Naringenin Prevents Oxidative Stress and Inflammation in LPS-Induced Liver Injury through the Regulation of LncRNA-mRNA in Male Mice.
Inflammation accompanies hepatic dysfunction resulting from tissue oxidative damage. Naringenin (Nar), a natural flavanone, has known antioxidant and anti-inflammatory activities, but its mechanism of action in the regulation of liver dysfunction requires further investigation. In this study, the role of naringenin in lipopolysaccharide (LPS)-induced hepatic oxidative stress and inflammation was explored, as well as its mechanism by transcriptome sequencing. The results indicated that compared with the LPS group, Nar treatment caused a significant increase in the mRNA levels of antioxidant factors glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM), yet the expression of related inflammatory factors (MCP1, TNFα, IL-1β and IL-6) showed less of an increase. RNA sequencing identified 36 differentially expressed lncRNAs and 603 differentially expressed mRNAs. KEGG enrichment analysis indicated that oxidative stress and inflammation pathways are meticulously linked with naringenin treatment. The Co-lncRNA-mRNA network was also constructed. Tissue expression profiles showed that lncRNA played a higher role in the liver. Subsequently, expression levels of inflammatory factors indicated that lncRNAs and target mRNAs were significantly reduced after naringenin treatment in mouse liver AML12 cells and obese mouse. These results suggest that naringenin helps to prevent liver dysfunction through the regulation of lncRNA-mRNA axis to reduce oxidative stress and inflammatory factors.


HMPAO SPECT in Parkinson's disease (PD) with major depression (MD) before and after antidepressant treatment.
Previously we suggested that major depression (MD) in Parkinson's disease (PD) could be an indication of a more advanced and widespread neurodegenerative process, as PD symptoms were more severe in those with depression. We also found a different antidepressant response with SSRI medication in PD patients with depression compared to depressed patients without PD. This indicates diverse underlying pathophysiological mechanisms. Investigations using single-photon emission computed tomography (SPECT), measuring regional cerebral blood flow (rCBF), may contribute to enlighten the neurobiological substrates linked to depressive symptoms. SPECT was performed in order to compare rCBF in MD patients with and without PD. The study included 11 MD patients with PD, 14 non-depressed PD patients and 12 MD patients without PD. All patients were followed for 12 weeks with repeated evaluation of depressive as well as PD symptoms. Anti-Parkinsonian treatment remained unchanged during the study. Antidepressant treatment with SSRI (citalopram) was given to all patients with MD. SPECT was performed before and after 12 weeks of antidepressant treatment. rCBF was found to differ between PD patients with and without MD, as well as between MD patients with and without PD, both at baseline and concerning the response to treatment with SSRI (citalopram). In patients with PD the rCBF was found to be decreased in preoccipital and occipital regions, a finding more common when PD was combined with MD. In summary, larger cortical areas were found to be involved in depressed PD patients, both with hyperactivity (reciprocal to basal degeneration in PD and maybe dopaminergic treatment) and with hypoactivity (probably due to organic lesions leading to hypoperfusion). These observations support our hypothesis that PD combined with MD is an expression of a more advanced and widespread neurodegenerative disorder.


Isolation and characterization of a bovine cDNA encoding a functional homolog of human P-selectin.
A cDNA encoding a homologue of human P-selectin has been isolated from a bovine capillary endothelial cDNA library. The 2.7 kb cDNA encodes a 646 amino acid polypeptide with 77% identity to the human P-selectin except that it lacks three of the consensus repeat domains found in human P-selectin. Human P-selectin, expressed in platelets and endothelium, is a Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. To determine if bovine P-selectin exhibits a similar binding activity, its cDNA was expressed in COS cells and the ability of the transfectants to bind HL-60 human myelogenous leukemia cells was examined. The bovine P-selectin bound the myeloid cells in a manner similar to human P-selectin, indicating that the altered domain structure of bovine P-selectin does not affect P-selectin function in this in vitro cell adhesion assay.


The use of text-matching software's similarity scores.
Popular text-matching software generates a percentage of similarity - called a "similarity score" or "Similarity Index" - that quantifies the matching text between a particular manuscript and content in the software's archives, on the Internet and in electronic databases. Many evaluators rely on these simple figures as a proxy for plagiarism and thus avoid the burdensome task of inspecting the longer, detailed Similarity Reports. Yet similarity scores, though alluringly straightforward, are never enough to judge the presence (or absence) of plagiarism. Ideally, evaluators should always examine the Similarity Reports. Given the persistent use of simplistic similarity score thresholds at some academic journals and educational institutions, however, and the time that can be saved by relying on the scores, a method is arguably needed that encourages examining the Similarity Reports but still also allows evaluators to rely on the scores in some instances. This article proposes a four-band method to accomplish this. Used together, the bands oblige evaluators to acknowledge the risk of relying on the similarity scores yet still allow them to ultimately determine whether they wish to accept that risk. The bands - for most rigor, high rigor, moderate rigor and less rigor - should be tailored to an evaluator's particular needs.


Genome-wide identification, evolution and expression analysis of mTERF gene family in maize.
Plant mitochondrial transcription termination factor (mTERF) genes comprise a large family with important roles in regulating organelle gene expression. In this study, a comprehensive database search yielded 31 potential mTERF genes in maize (Zea mays L.) and most of them were targeted to mitochondria or chloroplasts. Maize mTERF were divided into nine main groups based on phylogenetic analysis, and group IX represented the mitochondria and species-specific clade that diverged from other groups. Tandem and segmental duplication both contributed to the expansion of the mTERF gene family in the maize genome. Comprehensive expression analysis of these genes, using microarray data and RNA-seq data, revealed that these genes exhibit a variety of expression patterns. Environmental stimulus experiments revealed differential up or down-regulation expression of maize mTERF genes in seedlings exposed to light/dark, salts and plant hormones, respectively, suggesting various important roles of maize mTERF genes in light acclimation and stress-related responses. These results will be useful for elucidating the roles of mTERF genes in the growth, development and stress response of maize.


Health Research in the Wake of Disasters: Challenges and Opportunities for Sensor Science.
Disaster events adversely affect the health of millions of individuals each year. They create exposure to physical, chemical, biological, and psychosocial hazards while simultaneously exploiting community and individual-level vulnerabilities that allow such exposures to exert harm. Since 2013, the National Institute of Environmental Health Sciences (NIEHS) has led the development of the Disaster Research Response (DR2) program and infrastructure; however, research exploring the nature and effects of disasters on human health is lacking. One reason for this research gap is the challenge of developing and deploying cost-effective sensors for exposure assessment during disaster events. The objective of this commentary is to synergize the consensus findings and recommendations from a panel of experts on sensor science in support of DR2. The NIEHS convened the workshop, "Getting Smart about Sensors for Disaster Response Research" on 28 and 29 July 2021 to discuss current gaps and recommendations for moving the field forward. The workshop invited full discussion from multiple viewpoints, with the goal of identifying recommendations and opportunities for further development of this area of research. The panel of experts included leaders in engineering, epidemiology, social and physical sciences, and community engagement, many of whom had firsthand experience with DR2. The primary finding of this workshop is that exposure science in support of DR2 is severely lacking. We highlight unique barriers to DR2, such as the need for time-sensitive exposure data, the chaos and logistical challenges that ensue from a disaster event, and the lack of a robust market for sensor technologies in support of environmental health science. We highlight a need for sensor technologies that are more scalable, reliable, and versatile than those currently available to the research community. We also recommend that the environmental health community renew efforts in support of DR2 facilitation, collaboration, and preparedness. https://doi.org/10.1289/EHP12270.


Clinical Prediction Rules to Classify Types of Stroke at Prehospital Stage.
Background and Purpose- Endovascular therapy is effective against acute cerebral large vessel occlusion (LVO). However, many patients do not receive such interventions because of the lack of timely identification of the type of stroke. If the types of stroke (any stroke, LVO, intracranial hemorrhage [ICH], and subarachnoid hemorrhage [SAH]) were to be predicted at the prehospital stage, better access to appropriate interventions would be possible. Japan Urgent Stroke Triage (JUST) score was clinical prediction rule to classify suspected patients of acute stroke into different types at the prehospital stage. Methods- We obtained information for signs and symptoms and medical history of consecutive suspected patients of acute stroke at prehospital stage from paramedics and final diagnosis from the receiving hospital. We constructed derivation cohort in the historical multicenter cohort study from June 2015 to March 2016 and validation cohort in the prospective multicenter cohort study from August 2016 to July 2017. The derivation and the validation cohorts included 1229 and 1007 patients, respectively. We constructed multivariate logistic regression models with 21 variables to develop clinical prediction rules, which distinguish between different types of stroke: any stroke, LVO, ICH, and SAH. Results- Among the 1229 patients (median age, 72 years; 55% men) in the derivation cohort, 533 stroke, 104 LVO, 169 ICH, and 57 SAH cases were observed. The developed rules showed that the areas under the receiver operating curves were 0.88 for any stroke, 0.92 for LVO, 0.84 for ICH, and 0.89 for SAH. The validation cohort of 1007 patients (median age, 75 years; 56% men) showed that the areas under the curves of any stroke, LVO, ICH, and SAH were 0.80, 0.85, 0.77, and 0.94, respectively. Conclusions- These clinical prediction rules can help paramedics classify the suspected patients of stroke into any stroke, LVO, ICH, and SAH groups with excellent accuracy.


Antisense transcription in Pseudomonas aeruginosa.
A large number of antisense transcripts have been detected in diverse microbial genomes and considerable effort has been devoted to elucidating the functional role of antisense transcription. In this study, we reanalysed extensive RNA sequencing data from the opportunistic pathogen Pseudomonas aeruginosa and found that the majority of genes have a propensity for antisense transcription. Although antisense transcripts were found in more than 80 % of the genes of the P. aeruginosa genome, the majority of sequencing reads were mapping sense and only a minority (<2 %) were mapping antisense to genes. Similarly to the sense expression levels, the antisense expression levels varied under different environmental conditions, with the sense and antisense expression levels often being inversely regulated and modulated by the activity of alternative sigma factors. Environment-modulated antisense transcription showed a bias towards being antisense to genes within regions of genomic plasticity and to those encoding small regulatory RNAs. In the future, the validation and functional characterization of antisense transcripts, and novel transcripts that are antisense to small regulatory RNAs in particular, have the potential to contribute to our understanding of the various levels of transcriptional regulation and its dynamics in the bacterial pathogen P. aeruginosa.


