused by mucoid variants of certain bacilli presents a major problem for developing countries where cost of preservatives is prohibitive. Control of ropiness may be achieved by using propionic acid-producing bacteria in mixed culture with leavening yeasts. Therefore, interaction studies between Propionibacterium freudenreichii subsp. shermanii, Bacillus pumilus and Saccharomyces cerevisiae were conducted in a chemically defined medium to test the relevance of such an approach. Growth of vegetative cells and germination of spores of B. pumilus were inhibited in media preincubated with P. shermanii at 30 degrees C for 13 h. Inhibition was bacteriostatic for the first 6 h of incubation, becoming bactericidal between 6 and 12 h. Inhibition of B. pumilus spore germination was greater than inhibition of growth of vegetative cells of the bacterium. Culturing of either P. shermanii with S. cerevisiae or B. pumilus with S. cerevisiae did not produce inhibitory effects on any of the organisms. Inhibition of B. pumilus by P. shermanii may be useful for prevention of ropiness in bread prepared by the sponge method, involving fermentation of a portion of the dough.


Bacterial lipoxygenases, a new subfamily of enzymes? A phylogenetic approach.
Lipoxygenases (EC. 22.214.171.124) are a non-heme iron enzymes consisting of one polypeptide chain folded into two domains, the N-terminal domain and the catalytic moiety β-barrel domain. They catalyze the dioxygenation of 1Z,4Z-pentadiene moieties of polyunsaturated fatty acids obtaining hydroperoxy fatty acids. For years, the presence of lipoxygenases was considered a eukaryotic feature, present in mammals, plants, small marine invertebrates, and fungi, but now, some lipoxygenase sequences have been detected on prokaryotic organisms, changing the idea that lipoxygenases are exclusively a eukaryotic affair. Lipoxygenases are involved in different types of reactions on eukaryote organisms where the biological role and the structural characteristics of these enzymes are well studied. However, these aspects of the bacterial lipoxygenases have not yet been elucidated and are unknown. This revision discusses biochemical aspects, biological applications, and some characteristics of these enzymes and tries to determine the existence of a subfamily of bacterial lipoxygenases in the context of the phylogeny of prokaryotic lipoxygenases, supporting the results of phylogenetic analyzes with the comparison and discussion of structural information of the first prokaryotic lipoxygenase crystallized and other eukaryotic lipoxygenases structures.


Bone morphogenetic protein-4 inhibits corticotroph tumor cells: involvement in the retinoic acid inhibitory action.
The molecular mechanisms governing the pathogenesis of ACTH-secreting pituitary adenomas are still obscure. Furthermore, the pharmacological treatment of these tumors is limited. In this study, we report that bone morphogenetic protein-4 (BMP-4) is expressed in the corticotrophs of human normal adenohypophysis and its expression is reduced in corticotrophinomas obtained from Cushing's patients compared with the normal pituitary. BMP-4 treatment of AtT-20 mouse corticotrophinoma cells has an inhibitory effect on ACTH secretion and cell proliferation. AtT-20 cells stably transfected with a dominant-negative form of the BMP-4 signal cotransducer Smad-4 or the BMP-4 inhibitor noggin have increased tumorigenicity in nude mice, showing that BMP-4 has an inhibitory role on corticotroph tumorigenesis in vivo. Because the activation of the retinoic acid receptor has an inhibitory action on Cushing's disease progression, we analyzed the putative interaction of these two pathways. Indeed, retinoic acid induces both BMP-4 transcription and expression and its antiproliferative action is blocked in Smad-4dn- and noggin-transfected Att-20 cells that do not respond to BMP-4. Therefore, retinoic acid induces BMP-4, which participates in the antiproliferative effects of retinoic acid. This new mechanism is a potential target for therapeutic approaches for Cushing's disease.


[An anti-Taylor approach: the invention of a method for the cogovernance of health care institutions in order to produce freedom and compromise].
This paper describes a new health care management method. A triangular confrontation system was constructed, based on a theoretical review, empirical facts observed from health services, and the researcher's knowledge, jointly analyzed. This new management model was termed 'health-team-focused collegiate management', entailing several original organizational concepts: production unity, matrix-based reference team, collegiate management system, cogovernance, and product/production interface.


DNAJB1-PRKACA fusions occur in oncocytic pancreatic and biliary neoplasms and are not specific for fibrolamellar hepatocellular carcinoma.
Recently discovered DNAJB1-PRKACA oncogenic fusions have been considered diagnostic for fibrolamellar hepatocellular carcinoma. In this study, we describe six pancreatobiliary neoplasms with PRKACA fusions, five of which harbor the DNAJB1-PRKACA fusion. All neoplasms were subjected to a hybridization capture-based next-generation sequencing assay (MSK-IMPACT), which enables the identification of sequence mutations, copy number alterations, and selected structural rearrangements involving ≥410 genes (n = 6) and/or to a custom targeted, RNA-based panel (MSK-Fusion) that utilizes Archer Anchored Multiplex PCR technology and next-generation sequencing to detect gene fusions in 62 genes (n = 2). Selected neoplasms also underwent FISH analysis, albumin mRNA in-situ hybridization, and arginase-1 immunohistochemical labeling (n = 3). Five neoplasms were pancreatic, and one arose in the intrahepatic bile ducts. All revealed at least focal oncocytic morphology: three cases were diagnosed as intraductal oncocytic papillary neoplasms, and three as intraductal papillary mucinous neoplasms with mixed oncocytic and pancreatobiliary or gastric features. Four cases had an invasive carcinoma component composed of oncocytic cells. Five cases revealed DNAJB1-PRKACA fusions and one revealed an ATP1B1-PRKACA fusion. None of the cases tested were positive for albumin or arginase-1. Our data prove that DNAJB1-PRKACA fusion is neither exclusive nor diagnostic for fibrolamellar hepatocellular carcinoma, and caution should be exercised in diagnosing liver tumors with DNAJB1-PRKACA fusions as fibrolamellar hepatocellular carcinoma, particularly if a pancreatic lesion is present. Moreover, considering DNAJB1-PRKACA fusions lead to upregulated protein kinase activity and that this upregulated protein kinase activity has a significant role in tumorigenesis of fibrolamellar hepatocellular carcinoma, protein kinase inhibition could have therapeutic potential in the treatment of these pancreatobiliary neoplasms as well, once a suitable drug is developed.


Csn3 gene is regulated by all-trans retinoic acid during neural differentiation in mouse P19 cells.
κ-Casein (CSN3) is known to play an essential role in controlling the stability of the milk micelles. We found that the expression of Csn3 was induced by all-trans retinoic acid (ATRA) during neural differentiation in P19 embryonal carcinoma cells from our study using DNA microarray. In this paper, we describe the detailed time course of Csn3 expression and the induction mechanism of Csn3 transcription activation in this process. The Csn3 expression was induced rapidly and transiently within 24 h of ATRA treatment. Retinoic acid receptor (RAR)-specific agonists were used in expression analysis to identify the RAR subtype involved upregulation of Csn3; a RARα-specific agonist mimicked the effects of ATRA on induction of Csn3 expression. Therefore, RARα may be the RAR subtype mediating the effects of ATRA on the induction of Csn3 gene transcription in this differentiation-promoting process of P19 cells. We found that the promoter region of Csn3 contained a typical consensus retinoic acid response element (RARE), and this RARE was necessary for ATRA-dependent transcriptional regulation. We confirmed that RARα bound to this RARE sequence in P19 cells. These findings indicated that the Csn3 expression is upregulated via ATRA-bound RARα and binding of this receptor to the RARE in the Csn3 promoter region. This will certainly serve as a first step forward unraveling the mysteries of induction of Csn3 in the process of neural differentiation.


Metabolic studies on vaccinia-virus-infected oligodendrocytes in brain cell cultures.
Twelve-day-old cultures of dissociated newborn mouse brain were infected with neurotropic vaccinia virus strain WR. Using the indirect immuno-fluorescence staining technique the total destruction of galactocerebroside (GL) or myelin basic protein (MBP)-positive oligodendrocytes could be detected after 72 h of infection. The activity of the oligodendrocyte-specific enzymes, cerebroside sulfotransferase (CST) and 2'3'-cyclic nucleotide 3'-phosphohydrolase (CNP), was 27% and 17% respectively of the activity in noninfected controls. This reduction was not a result of viral-induced inhibition of host protein synthesis. In cultures treated with puromycin GC- and MBP- positive oligodendrocytes were detectable at a time at which no CST or CNP activity could detected.


Accelerated alkalinity regulation and long-term dry-wet aging durability for bauxite residue remediated with biomass pyrolysis.
Biomass fermentation provides a potential route toward the ecological disposal for the bauxite residue (BR) with high alkalinity issues. However, how to accelerate the remediation of the alkaline problem with a long-term durability is still a big challenge. Herein, we investigated the acceleration of the decomposition of straw toward organic acid species via a pyrolysis strategy as well as the pH stability during long-term dry-wet aging for the treated BR. The pH of pyrolytic BR at 300 °C is stabilized at around 8.90 after 70 days' dry-wet aging. During the aging, the main Ca-contained alkaline minerals of calcite and cancrinite are dissolved and the content of exchangeable Na+ is reduced. This pyrolysis process can decompose straw quickly and produce more organic matters that are easily degraded to fulvic and humic acid as evidenced by 3D fluorescence spectrum analysis. Compared to the fermentation with straw under natural conditions, the alkalinity regulation of BR after pyrolysis is featured with shorter period and lower pH as well as long-term pH stability. Therefore, the synergistic pyrolysis of BR with straw provides an alternative method to address the alkaline issues, which is conducive to promoting the soil formation of BR.


