Direct and Indirect Protection with Pediatric Quadrivalent Live-Attenuated Influenza Vaccination in Europe Estimated by a Dynamic Transmission Model.
Objectives: To estimate the public health impact of annual vaccination of children with a quadrivalent live-attenuated influenza vaccine (QLAIV) across Europe. Methods: A deterministic, age-structured, dynamic model was used to simulate influenza transmission across 14 European countries, comparing current vaccination coverage using a quadrivalent inactivated vaccine (QIV) to a scenario whereby vaccination coverage was extended to 50% of 2-17 year-old children, using QLAIV. Differential equations described demographic changes, exposure to infectious individuals, recovery and immunity dynamics. For each country, the basic reproduction number (R0) was calibrated to published influenza incidence statistics. Assumed vaccine efficacy for children was 80% (QLAIV) and 59% (QIV). Symptomatic cases cumulated over 10 years were calculated per 100 000 person-years. One-way sensitivity analyses were conducted on QLAIV efficacy in 7-17 year-olds (59% instead of 80%), durations of natural (±3 years; base case: 6, 12 years for influenza A, B respectively) and QLAIV vaccine-induced immunity (100% immunity loss after 1 season; base case: 30%), and R0 (+/-10% around all-year average value). Results: Across countries, annual QLAIV vaccination additionally prevents 1366-3604 symptomatic cases per 100 000 population (average 2495 /100 000, ie, a reduction of 47.6% of the cases which occur in the reference scenario with QIV vaccination only). Among children (2-17 years), QLAIV prevents 551-1555 cases per 100 000 population (average 990 /100 000, ie, 67.2% of current cases). Among adults, QLAIV indirectly prevents 726-2047 cases per 100 000 population (average 1466 /100 000, ie, 40.0% of current cases). The most impactful drivers of total protection were duration of natural immunity against influenza A, R0 and QLAIV immunity duration and efficacy. In all evaluated scenarios, there was a large direct and even larger indirect protection compared with the reference scenario. Conclusions: The model highlights direct and indirect protection benefits when vaccinating healthy children with QLAIV in Europe, across a range of demographic structures, contact patterns and vaccination coverage rates.


Arbidol exhibits strong inhibition towards UDP-glucuronosyltransferase (UGT) 1A9 and 2B7.
The aim of the present study was to investigate arbidol's inhibition towards UDP-glucuronosyltransferase (UGT) 1A9 and 2B7. The nonspecific probe substrate 4-methylumbelliferone (4-MU) and recombinant UGT enzymes (UGT1A9, UGT2B7) were firstly used to evaluate the inhibition of arbidol towards UGT1A9 and UGT2B7. Furthermore, specific substrates of UGT1A9 and UGT2B7 propofol and zidovudine (AZT) were used to determine the inhibition of arbidol towards UGT1A9 and UGT2B7. Inhibition type and inhibition kinetic parameters (Ki) were determined. In vitro-in vivo extrapolation (IV-IVE) was performed to predict in vivo DDI magnitude induced by arbidol. Arbidol was demonstrated to exhibit competitive inhibition towards UGT1A9 and UGT2B7 without substate-dependent behaviour. The inhibition kinetic parameters (Ki) were calculated to be 0.5 microM, 3.5 microM, 2.8 microM, 29.7 microM for UGT2B7-mediated 4-MU glucuronidation, UGT1A9-mediated 4-MU glucuronidation, UGT2B7-mediated AZT glucuronidation, and UGT1A9-mediated propofol glucuronidation, respectively. Using these parameters, the in vivo alteration of area under of concentration-time curve (AUC) was calculated to be 156%, 22%, 28% and 2.6%, respectively. Given that arbidol exhibits strong inhibition towards UGT1A9 and UGT2B7, clinical monitoring should be given when arbidol was co-administered with drugs mainly undergoing UGT1A9, UGT2B7-mediated metabolism.


Polynitrosated polyesters: preparation, characterization, and potential use for topical nitric oxide release.
New nitric oxide (NO) donor macromolecules, containing multiple S-nitrosothiol (S-NO) groups covalently attached to the polymer backbone, were prepared through the polycondensation reaction of diols (ethylene glycol and poly(ethylene glycol)) with mercaptosuccinic acid, followed by the S-nitrosation of the SH groups by a gaseous NO/O2 mixture. The polynitrosated polyesters (PNPEs) obtained were characterized by IR spectroscopy and gel permeation chromatography and displayed biological activity as vasodilators, leading to local hyperaemia when applied topically on healthy skin. Kinetic measurements in either dry or aqueous conditions have shown that PNPEs can provide sustained NO release for more than 20 h at physiological temperature. Their increased viscosity at low temperatures greatly reduces the rate of NO release, allowing for their storage for more than 90 days at -20 degrees C without decomposition. These results indicate that PNPEs have potential for topical delivery of NO in biomedical applications.


Identification of alternative transcripts of rat CD9 expressed by tumorigenic neural cell lines and in normal tissues.
CD9 is the best-studied member of the tetraspanin family of transmembrane proteins. It is involved in various fundamental cellular processes and its altered expression is a characteristic of malignant cells of different origins. Despite numerous investigations confirming its fundamental role, the heterogeneity of CD9 or other tetraspanin proteins was considered only to be caused by posttranslational modification, rather than alternative splicing. Here we describe the first identification of CD9 transcript variants expressed by cell lines derived from fetal rat brain cells. Variant mRNA-B lacks a potential translation initiation codon in the alternative exon 1 and seems to be characteristic of the tumorigenic BT cell lines. In contrast, variant mRNA-C can be translated from a functional initiation codon located in its extended exon 2, and substantial amounts of this form detected in various tissues suggest a contribution to CD9 functions. From the alternative sequence of variant C, a different membrane topology (5 transmembrane domains) and a deviating spectrum of functions can be expected.


[Appearance and diagnosis of odontomas].
Odontomata are relatively seldom encountered. The diagnosis is made accidentally or from abnormal findings such as persistance of a milk tooth, disturbances in tooth eruption, diastema and others. Localisation is established by X-ray.


The influence of H2 receptor antagonists on the plasma concentrations of midazolam and temazepam.
This study shows that 1 day's treatment with cimetidine or ranitidine causes a raised relative systemic availability of orally administered midazolam (p less than 0.01), but pretreatment with a common emulsion antacid does not alter bioavailability. Temazepam bioavailability after oral administration is unchanged after either H2 receptor antagonist, or after the emulsion antacid. The difference in the systemic availability of the two benzodiazepines following pretreatment with either cimetidine or ranitidine may be explained by inhibition of the mixed function oxidase system in the liver. Drugs with a relatively high liver extraction ratio, such as midazolam, are likely to be affected to a greater extent than those with a low extraction ratio, such as temazepam. The clinical relevance of these findings is yet to be determined.


Recognition of the acetylcholine receptor binding site of a long-chain neurotoxin by toxin-specific monoclonal antibodies.
The present paper reports the preparation and characterization of two neutralizing monoclonal antibodies (Mabs), called MST1 and MST2, which bind at the central loop of a long-chain neurotoxin from cobra venom. The central loop is a critical region for the binding of the toxin to the nicotinic acetylcholine receptor. Some of the residues incorporated in the epitopes recognized by MST1 and MST2 have been identified on the basis of competition experiments using a set of 'chemical mutants' of the toxin. We show that MST1 and MST2 bind at the base and at the tip of the central loop of the toxin, respectively, however, only MST2 actually overlaps the acetylcholine receptor binding site. Accordingly, only MST2 is capable of recognizing all homologous toxins so far examined. MST2, therefore, mimicks, at least partially, the site by which the nicotinic acetylcholine receptor recognizes a long-chain neurotoxin.


Soft X-ray spectroscopy of nanoparticles by velocity map imaging.
Velocity map imaging (VMI), a technique traditionally used to study chemical dynamics in the gas phase, is applied here to study X-ray photoemission from aerosol nanoparticles. Soft X-rays from the Advanced Light Source synchrotron, probe a beam of nanoparticles, and the resulting photoelectrons are velocity mapped to obtain their kinetic energy distributions. A new design of the VMI spectrometer is described. The spectrometer is benchmarked by measuring vacuum ultraviolet photoemission from gas phase xenon and squalene nanoparticles followed by measurements using soft X-rays. It is demonstrated that the photoelectron distribution from X-ray irradiated squalene nanoparticles is dominated by secondary electrons. By scanning the photon energies and measuring the intensities of these secondary electrons, a near edge X-ray absorption fine structure (NEXAFS) spectrum is obtained. The NEXAFS technique is used to obtain spectra of aqueous nanoparticles at the oxygen K edge. By varying the position of the aqueous nanoparticle beam relative to the incident X-ray beam, evidence is presented such that the VMI technique allows for NEXAFS spectroscopy of water in different physical states. Finally, we discuss the possibility of applying VMI methods to probe liquids and solids via X-ray spectroscopy.


Glandular inclusions in inguinal hernial sacs and spermatic cords. Müllerian-like remnants confused with functional reproductive structures.
Small, glandular inclusions are present in approximately 6% of hernial sacs from prepubertal males. Identical structures may be present in the spermatic cord. Histologically, these are composed of ciliated, low columnar epithelium with eosinophilic cytoplasm and basal nuclei. A mantle of fibrous tissue surrounds each gland-like structure. These epithelial inclusions may be confused with reproductive ducts of functional importance; however, specific histologic features allow ready distinction. The origin of these structures is uncertain, but it is most probable that they are remnants of Müllerian ducts.


Warm homes for older people: aims and methods of a randomised community-based trial for people with COPD.
Chronic Obstructive Pulmonary Disease (COPD) is of increasing importance with about one in four people estimated to be diagnosed with COPD during their lifetime. None of the existing medications for COPD has been shown to have much effect on the long-term decline in lung function and there have been few recent pharmacotherapeutic advances. Identifying preventive interventions that can reduce the frequency and severity of exacerbations could have important public health benefits. The Warm Homes for Elder New Zealanders study is a community-based trial, designed to test whether a NZ$500 electricity voucher paid into the electricity account of older people with COPD, with the expressed aim of enabling them to keep their homes warm, results in reduced exacerbations and hospitalisation rates. It will also examine whether these subsidies are cost-beneficial. Participants had a clinician diagnosis of COPD and had either been hospitalised or taken steroids or antibiotics for COPD in the previous three years; their median age was 71 years. Participants were recruited from three communities between 2009 to early 2011. Where possible, participants' houses were retrofitted with insulation. After baseline data were received, participants were randomised to either 'early' or 'late' intervention groups. The intervention was a voucher of $500 directly credited to the participants' electricity company account. Early group participants received the voucher the first winter they were enrolled in the study, late participants during the second winter. Objective measures included spirometry and indoor temperatures and subjective measures included questions about participant health and wellbeing, heating, medication and visits to health professionals. Objective health care usage data included hospitalisation and primary care visits. Assessments of electricity use were obtained through electricity companies using unique customer numbers. This community trial has successfully enrolled 522 older people with COPD. Baseline data showed that, despite having a chronic respiratory illness, participants are frequently cold in their houses and economise on heating. The clinical trial registration is http://NCT01627418.