Radiation exposure and thyroid cancer.
There are abundant experimental and clinical data to associate radiation exposure and thyroid cancer. The incidence of thyroid cancer increases with increasing doses of thyroidal radiation from 6.5 rads to 1,500 rads, but higher doses tend to destroy the gland and are associated with hypothyroidism rather than cancer. The peak occurrence of thyroid tumors is between five and 30 years after exposure, but a person may develop thyroid tumors as long as 50 years after irradiation. Multiple thyroidal lesions or disorders, including adenomas, thyroditis, and hypothyroidism as well as malignant neoplasms, can occur after radiation exposure. It is imperative, therefore, to study carefully all patients with a history of radiation exposure to the gland and to observe them carefully for life. Suggestions are made for the management of thyroid disease in these patients.


Assessment of metals in down feathers of female common eiders and their eggs from the Aleutians: arsenic, cadmium, chromium, lead, manganese, mercury, and selenium.
Concentrations of arsenic, cadmium, chromium, lead, manganese, mercury and selenium were examined in the down feathers and eggs of female common eiders (Somateria mollissima) from Amchitka and Kiska Islands in the Aleutian Chain of Alaska to determine whether there were (1) differences between levels in feathers and eggs, (2) differences between the two islands, (3) positive correlations between metal levels in females and their eggs, and (4) whether there was more variation within or among clutches. Mean levels in eggs (dry weight) were as follows: arsenic (769 ppb, ng/g), cadmium (1.49 ppb), chromium (414 ppb), lead (306 ppb), manganese (1,470 ppb), mercury (431 ppb) and selenium (1,730 ppb). Levels of arsenic were higher in eggs, while chromium, lead, manganese, and mercury were higher in feathers; there were no differences for selenium. There were no significant interisland differences in female feather levels, except for manganese (eider feathers from Amchitka were four times higher than feathers from Kiska). Levels of manganese in eggs were also higher from Amchitka than Kiska, and eider eggs from Kiska had significantly higher levels of arsenic, but lower levels of selenium. There were no significant correlations between the levels of any metals in down feathers of females and in their eggs. The levels of mercury in eggs were below ecological benchmark levels, and were below human health risk levels. However, Aleuts can seasonally consume several meals of bird eggs a week, suggesting cause for concern for sensitive (pregnant) women.


Effect of passage and topography on gene expression of temporomandibular joint disc cells.
The temporomandibular joint (TMJ) disc is maintained by a population of fibrochondrocytes. Although articular chondrocytes exhibit zonal differences and de-differentiate in monolayer culture, such variations are unknown for fibrochondrocytic populations. This study's objective was to define topographical cellular variations in the porcine TMJ disc and investigate changes in the disc's gene expression levels over multiple passages using quantitative reverse transcriptase polymerase chain reaction. For topographical characterization, samples were acquired from posterior, anterior, lateral, medial, and intermediate zone sections and subdivided into inferior and superior halves. For passage characterization, cells were plated and passaged for 35 days, with samples acquired at every passage. The medial region had the lowest expression of genes indicative of fibroblastic activity, but in general, topographical variations were limited. Passage effects were evident; gene expression levels of aggrecan, collagen type I, and collagen type II dropped 20%, 23%, and 73% per passage, respectively. In contrast, decorin and glyseraldehyde-3-phosphate dehydrogenase gene expression increased 33% and 27% per passage, respectively. These data indicate that TMJ disc cells undergo significant changes due to monolayer expansion, experiencing losses in major chondrocytic markers (aggrecan and collagen type II) and fibroblastic markers (collagen type I) and posing a serious impediment to studies in which cell passaging is required.


Preservation of the carrier envelope phase during cross-polarized wave generation.
The preservation of carrier envelope phase (CEP) during Cross-Polarized Wave Generation (XPWG) is demonstrated through two independent experiments based on the spatially and spectrally resolved interference fringes formed by the XPW beam and its fundamental. In a first measurement, we found that the vertical fringe position on the spatial detector was maintained over many consecutive laser shots, implying practically no change in relative CEP between the XPW and the fundamental. In a second experiment, we measured the change in relative CEP between the XPW and fundamental beam by systematically varying the amount of material dispersion inside the XPW arm of the interferometer. The recorded rate of relative phase change was in excellent agreement with the theoretical value.


Clinical considerations in the use of time-compressed speech.
The four lists of the Auditec of St. Louis recording of the 60% time-compressed NU 6 test were presented at 32 dB SL to 28 normal subjects and 28 subjects with sensorineural hearing loss. Significant list effects were found, with only lists I and IV being equivalent for both groups. A significant learning effect, greater for the normal subjects, also was present. Clinical recommendations are made regarding list and practice effects and considerations for use of this test in the presence of peripheral hearing impairment.


Endothelin in brain: receptors, mitogenesis, and biosynthesis in glial cells.
We have explored the cellular loci of endothelin (ET) actions and formation in the brain, using cerebellar mutant mice as well as primary and continuous cell cultures. A glial role is favored by several observations: (i) mutant mice lacking neuronal Purkinje cells display normal ET receptor binding and enhanced stimulation by ET of inositolphospholipid turnover; (ii) in weaver mice lacking neuronal granule cells, ET stimulation of inositolphospholipid turnover is not significantly diminished; (iii) C6 glioma cells and primary cultures of cerebellar astroglia exhibit substantial ET receptor binding and ET-induced stimulation of inositolphospholipid turnover; (iv) ET promotes mitogenesis of C6 glioma cells and primary cerebellar astroglia; and (v) primary cultures of cerebellar astroglia contain ET mRNA. ET also appears to have a neuronal role, since it stimulates inositolphospholipid turnover in primary cultures of cerebellar granule cells, and ET binding declines in granule cell-deficient mice. Thus, ET can be produced by glia and act upon both glia and neurons in a paracrine fashion.


Molecular evolution and population genetics of circadian clock genes.
This article discusses a number of common methodologies used in the field of population genetics and evolution and reviews their application within circadian rhythm research. We examine the basic principles behind phylogenetic analysis and how these can be used to illuminate clock gene evolution. We then discuss genetic variation between and within species and show how neutrality tests can reveal the signatures of selection or drift on clock genes. These tests are particularly important for moving beyond "just so" stories when discussing the evolution of clock phenotypes, and we provide relevant circadian examples. We also focus on methods that can be used to study genetic variation, such as quantitative trait loci analysis. We discuss the various bootstrapping or resampling techniques that can be applied to generate confidence intervals in the various methodologies and then examine the use of interspecific transformation studies, which can, and have, provide some useful insights, not only into clock gene evolution in particular, but "behavioral" gene evolution in general. Finally, we assess gene/protein alignments and protein structure predictions and their implicit evolutionary bases.


VDR and SRD5A2 polymorphisms combine to increase risk for prostate cancer in both non-Hispanic White and Hispanic White men.
Vitamin D and dihydrotestosterone pathways interact to promote the growth of prostatic tissue. The nuclear vitamin D receptor (VDR) moderates the actions of vitamin D. 5alpha-Reductase type II (SRD5A2) codes for the enzyme that converts testosterone to dihydrotestosterone in the prostate. This study tested the interactions of VDR (CDX2, FokI) and SRD5A2 (V89L, A49T) polymorphisms, and their associations with prostate cancer. This genetic association study included 932 non-Hispanic White (NHW) men and 414 Hispanic White (HW) men from South Texas. Cases had biopsy-confirmed cancer; controls had normal digital rectal exams and serum prostate-specific antigen levels of <2.5 ng/mL. Using logistic regression analyses to test associations with prostate cancer, only the V89L polymorphism (VV genotype compared with LL/LV) in HW men was statistically significant [odds ratios (OR), 0.64; 95% confidence intervals (95% CI), 0.41-0.99]. The interaction terms for FokI and V89L in NHW men and CDX2 and V89L in HW men in the logistic model were significant (P = 0.02 and 0.03, respectively). When stratified by V89L genotype, the FokI polymorphism (TT/TC versus CC) was significantly associated with prostate cancer in NHW men with the V89L VV genotype (FokI OR, 1.53; 95% CI, 1.06-2.23). The CDX2 polymorphism (GG versus AG/AA) was significantly associated with prostate cancer only in HW men with the V89L VV genotype (CDX2 OR, 3.16; 95% CI, 1.39-7.19; interaction term P = 0.02). Our results indicate that the SRD5A2 V89L VV genotype interacts with VDR FokI TT/CT genotypes in NHW men and VDR CDX2 GG genotypes in HW men to increase the risk for prostate cancer.


Recent approaches in designing bioadhesive materials inspired by mussel adhesive protein.
Marine mussels secret protein-based adhesives, which enable them to anchor to various surfaces in a saline, intertidal zone. Mussel foot proteins (Mfps) contain a large abundance of a unique, catecholic amino acid, Dopa, in their protein sequences. Catechol offers robust and durable adhesion to various substrate surfaces and contributes to the curing of the adhesive plaques. In this article, we review the unique features and the key functionalities of Mfps, catechol chemistry, and strategies for preparing catechol-functionalized polymers. Specifically, we reviewed recent findings on the contributions of various features of Mfps on interfacial binding, which include coacervate formation, surface drying properties, control of the oxidation state of catechol, among other features. We also summarized recent developments in designing advanced biomimetic materials including coacervate-forming adhesives, mechanically improved nano- and micro-composite adhesive hydrogels, as well as smart and self-healing materials. Finally, we review the applications of catechol-functionalized materials for the use as biomedical adhesives, therapeutic applications, and antifouling coatings. © 2016 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 9-33.


Profile of the West German health care system.
The health care system of the Federal Republic of Germany is characterized by comprehensive statutory insurance coverage, regulated fees for physicians' and hospitals' services, and strict separation between hospital care and ambulatory care provided by office-based physicians. This separation results in excessively long hospital length-of-stay, complicated by a non-uniform financing system of setting hospital rates on the basis of retrospective costs. While equal access to care is guaranteed under the health insurance scheme, reform proposals advocate modifying the system in the direction of increased competition.