Calpain-1-sensitive myofibrillar proteins of the human myocardium.
Calpain-1 is a ubiquitous intracellular Ca2+-activated protease, which has been implicated in the pathogenesis of reversible myocardial depression (i.e. myocardial stunning) that follows ischemia and reperfusion via myofibrillar protein degradation. However, the target proteins of this degradative process in the human myocardium have not yet been identified. In order to compare the levels of Calpain-1 susceptibility within a set of human myofibrillar proteins (titin, alpha-fodrin, desmin, troponin T (cTnT), troponin I (cTnI) and alpha-actinin), crude left ventricular tissue homogenates were incubated for 0.5, 15, 30, 60 or 120 min in the presence of Calpain-1 (1 U or 5 U). Differences in the kinetics and extents of protein degradation were subsequently evaluated by using silver-stained SDS-polyacrylamide gels and Western immunoblot analyses. These assays revealed myofibrillar proteins with high (titin and alpha-fodrin), moderate (desmin and cTnT), or low (cTnI and alpha-actinin) relative Calpain-1 susceptibilities. The level of phosphorylation of cTnI did not explain its relatively low Calpain-1 susceptibility. Moreover, the molecular mass distributions of the truncated alpha-fodrin, desmin and cTnI fragments resulting from Ca2+-dependent autoproteolysis exhibited marked similarities with those of their Calpain-1-clipped products. These in vitro results shed light on a number of structural (titin, alpha-fodrin, desmin and alpha-actinin) and regulatory (cTnT and cTnI) proteins within the contractile apparatus as potential targets of Calpain-1. Their degradation may contribute to the development of postischemic stunning in the human myocardium.


Correlations between serum homocysteine levels and RoPE score in patients with patent foramen ovale.
The pathophysiological relationship between elevated serum homocysteine (Hcy) levels and patent foramen ovale (PFO) has not yet been completely clarified. In the present study, we assess the correlation between serum homocysteine levels and the RoPE score in PFO patients. We retrospectively reviewed clinical and instrumental data of 244 subjects referred to a single tertiary center for PFO evaluation and/or treatment between January 2010 and January 2018,stratified as closure and control group, respectively. Patients in the closure group had an higher serum Hcy levels compared to the control group (28.5 ± 8.5 vs 10.2 ± 6.6 μg/dL, p < 0.0001). A significant direct correlation was observed between serum Hcy levels and the RoPE Score in the entire population. A positive significant correlation continued to exist also in the closure and control groups (r = 0.472, p < 0.0001 and r = 0.378, p < 0.0001, respectively). A receiver operating characteristics curve identified the optimal cutoff value of homocysteinemia as a predictor of RoPE score > 7 in the closure group (AUC 0.90, 95% CI 0.81-0.94, p < 0.0001) when 19.5 μg/dL. Multivariate logistic regression analysis demonstrated that an Hcy serum level ≥ 19.5 μg/dL predict an RoPE score > 7 (OR 3.21, 95% CI 2.82-3.26, p < 0.0001) in closed patients independently from the presence of permanent right-to-left (RLS) (OR 2.28, 95% CI 2.01-2.43, p = 0.001) and atrial septal aneurysm (ASA) (OR 3.04, 95% CI 2.64-3.51, p < 0.0001). Serum homocysteine levels in PFO patients are positively correlated with the RoPE score. Moreover, a homocysteinemia ≥ 19.5 μg/dL predicts an RoPE score > 7 independently from the presence of a permanent RLS and a concomitant ASA.


Comparison of the efficacy and safety of titrated oral misoprostol and a conventional oral regimen for cervical ripening and labor induction.
To compare the efficacy and safety of titrated oral misoprostol and a conventional oral regimen for cervical ripening and labor induction. A randomized double-blind trial of women with term singleton pregnancies with indications for labor induction. Participants were allocated to receive 20 mL of misoprostol solution (1 μg/mL) orally every 1 hour for 4 doses then titrated to 40 μg every 1 hour (titrated group) or 50 μg of misoprostol orally every 4 hours up to 12 hours (conventional group). Primary outcomes were success rate of cervical ripening within 12 hours, interval from first dose until more favorable cervix or active labor occurred, and total dose of misoprostol. Sixty-four participants were included. Mean total dose of misoprostol and incidence of tachysystole were significantly higher in the titrated compared with the conventional group (236.2±110.1 μg vs 103.1 ± 35.7 μg; P=0.001 and 25.0% vs 6.3%; P=0.03), whereas success rate, interval from drug administration to more favorable cervix and delivery, proportion of patients delivered vaginally within 12 hours and 24 hours, need for oxytocin augmentation, cesarean delivery rate, maternal adverse effects and complications, and neonatal outcome were not significantly different (P>0.05). Conventional oral misoprostol is as effective as titrated misoprostol for cervical ripening and labor induction, but has a lower incidence of tachysystole and a lower total dose of misoprostol is required. ClinicalTrial.gov: NCT00886860.


Mutually exclusive exon use and reactive center diversity in insect serpins.
We have isolated 38 cDNA clones for serpins from a lepidopteran insect, Manduca sexta, and have found that they are identical in sequence, except for a region encoding the carboxyl-terminal 40-45 residues, which includes the reactive center. Among these clones, there are 11 variants of the reactive center region, each encoded by a different version of the ninth exon in the serpin gene. Thus, evolution of this insect serpin gene has resulted from duplication and sequence divergence of only the exon encoding the reactive site. Alternative pre-mRNA splicing then generates inhibitor diversity and the potential to regulate a variety of proteinases, using the same protein framework joined to different reactive site region cassettes.


Energy transfer and visible-infrared quantum cutting photoluminescence modification in Tm-Yb codoped YPO(4) inverse opal photonic crystals.
YPO4: Tm, Yb inverse opal photonic crystals were successfully synthesized by the colloidal crystal templates method, and the visible-infrared quantum cutting (QC) photoluminescence properties of YPO4: Tm, Yb inverse opal photonic crystals were investigated. We obtained tetragonal phase YPO4 in all the samples when the samples sintered at 950°C for 5 h. The visible emission intensity of Tm3+ decreased significantly when the photonic bandgap was located at 650 nm under 480 nm excitation. On the contrary, the QC emission intensity of Yb3+ was enhanced as compared with the no photonic bandgap sample. When the photonic bandgap was located at 480 nm, the Yb3+ and Tm3+ light-emitting intensity weakened at the same time. We demonstrated that the energy transfer between Tm3+ and Yb3+ is enhanced by the suppression of the red emission of Tm3+. Additionally, the mechanisms for the influence of the photonic bandgap on the energy transfer process of the Tm3+, Yb3+ codoped YPO4 inverse opal are discussed.


A modular reaction pairing approach to the diversity-oriented synthesis of fused- and bridged-polycyclic sultams.
A reaction pairing strategy centered on utilization of a reaction triad (sulfonylation, S(N)Ar addition and Mitsunobu alkylation) generating skeletally diverse, tricyclic and bicyclic benzofused sultams is reported. Pairing sulfonylation and S(N)Ar reactions yields bridged, tricyclic and bicyclic benzofused sultams. Application of the Mitsunobu reaction in a sulfonylation-Mitsunobu-S(N)Ar pairing allows access to benzthiazocine-1,1-dioxides, while a simple change in the order of pairing to sulfonylation-S(N)Ar-Mitsunobu affords structurally different, bridged tricyclic benzofused sultams.


The roles of various plasma species in the plasma and plasma-catalytic removal of low-concentration formaldehyde in air.
The contributions of various plasma species to the removal of low-concentration formaldehyde (HCHO) in air by DC corona discharge plasma in the presence and absence of downstream MnO(x)/Al(2)O(3) catalyst were systematically investigated in this study. Experimental results show that HCHO can be removed not only by short-living active species in the discharge zone, but also by long-living species except O(3) downstream the plasma reactor. O(3) on its own is incapable of removing HCHO in the gas phase but when combined with the MnO(x)/Al(2)O(3) catalyst, considerable HCHO conversion is seen, well explaining the greatly enhanced HCHO removal by combining plasma with catalysis. The plasma-catalysis hybrid process where HCHO is introduced through the discharge zone and then the catalyst bed exhibits the highest energy efficiency concerning HCHO conversion, due to the best use of plasma-generated active species in a two-stage HCHO destruction process. Moreover, the presence of downstream MnO(x)/Al(2)O(3) catalyst significantly reduced the emission of discharge byproducts (O(3)) and organic intermediates (HCOOH).


Heterogeneous distribution of Plasmodium falciparum drug resistance haplotypes in subsets of the host population.
The emergence of drug resistance is a major problem in malaria control. For mathematical modelling of the transmission and spread of drug resistance the determinant parameters need to be identified and measured. The underlying hypothesis is that mutations associated with drug resistance incur fitness costs to the parasite in absence of drug pressure. The distribution of drug resistance haplotypes in different subsets of the host population was investigated. In particular newly acquired haplotypes after radical cure were characterized and compared to haplotypes from persistent infections. Mutations associated with antimalarial drug resistance were analysed in parasites from children, adults, and new infections occurring after treatment. Twenty-five known single nucleotide polymorphisms from four Plasmodium falciparum genes associated with drug resistance were genotyped by DNA chip technology. Haplotypes were found to differ between subsets of the host population. A seven-fold mutated haplotype was significantly reduced in adults compared to children and new infections, whereas parasites harbouring fewer mutations were more frequent in adults. The reduced frequency of highly mutated parasites in chronic infections in adults is likely a result of fitness costs of drug resistance that increases with number of mutations and is responsible for reduced survival of mutant parasites.


Physiological properties of the dorsal longitudinal flight muscle and the tergal depressor of the trochanter muscle of Drosophila melanogaster.
A prerequisite for using muscle mutants to study contraction in Drosophila melanogaster is a description of the mechanics of wild-type muscles. Here we describe the mechanics of two different wild-type muscles; the dorsal longitudinal flight muscle which is asynchronous (nerve impulses are not synchronised with each contraction), and a leg muscle, the tergal depressor of the trochanter, which is synchronous. We have compared their mechanics to those of the asynchronous flight and the synchronous leg muscle from the giant waterbug Lethocerus indicus. We found that the mechanics of the asynchronous flight muscles from the two species were similar. At rest length both muscles had a high relaxed stiffness, were partially activated by Ca2+ (low steady-state active tension) and, once activated, had a large delayed increase in tension, which was well maintained, in response to a rapid stretch. The rate constant for the delayed increase in tension was about 10 times greater for D. melanogaster than for L. indicus under the same conditions. The mechanics of the synchronous leg muscles from both species were different from those of the flight muscles and resembled those of other synchronous muscles such as vertebrate striated muscle. At rest length, both muscles had a lower relaxed stiffness than the flight muscles, were fully activated by Ca2+ (high steady-state active tension) and, once activated, had a small delayed increase in tension, which was less well maintained, in response to a rapid stretch. The rate constant for the delayed increase in tension was similar for the leg muscles of both species. The different mechanical properties of the flight and leg muscles must arise from differences in their contractile proteins. The demonstration that satisfactory mechanical responses can be obtained from the small (less than 1 mm long) muscles of D. melanogaster will enable future responses from mutant muscles to be tested.