Lower gastrointestinal neuroendocrine neoplasms associated with hereditary cancer syndromes: a case series.
Lower gastrointestinal (GI) neuroendocrine neoplasms (NENs) of the colon and rectum are uncommon and not traditionally associated with hereditary GI cancer syndromes. However, with widespread implementation of colorectal cancer screening programs, lower GI NENs are being identified with increasing frequency. We report the first case series of six patients with lower GI NENs who were diagnosed with hereditary GI cancer syndromes by germline testing. Two patients presented with poorly differentiated rectal neuroendocrine carcinoma (NECs) with colonic polyposis and were found to have Familial Adenomatous Polyposis and MYH-Associated Polyposis, respectively. Three patients with colorectal NENs (one well differentiated neuroendocrine tumor, NET, and two NECs), all of which displayed abnormal immunohistochemistry for mismatch repair proteins, were diagnosed with Lynch syndrome. One patient with a goblet cell carcinoid was diagnosed with CHEK2 mutations. All patients met genetic testing guidelines and the diagnosis was made utilizing next generation sequencing gene panel tests. Lower GI NETs should therefore be considered a potential hereditary GI cancer syndrome-associated malignancy in patients who otherwise meet criteria for genetic evaluation.


Previously unknown species of Aspergillus.
The use of multi-locus DNA sequence analysis has led to the description of previously unknown 'cryptic' Aspergillus species, whereas classical morphology-based identification of Aspergillus remains limited to the section or species-complex level. The current literature highlights two main features concerning these 'cryptic' Aspergillus species. First, the prevalence of such species in clinical samples is relatively high compared with emergent filamentous fungal taxa such as Mucorales, Scedosporium or Fusarium. Second, it is clearly important to identify these species in the clinical laboratory because of the high frequency of antifungal drug-resistant isolates of such Aspergillus species. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) has recently been shown to enable the identification of filamentous fungi with an accuracy similar to that of DNA sequence-based methods. As MALDI-TOF MS is well suited to the routine clinical laboratory workflow, it facilitates the identification of these 'cryptic' Aspergillus species at the routine mycology bench. The rapid establishment of enhanced filamentous fungi identification facilities will lead to a better understanding of the epidemiology and clinical importance of these emerging Aspergillus species. Based on routine MALDI-TOF MS-based identification results, we provide original insights into the key interpretation issues of a positive Aspergillus culture from a clinical sample. Which ubiquitous species that are frequently isolated from air samples are rarely involved in human invasive disease? Can both the species and the type of biological sample indicate Aspergillus carriage, colonization or infection in a patient? Highly accurate routine filamentous fungi identification is central to enhance the understanding of these previously unknown Aspergillus species, with a vital impact on further improved patient care.


Epidermal growth factor induces ubiquitination of Eps15.
Epidermal growth factor (EGF) receptor pathway substrate clone 15 (Eps15) has been described as a 142-kDa EGF receptor substrate. It has been shown to bind to the EGF receptor, adaptor protein-2, and clathrin and is present at clathrin-coated pits and vesicles. Upon stimulation of cells with EGF or transforming growth factor alpha, Eps15 becomes rapidly and transiently phosphorylated on tyrosine residues. This phosphorylation coincides with an increase of 8 kDa in molecular mass. Here we show that this increase in molecular mass is not due to tyrosine phosphorylation. Instead, we found both by Western blotting and protein sequencing that this EGF-induced increase in molecular mass is the result of monoubiquitination. Eps15 ubiquitination but not tyrosine phosphorylation was inhibited under conditions that blocked EGF-induced internalization of the EGF receptor. Our results establish ubiquitination as a second form of EGF-stimulated covalent modification of Eps15.


Dystonia in Spain: study of a Gypsy family and general survey.
A girl from a Spanish Gypsy family developed idiopathic torsion dystonia when 12 years old. Parents were first cousins and both the pattern of clinical involvement and the rate of progression corresponded to that usually found in the autosomal recessive form of the disorder. Serum dopamin-beta-hydroxylase activity in the patient and close family members were also in keeping with this hereditary form. A nationwide inquiry failed to detect further cases of torsion dystonia among Gypsies, but revealed a relatively large number of recessively inherited disorders of the nervous system in this inbred, genetically isolated population. Thirty-six additional cases of torsion dystonia were collected from the general Spanish population, including four with a family history for this condition. The gene responsible for the recessive illness appears to be rare in many countries, explaining the sporadic nature of the disorder and its eventual appearance only in genetic isolates or after consanguineous matings.


[Design an educational intervention to prevent falls of older people in social housing: description of a research method].
In a social environment in which prevention of falls in older people has become a public health issue, adaptation of housing for older people is particularly important. Based on the home-identity concept, the objective of this research was to design an educational model specifically adapted to the context of a Social Housing Company (SHC), focussing on elderly tenants who have experienced a fall in order to allow them to adapt their lodgings and avoid subsequent falls. This article describes design-based research (DBR), which enabled the research committee (composed of professionals, tenants, and researchers) to construct the educational intervention based on analysis of the SHC context. The creation of a common approach within the research committee and the production of design-linked intentions enabled the creation of a formal intervention composed of four educational sessions, involving a private occupational therapist, an SHC social worker and a caretaker. The use of DBR can be justified by the research goal, i.e. validation of an educational model (based on the theoretical home-identity model) that can be transposed to a SHC. As this research is still underway, its quality criteria will only be partially described and will be completed by field experimentation. This exploratory study could eventually result in interventional research designed to assess this model in a multifactorial therapeutic patient education programme for older people at high risk of falls (e.g.: Personnes Âgées En Risque de Perte d'Autonomie device).


Depression in Internet and face-to-face cancer support groups: a pilot study.
To examine depression in Internet cancer support groups as compared to traditional (face-to-face) cancer support groups and to explore the relationship between Internet use and levels of depression. Exploratory, descriptive. Traditional (face-to-face) and Internet cancer support groups. Convenience sample of 40 patients with cancer, 14 from traditional face-to-face groups and 26 from an Internet support group, with different cancer diagnoses. Traditional paper or Internet surveys consisting of an investigator-developed questionnaire including demographic information, brief medical history, support group history, and the Center for Epidemiologic Studies Depression Scale (CES-D). Depression scores on the CES-D. Participants in the face-to-face groups were 100% male. The online group was 56% male and 44% female. Groups did not differ significantly by income, health insurance status, or days since initial diagnosis. Groups differed significantly on level of depression. The traditional (face-to-face) group had a CES-D mean score of 1.86 (SD = 2.69), and the online group had a mean score of 29.27 (SD = 11.89, p less than 0.000). A comparison of CES-D scores of men in the face-to-face and Internet groups revealed that they differed significantly on level of depression. Men in the traditional group had a mean score of 1.86 (SD = 2.69), and men in the online group had a mean score of 27.42 (SD = 112.69, p less than 0.000). These data suggest that more depressed patients with cancer use Internet support groups instead of face-to-face support. Before online interventions can be implemented effectively, their efficacy needs to be evaluated. Patients with cancer are at increased risk for developing depression. This should be a consideration during nursing assessments. Traditional cancer support groups can help people cope with their cancer, but the efficacy of Internet cancer support groups in providing psychoeducation and psychotherapeutic intervention remains to be proven.


[Prognostic factors of uterine cervical cancer].
The large majority of gynecologic malignancies are comprised of uterine cervical cancer, endometrial cancer and ovarian cancer. Prognostic factors for each disease are based on various clinical pathological features, including clinical stage, tumor size, and lymph node metastatis for uterine cervical cancer. In addition to these factors, recent studies have investigated the role of various molecules including tumor markers and Hb level, apoptosis-related molecules as well as various genetic abnormalities as prognostic factor or indicators for uterine cervical cancer. This molecular background of uterine cervical cancer will shape future directions in the increasingly individualized basis of treatment.


Influence of adjuvants on the induction of autoantibodies to the thyrotropin receptor.
To determine the influence of adjuvant on the induction of antibodies to thyrotropin receptor (TSHR), we immunized BALB/c mice with a extracellular domain of the TSHR (ETSHR) protein in complete Freund's adjuvant (CFA), Titer Max (TM) and Gerbu. Similarly, control groups of mice were immunized with bovine serum albumin (BSA) in each of the different adjuvants. As determined by ELISA, ETSHR given along with CFA elicited high titers of antibodies to ETSHR which were mainly restricted to the IgG1 subclass. Mice immunized with ETSHR in TM also developed high titers of anti-ETSHR antibodies but had higher levels of both IgG1 and IgG2a. However, immunization with ETSHR in Gerbu resulted in low titers of antibodies, restricted to IgG1 subclass. Immunization of mice with BSA in each of the three adjuvants induced higher antibody titers to BSA. The subclass of antibodies in mice immunized with BSA in CFA and TM were predominantly IgG1 and IgG2a with lower levels of IgG2b, whereas in Gerbu treated group, antibody to BSA was restricted to IgG1 subclass. Analysis of specificity of antibodies against ETSHR, in mice immunized with ETSHR, revealed that irrespective of the adjuvant used, the dominant reactivity was against peptide 1 (AA 22-41) with weaker reactivity against several other. peptides. The only exception was in mice immunized with ETSHR in TM which also showed significant reactivity against peptide 23 (AA 352-371). Mice immunized with the ETSHR in CFA or in TM showed elevated levels of serum TSH binding inhibitory immunoglobulins (TBII). However, mice immunized with ETSHR in Gerbu, which had lower titers of antibodies to ETSHR, showed normal TBII levels. These studies showed that adjuvant composition could influence the titer, subclass and fine specificity of antibodies to ETSHR which in turn could affect the development of TBII activity.