Astrocyte activation and dysfunction and neuron death by HIV-1 Tat expression in astrocytes.
Human immunodeficiency virus type 1 (HIV-1) Tat protein plays an important role in HIV-associated neuropathogenesis. Astrocytosis and neuron death are two hallmarks of HIV-1 infection of the central nervous system (CNS). However, whether there is a direct link between Tat expression, astrocytosis and subsequent neuron death is not known. In this study, we expressed Tat in astrocytes and examined Tat effects on astrocyte function and subsequent neuronal survival. The results showed that Tat expression resulted in a significant increase in glial fibrillary acidic protein (GFAP) expression, a cellular marker of astrocyte activation or astrocytosis. The GFAP promoter-driven reporter gene assay showed that Tat transactivated GFAP expression at the transcriptional level. Furthermore, Tat expression markedly impaired glutamate uptake by astrocytes. Importantly, cell culture supernatants from Tat-expressing astrocytes induced dramatic neuron death. Taken together, these data provide evidence for the first time to directly link Tat expression in astrocytes to astrocytosis, astrocyte dysfunction, and subsequent neuron death. In addition, these data suggest that astrocyte dysfunction contributes, at least in part, to Tat neurotoxicity and subsequently HIV-associated neuropathogenesis.


Simulation TRaining for Operative vaginal Birth Evaluation: study protocol for an observational stepped-wedge interrupted time-series study (STROBE).
Operative vaginal birth is a common procedure used to expedite birth after full cervical dilatation where there is a clinical need to do so (15% of births in the UK in 2016). The acquisition of skills for operative vaginal birth is dependent on the exposure of junior obstetricians to situations in which they can undertake directly supervised learning from senior accouchers. The Royal College of Obstetricians and Gynaecologists has recently introduced the first structured course in operative vaginal birth. To date, there have been no attempts to determine the clinical impact of a structured training package for operative vaginal birth. The STROBE study is a quasi-experimental before-after interrupted time-series study of the effect of simulation training in operative vaginal birth for obstetricians on clinical outcomes of women and babies following operative vaginal birth. Similar to a stepped-wedge design, the intervention will be gradually implemented in all participating units but at different time periods. The primary outcome is failed operative vaginal birth with the first intended instrument. Secondary maternal outcomes are; use of second instrument to achieve operative vaginal birth, caesarean section, episiotomy, perineal trauma (1st, 2nd, 3rd, 4th degree tear), cervical tear requiring suturing, general anaesthesia and estimated blood loss. Secondary neonatal outcomes are; Apgar score at one, five, and ten minutes, Umbilical artery pH, shoulder dystocia, admission to Neonatal Intensive Care Unit and death within 28 days of birth. The analysis will be intention-to-treat (per unit) on the primary and secondary outcomes. The STROBE study received approval from the Health Research Authority and is sponsored by North Bristol NHS Trust. Results will be published in an open-access peer-reviewed medical journal within one year of completion of data gathering. The STROBE study will help establish our understanding of the effectiveness of locally-delivered simulation training for operative vaginal birth. Robust evidence supporting the effectiveness of such an approach would add weight to the argument supporting regular, local training for junior obstetricians in operative vaginal birth. ISRCTN11760611 05/03/2018 (retrospectively registered).


[Relations within the family as a health factor for adolescent girls].
The authors attempt to assess the effect of everyday relationships in a family on the health status of family members, adolescent girls. They emphasize the importance of further investigation and analysis of everyday family life, for the data of such studies will help plot new multifactorial models aimed at the maintenance, fortification, recovery, and development of the latent potentials of a family in order to provide its normal functioning in the society and adequate adaptation to ever changing socioeconomic conditions.


Fluoride therapy for bone disease.
The use of fluoride in the treatment of osteoporosis remains very controversial, despite its registration in many countries. Fluoride has been convincingly demonstrated to have a potent anabolic effect on osteoblastic trabecular bone formation, with a subsequent sustained increase in axial bone mass. However, its ability to reduce the vertebral fracture rate in established spinal osteoporosis is still debated, and questions have been raised regarding a potential negative effect on cortical bone mass and an increase in fractures of the peripheral skeleton, especially hip fractures. These data, including some very recent studies, are reviewed to draw some perspectives and recommendations for the use of fluoride in the treatment of osteoporosis.


Molecular cytogenetic characterization of pancreas cancer cell lines reveals high complexity chromosomal alterations.
Karyotype analysis can provide clues to significant genes involved in the genesis and growth of pancreas cancer. The genome of pancreas cancer is complex, and G-band analysis cannot resolve many of the karyotypic abnormalities seen. We studied the karyotypes of 15 recently established cell lines using molecular cytogenetic tools. Comparative genomic hybridization (CGH) analysis of all 15 lines identified genomic gains of 3q, 8q, 11q, 17q, and chromosome 20 in nine or more cell lines. CGH confirmed frequent loss of chromosome 18, 17p, 6q, and 8p. 14/15 cell lines demonstrated loss of chromosome 18q, either by loss of a copy of chromosome 18 (n = 5), all of 18q (n = 7) or portions of 18q (n = 2). Multicolor FISH (Spectral Karyotyping, or SKY) of 11 lines identified many complex structural chromosomal aberrations. 93 structurally abnormal chromosomes were evaluated, for which SKY added new information to 67. Several potentially site-specific recurrent rearrangements were observed. Chromosome region 18q11.2 was recurrently involved in nine cell lines, including formation of derivative chromosomes 18 from a t(18;22) (three cell lines), t(17;18) (two cell lines), and t(12;18), t(15;18), t(18;20), and ins(6;18) (one cell line each). To further define the breakpoints involved on chromosome 18, YACs from the 18q11.2 region, spanning approximately 8 Mb, were used to perform targeted FISH analyses of these lines. We found significant heterogeneity in the breakpoints despite their G-band similarity, including multiple independent regions of loss proximal to the already identified loss of DPC4 at 18q21.


Coacervation of dynamic covalent surfactants with polyacrylamides: properties and applications.
Dynamic covalent surfactants have been prepared from a mixture of 4-formyl-N,N,N-trimethylbenzenaminium iodide (FBA) with heptylamine (C7A) or octylamine (C8A) in alkaline aqueous solutions. The reversible pH-dependent nature of the imine bond is characterized by 1H NMR and fluorescence analysis. The dynamic covalent surfactants self-assemble into micelles under alkaline conditions and exhibit coacervation with 10% hydrolyzed polyacrylamide (PAM) over a wide concentration range. The coacervate phase with a network structure was found to effectively extract the anionic dye Conge Red (CR). When the solution is adjusted to acidity, the imine bond is hydrolyzed, leading to the transition of the coacervates into a homogeneous and clear solution, and the precipitation of CR into purple-black solids due to the protonation of sulfonic groups. Thus, the extraction and release of CR molecules are realized with this dynamic covalent surfactant/PAM system. Moreover the initial components, FBA, amine, and PAM, can be easily regenerated with hydrochloric acid. This method shows potential applications in wastewater treatment.


Design of trials for interrupting the transmission of endemic pathogens.
Many interventions against infectious diseases have geographically diffuse effects. This leads to contamination between arms in cluster-randomized trials (CRTs). Pathogen elimination is the goal of many intervention programs against infectious agents, but contamination means that standard CRT designs and analyses do not provide inferences about the potential of interventions to interrupt pathogen transmission at maximum scale-up. A generic model of disease transmission was used to simulate infections in stepped wedge cluster-randomized trials (SWCRTs) of a transmission-reducing intervention, where the intervention has spatially diffuse effects. Simulations of such trials were then used to examine the potential of such designs for providing generalizable causal inferences about the impact of such interventions, including measurements of the contamination effects. The simulations were applied to the geography of Rusinga Island, Lake Victoria, Kenya, the site of the SolarMal trial on the use of odor-baited mosquito traps to eliminate Plasmodium falciparum malaria. These were used to compare variants in the proposed SWCRT designs for the SolarMal trial. Measures of contamination effects were found that could be assessed in the simulated trials. Inspired by analyses of trials of insecticide-treated nets against malaria when applied to the geography of the SolarMal trial, these measures were found to be robust to different variants of SWCRT design. Analyses of the likely extent of contamination effects supported the choice of cluster size for the trial. The SWCRT is an appropriate design for trials that assess the feasibility of local elimination of a pathogen. The effects of incomplete coverage can be estimated by analyzing the extent of contamination between arms in such trials, and the estimates also support inferences about causality. The SolarMal example illustrates how generic transmission models incorporating spatial smoothing can be used to simulate such trials for a power calculation and optimization of cluster size and randomization strategies. The approach is applicable to a range of infectious diseases transmitted via environmental reservoirs or via arthropod vectors.


[Tubular carcinoma of the breast (clinico-morphological characteristics)].
The following four types of tubular carcinoma of the breast were identified as a result of the study of 39 cases: typical tubular carcinoma of the breast; tubular mammary carcinoma with ductal invasion; ductal invasive carcinoma with tubular structures predominating over more than half the area of section; ductal invasive carcinoma incorporating few tubular structures. A specific clinico-morphological picture and prognosis are peculiar to each type of carcinoma. Tubular carcinoma of the breast and ductal invasive tumor with predominant tubular structures have a favorable prognosis and a regional metastasis frequency of 23-28%, practically without distant metastases. Tubular carcinoma of the breast is considered an early form of ductal invasive carcinoma which develops into other histological patterns as tumor growth progresses.


Anti-Inflammatory Effect of Triterpene Saponins Isolated from Blue Cohosh (Caulophyllum thalictroides).
Blue cohosh has been used as a medicinal herb in eastern North America. It was commonly used as traditional medicines for the treatment of menopausal symptoms, rheumatic pain, and as anti-inflammatory remedy. Particularly, extract of blue cohosh roots has been used as anti-inflammatory antipyretic in traditional medicines. In the present study, we investigated the effects of blue cohosh components on the suppressive expression of iNOS or proinflammatory cytokines after the activation of microglia with lipopolysaccharide (LPS). The expression of iNOS, TNF-α, IL-1β, and IL-6 was determined by western blotting or gene expression. Blue cohosh treatment suppressed the elevation of LPS-induced iNOS expression in a concentration-dependent manner in microglia cells. Blue cohosh constituents also suppressed the expression of TNF-α, IL-1β, and IL-6. In addition, blue cohosh extract suppressed the expression of COX-2, iNOS, and proinflammatory cytokines in adrenal glands of mice. These results demonstrate that constituents of blue cohosh exert anti-inflammatory effects through the inhibition of expression of iNOS and proinflammatory cytokines. Therefore, blue cohosh may have therapeutic potential for the treatment of inflammation-related diseases.


