Behavioral and psychosocial correlates of road traffic injuries: evidence from a nationwide study on Chinese undergraduates.
Objective: The purpose of this study was to investigate the prevalence and behavioral and psychosocial correlates of road traffic injuries (RTIs) among Chinese university students.Methods: A cross-sectional survey was conducted among fifty universities in China, using a multi-stage sampling methodology. The participants were asked to report their RTIs in the past year. The chi-square test and binary logistic regression analysis were utilized to identify factors associated with RTIs, including specific types of RTIs.Results: Among the 11,770 participants, a total of 1,482 university students reported at least one RTI yielding an overall weighted injury prevalence of 12.96% over the past year. Estimated weighted prevalence by type was 6.10%, 5.94%, 5.12%, and 5.35% for automobile (car, truck, or bus), bicycle, motorcycle, and pedestrian injuries, respectively. Logistic regression analysis found that students who studied at low-level universities, smoked cigarettes, drank alcohol, slept less than 7 hours, went to bed after 12:00 am, or students with psychological distress were more likely to experience overall and four types of RTIs. Students who studied in the eastern universities had a higher likelihood of automobile injury, motorcycle injury and pedestrian injury than those who studied in western universities.Conclusions: Several critical factors associated with RTIs were identified. These findings have implications for the design and implementation of RTI prevention and interventions programs targeted at university students.


Entorhinal cortex pathology in Alzheimer's disease.
The anatomical distribution of pathological changes in Alzheimer's disease, although highly selective for only certain brain areas, can be widespread at the endstage of the illness and can affect many neural systems. Propriety for onset among these is a question of importance for clues to the etiology of the disease, but one that is formidable without an experimental animal model. The entorhinal cortex (Brodmann's area 28) of the ventromedial temporal lobe is an invariant focus of pathology in all cases of Alzheimer's disease with selective changes that alter some layers more than others. The authors' findings reveal that it is the most heavily damaged cortex in Alzheimer's disease. Neuroanatomical studies in higher mammals reveal that the entorhinal cortex gives rise to axons that interconnect the hippocampal formation bidirectionally with the rest of the cortex. Their destruction in Alzheimer's disease could play a prominent role in the memory deficits that herald the onset of Alzheimer's disease and that characterize it throughout its course.


Anchoring fibrils contain the carboxyl-terminal globular domain of type VII procollagen, but lack the amino-terminal globular domain.
Type VII procollagen has been characterized as a product of epithelial cell lines. As secreted, it contains a large triple-helical domain terminated by a multi-globular-domained carboxyl terminus (NC-1), and a smaller amino-terminal globule (NC-2). The triple helix and the NC-1 domain have previously been identified in anchoring fibril-containing tissues by biochemical and immunochemical means, leading to the conclusion that type VII collagen is a major component of anchoring fibrils. In order to better characterize the tissue form of type VII collagen, we have produced a panel of monoclonal antibodies which recognize the NC-1 domain. Peptide mapping of these epitopes indicate that they are independent and span approximately 125,000 kDa of the total 150,000 kDa of each alpha chain contained in NC-1. All these antibodies elicit immunofluorescent staining of the basement membrane zone in tissues. Type VII collagen has been extracted from tissues. As previously reported, it is smaller than type VII procollagen, (Woodley, D. T., Burgeson, R. E., Lunstrum, G. P., Bruckner-Tuderman, L., and Briggaman, R. A., submitted for publication), and we now find that it predominantly occurs as a dimer. Following clostridial collagenase digestion, intact NC-1 has been recognized, indicating that the difference in apparent Mr between the tissue form of the molecule and type VII procollagen results from modification of the amino terminus. The size of the amino-terminal globule has been determined to be between approximately 96 and 102 kDa. Rotary shadowing analyses of extracted molecules indicate that dimeric molecules contain the NC-1 domain, but are missing intact NC-2. We propose that the tissue form monomer, Mr = 960,000, be referred to as "type VII collagen." These studies strongly suggest that anchoring fibrils contain dimeric molecules with intact NC-1 domains. The data also support the previous suggestion that the NC-2 domain is involved in the formation of disulfide bond-stabilized type VII collagen dimers, and is subsequently removed by physiological proteolytic processing.


Regulation of major histocompatibility class II gene expression in FRTL-5 thyrocytes: opposite effects of interferon and methimazole.
Aberrant expression of major histocompatibility complex (MHC) class II antigens is associated with autoimmune thyroid disease; aberrant expression duplicating the autoimmune state can be induced by interferon-gamma (IFNgamma). We have studied IFNgamma-induced human leukocyte antigen (HLA)-DR alpha gene expression in rat FRTL-5 thyroid cells to identify the elements and factors important for aberrant expression. Using an HLA-DR alpha 5'-flanking region construct from -176 to +45 bp coupled to the chloramphenicol acetyltransferase reporter gene, we show that there is no basal class II gene expression in FRTL-5 thyroid cells, that IFNgamma can induce expression, and, as is the case for antigen-presenting cells from the immune system, that IFNgamma-induced expression requires several highly conserved elements on the 5'-flanking region, which, from 5' to 3', are the S, X1, X2, and Y boxes. Methimazole (MMI), a drug used to treat patients with Graves' disease and experimental thyroiditis in rats or mice, can suppress the IFNgamma-induced increase in HLA-DR alpha gene expression as a function of time and concentration; MMI simultaneously decreases IFNgamma-induced endogenous antigen presentation by the cell. Using gel shift assays and the HLA-DR alpha 5'-flanking region from -176 or -137 to +45 bp as radiolabeled probes, we observed the formation of a major protein-DNA complex with extracts from FRTL-5 cells untreated with IFNgamma, termed the basal or constitutive complex, and formation of an additional complex with a slightly faster mobility in extracts from cells treated with IFNgamma. MMI treatment of cells prevents IFNgamma from increasing the formation of this faster migrating complex. Formation of both complexes is specific, as evidenced in competition studies with unlabeled fragments between -137 and -38 bp from the start of transcription; nevertheless, they can be distinguished in such studies. Thus, high concentrations of double stranded oligonucleotides containing the sequence of the Y box, but not S, X1, or X2 box sequences, can prevent formation of the IFNgamma-increased faster migrating complex, but not the basal complex. Both complexes involve multiple proteins and can be distinguished by differences in their protein composition. Thus, using specific antisera, we show that two cAMP response element-binding proteins, activating transcription factor-1 and/or -2, are dominant proteins in the upper or basal complex. The upper or basal complex also includes c-Fos, Fra-2, Ets-2, and Oct-1. A dominant protein that distinguishes the IFNgamma-increased lower complex is CREB-binding protein (CBP), a coactivator of cAMP response element-binding proteins. We, therefore, show that aberrant expression of MHC class II in thyrocytes, induced by IFNgamma, is associated with the induction or increased formation of a novel protein-DNA complex and that its formation as well as aberrant class II expression are suppressed by MMI, a drug used to treat human and experimental autoimmune thyroid disease. Its component proteins differ from those in a major, basal, or constitutive protein-DNA complex formed with the class II 5'-flanking region in cells that are not treated with IFNgamma and that do not express the class II gene.


