[Characterization of stroke patients attended at IMSS hospitals in Mexico City].
Cerebrovascular disease (CD) is considered a problem of huge social, economic and public health implications worldwide in adults and elderly. In Mexico, the information concerning the provision of services to people and their characteristics is limited. The objective is to describe the characteristics of patients with CV who attended the hospitals of the Instituto Mexicano del Seguro Social (IMSS) in Mexico City. It was carried out a cohort study of patients with ischemic or hemorrhagic CD who arrived to IMSS. Patients were recruited from seven IMSS general hospitals in Mexico City from June, 2013, to October, 2014. We assigned 430 subjects with CD (78.14% had ischemic CD). There were no statistical differences regarding gender. The median age of patients was 74 years. During their first 72 hours of hospital stay, it was assessed language proficiency in 90%, the ability to walk in 16.3% and the ability to move extremities in 94%. The main risk factors were hypertension, 84%; diabetes mellitus, 46.3%; history of CD, 25.1%; smoking history, 13.7%. 80% of patients reported that their health was regular or poor. General characteristics of patients and vascular risk factors are similar to those reported by other studies. Secondary prevention strategies are performed in less time than that recommended by international standards. It is urgent to design strategies to build better ways of care during the acute phase of patients with CD.


Playing With Ideas: Evaluating the Impact of the Ultimate Block Party, a Collective Experiential Intervention to Enrich Perceptions of Play.
Parental attitudes shape play opportunities afforded to children in home, community, and school settings. This study presents evaluation of an intervention designed to enrich parent's conception of play and its relationship with socially valued skills and capacities. On the basis of data from 291 racially and ethnically diverse parents/caregivers of young children (median age between 3 and 6) attending an event in NYC, we find the intervention helped parents conceptualize play in complex ways and altered perceptions of its impact on children's current-but not future-lives. Multivariate analyses reveal the causal pathway for these changes as exposure to multiple play sites, rather than time at the event-a finding with direct implications for exposing parents to developmental science in community settings.


GDPR and Health Personal Data; Tricks and Traps of Compliance.
The GDPR fixes general rules applying to any kind of personal data processing as well as specific rules applying to the processing of special categories of personal data such as health data taking place in the context of scientific research or clinical software development. A short overview of new rules about how to consider where scientific and professional projects include the processing of personal health data, genetic data or biometric data and other kinds of sensitive information whose use is strictly regulated by the GDPR is provided. Some key facts to researchers and developers to adapt their practices and ensure compliance to the EU laws are included.


Psychedelic Assisted Psychotherapy preparing your target using psychohistoriography: a Jamaican perspective.
The efficacy of psilocybin and other psychedelics as modes of treatment have been demonstrated through clinical trials and other studies in the management of a number of mental illnesses, including some treatment resistant cases. In Psychedelic Assisted Psychotherapy (PAP), psychedelics catalyze or enhance the experience fostered by psychotherapeutic methods. Psychohistoriographic Brief Psychotherapy, conceptualized by the late Professor Frederick Hickling in the 1970's in Kingston, Jamaica, offers a pathway for exploration in the Jamaican context. Applied to individuals, Psychohistoriographic Brief Therapy (PBT) has already shown success in patients with personality disorders in Jamaica through a process which includes documenting life experiences in a psychohistoriogram. In the De La Haye psilocybin Treatment Protocol (DPTP), micro-doses of crushed, dried psilocybin mushrooms are taken throughout an 8-week outpatient process of documenting the components of the psychohistoriogram, making use of the increased openness and empathy associated with the use of psychedelic agents. These sessions are followed by supervised in-office therapeutic/mystical doses of crushed, dried psilocybin mushrooms in the 9th week. Given the legal status and availability of psilocybin containing products in a few countries like Jamaica, there is a potential role for a regulated psychedelic industry contributing to the body of useful and rigorous clinical research which is needed in this area. Clients could benefit as we venture into this new frontier in psychiatry.


Duration of Respiratory and Gastrointestinal Viral Shedding in Children With SARS-CoV-2: A Systematic Review and Synthesis of Data.
Children with coronavirus disease 2019 (COVID-19) are more likely to have mild or no symptoms compared with adults and may represent important vectors for transmitting the virus. Little is known about the duration of respiratory and gastrointestinal viral shedding in children with COVID-19. To determine the average shedding times of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via the respiratory and gastrointestinal tracts in children. We performed a systematic search of Ovid MEDLINE, Embase and Cochrane CENTRAL databases for studies reporting real-time reverse transcriptase polymerase chain reaction (rt-PCR) results in children with COVID-19, then extracted and synthesized data on duration of viral shedding from symptom onset in respiratory and gastrointestinal samples. Based on data compiled from 69 pediatric cases, the duration of viral shedding through the respiratory tract is up to 24 days from symptom onset with a mean of 11.1 ± 5.8 days. Of the children who underwent testing with stool PCR, rectal swab or anal swab, 86% returned a positive result. The mean duration of viral shedding via the gastrointestinal tract was 23.6 ± 8.8 days from symptom onset. In 89% of cases, viral shedding via the gastrointestinal tract persisted after nasopharyngeal or throat swabs became negative, for as long as 4 weeks. To our knowledge, this is the first attempt to systematically review the duration of respiratory and gastrointestinal viral shedding of SARS-CoV-2 in pediatric patients. These findings may have important implications for infection control strategies during the COVID-19 pandemic.


Human nucleolar protein SURF6/RRP14 participates in early steps of pre-rRNA processing.
The biogenesis of ribosomes requires tightly controlled transcription and processing of pre-rRNA which comprises ribosomal RNAs forming the core of large and small ribosomal subunits. Early steps of the pre-rRNA processing and assembly of the ribosomal subunits require a large set of proteins that perform folding and nucleolytic cleavage of pre-rRNAs in the nucleoli. Structure and functions of proteins involved in the pre-rRNA processing have been extensively studied in the budding yeast S. cerevisiae. Functional characterization of their human homologues is complicated by the complexity of mammalian ribosomes and increased number of protein factors involved in the ribosomal biogenesis. Homologues of human nucleolar protein SURF6 from yeast and mouse, Rrp14 and Surf6, respectively, had been shown to be involved in the early steps of pre-rRNA processing. Rrp14 works as RNA chaperone in complex with proteins Ssf1 and Rrp15. Human SURF6 knockdown and overexpression were used to clarify a role of SURF6 in the early steps of pre-rRNA processing in human cell lines HeLa and HTC116. By analyzing the abundance of the rRNA precursors in cells with decreased level or overexpression of SURF6, we demonstrated that human SURF6 is involved in the maturation of rRNAs from both small and large ribosomal subunits. Changes in the SURF6 level caused by knockdown or overexpression of the protein do not result in the death of HeLa cells in contrast to murine embryonic fibroblasts, but significantly alter the distribution of cells among the phases of the cell cycle. SURF6 knockdown in both p53 sufficient and p53 deficient HCT116 human cancer cells results in elongation of G0/G1 and shortening of G2/M phase. This surprising result suggests p53 independence of SURF6 effects on the cell cycle and possible multiple functions of SURF6. Our data point to the shift from pathway 1 to pathway 2 of the rRNA biogenesis caused by the SURF6 knockdown and its likely association with p53 pathway.


Phosphorus complexes of N-fused porphyrin and its reduced derivatives: new isomers of porphyrin stabilized via coordination.
N-fused isophlorin 3 and its tautomeric phlorin forms 4 and 5, the new constitutional isomers of porphyrin which preserve the basic skeleton of their maternal N-fused porphyrin, have been identified in the course of investigation of phosphorus insertion into N-fused porphyrin 2. N-fused porphyrin reacts with PCl3 in toluene yielding phosphorus(V) N-fused isophlorin 3-P wherein the macrocycle acts as a trianionic tridentate ligand. The identical product has been formed in the reaction of N-confused porphyrin 1 and POCl3 or PCl3. The coordinating environment of phosphorus(V) in 3-P as determined by X-ray crystallography resembles a distorted trigonal pyramid with the nitrogen atoms occupying equatorial positions with the oxygen atom lying at the unique apex. Phosphorus(V) is significantly displaced by 0.732(1) A from the N3 plane. The P-N distances are as follows P-N(22) 1.664(2), P-N(23) 1.645(2), and P-N(24) 1.672(2). All P-N(pyrrolic) bond lengths are markedly shorter than the P-N distances in phosphorus porphyrins. 3-P is susceptible to proton addition at the inner C(9) carbon atom, yielding aromatic 4-P. The modified macrocycle acts as a dianionic ligand and allows the efficient 18 pi-electron delocalization pathway. Two stereoisomers affording the syn (4-P syn) and anti (4-P anti) location of the H(9) atom with respect to the oxygen atom of the PO unit have been identified by (1)H NMR. A regioselective reduction of free base N-fused porphyrin 2 with NaBH4 yielded a nonaromatic isomer of 4, that is, N-fused phlorin 5 due to an addition of a hydride to the C(15) carbon and a proton to one of the pyrrolic nitrogens. The isomer 5 reacts with PCl 3 yielding phosphorus(V) fused isophlorin 3-P. Density functional theory has been applied to model the molecular and electronic structure of porphyrin isomers 3, 4, and 5 and their phosphorus(V) complexes.


Simultaneous double interphalangeal joints dislocation in a finger in a teenager.
The English literature reports a mere handful of cases involving simultaneous dislocation of two joints in the same finger. To our knowledge, all cases reported to date have been in skeletally mature individuals. We report a case of simultaneous proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints dislocations in one finger in a 14-year-old rugby player, managed by closed reduction and early mobilization, with excellent outcome. Proximal interphalangeal joint, Distal interphalangeal joint, Dislocation, Skeletally immature.


CONTRASTING THE UNDERLYING PATTERNS OF ACTIVE TRENDS IN MORPHOLOGIC EVOLUTION.
Gastropod evolution during the early Paleozoic featured active trends (i.e., differential replacement of morphologies) for at least three shell characters. Selective sorting, either of individual organisms or of whole species, is an obvious mechanism for such active trends. Sorting of individuals should result in a disproportionate number of ancestor to descendant transitions being in the same direction as the trend, whereas sorting of species should result in species with particular morphologies producing more daughter species. Sorting of species can occur over long periods of time or it can be concentrated over a particular interval, such as an extinction event. Constraints on morphologic evolution also can drive trends, especially in cases where it is easier to produce a particular morphology than it is to change it. Finally, active trends can be artifacts of unrelated differential diversification within a clade (i.e., species hitchhiking), which might result from sorting of species based on phylogenetically associated characters or simply by chance. Unlike other active trends, trends attributable to species hitchhiking do not support hypotheses about selection or evolutionary constraints.