Expression of interleukin-17 in autoimmune dacryoadenitis in MRL/lpr mice.
Th-cytokines play important roles in dacryoadenitis associated with Sjögren's syndrome (SS). The aims of this study were to (i) investigate whether interleukin (IL)-17, a newly identified Th-cytokine, participates in autoimmune dacryoadenitis of MRL/lpr mice and (ii) examine the relationships among IL-17, IL-4, and interferon (IFN)-γ in these mice. Three-month-old MRL/lpr mice with lacrimal gland inflammation and 3-month-old control BALB/c mice were used. Frozen sections of lacrimal glands and submandibular lymph nodes were stained with monoclonal antibodies to cytokines IL-17, IL-4, and IFN-γ. Concentrations of IL-17 in serum and 48-h splenocyte culture supernatants were detected by ELISA. Marked lacrimal gland inflammation was observed in all MRL/lpr mice but not in any BALB/c control mice. In the lacrimal glands of MRL/lpr mice, the proportions of cells that stained were 5 ± 3% for IL-17, 32 ± 14% for IL-4, and 4 ± 2% for IFN-γ. In the submandibular lymph nodes of MRL/lpr mice, expression of IL-17 and IL-4 was significantly higher than that of IFN-γ, and all three cytokines were significantly higher in MRL/lpr mice than in BALB/c mice. Concentrations of IL-17 in both serum and splenocyte culture supernatants of MRL/lpr mice were elevated compared to BALB/c controls. Since expression of IL-17 is elevated in 3-month-old MRL/lpr mice, we suggest that it plays a role in the pathophysiology of autoimmune dacryoadenitis in these mice.


Health service use among adults with cerebral palsy: a mixed-methods systematic review.
To determine the proportion of adults with cerebral palsy (CP) using health services and frequency of use, and to explore experiences and perceptions of health services for this population. A mixed-methods systematic review was conducted using the Joanna Briggs Institute methodology. Five databases were searched to September 2020. Observational and qualitative studies were included. Two reviewers screened titles, abstracts, and full texts; extracted data; and assessed the quality of included studies. Separate meta-analyses were used to pool the proportion of adults using each service and frequency of use. A meta-aggregation approach was used to synthesize qualitative data. Quantitative and qualitative findings were integrated using the Andersen and Newman Model of health care utilization. Fifty-seven studies (31 quantitative, 26 qualitative) of 14 300 adults with CP were included. The proportion of adults using services ranged from 7% (95% confidence interval [CI]: 2-13%) for urologists to 84% (95% CI: 78-90%) for general practitioners. Incidence of visits ranged from 67 (95% CI: 37-123) hospital admissions to 404 (95% CI: 175-934) general practitioner visits per 100 person-years. Qualitative themes highlighted issues regarding accessibility, caregivers' involvement, health workers' expertise, unmet ageing needs, transition, and health system challenges. Adults with CP used a wide range of health services but faced context-specific challenges in accessing required care. Appropriate service delivery models for adults with CP are required. This review emphasizes a need to develop an appropriate service model for adults with CP to meet their needs.


Chromatin changes in the development and pathology of the Fragile X-associated disorders and Friedreich ataxia.
The Fragile X-associated disorders (FXDs) and Friedreich ataxia (FRDA) are genetic conditions resulting from expansion of a trinucleotide repeat in a region of the affected gene that is transcribed but not translated. In the case of the FXDs, pathology results from expansion of CGG•CCG-repeat tract in the 5' UTR of the FMR1 gene, while pathology in FRDA results from expansion of a GAA•TTC-repeat in intron 1 of the FXN gene. Expansion occurs during gametogenesis or early embryogenesis by a mechanism that is not well understood. Associated Expansion then produces disease pathology in various ways that are not completely understood either. In the case of the FXDs, alleles with 55-200 repeats express higher than normal levels of a transcript that is thought to be toxic, while alleles with >200 repeats are silenced. In addition, alleles with >200 repeats are associated with a cytogenetic abnormality known as a fragile site, which is apparent as a constriction or gap in the chromatin that is seen when cells are grown in presence of inhibitors of thymidylate synthase. FRDA alleles show a deficit of the FXN transcript. This review will address the role of repeat-mediated chromatin changes in these aspects of FXD and FRDA disease pathology. This article is part of a Special Issue entitled: Chromatin in time and space.


Clinical significance of RCAS1 as a biomarker of uterine cancer.
Expression of RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is associated with prognosis of various malignancies including uterine cancer. Proteolytic cleavage of RCAS1 at extracellular domains (ectodomain shedding) yields soluble RCAS1. Although RCAS1 can induce apoptosis in normal peripheral lymphocytes, its biologic function in cancer patients is unclear. Here, we evaluated serum RCAS1 concentrations to clarify its biologic activity in uterine cancer. Via ELISA, we measured serum RCAS1 concentrations in samples from 54 healthy blood donors and 113 patients-63 with cervical cancer and 50 with endometrial cancer. We also counted the peripheral lymphocyte number. We correlated via statistical means the RCAS1 values with patients' clinicopathologic variables. We assessed inhibition of growth of K562 cells, which express the putative RCAS1 receptor, via WST-1 assay of serum samples to clarify RCAS1's biologic activity. Uterine cancer patients had significantly higher serum RCAS1 concentrations than did healthy blood donors (P<0.05). Patients with adenocarcinoma had significantly higher RCAS1 concentrations than did those with squamous cell carcinoma (P=0.0340). RCAS1 values were also significantly associated with response to treatment (P<0.001). FasL and TNF-alpha serum concentrations were not significantly different for the different groups, however. The WST-1 assay showed that patients' serum induced K562 cell growth inhibition, but this effect partially recovered after immunodepletion of RCAS1. Peripheral lymphocyte number and serum RCAS1 concentration were inversely related (P=0.0310). RCAS1 may be a biomarker of uterine cancer because of its potential to predict results of uterine cancer treatment and inhibit growth of immune cells.


A Bayesian multi-arm multi-stage clinical trial design incorporating information about treatment ordering.
Multi-Arm Multi-Stage (MAMS) designs can notably improve efficiency in later stages of drug development, but they can be suboptimal when an order in the effects of the arms can be assumed. In this work, we propose a Bayesian multi-arm multi-stage trial design that selects all promising treatments with high probability and can efficiently incorporate information about the order in the treatment effects as well as incorporate prior knowledge on the treatments. A distinguishing feature of the proposed design is that it allows taking into account the uncertainty of the treatment effect order assumption and does not assume any parametric arm-response model. The design can provide control of the family-wise error rate under specific values of the control mean and we illustrate its operating characteristics in a study of symptomatic asthma. Via simulations, we compare the novel Bayesian design with frequentist multi-arm multi-stage designs and a frequentist order restricted design that does not account for the order uncertainty and demonstrate the gains in the sample sizes the proposed design can provide. We also find that the proposed design is robust to violations of the assumptions on the order.


Molecular and functional characterisation of the zebrafish (Danio rerio) PEPT1-type peptide transporter.
We report the molecular and functional characterisation of a novel peptide transporter from zebrafish, orthologue to mammalian and avian PEPT1. Zebrafish PEPT1 is a low-affinity/high-capacity system. However, in contrast to higher vertebrate counterparts in which maximal transport activity is independent of extracellular pH, zebrafish PEPT1 maximal transport rates unexpectedly increase at alkaline extracellular pH. Zebrafish pept1 is highly expressed in the proximal intestine since day 4 post-fertilisation, thus preceding functional maturation of the gut, first feeding and complete yolk resorption. Zebrafish PEPT1 might help to understand the evolutionary and functional relationships among vertebrate peptide transporters. Moreover, zebrafish pept1 can be a useful marker for screening mutations that affect gut regionalisation, differentiation and morphogenesis.


Potassium currents of acutely isolated adult rat superior cervical ganglion neurons.
K+ currents of adult rat superior cervical ganglion neurons were studied using the voltage-clamp technique. Neuronal somata were dissociated from the ganglion using an enzymatic dispersion technique and voltage-clamped using the whole-cell patch-clamp technique. In solutions designed to isolate K+ currents, depolarization from a prepulse potential of -100 mV induced both transient and sustained outward current components. The transient current was completely eliminated by depolarization to -50 mV. The remaining sustained current component could be separated further into Ca2+-sensitive and Ca2+-insensitive components by superfusion with a Ca2+-free external solution. The transient current, which could be isolated by digital subtraction, rose rapidly and decayed over the subsequent 80 ms. Reversal potential determinations in different K+-containing solutions demonstrated that the current was carried primarily by K+. The transient current showed voltage-dependent inactivation, showing 50% inactivation near -87 mV and was completely inactivated at potentials more positive than -60 mV. The transient current recovered from inactivation with a voltage-dependent time course, the time course of inactivation decreasing with hyperpolarization. This transient outward current had characteristics of IA. The sustained Ca2+-insensitive outward current showed little decay over 800 ms and was also carried primarily by K+. This current component had characteristics similar to the delayed rectifier. A third sustained outward current eliminated by superfusion with Ca2+-free external solution had characteristics similar to the Ca2+-dependent K+ current.


AIDS: state of the art, spring 1988.
In this article I have addressed many of the AIDS issues of concern to immunologists and allergists, both as citizens, physicians, and as specialists. HIV infection (AIDS) is going to be with us for some time to come. However, I think some solace can be gained from the fact that the human race has faced many such contagions in the past for example, bubonic plague, cholera, syphilis, and most recently, polio, to name a few. We are very fortunate today to have the scientific and medical tools that have provided us with tremendous insight into the basic and clinical aspects of this disease. These tools and a large cadre of dedicated people who have declared a war on AIDS will provide the answers.