Six key topics informal carers of patients with breathlessness in advanced disease want to learn about and why: MRC phase I study to inform an educational intervention.
Breathlessness is a common symptom of advanced disease placing a huge burden on patients, health systems and informal carers (families and friends providing daily help and support). It causes distress and isolation. Carers provide complex personal, practical and emotional support yet often feel ill-prepared to care. They lack knowledge and confidence in their caring role. The need to educate carers and families about breathlessness is established, yet we lack robustly developed carer-targeted educational interventions to meet their needs. We conducted a qualitative interview study with twenty five purposively-sampled patient-carer dyads living with breathlessness in advanced disease (half living with advanced cancer and half with advanced chronic obstructive pulmonary disease (COPD). We sought to identify carers' educational needs (including what they wanted to learn about) and explore differences by diagnostic group in order to inform an educational intervention for carers of patients with breathlessness in advanced disease. There was a strong desire among carers for an educational intervention on breathlessness. Six key topics emerged as salient for them: 1) understanding breathlessness, 2) managing anxiety, panic and breathlessness, 3) managing infections, 4) keeping active, 5) living positively and 6) knowing what to expect in the future. A cross-cutting theme was relationship management: there were tensions within dyads resulting from mismatched expectations related to most topics. Carers felt that knowledge-gains would not only help them to support the patient better, but also help them to manage their own frustrations, anxieties, and quality of life. Different drivers for education need were identified by diagnostic group, possibly related to differences in caring role duration and resulting impacts. Meeting the educational needs of carers requires robustly developed and evaluated interventions. This study provides the evidence-base for the content of an educational intervention for carers of patients with breathlessness in advanced disease.


The effect of inorganic phosphate on the activity of bacterial ribokinase.
Ribokinase and adenosine kinase are both members of the PfkB family of carbohydrate kinases. The activity of mammalian adenosine kinase was previously shown to be affected by pentavalent ions (PVI). We now present evidence that the catalytic activity of E. coli ribokinase is also affected by PVI, increasing both the velocity and affinity of the enzyme for D-ribose. The Km, for ribose decreased from 0.61 mM to 0.21, 0.25, and 0.33 mM in the presence of 20 mM phosphate, arsenate, and vanadate, respectively. The activity of ribokinase was stimulated in a hyperbolic fashion, with the maximum velocity increasing 23-fold, 13-fold, and 11-fold under the same conditions, respectively. Activity was also affected upon the addition of phosphoenolpyruvate, suggesting that phosphorylated metabolites could be involved in enzymatic control. The similar effect of PVI on distantly related enzymes suggests that a common mechanism for activity is shared among PfkB family members.


The Recruitment of Shifting and Inhibition in On-line Science and Mathematics Tasks.
Prior research has investigated the recruitment of inhibition in the use of science/mathematics concepts in tasks that require the rejection of a conflicting, nonscientific initial concept. The present research examines if inhibition is the only EF skill recruited in such tasks and investigates whether shifting is also involved. It also investigates whether inhibition and/or shifting are recruited in tasks in which the use of science/mathematics concepts does not require the rejection of an initial concept, or which require only the use of initial concepts. One hundred and thirty-three third- and fifth-grade children participated in two inhibition and shifting tasks and two science and mathematics conceptual understanding and conceptual change (CU&C) tasks. All the tasks were on-line, and performance was measured in accuracy and RTs. The CU&C tasks involved the use of initial concepts and of science/mathematics concepts which required conceptual changes for their initial formation. Only in one of the tasks the use of the science/mathematics concepts required the concurrent rejection of an initial concept. The results confirmed that in this task inhibition was recruited and also showed that the speed of shifting was a significant predictor of performance. Shifting was a significant predictor of performance in all the tasks, regardless of whether they involved science/mathematics or initial concepts. It is argued that shifting is likely to be recruited in complex tasks that require multiple comparisons of stimuli and the entertainment of different perspectives. Inhibition seems to be a more selective cognitive skill likely to be recruited when the use of science/mathematics concepts requires the rejection of a conflicting initial concept.


Predictors of extent of resection and recurrence following endoscopic endonasal resection of craniopharyngioma.
Craniopharyngioma is a benign but surgically challenging brain tumor. Controversies exist regarding its ideal treatment strategy, goals of surgery, efficacy of radiation, and the long-term outcomes of these decisions. The authors of this study performed a detailed analysis of factors predictive of the extent of resection and recurrence in large series of craniopharyngiomas removed via an endoscopic endonasal approach (EEA) with long-term follow-up. From a prospective database of all EEAs done at Weill Cornell Medical College by the senior author from 2004 to 2022, a consecutive series of histologically proven craniopharyngiomas were identified. Gross-total resection (GTR) was generally the goal of surgery. Radiation was often given if GTR had not been achieved. The stalk was preserved if not infiltrated with tumor but was sacrificed to achieve GTR. Intentional subtotal resection (STR) was performed in select cases to avoid hypothalamic injury. Among the 111 identified cases were 88 adults and 23 children. Newly diagnosed cases comprised 58.6% of the series. GTR was attempted in 77.5% of the patients and among those cases was achieved in 89.5% of treatment-naive tumors and 72.4% of recurrent tumors. An inability to achieve GTR was predicted by prior surgical treatment (OR 0.13, 95% CI 0.03-0.6, p = 0.009), tumor diameter ≥ 3.5 cm (OR 0.11, 95% CI 0.02-0.53, p = 0.006), and encasement of the optic nerve or a major artery (OR 0.11, 95% CI 0.01-0.8, p = 0.03). GTR with stalk preservation maintained some anterior pituitary function in 64.5% of cases and prevented diabetes insipidus in 25.8%. After a median follow-up of 51 months (IQR 17-80 months), the recurrence rate after GTR was 12.5% compared with 38.5% after non-GTR. The median recurrence-free survival was 5.5 years after STR, 8.3 years after near-total resection (≥ 98%), and not reached after GTR (p = 0.004, log-rank test). GTR was the strongest predictor of recurrence-free survival (OR 0.09, 95% CI 0.02-0.42, p = 0.002), whereas radiation did not show a statistically significant impact (OR 1.17, 95% CI 0.45-3.08). In GTR cases, the recurrence rate was higher if the stalk had been preserved (22.6%) as opposed to a sacrificed stalk (4.9%; OR 5.69, 95% CI 1.09-29.67). The study data show that GTR should be the goal of surgery in craniopharyngiomas if it can be achieved safely. Although stalk preservation can maintain some endocrine function, the risk of recurrence is higher in such cases. Radiation may not be as effective as previously reported.


ICU triage: the potential legal liability of withdrawing ICU care during a catastrophic event.
In the event of a catastrophic disaster, healthcare resources may be completely overwhelmed. To address this, the federal Agency for Healthcare Research and Quality has recommended using "crisis standards of care"during such an event. These standards would recommend allocating scarce medical resources to do the greatest good for the greatest number of patients. In a dire catastrophic event, such standards may include the allocation of intensive care unit (ICU) resources to maximize patient survival. Triage protocols that seek to efficiently allocate ICU resources during a disaster have been reviewed by the Institute of Medicine. Such protocols suggest the exclusion of patients with high mortality or high resource requirements from ICU care to do the most good for the greatest number of patients. In extreme circumstances, these protocols recommend withdrawing ICU resources from sicker patients in favor of more salvageable patients. However, if providers were to follow the earlier protocols in a disaster and withdraw and reallocate ICU care, criminal or civil liability could result. Two legal solutions to avoid this potential for liability have been suggested in this article.


P-selectin, a granule membrane protein of platelets and endothelial cells, follows the regulated secretory pathway in AtT-20 cells.
P-selectin (PADGEM, GMP-140, CD62) is a transmembrane protein specific to alpha granules of platelets and Weibel-Palade bodies of endotheial cells. Upon stimulation of these cells, P-selectin is translocated to the plasma membrane where it functions as a receptor for monocytes and neutrophils. To investigate whether the mechanism of targeting of P-selectin to granules is specific for megakaryocytes and endothelial cells and/or dependent on von Willebrand factor, a soluble adhesive protein that is stored in the same granules, we have expressed the cDNA for P-selectin in AtT-20 cells. AtT-20 cells are a mouse pituitary cell line that can store proteins in a regulated fashion. By double-label immunofluorescence, P-selectin was visible as a punctate pattern at the tips of cell processes. This pattern closely resembled the localization of ACTH, the endogenous hormone produced and stored by the AtT-20 cells. Fractionation of the transfected cells resulted in the codistribution of P-selectin and ACTH in cellular compartments of the same density. Immunoelectron microscopy using a polyclonal anti-P-selectin antibody demonstrated immunogold localization in dense granules, morphologically indistinguishable from the ACTH granules. Binding experiments with radiolabeled monoclonal antibody to P-selectin indicated that there was also surface expression of P-selectin on the AtT-20 cells. After stimulation with the secretagogue 8-Bromo-cAMP the surface expression increased twofold, concomitant with the release of ACTH. In contrast, the surface expression of P-selectin transfected into CHO cells, which do not have a regulated pathway of secretion, did not change with 8-Br-cAMP treatment. In conclusion, we provide evidence for the regulated secretion of a transmembrane protein (P-selectin) in a heterologous cell line, which indicates that P-selectin contains an independent sorting signal directing it to storage granules.


Note: Determination of temperature dependence of GaP bandgap energy from diode temperature response characteristics.
A simple method of E(g)(T) dependence determination for active areas of semiconductor devices based on wide bandgap semiconductors has been proposed and developed. Verification of the method has been carried out while determining E(g)(T) dependence in a base area of p(+)-n-type GaP diodes in the temperature range 77-523 K. The method is based on U-T characterization of the diodes and calculation of E(g)(T) dependence according to the expression obtained within present study. Satisfactory agreement between experimental and theoretical results has been achieved including references available on gallium phosphide. The method proposed could be applied to experimental data processing in high-temperature thermometry.