Clinical perspectives on xenobiotic-induced hepatotoxicity.
Drug-induced hepatotoxicity is an important cause of liver disease with significant medical, economic, legal, and regulatory implications. Clinically, it presents a diagnostic challenge to health care professionals since drug-induced liver disease can mimic the clinicopathologic features of all other acute and chronic liver diseases. However, individual drugs tend to have a characteristic clinical signature. Early identification of hepatotoxicity by either laboratory monitoring or patients' awareness as a result of education may avert serious liver injury in delayed idiosyncratic toxicity. Most adverse hepatic reactions require metabolism of the drug to reactive metabolites and free radicals, which then either lead to direct overwhelming lethal insult, nonlethal sensitization to the lethal effects of the innate immune system, or haptenization eliciting an immunoallergic response of the adaptive immune system. Besides licensed drugs, herbal and natural supplements are recognized as causing hepatotoxicity with increasing frequency as patients turn more and more to alternative medicine.


A new immunoglobulin-binding protein, EibG, is responsible for the chain-like adhesion phenotype of locus of enterocyte effacement-negative, shiga toxin-producing Escherichia coli.
Shiga toxin-producing Escherichia coli (STEC) are important enteropathogens causing severe diseases such as hemorrhagic colitis and hemolytic-uremic syndrome in humans. The majority of STEC strains of serogroups O157, O26, or O111 associated with severe cases of these diseases possess a pathogenicity island termed the locus of enterocyte effacement (LEE). LEE, which is responsible for the formation of attaching-and-effacing lesions on intestinal epithelial cells, is important for the full virulence of STEC. Nonetheless, LEE-negative STEC strains have repeatedly been reported to be associated with severe diseases in humans. In this study, we characterized adhesion to cultured epithelial cells of certain LEE-negative STEC isolated from humans with or without bloody diarrhea. Several LEE-negative STEC belonging to serogroup O91 showed an unusual, chain-like adhesion pattern to HEp-2 cells. Using Tn5-based transposon mutagenesis, we identified the gene essential for the chain-like adhesion phenotype of this O91 STEC strain. Sequence analysis of the Tn5-inserted allele identified a novel chromosomal open reading frame (ORF) encoding a polypeptide with a high degree of similarity to the E. coli immunoglobulin-binding (Eib) proteins EibA, -C, -D, -E, and -F. Therefore, the ORF was designated EibG. Laboratory E. coli strain MC4100 transformed with a multicopy plasmid carrying eibG showed chain-like adhesion to HEp-2 cells, and whole-cell lysates of the strain bound to human-derived immunoglobulin G (IgG) Fc and IgA. These results indicate that EibG acts as an IgG Fc- and IgA-binding protein, as well as an adhesin of LEE-negative STEC.


Evaluation of a brief cognitive behavioral group therapy for psychological distress among female Icelandic University students.
A study of a brief cognitive behavioral group therapy intervention for psychologically distressed Icelandic female university students was conducted using a pre-post test quasi-experimental design with intervention and control group conditions. Students were randomly allocated to control and intervention group conditions (n = 30). The intervention group received four sessions of cognitive behavioral group therapy, delivered by two advanced practice psychiatric nurses. Assessment of distress included self-reported depression and anxiety symptoms. Students in the intervention group experienced significantly lower levels of depression and anxiety symptoms compared to the control group post-test providing preliminary evidence concerning intervention effectiveness for Icelandic students.


A Case Review: Reframing School-Based Practices Using a Critical Perspective.
It is well established in the literature that school-based practice is fraught with challenges such as acquisition of appropriate and sufficient resources, communication barriers among professionals, parental burden, and redundancies and gaps in services. The purpose of this perspective paper is to reframe potentially problematic school-based practices using a critical social science perspective, suggesting a vision and strategies for therapists working in the context of school-based practice. We illustrate our approach with a case example. To reframe school-based practices, we begin with Jill's case, exploring it through a critical lens to identify potential issues and opportunities for change. We then trace these findings to our larger dataset from an ongoing program of research to ensure relevance to the broader context of school-based practice. Reframing of three school-based practice issues is discussed from: (a) advocacy by proxy to collaborative dialogue, (b) governing texts to guiding texts, and (c) playing the "right" part to having a voice. Although this is a perspective paper based on a case exemplar, we posit how we may reframe and rethink school-based practices in pediatric rehabilitation. We suggest that only with a genuine shift in our professional values will we see the enactment of collaborative practice in school-based settings.


Multiple embolic cerebral infarcts as the first manifestation of metastatic ovarian cancer.
A 36-year-old woman presented to the emergency department with a 3-day history of an occipital headache associated with transient visual impairment and short-term memory loss. MRI of the brain showed innumerable focal embolic infarcts of differing ages, for which a cause could not be determined. The patient was discharged and readmitted 7 weeks later with acute aphasia and a right-sided hemiplegia. CT of the abdomen revealed a right-sided ovarian mass and prominent retroperitoneal nodes, which cytology confirmed to be metastatic ovarian cancer.


Child Abuse and the Eye in an African Population.
There is a paucity of data on child abuse and the eye in West Africa. Therefore, a need exists to determine the causes and circumstances surrounding these occurrences and their effects on the eye and vision in a pediatric population. A 3-year study of consecutive cases of ocular features that presented to an eye clinic following a history suggestive of child abuse along with any associated eye injury was carried out. Socio-demographic characteristics were obtained, as were the presenting and posttreatment visual acuity, and a full clinical eye examination was also done. Fifty-six children with 56 affected eyes were examined. The male to female ratio was 1.8 : 1; the mean age was 8.25 ± 3.5 years; and the subjects were predominately primary school children 30 (53.6%). The most common ocular disorders were conjunctiva hyperemia (46.4%), corneal abrasion/ulcer (25.4%), hyphema/uveitis (42.9%), retinal detachment (7.1%), sclera rupture (7.1%), and globe perforation (21.4%). The intraocular pressure was raised in 17.9% of participants. Presenting versus posttreatment visual acuities showed normal vision in four (7.1%) vs. eighteen (32.1%), visual impairment in 12 (21.4%) vs. six (10.7%), severe visual impairment in 20 (35.7%) vs. 12 (21.4%), and blindness in 12 (21.4%) vs. 14 (25%), p < 0.001. The most common injurious agents were canes (25.0%) and sticks (17.9%). The people who inflicted the injuries were parents/relatives (uncles) in 35.7% of cases and the children themselves (accidents) in 21.4% of cases. Circumstances predisposing participants to eye injuries were child labor in 39.3% and beatings in 25.0%. Complications were cataracts (25.0%), corneal opacity (39.3%), and retinal detachment (7.1%). Injuries commonly resulted from canes and sticks used during beatings, as well as from child labor, corporal punishment, accidents, and assaults. Legislation and laws need to be enacted to prevent negative psychosocial and economic impacts on the child, family and country as a whole.


A Ratiometric Sensor for Imaging Insulin Secretion in Single β Cells.
Despite the urgent need for assays to visualize insulin secretion there is to date no reliable method available for measuring insulin release from single cells. To address this need, we developed a genetically encoded reporter termed RINS1 based on proinsulin superfolder GFP (sfGFP) and mCherry fusions for monitoring insulin secretion. RINS1 expression in MIN6 β cells resulted in proper processing yielding single-labeled insulin species. Unexpectedly, glucose or drug stimulation of insulin secretion in β cells led to the preferential release of the insulin-sfGFP construct, while the mCherry-fused C-peptide remained trapped in exocytic granules. This physical separation was used to monitor glucose-stimulated insulin secretion ratiometrically by total internal reflection fluorescence microscopy in single MIN6 and primary mouse β cells. Further, RINS1 enabled parallel monitoring of pulsatile insulin release in tolbutamide-treated β cells, demonstrating the potential of RINS1 for investigations of antidiabetic drug candidates at the single-cell level.


Phylogenomic analysis provides insights into MADS-box and TCP gene diversification and floral development of the Asteraceae, supported by de novo genome and transcriptome sequences from dandelion (Taraxacum officinale).
The Asteraceae is the largest angiosperm family with more than 25,000 species. Individual studies have shown that MADS-box and TCP transcription factors are regulators of the development and symmetry of flowers, contributing to their iconic flower-head (capitulum) and floret. However, a systematic study of MADS-box and TCP genes across the Asteraceae is lacking. We performed a comparative analysis of genome sequences of 33 angiosperm species including our de novo assembly of diploid sexual dandelion (Taraxacum officinale) and 11 other Asteraceae to investigate the lineage-specific evolution of MADS-box and TCP genes in the Asteraceae. We compared the phylogenomic results of MADS-box and TCP genes with their expression in T. officinale floral tissues at different developmental stages to demonstrate the regulation of genes with Asteraceae-specific attributes. Here, we show that MADS-box MIKC c and TCP-CYCLOIDEA (CYC) genes have expanded in the Asteraceae. The phylogenomic analysis identified AGAMOUS-like (AG-like: SEEDSTICK [STK]-like), SEPALATA-like (SEP3-like), and TCP-PROLIFERATING CELL FACTOR (PCF)-like copies with lineage-specific genomic contexts in the Asteraceae, Cichorioideae, or dandelion. Different expression patterns of some of these gene copies suggest functional divergence. We also confirm the presence and revisit the evolutionary history of previously named "Asteraceae-Specific MADS-box genes (AS-MADS)." Specifically, we identify non-Asteraceae homologs, indicating a more ancient origin of this gene clade. Syntenic relationships support that AS-MADS is paralogous to FLOWERING LOCUS C (FLC) as demonstrated by the shared ancient duplication of FLC and SEP3.


Novel complement factor H gene mutation causing atypical haemolytic uraemic syndrome: early Eculizumab prevents acute dialysis.
We describe the clinical course and response to treatment of atypical haemolytic uraemic syndrome (aHUS) in two sisters presenting to our hospital 6 years apart with a novel complement factor H mutation that has not been described previously in literature and demonstrates the genetic complexity of this ultra-rare disease. The contrast in course and outcome of disease between the two sisters highlights the rapid evolution of management of aHUS, the importance of rapidly establishing a diagnosis, and how minimizing time to eculizumab therapy significantly reduces associated morbidity and mortality.