Quality of communication experience: definition, measurement, and implications for intercultural negotiations.
In an increasingly globalized workplace, the ability to communicate effectively across cultures is critical. We propose that the quality of communication experienced by individuals plays a significant role in the outcomes of intercultural interactions, such as cross-border negotiations. In 4 studies, we developed and validated a multidimensional conceptualization of quality of communication experience (QCE) and examined its consequences in intracultural versus intercultural business negotiations. We proposed and found 3 dimensions of QCE-namely, Clarity, Responsiveness, and Comfort. Findings from intercultural and same-cultural negotiations supported the hypotheses that QCE is lower in intercultural negotiation than in intracultural negotiation and that a higher degree of QCE leads to better negotiation outcomes. Moreover, we found evidence that the beneficial effects of higher QCE on negotiation outcomes are more pronounced in intercultural than in intracultural negotiations. We propose an agenda for future research and identify implications for practice.


Airway constriction measured from tantalum bronchograms in conscious mice in response to methacholine.
A single-projection X-ray technique showed an increase in functional residual capacity (FRC) in conscious mice in response to aerosolized methacholine (MCh) with little change in airway resistance (Raw) measured using barometric plethysmography (Lai-Fook SJ, Houtz PK, Lai Y-L. J Appl Physiol 104: 521-533, 2008). The increase in FRC presumably prevented airway constriction by offsetting airway contractility. We sought a more direct measure of airway constriction. Anesthetized Balb/c mice were intubated with a 22-G catheter, and tantalum dust was insufflated into the lungs to produce a well-defined bronchogram. After overnight recovery, the conscious mouse was placed in a sealed box, and bronchograms were taken at maximum and minimum points of the box pressure cycle before (control) and after 1-min exposures to 25, 50, and 100 mg/ml MCh aerosol. After overnight recovery, each mouse was studied under both room and body temperature box air conditions to correct for gas compression effects on the control tidal volume (Vt) and to determine Vt and Raw with MCh. Airway diameter (D), FRC, and Vt were measured from the X-ray images. Compared with control, D decreased by 24%, frequency decreased by 35%, FRC increased by 120%, and Raw doubled, to reach limiting values with 100 mg/ml MCh. Vt was unchanged with MCh. The limiting D occurred near zero airway elastic recoil, where the maximal contractility was relatively small. The conscious mouse adapted to MCh by breathing at a higher lung volume and reduced frequency to reach a limit in constriction.


Differences in intracellular transport of a fluorescent phosphatidylcholine analog in established cell lines.
The transport and metabolism of a fluorescent phosphatidylcholine analog, 1-palmitoyl-2-(N-4-nitrobenzo-2-oxa-1,3-diazole)- aminocaproyl-phosphatidylcholine [palmitoyl, C6-NBD)-PC), in BHK, CHO-K1, CHO-15B, MDCK, VA-2, Vero, V79 and WI-38 cells has been investigated. When liposomes containing (palmitoyl, C6-NBD)-PC were incubated with cells at 2 degrees C, spontaneous transfer of the fluorescent lipid from the liposomes to the cells' plasma membranes occurred. Most of the lipid transferred to the cells could be removed by incubating the cells in the presence of nonfluorescent liposomes or media containing 10% serum, suggesting that the fluorescent probe resided exclusively in the outer leaflet of the plasma membrane at 2 degrees C. After insertion into the plasma membrane, internalization of (palmitoyl, C6-NBD)-PC occurred when the cells were warmed to 37 degrees C. This resulted in four different labeling patterns: (1) little or no internalization of (palmitoyl, C6-NBD)-PC into punctate vesicles was observed in Vero cells. (2) Transport of (palmitoyl, C6-NBD)-PC to the region of the Golgi apparatus and to a small number of intracellular vesicles was observed in both V79 and CHO-K1 cell lines. (3) A large number of fluorescently labeled intracellular vesicles with little or no labeling in the region of the Golgi apparatus appeared after the internalization of (palmitoyl, C6-NBD)-PC in BHK, CHO-15B, MDCK and WI-38 cell lines. (4) Accumulation of (palmitoyl, C6-NBD)-PC in small vesicles, mitochondria and the nuclear envelope was observed in VA-2 cells. In addition, cells having a defect in glycoprotein processing and those transformed with simian virus 40 (SV40) internalized the fluorescent lipid probe differently compared with parental lines. Neither differences in rates of endocytosis nor rates of (palmitoyl, C6-NBD)-PC degradation between cell types appears to cause the observed dissimilarities in intracellular lipid transport. We suggest that these different cell types may have dissimilar pathways of intracellular lipid trafficking or differential regulation of a common transport pathway, and that the predominant pathway of lipid translocation can be altered in cells by changing the composition of their glycoproteins or by viral transformation.