Status epilepticus: clinical analysis of a treatment protocol based on midazolam and phenytoin.
The efficacy of a combination of midazolam and phenytoin in treating generalized convulsive status epilepticus in children was studied retrospectively. The patient group comprised all patients admitted for generalized convulsive status epilepticus to the pediatric intensive care unit over 7 years. Patients treated according to the protocol were included (N = 122). These patients were treated with the following regimen; each subsequent step was taken if clinical evidence of epileptic activity persisted: midazolam 0.5 mg/kg rectally or 0.1 mg/kg intravenously. After 10 minutes: midazolam 0.1 mg/kg intravenously. After 10 minutes: phenytoin 20 mg/kg intravenously in 20 minutes. After phenytoin load: midazolam 0.2 mg/kg intravenously followed by midazolam 0.1 mg/kg/hour continuously, increased by 0.1 mg/kg/hour every 10 minutes to maximum 1 mg/kg/hour. Phenobarbital 20 mg/kg intravenously or pentobarbital 2 to 5 mg/kg intravenous load, 1 to 2 mg/kg/hour continuously intravenously. Patients who received initial rectal diazepam were included. Patients were categorized according to the cause of generalized convulsive status epilepticus. These categories were then related to the level of antiepileptic therapy needed. Patients' ages ranged from 0.5 to 197.4 months. The cause of generalized convulsive status epilepticus was idiopathic or febrile convulsions in two thirds of cases. Most (89%) patients were managed on midazolam and phenytoin. Generalized convulsive status epilepticus was terminated with midazolam alone in 58 patients, with the addition of phenytoin in 19 patients and with continuous midazolam in 32 patients. Thirteen patients needed additional barbiturates. The relationship between the level of antiepileptic therapy and etiology was not significant. Fifty-two patients needed artificial ventilation. Seven patients died; no deaths were directly attributable to generalized convulsive status epilepticus itself. With the use of the proposed protocol, combining midazolam and phenytoin, 89% of the cases of generalized convulsive status epilepticus could be successfully managed.


Outcomes of transcarotid artery revascularization with dynamic flow reversal in patients with contralateral carotid artery occlusion.
The outcomes of carotid revascularization in patients with contralateral carotid artery occlusion (CCO) are controversial. CCO has been defined by the Centers for Medicare and Medicaid Services as a high-risk criterion and is used as an indication for transfemoral carotid artery stenting. With the promising outcomes associated with transcarotid artery revascularization (TCAR), we aimed to study the perioperative outcomes of TCAR in patients with CCO and to assess the feasibility of TCAR in these high-risk patients. All patients in the Vascular Quality Initiative database who underwent TCAR with flow reversal between September 2016 and May 2019 were included. Patients with trauma, dissection, or more than two treated lesions were excluded. Univariable and multivariable logistic analyses were used to compare the primary outcome of in-hospital stroke or death after TCAR in patients with CCO and those without CCO (patent and <99% stenosis). Secondary outcomes included intraoperative neurologic changes and the individual outcomes of in-hospital stroke, death, and myocardial infarction as well as 30-day mortality. A total of 5485 TCAR cases were included, of which 593 (10.8%) had CCO. In patients with CCO, mean flow reversal time was shorter (10.1 ± 6.7 minutes vs 11.1 ± 7.8 minutes; P < .01); intraoperative neurologic changes occurred in 1% of these patients compared with 0.7% of those with patent contralateral carotid arteries (P = .43). On univariable analysis, no significant difference in in-hospital stroke or death was shown between patients with and patients without CCO (1.7% vs 1.5%; P = .65). Similarly, no significant differences were noted between the groups in terms of in-hospital death (0.7% vs 0.4%; P = .27), stroke (1.7% vs 1.2%; P = .32), and stroke/death/myocardial infarction (2.2% vs 1.8%; P = .53) as well as 30-day mortality (0.8% vs 0.6%; P = .55). The results remained statistically nonsignificant after adjustment for baseline differences between the groups; the adjusted odds ratio (OR) of in-hospital stroke/death in patients with CCO compared with those with patent contralateral carotid arteries was not significant (OR, 1.39; 95% confidence interval, 0.65-3.0; P = .40). In symptomatic patients presenting with prior stroke, CCO was associated with significantly higher odds of stroke or death (OR, 4.63; 95% confidence interval, 1.39-15.4; P = .01) compared with no CCO. On the other hand, in asymptomatic patients, no significant difference in outcomes was observed between the groups. In this analysis, TCAR seems to be safe in patients with CCO. Caution should be taken in symptomatic patients with CCO and a history of prior stroke as they might have worse outcomes compared with patients with patent contralateral carotid arteries. Studies with larger sample size and longer follow-up are needed to assess the perioperative and long-term outcomes of TCAR in patients with CCO in comparison to other procedures.


Non-small cell lung cancer treatment (r)evolution: ten years of advances and more to come.
Diagnostic and treatment algorithms in non-small cell lung cancer (NSCLC) are evolving at a never-before-seen pace. Histological subtyping to maximise treatment efficacy and avoid toxicity has marked the beginning of the revolution, opening the way to molecular characterisation to guide genomically driven treatments with targeted agents, led by Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) inhibitors. More recently, agents against the Program Death 1 receptor (PD-1) and ligand 1 (PD-L1) have entered the clinical arena, offering new hope to NSCLC patients, although several uncertainties remain to be elucidated. Here, we review the most clinically relevant advances in the diagnosis and treatment of NSCLC in the past decade.


Comparison of triflusal and aspirin for prevention of vascular events in patients after cerebral infarction: the TACIP Study: a randomized, double-blind, multicenter trial.
The efficacy of the antiplatelet agent triflusal for prevention of vascular events after stroke has been reported in a pilot study. However, there is a need to confirm those results in a larger study. We performed a randomized, double-blind, multicenter study to test the efficacy of triflusal (600 mg/d) versus aspirin (325 mg/d) for prevention of vascular events in patients with stroke or transient ischemic attack (Triflusal versus Aspirin in Cerebral Infarction Prevention [TACIP]). We assessed a combined end point (incidence of nonfatal ischemic stroke, nonfatal acute myocardial infarction, or vascular death) as well as the incidence of these events separately and the incidence of major hemorrhage. Of 2113 patients, 1058 received triflusal and 1055 aspirin. The mean follow-up period was 30.1 months. The incidence of combined end point (13.1% for triflusal, 12.4% for aspirin) as well the survival analysis (hazard ratio [HR] for triflusal versus aspirin, 1.09; 95% CI, 0.85 to 1.38) showed no differences between groups. The incidence of nonfatal stroke (HR, 1.09; 95% CI, 0.82 to 1.44), nonfatal acute myocardial infarction (HR, 0.95; 95% CI, 0.46 to 1.98,) and vascular death (HR, 1.22; 95% CI, 0.75 to 1.96) was also similar. A significantly higher incidence of major hemorrhages in the aspirin group was recorded (HR, 0.48; 95% CI, 0.28 to 0.82). The overall incidence of hemorrhage was significantly lower in the triflusal group (16.7% versus 25.2%) (odds ratio, 0.76; 95% CI, 0.67 to 0.86; P<0.001). This study failed to show significantly superior efficacy of triflusal over aspirin in the long-term prevention of vascular events after stroke, but triflusal was associated with a significantly lower rate of hemorrhagic complications.


Increased activity of superoxide dismutase in advanced stages of head and neck squamous cell carcinoma with locoregional metastases.
The aim of the study was to investigate relationship between activity of superoxide dismutase (SOD), malondialdehyde (MDA) and tumor necrosis factor alpha (TNFalpha) and between Ala-9Val polymorphism in the gene encoding MnSOD (SOD2) and the initial stage and prognosis of the head and neck squamous cell carcinoma (HNSCC). Prospective study cohort comprised 88 patients who underwent surgical treatment for the diagnosis of HNSCC (53 patients were diagnosed with locoregional metastatic spread (N+) at the time of diagnosis). After the initial surgery subjects were followed for the subsequent period of 26 months during which 14 manifested relapse. Genotypes were detected by the PCR-based methodology. Activity of p-SOD, ery-SOD and TNFalpha were determined by ELISA, and the concentration of MDA by high performance liquid chromatography. Genotype and allele frequencies of the Ala-9Val differed neither between groups defined according to the stage of primary disease (TNM), nor between relapse vs. remission groups after the follow-up (p>0.05). Activity of p-SOD was significantly higher in T3/4 stage compared to T1/2 (p=0.01) and was also higher in N+ compared to N0 patients (p=0.002). Carriers of the Ala/Ala genotype had higher p-SOD activity (p=0.04). There was no significant difference in DFI between SOD2 genotype groups (p>0.05), however, the Ala/Ala group exhibited the shortest median DFI. In conclusion, our results suggest that increased p-SOD at the time of the initial treatment for HNSCC is connected with greater extent and nodal metastatic spread of the initial disease and with an earlier relapse of the disease. Progression of the disease might be further modified by the presence of Ala/Ala genotype of the SOD2. Activity of p-SOD could thus offer diagnostic as well as prognostic value.


[Acute inferior myocardial infarction with right ventricular involvement complicated by interventricular septum rupture - a case report].
A case of a 62-year-old female with acute inferior myocardial infarction with right ventricular involvement is presented. The patient developed cardiogenic shock due to interventricular septum rupture. Pharmacological agents and intraaortic balloon counterpulsation restored normal circulation which enabled elective surgical treatment 14 days after the onset of symptoms.


The responses of serum transferrin receptors to iron supplements in subjects with iron-deficiency erythropoiesis and iron-deficiency anaemia.
We aimed to study the response of serum transferrin receptors (sTfR) to Fe supplementation in women of childbearing age with Fe-deficiency erythropoiesis (IDE) and Fe-deficiency anaemia (IDA). Primary screening was performed in 942 women ranging in age from 18 to 45 years. After Fe-related biochemical indices such as serum ferritin, Zn protoporphyrin and Hb were determined, the subjects were divided into four groups: normal, Fe store depletion, IDE and IDA. A total of 131 women were randomly selected from the normal, IDE and IDA groups. Subsequently, seventy-six women with IDE and IDA were given various doses of Fe (14 mg/d for IDE; 28 mg/d for IDA) with ferrous l-threonate capsules for twelve consecutive weeks. After receiving Fe supplements, the levels of Fe and sTfR were determined at weeks 0, 3, 6, 9 and 12. The levels of sTfR in women of childbearing age with IDE and IDA were significantly higher than those in the normal group. After receiving Fe supplements, the levels of sTfR were significantly decreased in women of childbearing age with IDE and IDA, while the levels of serum ferritin were significantly increased. In conclusion, STfR can be used as a reliable indicator for assessing the efficacy of Fe supplements.


DRG-based cost management at Norwest Corporation.
A large financial holding company, Norwest has been studying employee health benefit utilization, provider performance and more by comparing actual experience to projected norms using a DRG-based methodology. The Hewitt Associates Consultant who works with the Company explains how this process has revealed new facts crucial to health cost management planning.