[Use of the LAL test for quantitative determination of Bacteroids fragilis endotoxin].
The aim of this study was the evaluation of LAL test with chromogenic substrate usefulness for the quantitative detection of B. fragilis endotoxin and the determination of the amount of endotoxin in culture filtrates of the strains of this species. Also, the trial was undertaken to determine the influence of clindamycin on endotoxin release from B. fragilis rods to the culture medium. Four B. fragilis strains were examined: one nonenterotoxigenic (NTBF) and three enterotoxigenic (ETBF). The growth of cultures was determined and endotoxin liberated to the culture medium during growth of strains was detected. BHI broth and BHI broth with addition of sub inhibitory doses (sub-MIC) of clindamycin were applied. Bacterial cultures were incubated for 48 hours at 37 degrees C. Samples of bacterial cultures were collected after 4, 8, 16, 24 and 48 hours of cultivation, and the optical density was measured. Then the samples were centrifuged, supernatants were filtered through 0.45 micron filters and concentrated three times with 5000 D ultrafilters. Prepared samples were kept frozen at -70 degrees C until used. The amount of endotoxin in samples was determined using quantitative LAL test with chromogenic substrate S-2423. The results of the experiments indicate that LAL test is the useful method for determination of B. fragilis endotoxin concentration. This endotoxin activates the enzymatic system present in Limulus polyphemus amebocyte lysate. Endotoxin is shed spontaneously by B. fragilis rods to the culture medium during growth. Clindamycin at subinhibitory concentrations (sub-MIC) inhibits the growth of cultures of examined strains. The antibiotic caused increase in endotoxin amount in culture medium.


The role of microRNA-23b-5p in regulating brown adipogenesis and thermogenic program.
Enhanced brown adipose tissue (BAT) mass and activity have been demonstrated to promote the expenditure of excess stored energy and reduce prevalence of obesity. Cold is known as a potent stimulator of BAT and activates BAT primarily through the β3-adrenergic-cAMP signaling. Here, we performed RNA-sequencing to identify differential miRNAs in mouse BAT upon cold exposure and a total of 20 miRNAs were validated. With the treatment of CL-316,243 (CL) and forskolin (Fsk) in mouse and human differentiated brown adipocyte cells in vitro, miR-23b-5p, miR-133a-3p, miR-135-5p, miR-491-5p, and miR-150-3p expression decreased and miR-455-5p expression increased. Among these deferentially expressed miRNAs, miR-23b-5p expression was differentially regulated in activated and aging mouse BAT and negatively correlated with Ucp1 expression. Overexpression of miR-23b-5p in the precursor cells from BAT revealed no significant effects on lipid accumulation, but diminished mitochondrial function and decreased expression of BAT specific markers. Though luciferase reporter assays did not confirm the positive association of miR-23b-5p with the 3'UTRs of the predicted target Ern1, miR-23b-5p overexpression may affect brown adipocyte thermogenic capacity mainly through regulating genes expression involving in lipolysis and fatty acid β-oxidation pathways. Our results suggest that miRNAs are involved in cold-mediated BAT thermogenic activation and further acknowledged miR-23b-5p as a negative regulator in controlling thermogenic programs, further providing potential molecular therapeutic targets to increase surplus energy and treat obesity.


Moderating effect of age on the association between future time perspective and preventive coping.
The present study aimed to investigate the moderating effect of age on the relationship between future time perspective (FTP) and future-oriented coping. A total of 1,915 participants aged 9-84 years completed measures of FTP and future-oriented coping. Moderation analyses were conducted to examine whether age played a role in the association between FTP and future-oriented coping (proactive and preventive). Results showed that proactive and preventive coping were negatively correlated with age, and age moderated the association between FTP and preventive coping but not proactive coping. Furthermore, the strength of the positive association between FTP and preventive coping was strongest among the older participants, moderate among the middle-aged participants, and weakest among the younger participants. These results suggest that the association between FTP and preventive coping varies across the lifespan.


Modular Customization and Regulation of Metal-Organic Frameworks for Efficient Membrane Separations.
Metal-organic frameworks (MOFs) are considered ideal membrane candidates for energy-efficient separations. However, the MOF membrane amount to date is only a drop in the bucket compared to the material collections. The fabrication of an arbitrary MOF membrane exhibiting inherent separation capacity of the material remains a long-standing challenge. Herein, we report a MOF modular customization strategy by employing four MOFs with diverse structures and physicochemical properties and achieving innovative defect-free membranes for efficient separation validation. Each membrane fully displays the separation potential according to the MOF pore/channel microenvironment, and consequently, an intriguing H2 /CO2 separation performance sequence is achieved (separation factor of 1656-5.4, H2 permeance of 964-2745 gas permeation unit). Taking advantage of this strategy, separation performance can be manipulated by a non-destructive modification separately towards the MOF module. This work establishes a universal full-chain demonstration for membrane fabrication-separation validation-microstructure modification and opens an avenue for exclusive customization of membranes for important separations.


Genetic Variations in Attention Deficit Hyperactivity Disorder Subtypes and Treatment Resistant Cases.
ObjectiveaaWe evaluated the distribution of alpha-2A adrenergic receptor (ADRA2A) and catechol-o-methyltransferase (COMT) single nucleotide polymorphisms (SNPs) among ADHD subtypes and other homogeneous patient populations including treatment-resistant cases and patients with high symptom severity. Methodsaa121 ADHD patients aged 6-18 years were included in the study. Diagnosis and subtypes designation were confirmed using the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) and symptoms were evaluated using the Conners' Parent (CPRS) and Teacher Rating Scales (CTRS). The response to methylphenidate was assessed objectively using the Clinical Global Impression-Severity Scale (CGI-S) and Global Assessment of Functioning Scale (GAS) as well as the Continuous Performance (CPT) and Trail Making tests (TMT-A, B). Patients were genotyped for ADRA2A (rs1800544) and COMT (rs4680) SNPs by PCR/RFLP and compared to a gender-matched control group. Although there was no association of COMT (rs4680) SNP with symptoms or diagnosis, the ADRA2A polymorphism, low socioeconomic status (SES), and comorbid psychiatric diagnosis were all associated with poor response to methylphenidate in logistic regression analysis. Clinicians may consider adjuvant strategies when these negative factors are present to increase the success of tailored ADHD treatments in the future.


Meta-analysis study on the role of bone-derived neurotrophic factor Val66Met polymorphism in Parkinson's disease.
To evaluate a possible involvement of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism in susceptibility to Parkinson's disease (PD), we performed a meta-analysis of all studies on the topic published from 2002 to 2014. This article reviews and compares the data from two previous meta-analyses, including two studies not previously considered. We selected studies referring to a genetic comparison between PD patients and healthy controls, so 15 studies involving 3754 cases and 4026 controls were included in our meta-analysis. We found no association between the Val66Met polymorphism and the risk of developing PD in our overall analysis. The ethnicity-specific meta-analysis produced no significant association either. Our data do not support a major role for the BDNF Val66Met polymorphism in the pathogenesis of PD.


Imaging of the Microstructural Failure Mechanism in the Human Hip.
Imaging the bone microstructure under progressively increasing loads allows for observing the microstructural failure behavior of bone. Here, we describe a protocol for obtaining a sequence of three-dimensional microstructural images of the entire proximal femur under progressively increasing deformation, causing clinically relevant fractures of the femoral neck. The protocol is demonstrated using four femora from female donors aged 66-80 years at the lower end of bone mineral density in the population (T-score range = -2.09 to -4.75). A radio-transparent compressive stage was designed for loading the specimens replicating a one-leg stance, while recording the applied load during micro-computed tomography (micro-CT) imaging. The field of view was 146 mm wide and 132 mm high, and the isotropic pixel size was 0.03 mm. The force increment was based on finite-element predictions of the fracture load. The compressive stage was used to apply the displacement to the specimen and enact the prescribed force increments. Sub-capital fractures due to opening and shear of the femoral neck occurred after four to five load increments. The micro-CT images and the reaction force measurements were processed to study the bone strain and energy absorption capacity. Instability of the cortex appeared at the early loading steps. The subchondral bone in the femoral head displayed large deformations reaching 16% before fracture, and a progressive increase in the support capacity up to fracture. The deformation energy linearly increased with the displacement up to fracture, while the stiffness decreased to near-zero values immediately before fracture. Three-fourths of the fracture energy was taken by the specimen during the final 25% force increment. In conclusion, the protocol developed revealed a remarkable energy absorption capacity, or damage tolerance, and a synergic interaction between the cortical and trabecular bone at an advanced donor age.


X-ray crystal structure of rac-[Ru(phen)2dppz]2+ with d(ATGCAT)2 shows enantiomer orientations and water ordering.
We report an atomic resolution X-ray crystal structure containing both enantiomers of rac-[Ru(phen)2dppz](2+) with the d(ATGCAT)2 DNA duplex (phen = phenanthroline; dppz = dipyridophenazine). The first example of any enantiomeric pair crystallized with a DNA duplex shows different orientations of the Λ and Δ binding sites, separated by a clearly defined structured water monolayer. Job plots show that the same species is present in solution. Each enantiomer is bound at a TG/CA step and shows intercalation from the minor groove. One water molecule is directly located on one phenazine N atom in the Δ-enantiomer only.


[Evaluation of the effect of carvedilol in children with dilated cardiomyopathy].
To evaluate the effect of carvedilol administrated during 8 months in children with heart failure secondary to dilated cardiomyopathy. We initiated carvedilol in patients who, despite optimization of standard treatment, had persistent left ventricular ejection fraction < or = 40% and evaluated the systolic and diastolic left ventricular function before and after 4 and 8 months of treatment. 19 patients were included in the study, 10 women; median age: 6.7 years and 17 +/- 12.4 months after the diagnosis. The ejection fraction improved significantly from entry to eight months (median: 33.5 to 52.6%, p = 0.01) as did the shortening fraction (m: 14.8 to 25.8%, p = 0.01). The myocardial performance index abnormal in all 19 patients became normal in 5 at the end of study. In addition mitral Doppler flow which was altered in 9 improved in 3 and pulmonary venous flow abnormal in all patients improved in 13. Only 1 patient presented minimal adverse effects. Carvedilol added to standard therapy for dilated cardiomyopathy improves left ventricular function, is well tolerated, and has minimal adverse effects in childhood.