Current integration of tuberculosis (TB) and HIV services in South Africa, 2011.
Public Health Facilities in South Africa. To assess the current integration of TB and HIV services in South Africa, 2011. Cross-sectional study of 49 randomly selected health facilities in South Africa. Trained interviewers administered a standardized questionnaire to one staff member responsible for TB and HIV in each facility on aspects of TB/HIV policy, integration and recording and reporting. We calculated and compared descriptive statistics by province and facility type. Of the 49 health facilities 35 (71%) provided isoniazid preventive therapy (IPT) and 35 (71%) offered antiretroviral therapy (ART). Among assessed sites in February 2011, 2,512 patients were newly diagnosed with HIV infection, of whom 1,913 (76%) were screened for TB symptoms, and 616 of 1,332 (46%) of those screened negative for TB were initiated on IPT. Of 1,072 patients newly registered with TB in February 2011, 144 (13%) were already on ART prior to Tb clinical diagnosis, and 451 (42%) were newly diagnosed with HIV infection. Of those, 84 (19%) were initiated on ART. Primary health clinics were less likely to offer ART compared to district hospitals or community health centers (p<0.001). As of February 2011, integration of TB and HIV services is taking place in public medical facilities in South Africa. Among these services, IPT in people living with HIV and ART in TB patients are the least available.


It's All in the Wrist: Diagnosis and Management of Carpal Tunnel Syndrome.
Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy accounting for 90% of similar disorders, occurring in 3.8% of the population, common in adults aged 40-60 years, and is associated with an average 32 lost days of work and lost productivity. In addition to occupational exposure, there are several common chronic disorders that can preclude CTS, obesity, diabetes mellitus, rheumatoid arthritis, pregnancy, metabolic syndrome, and thyroid disorder, to name a few. Therefore, it is important for the primary care provider to have knowledge in this syndrome. The purpose of the article is to inform the provider about the etiology, presentation, diagnosis, and treatment of CTS, as well as the implications for job-associated CTS.


25th anniversary article: label-free electrical biodetection using carbon nanostructures.
Nanostructures are promising candidates for use as active materials for the detection of chemical and biological species, mainly due to the high surface-to-volume ratio and the unique physical properties arising at the nanoscale. Among the various nanostructures, materials comprised of sp(2) -carbon enjoy a unique position due to the possibility to readily prepare them in various dimensions ranging from 0D, through 1D to 2D. This review focuses on the use of 1D (carbon nanotubes) and 2D (graphene) carbon nanostructures for the detection of biologically relevant molecules. A key advantage is the possibility to perform the sensing operation without the use of any labels or complex reaction schemes. Along this spirit, various strategies reported for the label-free electrical detection of biomolecules using carbon nanostructures are discussed. With their promise for ultimate sensitivity and the capability to attain high selectivity through controlled chemical functionalization, carbon-based nanobiosensors are expected to open avenues to novel diagnostic tools as well as to obtain new fundamental insight into biomolecular interactions down to the single molecule level.


Dimeric capsules formed by tetra-CMPO derivatives of (thia)calix[4]arenes.
Thiacalix[4]arene 2, calix[4]arene 3a and its tetraether fixed in the cone conformation 3b form homo- and heterodimeric capsules in apolar solvents, which are held together by a seam of NH...O=P hydrogen bonds between carbamoylmethyl phosphine oxide functions attached to their wide rim. Their internal volume of approximately 370 A(3) requires the inclusion of a suitable guest. Although neutral molecules such as adamantane (derivatives) or tetraethylammonium cations form kinetically stable complexes ((1)H- and (31)P-time scale), the included solvent is rapidly exchanged. The internal mobility of the included tetraethylammonium cation is distinctly higher (DeltaG=42.5 and 49.7 kJ mol(-1) for 3a and 3b) than that for similar capsules of tetraurea calix[4]arenes 1. Mixtures of 1 with 2, 3a, or 3b contain only the two homodimers but the heterodimerization occurs with the tetraloop tetraurea 6, which cannot form homodimers. Two dimers with cationic guests (2.(C(5)H(5))(2)Co(+).2 and 3a.Et(3)NH(+).H(2)O.3a) were confirmed by single-crystal X-ray analysis.


microRNAs associated with the different human Argonaute proteins.
MicroRNAs (miRNAs) are small noncoding RNAs that function in literally all cellular processes. miRNAs interact with Argonaute (Ago) proteins and guide them to specific target sites located in the 3'-untranslated region (3'-UTR) of target mRNAs leading to translational repression and deadenylation-induced mRNA degradation. Most miRNAs are processed from hairpin-structured precursors by the consecutive action of the RNase III enzymes Drosha and Dicer. However, processing of miR-451 is Dicer independent and cleavage is mediated by the endonuclease Ago2. Here we have characterized miR-451 sequence and structure requirements for processing as well as sorting of miRNAs into different Ago proteins. Pre-miR-451 appears to be optimized for Ago2 cleavage and changes result in reduced processing. In addition, we show that the mature miR-451 only associates with Ago2 suggesting that mature miRNAs are not exchanged between different members of the Ago protein family. Based on cloning and deep sequencing of endogenous miRNAs associated with Ago1-3, we do not find evidence for miRNA sorting in human cells. However, Ago identity appears to influence the length of some miRNAs, while others remain unaffected.