The impact of type 1 diabetes and eating disorders: the perspective of individuals.
To describe the perspective of individuals living with the chronic conditions of both type 1 diabetes (T1D) and eating disorders. The TID and eating disorders are major concerns in Western society with the consequence of more prevalent and severe health complications. This paper arose from research on the impact of T1D on the self of adolescents and young adults. In a larger longitudinal study (doctoral) of 27 participants (both male and females), data were collected from 1994 from 2001 using in-depth semi-structured interviews and a grounded theory approach; four female participants reported that they were experiencing T1D and an eating disorder. This subset of four participants from the original study was case analysed and the issues that arose for the participants are described using secondary analysis. Issues uncovered included the complexity of managing the interactions of the physical, emotional and social dimensions as well as personal relationships for the participants. These interrelated issues interfere with all-round management of T1D and eating disorders. Recognition and management of the comorbidity that exits in substantial numbers are of paramount importance in clinical practice. It is also necessary to incorporate the support of significant others in the health care partnership. Health professionals who treat individuals with T1D need to be aware of the incidence of eating disorders among people with TID. Unhealthy weight control practices are of particular concern because they lead to poorer metabolic control which has a flow on effect causing micro vascular complications.


Efficient microwave-assisted tandem N- to S-acyl transfer and thioester exchange for the preparation of a glycosylated peptide thioester.
A peptide carrying a mercaptomethylated proline derivative at the C-terminus was prepared by solid-phase peptide synthesis (SPPS) and converted to the thioester of 3-mercaptopropionic acid (MPA) by aqueous MPA under microwave irradiation conditions. This post-SPPS thioesterification reaction was successfully applied to the synthesis of a glycopeptide thioester composed of 25 amino acid (AA) residues, which was then used for the preparation of a 61-AA glycopeptide by the thioester condensation method.


Immunoassay for human serum erythroferrone.
Erythroferrone (ERFE) is a glycoprotein hormone secreted by erythroblasts in response to stimulation by erythropoietin (EPO). We previously demonstrated that ERFE messenger RNA expression and serum protein concentration increase in mice subjected to hemorrhage or EPO therapy, that ERFE acts on hepatocytes to suppress hepcidin, and that the resulting decrease in hepcidin augments iron delivery for intensified erythropoiesis. We also showed that ERFE contributes to pathological hepcidin suppression and iron overload in mice with nontransfused β-thalassemia. We now report the development and technical validation of a rabbit monoclonal antibody-based sandwich immunoassay for human ERFE. We use this assay to show that blood loss or EPO administration increases serum ERFE concentrations in humans, and that patients with both nontransfused and transfused β-thalassemia have very high serum ERFE levels, which decrease after blood transfusion. The assay should be useful for human studies of normal and disordered erythropoiesis and its effect on iron homeostasis.


Phospholipase activity in bacteriophage-infected Escherichia coli. III. Phopholipase A involvement in lysis of T4-infected cells.
Bacteriophage studies with Escherichia coli K-12 (gamma)DR-DS-, a mutant lacking the major known fatty acyl hydrolases (phospholipases), and its wild-type parent showed equivalent phage infection with regard to phage production and time of phage release. Further examination of the DR-DS- mutant, however, revealed that the progeny bacteriophage were released without complete dissolution of the host cell. Prolonged cell integrity of the infected mutant was noted by spectrophotometry and supported by direct microscope examination. The phage release occurred at normal "lysis" time with phage yields comparable to that of the wild-type bacteria. Inner membrane degradation was indicated by the release of beta-galactosidase, a cytoplasmic enzyme, and of trichloracetic acid-precipitable RNA. Thus, outer membrane degradation is required for dissolution of phage-infected cells, and this degradation is at least partly dependent on activation of host phospholipases.


Situation awareness.
What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The CPD article discussed situation awareness, which refers to the ways people collect (perceive), interpret (comprehend) and use information and make decisions (projection).


Surgical excision of scalp mycetoma due to Nocardia.
A 60-year-old patient presented with a mycetoma of the scalp with multiple chronic sinuses due to nocardiosis of the scalp. Recurrent bleeding from the sinuses necessitated surgical excision which led to a gratifying result. The case illustrates the importance of fungal culture in the diagnosis of cutaneous lesions and emphasises the role of surgery in mycetoma that are resistant to conventional therapy.


Clinical and bacterial characteristics of acute bacterial conjunctivitis in children in the antibiotic resistance era.
Acute conjunctivitis is the most common eye disorder in young children. Bacteria are responsible for 54-73% of all cases. The goals of the study were to identify the rates of Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis in cases of bacterial conjunctivitis in children and to define antibiotic resistance rates. During a 2-year study period, conjunctival swabs of children 2-36 months old were collected prospectively. Nontypable H. influenzae, S. pneumoniae and M. catarrhalis were defined as the study pathogens. Analyzed variables included demography, clinical presentation, bacteriologic results and susceptibility patterns. There were 428 patients enrolled. Of all cultures, 55% (237 of 428) yielded at least 1 of the study pathogens. H. influenzae and S. pneumoniae were isolated from 29 and 20% of cultures, respectively. beta-Lactamase production was found in 29% of H. influenzae isolates, and penicillin nonsusceptibility was observed in 60% of S. pneumoniae isolates. The most common S. pneumoniae serotypes were: 19F (14%); 6A and 14 (11% each). Nontypable S. pneumoniae was found in 12%. The 7-valent pneumococcal conjugate vaccine (PCV-7) could potentially cover 44% of all isolates. Conjunctivitis-otitis syndrome was found in 32% of patients, of whom 82% of cultures yielded H. influenzae. Antibiotic resistance rates are alarmingly high. Conjunctivitis-otitis syndrome, predominantly caused by H. influenzae, is quite common. The potential coverage of the PCV-7 in conjunctivitis is relatively lower than that reported in other pneumococcal infections. Our findings should alert physicians on the choice of appropriate antibiotic treatment, on the frequent copresence of acute otitis media and on the potential role of conjunctivitis in the spread of antibiotic-resistant pathogens.


Aromatic-dependent Salmonella typhimurium as modified live vaccines for calves.
Strains of Salmonella sp with complete nonreverting aromatic biosynthesis (aro) defects are expected to be nonvirulent, in respect to invasive infection, because they need the aromatic metabolites paraaminobenzoate (for making folate) and dihydroxybenzoate (for making enterochelin) which are not available in host tissues. Derivatives with transposon-generated complete nonreverting aro-defects were prepared from 3 mouse-virulent strains of S typhimurium, namely, FIRN, WRAY, and UCD. The latter 2 parent strains originally were isolated from calves and are known to be calf-virulent. The resultant aromatic-dependent (aro-) strains were used to vaccinate 27 calves (2 to 3 weeks old), usually giving 2 doses by the IM route (10(9) bacteria) or orally (1.5 X 10(11)). Vaccination did not cause severe ill effects in any calf. Thus aro- defects cause loss of virulence for calves, as previously shown for mice. Vaccinated and control calves were challenge exposed, usually at 5 weeks of age, by feeding 1.5 X 10(11) cells of 1 of 2 calf-virulent S typhimurium strains, either UCD 108-11 or SL1323. Of the 16 challenge-exposed control calves, all became anorectic and depressed (CNS), and 15 had diarrhea. Fourteen of the 16 died; all tested tissues were bacteriologically culture-positive for Salmonella at necropsy. Vaccination with the live UCD aro- vaccine strain, SL1479 by either of 2 schedules (IM or orally) appeared effective.(ABSTRACT TRUNCATED AT 250 WORDS)


A Rare Case of Thyroid Cartilage Metastases Detected on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.
The thyroid cartilage metastatic involvement is an extremely rare entity. It can be asymptomatic at the earlier stage and can become symptomatic later on. Involvement of thyroid cartilage is frequent in melanoma and renal and rarely reported in an advanced stage of carcinoma prostate, breast, and lung. These cases were usually reported on positron emission tomography/computed tomography (PET/CT) as can often easily be missed on computed tomography scan alone. We present a case report of metastatic involvement of thyroid cartilage in squamous cell carcinoma of buccal mucosa detected on the whole-body 18F-fluorodeoxyglucose PET/CT.


Molecular mechanisms of directed growth cone motility.
Establishing molecular mechanisms of axon guidance presents one of the greatest challenges in understanding the development of the nervous system. There are many neurons, and each neuron by virtue of its location, biochemistry, and time of development, may generate a unique axon morphology in its response to environmental cues that may also change during development. The context dependence and combinatorial nature of these interactions make analysis of axon guidance particularly difficult. This article will focus on the neuronal growth cone as axon guidance is controlled by interaction of the growth cone with its environment. I present here an overview of growth cone motility from the perspective of cytoskeletal dynamics. I conclude with a discussion of our application of regional laser inactivation of growth cone proteins to address what proteins might be involved in locally modulating the cytoskeleton and how they affect growth cone motility.


Modeling the binding and diffusion of receptor-targeted nanoparticles topically applied on fresh tissue specimens.
Nanoparticle (NP) contrast agents targeted to cancer biomarkers are increasingly being engineered for the early detection of cancer, guidance of therapy, and monitoring of response. There have been recent efforts to topically apply biomarker-targeted NPs on tissue surfaces to image the expression of cell-surface receptors over large surface areas as a means of evaluating tumor margins to guide wide local excision surgeries. However, diffusion and nonspecific binding of the NPs present challenges for relating NP retention on the tissue surface with the expression of cancer cell receptors. Paired-agent methods that employ a secondary 'control' NP to account for these nonspecific effects can improve cancer detection. Yet these paired-agent methods introduce multidimensional complexity (with tissue staining, rinsing, imaging, and data analysis protocols all being subject to alteration), and could be greatly simplified with accurate, predictive in silico models of NP binding and diffusion. Here, we outline and validate such a model to predict the diffusion, as well as specific and nonspecific binding, of targeted and control NPs topically applied on tissue surfaces. In order to inform the model, in vitro experiments were performed to determine relevant NP diffusion and binding rate constants in tissues. The predictive capacity of the model was validated by comparing simulated distributions of various sizes of NPs in comparison with experimental results. The regression of predicted and experimentally measured concentration-depth profiles yielded <15% error (compared to ~70% error obtained using a previous model of NP diffusion and binding).