[Effect of therapy with cytostatic drugs on the hemostasis system in patients with small cell and non-small cell bronchial cancers, malignant lymphomas and plasmacytomas].
Hemostatic analyses were carried out on 43 patients with small and non-small cell lung cancer, malignant lymphomas and plasmacytomas prior to, 4 h and 24 h after application of chemotherapy. The fibrinopeptide A (FPA) level and the FPA in vitro generation rate (delta FPA) increased significantly only in the small cell lung cancer and malignant lymphomas after 4 h. This supports the thesis of the clotting activation after cytostatic-induced exposition of the tumour cell thromboplastins. An increase in the FPA was observed in those tumor patients, where a high therapy-induced cell destruction was expected. An increase in the activity of factor VIII, as was seen in acute phase reactions, also led to hypercoagulability. Fibrinogen and plasminogen decreased significantly after chemotherapy. Evidence of relevant contact activation was not found in the missing deviation of the C1 inhibitor. The increase in protein C may possibly be attributed to the high-dose corticoid therapy.


Mapping of linear epitopes on the capsid proteins of swine vesicular disease virus using monoclonal antibodies.
The antigenic linear map of swine vesicular disease virus (SVDV) has been studied using a repertoire of monoclonal antibodies (mAbs) raised against a recombinant SVDV polyprotein, P1. Peptide-scanning analyses, cross-reactivity studies with homologous and heterologous viruses and predicted location on a computer-generated three-dimensional model of the capsid proteins have allowed the identification of five main linear sites. Two sites, the N terminus of VP3 and amino acids 51-60 on VP1, correspond to internal areas, conserved not only between SVDV isolates but also in the related enterovirus coxsackievirus B5. In contrast, three other regions, amino acids 142-161 of VP2, 61-70 of VP3 and the C terminus of VP1, are exposed on the external face of the capsid and subjected to antigenic variation, even among different SVDV isolates. Further minor sites that were antigenically conserved were identified on VP4. In contrast with conformational sites described previously, none of the linear epitopes identified in this work is involved in neutralization of virus infectivity and post-infection swine sera did not inhibit the binding of mAbs with the relevant epitopes. Both of these observations suggest that linear epitopes are poorly immunogenic in pigs. The characterization of linear sites has contributed to a better understanding of the antigenic structure of SVDV and mAbs used to this purpose may provide a useful tool for the improvement of diagnostic methods, such as antigen detection systems, and analyses of the antigenic profile of SVDV isolates.


Biological formation of ethylene.
This review summarizes the structures, biochemical properties, and mechanisms of two major biological sources of ethylene, the ethylene-forming enzyme (EFE) and 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase (ACCO). EFE is found in selected bacteria and fungi where it catalyzes two reactions: (1) the oxygen-dependent conversion of 2-oxoglutarate (2OG) to ethylene plus three molecules of CO2/bicarbonate and (2) the oxidative decarboxylation of 2OG while transforming l-arginine to guanidine and l-Δ1-pyrroline-5-carboxylic acid. ACCO is present in plants where it makes the plant hormone by transforming ACC, O2, and an external reductant to ethylene, HCN, CO2, and water. Despite catalyzing distinct chemical reactions, EFE and ACCO are related in sequence and structure, and both enzymes require Fe(ii) for their activity. Advances in our understanding of EFE, derived from both experimental and computational approaches, have clarified how this enzyme catalyzes its dual reactions. Drawing on the published mechanistic studies of ACCO and noting the parallels between this enzyme and EFE, we propose a novel reaction mechanism for ACCO.


'Voices of concern'-a study of verbal communication about patients in a psychiatric day unit.
In this study, the author employs observations from a psychiatric day unit in an analysis of regularly occurring forms of 'professional talk'. Considerable staff time is scheduled for such talk, which must be considered as part of the health professional's work. Much of the talk which occurs may be analysed as having 'technical' significance in programming staff to behave appropriately towards different patients, so as to maximize the effectiveness of hospital treatment. Very much more time than is technically necessary, however, is devoted to talking about patients. Rather than seeing this 'superfluity' of talk as an indication of inefficiency within the system, the author examines its functions in maintaining the social structure of the unit and meeting the personal needs of the staff. This appears to be of particular importance against the background (common to many psychiatric settings) of staff-patient and interdisciplinary role ambiguity, high patient chronicity, and the absence of many of the structural and symbolic 'props' of a conventional hospital. This 'excess talk' is expensive in terms of professional time, and takes time away from direct patient contact. None the less, it may be a necessary cost if staff are to continue to pursue therapeutic goals within a deliberately 'informal' psychiatric setting.


Role of soluble myosin in cortical contractions of Xenopus eggs.
The layer of cytoplasm underlying the plasmalemma of Xenopus eggs has contractile activity which is of vital importance in fertilization and early development, being involved in such processes as sperm engulfment, cortical granule exocytosis, development of the axes of embryonic symmetry and cleavage. In amphibian eggs this layer is also involved in wound healing and changes of cellular shape at gastrulation. Two kinds of contractile structures can be distinguished near the surface of Xenopus eggs. To characterize the mechanism and regulation of this contractile activity, we have experimentally induced cortical contractions in bisected living Xenopus eggs. We have shown previously that cortical contractions are induced by calcium ions in the bisected egg. Here we show that extraction of soluble cytoplasmic components prevents the calcium-induced contractions, but that addition of exogenous soluble myosin restores them. In oocytes, both soluble and insoluble components of the cortical cytoplasm are unable to support contraction. Thus, during meiotic maturation of oocytes into eggs, both of the components of the cortical cytoplasm must change so as to become competent for contraction.


The screen team.
Breast cancer screening take-up is very low among women with a learning disability. Nurses in Leeds are trying to change the situation.


Quantum anomalous Hall effect and topological phase transition in two-dimensional antiferromagnetic Chern insulator NiOsCl6.
By doing calculations based on density functional theory, we predict that the two-dimensional anti-ferromagnetic (AFM) NiOsCl6 as a Chern insulator can realize the quantum anomalous Hall (QAH) effect. We investigate the magnetocrystalline anisotropy energies in different magnetic configurations and the Néel AFM configuration is proved to be ground state. When considering spin-orbit coupling (SOC), this layered material with spins perpendicular to the plane shows properties as a Chern insulator characterized by an inversion band structure and a nonzero Chern number. The nontrivial band gap is 37 meV and the Chern number C = -1, which are induced by a strong SOC and AFM order. With strong SOC, the NiOsCl6 system performs a continuous topological phase transition from the Chern insulator to the trivial insulator upon the increasing Coulomb repulsion U. The critical U c is indicated as 0.23 eV, at which the system is in a metallic phase with [Formula: see text]. Upon increasing U, the E g reduces linearly with C = -1 for 0 < U < U c and increases linearly with C = 0 for U > U c . At last we analysis the QAH properties and this continuous topological phase transition theoretically in a two-band [Formula: see text] model. This AFM Chern insulator NiOsCl6 proposes not only a promising way to realize the QAH effect, but also a new material to study the continuous topological phase transition.


Thermal adjustment to cold-water exposure in resting men and women.
Thermoregulatory responses were studied in 10 men and 8 women at rest in air and during 1-h immersion in water at 20, 24, and 28 degrees C. For men of high body fat (27.6%), rectal temperature (Tre) and oxygen consumption (VO2) were maintained at air values at all water temperatures (Tw). For men of average (16.8%) and low (9.2%) fat the change in Tre (delta Tre) was inversely related to body fat at all Tw with VO2 increasing to 1.07 l X min-1 for a -1.6 degrees C delta Tre for lean men. For women of average (25.2%) and low (18.5%) fat Tre decreased steadily during immersion at all Tw. The greatest changes occurred at 20 degrees C with little differences in delta Tre and VO2 noted between these groups of women. In comparison with males of similar percent fat, Tre dropped to a greater extent (P less than 0.05) in females at 20 and 24 degrees C. Stated somewhat differently, lean women with twice the percentage of fat have similar delta Tre as lean men at all Tw. For delta Tre greater than -1.0 degree C men showed significantly greater (P less than 0.05) thermogenesis compared with women. The differences in thermoregulation between men and women during cold stress at rest may be due partly to the sensitivity of the thermogenic response as well as the significant differences in lean body weight and surface area-to-mass ratio between the sexes.


Dynamics of dissolved and particulate phosphorus influenced by seasonal hypoxia in Green Bay, Lake Michigan.
Despite major investments in point source reductions, portions of the Great Lakes, like Green Bay, remain hypereutrophic and are subject to persistent seasonal hypoxia. Phosphorus (P) is generally a limiting nutrient in the Great Lakes ecosystem, but not all P species are equally bioavailable, and the dynamics of nutrients and their correlation to algal bloom remain poorly characterized, in part, due to a lack of adequate quantification of P chemical speciation. During summer 2014, water samples were collected from seasonally hypoxic Green Bay for measurements of dissolved and particulate inorganic and organic P to examine P cycling dynamics along a steep nutrient gradient ranging from Fox River inflow dominated eutrophic waters in the southern bay to mesotrophic northern waters near the bay's connection with open Lake Michigan. River-derived dissolved and particulate P was quickly removed from the water column in southern Green Bay through biological uptake and sedimentation. Concentrations of phosphate or dissolved inorganic P (DIP) dramatically decreased from 828 ± 216 nM in the Fox River, comprising 57 ± 1% of the total dissolved P, to 24 ± 9 nM in northern Green Bay where dissolved organic P (DOP) became predominant (>80%). Generally low phosphate concentrations and extremely high dissolved organic C/P ratios (2090 ± 1160 in August 2014) suggested high DOP turnover rates and active transformation between DOP and DIP through organic degradation during P-limited conditions in Green Bay. Elevated DIP levels were accompanied by low dissolved oxygen in deeper waters (10-15m) of central Green Bay where hypoxia-development occurred, suggesting the release of DIP through particle regeneration under hypoxic conditions enhanced by lateral transport and sediment resuspension. High partition coefficients (Kd) of both inorganic and organic P and their significant negative correlation with suspended particulate matter concentrations indicated the particle-reactive nature of P in freshwater environments and may imply that DOP could also be bioavailable under P-limitation.


Brushing up from "anywhere" under sunlight: a universal surface-initiated polymerization from polydopamine-coated surfaces.
We describe a simple yet extremely versatile and generalized surface polymer modification approach based on a surface initiated polymerization from a polydopamine (PDA) layer. PDA deposits on virtually any substrate independent of specific surface chemistries and can act as a photoinitiating layer to initiate the radical polymerization of a variety of (methyl)acrylic/styrene monomers. It does not require any metal/ligand catalyst, additional photoinitiator or dye sensitizer. Another attractive feature of this novel strategy is the ability to spatially control the architectures (pattern, gradient) of the polymer films by altering the areas of light irradiation. It is also adaptable to large area grafting with an ultra-small amount of monomer solution (a thin monomer solution layer).