Fibroproliferative phase of ARDS. Clinical findings and effects of corticosteroids.
Most patients with adult respiratory distress syndrome (ARDS) survive the initial insult which caused respiratory failure only to succumb later to sepsis caused by nosocomial pneumonia or to pulmonary fibrosis. Clinical criteria and analysis of the tracheal aspirate are notoriously inadequate for establishing a diagnosis of ventilator-associated pneumonia. We implemented a comprehensive diagnostic protocol to determine the cause of sepsis in ARDS patients who had been ventilated for more than three days and who had no bronchoscopic evidence of pneumonia. Nine patients with late ARDS who had fever (89 percent), leukocytosis (89 percent), a new localized infiltrate (78 percent), purulent tracheal secretions (89 percent), low systemic vascular resistance (50 percent), and marked uptake of gallium in the lungs (100 percent) had no source of infection identified. Open-lung biopsy specimens from seven patients showed the fibroproliferative phase of diffuse alveolar damage and confirmed absence of pneumonia. Treatment with prolonged high doses of corticosteroids was associated with a marked and rapid improvement in lung injury score (p less than 0.003 at five days). Our findings indicate that the fibroproliferative process occurring in the lungs of patients with late ARDS gives rise to clinical manifestations identical to those of pneumonia and is potentially responsive to steroid treatment.


YAP signaling induces PIEZO1 to promote oral squamous cell carcinoma cell proliferation.
Most cancer cells are exposed to altered extracellular environments, such as an increase in extracellular matrix (ECM) stiffness and soluble signals consisting of growth factors and cytokines. It is therefore conceivable that changes in tumor extracellular environments affect tumor cell behavior. The Hippo pathway reportedly responds to the extracellular environment and regulates the nuclear localization of the transcription co-activator, yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ). Inactivation of the Hippo pathway with nuclear translocation of YAP/TAZ stimulates cell proliferation. Its pathway also regulates gene expression, but the precise molecule(s) meditating the cell-proliferating effect of YAP signaling on oral squamous cell carcinoma (OSCC) is unclear. First, we examined the effects of YAP signaling on OSCC tumorigenesis. Loss-of-function experiments using siRNA or an inhibitor, and immunohistochemical analyses of tissue specimens obtained from OSCC patients demonstrated that YAP signaling was involved in OSCC cell proliferation. Second, we identified Piezo-type mechanosensitive ion channel component 1 (PIEZO1), a Ca2+ channel, as a transcriptional target of YAP signaling and showed that elevated PIEZO1 was required for PIEZO1 agonist-dependent Ca2+ entry and cell proliferation in OSCC cells. Experiments using three-dimensional and suspension culture revealed that PIEZO1 was involved in OSCC cellular growth. Finally, YAP overexpression in the nucleus and/or cytoplasm was immunohistochemically detected in tumor lesions with frequent expression of both PIEZO1 and Ki-67, but not in non-tumor regions of OSCC specimens. These results suggest that the YAP/PIEZO1 axis promotes OSCC cell growth. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Growth, spectroscopy and laser operation of Yb:KGd(PO(3))(4) single crystals.
Macrodefect-free single crystals of Yb-doped KGd(PO(3)), a noncentrosymmetric laser host which possesses second-order nonlinear susceptibility, were grown using the top seeded solution growth slow-cooling (TSSG-SC) technique, reaching a maximum ytterbium concentration in the crystal of approximately 3.2x10(20) at/cm(3). In order to evaluate the potential for self-frequency doubling, the dispersion of the refractive indices of KGd(PO(3))(4) was studied and Sellmeier equations were constructed which are valid in the visible and near-infrared. The Stark splitting of the two electronic states of ytterbium was determined from absorption and emission measurements at room and low temperatures, and this allowed to compute the emission cross sections at room temperature. The fluorescence decay time is quite long, 1.22+/-0.01 ms. Laser generation in the 1 mum range is demonstrated with this new Yb host for the first time. Although the maximum output power achieved, of the order of 100 mW, was limited by the available crystal size and doping level, the more than 55% slope efficiency obtained with this first sample is rather promising for the future.


Otimum kinetic enzymatic procedures for glucose and triglycerides in plasma and serum.
I describe optimum kinetic procedures for measuring glucose and triglycerides in plasma and serum by enzymatic techniques. Glucose was measured by the hexokinase method at a 1000-fold sample dilution. Absorbance and concentration are linearly related for concentrations up to 4 g/liter. Results are reproducible to about 25 mg/liter (standard error). Comparisons between the kinetic glucose method described here and an automated o-toluidine and a manual end-point method showed no apparent bias between the methods; correlation coefficients were 0.998 and 0.991, respectively. Triglycerides (triacylglycerols) were measured in a fully enzymatic system by measuring free glycerol after hydrolysis with lipase. Absorbance and concentration are linearly related to greater than 2.5 g/liter at a 300-fold sample dilution. Repeatability was about 30 mg/liter (standard error). Compared with a manual method, the correlation coefficient was 0.978, with a slope of 0.93.


Integrative mental health care: from theory to practice, Part 2.
Integrative approaches will lead to more accurate and different understandings of mental illness. Beneficial responses to complementary and alternative therapies provide important clues about the phenomenal nature of the human body in space-time and disparate biological, informational, and energetic factors associated with normal and abnormal psychological functioning. The conceptual framework of contemporary Western psychiatry includes multiple theoretical viewpoints, and there is no single best explanatory model of mental illness. Future theories of mental illness causation will not depend exclusively on empirical verification of strictly biological processes but will take into account both classically described biological processes and non-classical models, including complexity theory, resulting in more complete explanations of the characteristics and causes of symptoms and mechanisms of action that result in beneficial responses to treatments. Part 1 of this article examined the limitations of the theory and contemporary clinical methods employed in Western psychiatry and discussed implications of emerging paradigms in physics and the biological sciences for the future of psychiatry. In part 2, a practical methodology, for planning integrative assessment and treatment strategies in mental health care is proposed. Using this methodology the integrative management of moderate and severe psychiatric symptoms is reviewed in detail. As the conceptual framework of Western medicine evolves toward an increasingly integrative perspective, novel understanding of complex relationships between biological, informational, and energetic processes associated with normal psychological functioning and mental illness will lead to more effective integrative assessment and treatment strategies addressing the causes or meanings of symptoms at multiple hierarchic levels of body-brain-mind.