Quantitative analysis of chromosome in situ hybridization signal in paraffin-embedded tissue sections.
Interphase cytogenetic analysis using chromosome-specific probes is increasingly being used to detect chromosomal aberrations on paraffin-embedded tissue sections. However, quantitative analysis of the hybridization signal is confounded by the nuclear slicing that occurs during sectioning. To determine the sensitivity and accuracy of chromosome in situ hybridization for detecting numerical chromosomal aberrations on paraffin-embedded sections, in situ hybridization was performed on sections derived from mixtures of cell populations with known frequencies of numerical chromosomal aberrations and the Chromosome Index (CI) was calculated (i.e., total number of signal spots/number of nuclei counted) as a quantitative measure of chromosome copy number. The presence of 25% or more monosomic or tetrasomic cells in a given population was easily detected as a change in CI (P < 0.05). Lower degrees of polysomy could be detected as a small percentage of nuclear fragments with > 2 signal spots. The CI was not significantly influenced by a change in section thickness from 4 to 8 microM, by an increase in cell size from 478 to 986 microM3, or by the choice of detection method (fluorescence vs. conventional bright-field microscopy). Comparative analysis of touch preparations and tissue sections from the corresponding breast tumors showed that CI accurately reflects the average copy number of chromosomes in intact nuclei and may actually be superior to in situ hybridization on whole nuclei for the detection of numerical chromosomal changes in defined histologic areas. This method is thus a sensitive and accurate means of studying genetic changes in premalignant and malignant tissue, and of assessing the genetic changes associated with specific phenotypes.


Novel inhibitory effect of the antidiabetic drug voglibose on melanogenesis.
Overproduction of melanin can lead to medical disorders such as postinflammatory melanoderma and melasma. Therefore, developing antimelanogenic agents is important for both medical and cosmetic purposes. In this report, we demonstrated for the first time that the antidiabetic drug voglibose is a potent antimelanogenic agent. Voglibose is a representative antidiabetic drug possessing inhibitory activity towards human α-glucosidase; it blocked the proper N-glycan modification of tyrosinase, resulting in a dramatic reduction of the tyrosinase protein level by altering its stability and subsequently decreasing melanin production. Acarbose, another antihyperglycaemic drug that has a lower inhibitory effect on human intracellular α-glucosidase compared with voglibose, did not cause any changes in either the N-glycan modification of tyrosinase or the tyrosinase protein level, indicating that voglibose was the most efficient antimelanogenic agent among the widely used antihyperglycaemic agents. Considering that voglibose was originally selected from the valiolamine derivatives in a screen for an oral antidiabetic drug with a strong inhibitory activity towards intestinal α-glucosidase and low cell permeability, we propose an alternative strategy for screening compounds from valiolamine derivatives that show high inhibitory activity towards human intracellular α-glucosidases and high cell permeability, with the goal of obtaining antimelanogenic agents that are effective inside the cells.


Understanding the oxidation mechanism of methanesulfinic acid by ozone in the atmosphere.
Methanesulfinic acid (MSIA) is an important intermediate in the oxidation of dimethyl sulfide (DMS) in the marine boundary layer. The oxidation of MSIA by ozone in the gas phase to form methanesulfonic acid (MSA) was investigated using theoretical calculations in this paper. Three pathways can be found for the reaction of MSIA with ozone. The highest energy barrier is 13.02 kcal mol-1 in the most favorable pathway. By comparing the reaction rate of MSIA + O3 with that of MSIA + OH, it can be concluded that the oxidation of MSIA by O3 to form MSA is of minor significance relative to its oxidation by OH radical in the gas phase. This study can provide some information for the theoretical and experimental studies in the significantly heterogeneous and aqueous-phase oxidation of MSIA by O3.


Hallux Valgus Plantar Pressure Distribution Before and After Surgery.
Hallux valgus is a common foot deformity that may cause pain and functional limitation, and often requires surgical correction. Clinical and radiographic parameters are typically used to assess postoperative outcomes. Plantar pressure distribution systems represent an innovative additional tool to evaluate hallux functional outcome after surgery. A systematic review of the current literature was performed to assess evaluation systems used for plantar pressure analysis and differences before and after hallux valgus surgery, and a possible relationship between different surgical techniques and clinical and radiographic results. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used for this review. Initial search results yielded 40 studies. Two additional studies were found through cross-reference. Twenty-five studies were screened. A total of 10 articles were included in the review process. Two main plantar pressure analysis systems were identified. Hallux function restoration based on plantar pressure measurement did not always occur. No relevant relationships between plantar pressure distribution data and different surgical techniques were established. All patients achieved satisfactory clinical and radiographic outcomes, regardless of surgical techniques used; however, no clear relationships were observed between clinical and radiographic results and the change in foot plantar pressure patterns. The current literature on this topic showed several methodologic limitations. Therefore, it is not possible to provide sufficiently supported evidence-based data regarding plantar pressure distribution rebalance after surgery using current plantar pressure analysis systems. Further investigations are needed to fill these gaps in evidence.


Counting Grasping Action Using Force Myography: An Exploratory Study With Healthy Individuals.
Functional arm movements generally require grasping an object. The possibility of detecting and counting the action of grasping is believed to be of importance for individual with motor function deficits of the arm, as it could be an indication of the number of the functional arm movements performed by the individuals during rehabilitation. In this exploratory work, the feasibility of using armbands recording radial displacements of forearm muscles and tendons (ie, force myography, FMG) to estimate hand grasping with healthy individuals was investigated. In contrast to previous studies, this exploratory study investigates the feasibility of (1) detecting grasping when the participants move their arms, which could introduce large artifacts to the point of potentially preventing the practical use of the proposed technology, and (2) counting grasping during arm-reaching tasks. The aim of this study was to determine the usefulness of FMG in the detection of functional arm movements. The use of FMG straps placed on the forearm is proposed for counting the number of grasping actions in the presence of arm movements. Ten healthy volunteers participated in this study to perform a pick-and-place exercise after providing informed consent. FMG signals were simultaneously collected using 2 FMG straps worn on their wrist and at the midposition of their forearm, respectively. Raw FMG signals and 3 additional FMG features (ie, root mean square, wavelength, and window symmetry) were extracted and fed into a linear discriminant analysis classifier to predict grasping states. The transition from nongrasping to grasping states was detected during the process of counting the number of grasping actions. The median accuracy for detecting grasping events using FMG recorded from the wrist was 95%, and the corresponding interquartile range (IQR) was 5%. For forearm FMG classification, the median accuracy was 92%, and the corresponding IQR was 3%. The difference between the 2 median accuracies was statistically significant (P<.001) when using a paired 2-tailed sign test. The median percentage error for counting grasping events when FMG was recorded from the wrist was 1%, and the corresponding IQR was 2%. The median percentage error for FMG recorded from the forearm was 2%, and the corresponding IQR was also 2%. While the median percentage error for the wrist was lower than that of the forearm, the difference between the 2 was not statistically significant based on a paired 2-tailed sign test (P=.29). This study reports that grasping can reliably be counted using an unobtrusive and simple FMG strap even in the presence of arm movements. Such a result supports the foundation for future research evaluating the feasibility of monitoring hand grasping during unsupervised ADL, leading to further investigations with individuals with motor function deficits of the arm.


HIV and malaria: interactions and implications.
This review summarizes accumulating evidence of interactions between HIV and malaria and implications related to prevention and treatment of coinfection. HIV-infected persons are at increased risk for clinical malaria; the risk is greatest when immune suppression is advanced. Adults with advanced HIV may be at risk for failure of malaria treatment, especially with sulfa-based therapies. Malaria is associated with increases in HIV viral load that, while modest, may impact HIV progression or the risk of HIV transmission. Cotrimoxazole prophylaxis greatly reduces the risk of malaria in people with HIV; the risk can be further reduced with antiretroviral treatment and the use of insecticide treated mosquito nets. Increased numbers of doses of intermittent preventive treatment during pregnancy can reduce the risk of placental malaria in women with HIV. Interactions between malaria and HIV have important public health implications. People with HIV should use cotrimoxazole and insecticide treated mosquito nets. Malaria prevention is particularly important for pregnant women with HIV, although more information is needed about the best combination of strategies for prevention. In people with HIV, malaria diagnoses should be confirmed, highly effective drugs should be used for treatment, and possible drug interactions should be considered.


Plasminogen activator inhibitor-1 is elevated in patients with COPD independent of metabolic and cardiovascular function.
Plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of fibrinolysis, is associated with thrombosis, obesity, insulin resistance, dyslipidemia, and premature aging, which all are coexisting conditions of chronic obstructive pulmonary disease (COPD). The role of PAI-1 in COPD with respect to metabolic and cardiovascular functions is unclear. In this study, which was nested within a prospective cohort study, the serum levels of PAI-1 were cross-sectionally measured in 74 stable COPD patients (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stages I-IV) and 18 controls without lung disease. In addition, triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, waist circumference, blood pressure, smoking status, high-sensitive C-reactive protein (hs-CRP), adiponectin, ankle-brachial index, N-terminal pro-B-type natriuretic peptide, and history of comorbidities were also determined. The serum levels of PAI-1 were significantly higher in COPD patients than in controls, independent of a broad spectrum of possible confounders including metabolic and cardiovascular dysfunction. A multivariate regression analysis revealed triglyceride and hs-CRP levels to be the best predictors of PAI-1 within COPD. GOLD Stages II and III remained independently associated with higher PAI-1 levels in a final regression analysis. The data from the present study showed that the serum levels of PAI-1 are higher in patients with COPD and that moderate-to-severe airflow limitation, hypertriglyceridemia, and systemic inflammation are independent predictors of an elevated PAI-1 level. PAI-1 may be a potential biomarker candidate for COPD-specific and extra-pulmonary manifestations.


Protective role of renal nerves in the development of diabetic nephropathy.
Although a significant correlation between the stage of nephropathy and severity of autonomic neuropathy has been demonstrated in diabetes, the mechanism of interaction between these complications is not clear. I studied the role of the renal sympathetic nerves in the development of microalbuminuria in streptozotocin-induced diabetic rats. Sprague-Dawley rats were assigned randomly to one of four groups: 1) non-diabetic sham operated group, 2) non-diabetic renal denervated group, 3) diabetic sham operated group, and 4) diabetic renal denervated group (n = 6 in each group). After recovery of renal denervation and sham operation, diabetes was induced by streptozotocin. Throughout 6 wk of the experiment, diabetes was moderately controlled with ultralente insulin (plasma glucose = 10-24mM). Urinary albumin excretion rose throughout the experiment in all groups, although the rate of increase varied between groups. Among diabetic rats, albuminuria was 3.5 fold higher in renal denervated rats than sham-operated rats in the 6th wk. Among denervated rats, diabetic rats excreted 4.9 fold higher albumin than non-diabetic rats at the end of experiment. Thus, renal denervation appears to exacerbate the progress of diabetic nephropathy in streptozotocin treated rats as judged through assessment of urinary albumin excretion. This suggests that the renal nerves may provide some protection against the progression of diabetic nephropathy. Loss of this protective role may be one mechanism by which diabetic autonomic dysfunction may aggravate the progression of diabetic nephropathy.