Immunoglobulin subunits of murine B lymphocytes: structure and associations with other membrane proteins.
The Ig subunit structure of murine B lymphocytes was studied by employing different radiolabelling techniques in combination with chemical cross-linking. The main membrane structure of IgM was a half molecule that was disulphide-linked to proteins with MW 30,000, 45,000 and 55,000, respectively. Small amounts of mu 2L2, microL disulphide-linked to a protein with MW 50,000, and free microL were also detected. The main IgD structures were half molecules disulphide-linked to two proteins with MW 14,000 and two proteins with MW 16,000. Furthermore, IgD half molecules disulphide-linked to a protein with MW 16,000 and free half molecules could be demonstrated. Labelling with hydrophobic reagents showed that all Ig molecules and the protein with MW 50,000, linked to microL, penetrated the lipid bilayer, whereas the other IgM- and IgD-linked proteins probably did not. Additional proteins which were associated exclusively with IgM were detected by chemical cross-linking. These findings offer new possibilities for the investigation of the function(s) of antigen receptors on B cells.


[History of the Department of Neurology at the University of Buenos Aires (1887-2007)].
In 1887, only five years after Jean-Martin Charcot was awarded the Head of Neurology at "La Salpetrière" in Paris, José María Ramos Mejía became the first professor of Neurology in South America, at the School of Medicine of the University of Buenos Aires. Ramos Mejía convoked three assistants, the neuropathologist Christofredo Jakob, the clinician José A. Esteves and José Ingenieros. Hence it followed that Neurology in Argentina took a stand based on a clinical neurology-neuropathology approach (1941-1987) followed by a clinical-semiological attitude, finally inserting itself within the modern times (1987-present) by creating subspecialties. Throughout its history, Argentina has made remarkable contributions to Neurology, such as the diagnosis and pathogenesis of the nervous system involvement occurring in some regional endemic disorders -for instance, Chagas' disease-, the clinical approach to the diagnosis of dementias, and the pathogenesis of extrapyramidal illnesses and other primary degenerative diseases of the central nervous system, mainly amyotrophic lateral sclerosis. On the other hand, in recent years globalization allowed neurologists to participate in international cooperative projects, favoring a swifter development in the practice of this discipline.


Assessment of a Novel Standardized Training System for Mandibular Contour Surgeries.
Mandibular contour surgeries (MCS) involving reduction gonioplasty and genioplasty are rewarding for patients with square faces; however, the procedure has inherently difficult clinician learning curves and unpredictable skill acquisitions. To our knowledge, there has been no effective, validated training model that might improve training and surgical outcomes for MCS. To establish and evaluate a standardized intraoral MCS training system. Intraoral MCS training models were constructed by 3-dimensional (3D) skull models covered with elastic head cloths. From April 2016 to April 2018, 90 consecutive MCS patients (30 per group) and 15 craniofacial surgery fellow physicians (5 per group) were enrolled in the prospective observational study. They were randomly divided into intervention groups (A and B) and a control group (C). Intervention groups A and B completed 5 training sessions on the intraoral MCS training models before each clinical case. Group A performed both the model training sessions and clinical surgeries with surgical templates. Control group C had no extra training before clinical surgeries. All groups completed clinical surgery under supervision on 6 patients. The duration of follow-up was at least 3 months postoperatively. Intraoral MCS training models were provided to intervention groups (A and B) before clinical surgeries. Surgical templates were provided to intervention group A both in training sessions and clinical surgeries. The completion time, surgical accuracy, learning curves, operating confidence, surgical skill, and outcome satisfaction of each procedure were recorded and analyzed with paired t test and 1-way analysis of variance test by blinded observers. All 90 patients (14 men, 76 women; mean [SD] age, 26 [5] years) were satisfied with their postoperative mandible contours. The intervention groups (A and B), especially the group with surgical templates (A) showed improvements in clinical surgery time (mean [SD], group A 147.2 [24.71] min; group B, 184.47 [16.28] min; group C, 219.3 [35.3] min; P = .001), surgical accuracy (mean [SD], group A, 0.68 [0.22] mm; group B, 1.22 [0.38] mm; group C, 1.88 [0.54] mm; P < .001), learning curves, and operators' confidence and surgical skill. The intraoral MCS training model was effective and practical. The optimal intraoral MCS training system included intraoral MCS training models and surgical templates. The system significantly decreased clinical surgery time, improved surgical accuracy, shortened the learning curve, boosted operators' confidence, and was associated with better acquisition of surgical skills. NA.


HOXA11-AS: a novel regulator in human cancer proliferation and metastasis.
Multiple studies have demonstrated that lncRNAs extensively participate in human cancer proliferation and metastasis. Epigenetic modification, transcriptional and posttranscriptional regulatory mechanisms are involved in lncRNA-led tumorigenesis and transfer. Recently, a novel identified homeobox (HOX) A11 antisense lncRNA, HOXA11-AS, 1,628 bp in length, has been excessively highlighted to be an essential initiator and facilitator in the process of malignant tumor proliferation and metastasis. As found in many reports, HOXA11-AS can not only act as a molecular scaffold of PRC2, LSD1 and DNMT1 to epigenetically modify chromosomes in the nucleus but also occur as ceRNA competitively sponging miRNAs in the cytoplasm. Furthermore, HOXA11-AS may function as a potential biomarker for cancer diagnosis and prognosis. In this review, we summarize the evolvement and mechanisms of HOXA11-AS in proliferation and metastasis of various human cancers.


How Electronic Cigarette Affects the Vascular System.
The popularity of the electronic cigarette has soared in the last decades. However, the health effect of smoking electronic cigarettes on the vascular system is unclear. This systematic review examines the electronic cigarettes' effect on the vascular system from recent evidence. A systematic search was conducted in MEDLINE (PubMed) database from January 2016 to August 2021 for studies assessing the vascular effect of chronic use of electronic cigarettes on human and animal. The Cochrane Risk of Bias 2, NIH Quality Assessment for Cross-Sectional Study, and SYRCLE's Risk of Bias were used to assess the risk of bias in interventional, observational, and animal study, respectively. A narrative synthesis of evidence is provided to describe results. From 101 retrieved studies related to electronic cigarettes effect on the vascular system, a total of 16 studies are included in this review. The overall results indicated that electronic cigarette use is associated with adverse events in the vascular, including the incident of elevated oxidative stress, endothelial dysfunction, inflammation, arterial stiffness, and the development of atherosclerotic lesion. Further studies should broaden perspectives and reveal more about the mechanism of how electronic cigarettes impact on vascular system.


Uptake of Pb(II) and Cd(II) on Chitosan Microsphere Surface Successively Grafted by Methyl Acrylate and Diethylenetriamine.
A novel adsorbent, CS-MA-DETA microspheres, for uptake of heavy metal ions from aqueous solutions was first fabricated via two-step grafting methyl acrylate (MA) and diethylenetriamine (DETA) onto chitosan (CS) microsphere surface in the absence of cross-linkers. CS-MA-DETA microspheres of 3.04 μm in mean diameter were of uniformly wrinkle-like topography sketched out by SEM, whose surface after decoration by MA and DETA was stable and beneficial to metal ion capture. Its chemical composition, microstructure, and thermal property were characterized by elemental analysis, FTIR, XRD, BET, and TGA techniques, and the achieved quantitative results mainly included C/N ratio (4.76), crystallinity (31.20%, 19.75% of CS), specific surface area (27.806 m2 g-1), pore diameter (3.452 nm), and mass loss at the first stage (3%, around 10% of CS), which indicated a successful synthesis, well-defined structure, and good thermostability. Adsorption tests of CS-MA-DETA microspheres were performed in Pb(II) and/or Cd(II) solution(s) at various pH values, contact time, and initial concentrations, exhibiting an excellent adsorption capability. Its maximum adsorption capacity calculated by Langmuir model was 239.2 mg Pb(II)/g, or 201.6 mg Cd(II)/g, which was higher than those of most available CS-based adsorbents. Furthermore, several adsorption kinetic and isotherm models were employed to investigate its uptake behavior, implying that it was mainly a monolayer adsorption and chemisorption process. Five-cycle reusability tests demonstrated CS-MA-DETA microspheres could be repeatedly used without significant capacity loss (<10%). Additionally, several potential bonding modes and adsorption sites for both metal ions were also proposed. Overall, CS-MA-DETA microspheres with outstanding adsorption performance toward Pb(II) and/or Cd(II) might serve as a new absorbent for wastewater purification.


Global analysis of the human pathophenotypic similarity gene network merges disease module components.
The molecular complexity of genetic diseases requires novel approaches to break it down into coherent biological modules. For this purpose, many disease network models have been created and analyzed. We highlight two of them, "the human diseases networks" (HDN) and "the orphan disease networks" (ODN). However, in these models, each single node represents one disease or an ambiguous group of diseases. In these cases, the notion of diseases as unique entities reduces the usefulness of network-based methods. We hypothesize that using the clinical features (pathophenotypes) to define pathophenotypic connections between disease-causing genes improve our understanding of the molecular events originated by genetic disturbances. For this, we have built a pathophenotypic similarity gene network (PSGN) and compared it with the unipartite projections (based on gene-to-gene edges) similar to those used in previous network models (HDN and ODN). Unlike these disease network models, the PSGN uses semantic similarities. This pathophenotypic similarity has been calculated by comparing pathophenotypic annotations of genes (human abnormalities of HPO terms) in the "Human Phenotype Ontology". The resulting network contains 1075 genes (nodes) and 26197 significant pathophenotypic similarities (edges). A global analysis of this network reveals: unnoticed pairs of genes showing significant pathophenotypic similarity, a biological meaningful re-arrangement of the pathological relationships between genes, correlations of biochemical interactions with higher similarity scores and functional biases in metabolic and essential genes toward the pathophenotypic specificity and the pleiotropy, respectively. Additionally, pathophenotypic similarities and metabolic interactions of genes associated with maple syrup urine disease (MSUD) have been used to merge into a coherent pathological module.Our results indicate that pathophenotypes contribute to identify underlying co-dependencies among disease-causing genes that are useful to describe disease modularity.


[Analysis of 16S rDNA sequence of Cronobacter spp].
To analyse the sequence of 16S rDNA of twenty-nine Cronobacter spp. strains isolated from food as well as two type strains. Using polymerase chain reaction to obtain the sequences of 16S rDNA of all strains. The multiple cluster analysis and phylogenetic analysis of them were studied by BioNumerics software. All strains, except ATCC51329 and ES 014, were clustered with the Cronobacter spp. type strain ATCC29544. The Cronobacter spp. type strain ATCC51329 and ES 014 belonged to a different branch. From the sequence analysis of 16S rDNA, all these isolates of Cronobacter spp. except ES 014 could be identified accurately by gene analysis. All Cronobacter spp. strains isolated from food were identified on genetic level. The phylogenetic relationships among related Cronobacter spp. isolates were studied.