Impact of a pharmacist-led education and counseling interventions on quality of life in epilepsy: A randomized controlled trial.
The impact of epilepsy on the quality of life of the patient can be considerably high with far-reaching and life-long consequences. The goal of patient counseling and education is to achieve positive clinical outcomes and optimize the patient's health-related quality of life. To evaluate the impact of a pharmacist-led education and counselling interventions on the health-related quality of life of patients living with epilepsy. A randomized controlled trial was carried out on epilepsy patients attending the neurology/medical out-patient clinics of two tertiary hospitals. Patients in the intervention group were offered education and counselling services. The impact of the interventions on the patients' quality of life in epilepsy was evaluated using the QOLIE-10P questionnaire. The research protocol was approved by the Health Research Ethics Committees of the University of Uyo Teaching Hospital and University of Calabar Teaching Hospital (Reference numbers: UUTH/AD/S/96/VOL.XIV/571 & UCTH/HREC/33/454). There was a statistically significant difference between the usual care (UC) and the pharmaceutical care (PC) group on the quality of life in epilepsy scores post-intervention. Comparisons between groups (UC versus PC) revealed that patients in the PC group had a significantly higher QOLIE score than those in the UC group at 3 months and 6 months - (Pre-intervention: 8.73 versus 7.91; t = 0.619; p = 0.537), (3 months: 9.74 versus 15.37; t = -3.34; p = 0.01), (6 months: 11.59 versus 17.01; t = -3.137; p = 0.01). Pharmacist-led education and counselling interventions may significantly improve the quality of life of patients with epilepsy.


A graphical user interface for infant ERP analysis.
Recording of event-related potentials (ERPs) is one of the best-suited technologies for examining brain function in human infants. Yet the existing software packages are not optimized for the unique requirements of analyzing artifact-prone ERP data from infants. We developed a new graphical user interface that enables an efficient implementation of a two-stage approach to the analysis of infant ERPs. In the first stage, video records of infant behavior are synchronized with ERPs at the level of individual trials to reject epochs with noncompliant behavior and other artifacts. In the second stage, the interface calls MATLAB and EEGLAB (Delorme & Makeig, Journal of Neuroscience Methods 134(1):9-21, 2004) functions for further preprocessing of the ERP signal itself (i.e., filtering, artifact removal, interpolation, and rereferencing). Finally, methods are included for data visualization and analysis by using bootstrapped group averages. Analyses of simulated and real EEG data demonstrated that the proposed approach can be effectively used to establish task compliance, remove various types of artifacts, and perform representative visualizations and statistical comparisons of ERPs. The interface is available for download from http://www.uta.fi/med/icl/methods/eeg.html in a format that is widely applicable to ERP studies with special populations and open for further editing by users.


Epstein-Barr virus lymphoproliferative disease after hematopoietic stem cell transplant.
Epstein-Barr virus (EBV) reactivation can cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplant. Delays in reconstitution of EBV-specific T lymphocyte activity can lead to life-threatening EBV lymphoproliferative disease (EBV-PTLD). This review highlights recent advances in the understanding of pathophysiology, risk factors, diagnosis, and management of EBV viremia and PTLD. During the past decade, early detection strategies, such as serial measurement of EBV-DNA load, have helped identify high-risk patients and diagnose early lymphoproliferation. The most significant advances have come in the form of innovative treatment options, including manipulation of the balance between outgrowing EBV-infected B cells and the EBV cytotoxic T lymphocyte response, and targeting infected B cells with monoclonal antibodies, chemotherapy, unmanipulated donor lymphocytes, and donor or more recently third-party EBV cytotoxic T lymphocytes. Defining criteria for preemptive therapy remains a challenge. EBV reactivation is a significant complication after stem cell transplant. Continued improvements in risk stratification and treatment options are required to improve the morbidity and mortality caused by EBV-associated diseases. Current approaches use rituximab to deplete B cells or adoptive transfer of EBV cytotoxic T lymphocyte to reconstitute immunity. The availability of rapid EBV-specific T cell products offers the possibility of improved outcomes.


Effect of Lactobacillus rhamnosus HN001 in Pregnancy on Postpartum Symptoms of Depression and Anxiety: A Randomised Double-blind Placebo-controlled Trial.
Probiotics may help to prevent symptoms of anxiety and depression through several putative mechanisms. The aim of this study was to evaluate the effect of Lactobacillus rhamnosus HN001 (HN001) given in pregnancy and postpartum on symptoms of maternal depression and anxiety in the postpartum period. This was a secondary outcome, the primary outcome being eczema in the offspring at 12months of age. A randomised, double-blind, placebo-controlled trial of the effect of HN001 on postnatal mood was conducted in 423 women in Auckland and Wellington, New Zealand. Women were recruited at 14-16weeks gestation. Women were randomised to receive either placebo or HN001 daily from enrolment until 6months postpartum if breastfeeding. Modified versions of the Edinburgh Postnatal Depression Scale and State Trait Anxiety Inventory were used to assess symptoms of depression and anxiety postpartum. Australia NZ Clinical Trials Registry: ACTRN12612000196842. 423 women were recruited between December 2012 and November 2014. 212 women were randomised to HN001 and 211 to placebo. 380 women (89.8%) completed the questionnaire on psychological outcomes, 193 (91.0%) in the treatment group and 187 (88.6%) in the placebo group. Mothers in the probiotic treatment group reported significantly lower depression scores (HN001 mean=7·7 (SD=5·4), placebo 9·0 (6·0); effect size -1·2, (95% CI -2·3, -0·1), p=0·037) and anxiety scores (HN001 12·0 (4·0), placebo 13·0 (4·0); effect size -1·0 (-1·9, -0·2), p=0·014) than those in the placebo group. Rates of clinically relevant anxiety on screening (score>15) were significantly lower in the HN001 treated mothers (OR=0·44 (0·26, 0·73), p=0·002). Women who received HN001 had significantly lower depression and anxiety scores in the postpartum period. This probiotic may be useful for the prevention or treatment of symptoms of depression and anxiety postpartum. Health Research Council of New Zealand (11/318) and Fonterra Co-operative Group Ltd.