[Chagas' disease among blood donors in Bolivia].
A questionnaire survey of blood donors at Santa Cruz General Hospital, Bolivia, showed that while there were no seropositive cases of syphilis, HBsAg, and HIV, the prevalence of Chagas' disease was very high (23%) among the 225 blood donors who responded to this questionnaire. Actual cases of Chagasic seropositive blood being used for blood transfusion were seen, including the urgent need for a program for Chagas' disease in Bolivia. From the results of this study, it is recommended that for blood donors from South American countries, the presence/absence of Chagas' disease should be confirmed.


Risk factors for benign breast disease according to histopathological type: comparisons with risk factors for breast cancer.
We evaluated risk factors for benign breast disease by using a case-control study method. The series was taken from participants in breast cancer screening programs during 1978-1986 in Miyagi Prefecture, Japan. All benign breast lesions diagnosed during this period were reviewed and reclassified into proliferative and non-proliferative types based on the Dupont and Page classification. Data on 382 benign breast disease cases (130 proliferative-type cases and 252 non-proliferative-type cases) and 1,489 screening year-, age- and screening area-matched normal controls were used for analysis. Nulliparity or low parity and family history of breast cancer in mother or sisters were significantly associated with an increased risk of proliferative type. Premenopausal status was significantly associated with an increased risk of non-proliferative type. No significant association with history of lactation for the last child was observed in either type, but the risk of proliferative type increased with increasing duration of lactation (P=0.08). A comparison between the present findings and the risk factors for breast cancer indicated epidemiologic similarities between proliferative benign and malignant breast lesions in general. The associations of these two lesions with lactation patterns were, however, dissimilar.


Multiple TonB Homologs are Important for Carbohydrate Utilization by Bacteroides thetaiotaomicron.
The human gut microbiota is able to degrade otherwise undigestible polysaccharides, largely through the activity of the Bacteroides. Uptake of polysaccharides into Bacteroides is controlled by TonB-dependent transporters (TBDT) whose transport is energized by an inner membrane complex composed of the proteins TonB, ExbB, and ExbD. Bacteroides thetaiotaomicron (B. theta) encodes 11 TonB homologs which are predicted to be able to contact TBDTs to facilitate transport. However, it is not clear which TonBs are important for polysaccharide uptake. Using strains in which each of the 11 predicted tonB genes are deleted, we show that TonB4 (BT2059) is important but not essential for proper growth on starch. In the absence of TonB4, we observed an increase in abundance of TonB6 (BT2762) in the membrane of B. theta, suggesting functional redundancy of these TonB proteins. Growth of the single deletion strains on pectin galactan, chondroitin sulfate, arabinan, and levan suggests a similar functional redundancy of the TonB proteins. A search for highly homologous proteins across other Bacteroides species and recent work in B. fragilis suggests that TonB4 is widely conserved and may play a common role in polysaccharide uptake. However, proteins similar to TonB6 are found only in B. theta and closely related species suggesting that the functional redundancy of TonB4 and TonB6 may be limited across the Bacteroides. This study extends our understanding of the protein network required for polysaccharide utilization in B. theta and highlights differences in TonB complexes across Bacteroides species.


Medetomidine-induced alterations of intraocular pressure and contraction of the nictitating membrane.
The alpha-2 adrenoceptor agonist, medotomidine (MED), was examined for effects on: (1) intraocular pressure (IOP) in normal and sympathectomized (SX) rabbits; (2) IOP in normal rabbits pretreated with the alpha-2 antagonist idazoxan; (3) contractions of the cat nictitating membrane (CNM) elicited by nerve stimulation and intra-arterial (IA) norepinephrine. Unilateral topical administration of MED (7.5-75 micrograms) caused dose-dependent, bilateral IOP reduction in normal eyes, but MED (25 micrograms) had no appreciable hypotensive activity in SX eyes. The ocular hypotensive effect of MED (25 micrograms) was antagonized by treatment with idazoxan (100 micrograms, bilaterally), a relatively selective alpha-2 antagonist. MED and dexmedetomidine (DMED) also inhibited frequency-related contractions of CNM induced by electrical stimulation of the cervical sympathetic trunk. Rauwolscine (100 micrograms, IA) shifted the MED dose response in the CNM to the right indicative competitive antagonism, whereas SK&F 104078 (300 micrograms, IA), a relatively dose-selective postjunctional alpha-2 antagonist, had no effect on DMED suppression. These results show that MED lowers IOP in part, by interacting with alpha-2 adrenoceptors located on sympathetic nerve endings. An effect of MED on imidazoline sites may also be possible.


Amniotic fluid embolism: a review of 10 fatal cases.
A study of 10 fatal cases of amniotic fluid embolism, confirmed by autopsy and post-mortem histological examination, that occurred in Singapore between 1983-1992, showed that the majority (9 cases) were multiparous, with between 2-4 previous normal pregnancies each. Seven had uneventful antenatal histories. In all cases, the clinical onset was sudden and unexpected, having occurred during the first stage of labour in 8 subjects and being associated with convulsions in 5. There were seven cases of coagulopathy, with 6 of disseminated intravascular coagulation. Overall, foetal survival was poor. Three cases were associated with induction of labour, while another 3 occurred after augmentation. Emergency caesarean sections were performed in 5 cases. Autopsy demonstrated moderate to severe pulmonary oedema in 9 cases, accompanied by pulmonary haemorrhage in 6. Mild coronary atheroma was present in 6 cases, with 3 showing subendocardial haemorrhage. Significant utero-cervical ruptures or lacerations were found in 3 cases. Microscopy demonstrated the presence of squamous epithelial emboli within the pulmonary vasculature in all cases. Other histological features included fibrin microthrombi (3 cases), alveolar and pulmonary interstitial inflammation, focal myocardial and hepatocellular necrosis, and myocardial interstitial inflammation. Although the precise pathogenesis of amniotic fluid embolism has remained somewhat enigmatic, recent evidence points towards a combination of a severe haemodynamic disturbance followed by secondary coagulopathy in about 40% of patients who survive the initial event. Leucotrienes, prostaglandins and other vasoactive substances contained in amniotic fluid are postulated to play a fundamental role in its pathogenesis. Amniotic fluid is also thought to possess thromboplastin-like properties.(ABSTRACT TRUNCATED AT 250 WORDS)


Physician, Steel Thyself.
A family physician who has long tried to prevent patients from falling victim to health scams and disinformation recently confronted an unexpected challenge of his own.


Nasal administration of multiple antigens suppresses experimental autoimmune myasthenia gravis, encephalomyelitis and neuritis.
Oral tolerization with acetylcholine receptor (AChR) and myelin basic protein (MBP) prior to immunization with AChR+MBP+ complete Freund's adjuvant (CFA) alleviated clinical signs of experimental autoimmune myasthenia gravis (EAMG)+experimental allergic encephalomyelitis (EAE) and AChR- or MBP-specific T and B cell responses. Tolerance induced via the nasal route needs much less tolerogen and may still be as effective as oral tolerance induction. We now immunized Lewis rats with AChR+MBP+bovine peripheral nerve myelin (BPM)+CFA, which resulted in a multiphasic clinical picture with a combination of clinical signs of the EAMG+EAE+experimental allergic neuritis (EAN), accompanied by massive macrophage infiltrations in sections of muscle, spinal cord and sciatic nerve, and strong T and B cell responses to AChR, MBP and BPM in lymphoid organs. Nasal administration of microg doses of AChR+MBP+BPM prior to immunization with a mixture of these antigens+CFA effectively suppressed the incidence and severity of clinical disease, reduced macrophage infiltrations in sections of muscle, spinal cord and sciatic nerve, and down-regulated autoreactive T cell responses to the three antigens in lymphoid organs. Numbers of AChR-, MBP-, BPM-reactive Th1 type of cytokine interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha mRNA expression in lymph node cells were markedly suppressed, while transforming growth factor-beta (TGF-beta) mRNA expression was upregulated from nasally tolerized rats, suggesting an active suppression mechanism may act partly in the induction of tolerance. The results implicate the possibility to establish multiple autoantigen-based vaccination for the prevention of autoimmune diseases in humans.


Changes in levels of mRNA coding for catecholamine synthesizing enzymes and neuropeptide Y in the adrenal medulla of the newborn rat.
We have measured levels of mRNA coding for the catecholamine synthesizing enzymes tyrosine hydroxylase (TH), dopamine beta-hydroxylase (D beta H), phenylethanolamine N-methyltransferase (PNMT) and for neuropeptide Y (NPY) in rat adrenal medulla by using in situ hybridization histochemistry. Ages of one day before birth (E21), 12 h, 24 h, 2 days and 4 days after birth and in adults were studied. TH, D beta H and NPY mRNA levels increased markedly postnatally. Twelve hours after birth the levels of mRNA for TH, D beta H and NPY were, respectively, 512 +/- 18%, 370 +/- 24% and 253 +/- 21% of E21 levels. At 24 h of age NPY mRNA level was 437 +/- 73% of fetal value. In contrast, the levels of mRNA coding for PNMT increased more slowly and reached 196 +/- 9% of E21 level on postnatal day four and was further increased in adult rats.


[The eye as an effector of allergic reaction].
In this work the symptoms of allergic diseases of the eye were shortly described. The role of mast cells, eosinophils and lymphocytes taking part in allergic reaction was presented. The cellular mechanisms which lead to symptoms of allergic diseases of the eye were discussed. Histopathological changes in the eye tissues and their clinical importance were taken into consideration. The analysis of allergic symptoms of the eye on the basis of the knowledge of pathophysiological processes gives important information both for ophthalmologists and allergologists.