[Intraoperative coagulation activity--a defined group of trauma surgery patients].
Analyses of blood coagulation in a defined group of patients before, during, and after trauma-surgery confirms an intraoperative trigger-mechanism, that causes postoperative thromboembolic complications. They also proof the correlation between extent of tissue-lesion and extent of triggering, this was previously presumed from the postoperative incidence of thromboembolic complications. Apart from the usual blood coagulation tests the following parameters where analysed: Factor VIII: C, Ristocetin-Co-factor, Factor Xa, AT III, TAT, Reptilase-time, tPA, D-dimers, and FPA. Simultaneously, it was shown, that a preoperative prophylaxis of thrombosis can prevent an intraoperative increase of Factor Xa, that plays a key role in postoperative thromboembolic complication. The increased intraoperative turnover of coagulation factors, which is necessary for physiologic blood coagulation, is not prevented.


Specificity of the photoreaction of 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen with ribonucleic acid. Identification of reactive sites in Escherichia coli phenylalanine-accepting transfer ribonucleic acid.
In order to test the potential of psoralen photoaddition for the probing of RNA conformation at sequence resolution, we have analyzed the specificity of the reaction of 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen (HMT) with Escherichia coli tRNAPhe. The sites of HMT covalent addition have been identified by a combination of analytical techniques involving chemical cleavage of the tRNAPhe molecule at the m7G site and gel electrophoresis of RNase T1 digests together with paper electrophoretic characterization of HMT-modified nucleotides and oligonucleotides. In addition, we have taken advantage of the alteration of the cleavage rate of pancreatic RNase adjacent to a photoadduct. HMT photoaddition shows a very high preference for uracil residues. However, important differences in HMT photoreactivity are observed for various U sites of the tRNAPhe molecule. Reactivity of specific bases has been correlated with partial melting of the molecule. Data available so far indicate a strong preference of the photoreactive probe for a "loose" helical conformation as compared with a tight helix, whereas a random coil appears poorly reactive.


STA-MCA Bypass as a "Bridge" to Pituitary Surgery in a Patient with an Adenoma Occluding the Internal Carotid Artery: Case Report and Review of the Literature.
Occlusion of the intracranial internal carotid artery (ICA) by a pituitary adenoma with resulting cerebral ischemia is a very rare but devastating occurrence. The authors present a case in which a condition of symptomatic ICA occlusion due to a giant pituitary adenoma was successfully treated using a preliminary extraintracranial bypass as a "bridge" to the tumor removal. A 52-year-old patient presented with a minor stroke followed by pressure-dependent transient ischemic attacks consistent with a condition of hypoperfusion. MR imaging and a digital subtraction angiography revealed a pituitary adenoma occluding the ICA on the right side. He underwent a superficial temporal artery to middle cerebral artery (STA-MCA) bypass with the aim of revascularizing the ischemic hemisphere and reducing the risk of perioperative stroke or stroke evolution. The patient was subsequently operated on to remove the adenoma through a transsphenoidal approach. The postoperative course was uneventful and the patient has suffered no further ischemic events. When there are no emergency indications to decompress the optical pathways but the patient is at risk of impending stroke because of ICA occlusion, a two-step strategy consisting of a bypass and subsequent removal of the pituitary adenoma may be a valuable option.


Serotoninergic dysfunction in the 47, XYY syndrome.
In six XYY patients suffering from aggressiveness and admitted by order of law into a security setting for acts of violence, the estimation of cerebrospinal fluid amine metabolites before and after a probenecid test revealed a clear decrease in the turnover of central serotonin (5-HT) while that of dopamine (DA) was unchanged. The treatment with the 5-HT precursor, L-5-hydroxytryptophan (L-5-HTP), in five of the XYYs resulted in a clinical status equivalent to that observed when the patients were previously treated by conventional neuroleptics.


Impact comparison of ketamine and sodium thiopental on anesthesia during electroconvulsive therapy in major depression patients with drug-resistant; a double-blind randomized clinical trial.
Electroconvulsive therapy (ECT) is one of the available and the most effective therapies for the treatment of resistant depression. Considering the crucial role of seizure duration on therapeutic response in patients treated with ECT, this study aimed to compare the effect of ketamine and sodium thiopental anesthesia during ECT for treatment of patients with drug-resistant major depression (DRMD). In a double-blind randomized clinical trial, 160 patients with DRMD were selected consequently and were assigned randomly into two groups including ketamine 0.8 mg/kg and sodium thiopental 1.5 mg/kg. The seizure duration, recovery time, and the side effects of anesthesia were evaluated after 1-h after anesthesia. Data of recovery time and complication collected in 2 nd , 4 th , 6 th , and 8 th ECT. Depression was assessed by Hamilton depression scale. The results indicated that ketamine and sodium thiopental had a significant effect on the reduction of depression scores in patients with DRMD (P < 0.05). Complications such as a headache, nausea, pain at the injection site, short-term delirium, and long-term delirium were higher in ketamine group (P > 0.05). But ketamine was more effective in improvement of depression score and increasing systolic and diastolic blood pressure (P < 0.05). The mean of seizure duration showed a decreasing trend and was significant between two study groups (P < 0.05). Anesthesia induced by ketamine during ECT therapy increased blood pressure and seizure duration. Therefore, due to lower medical complication and attack rate of seizure, ketamine is an appropriate option for anesthesia with ECT in patients with DRMD.


Memory T Cell Migration.
Immunological memory is a key feature of adaptive immunity. It provides the organism with long-lived and robust protection against infection. In organ transplantation, memory T cells pose a significant threat by causing allograft rejection that is generally resistant to immunosuppressive therapy. Therefore, a more thorough understanding of memory T cell biology is needed to improve the survival of transplanted organs without compromising the host's ability to fight infections. This review will focus on the mechanisms by which memory T cells migrate to the site where their target antigen is present, with particular emphasis on their migration to transplanted organs. First, we will define the known subsets of memory T cells (central, effector, and tissue resident) and their circulation patterns. Second, we will review the cellular and molecular mechanisms by which memory T cells migrate to inflamed and non-inflamed tissues and highlight the emerging paradigm of antigen-driven, trans-endothelial migration. Third, we will discuss the relevance of this knowledge to organ transplantation and the prevention or treatment of allograft rejection.


Multiple sclerosis and pregnancy prescriptions.
Multiple sclerosis (MS) is a major neurologic disorder which preferentially affects young women of childbearing age. In the last two decades, a number of disease-modifying therapies have become available to treat relapsing forms of MS. None of these agents is approved for use in pregnancy. The timing of treatment versus conception, and risk of drug pregnancy exposures, are frequent discussion topics when caring for MS patients. This editorial will try to put into context available data, approaches, controversies and future needs.


Combined effects of clenbuterol and various concentrations of protein on performance of broiler chickens.
1. The effects of the beta-adrenergic agonist, clenbuterol (1 mg/kg diet) on the growth and muscle composition in female broiler chickens (14 to 32 d of age) fed on diets containing various concentrations of protein (220, 240 or 260 g protein/kg) were examined. 2. Body weight gain over the 18 d period increased linearly with increasing protein intake. The rate of gain was significantly higher in clenbuterol-treated chickens than in control birds. 3. Dietary clenbuterol increased thigh muscle weight and protein concentration of breast and thigh muscle, regardless of dietary protein content. Protein/DNA ratio in thigh muscle was enhanced by clenbuterol feeding, and the magnitude of difference of the ratio was higher in chickens fed on the 240 and 260 g CP/kg diets than in those fed the 220 g CP/kg diet. 4. It was concluded that clenbuterol-treated chickens require increased dietary protein to maintain maximal growth, and that increased protein consumption is an important factor in improving growth in clenbuterol-fed broilers.


Buerger's disease: clinical and histomorphological study.
There is an extremely high prevalence of Thromboangiitis Obliterans (TAO) or Buerger's disease (BD) in India among people of low socioeconomic class who smoke beedies (homemade cigarettes with raw tobacco). The aim of this study was to study the clinical and histo-morphological aspects of Buerger's disease with relevance to age at presentation in the local population. The study comprised of 25 cases (all were men and were smokers) of clinically diagnosed BD based on Shionoya's criteria. The mean age was 47 years. The specimens consisted of 21 biopsies, 2 end-arterectomies and 2 amputations. Formalin fixed, routinely processed, paraffin embedded tissue sections were stained with Haematoxylin and Eosin (H and E) and Verhoeff's elastic stain. They had claudication pain either in the ankle (5) or in the calf (2) or both (13). 24 had infrapopliteal disease and 9 showed upper limb involvement. 21 showed migratory thrombophlebitis also. Histomorphological presentation included the following features: Luminal thrombosis (14), fresh thrombosis (4), chronic inflammation in the vessel wall (10), within the thrombus (1) and around perivascular channels and nerve bundles (4). Internal elastic lamina showed reduplication in 13, undulation in 9 and fragmentation in 9 cases. Media of the vessel showed the following features: fibrosis (9), hypertrophy (9) and calcification (5) Adventitial haemorrhage, cholesterol clefts and atherosclerotic plaque formation were the other changes seen. In our study the following histopathological features were consistently seen. Thrombus (with or without recanalisation), inflammatory cell infiltrate (within the thrombus wall or periadventitial tissue), subintimal and medial fibrosis and changes in internal elastic lamina. These features were also highlighted in other studies. However in our study, medial hypertrophy and calcification were observed as additional features.