BRD4 Protein as a Target for Lung Cancer and Hematological Cancer Therapy: A Review.
The BET protein family plays a crucial role in regulating the epigenetic landscape of the genome. Their role in regulating tumor-related gene expression and its impact on the survival of tumor cells is widely acknowledged. Among the BET family constituents, BRD4 is a significant protein. It is a bromodomain-containing protein located at the outer terminal that recognizes histones that have undergone acetylation. It is present in the promoter or enhancer region of the target gene and is responsible for initiating and sustaining the expression of genes associated with tumorigenesis. BRD4 expression is significantly elevated in various tumor types. Research has indicated that BRD4 plays a significant role in regulating various transcription factors and chromatin modification, as well as in repairing DNA damage and preserving telomere function, ultimately contributing to the survival of cancerous cells. The protein BRD4 has a significant impact on antitumor therapy, particularly in the management of lung cancer and hematological malignancies, and the promising potential of BRD4 inhibitors in the realm of cancer prevention and treatment is a topic of great interest. Therefore, BRD4 is considered a promising candidate for prophylaxis and therapy of neoplastic diseases. However, further research is required to fully comprehend the significance and indispensability of BRD4 in cancer and its potential as a therapeutic target.


Burden of viral respiratory disease hospitalizations among children in a community of Seoul, Republic of Korea, 1995 - 2005.
Our objective was to describe respiratory disease hospitalizations among children in a community of Seoul, Republic of Korea. Discharge data (January 1995-December 2005) from Guro Hospital (Seoul, Republic of Korea) were collected from the hospital medical records office. Respiratory virus test results (March 2004-December 2005) and hospitalization charges to the National Health Insurance Corporation (January 2002-December 2005) were provided by hospital laboratory and administrative departments. Variations in hospitalizations, test results and total hospitalization-associated medical charges were described by age, clinical complaint, discharge month and length of stay. Over the 11-y period, 4247 paediatric hospitalizations for lower respiratory disease occurred. Semi-annual epidemics were identified in October-December and April-May. Among a subset (n=400) of patients, 48% had respiratory syncytial virus, 16% parainfluenza virus, 19% influenza viruses and 17% adenovirus infection. On admission, children had respiratory problems (53%), fever (39%), or other systemic problems (8%). The median charge of a lower respiratory disease hospitalization was highest in January ($1334) and lowest in October ($1076). Median hospitalization charges were highest among children 8-15 years of age compared with younger children </=2 years and those 3-7 years of age. Respiratory disease hospitalizations among children demonstrated annual variations reflecting patterns of children with laboratory-confirmed respiratory viral infections. In the Republic of Korea, prospective studies that use standardized laboratory testing for respiratory pathogens in children will help to estimate the total burden of viral lower respiratory tract disease.


Impact of Abdominal Wall Metastases on Prognosis in Epithelial Ovarian Cancer.
Epithelial ovarian cancer (EOC) patients with the presence of abdominal wall metastasis (AWM) are categorized as stage International Federation of Gynecology and Obstetrics (FIGO) IVB, irrespective of other biologic factors or preceding invasive intervention before final surgery. We evaluated the impact of AWM on patients' overall survival (OS). In this exploratory study, 634 consecutive patients with advanced EOC treated in our center from 2000 to 2014 were included. Patients were categorized into FIGO IIIC (n = 308), FIGO IVB AWM only (n = 86), and FIGO IV others (metastases other than AWM, n = 240). Clinicopathological parameters and survival data were extracted from our prospectively maintained tumor registry. Survival analyses were calculated using Kaplan-Meier method and Cox regression models. In 75 (87.2%) of 86 cases, AWM was seen after a preceding intervention, and only in 12.7%, the deposits were spontaneously established. The median OS in patients with stage FIGO IIIC, FIGO IVB AWM only, and FIGO IV others was 37, 58, and 25 months (P < 0.001), respectively. Patients with FIGO IVB AWM only had a significantly better OS than patients with FIGO IV others (P < 0.001). The numeric longer OS of patients with FIGO IVB AWM only compared with patients with FIGO IIIC was not statistically significant (P = 0.151). In multivariate analysis considering all confounding factors including residual disease, OS of patients with FIGO IIIC did not differ from patients with FIGO AWM only (hazard ratio, 0.84; 95% confidence interval, 0.56-12.26; P = 0.398). Most AWM are acquired after preceding intervention (puncture or laparoscopy). Prognosis of patients with AWM as the only site of distant metastasis is superior compared with other stage FIGO IV patients. Therefore, up-staging of patients only because of AWM to FIGO IVB may be questioned. A revision/clarification of the FIGO classification system should be considered to avoid unnecessary stigmatization of patients and to classify these patients more appropriately according to prognosis.


Catheter related sepsis during long-term parenteral nutrition in paediatric gastroenterology patients: a study of 185 consecutive central venous catheters.
We report the results of a prospective study of catheter-related sepsis (CRS) in 154 gastroenterology paediatric patients treated for medical (n = 102) or surgical (n = 52) disorders. Over 2 years, 185 central venous catheters (CVC) were placed, including 155 Broviac and 30 Jonathan Shaw CVC. CVC remained in place 13,331 days (6,539 days of cyclic parenteral nutrition), with a mean catheter life of 72 days. Forty-eight episodes of CRS occurred, most of them due to coagulase-negative staphylococci (n = 29) and Staphylococcus aureus (n = 17). CRS rate was 0.26, with an overall incidence of 1 infection per 278 days of parenteral nutrition (PN). Factors significantly associated with CRS were: age 1-5 years (p < 0.01), a medical indication for treatment (p < 0.001) and summer months of PN (p < 0.01). Interestingly, CRS occurred predominantly (65%) within the first 2 months following CVC placement and the risk of infection correlated with local haemorrhage at the time of insertion (p < 0.01). Appropriate systemic therapy, without removing the catheter, permitted resolution of 90.9% (40/44) of all CRS and 100% (28/28) of CRS due to coagulase-negative staphylococci.