Infrared spectra and ab initio calculations for the F- -(CH4)n (n = 1-8) anion clusters.
Infrared spectra of mass-selected F- -(CH4)n (n = 1-8) clusters are recorded in the CH stretching region (2500-3100 cm-1). Spectra for the n = 1-3 clusters are interpreted with the aid of ab initio calculations at the MP2/6-311++G(2df 2p) level, which suggest that the CH4 ligands bind to F- by equivalent, linear hydrogen bonds. Anharmonic frequencies for CH4 and F--CH4 are determined using the vibrational self-consistent field method with second-order perturbation theory correction. The n = 1 complex is predicted to have a C3v structure with a single CH group hydrogen bonded to F-. Its spectrum exhibits a parallel band associated with a stretching vibration of the hydrogen-bonded CH group that is red-shifted by 380 cm-1 from the nu1 band of free CH4 and a perpendicular band associated with the asymmetric stretching motion of the nonbonded CH groups, slightly red-shifted from the nu3 band of free CH4. As n increases, additional vibrational bands appear as a result of Fermi resonances between the hydrogen-bonded CH stretching vibrational mode and the 2nu4 overtone and nu2+nu4 combination levels of the methane solvent molecules. For clusters with n < or = 8, it appears that the CH4 molecules are accommodated in the first solvation shell, each being attached to the F- anion by equivalent hydrogen bonds.


Risk factors for the comorbidity of osteoporosis/osteopenia and kidney stones: a cross-sectional study.
Low femoral neck bone mineral density (BMD) was associated with the increased risk of kidney stones. Low dietary magnesium intake and increased serum alkaline phosphatase were associated with the increased risk of low femoral neck BMD in kidney stone formers. To evaluate whether low femoral neck bone mineral density (BMD) was associated with a higher risk of kidney stones, and identify risk factors for the comorbidity of osteoporosis/osteopenia and kidney stones. We analyzed individuals aged ≥ 20 years from National Health and Nutrition Examination Survey 2007-2020 data. Osteoporosis/osteopenia is defined as any T-score < -1.0 of femoral neck, total femoral, and mean lumbar spine (L1-L4) BMD. Dietary intakes (sodium, potassium, magnesium, calcium, phosphorus, calcium/phosphorus, vitamin D (25OHD2+25OHD3)) and serum parameters (sodium, potassium, calcium, phosphorus, bicarbonate, vitamin D, alkaline phosphatase (ALP)) were screened for identifying risk factors for the comorbidity. The prevalence of comorbidity of osteoporosis/osteopenia and kidney stones was 4.82%. Femoral neck BMD T-score was negatively associated with the prevalence of kidney stones (n=11,864). Dietary magnesium intake, serum phosphorus, and bicarbonate were negatively associated with the comorbidity prevalence, and serum ALP was positively associated with the comorbidity prevalence (n=6978). Additionally, there remain significant associations of dietary magnesium intake, serum ALP, and bicarbonate with not only femoral neck BMD T-score (n=11331), but also the prevalence of kidney stones (n=23,111) in general population. Furthermore, dietary magnesium intake was positively correlated to femoral neck BMD T-score in stone formers (SFs), while serum ALP was negatively correlated to femoral neck BMD T-score in SFs (n=1163). Low femoral neck BMD was closely associated with an increased risk of kidney stones. Low magnesium intake and increased serum ALP were associated with the increased risk of the comorbidity, as well as indicative of low femoral neck BMD T-score in SFs, which offered a clue to further clarify the mechanism leading to paradoxical calcification of bone resorption and kidney stones, and had the potential to perform personalized diagnostic workup for low BMD in SFs.


Data management in life cycle assessment: a case study of wastewater treatment.
To assess the environmental impact of wastewater treatment, life cycle assessment (LCA) is a frequently applied instrument. However, these studies often require large amounts of data. The complexity and heterogeneity of these data result in the need for a systematic data management approach. Especially the generation of the life cycle inventory (LCI) holds the potential to be facilitated by automation. A case study in the wastewater sector was used to demonstrate the implementation of data management. A database structure was developed to store the raw data of the wastewater plants (WWTPs) and make it accessible through code. The code interacted with the database, implemented calculations, and automatically created the inventory based on the processed data. The database provides a consistent structure for the raw data and can also be used for backup purposes. Because it is machine-readable it can be accessed through the code that enables the automated generation of the LCI. As a proof of concept, a sequence of the code is provided with a user interface and can be tested online. We found that for most use cases, basic programming tools were sufficient for systematic data management, and, therefore, the approach is considered accessible for LCA practitioners.


Analysis of Complications of Percutaneous Transthoracic Needle Biopsy Using CT-Guidance Modalities In a Multicenter Cohort of 10568 Biopsies.
To analyze the complications of percutaneous transthoracic needle biopsy using CT-based imaging modalities for needle guidance in comparison with fluoroscopy in a large retrospective cohort. This study was approved by multiple Institutional Review Boards and the requirement for informed consent was waived. We retrospectively included 10568 biopsies from eight referral hospitals from 2010 through 2014. In univariate and multivariate logistic analyses, 3 CT-based guidance modalities (CT, CT fluoroscopy, and cone-beam CT) were compared with fluoroscopy in terms of the risk of pneumothorax, pneumothorax requiring chest tube insertion, and hemoptysis, with adjustment for other risk factors. Pneumothorax occurred in 2298 of the 10568 biopsies (21.7%). Tube insertion was required after 316 biopsies (3.0%), and hemoptysis occurred in 550 cases (5.2%). In the multivariate analysis, pneumothorax was more frequently detected with CT {odds ratio (OR), 2.752 (95% confidence interval [CI], 2.325-3.258), p < 0.001}, CT fluoroscopy (OR, 1.440 [95% CI, 1.176-1.762], p < 0.001), and cone-beam CT (OR, 2.906 [95% CI, 2.235-3.779], p < 0.001), but no significant relationship was found for pneumothorax requiring chest tube insertion (p = 0.497, p = 0.222, and p = 0.216, respectively). The incidence of hemoptysis was significantly lower under CT (OR, 0.348 [95% CI, 0.247-0.491], p < 0.001), CT fluoroscopy (OR, 0.594 [95% CI, 0.419-0.843], p = 0.004), and cone-beam CT (OR, 0.479 [95% CI, 0.317-0.724], p < 0.001) guidance. Hemoptysis occurred less frequently with CT-based guidance modalities in comparison with fluoroscopy. Although pneumothorax requiring chest tube insertion showed a similar incidence, pneumothorax was more frequently detected using CT-based guidance modalities.


[Cyclin E overexpression and centrosome amplification in squamous cell carcinoma of oral cavity].
To study the correlation between cyclin E protein overexpression and centrosome amplification in oral squamous cell carcinoma (OSCC). Formalin-fixed, paraffin-embedded tissues from 12 normal oral epithelium cases and 46 cases of OSCC were studied. Their centrosome status was analyzed by indirect immunofluorescence double staining with antibodies to centrosome protein gamma-tubulin and cytokeratin. The expression of cyclin E protein was studied by immunohistochemical methods. The correlation between cyclin E protein expression and centrosome amplification in OSCC was statistically analyzed by SPSS 12.0. Thirty-seven of the 46 OSCC cases (80.4%) studied showed evidence of centrosome amplification, as signified by enlargement and/or increase in number of centrosomes, while normal oral epithelium possessed centromeres of normal size and number. Positive staining for cyclin E protein was observed in 30 of the 46 OSCC cases (65.2%), while all the normal oral epithelium cases were cyclin E protein-negative. The percentage of centrosome amplification in OSCC with positive cyclin E protein staining (90.0%, 27/30) was higher than that in OSCC with negative cyclin E protein staining (62.5%, 10/16) (chi(2) = 5.014, P < 0.05). Centrosome amplification showed positive correlation with cyclin E protein overexpression (r = 0.330, P < 0.05). Up-regulation of cyclin E protein may represent one of the possible mechanisms for centrosome amplification in OSCC.


Aberrant activation of hedgehog signaling pathway in ovarian cancers: effect on prognosis, cell invasion and differentiation.
Aberrant activation of hedgehog (HH) pathway has been implicated in the development of human malignancies. This study aimed at investigating the role of HH molecules in human ovarian carcinogenesis. The expression profiles of HH molecules were examined in ovarian tumor samples and ovarian cancer cell lines and the in vitro effects of HH molecules on cell proliferation, apoptosis, migration, invasion and cell differentiation as well as related downstream target genes were assessed. Overexpression of Patched and Gli1 protein in ovarian cancers correlated with poor survival of the patients (P = 0.008; P = 0.004). Significantly elevated expression of Sonic hedgehog messenger RNA was observed in ovarian cancers compared with normal tissues and benign ovarian tumors and such differential expression was specific to histological types (P < 0.05). Ectopic Gli1 overexpression in ovarian cancer cells conferred increased cell proliferation, cell mobility, invasiveness and change in differentiation in association with increased expression of E-cadherin, vimentin, Bcl-2, caspases as well as beta1 integrin, membrane type 1 matrix metalloproteinase (MT1-MMP) and vascular endothelial growth factor (VEGF). Treatment with 3-keto-N-(aminoethyl-aminocaproyl-dihydrocinnamoyl)-cyclopamine induced cancer cell apoptosis, suppressed cell growth, mobility and invasiveness and induced cancer cell dedifferentiation with decreased expression of E-cadherin, cytokeratin 7, Snail, calretinin, vimentin, Bcl-2, caspases, beta1 integrin, MT1-MMP and VEGF. Our data suggested that abnormal HH signaling activation plays important roles in the development and progression of ovarian cancers. Gli1 expression is an independent prognostic marker. Inhibition of the HH pathway molecules might be a valid therapeutic strategy for ovarian cancers.


Treating multiple sclerosis with monoclonal antibodies: a 2013 update.
The third part of this in-depth review series on the treatment of multiple sclerosis (MS) with monoclonal antibodies covers the years 2010-2012. The natalizumab section gives a progressive multifocal leukoencephalopathy update, focusing on clinically relevant aspects. Furthermore, it outlines problems around natalizumab cessation and current evidence on therapeutic strategies thereafter. Finally, it reviews evidence on Janus-faced modes of natalizumab action besides anti-inflammatory effects, including proinflammatory effects. The section on alemtuzumab critically analyzes recent Phase III results and discusses which patients might be best suited for alemtuzumab treatment, and reviews the long-term immunological impact of this anti-CD52 antibody. The daclizumab section critically summarizes results from the Phase IIb SELECT/SELECTION trial and introduces the Phase III program. The section on anti-CD20 antibodies reviews Phase II results on ocrelizumab and ofatumumab, and discusses current perspectives of these antibodies for MS therapy. Promising recent Phase II results on the anti-IL-17A antibody secukinumab (AIN457) are outlined and a short update on tabalumab (LY2127399) is given. Other highlighted antibodies currently being tested in MS patients include GNbAC1, BIIB033, MOR103 and MEDI-551. Finally, the authors give an update on the role monoclonal antibodies could play in the therapeutic armamentarium for MS in the medium term.