A validation and modification of PLASMIC score by adjusting the criteria of mean corpuscular volume and international normalized ratio.
The PLASMIC score was developed for distinguishing thrombotic thrombocytopenic purpura (TTP) from other types of thrombotic microangiopathy. However, two components of the PLASMIC score, mean corpuscular volume (MCV) and international normalized ratio (INR), showed non-significant differences between TTP and non-TTP patients in previous validations. Here, we validate the PLASMIC score and aim to modify it by adjusting the criteria of MCV and INR. A retrospective validation of suspected TTP patients was performed by reviewing electronic medical records from two medical centers in Taiwan. The performance of different modified types of the PLASMIC score was carried out. Among 50 patients included in the final analysis, 12 were diagnosed with TTP based on deficiency of ADAMTS13 activity and clinical judgement. When stratified by high (score ≥ 6) and low-intermediate risk (score < 6), the positive predictive value (PPV) of the PLASMIC score to predict TTP was 0.45 (95% confidence interval [CI]: 0.29-0.61). The area under curve (AUC) was 0.70 (95% CI: 0.56-0.82). When adjusting the criteria of the PLASMIC score from MCV < 90 fL to MCV ≥ 90 fL, the PPV increased to 0.57 (95% CI: 0.37-0.75). The AUC was 0.75 (95% CI: 0.61-0.87). When adjusting the INR from >1.5 to >1.1, the PPV increased to 0.56 (95% CI: 0.39-0.71). The AUC was 0.81 (95% CI: 0.68-0.90). MCV ≥ 90 fL and/or INR > 1.1 might be suitable modifications for PLASMIC score but should be validated in a larger sample size.


DNA Vaccines: Experiences in the Swine Model.
DNA vaccination is one of the most fascinating vaccine-strategies currently in development. Two of the main advantages of DNA immunization rely on its simplicity and flexibility, being ideal to dissect both the immune mechanisms and the antigens involved in protection against a given pathogen. Here, we describe several strategies used to enhance the immune responses induced and the protection afforded by experimental DNA vaccines tested in swine and provide with very basic protocol describing the generation and in vivo application of a prototypic DNA vaccine. Only time will tell the last word regarding the definitive implementation of DNA vaccination in the field.


Documentation of electrode localization.
In evaluating the success of deep brain stimulation (DBS), the benefit for the patient is the most important criteria. Nevertheless, correct placement of electrodes should also be determined in terms of their anatomic position. Therefore, we propose a suite of different imaging modalities and further processing, which leads to an exact anatomic and statistically comparable documentation of electrode localization. Forty-three consecutive patients with a total of 85 implanted DBS electrodes were evaluated with respect to postoperative imaging. T1-weighted magnetic resonance imaging (T1-MRI) was performed in all patients, 34 patients received T2-MRI, in 18 patients stereotactic X-ray of the scull was performed in anteroposterior and lateral projections, whereas 6 patients were additionally evaluated by pre- and postoperative MR-image fusion between T1-data sets and calculation of coordinates for electrode contacts. In T1-MRI, the artefacts of each electrode contact could be delineated in relation to anatomic reference structures, whereas T2-MRI allowed reproducibly for delineation of electrode artefacts within subthalamic nucleus or globus pallidus pars interna. By MR-image fusion it could be shown that the difference between planned target coordinates and coordinates of the active electrode contact ranged below 1 mm except for the z axis. The comparison with values obtained from stereotactic X-ray confirmed these results. The sequential and complementary use of the described imaging modalities and further image processing provide clinically reliable and statistically comparable results to prove the exact anatomic electrode positioning in DBS in addition to the objective and subjective improvements of the patients' symptoms.


Age at Introduction of Solid Food and Obesity Throughout the Life Course.
This study aimed to examine the association between age at solid food (SF) introduction and obesity throughout the life course. Among 31,816 mother- nurse daughter dyads in the Nurses' Mothers' Cohort Study and the Nurses' Health Study II, information was collected on age at SF introduction, body somatotype at ages 5 and 10, and Body Mass Index at age 18 and in adulthood. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for obesity throughout life were estimated using logistic regression models with adjustment for parental and nurse daughter covariates. Nurse daughters introduced to SF at ≥ 9 months versus 6 to 9 months had marginally higher age-adjusted (OR: 1.21; 95% CI: 1.01, 1.47) and covariate-adjusted (OR: 1.22; 95% CI: 1.01, 1.47) odds of obesity at age 5. Age at SF introduction was not related to obesity at ages 10 and 18 or in adulthood. Late age at SF introduction was marginally associated with obesity at age 5, but this association did not persist throughout the life course.


Validation of a self-report version of the diabetes self-management profile.
Inadequate treatment adherence impedes achievement of glycemic control targets in type 1 diabetes (T1D). Valid and reliable measurement of treatment adherence is a prerequisite to rigorous evaluation of pertinent interventions. The diabetes self-management profile (DSMP), a structured interview measure of T1D adherence, is valid and reliable but it requires trained interviewers, it is labor intensive to administer and it is burdensome for research participants. We adapted the DSMP interview to create the DSMP-self-report questionnaire (DSMP-SR) for completion by parents and youth ≥11 yr old. The DSMP-SR was obtained during a cross-sectional study of 151 youth within the age range of 8 to <18 yr with T1D [male, 50.7%; racial minorities, 23%; mean age, 13.9 yr; T1D duration, 5.5 yr; hemoglobin A1c (HbA1c), 8.7%] and a parent of each. Parents and youth ≥11 yr old completed the DSMP-SR independently. The DSMP-SR had sound internal consistency (Cronbach's α: youth, 0.82; parent, 0.80), and parent-youth agreement, (r = 0.60, p < 0.001) and significant associations with HbA1c (r = -0.35 for youth and -0.46 for parents, p < 0.001), PedsQL quality of life scale (youth: r = -0.41, p < 0.001; parent: r = -0.40, p < 0.001) and, for parents but not youth, the Revised Diabetes Family Conflict Scale (r = -0.47, p < 0.001). Higher DSMP-SR scores were associated with lower HbA1c, better quality of life, and less family conflict. The DSMP-SR has similar psychometric properties to those reported elsewhere for the DSMP, yielding a convenient measure of T1D adherence.


Using a synoptophore to test Listing's law during vergence in normal subjects and strabismic patients.
The synoptophore was used to measure torsional interocular disparity. This, in turn, was used to compute how much the angle between the Listing's plane (LP) of the two eyes changes as a function of the vergence angle. The ratio of these two angles was defined as G. We measured G in normals and in patients suffering from intermittent horizontal strabismus. Consistent with previous search-coil experiments and with our previous visual test measures, the results using the synoptophore suggest that, for normals, G is less than 1. In the patient group the mean G was similar in magnitude but more variable. The variations in G did not appear to be related to the patient's measurement of ocular deviation. This result suggests that the vergence-related rotation of LP in these patients may be related to other factors besides the effort required to fuse the lines of sight.


Impact of COVID-19 on pediatric emergency fellowship training in Saudi Arabia.
To assess the impact of the COVID-19 pandemic on the academic and clinical processes of pediatric emergency medicine (PEM) fellowship training held by the Saudi Commission for Health Specialties (SCHS). A cross-sectional, nationwide, survey-based study was conducted between June and December 2020. PEM program directors as well as fellowship trainees were eligible. The collected data were under the following domains: (1) sociodemographic and work-related characteristics; (2) impact of the COVID-19 pandemic on patient flow and PEM procedures; (3) impact on emergency skills and competence; (4) impact on academic performance; and (5) attitudes toward PEM practice and potential solutions. Monthly reports of PEM visits and procedures were also collected from program directors. A total of 11 PEM program directors and 42 fellows responded. During the pandemic, the number of total ED visits decreased by 70.1%, ED inpatient admissions fell by 57.3%, and the number of intraosseous need insertion and lumbar puncture procedures fell by 76.7% and 62.3%, respectively; the temporal differences in the median frequencies were statistically significant. The pandemic has influenced the knowledge acquisition and leadership skills of one-third of program directors (36.4% and 27.3%, respectively) and the skills and competence of fellows (31.0%). The majority of directors and fellows showed that online classes/webinars were useful (100% and 95.2%, respectively), and there was no need to extend the current fellowship training to compensate for learning deficits (62.7% and 78.6%, respectively). The importance of dedicated modalities to fill in the training gap increased by 62.5% of program directors and 35.7% of fellows. The COVID-19 pandemic had significant effects on clinical procedures and academic activities in the PEM fellowship program. The impact was consistently perceived across PEM program directors and fellows. Technology-driven solutions are warranted to mitigate the expected learning and clinical deficits due to reduced clinical exposure.


Atopic dermatitis is associated with Caesarean sections in Korean adolescents, but asthma is not.
Studies on the associations between mode of delivery and allergic diseases have produced different results, and research has rarely been conducted in Asian countries such as South Korea. This study assessed the relationship between mode of delivery and atopic dermatitis and asthma in Korean adolescents. Data collected from the Korea National Health and Nutrition Examination Survey between 2010 and 2011 were used. We included 1302 adolescents aged from 12 to 18 years, and multivariable logistic regression analysis was performed. The odds ratio (OR) of having atopic dermatitis in adolescents born by Caesarean section compared with vaginal delivery was 1.50, with a 95% confidence interval (95% CI) of 1.01-2.22, after adjusting for age and sex. The association remained significant after further adjustments for body mass index, breastfeeding and serum 25-hydroxyvitamin D level (OR = 1.61, 95% CI = 1.05-2.47) and when fat intake was added to those variables (OR = 1.80, 95% CI = 1.14-2.85). However, asthma was not associated with mode of delivery in any of the models. Atopic dermatitis in adolescents was associated with Caesarean delivery, which is common in South Korea. The findings suggest that the frequency of this practice should be reconsidered and that further research with longitudinal evaluation of relevant mechanisms is needed.