Microbiological, rheological and physical-chemical characteristics of bovine meat subjected to a prolonged ageing period.
The aim of this study was to evaluate the effects of a long ageing period on the microbiological, rheological and physicalchemical characteristics of bovine beef. For the trial n. 3 Marchigiana bovine breed (live weight of 760 kg approximately), slaughtered at 34 months were chosen and the loin muscles were undergone to a prolonged ageing process. The analytical determinations performed were: pH and aw values, texture profile analysis, Warner-Bratzler shear force, colour (CIE L*a*b*), centesimal analysis, total bacterial count, Enterobacteriaceae, Listeria monocytogenes, yeasts and moulds. The results indicate that extended ageing has a negative effect on weight loss but, by the means of the standardization of dry aging parameters, reduce lipid oxidation and improve tenderness.


[Change of serological properties of museum strains of Shigella flexneri in different terms of storage].
The viability, purity, biological and serological properties of museum strains of Shigella flexneri which were kept in lyophilized state during above 30 years were studied. Primary serological characteristics were specified, it was established that type 2a is the predominant serotype independent of the years and regions of isolation. Some strains lost antigens as a result of the long-term preservation or reinoculation on agar media.


Dust exposure and mortality in an American chrysotile asbestos friction products plant.
Cohort studies in three American asbestos factories were undertaken to investigate the effect of fibre type and manufacturing process on lung cancer, mesothelioma, and asbestosis. Reports have been published on a chrysotile textile plant in South Carolina and a mainly textile plant in Pennsylvania, which also used amphiboles. In the third plant in Connecticut friction products and packings were made from chrysotile only. In a cohort of 3641 men employed for one month or more, 1938-58, 3513 (96.5%) were traced, 1267 (36%) had died, and death certificates were obtained for 1228 (96.9%). Individual exposures were estimated (in mcpf . years) from impinger measurements. Life table analyses using Connecticut mortality rates gave an SMR for all causes of 108.5 (USA 107.9). The SMR (all causes) for men who had worked for less than a year was 129.9 and for those who had worked for a year or more, 101.2. The equivalent SMRs for respiratory cancer were 167.4 and 136.7 respectively. Excluding men who had worked for less than a year, there was possible evidence of some increase in risk of lung cancer with increasing exposure, supported also by a "log-rank" (case-control) analysis, of the same order as that observed in chrysotile mining and milling. These findings may be compared with chrysotile textile manufacture where the risk of lung cancer was some 50-fold greater. It is suggested that the differences in risk are perhaps related to the higher proportion of submicroscopic fibres in textile manufacture that may result from the traumatic carding , spinning, and weaving processes. No case of mesothelioma was found, consistent with a much lower risk of this tumour with chrysotile than with amphiboles. Twelve deaths (nine in men with very short and low asbestos exposure) were given ICD code 523 (pneumoconiosis); all but two were ascribed to anthracosilicosis or silicosis and none to asbestosis.


Anatomical Mitral Valve Repair: Mathematical Prediction of Artificial Chordae Length in Para-Commissural Regions.
To develop a mathematical formula for calculating the length of ruptured mitral valve chordae (with a view to surgically replacing them with artificial chordae) when rupture occurs at scallop A1, A3, P1, or P3. We studied human cadaver hearts collected by the Faculty of Medicine at Amiens Picardy University Hospital. The donors' mean age standard deviation age at death was 79 ± 10. After weighing and dissection, we counted the number of para-commissural chordae per scallop and measured their length with a digital calliper. A total of 31 human cadaver hearts (14 from females and 17 from males) were analyzed. The mean lengths of scallops A1, A2, A3, P1, P2, and P3 were 17.45, 19.42, 17.58, 13.32, 14.52, and 13.26 mm, respectively. A linear regression gave the following mathematical equations: A1 = 0.96 × A2- - 1.3 (R: 0.99; P < 0.001); A3 = 0.9 × A2 + 0.17 (R: 0.95; P < 0.01); P1 = 0.87 × P2 +0.74 (R: 0.89; P < 0.001), and P3 = 0.91 × P2 - 0.01 (R: 0.87; P < 0.0001). When the patient's anatomy prevents manual measurements of the chordae during mitral valve repair surgery, the mathematical formulae derived here can be used to predict the length of the chordae on A1, A3, P1, and P3 from the length of the chordae on A2 and P2. The mitral chordae can therefore be replaced with prostheses with a great degree of precision.


A Changing Landscape of Mortality for Systemic Light Chain Amyloidosis.
The purpose of this study was to address the overall trends in mortality since the adoption of modern therapies for treatment of systemic amyloidosis, and to reconsider the prognostic significance of individual components of the current staging system. Systemic light chain (AL) amyloidosis involves deposition of immunoglobulin light chains in organs throughout the body and is known to have the highest mortality when significant cardiac involvement is present. Survival has historically been poor but may be improving as systemic therapies continue to advance. This study assesses whether recent advancements in light chain directed therapy have led to improved survival in patients with systemic AL amyloidosis. We reviewed all cases of patients who were evaluated for a new diagnosis of AL amyloidosis at the Stanford Amyloid Center between 2009 and 2016. Patients' stage at diagnosis was determined according to the most commonly used staging system. Clinical data, overall survival from diagnosis, and the independent influence of each component of the staging system were analyzed. At total of 194 patients were identified with a new diagnosis of systemic AL amyloidosis. Median overall survival was 59 months and 6 months for stage 3 and 4 patients, respectively. Median overall survival was not reached in stage 1 and 2 groups, as survival was >50% by the end of the study. Mean overall survival was 118 months, 76 months, 64 months, and 27 months in Stages 1, 2, 3, and 4 patients, respectively. Although N-terminal pro-B-type natriuretic peptide and troponin I concentrations had large effects on prognosis, differences in serum free light chains (dFLC) on initial staging laboratory results ≥18 mg/dl, part of the current staging system, did not contribute significantly to prognosis for values ≥5 mg/dl. Survival for patients with systemic AL amyloidosis has improved for patients at all stages of disease in the present era of rapid advancements in light chain-reducing therapies. Cardiac biomarkers at diagnosis, but not baseline dFLC ≥18 mg/dl, continue to provide important prognostic information.