The comprehensive review of gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) from diagnosis and treatment.
Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) was first proposed by Wothley et al. in 2012 as a rare familial gastric cancer syndrome associated with an autosomal dominant form of inheritance. GAPPS is characterized by gastric basal gland polyposis from the hilum to the body of the stomach. Li et al. in 2016 showed that the cause of the disease is a point mutation in the promotor 1B region of the APC gene, and genetic testing was used to confirm the diagnosis. If the patient has already developed gastric cancer, treatment should be based on the usual treatment for gastric cancer. If no distant metastases exist, a good prognosis can be expected by performing a total gastrectomy. On the other hand, patients with distant metastasis have a poor prognosis. In the case of dysplasia, prophylactic total gastrectomy is recommended, but because it is highly invasive and postoperative postgastrectomy syndrome must be considered, the decision should be made with careful consideration of the patient's background. Therefore, there are no guidelines for screening for GAPPS, the timing of prophylactic total gastrectomy, or methods of endoscopic surveillance. Because GAPPS is a rare disease, its natural history is still unclear. Further case series are needed to elucidate the molecular biology and clinicopathological features of GAPPS and to establish clinical management, including diagnosis, treatment, and surveillance. In this review, we provide an overview of GAPPS, its clinical management, and its problems, which will be useful for the treatment of GAPPS.


Keratin 19 interacts with GSK3β to regulate its nuclear accumulation and degradation of cyclin D3.
Cyclin D3 regulates the G1/S transition and is frequently overexpressed in several cancer types including breast cancer, where it promotes tumor progression. Here we show that a cytoskeletal protein keratin 19 (K19) physically interacts with a serine/threonine kinase GSK3β and prevents GSK3β-dependent degradation of cyclin D3. The absence of K19 allowed active GSK3β to accumulate in the nucleus and degrade cyclin D3. Specifically, the head (H) domain of K19 was required to sustain inhibitory phosphorylation of GSK3β Ser9, prevent nuclear accumulation of GSK3β, and maintain cyclin D3 levels and cell proliferation. K19 was found to interact with GSK3β and K19-GSK3β interaction was mapped out to require Ser10 and Ser35 residues on the H domain of K19. Unlike wildtype K19, S10A and S35A mutants failed to maintain total and nuclear cyclin D3 levels and induce cell proliferation. Finally, we show that the K19-GSK3β-cyclin D3 pathway affected sensitivity of cells toward inhibitors to cyclin-dependent kinase 4 and 6 (CDK4/6). Overall, these findings establish a role for K19 in the regulation of GSK3β-cyclin D3 pathway and demonstrate a potential strategy for overcoming resistance to CDK4/6 inhibitors.


Protein transport into canine pancreatic microsomes: a quantitative approach.
Transport of presecretory proteins into the mammalian rough endoplasmic reticulum involves a protein translocase that comprises the integral membrane proteins Sec61alphap, Sec61betap, and Sec61gammap as core components. Electron microscopic analysis of protein translocase in rough microsomal membranes suggested that between three and four heterotrimeric Sec61p complexes form the central unit of protein translocase. Here we analyzed the stoichiometry of heterotrimeric Sec61p complexes present in cotranslationally active protein translocases of canine pancreatic microsomes and various other lumenal and membrane components believed to be subunits of protein translocase and to be involved in covalent modifications. Based on these numbers, the capacity for cotranslational transport was estimated for the endoplasmic reticulum of the human pancreas.


Anomalous Radial Artery as an Incidental Finding During a Routine Carpal Tunnel Release.
Compression of the median nerve at the wrist, or carpal tunnel syndrome, is the most commonly recognized nerve entrapment syndrome. Carpal tunnel syndrome is usually caused by compression of the median nerve due to synovial swelling, tumor, or anomalous anatomical structure within the carpal tunnel. During a routine carpal tunnel decompression, a large vessel was identified within the carpal tunnel. The large vessel was the radial artery. It ran along the radial aspect of the carpal tunnel just adjacent to the median nerve. The unusual presence of the radial artery within the carpal tunnel could be a contributing factor to the development of carpal tunnel syndrome. In this case, after surgical carpal tunnel release, all symptoms of carpal tunnel syndrome resolved.


Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study.
A prospective randomized multicenter trial was performed to evaluate the contribution of simultaneously administered chemotherapy (CT) and radiotherapy (RT) in previously untreated patients with unresectable stage III/IV head and neck cancer. Patients with locoregionally advanced head and neck cancer were treated either with RT alone (arm A) or simultaneous RT plus CT (RCT; arm B). RT was identical in both arms and administered in three courses with 13 fractions of 1.8 Gy each twice daily. During one course, from day 3 to 11, 23.4 Gy was delivered. In arm B, cisplatin (CDDP) 60 mg/m2, fluorouracil (5-FU) 350 mg/m2 by intravenous (i.v.) bolus, and leucovorin (LV) 50 mg/m2 by i.v. bolus were given on day 2, and 5-FU 350 mg/m2/24 hour by continuous infusion and LV 100 mg/m2/24 hours by continuous infusion were given from day 2 to 5. Treatment was repeated on days 22 and 44; a total RT dose of 70.2 Gy was administered. Treatment breaks were scheduled from days 12 to 21 and days 34 to 43. From 1989 to 1993, 298 patients were enrolled and 270 patients were assessable. Acute mucositis grade 3 or 4 was more frequent in arm B (38%) than in arm A (16%) (P < .001). Total treatment time was significantly longer in arm B than in arm A (P < .001) due to prolonged breaks. According to hematologic toxicity, scheduled drug doses were given in 74% of patients for the second course and 46% for the third course. The 3-year overall survival rate was 24% in arm A and 48% in arm B (P < .0003). The 3-year locoregional control rate was 17% in arm A and 36% in arm B (P < .004). Both arms showed similar distant failure patterns (arm A, 13 of 140; arm B, 12 of 130). Serious late side effects were not significantly different between treatment arms (arm A, 6.4%; arm B, 10%; not significant). Concomitant CT offered improved disease control and survival in advanced head and neck cancer patients. Due to increased acute toxicity, more supportive care is demanded when CT is given simultaneously. Increased total treatment time does not exert a negative impact on outcome in this combined modality regimen.


The teratogenicity of drugs for nausea and vomiting of pregnancy: perceived versus true risk.
Women and health care providers commonly overestimate the teratogenic risk of medications in pregnancy. With regard to nausea and vomiting of pregnancy, this leads to an underutilization of pharmacologic therapy. Pregnancy termination has even been elected in some circumstances when safe and effective alternatives for nausea have not been attempted. The misperception of teratogenic risk is partly the result of the way data on safety are presented. An awareness of this can lead to more balanced patient and physician educational materials. To facilitate rational use of medicinal and nonmedicinal therapy for nausea and vomiting of pregnancy, we have developed an algorithm based on a recent systematic review of safety and efficacy in management of the problem. The hierarchical use of medication is based on strength of evidence of fetal safety.


An Integrative Review of Clinical Reasoning Teaching Strategies and Outcome Evaluation in Nursing Education.
This study explored teaching strategies used to promote clinical reasoning in nursing education and identify outcomes used to evaluate effectiveness. The integrative review framework by Whittemore and Knafl (2005) was used in this study. Strategies included simulation (n = 10); active learning strategies such as case studies, reflection, journaling, and collaborative learning (n = 13); teaching strategies such as think aloud or case studies with simulation (n = 12); and experiential or clinical experiences (n = 2). Although most studies used exams, worksheets (n = 19), or observations by clinical instructors (n = 2) to measure effectiveness, some studies (n = 8) also used surveys to measure student satisfaction, engagement, or perception; three studies measured the student's ability to use the instrument. Improving clinical thinking requires development of innovative, effective teaching strategies. Instruments that can accurately evaluate teaching and learning strategies are needed to advance this educational initiative and improve quality of care.


Supersolidity in the triangular lattice spin-1/2 XXZ model: a variational perspective.
We study the spin-1/2 XXZ model on the triangular lattice with a nearest neighbor antiferromagnetic Ising coupling J(z) > 0 and unfrustrated (J(perpendicular) < 0) or frustrated (J(perpendicular) >0) kinetic terms in a zero magnetic field. Incorporating long-range Jastrow correlations over a mean-field spin state, we obtain the variational phase diagram of this model on large lattices for arbitrary J(z) and either sign of J(perpendicular). For J(perpendicular) < 0, we find a square root(3) x square root(3) supersolid for J(z)/J(perpendicular)| approximately > 4.7, in excellent agreement with quantum Monte Carlo data. For J(perpendicular) > 0, a distinct square root(3) x square root(3) supersolid is found to emerge for J(z)/J(perpendicular) > or = 1. Both supersolids exhibit a spontaneous density deviation from half-filling. At J(z)/J(perpendicular) = infinity, the crystalline order parameters of these two supersolids are nearly identical, consistent with exact results.


[Analysis of the geographical distribution of cases of leprosy. Rio de Janeiro, 2001-2012].
Studies have demonstrated that the geographical distribution of leprosy is related to different socioeconomic factors. This article aims to study the geographical distribution of leprosy in the state of Rio de Janeiro. The cases of leprosy reported in the 2001-2012 period were mapped according to municipality. Epidemiological and socioeconomic indicators were calculated. The ArcMap program was used for the construction of maps and Earth View to calculate the Bayesian rate. It was observed that leprosy is presented in hyper-endemic levels especially in the metropolitan area. However, there is also a reduction of the detection rate in the most recent study period. In municipalities in the metropolitan region and the north western region detection in children under 15 is high, indicating an active transmission situation. In municipalities in the south-central region and especially in the coastal region, there was a high proportion of cases diagnosed with level II disability, reflecting late diagnosis. There was no linear correlation between socioeconomic indicators and leprosy rate. These results contribute to the analysis of the geographical distribution of leprosy, important for the identification of areas for resource allocation, aiming to control and eliminate the disease.


A classification system for hip disease in cerebral palsy.
In population-based studies, hip displacement affects approximately one-third of children with cerebral palsy (CP). Given the extreme range of clinical phenotypes in the CP spectrum, it is unsurprising that hip development varies from normality, to dislocation and degenerative arthritis. Numerous radiological indices are available to measure hip displacement in children with CP; however, there is no grading system for assessing hip status in broad categorical terms. This makes it difficult to audit the incidence of hip displacement, determine the relationship between hip displacement and CP subtypes, assess the outcome of intervention studies, and to communicate hip status between health care professionals. We developed a categorical, radiographic classification of hip morphology based on qualitative indices and measurement of the key continuous variable, the migration percentage of Reimers. One hundred and thirty-four radiographs were reviewed of 52 female and 82 male adolescents with CP who were at, or close to, skeletal maturity (mean age 16y 1mo [SD 1y 4mo] range 14y to 19y 1mo). Twenty-nine were classified at Gross Motor Function Classification System level I, 25 at level II, 27 at level III, 24 at level IV, and 29 at level V. A classification system was developed to encapsulate the full spectrum of hip morphology in CP, with and without intervention.