Spinocerebellar projections from the upper lumbar segments in the cat, as studied by anterograde transport of wheat germ agglutinin-horseradish peroxidase.
The projection fields of the dorsal spinocerebellar tract (DSCT) arising from Clarke's column, marginal neurons of Clarke's column, and lamina V neurons in the upper lumbar segments were studied by the anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) in the cat. To label only these neuron groups with uncrossed ascending axons, the spinal cord was lesioned rostral and contralateral to the WGA-HRP injections. Following injections of WGA-HRP into the L1-L4 segments, labeled terminals were seen in sublobules Ia-VIc and VIIb-VIIIb, the simple lobule, the paramedian lobule, and the dorsal paraflocculus. About 70-80% and 20-30% of the total number of labeled terminals were in the anterior and the posterior lobe, respectively; the projections were predominantly ipsilateral to the cells of origin (about 87% or more labeled terminals of the total number in each of sublobules IIb-Va). The labeled terminals were abundant in sublobule IIb (6-11%), lobule III (12-27%), and sublobules IVa (14-17%) and IVb (14-21%). In the mediolateral extent of the lobules in the anterior lobe, the labeled terminals were most numerous between 1.1 and 3.0 mm lateral to the midline (45-75% of the total number of labeled terminals on the ipsilateral side). In the posterior lobe labeled terminals were numerous in sublobule VIIIb (13.6%) and sublobule C of the paramedian lobule (15-19%). The projection fields in the horizontal plane of the lobules were reconstructed from a series of cross sections through each lobule. In the anterior lobe the labeled terminals were distributed in eight major areas. In sublobules IIb-III, areas 1-3 were located within 1.0 mm of the midline in zone A of Voogd; areas 4-6, between 1.0 and 2.5 mm lateral to the midline in zones B-C1; and areas 7 and 8, lateral to 3.0 mm from the midline in zones C2 and C3. Areas 1-6 extended apicobasally in the middle part of the lobules. In sublobule VIIIb projections were confined to three longitudinal areas whereas in the paramedian lobule the projection areas were less distinct. The projection pattern of the lumbar DSCT was different from that of the thoracic DSCT reported previously. In the anterior lobe the thoracic DSCT projects to five areas in the medial (zone A) and the lateral part (zone B) of the vermis and to four areas in the intermediate region of the hemisphere (zones C1-C3).


Polymorphism of human pituitary lutropin (LH). Isolation and partial characterization of seven isohormones.
The complete microheterogeneous system of human pituitary lutropin was demonstrated by gel isoelectric focusing. In addition 7 LH isohormones could be isolated by preparative column focusing and characterized with respect to physicochemical, biological and immunological properties. The in vivo biopotencies ranged from 4.50-11.50 IU/mg, the in vitro bioactivity was from 1.20-10.10 IU/mg, and the immunological activity was from 3.10-7.55 IU/mg. The sialic acid content was found to be 1.8-3.2%. Treatment with neuraminidase resulted in a shift of all bands to the alkaline region, however the 7 LH forms were still present.


Systematics: use of protein nearest neighbour frequency distribution as an objective key.
Although it is one of the oldest of modern disciplines, systematics has always been a science practised in a highly personalised and subjective way because of the need to rely on morphological characteristics of the living organisms, as well as the fossil remains, for their classification. Recent studies on the amino acid nearest neighbours, however, enable one to have an objective key for classifying organisms as well as their relationships.


Mitogen-induced tyrosine-phosphorylated 41- and 43-kDa proteins are family members of extracellular signal-regulated kinases/microtubule-associated protein 2 kinases.
Two antipeptide antibodies, one against the peptide corresponding to residues 307-327 (alpha Y91) and one against the peptide corresponding to the C-terminal portion (alpha C92) of the deduced amino acid sequence of the extracellular signal-regulated kinase 1 (ERK1), precipitated two 41-kDa and/or two 43-kDa phospho-proteins from mitogen-stimulated Swiss 3T3 cells. Electrophoretic mobilities on two-dimensional gels of the immunoprecipitated 41- and 43-kDa phosphoproteins were similar to those of the 41- and 43-kDa cytosol proteins, whose increased tyrosine phosphorylation we and others had originally identified in various mitogen-stimulated cells (Cooper, J. A., Sefton, B. M., and Hunter, T. (1984) Mol. Cell. Biol. 4, 30-37; Kohno, M. (1985) J. Biol. Chem. 260, 1771-1779); phosphopeptide map analysis revealed that they were respectively identical molecules. All those phosphoproteins contained phosphotyrosine, and the more acidic forms contained additional phosphothreonine. Immunoprecipitated 41- and 43-kDa phosphoproteins had serine/threonine kinase activity toward myelin basic protein (MBP) and microtuble-associated protein 2 (MAP2). With the combination of two-dimensional gel electrophoresis and the kinase assay in MBP-containing polyacrylamide gels of the alpha Y91 immunoprecipitates, with or without phosphatase 2A treatment, we showed that only their acidic forms were active. These results clearly indicate that 41- and 43-kDa proteins, the increased tyrosine phosphorylation of which is rapidly and commonly induced by mitogen stimulation of fibroblasts, are family members of ERKs/MAP2 kinases and that phosphorylation both on tyrosine and threonine residues is necessary for their activation.


Posterior dislocation of the acromio-clavicular joint: a rare or an easily overlooked lesion?
The authors describe a case of posterior acromio-clavicular dislocation treated operatively. The etiology and pathological anatomy are discussed and the importance of an axial radiographic projection is emphasized. Radiographic comparison with the normal shoulder is helpful in leading to a correct diagnosis.


Influence of hydrocarbons on hydrogen chloride removal from refinery off-gas by zeolite NaY derived from rice husks.
The removal of gaseous hydrochloric acid (HCl) in refineries and petrochemical plants is essential to prevent potential catalyst poisoning, equipment corrosion, and several associated public health and environmental hazards when the acid contaminates the hydrogen-hydrocarbon feedstock. In the present work, the effect of alkanes, alkenes, and liquid aromatic hydrocarbons on the removal of HCl from refinery off-gas using zeolite NaY was evaluated. Zeolite NaY was synthesized from rice husks via a hydrothermal route. Adsorbent characterization analyses such as XRD, SEM-EDS, FT-IR, BET and particle size distribution were employed. Fixed-bed experiments were operated under feed condition of 600 ppm HCl and gas hourly space velocity of 640 mL/h·cm3. Gaseous HCl was combined with H2, H2-alkanes and H2-alkenes to simulate the main components of refinery-off gas. Experimental breakthrough curves were used to determine the adsorption capacities of zeolite NaY pellets at breakthrough and saturation. HCl removal by fresh zeolite NaY was inhibited by light alkanes but improved in the presence of alkenes. The adsorption capacity at breakthrough for fresh zeolite with combined hydrogen and light alkenes was measured at 0.1507 g/g. In the presence of aromatics, significant reduction in adsorption capacities to 0.1247, 0.1379 and 0.1437 g/g were obtained for adsorbents subjected to H2, H2-alkanes and H2-alkenes respectively. Zeolite NaY consistently showed higher performance for HCl removal in the presence of H2 feed mixed with light hydrocarbons compared with a commercial adsorbent.


Early menopause and premature ovarian insufficiency may increase the risk of sarcopenia: A systematic review and meta-analysis.
Menopausal transition, resulting from a decline in estrogen concentrations, may compromise musculoskeletal health. However, it is unclear if early menopause (defined as age at menopause <45 years) and premature ovarian insufficiency (defined as age at menopause <40 years) are associated with increased risk of sarcopenia. The aim of this systematic review and meta-analysis was to synthesize studies evaluating the association between age at menopause and risk of sarcopenia. A comprehensive search was conducted in PubMed, CENTRAL and Scopus, up to 31 December 2022. Data were expressed as standardized mean difference with 95 % confidence intervals. The I2 index was employed to evaluate heterogeneity. Six studies were included in the qualitative and quantitative analysis, with a total of 18,291 post-menopausal women. Compared with women of normal age at menopause (>45 years), women with early menopause demonstrated lower muscle mass, assessed by appendicular skeletal muscle mass/body mass index [standardized mean difference (SMD) -0.14, 95 % confidence interval (CI) -0.20 to -0.07, p < 0.001; I2 0%]. However, no differences in muscle strength, assessed by handgrip strength (SMD -0.15, 95 % CI -0.31 to 0.01, p = 0.071; I2 72%), and muscle performance, assessed by gait speed (SMD -0.11, 95 % CI -0.29 to 0.05, p = 0.18; I2 79%), were found. Women with premature ovarian insufficiency had lower handgrip strength (SMD -0.3, 95 % CI -0.58 to -0.01, p = 0.04; I2 74.6 %) and gait speed (SMD -0.13, 95 % CI -0.23 to -0.04, p = 0.004; I2 0%) compared with women of normal age at menopause. Early menopause is associated with reduced muscle mass and premature ovarian insufficiency with reduced muscle strength and performance compared with normal age at menopause.


Photochemical deposition of SERS active silver nanoparticles on silica gel and their application as catalysts for the reduction of aromatic nitro compounds.
We report an impregnation technique for immobilization of silver(I) gelatin complex on silica gel. Subsequent UV exposure of the dry impregnated silica gel deposited silver nanoparticles on the solid matrix. Conventional techniques (UV-visible spectroscopy, TEM, EDAX, and thermal analysis) have been used to identify and characterize silver particles on silica surfaces. The photoproduced silver particles have shown unique SERS activity that authenticates the presence of silver nanoclusters in the silica matrix. Hence, the surface of the silica matrix remains SERS-active for months. This surface activity of the silica matrix inspired us to successfully study the catalytic reduction of nitro-compounds in aqueous, organic, and three different micellar media. Different thermodynamic parameters for the reduction processes have also been evaluated. Catalytic activity of the particles in micelles is explained in the light of hydrophobic and electrostatic interactions between the substrate and the micelles.


Superior sagittal sinus thrombosis associated with raised intracranial pressure in closed head injury with depressed skull fracture.
A case of delayed signs of intracranial hypertension following closed head injury with a depressed cranial fracture and superior sagittal sinus thrombosis is reported. Conservative treatment of intracranial hypertension, including just repeated lumbar puncture and oral acetazolamide, was performed. Spontaneous recanalization of the superior sagittal sinus was observed. Pathogenesis and different modalities of treatment are discussed.