[Measurement of output sound pressure in a real ear to raise efficacy of electroacoustic hearing correction].
Fifty adult patients with neurosensory hypoacusis of different severity participated in the study of feasibility of using analytic computer systems in selection of optimal regimes of acoustic aid function with use of pressure measurement in the real ear. The results have shown that measurement of the frequency response in the camera of 2 sm(3) in volume is unable to predict the function of the acoustic aid in each individual case. Most of the acoustic aid users need correction of the program adjustment. The efficacy of electroacoustic correction should be evaluated on the basis of measurements of output sound pressure in a real ear as most reliable and significant. The results of the study are useful in conduction of hearing prosthetic correction.


Analysis of the status and factors influencing physical activity in patients undergoing ovarian cancer chemotherapy.
Ovarian cancer is a common gynecological malignancy, leading to approximately 200,000 deaths globally in 2020. Research has shown that regular physical activity can reduce the toxic side effects of cancer treatment, reduce morbidity and mortality, extend survival time, and improve quality of life. We aimed to evaluate physical activity regimens in patients undergoing chemotherapy for ovarian cancer and analyze the factors influencing physical activity levels. To facilitate the selection of patients with ovarian cancer hospitalized for chemotherapy in the Third Affiliated Hospital of Zhengzhou University and the First Affiliated Hospital of Zhengzhou University from August 2022 to February 2023, questionnaire surveys were conducted using the General Information Questionnaire, International Physical Activity Questionnaire, Hospital Anxiety and Depression Scale, and Revised Piper Fatigue Scale. Data were collected from 167 patients with ovarian cancer. Overall, 96 (57.5%) patients had low physical activity levels, 53 (31.7%) had moderate physical activity levels, and 18 (10.8%) had high physical activity levels. Logistic regression analysis revealed that sleep status, social support, anxiety, depression, and cancer-related fatigue were the main factors influencing physical activity in patients undergoing chemotherapy for ovarian cancer. Physical activity levels of patients undergoing ovarian cancer chemotherapy were generally low. Therefore, healthcare professionals should pay greater attention to the physical activity in these patients. Targeted and individualized health guidance is recommended, and activity interventions should be implemented according to the influencing factors to promote disease understanding and increase physical activity levels.


Serum neopterin and somatization in women with chemical intolerance, depressives, and normals.
The symptom of intolerance to low levels of environmental chemicals (CI, chemical intolerance) is a feature of several controversial polysymptomatic conditions that overlap symptomatically with depression and somatization, i.e., chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivity, and Persian Gulf syndrome. These syndromes can involve many somatic symptoms consistent with possible inflammation. Immunological or neurogenic triggering might account for such inflammation. Serum neopterin, which has an inverse relationship with l-tryptophan availability, may offer a marker of inflammation and macrophage/monocyte activation. This study compared middle-aged women with CI (who had high levels of affective distress; n = 14), depressives without CI (n = 10), and normals (n = 11). Groups did not differ in 4 p.m. resting levels of serum neopterin. However, the CI alone had strong positive correlations between neopterin and all of the scales measuring somatization. These preliminary findings suggest the need for additional research on biological correlates of 'unexplained' multiple somatic symptoms in subtypes of apparent somatizing disorders.


[Adenosine deaminase in the complex diagnosis of different forms of extrapulmonary tuberculosis].
The paper summarizes the results of studies of the activity of adenosine deaminase (ADA) in biological fluids (including that during tuberculin tests) as a tool for the differential diagnosis of different forms of extrapulmonary tuberculosis, such as pleuritis, synovitis, meningitis, tuberculosis of female genitals and peripheral lymph nodes, and uveitis. The threshold for the activity of ADA or the magnitude of its increase in antigenic stimulation, which provides the optimum ratio of the sensitivity to specificity of the tests and their maximum diagnostic efficiency, are given. The optimization of diagnosis of tuberculous synovitis is shown to facilitate the study of ADA activity concomitantly with the determination of the level of antituberculosis antibodies. The tests under discussion are economically sound and yield results in several hours and, in case of a provocative test, in 3 days.


Toward a biochemical classification of depressive disorders. X. Urinary catecholamines, their metabolites, and D-type scores in subgroups of depressive disorders.
Data on 24-hour urinary levels of catecholamines and metabolites were determined in 114 depressed patients. For each patient, a D-type score was calculated, using a discriminant function equation that was previously derived using data from an independent group of depressed patients. Of all measures, D-type scores provided the highest sensitivity and specificity for separating bipolar/schizoaffective-depressed patients from all remaining patients or from those patients with unipolar nonendogenous depressions. Using Research Diagnostic Criteria (RDC), bipolar I patients demonstrated significantly lower D-type scores than did all other RDC depressive subtypes, including bipolar II disorders. Similar findings were observed using the Clinical Inventory for the Diagnosis and Classification of Affective Disorders (CIDCAD) system: bipolar/schizoaffective patients demonstrated significantly lower D-type scores than all remaining subtypes, including diagnostically unclassifiable, probable bipolar patients (a category somewhat akin to RDC bipolar II disorder). Data pointed to the heterogeneity of bipolar disorders. Catecholamine and metabolite data in this study were compared with recent studies of others.


From personal crisis care to convenience shopping: an interpretive description of the experiences of people with mental illness and addictions in community pharmacies.
The role of community pharmacists is changing globally with pharmacists engaging in more clinically-oriented roles, including in mental health care. Pharmacists' interventions have been shown to improve mental health related outcomes but various barriers can limit pharmacists in their care of patients. We aimed to explore the experiences of people with lived experience of mental illness and addictions in community pharmacies to generate findings to inform practice improvements. We used interpretive description methodology with analytic procedures of thematic analysis to explore the experiences of people with lived experience of mental illness and addictions with community pharmacy services. Participants were recruited through multiple mechanisms (e.g., paper and online advertisements), offered honorarium for their time, and given the option of a focus group or interview for participation in our study. Data were gathered during July to September of 2012. Interviews and focus groups were audio-recorded, transcribed verbatim, and analyzed by two researchers. We collected approximately nine hours of audio data from 18 individuals in two focus groups (n = 12) and six individual interviews. Fourteen participants were female and the average age was 41 years (range 24 to 57 years). Expectations, decision-making, and supports were identified as central themes underlying the community pharmacy experiences of people with lived experience of mental illness and addictions. Eight subthemes were identified including: relationships with pharmacy staff; patient's role in the pharmacist-patient relationship; crisis and triage; privacy and confidentiality; time; stigma and judgment; medication-related and other services; and transparency. People with lived experience of mental illness and addictions demonstrate a high regard and respect for pharmacist's knowledge and abilities but hold conservative expectations of pharmacy health services shaped by experience, observations, and assumptions. To some extent, expectation management occurs with the recognition of the demands on pharmacists and constraints inherent to community pharmacy practice. Relationships with pharmacy staff are critical to people with lived experience and influence their decision-making. Research in the area of pharmacists' roles in crises and triage, especially in the area of suicide assessment and mitigation, is needed urgently.


Serotonin transporter polymorphism is associated with increased apnea-hypopnea index in older adults.
A functional polymorphism of the serotonin transporter gene (5-HTTLPR) has previously been related to upper airway pathology, but its contribution to obstructive sleep apnea (OSA), a highly prevalent sleep disorder in older adults, remains unclear. We aimed to investigate the relationship between apnea-hypopnea index (AHI) and genetic variations in the promoter region of the 5-HTTLPR in older adults. DNA samples from 94 community-dwelling older adults (57% female, mean age 72 ± 8) were genotyped for the 5-HTTLPR polymorphism. All participants were assessed in their homes with full ambulatory polysomnography in order to determine AHI and related parameters such as hypoxia, sleep fragmentation, and self-reported daytime sleepiness. The 5-HTT l allele was significantly associated with AHI (p = 0.019), with l allele carriers displaying a higher AHI than s allele homozygotes. A single allele change in 5-HTTLPR genotype from s to l resulted in an increase of AHI by 4.46 per hour of sleep (95% CI, 0.75-8.17). The l allele was also associated with increased time during sleep spent at oxygen saturation levels below 90% (p = 0.014). The observed significant association between the 5-HTTLPR l allele and severity of OSA in older adults suggests that the l allele may be important to consider when assessing for OSA in this age group. This association may also explain some of the observed variability among serotonergic pharmacological treatment studies for OSA, and 5-HTT genotype status may have to be taken into account in future therapeutic trials involving serotonergic agents.


Robot-Assisted Surgery Avoids Mandibulotomy in a Case of Adenoid Cystic Carcinoma of Base of the Tongue.
Surgical management is increasingly preferred in human papilloma-related oropharyngeal squamous cell carcinoma. Robotic surgery has a different role to play in oropharyngeal salivary origin tumors, where surgery is the primary essential modality. This modality may be used for better access to the oropharynx, avoiding a lip split approach with mandibulotomy. The organ preservation approach such as in oropharyngeal squamous cell carcinoma, with nonsurgical modalities like chemoradiotherapy, is not preferred in such cancers, as in the present case. In this context, robot-assisted surgery helps in reducing the morbidity by avoiding the mandibulotomy.


Chitosan-based nanoscale systems for doxorubicin delivery: Exploring biomedical application in cancer therapy.
Green chemistry has been a growing multidisciplinary field in recent years showing great promise in biomedical applications, especially for cancer therapy. Chitosan (CS) is an abundant biopolymer derived from chitin and is present in insects and fungi. This polysaccharide has favorable characteristics, including biocompatibility, biodegradability, and ease of modification by enzymes and chemicals. CS-based nanoparticles (CS-NPs) have shown potential in the treatment of cancer and other diseases, affording targeted delivery and overcoming drug resistance. The current review emphasizes on the application of CS-NPs for the delivery of a chemotherapeutic agent, doxorubicin (DOX), in cancer therapy as they promote internalization of DOX in cancer cells and prevent the activity of P-glycoprotein (P-gp) to reverse drug resistance. These nanoarchitectures can provide co-delivery of DOX with antitumor agents such as curcumin and cisplatin to induce synergistic cancer therapy. Furthermore, co-loading of DOX with siRNA, shRNA, and miRNA can suppress tumor progression and provide chemosensitivity. Various nanostructures, including lipid-, carbon-, polymeric- and metal-based nanoparticles, are modifiable with CS for DOX delivery, while functionalization of CS-NPs with ligands such as hyaluronic acid promotes selectivity toward tumor cells and prevents DOX resistance. The CS-NPs demonstrate high encapsulation efficiency and due to protonation of amine groups of CS, pH-sensitive release of DOX can occur. Furthermore, redox- and light-responsive CS-NPs have been prepared for DOX delivery in cancer treatment. Leveraging these characteristics and in view of the biocompatibility of CS-NPs, we expect to soon see significant progress towards clinical translation.