Morphological analysis for neuronal pathway from the hindbrain ependymocytes to the hypothalamic kisspeptin neurons.
Hindbrain ependymocytes are postulated to have a glucose-sensing role in regulating gonadal functions. Previous studies have suggested that malnutrition-induced suppression of gonadotropin secretion is mediated by noradrenergic inputs from the A2 region in the solitary tract nucleus to the paraventricular nucleus (PVN), and by corticotropin-releasing hormone (CRH) release in the hypothalamus. However, no morphological evidence to indicate the neural pathway from the hindbrain ependymocytes to hypothalamic kisspeptin neurons, a center for reproductive function in mammals, currently exists. The present study aimed to examine the existence of a neuronal pathway from the hindbrain ependymocytes to kisspeptin neurons in the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). To determine this, wheat-germ agglutinin (WGA), a trans-synaptic tracer, was injected into the fourth ventricle (4V) in heterozygous Kiss1-tandem dimer Tomato (tdTomato) rats, where kisspeptin neurons were visualized by tdTomato fluorescence. 48 h after the WGA injection, brain sections were taken from the forebrain, midbrain and hindbrain and subjected to double immunohistochemistry for WGA and dopamine β-hydroxylase (DBH) or CRH. WGA immunoreactivities were found in vimentin-immunopositive ependymocytes of the 4V and the central canal (CC), but not in the third ventricle. The WGA immunoreactivities were detected in some tdTomato-expressing cells in the ARC and AVPV, DBH-immunopositive cells in the A1-A7 noradrenergic nuclei, and CRH-immunopositive cells in the PVN. These results suggest that the hindbrain ependymocytes have neuronal connections with the kisspeptin neurons, most probably via hindbrain noradrenergic and CRH neurons to relay low energetic signals for regulation of reproduction.


beta A4 amyloid protein deposition in brain after head trauma.
Previous reports have suggested that both repetitive head trauma and a single injury can be associated with the presence of diffuse beta A4 amyloid protein plaques in long-term survivors. We have studied sixteen patients (aged 10-63 years) who sustained head injury and survived for only 6-18 days. Immunostaining with an antibody to beta A4 amyloid showed extensive deposits of the protein in the cortex in six of the sixteen patients (38%). Thus, severe head injury can trigger beta A4 deposition in the brain within days.


Congenital abdominal aortic aneurysm in a young adult. Case report.
A 30-year-old man presented with threatened rupture of an infrarenal aortic aneurysm. Clinical and laboratory investigations revealed no traumatic, atherosclerotic, infectious or inflammatory cause. Histologic examination of the aortic wall showed cystic degeneration of the media. Consequently the case could be classified as congenital abdominal aortic aneurysm in an adult.


Metal-Free Addition/Head-to-Tail Polymerization of Transient Phosphinoboranes, RPH-BH2: A Route to Poly(alkylphosphinoboranes).
Mild thermolysis of Lewis base stabilized phosphinoborane monomers R(1)R(2)P-BH2⋅NMe3 (R(1),R(2)=H, Ph, or tBu/H) at room temperature to 100 °C provides a convenient new route to oligo- and polyphosphinoboranes [R(1)R(2)P-BH2]n. The polymerization appears to proceed via the addition/head-to-tail polymerization of short-lived free phosphinoborane monomers, R(1)R(2)P-BH2. This method offers access to high molar mass materials, as exemplified by poly(tert-butylphosphinoborane), that are currently inaccessible using other routes (e.g. catalytic dehydrocoupling).


Morphology of human palmaris longus tendon.
A systematic morphological investigation of human palmaris longus tendons by polarisation microscopy and low angle x-ray diffraction is reported. It is shown that contrary to some previously reported observations, and in common with other tension bearing soft collagenous tissues, the fibres in this tendon are crimped. A new method of preparation of the tissue enabling one to see directly the crimped organisation in scanning electron microscopy was used to reinforce the findings by other methods.


AGREEMENT BETWEEN CLINICAL AND ANATOMOPATHOLOGICAL DIAGNOSES IN PEDIATRIC INTENSIVE CARE.
Although autopsy is deemed the gold standard for diagnosis, its performance has been decreasing while adverse events have been increasing, of which 17% consist in diagnostic errors. The purpose of this study was to estimate the prevalence of diagnostic errors based on anatomopathological diagnosis in a Pediatric Intensive Care Unit (PICU). This is a cross-sectional, retrospective study on 31patients who died between 2004 and 2014. Diagnoses were compared in order to assess whether there was agreement between clinical major diagnosis (CMD) and the cause of death as described in the autopsy record (CDAR), which were classified according to the Goldman Criteria. Of 3,117 patients, 263 died (8.4%). Autopsy was conducted in 38 cases (14.4%), and 31 were included in the study. Therewas a 67% decrease in the number of autopsies over the last 10years. Absolute agreement between the diagnoses (class V) was observed in 18 cases (58.0%), and disagreement (class I), in 11 (35.4%). Therewas greater difficulty in diagnosing acute diseases and diseases of rapid fatal evolution such as myocarditis. Sevenpatients were admitted in critical health conditions and died within the first 24 hours of hospitalization. Autopsy not only enables to identify diagnostic errors, but also provides the opportunity to learn from mistakes. The results emphasize the relevance of the autopsy examination for diagnostic elucidation and the creation of an information database concerning the main diagnoses of patients who rapidly progress to death in PICU, increasing the index of clinical suspicion of the team working at this unit.


Connexin43, but not connexin30, contributes to adult neurogenesis in the dentate gyrus.
The subgranular zone of the dentate gyrus represents a niche in which radial glia (RG)-like cells generate new neurons throughout postnatal life in the mammalian brain. Previous data showed that RG-like cells are coupled through gap junction channels, primarily formed by connexin43 (Cx43) and Cx30, and that the expression of these proteins is required for adult neurogenesis in the hippocampus. However, their individual function and underlying mechanisms remain unclear. Here we demonstrate that Cx43, but not Cx30, is crucial for adult neurogenesis. To assess whether Cx43-dependent intercellular coupling between RG-like cells or rather channel-independent interactions of the protein regulate neurogenesis, mice bearing a Cx43 point mutation (Cx43G138R) in RG-like cells and protoplasmic astrocytes cells were employed, which was expected to cause channel closure without affecting the trafficking of the protein to the membrane. We confirmed the disruption of coupling between RG-like cells and astrocytes in the hippocampus of Cx43G138R mice. Proliferative activity and neurogenesis in the DG were significantly decreased in the mutant mouse line, indicating that functional Cx43 channels are essential for proper adult neurogenesis. The fate of proliferating cells in the DG was not affected by Cx43 mutation as revealed by 5-bromo-2-deoxyuridine (BrdU) incorporation assays. Together, these findings suggest that adult neurogenesis in the hippocampus does not require Cx30 but channel-dependent functions of Cx43.


Development and Psychometric Validation of a Screening Questionnaire to Detect Excessive Menstrual Blood Loss That Interferes in Quality of Life: The SAMANTA Questionnaire.
Background: Heavy menstrual bleeding (HMB) affects up to 35% of women at some point in their lives, and has an important impact on their quality of life (QoL). Current techniques to assess and quantify menstrual blood loss are inconvenient and the correlation between actual and perceived blood loss is poor. This study aimed to develop and validate a screening questionnaire in Spanish to identify HMB in women of reproductive age. Methods: The study consisted of two phases: the conceptual development of a set of items to discriminate between women with and without HMB and the assessment of the sensitivity and specificity of these items. Correlation of the screening tool with women's perception of the intensity of bleeding and the interference in their daily life activities was also assessed. Results: An initial set of 46 items were identified, from which 21 items were selected following the cognitive interviews. For the psychometric validation phase, 389 patients were enrolled, of whom 364 were assessable: 211 cases with Pictorial Blood loss Assessment Chart-confirmed excessive menstrual loss (EML) and 153 controls. Six items met entry criteria in the model and together yielded a sensitivity of 86.7% and specificity of 89.5% to identify cases and controls. These items were weighted according to their contribution to the final model to yield a tool that can be scored from 0 to 10 being 3 the cutoff point to diagnose EML that interferes in QoL. Conclusions: The 6-item SAMANTA questionnaire represents a valid screening tool to easily identify women with EML that interfere with QoL.


Bifid Uvula-An Enigma.
Facial development involves an intricate regulatory mechanism that accounts for numerous craniofacial abnormalities, common being orofacial clefts. Although cleft in the secondary palate accounts for one-third of orofacial clefts stills remains an under-researched domain. Hence, in this work, the authors put forth two non-syndromic, asymptomatic cleft uvulae reported among bimodal male patients of the Indian-Asiatic population who came up for dental screening. Most of the time, isolated/asymptomatic cleft uvula patients will be reluctant to further investigations and treatment. Although bifid uvula looks benign in most patients, it may sometimes be associated with catastrophic complications. To conclude, whenever bifid uvula is an incidental finding, it is the responsibility of the healthcare worker to plan a thorough patient workup as a primary preventive measure to rule out any complications whenever feasible. It can help us overcome many future unforeseen sequelae and emergency management due to bifid uvula.


Ginkgolide B Modulates BDNF Expression in Acute Ischemic Stroke.
To investigate the neuroprotective effects of Ginkgolide B (GB) against ischemic stroke-induced injury in vivo and in vitro, and further explore the possible mechanisms concerned. Transient middle cerebral artery occlusion (tMCAO) mice and oxygen-glucose deprivation/reoxygenation (OGD/R)-treated N2a cells were used to explore the neuroprotective effects of GB. The expression of brain-derived neurotrophic factor (BDNF) was detected via Western blot and qRT-PCR. GB treatment (4 mg/kg, i. p., bid) significantly reduced neurological deficits, water content, and cerebral infarct volume in tMCAO mice. GB also significantly increased Bcl-2/Bax ratio, reduced the expression of caspase-3, and protected against OGD/R-induced neuronal apoptosis. Meanwhile, GB caused the up-regulation of BDNF protein in vivo and in vitro. Our data suggest that GB might protect the brain against ischemic insult partly via modulating BDNF expression.