Porous Molecular Capsules as Non-Polymeric Transducers of Mechanical Forces to Mechanophores.
Mechanical grinding/milling can be regarded as historically the first technology for changing the properties of matter. Mechanically activated molecular units (mechanophores) can be present in various structures: polymers, macromolecules, or small molecules. However, only polymers have been reported to effectively transduce energy to mechanophores, which induces breakage of covalent bonds. In this paper, a second possibility is presented-molecular capsules as stress-sensitive units. Mechanochemical encapsulation of fullerenes in cystine-based covalent capsules indicates that complexation takes place in the solid state, despite the fact that the capsules do not possess large enough entrance portals. By using a set of solvent-free MALDI (sf-MALDI) and solid-state NMR (ss-NMR) experiments, it has been proven that encapsulation proceeds during milling and in this process hydrazones and disulfides get activated for breakage, exchange, and re-forming. The capsules are porous and therefore prone to collapse under solvent-free conditions and their conformational rigidity promotes the collapse by the breaking of covalent bonds.


Assessment of postural stability using foam posturography at the chronic stage after acute unilateral peripheral vestibular dysfunction.
To investigate the utility of foam posturography for assessing equilibrium at the chronic stage after acute unilateral peripheral vestibulopathy. Thirty-four consecutive patients (16 patients at the chronic stage) with acute unilateral peripheral vestibulopathy and absent caloric responses unilaterally were recruited, along with 66 healthy control subjects. Two-legged stance tasks were performed in 4 conditions: with eyes open or closed, with or without using foam rubber. We adopted 6 parameters: the movement velocity of the center of pressure, the envelopment area traced by the movement of the center of pressure with eyes closed/foam rubber, Romberg's ratios of velocity and area with foam rubber, and the foam ratios (the ratio of a parameter measured with and without foam rubber) of velocity and area with eyes closed. All 6 parameters were significantly higher in the patients in the acute/subacute stage (<3 mo) than in the control subjects (p < 0.0001). Five parameters, excluding the foam ratio of the area with eyes closed, were still significantly higher in the patients at the chronic stage (>3 mo) than in the control subjects (p < 0.01). Foam posturography is useful for assessing equilibrium even at the chronic stage after acute unilateral peripheral vestibulopathy.


Shotgun wound and pellet embolism to the intracranial carotid artery.
Missile embolism into the cerebral circulation is a very unusual complication of shotgun wounds to the chest or neck. We report a case of an 11-year-old boy who sustained an air gunshot wound and pellet embolism to the intracranial carotid artery. The cerebral artery pellet embolus resulted in contralateral hemiplegia. The patient was successfully treated by emergency flow reversal and embolectomy. Because this injury is extremely rare, the literature is reviewed, and several principles are suggested to improve the management.


VHH characterization.Recombinant VHHs: Production, characterization and affinity.
Among the biological approaches to therapeutics, are the cells, such as CAR-T cells engineered or not, the antibodies armed or not, and the smaller protein scaffolds that can be modified to render them specific of other proteins, à la façon of antibodies. For several years, we explored ways to substitute antibodies by nanobodies (also known as VHHs), the smallest recognizing part of camelids' heavy-chain antibodies: production of those small proteins in host microorganisms, minute analyses, characterization, and qualification of their affinity towards designed targets. Here, we present three standard VHHs described in the literature: anti-albumin, anti-EGF receptor and anti-HER2, a typical cancer cell surface -associated protein. Because they differ slightly in global structure, they are good models to assess our body of analytical methodologies. The VHHs were expressed in several bacteria strains in order to identify and overcome the bottlenecks to obtain homogeneous preparations of this protein. A large panel of biophysical tools, ranging from spectroscopy to mass spectrometry, was here combined to assess VHH structural features and the impact of the disulfide bond. The routes are now ready to move to more complex VHHs raised against specific targets in numerous areas including oncology.


Dengue outbreak and severity prediction: current methods and the future scope.
Dengue virus (DENV) is the causative agent of dengue fever and severe dengue. Every year, millions of people are infected with this virus. There is no vaccine available for this disease. Dengue virus is present in four serologically varying strains, DENV 1, 2, 3, and 4, and each of these serotypes is further classified into various genotypes based on the geographic distribution and genetic variance. Mosquitoes play the role of vectors for this disease. Tropical countries and some temperate parts of the world witness outbreaks of dengue mainly during the monsoon (rainy) seasons. Several algorithms have been developed to predict the occurrence and prognosis of dengue disease. These algorithms are mainly based on epidemiological data, climate factors, and online search patterns in the infected area. Most of these algorithms are based on either machine learning or deep learning techniques. We summarize the different software tools available for predicting the outbreaks of dengue based on the aforementioned factors, briefly outline the methodology used in these algorithms, and provide a comprehensive list of programs available for the same in this article.


Doing a Literature Review in Nursing, Health and Social Care (Second edition) Coughlan Michael and Cronin Patricia Doing a Literature Review in Nursing, Health and Social Care (Second edition) 184pp £19.99 Sage Publishing 9781412962049 1412962048 [Formula: see text].
This book provides a concise and informative guide to the process of literature review in nursing, health and social care, and is applicable to students and professionals.


Combined temozolomide and sunitinib treatment leads to better tumour control but increased vascular resistance in O6-methylguanine methyltransferase-methylated gliomas.
Combined antiangiogenic and cytotoxic treatment represents an appealing treatment approach for malignant glioma. In this study we characterised the antitumoural and microvascular consequences of sunitinib (Su) and temozolomide (TMZ) therapy and verified the ideal treatment protocol, with special focus on a potential therapeutic window for combined scheduling. O(6)-Methylguanine methyltransferase (MGMT) status was analysed by pyrosequencing. Tumour growth of subcutaneous xenografts was assessed under different treatment protocols (TMZ, SU, SU followed by TMZ, TMZ followed by SU, combined TMZ/SU). Intravital microscopy (dorsal skinfold chamber model) assessed microvascular consequences. Immunohistochemistry included tumour and endothelial cell proliferation, apoptosis and vascular pericyte coverage. Real-time polymerase chain reaction (RT-PCR) analysed the expression of angiogenesis-related pathways in response to therapy. Combined TMZ/SU resulted in significantly reduced tumour growth compared to either monotreatment (TMZ: 106 ± 13 mm(3); SU: 114 ± 53 mm(3); TMZ/SU: 34 ± 7 mm(3)) by additional antiangiogenic effects and synergistic induction of apoptosis versus TMZ monotreatment. Sequential treatment protocols did not show additive antitumour responses. TMZ/SU aggravated vascular resistance mechanisms characterised by significantly higher blood flow rate (TMZ: 74 ± 34 μl/s; SU: 164 ± 36 μl/s; TMZ/SU: 254 ± 95 μl/s), reduced permeability (TMZ: 1.05 ± 0.02; SU: 0.99 ± 0.07; TMZ/SU: 0.89 ± 0.05) and recovery of pericyte-endothelial interactions (TMZ: 89 ± 7%; SU: 67 ± 9%, TMZ/SU:80 ± 10%) versus either monotreatment. Vascular resistance was paralleled by an increase in Ang-1 and Tie-2 and by the downregulation of Dll4. Sequential application of TMZ and SU in the angiogenic window does not add antitumour efficacy to monotherapy. Simultaneous application yields beneficial tumour control due to additive antiangiogenic and proapoptotic effects. Combined treatment may aggravate pericyte-mediated vascular resistance mechanisms by altering Ang-1-Tie-2 and Dll4/Notch pathways.


Large cameral coronary artery fistula in a 5 months old infant with unusual presentation and fatal outcome: -case report.
Congenital coronary fistulas (CAFs) are uncommon abnormalities communicating the coronary arteries with the cardiac chambers or portion of the systemic or pulmonary circulation. Over 90% of the cases drain into the right side of the heart with only 3% terminating in the left ventricle. Infants with a large CAFs may develop congestive heart failure. A 5 months old female infant presented with labored breathing and worsening of bluish discoloration of the lips and extremities following a prolonged cry. She had a history of breastfeeding difficulty and noticeable bluish discoloration of the lips and extremities since birth. The infant was wasted and had a fast heart rate, bluish lips, and nail beds with clubbing of fingers and toes. A cardiac murmur was noted during her medical checkup. Chest x-ray showed cardiomegaly. Echocardiography and CT angiography showed large Cameral CAF involving the left main and left anterior descending artery draining into the left ventricle. The tricuspid valve was dysplastic, there was secundum ASD, and VSD with a right to left shunt. The patient developed episode of cyanotic spells after crying excessively following a CT angiographic procedure which culminated in respiratory arrest and her demise. She was managed as a case of hypoxic spells in the ICU before her death. This report unveiled unfamiliar case of Cameral coronary artery fistula with left-to-left shunting, cyanosis, and dysplastic tricuspid valve.


Symptomatic Cholelithiasis: Do Minority Patients Experience Delays to Surgery?
Cholecystectomy is one of the most common surgeries and the majority are performed to treat symptomatic cholelithiasis (SC). While surgery is often elective, poor access or delays in care may lead to urgent cases, which are potentially associated with higher complication rates. This study aims to determine if minority patients with SC have higher rates of urgent cholecystectomy and postoperative complications. Analysis of patients undergoing cholecystectomy for SC utilizing American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) from 2017 to 2019. Primary outcome was acuity of cholecystectomy (i.e., urgent versus elective). Secondary outcomes were any post-operative complication and length of stay. Patients who underwent cholecystectomy for SC between 2017 to 2019 (N: 13,390) were analyzed. Hispanic and non-Hispanic Black patients had higher odds of undergoing urgent surgery as compared to non-Hispanic White patients, and Hispanics had over twice the odds (adjusted odds ratio (aOR), 2.16; 95% CI 1.93-2.43), adjusting for age, sex, and comorbidities. Having urgent surgery was associated with higher odds for developing any postoperative complication and experiencing longer length of stay. After adjusting for urgency of surgery, Non-Hispanic Black and Asian patients were at risk for higher postoperative length of stay. Hispanic and non-Hispanic Black patients were more likely to undergo urgent cholecystectomy as compared to non-Hispanic White patients for SC. Urgent surgery was independently associated with a higher complication rate and longer length of stay. Further characterization of the delays to surgery that lead to these differences are critical to prevent further treatment disparities.