[Intervention of the case management nurse in hospital admissions of patients with HIV infection].
In countries with access to antiretroviral treatment such as ours, HIV is a chronic disease both characterized for being treated only in hospitals and for the aging of the affected population, the persistence of opportunist infections, the complexity of the antiretroviral treatment, the frequency of adverse effects due to therapies, drug interactions and the high costs of this disease for the Healthcare System. This could justify the need for the creation of the position of nurse case manager to monitor patients with HIV infection, admitted to conventional hospital wards, as a unifying element of the individual's needs and coordinate resources through proper planning and care management.


The contributions of NMDA, non-NMDA, and GABA receptors to postsynaptic responses in neurons of the optic tectum.
Activation of the NMDA subtype of glutamate receptor has been implicated in activity-dependent development and plasticity in several systems, including the retinotectal system of amphibians. To gain a better understanding of the response properties of tectal neurons, with particular emphasis on the role of both non-NMDA and NMDA glutamate receptors, we have developed an in vitro slice preparation of the diencephalon and midbrain of frog (Rana pipiens) tadpoles. In these slices, we electrically stimulated the optic tract and recorded both mono- and polysynaptic responses in single tectal neurons using whole-cell voltage clamp or current clamp. By including biocytin in the recording electrode, we were also able to determine the location and morphology of many of these neurons. Using these techniques, we found that the current-voltage (I-V) relations for both mono- and polysynaptic responses of tectal neurons showed voltage dependence only in the presence of extracellular Mg2+. This dependence reflects the hyperpolarization-dependent block of the NMDA channel by Mg2+. Bath application of 6-cyano-7-nitroquinoxaline-2,3-dione, a non-NMDA glutamate receptor antagonist, reduced both mono- and polysynaptic responses of tectal neurons. Bath application of the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (DL-APV) strongly reduced polysynaptic responses. When neurons were depolarized by the voltage clamp, relieving the Mg(2+)-dependent block of the NMDA channel, DL-APV application also reduced monosynaptic responses. Application of the GABAA receptor antagonist (-)bicuculline methiodide significantly increased the polysynaptic responses of tectal neurons, reflecting block of inhibition. We further confirmed the presence of these three types of receptors by examining postsynaptic currents evoked by iontophoretic application of the three agonists, NMDA, (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), and GABA. These results confirm that the dominant excitatory transmitter in the tectum appears to be glutamate. Furthermore, the retinotectal synapses (i.e., monosynaptic currents) express functional NMDA receptors that are voltage dependent and are not responsible for the bulk of normal excitatory transmission. Polysynaptic responses, however, are mediated by both non-NMDA and NMDA receptors, and inhibition plays a significant role in sculpting these polysynaptic responses.


Resonantly pumped 1.645 μm single longitudinal mode Er:YAG laser with intracavity etalons.
We report on a 1.645 μm single longitudinal mode Er:YAG laser that was resonantly pumped by a 1.532 μm fiber laser, using intracavity etalons to generate single longitudinal mode operation. We obtained 0.749 W single longitudinal mode output power at 1.645 μm from an Er:YAG laser with two intracavity etalons. The M2-factors of the Er:YAG laser were 1.041 and 1.068 in the x and y directions, respectively.


Efficacy of cisplatin plus vinorelbine adjuvant chemotherapy with split-dose administration of cisplatin after complete resection of stage II-IIIA non-small cell lung cancer.
Although co-administration of cisplatin (CDDP) and vinorelbine (VNR) has been established as a standard of care adjuvant chemotherapy for non-small cell lung cancer (NSCLC), there is a lack of clinical data on its safety and efficacy in Japanese patients receiving split-dose administration of CDDP. The present study analyzed patients who received CDDP + VNR with split-dose administration of CDDP after undergoing complete resection of NSCLC. Patients received four courses of CDDP (40 mg/m2) and VNR (25 mg/m2) on days 1 and 8, every 3 weeks. There were 27 male and 13 female patients; the mean age was 65 years (range 38-78 years), the postoperative disease staging distribution was IIA/IIB/IIIA: 14/8/18 patients, and histological distribution was adenocarcinoma/squamous cell carcinoma/others: 24/12/4 patients, respectively. Of the 40 patients, 28 (70%) completed the four courses of treatment. The mean total dose administered was 279 mg/m2 CDDP (87.2%) and 172 mg/m2 VNR (86%). The major adverse events included Grade (G) 3 or higher neutropenia (80%), G3 phlebitis (5%) and vomiting (2.5%). There was no G2 or higher serum creatinine level elevation, G3 or higher anorexia and nausea, or any treatment-related deaths. The overall completion rate of four courses was 70 and 62.5% for patients aged 70 years and older, whereas the overall percentage of patients that could complete three or more courses was 85 and 87.5% for patients aged 70 years and older. The relapse-free survival rate was 60% at 3 years and 57.5% at 5 years. Overall survival rate was 80% at 3 years and 60% at 5 years. The present study demonstrated the sufficient tolerability, safety and efficacy of combined CDDP + VNR adjuvant chemotherapy with split-dose administration of CDDP, with a low risk of gastrointestinal toxicities or nephrotoxicity.


Water exchange mechanism in the first excited state of hydrated uranyl(VI).
The water exchange mechanism of the uranyl(VI) aquo ion in the luminescent state, (3)Delta(g) in the spin-orbit free nomenclature, has been investigated using quantum chemical methods and compared to the corresponding reaction in the electronic ground state. The reaction mechanism was studied by calculation of the enthalpy of reaction of the A- and D- intermediates relative to the reactant, using a penta-aquo ion model with one additional water molecule in the second hydration sphere. The reaction barriers around the intermediates are low, and they are therefore a good approximation for the activation enthalpy. The energy of the D-intermediate is significantly larger than that of the A-intermediate both in the luminescent and in the ground states, suggesting that the water exchange is the same in both states. This suggestion is supported by the experimental rate constants for luminescence decay and water exchange in the electronic ground state that are 0.5 x 10(6) s(-1) and 1.3 x 10(6) s(-1), respectively.


Evaluating the evidence for biotypes of depression: Methodological replication and extension of.
Psychiatric disorders are highly heterogeneous, defined based on symptoms with little connection to potential underlying biological mechanisms. A possible approach to dissect biological heterogeneity is to look for biologically meaningful subtypes. A recent study Drysdale et al. (2017) showed promising results along this line by simultaneously using resting state fMRI and clinical data and identified four distinct subtypes of depression with different clinical profiles and abnormal resting state fMRI connectivity. These subtypes were predictive of treatment response to transcranial magnetic stimulation therapy. Here, we attempted to replicate the procedure followed in the Drysdale et al. study and their findings in a different clinical population and a more heterogeneous sample of 187 participants with depression and anxiety. We aimed to answer the following questions: 1) Using the same procedure, can we find a statistically significant and reliable relationship between brain connectivity and clinical symptoms? 2) Is the observed relationship similar to the one found in the original study? 3) Can we identify distinct and reliable subtypes? 4) Do they have similar clinical profiles as the subtypes identified in the original study? We followed the original procedure as closely as possible, including a canonical correlation analysis to find a low dimensional representation of clinically relevant resting state fMRI features, followed by hierarchical clustering to identify subtypes. We extended the original procedure using additional statistical tests, to test the statistical significance of the relationship between resting state fMRI and clinical data, and the existence of distinct subtypes. Furthermore, we examined the stability of the whole procedure using resampling. As in the original study, we found extremely high canonical correlations between functional connectivity and clinical symptoms, and an optimal three-cluster solution. However, neither canonical correlations nor clusters were statistically significant. On the basis of our extensive evaluations of the analysis methodology used and within the limits of comparison of our sample relative to the sample used in Drysdale et al., we argue that the evidence for the existence of the distinct resting state connectivity-based subtypes of depression should be interpreted with caution.


Multimorbidity and fit note receipt in working-age adults with long-term health conditions.
Research on sickness absence has typically focussed on single diagnoses, despite increasing recognition that long-term health conditions are highly multimorbid and clusters comprising coexisting mental and physical conditions are associated with poorer clinical and functional outcomes. The digitisation of sickness certification in the UK offers an opportunity to address sickness absence in a large primary care population. Lambeth Datanet is a primary care database which collects individual-level data on general practitioner consultations, prescriptions, Quality and Outcomes Framework diagnostic data, sickness certification (fit note receipt) and demographic information (including age, gender, self-identified ethnicity, and truncated postcode). We analysed 326 415 people's records covering a 40-month period from January 2014 to April 2017. We found significant variation in multimorbidity by demographic variables, most notably by self-defined ethnicity. Multimorbid health conditions were associated with increased fit note receipt. Comorbid depression had the largest impact on first fit note receipt, more than any other comorbid diagnoses. Highest rates of first fit note receipt after adjustment for demographics were for comorbid epilepsy and rheumatoid arthritis (HR 4.69; 95% CI 1.73-12.68), followed by epilepsy and depression (HR 4.19; 95% CI 3.60-4.87), chronic pain and depression (HR 4.14; 95% CI 3.69-4.65), cardiac condition and depression (HR 4.08; 95% CI 3.36-4.95). Our results show striking variation in multimorbid conditions by gender, deprivation and ethnicity, and highlight the importance of multimorbidity, in particular comorbid depression, as a leading cause of disability among working-age adults.


Sensory nerves affect the recruitment and differentiation of rat periovarian brown adipocytes during cold acclimation.
Rat periovarian adipose tissue contains a low number of uncoupling protein-expressing brown adipocytes scattered into lobules of white fat. Their increase following cold acclimation is matched by a major increase in noradrenergic and neuropeptide Y-, substance P- and calcitonin gene-related peptide-containing nerves. To ascertain whether periovarian fat is provided with sensory nerves, and whether any relationship exists between such nerves (in particular the calcitonin gene-related peptide-containing fibers found in cold-acclimated rats in close association with brown adipocytes) and brown fat recruitment, the effects of capsaicin desensitization on neuropeptide-containing nerves and brown adipocyte density were studied in the periovarian tissue of rats kept at 20 degrees C and on a group acclimated to 4 degrees C for 14 days. In both groups, systemic capsaicin administration considerably reduced the expression of substance P and calcitonin gene-related peptide in vascular-nerve bundles and parenchyma. In cold-acclimated rats, the increase in brown adipocyte density was significantly checked by capsaicin administration (21.11 versus 7.96 brown adipocytes/mm2, P<0.05). Finally, ultrastructural investigation showed the occurrence of brown adipocyte precursors filled with aggregates of glycogen and poorly differentiated multilocular adipocytes in capsaicin-treated cold-acclimated rats. These data suggest that periovarian adipose tissue is indeed provided with sensory neuropeptide-containing nerves and that they play a role in the recruitment and differentiation of brown adipocytes.