Lysophosphatidylcholines containing polyunsaturated fatty acids were found as Na+, K+-ATPase inhibitors in acutely volume-expanded hog.
Na+, K+-ATPase inhibitors possessing inhibitory activities against the specific binding of ouabain to Na+, K+-ATPase and 86Rb uptake into hog erythrocytes have been purified from the plasma of acutely saline-infused hog. The purifications were performed by a combination of Amberlite XAD-2 adsorption chromatography and four steps of high-performance liquid chromatography with four different types of columns. Fast atom bombardment (FAB) mass and proton NMR spectrometric studies identified the purified substances as gamma-arachidoyl- [LPCA(gamma), 34%], beta-arachidoyl- [LPCA(beta), 4%], gamma-linoleoyl- (LPCL, 33%), and gamma-oleoyl- (LPCO, 25%) lysophosphatidylcholine, expressed in molar ratio in the plasma. Small amounts of gamma-docosapentaenoyl-, gamma-eicosatrienoyl-, and gamma-palmitoyllysophosphatidylcholine were also detected by both FAB mass and 1H NMR spectrometric studies. Only gamma-acyl-LPC's showed inhibitory activities on Na+,K+-ATPase and ouabain-binding activities. These LPC's were effective at 100 microM levels in attaining 50% inhibition of the enzyme activity. The inhibition of Na+,K+-ATPase activity due to these compounds was always more sensitive than that of both ouabain-binding and 86Rb uptake activities. The ouabain-displacing activity in plasma due to these compounds increased with time during saline infusion. The maximal plasma level was approximately 10 times higher than that in the preinfusion plasma sample. Although these results suggest the gamma-acyl-LPC's with long-chain polyunsaturated fatty acids are not simple competitive inhibitors to Na+, K+ -ATPase, these compounds could be implicated in the pathogenesis of the circulation abnormality through the modulation of membrane enzyme.


Viral safety of recombinant factor IX.
The viral safety of Chinese hamster ovary (CHO)-cell-based pharmaceuticals is well established. There have been more than 100 million infusions of CHO-derived pharmaceuticals without a single documented case of viral transmission. The recombinant factor IX (rFIX) process builds on this safety record by using a state-of-the-art multitiered approach to viral safety. This includes extensive testing of the CHO cells used to produce rFIX, routine viral monitoring of the cell culture production process, a manufacturing process and formulation that do not use blood or plasma products, and validation of the viral removal capacity of the purification process. The multifaceted viral safety program for rFIX has sufficient redundancy between approaches to compensate for potential limitations of any single safety measure. Together, the elements of the rFIX multitiered viral safety program offer patients and physicians a product that is inherently free of human blood-borne pathogens, including any risk of human immunodeficiency virus (HIV) hepatitis, parvovirus, and Creutzfeldt-Jakob disease (CJD).


Fabrication of ZnO nanospikes and nanopillars on ITO glass by templateless seed-layer-free electrodeposition and their field-emission properties.
A simple and direct electrodeposition technique is employed to fabricate ZnO nanospikes and nanopillars on indium-tin oxide glass substrates at 70 degrees C without using any template, catalyst, or seed layer. Both ZnO nanospikes and nanopillars exhibit highly crystalline ZnO wurtzite structure with a preferred (0001) plane orientation in their high-resolution transmission electron microscopic images and X-ray diffraction patterns. The corresponding Raman spectra provide evidence for the presence of defects and oxygen vacancies in these nanostructures, which could produce the photoluminescence observed in the visible region. X-ray photoelectron spectroscopy further indicates the presence of a Zn(OH)2-rich surface region in these ZnO nanostructures and that a higher Zn(OH)2 surface moiety is found for nanospikes than nanopillars. In contrast to the nanopillars with flat tops, the nanospikes with tapered tips of 20-50 nm diameter provide a favorable geometry to facilitate excellent field-emission performance, with a low turn-on electric field of 3.2 V/microm for 1.0 microA/cm(2) and a threshold field of 6.6 V/microm for 1.0 mA/cm(2). The superior field-emission property makes the nanospikes among the best ZnO field emitters fabricated on a glass substrate at low temperature.


Indoor Airborne Ultrasonic Wireless Communication Using OFDM Methods.
Concerns still exist over the safety of prolonged exposure to radio frequency (RF) wireless transmissions and there are also potential data security issues due to remote signal interception techniques such as Bluesniping. Airborne ultrasound may be used as an alternative to RF for indoor wireless communication systems for securely transmitting data over short ranges, as signals are difficult to intercept from outside the room. Two types of air-coupled capacitive ultrasonic transducer were used in the implementation of an indoor airborne wireless communication system. One was a commercially available SensComp series 600 ultrasonic transducer with a nominal frequency of 50 kHz, and the other was a prototype transducer with a high- k dielectric layer operating at higher frequencies from 200 to 400 kHz. Binary phase-shift keying (BPSK), quadrature phase-shift keying (QPSK), and quadrature amplitude modulation (QAM)-based orthogonal frequency division multiplexing modulation methods were successfully implemented using multiple orthogonal subchannels. The modulated ultrasonic signal packets were synchronized using a wireless link, and a least-squares channel estimation algorithm was used to compensate the phase and amplitude distortion introduced by the air channel. By sending and receiving the ultrasonic signals using the SensComp transducers, the achieved maximum system data rate was up to 180 kb/s using 16-QAM with ultrasonic channels from 55 to 99 kHz, over a line-of-sight transmission distance of 6 m with no detectable errors. The transmission range could be extended to 9 and 11 m using QPSK and BPSK modulation schemes, respectively. The achieved data rates for the QPSK and BPSK schemes were 90 and 45 kb/s using the same bandwidth. For the high- k ultrasonic transducers, a maximum data rate up to 800 kb/s with no measurable errors was achieved up to a range of 0.7 m. The attainable transmission ranges were increased to 1.1 and 1.2 m with data rates of 400 and 200 kb/s using QPSK and BPSK, respectively.


Applying GRADE-CERQual to qualitative evidence synthesis findings-paper 3: how to assess methodological limitations.
The GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research) approach has been developed by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group. The approach has been developed to support the use of findings from qualitative evidence syntheses in decision-making, including guideline development and policy formulation. CERQual includes four components for assessing how much confidence to place in findings from reviews of qualitative research (also referred to as qualitative evidence syntheses): (1) methodological limitations, (2) coherence, (3) adequacy of data and (4) relevance. This paper is part of a series providing guidance on how to apply CERQual and focuses on CERQual's methodological limitations component. We developed the methodological limitations component by searching the literature for definitions, gathering feedback from relevant research communities and developing consensus through project group meetings. We tested the CERQual methodological limitations component within several qualitative evidence syntheses before agreeing on the current definition and principles for application. When applying CERQual, we define methodological limitations as the extent to which there are concerns about the design or conduct of the primary studies that contributed evidence to an individual review finding. In this paper, we describe the methodological limitations component and its rationale and offer guidance on how to assess methodological limitations of a review finding as part of the CERQual approach. This guidance outlines the information required to assess methodological limitations component, the steps that need to be taken to assess methodological limitations of data contributing to a review finding and examples of methodological limitation assessments. This paper provides guidance for review authors and others on undertaking an assessment of methodological limitations in the context of the CERQual approach. More work is needed to determine which criteria critical appraisal tools should include when assessing methodological limitations. We currently recommend that whichever tool is used, review authors provide a transparent description of their assessments of methodological limitations in a review finding. We expect the CERQual approach and its individual components to develop further as our experiences with the practical implementation of the approach increase.


Arylation of hydrocarbons enabled by organosilicon reagents and weakly coordinating anions.
Over the past 80 years, phenyl cation intermediates have been implicated in a variety of C-H arylation reactions. Although these examples have inspired several theoretical and mechanistic studies, aryl cation equivalents have received limited attention in organic methodology. Their high-energy, promiscuous reactivity profiles have hampered applications in selective intermolecular processes. We report a reaction design that overcomes these challenges. Specifically, we found that β-silicon-stabilized aryl cation equivalents, generated via silylium-mediated fluoride activation, undergo insertion into sp3 and sp2 C-H bonds. This reaction manifold provides a framework for the catalytic arylation of hydrocarbons, including simple alkanes such as methane. This process uses low loadings of Earth-abundant initiators (1 to 5 mole percent) and occurs under mild conditions (30° to 100°C).


Madelung disease (multiple symmetric lipomatosis).
Madelung disease or multiple symmetric lipomatosis (MSL) is a rare entity among the overgrowth syndromes. It is characterized by painless non-encapsulated and symmetric fatty deposits in the neck, torso, mammary, and abdominal areas, and in the upper and lower limbs. The etiology of the disease is still unknown. Chronic alcohol consumption may play a role in adipocyte hyperplasia in genetically susceptible individuals. Besides the overgrowth of adipose tissue, patients with MSL present features of metabolic syndrome. Patients seek medical attention usually for esthetic reasons. We present the case of a middle-aged man who sought the outpatient clinic complaining of bulging masses in the posterior upper part of the thorax, the occipital area, and the neck. The masses grew over a period of 2 years. The physical examination and imaging study revealed the presence of symmetric lipomatosis. A two-step surgical treatment was undertaken for the excision of the lipomatous tissue. The postoperative outcome was uneventful with satisfactory esthetic results.


Telling Your Right Hand from Your Left: The Effects of DNA Supercoil Handedness on the Actions of Type II Topoisomerases.
Type II topoisomerases are essential enzymes that modulate the topological state of DNA supercoiling in all living organisms. These enzymes alter DNA topology by performing double-stranded passage reactions on over- or underwound DNA substrates. This strand passage reaction generates a transient covalent enzyme-cleaved DNA structure known as the cleavage complex. Al-though the cleavage complex is a requisite catalytic intermediate, it is also intrinsically dangerous to genomic stability in biological systems. The potential threat of type II topoisomerase function can also vary based on the nature of the supercoiled DNA substrate. During essential processes such as DNA replication and transcription, cleavage complex formation can be inherently more dangerous on overwound versus underwound DNA substrates. As such, it is important to understand the profound effects that DNA topology can have on the cellular functions of type II topoisomerases. This review will provide a broad assessment of how human and bacterial type II topoisomerases recognize and act on their substrates of various topological states.


Heparin induced thrombocytopenia.
Heparin induced thrombocytopenia (HIT) is a serious and life endangering complication of heparin therapy. It usually occurs after 5-14 days of continuous heparin therapy. It is immune mediated. Heparin, in the affected individual binds with platelet factor 4 (PF-4) and forms a highly antigenic Heparin PF-4 complex which leads to the generation of specific IgG Heparin PF4 antibodies (also called HIT antibodies). HIT antibodies may activate the platelets via Fcy receptor causing the release of highly coagulable micro particles which promote thrombosis--both venous and arterial. However, all patients with HIT antibodies do not progress to HIT with thrombosis (HITT). HIT can present as asymptomatic thrombocytopenia. It can also present with alarming features of venous and/or arterial thromboembolism, for example, pulmonary embolism from deep vein thrombosis (DVT), limb gangrene warranting amputation, cerebrovascular attack (CVA) or myocardial infarction (MI). Rare manifestation of HIT includes necrotizing skin lesion, acute anaphylactoid reaction following IV heparin bolus and acute adrenal apoplexy due to massive adrenal vein thrombosis. The diagnosis is based upon the combination of unexplained thrombocytopenia, demonstration of HIT antibodies, clinical profile and outcome of the case following withdrawal of heparin and administration of non-heparin anticoagulant like Lepirudin, Argatroban or Danaparoid. The choice of alternative anticoagulant depends upon the availability, cost, monitoring facilities and administrative guidelines.