Intentional presence and the accompaniment of dying patients.
In this paper, we offer a phenomenological and hermeneutical perspective on the presence of clinicians who care for the suffering and dying patients in the context of end-of-life care. Clinician presence is described as a way of (1) being present to the patient and to oneself, (2) being in the present moment, and (3) receiving and giving a presence (in the sense of a gift). We discuss how presence is a way of restoring human beings' relational and dialogical nature. To inform a different perspective on relational ethics, we also discuss how accompaniment refers to the clinician's awareness of the human condition and its existential limits.


The effects of the mirror therapy on shoulder function in patients with breast cancer following surgery: a randomized controlled trial.
Shoulder dysfunction is one of the most bothersome questions for breast cancer survivors. Studies show that mirror therapy can improve shoulder function in patients with a limited shoulder range of motion and shoulder pain. Here, this article reports the results of a randomized controlled trial investigating the effects of the mirror therapy on shoulder function in patients with breast cancer following surgical treatments. Totally, 79 participants were divided to two groups receiving active range-of-motion upper limb exercise based on the mirror therapy or active range-of-motion upper limb exercise respectively for 8 weeks. Shoulder range of motion, Constant-Murley Score, Disabilities of Arm, Shoulder, and Hand Questionnaire, Tampa Scale of Kinesiophobia, Visual analog scale, and grip strength were measured at baseline (T0), 2 weeks (T1), 4 weeks (T2), and 8 weeks (T3). The effects of the intervention on shoulder function were analyzed in generalized estimation equation, from group, time, and the interactions between group and time based on the data from participants who completed at least one post-baseline observation RESULTS: At least one post-baseline observation was performed by 69 participants (n=34 mirror group, n=35 control group). 28(82.35%) participants in the mirror group adhered to the exercise compared to 30(85.71%) in the control group. Generalized estimation equation model showed group had main effects on forward flexion (Waldχ²=6.476, P=0.011), with the Cohen's d=0.54. The effects of the group on abduction, Constant-Murley Score, and Disabilities of Arm, Shoulder, and Hand Questionnaire were significant when fix the effects of the time. At 8 weeks, participants in the mirror group showed an improvement in abduction compared to the control group (P=0.005), the Cohen's d was 0.70. At 8 weeks, participants in the mirror group had a higher Constant-Murley Score than control group (P=0.009), with Cohen's effect size value of d=0.64. The mirror group showed a greater improvement on the Disability of Arm, Shoulder, and Hand Questionnaire than control group at 2 weeks, 4 weeks, and 8 weeks (P≤0.032), but with a weak effect size value of all (r≤0.32). Group had main effects on Tampa Scale of Kinesiophobia (Waldχ²=6.631, P=0.010), with the Cohen's effect size value of d=0.56. Mirror therapy improved shoulder flexion, abduction, shoulder function in daily life, and arm function and symptom of the affected shoulder in patients with breast cancer following surgical treatment, while decreasing fear of movement/(re)injury. Mirror configuration needs to be improved in further research to increase its feasibility. Breast cancer survivors can try mirror therapy as a practical and effective method in shoulder rehabilitation for a promotion on effects. ClinicalTrial.gov Identifier: ChiCTR2000033080.


RU486 is not an antiprogestin in the hamster.
The biological activity and progestin receptor binding activity of the synthetic steroid RU486 (RU38486; 17-beta-hydroxy-11-beta-(4-dimethylaminophenyl)-17-alpha-(1-propynl++ +)- estra-4,9-diene-3-one) were investigated in the hamster. RU486 demonstrated no antiprogestational activity in the female hamster in that it was ineffective in blocking decidualization or interrupting early pregnancy. Competitive binding assays showed RU486 did not compete from hamster uterine progestin receptor. It is concluded that hamster uterine progestin receptor has unique steroid binding specificity.


Pseudoaneurysm of atrioventricular groove. A late complication of mitral valve replacement.
This report describes an unusual late complication of mitral valve replacement in which a false aneurysm of the atrioventricular groove produced compression on the circumflex coronary artery and myocardial infarction. The cause of this condition is not well explained, but its potential is present whenever there is early separation of the mitral anulus from the fibrous skeleton of the heart. Early hematoma formation resulting in frank perforation and hemorrhage has been reported, but late pseudoaneurysm formation after initial mitral valve replacement appears to be a rare occurrence.


Integrated miRNA-risk gene-pathway pair network analysis provides prognostic biomarkers for gastric cancer.
This study aimed to identify molecular prognostic biomarkers for gastric cancer. mRNA and miRNA expression profiles of eligible gastric cancer and control samples were downloaded from Gene Expression Omnibus to screen the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRs), using MetaDE and limma packages, respectively. Target genes of the DEmiRs were also collected from both predictive and experimentally validated target databases of miRNAs. The overlapping genes between selected targets and DEGs were identified as risk genes, followed by functional enrichment analysis. Human pathways and their corresponding genes were downloaded from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for the expression analysis of each pathway in gastric cancer samples. Next, co-pathway pairs were selected according to the Pearson correlation coefficients. Finally, the co-pathway pairs, miRNA-target pairs, and risk gene-pathway pairs were merged into a complex interaction network, the most important nodes (miRNAs/target genes/co-pathway pairs) of which were selected by calculating their degrees. Totally, 1,260 DEGs and 144 DEmiRs were identified. There were 336 risk genes found in the 9,572 miRNA-target pairs. Judging from the pathway expression files, 45 co-pathway pairs were screened out. There were 1,389 interactive pairs and 480 nodes in the integrated network. Among all nodes in the network, focal adhesion/extracellular matrix-receptor interaction pathways, CALM2, miR-19b, and miR-181b were the hub nodes with higher degrees. CALM2, hsa-miR-19b, and hsa-miR-181b might be used as potential prognostic targets for gastric cancer.


CDX2 inhibits epithelial-mesenchymal transition in colorectal cancer by modulation of Snail expression and β-catenin stabilisation via transactivation of PTEN expression.
Emerging evidence suggests the involvement of caudal-related homoeobox transcription factor 2 (CDX2) in tumorigenesis of various cancers. Although CDX2 functions in cancer invasion and metastasis, fewer studies focus on the role of CDX2 during the induction of epithelial-mesenchymal transition (EMT) in colorectal cancer (CRC). Immunohistochemical analysis of CDX2 was performed. A series of in vitro and in vivo experiments were conducted to reveal the role of CDX2 in the invasion and metastasis of CRC. CDX2 was downregulated in CRC tissues and reduced CDX2 correlated with poor prognosis. Knockdown of CDX2 promoted colon cancer cell invasion in vitro and facilitated liver metastasis in vivo with inducing EMT phenotypes. Further investigation indicated that CDX2 retarded Akt and GSK-3β phosphorylation, and thereby diminished Snail expression, β-catenin stabilisation and nuclear translocation. The depletion of β-catenin neutralised the regulation of Slug and ZEB1 by CDX2 knockdown. Mechanistically, CDX2 antagonised PI3K/Akt activity in CRC by modulating PTEN expression. CDX2 directly bound to the promoter of PTEN and transactivated its expression. Our study first uncovered that CDX2 inhibits EMT and metastasis of CRC by regulation of Snail expression and β-catenin stabilisation via transactivation of PTEN expression.


Clinical seizure semiology is subtle and identification of seizures by parents is unreliable in infants with tuberous sclerosis complex.
The objectives of this study were to assess the accuracy of parental seizure detection in infants with antenatally diagnosed tuberous sclerosis complex (TSC), and to document the total seizure burden (clinical and subclinical) in those patients who met criteria for prolonged electroencephalography (EEG) recording. Consecutive infants at a single institution with antenatally diagnosed TSC who met criteria for prolonged video-EEG (vEEG) were recruited to this study. The vEEG data were reviewed and when a seizure was identified on EEG, the video and audio recording was assessed for evidence of clinical seizure and, if present, whether there was evidence of parent seizure identification. Nine infants were enrolled, for whom 674 focal seizures were identified in eight of nine patients across 24 prolonged vEEG recordings, with vEEG total duration of 634 h 49 min (average seizure frequency of 1 focal seizure/h). Only 220 of 674 (32.6%) were clinical seizures, 395 of 674 (58.6%) were subclinical seizures, and 59 of 674 seizures could not be classified. Only 63 of 220 clinical seizures (28.6%) were identified by parents, with 157 of 220 (71.4%) not identified. Thirty clusters of epileptic spasms were detected in one patient. At least one clinical epileptic spasm occurred in 2 of 30 clusters (6.7%), 24 of 30 clusters of epileptic spasms (80%) were electrographic only, and classification was uncertain for 4 of 30 clusters (13.3%). No clinical epileptic spasms were detected by parents. Clinical seizure frequency was significantly underestimated by parents for all patients. This study demonstrates that in infants with TSC who met criteria for prolonged vEEG, (1) parents significantly under recognize total clinical seizure count, (2) parents fail to identify epileptic spasms, and (3) seizure frequency is high. This highlights that epilepsy treatment decisions should not be based solely on parental clinical seizure identification. Prolonged vEEG monitoring may have an important role in the routine epilepsy care of infants with TSC, as demonstrating undetected high clinical seizure frequency may allow improved epilepsy management decisions.


Echo-enhanced duplex sonography of extracranial vertebral arteries.
We sought to investigate the potential benefit in examining extracranial vertebral arteries (ExVA) with an echo contrast agent. A total of 26 patients with insufficiently assessable ExVA underwent extracranial duplex sonography without and with an echo contrast medium. All examinations were recorded and analysed independently by two experienced sonographers. Interrater agreement was fair in assessment of B-mode quality, colour-coding, blooming artefacts, change of vmax, good to very good in all other rated categories. Using an echo contrast medium reduced overall inassessable ExVA by 48% and 36% according to the two raters, respectively. After contrast enhancement, diagnosis was clarified in ExVA formerly inassessable for hypoplasia in 60% vs. 56%, extracranial occlusion in 67% vs. 56% and resistance signal in 63% vs. 45%, respectively. Application of an echo contrast agent leads to clarification of ExVA sonographic diagnosis in approximately one third of poorly examinable patients (35% and 30%, respectively), and contributes in ruling out extracranial occlusion, hypoplasia and resistance signal.