Synthesis and in vitro preliminary evaluation of prostate-specific membrane antigen targeted upconversion nanoparticles as a first step towards radio/fluorescence-guided surgery of prostate cancer.
Over the last decade, upconversion nanoparticles (UCNP) have been widely investigated in nanomedicine due to their high potential as imaging agents in the near-infrared (NIR) optical window of biological tissues. Here, we successfully develop active targeted UCNP as potential probes for dual NIR-NIR fluorescence and radioactive-guided surgery of prostate-specific membrane antigen (PSMA)(+) prostate cancers. We designed a one-pot thermolysis synthesis method to obtain oleic acid-coated spherical NaYF4:Yb,Tm@NaYF4 core/shell UCNP with narrow particle size distribution (30.0 ± 0.1 nm, as estimated by SAXS analysis) and efficient upconversion luminescence. Polyethylene glycol (PEG) ligands bearing different anchoring groups (phosphate, bis- and tetra-phosphonate-based) were synthesized and used to hydrophilize the UCNP. DLS studies led to the selection of a tetra-phosphonate PEG(2000) ligand affording water-dispersible UCNP with sustained colloidal stability in several aqueous media. PSMA-targeting ligands (i.e., glutamate-urea-lysine derivatives called KuEs) and fluorescent or radiolabelled prosthetic groups were grafted onto the UCNP surface by strain-promoted azide-alkyne cycloaddition (SPAAC). These UCNP, coated with 10 or 100% surface density of KuE ligands, did not induce cytotoxicity over 24 h incubation in LNCaP-Luc or PC3-Luc prostate cancer cell lines or in human fibroblasts for any of the concentrations evaluated. Competitive binding assays and flow cytometry demonstrated the excellent affinity of UCNP@KuE for PSMA-positive LNCaP-Luc cells compared with non-targeted UCNP@CO2H. Furthermore, the binding of UCNP@KuE to prostate tumour cells was positively correlated with the surface density of PSMA-targeting ligands and maintained after 125I-radiolabelling. Finally, a preliminary biodistribution study in LNCaP-Luc-bearing mice demonstrated the radiochemical stability of non-targeted [125I]UCNP paving the way for future in vivo assessments.


Solvent effects in calculated vibrational Raman optical activity spectra of α-helices.
We study the influence of solvation effects on vibrational Raman optical activity spectra of α-helices by means of quantum chemical calculations. Solvent effects are considered in the calculations via the conductor-like screening model COSMO and, in addition, via explicit water molecules. The so-called external type of hydration is employed. In this hydration pattern, the water molecules form hydrogen bonds to the carbonyl groups of the α-helical (Ala)20 model. It is found that the amide I bands are significantly shifted to lower wavenumbers if solvent effects are incorporated into the calculations. These computational results, obtained within the static picture employed in this work, suggest that the amide I bands may serve as a signature for the hydration of α-helices.


Ocular Manifestations of the Sturge-Weber Syndrome.
Sturge-Weber syndrome (SWS) or encephalotrigeminal angiomatosis is a non-inherited congenital disorder characterized by neurologic, skin, and ocular abnormalities. A somatic activating mutation (R183Q) in the GNAQ gene during early embryogenesis has been recently recognized as the etiology of vascular abnormalities in SWS. Approximately, half of the patients with SWS manifest ocular involvement including glaucoma as the most common ocular abnormality followed by choroidal hemangioma (CH). The underlying pathophysiology of glaucoma in SWS has not been completely understood yet. Early onset glaucoma comprising 60% of SWS glaucoma have lower success rates after medical and surgical treatments compared with primary congenital glaucoma. Primary angle surgery is associated with modest success in the early onset SWS glaucoma while the success rate significantly decreases in late onset glaucoma. Filtration surgery is associated with a higher risk of intraoperative and postoperative choroidal effusion and suprachoroidal hemorrhage. CH is reported in 40-50% of SWS patients. The goal of treatment in patients with CH is to induce involution of the hemangioma, with reduction of subretinal and intraretinal fluid and minimal damage to the neurosensory retina. The decision for treating diffuse CHs highly depends on the patient's visual acuity, the need for glaucoma surgery, the presence of subretinal fluid (SRF), its chronicity, and the potential for visual recovery.


[Interpopulation diversity of the gene pool: beta distribution of Wright's F(ST) statistics].
The distribution of FST(i) estimates were studied in representative samples of ith genes for the gene pools of the major human populations, including the populations of Europe, Asia, Africa, Australia, America, North-eastern Eurasia, and five subregions of the latter. An average of 80 FST(i) estimates were analyzed for each sample of marker genes with a level of polymorphism (q) from 0.05 to 0.95. For each gene pool, the empirical distributions of FST(i) estimates were approximated by the main types of theoretical distributions--the normal, chi 2, Weibull, gamma, and beta distributions. In all gene pools, only beta distributions were good approximations of the empirical FST(i) distributions. The parameters of the beta distributions are reported in this study. It was demonstrated that the characteristics of beta distributions for all major gene pools studied could be interpolated to the smaller constituent gene pools. since the use of the traditional parametric tests starts from an assumption of normal distribution, they are inapplicable to analysis of FST statistics. Therefore, the obtained parameters of beta distributions should be used. These parameters allow the confidence intervals of the average FST values to be determined and permit correct comparison between the characteristics of both individual genes and gene pools to be performed.


Basilar artery hypoplasia.
A rare case of segmental hypoplasia of the basilar artery is described in a 49-year-old man with transient vertebrobasilar ischemia, explored by magnetic resonance imaging (MRI) and digital angiography (DA). The embryology, clinical relevance and magnetic resonance findings of this arterial anomaly are discussed, with a review of six previously reported cases. Segmental aplasia was suggested in our case by magnetic resonance, and subsequently confirmed not only by time-of-flight magnetic resonance, but also by DA. Only ultrathin-slice T2-weighted images revealed the real finding of basilar artery hypoplasia. This sequence, not employed in previously reported cases, is mandatory to allow a clear differential diagnosis between basilar artery aplasia and hypoplasia.


[Studies on improving the ability of learning and memories of yangshoudan].
To observe the effects of Yangshoudan(YSD) on the ability of learning and memories in experimental animals. The tests of darkness-avoidance response in normal young mice and rats, aged mice, as well as in model mice with dysmnesia induced by anisodine, model rats with dysmnesia induced by scopolamine hydrobromide and with orientation disturbance induced by pentobarbital sodium. In normal young mice and rats, the error times in five minutes in learning and memories tests was reduced (P < 0.01-0.05) by YSD, while in dysmnesia groups the error times in five minutes also reduced (P < 0.01-0.05) and the incubation period of memories could be shortened by YSD. In orientation disturbance mice, the averages and percentages of correct response times increased by YSD. YSD could improve the memory ability both in normal and dysmnesia which either induced by drugs or due to age. This indicates primarily that YSD has the effects of improving the ability of learning and memories and of antidementia.


Changes in axial length following trabeculectomy and glaucoma drainage device surgery.
This study examines the changes in axial length (AL) after trabeculectomy and glaucoma drainage device (GDD) surgery and enabled an equation to be derived allowing prediction of AL change after filtering surgery. This was a prospective, interventional case series from the Glaucoma Service of the Doheny Eye Institute. One eye of 39 patients undergoing trabeculectomy and 22 undergoing Baerveldt tube shunt implantation for uncontrolled glaucoma. These patients had AL measurements by non-contact, partial coherence interferometry preoperatively, at 1 week, 1 month, and >3 months after surgery. Axial length and intraocular pressure were compared at preoperative and postoperative visits. Postoperative intraocular pressure (IOP) was categorised as hypotonous (0-4 mm Hg), low (5-9), normal (10-17), and high (18 or more). There was a statistically significant reduction in IOP after 3 months of -12.8 (SD 1.5) mm Hg following trabeculectomy (p<0.001), and -10.7 (1.9) mm Hg after GDD (p<0.001). There was a statistically significant reduction in AL, which was similar after trabeculectomy and GDD at all time points (p<0.001), of -0.15 (0.03) and -0.21 (0.04) mm (1 week), -0.18 (0.02) and -0.10 (0.02) mm (1 month), and -0.16 (0.03) and -0.15 (0.03) mm (3 months). At 3 months or later the AL reduction was related to postoperative IOP and to the amount of IOP reduction (p<0.05, stepwise multiple regression). 10.2% (4/39) of trabeculectomy patients had hypotony after 3 months, with a mean AL reduction (-0.39 (0.11)) that was statistically significantly lower (p<0.01) than the other trabeculectomy eyes (-0.14 (0.15)). There is a small but statistically significant decrease in AL after both trabeculectomy and GDD surgery, greater in eyes that are hypotonous after surgery. The authors suggest that AL reduction can be predicted after 3 months by the formula: AL reduction (mm) = -199+0.006 x IOP reduction+0.008 x final IOP.


Post-infectious irritable bowel syndrome.
Irritable bowel syndrome (IBS) is a common disorder associated with abdominal pain or discomfort and altered bowel habits. The majority of patients describe an insidious onset of symptoms; however, a subset report a fairly precise time of onset following an attack of acute gastroenteritis. Typically, the potential acute infectious symptoms, such as fever and vomiting, resolve after several days, but abdominal discomfort, bloating, and diarrhea persist. Although the underlying mechanism of post-infectious IBS (PI-IBS) has not been established, ongoing inflammation appears to play a role, with an increase in serotonin-containing enterochromaffin cells, T lymphocytes, mast cells, proinflammatory cytokines, and intestinal permeability. Psychiatric comorbidities are less common in PI-IBS, compared with IBS patients in general; however, the prevalence of psychological disorders is still higher compared with that in the general population and is associated with a poorer prognosis. Overall, patients with PI-IBS have a slightly improved prognosis compared with those with IBS without an infectious onset.