National BTS bronchiectasis audit 2012: is the quality standard being adhered to in adult secondary care?
A significant step towards improving care of patients with non-cystic fibrosis bronchiectasis was the creation of the British Thoracic Society (BTS) national guidelines and the quality standard. A BTS bronchiectasis audit was conducted between 1 October and 30 November 2012, in adult patients with bronchiectasis attending secondary care, against the BTS quality standard. Ninety-eight institutions took part, submitting a total of 3147 patient records. The audit highlighted the variable adoption of the quality standard. It will allow the host institutions to benchmark against UK figures and drive quality improvement programmes to promote the quality standard and improve patient care.


Assessment of low level whole-body soman vapor exposure in rats.
We evaluated biochemical and behavioral effects of single, low-level exposures to the chemical warfare nerve agent soman (GD). Male Sprague-Dawley rats were trained on a variable-interval, 56-sec schedule of food reinforcement (VI56). The schedule specifies that a single lever press, following an average interval of 56 s, produces food reinforcement (i.e., a single food pellet). After training, rats received a single 60 min exposure to soman vapor at concentrations of 1.0-7.0 mg/m(3), or air control (n=8 for each treatment condition). Blood was sampled before and after the exposure. Following exposures, performance on the VI56 was evaluated for approximately 11 weeks. Additionally, the acquisition and maintenance of a radial-arm maze (RAM) spatial memory task were evaluated in the same subjects during the same 11-week period. Soman exposures produced miosis in all subjects but were otherwise essentially asymptomatic. That is, no convulsions or major signs of toxicity were observed in any subjects, a result consistent with a low-level concentration. Soman exposures produced significant and concentration-dependent decreases in circulating acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity. Soman exposures also produced concentration-dependent levels of regenerated soman in plasma and red blood cell fractions that served to verify the systemic exposure and estimate the total body burden. Soman exposure did not disrupt performance on the VI56 schedule as responding was maintained at pre-exposure levels throughout the 11-week period in all treatment groups. All subjects acquired, and maintained, performance on the RAM task and no significant differences were observed as a result of soman exposure. That is, soman-exposed rats learned the RAM task at the same general rate and to the same general level of accuracy as air-control rats. No delayed effects from exposures were observed. These results demonstrate that, in rats, single exposures to soman vapors at levels that produce substantial AChE and BChE inhibition, but below those producing convulsions and other severe clinical signs of toxicity, may not produce observable effects on the performance of a previously learned task or the acquisition of a new task.


Changes of meibomian glands in the early stage of post hematopoietic stem cell transplantation.
Hematopoietic stem cell transplantation (HSCT) is the most effective cure for hematologic malignancies. Graft-versus-host disease (GVHD) is a major complication following allogeneic HSCT, which significantly affects non-relapse mortality. And ocular manifestations of GVHD are known to occurin 60-90% of patients with chronic GVHD. Although the pathogenesis of ocular GVHD is not clearly known, it is known to progress into inflammation and fibrosis through presentation of antigens on CD4 and CD8 T cells. There is much evidence that the ocular surface and meibomian glands are severely damaged in ocular GVHD patients, and there are few observational studies on the early changes. In this review, we will discuss the various changes in the meibomian glands and ocular surface, and tear dynamics in the early stage following HSCT. These results show that tear film break-up time (TFBUT) decreased and the corneal staining score was significantly higher 2-3 months after HSCT. The upper eyelid and total eyelid meiboscore increased after 3 months following HSCT. The information of the early changes of meibomian glands morphology would be helpful to further examine the pathogenesis of meibomian gland dysfunction.


Effect of Annual Influenza Vaccination on the Risk of Lung Cancer Among Patients With Hypertension: A Population-Based Cohort Study in Taiwan.
Objectives: Lung cancer is a main contributor to all newly diagnosed cancers worldwide. The chemoprotective effect of the influenza vaccine among patients with hypertension remains unclear. Methods: A total of 37,022 patients with hypertension were retrospectively enrolled from the Taiwan National Health Insurance Research Database. These patients were further divided into a vaccinated group (n = 15,697) and an unvaccinated group (n = 21,325). Results: After adjusting for sex, age, comorbidities, medications, level of urbanization and monthly income, vaccinated patients had a significantly lower risk of lung cancer occurrence than unvaccinated patients (adjusted hazard ratio [aHR]: 0.56, 95% confidence interval [CI]: 0.47-0.67). A potential protective effect was observed for both sexes and in the elderly age group. With a greater total number of vaccinations, a potentially greater protective effect was observed (aHR: 0.75, 95% CI 0.60-0.95; aHR: 0.66, 95% CI: 0.53-0.82; aHR: 0.26, 95% CI: 0.19-0.36, after receiving 1, 2-3 and ≥4 vaccinations, respectively). Conclusion: Influenza vaccination was associated with a lower risk of lung cancer among patients with hypertension. The potentially chemoprotective effect appeared to be dose dependent.


Differentiation of influenza B lineages from clinical samples by one-step real-time RT-PCR.
Influenza viruses type A and type B are a leading cause of annual epidemics in human populations. Since the 1970s, influenza B viruses have diverged into two antigenically distinct virus lineages called the Yamagata and Victoria lineages. We describe the validation and implementation of a one-step real-time RT-PCR (rRT-PCR) assay that can differentiate between the two genetic lineages of type B. Validation of rRT-PCR method was carried out using quantified positive control and reference influenza viruses with specific minor groove binder (MGB) probes. The assay was applied on 102 clinical specimens detected positive for influenza type B. Detection limit was found to be as low as 7.95 RNA copies per reaction. The interassay variability and intra-assay variability were found to be low, and comparable for Yamagata and Victoria lineages. No cross-reactivity with the tested subtypes of influenza type A, known to cause human infections, was noticed. Differentiation of influenza B lineages by rRT-PCR was successfully achieved on all of the known positive type B samples. From the total number of clinical specimens tested, 85 samples belonged to B/Yamagata and 17 samples to B/Victoria lineage. Differentiation of genetic lineage B influenza virus circulating in Romania in the next seasons by one-step real-time RT-PCR method will supplement the classical test, haemagglutination inhibition (HI), which requires growing of the virus. This method can be advantageous for a balanced selection of samples, in case of lineages co-circulation, for genetic and antigenic characterization.


A study on toxicity of gasoline and GM-10 on liver of mice and it's amelioration by black tea extract.
The aim of present study is to investigate the ameliorative effect of black tea extract on gasoline and GM-10 induced toxicity in liver of mice. Eighty healthy male mice weighing 38-40 g approximately were divided into eight groups which included untreated control and various treated groups. Mice were treated with Gasoline 462 mg/kg/day and GM-10 low dose (206 mg/kg/day) and high dose (412 mg/kg/day) subcutaneously for 30 days. Black tea extract was given as 2 g/100 mL drinking water (2% w/v) instead of pure drinking water. All the animals were sacrificed on 31st day by cervical dislocation and livers were isolated and weighed. Parameters such as lipid peroxidation, catalase, superoxide dismutase, glutathione peroxidase, glutathione and total ascorbic acid were studied. The results revealed dose-dependent toxicity of gasoline and GM-10 on liver. Administration of black tea extract ameliorates this toxicity of gasoline and GM-10 in liver of mice. This proves the effective ameliorative effect of black tea extract.


The cell cycle biomarkers: promising research, but do not oversell them.
This review focuses on the most recent scientific and clinical information on the development and clinical applicability of the cell cycle biomarkers TIMP-2 and IGFBP-7 in the diagnosis and prognosis of patients at risk for and suffering from acute kidney injury (AKI). A number of evaluation studies have demonstrated that compared with existing biomarkers, urinary excretion of the product of both biomarkers, [TIMP-2]•[IGFBP-7], improved diagnostic performance in assessing the risk for AKI, predicting the need for renal replacement therapy, AKI-related complications and short- and long-term prognoses. The reference intervals for these biomarkers, measured by the recently approved NephroCheck test, have been determined in apparently healthy adults and those with stable chronic morbid conditions without AKI. This review recognizes that the combination of these two cell cycle arrest markers for the early detection of AKI is promising but concludes that its clinical impact is still unproved. Clinicians should understand the utility and limitations of this test before deciding whether to make it available at their institution.


Nonpeptide glycoprotein IIb/IIIa inhibitors. 15. Antithrombotic efficacy of L-738,167, a long-acting GPIIb/IIIa antagonist, correlates with inhibition of adenosine diphosphate-induced platelet aggregation but not with bleeding time prolongation.
The nonpeptide platelet glycoprotein IIb/IIIa antagonist, L-738, 167, was characterized in dog and nonhuman primate. In an anesthetized canine model of coronary artery electrolytic lesion, L-738,167 elicited dose-dependent (3, 4, 4.5 and 5 micrograms/kg i.v.) decreases in incidence of occlusion, reductions in thrombus mass and elevations in bleeding time. Antithrombotic efficacy correlated with inhibition of adenosine diphosphate-induced platelet aggregation but was dissociated from marked bleeding time elevation. Similarly, suppression of platelet-dependent cyclic flow reductions with L-738,167 in the canine coronary artery (5 micrograms/kg i.v.) and African green monkey carotid artery (10 micrograms/kg i.v.) correlated with inhibition of adenosine diphosphate-induced platelet aggregation but not with inhibition of thrombin-induced platelet aggregation or significant prolongation of bleeding time. In conscious dogs and sedated chimpanzees, single dose intravenous bolus (5-20 micrograms/kg) and oral (25-200 micrograms/kg) administration of L-738,167 exhibited long duration (> or = 8 hr) inhibition of ex vivo platelet aggregation. Once daily oral administration to conscious dogs (10-30 micrograms/kg/day for 15 days) and rhesus monkeys (200-250 micrograms/kg/day for 11 days) maintained significant but submaximal (50-90% inhibition) trough levels of inhibition of adenosine diphosphate-induced ex vivo platelet aggregation. Platelet sensitivity to adenosine diphosphate after multiple days of oral dosing in dogs was similar to pretreatment sensitivity. L-738,167 showed characteristics suitable for chronic oral therapy with a glycoprotein IIb/IIIa inhibitor.