Solubility of cobalt in cement.
Unlike chromate, cobalt occurring as cobalt oxides in cement is not water-soluble in a detectable amount. Cobalt oxides are to some extent soluble in the presence of amino acids with which cobalt forms complexes. Such complexes can elicit patch test reactions. It is postulated that cobalt is more readily dissolved by forming complexes in eczematous skin than in normal skin. This may explain why cobalt sensitization in cement eczemas is secondary to chromate sensitivity.


Non-protein-bound iron and 4-hydroxynonenal protein adducts in classic autism.
A link between oxidative stress and autism spectrum disorders (ASDs) remains controversial with opposing views on its role in the pathogenesis of the disease. We investigated for the first time the levels of non-protein-bound iron (NPBI), a pro-oxidant factor, and 4-hydroxynonenal protein adducts (4-HNE PAs), as a marker of lipid peroxidation-induced protein damage, in classic autism. Patients with classic autism (n=20, mean age 12.0±6.2years) and healthy controls (n=18, mean age 11.7±6.5years) were examined. Intraerythrocyte and plasma NPBI were measured by high performance liquid chromatography (HPLC), and 4-HNE PAs in erythrocyte membranes and plasma were detected by Western blotting. The antioxidant defences were evaluated as erythrocyte glutathione (GSH) levels using a spectrophotometric assay. Intraerythrocyte and plasma NPBI levels were significantly increased (1.98- and 3.56-folds) in autistic patients, as compared to controls (p=0.0019 and p<0.0001, respectively); likewise, 4-HNE PAs were significantly higher in erythrocyte membranes and in plasma (1.58- and 1.6-folds, respectively) from autistic patients than controls (p=0.0043 and p=0.0001, respectively). Erythrocyte GSH was slightly decreased (-10.34%) in patients compared to controls (p=0.0215). Our findings indicate an impairment of the redox status in classic autism patients, with a consequent imbalance between oxidative stress and antioxidant defences. Increased levels of NPBI could contribute to lipid peroxidation and, consequently, to increased plasma and erythrocyte membranes 4-HNE PAs thus amplifying the oxidative damage, potentially contributing to the autistic phenotype.


Endovascular treatment beyond 24 hours from the onset of acute ischemic stroke: the Italian Registry of Endovascular Thrombectomy in Acute Stroke (IRETAS).
Clinical trials and observational studies have demonstrated the benefit of thrombectomy up to 16 or 24 hours after the patient was last known to be well. This study aimed to evaluate the outcome of stroke patients treated beyond 24 hours from onset. We analyzed the outcome of 34 stroke patients (mean age 70.7±12.3 years; median National Institutes of Health Stroke Scale (NIHSS) score 13) treated with endovascular thrombectomy beyond 24 hours from onset who were recruited in the Italian Registry of Endovascular Thrombectomy in Acute Stroke. Selection criteria for patients were: pre-stroke modified Rankin scale (mRS) score of ≤2, non-contrast CT Alberta Stroke Program Early CT score of ≥6, good collaterals on single phase CT angiography (CTA) or multiphase CTA, and CT perfusion mismatch with an infarct core size ≤50% of the total hypoperfusion extent or involving less than one-third of the extent of the middle cerebral artery territory evaluated by visual inspection. The primary outcome measure was functional independence assessed by the mRS at 90 days after onset. Safety outcomes were 90 day mortality and the occurrence of symptomatic intracranial hemorrhage (sICH). Successful recanalization (Thrombolysis in Cerebral Infarction score of 2b or 3) was present in 76.5% of patients. Three month functional independence (mRS score 0-2) was observed in 41.1% of patients. The case fatality rate was 26.5%. and the incidence of sICH was 8.8%. These findings suggest that, in a real world setting, very late endovascular therapy is feasible in appropriately selected patients.


Classification of Nebbiolo-based wines from Piedmont (Italy) by means of solid-phase microextraction-gas chromatography-mass spectrometry of volatile compounds.
Sixty-eight samples of wines from Piedmont (Italy) were analysed to determine their content of volatile compounds, using the solid-phase microextraction (SPME) technique coupled with gas chromatography-mass spectrometry (GC-MS). Samples were from five groups of wines: Barolo, Barbaresco, Nebbiolo d'Alba, Roero and Langhe Nebbiolo, all produced from the Nebbiolo grape in the Langhe and Roero areas (province of Cuneo, Piedmont) but differing in vintage (respectively, 3 years, 2 years, 1 year, 8 months and few months) and production zone. Thirty-five analytes were identified; peak area data, corrected for internal standard, were used for pattern recognition treatments. Principal components analysis, hierarchical cluster analysis, Kohonen self organising map, stepwise linear discriminant analysis and soft independent modelling of class analogy were applied to the data, revealing a good separation between the five groups. A main factor, strictly connected to wine vintage, was identified and found to be related to some analytes.


Thin film composite nanofiltration membranes fabricated from quaternized poly(ether ether ketone) with crosslinkable moiety using a benign solvent.
Thin film composite nanofiltration membranes were fabricated through dip-coating and in situ cross-linking of quaternized poly(ether ether ketone) containing a certain amount of tertiary amine groups (QAPEEKs) on polyacrylonitrile (PAN) support. The effects of the variables in membrane formation such as the coating polymer concentration, the curing temperature, and the cross-linking agent types on resultant membrane were studied and the membrane properties such as the barrier layer chemical structure, the surface element composition and morphology were investigated. The obtained performance of uncross-linked and cross-linked QAPEEK-70 thin film composites in nanofiltration test was compared. The results indicated that the cross-linking improved the composite membranes' performance. For instance, the membrane cross-linked by bisphenol A diglycidyl ether (BPADGE) named M-C-BPADGE exhibited a MgCl2 rejection of 97.8%, a water flux of 11.8Lm(-2)h(-1), a MWCO of 800Da and corresponding pore size of 0.69nm, while for its uncross-linked membrane named M-U, a MgCl2 rejection of 91.2%, a water flux of 13.5Lm(-2)h(-1), a MWCO with 960Da and a pore size of 0.77nm were found. Furthermore, the M-C-BPADGE membrane exhibited selectivities of 16.0 for separation of mixed Mg(2+) and Na(+) cations, much larger than selectivity of 5.2 obtained for M-U, suggesting that the cross-linked membranes are promising in cation separation.


Intravascular ultrasound for endovascular precision in pediatrics.
Intravascular ultrasound (IVUS) is used as a diagnostic adjunct to angiography and has become a valuable diagnostic and interventional tool with a well-documented safety profile. The American College of Cardiology and the European Society of Cardiology have published guidelines regarding the use of IVUS in the setting of percutaneous coronary intervention. IVUS has gained popularity in the interventional radiology (IR) community in recent years; however, there are no consensus guidelines for utilization. Furthermore, IVUS remains an infrequently used modality in pediatric IR, likely because of unfamiliarity with the equipment and techniques, as well as concerns over the compatibility of these instruments with pediatric anatomy. IVUS can be safely used as a helpful and sometimes necessary tool for pediatric interventions in appropriately selected patients. The utility of IVUS for reducing both fluoroscopy time and contrast agent volume makes it particularly valuable in pediatric practice. This article presents an overview of both the rotational and phased-array IVUS types and an in-depth discussion on the most common applications of these techniques in the pediatric setting across multiple procedure categories.


Biosynthesis, structural characterization and antimicrobial activity of gold and silver nanoparticles.
An eco friendly simple biosynthetic route was used for the preparation of monodisperse and highly crystalline gold and silver nanoparticles using cell free extract of fungus, Candida albicans. Transmission electron microscopic studies show the formation of gold and silver nanocrystals of average size of 5 nm and 30 nm with the specific surface areas of 18.9 m(2)/g and 184.4 m(2)/g respectively. The interaction of gold and silver nanoparticles with proteins has been formulated by FT-IR spectroscopy and thermal gravimetric analysis. The formation of gold and silver nanoparticles was also confirmed by the appearance of a surface plasmon band at 540 nm and 450 nm respectively. The antimicrobial activity of the synthesized gold and silver nanoparticles was investigated against both Staphylococcus aureus and Escherichia coli. The results suggest that these nanoparticles can be used as effective growth inhibitors against the test microorganisms. Greater bactericidal activity was observed for silver nanoparticles. The E. coli, a gram negative bacterium was found to be more susceptible to gold and silver nanoparticles than the S. aureus, a gram positive bacterium.


Atypical cervical spondylotic myelopathy mimicking intramedullary tumor.
Case report and a review of the literature. We report the case of a young man with a short course of progressive cervical myelopathy (CM). Cervical magnetic resonance imaging (MRI) revealed a stenosis of the cervical spinal canal at C4-C6 and an atypically enlarged intramedullary high intensity extending from C1-T1 (T2-weighted) with contrast enhancement at C4-C5 (T1-weighted). Neurologic and radiologic diagnosis therefore favored a tumor of the spinal cord. CM is a clinical diagnosis of mostly degenerative origin in older patients that features circumscribed high-intensity signals near the point of compression in T2-weighted MRI. Contrast enhancement in those high-intense areas is rarely described in the literature, and the differentiation from neoplastic and infective lesions might be very difficult in these cases. Retrospective case study with follow-up examination and MRI-control 3 months after surgery. The patient was decompressed and stabilized from dorsally, and a biopsy was taken. The exact diagnosis of a myelopathy and an exclusion of a neoplastic origin succeeded through histopathological examination. Three months after first surgery, the patient had improved significantly and underwent an additional anterior stabilization, while the MRI remained almost unchanged. In case of a fast progressive CM with atypical radiographic appearance initial decompression with inspection of the spinal cord and a short-term clinical follow-up with an MRI control might be the procedure of choice, if a clear diagnosis for a causative treatment cannot be made. In still suspicious cases, a biopsy could be considered to exclude a neoplastic or inflammatory process.


Efficient synthesis of C-terminal modified peptide ketones for chemical ligations.
Synthesis of a C-terminal modified peptide with an alpha-amido methylketone was efficiently carried out using a backbone-amide-type linker loading with a monofunctionalized diamine, provided that no base such as piperidine or diisopropylethylamine or a reducing agent such as triisopopylsilane was used for the synthetic pathway. The ketoxime-forming chemoselective ligation between a methylketone and an aminooxy was quantitative in 5h at pH 2.