Design of matching networks for low noise preamplifiers.
This paper discusses matching networks that minimize inductive coupling between the antennas within an array while simultaneously insuring minimum noise contributions from preamplifiers. Typical low noise preamplifier designs require a strong mismatch between the source impedance and the amplifier input impedance (reflection coefficient close to one) to achieve optimal noise performance. This is in contrast to the familiar impedance match known from communication theory where input and source impedances have complex conjugate values for maximizing the power transfer from source to amplifier. The high input reflection coefficient of low noise amplifiers can be exploited to reduce antenna currents by using lossless impedance transformations to create a high impedance at the coil terminals while simultaneously maintaining a low noise figure for the amplifier. The networks presented here constitute an improvement over previous work because they give additional freedoms regarding the values of the network components and the amplifier input impedance. The technique has been formalized and coded in MathCad, making the design of realizable networks a simple process.


Chartis System Corrected a Misjudged Location of a Giant Bulla Facilitating a Successful Bronchoscopic Bullectomy with Valves: A Case Report.
The recommended standard treatment for giant bullae is surgical bullectomy. However, with a relatively high risk for perioperative morbidity and mortality, it is unsuitable for some patients. Recently, bronchoscopic bullectomy with one-way valves has shown efficacy and safety in some cases. Locating the giant bulla and confirming the negative collateral ventilation are essential for the bronchoscopic bullectomy with valves. Here, we report a case with a giant bulla using the Chartis System to correct the previous mislocation by the high-resolution computed tomography (HRCT), thus helping to achieve a great efficacy in the bronchoscopic bullectomy with valves. Our case suggests that bronchoscopic bullectomy with valves could be an effective and safe choice. Chartis system can be helpful in determining the location of a bulla when difficulty is encountered using HRCT.


[Relationship of oxidative stress and weight loss achieved in morbid obese patients by means of bariatric surgery using the duodenal switch technique].
Oxidative stress (OS), which is overtly present in morbid obesity, is an indicator of a chronic inflammatory state associated to obesity and possibly related with the associated comorbidities, some of which represent an important risk factor for the occurrence of cardiovascular diseases, so that decreasing its intensity has become a treatment priority. he have consecutively performed the duodenal crossing surgical technique in 28 patients suffering from morbid obesity, assessing the level of oxidative stress by the determination of the products of molecular oxidation and antioxidants before the surgery and throughout one year after the surgery. Weight evolution and the progression of the comorbidities already present were assessed. the mean age of the patients in this series was 43 ± 1 years and the mean BMI 50.3. 82% had associated comorbidities. After the surgery, all the patients progressively lost weight throughout the study period, with a parallel improvement of the comorbidities and a progressive decrease in OS values and improvement of the antioxidant systems, the OS values being similar to those of a normal population at the end of the study. The weight loss achieved allows improving the comorbidities and the oxidative stress values so that at the end of the study the results obtained are similar to those of a normal population.


Hemodynamic directed CPR improves cerebral perfusion pressure and brain tissue oxygenation.
Advances in cardiopulmonary resuscitation (CPR) have focused on the generation and maintenance of adequate myocardial blood flow to optimize the return of spontaneous circulation and survival. Much of the morbidity associated with cardiac arrest survivors can be attributed to global brain hypoxic ischemic injury. The objective of this study was to compare cerebral physiological variables using a hemodynamic directed resuscitation strategy versus an absolute depth-guided approach in a porcine model of ventricular fibrillation (VF) cardiac arrest. Intracranial pressure and brain tissue oxygen tension probes were placed in the frontal cortex prior to induction of VF in 21 female 3-month-old swine. After 7 min of VF, animals were randomized to receive one of three resuscitation strategies: (1) hemodynamic directed care (CPP-20): chest compressions (CCs) with depth titrated to a target systolic blood pressure of 100 mmHg and titration of vasopressors to maintain coronary perfusion pressure (CPP)>20 mmHg; (2) depth 33 mm (D33): target CC depth of 33 mm with standard American Heart Association (AHA) epinephrine dosing; or (3) depth 51 mm (D51): target CC depth of 51 mm with standard AHA epinephrine dosing. Cerebral perfusion pressures (CerePP) were significantly higher in the CPP-20 group compared to both D33 (p<0.01) and D51 (p=0.046), and higher in survivors compared to non-survivors irrespective of treatment group (p<0.01). Brain tissue oxygen tension was also higher in the CPP-20 group compared to both D33 (p<0.01) and D51 (p=0.013), and higher in survivors compared to non-survivors irrespective of treatment group (p<0.01). Subjects with a CPP>20 mmHg were 2.7 times more likely to have a CerePP>30 mmHg (p<0.001). Hemodynamic directed resuscitation strategy targeting coronary perfusion pressure>20 mmHg following VF arrest was associated with higher cerebral perfusion pressures and brain tissue oxygen tensions during CPR.


Chromosomal aberrations in squamous cell carcinoma and solar keratoses revealed by comparative genomic hybridization.
To identify chromosomal copy numbers of frequent genetic aberrations within squamous cell carcinomas (SCCs) and solar keratoses (SKs), and provide further evidence to support or challenge current dogma concerning the relationship between these lesions. Retrospective analysis of genetic aberrations in DNA from SK and SCC biopsy specimens by comparative genomic hybridization. University-based research laboratory in Queensland, Australia. Twenty-two biopsy specimens from patients with diagnosed SKs (n = 7), cutaneous SCCs (n = 10), or adjoining lesions (n = 5). Identification of frequent genetic aberrations both specific to SK and SCC and shared by these lesions to investigate their clonal relationship. Shared genomic imbalances were identified in SK and SCC. Frequent gains were located at chromosome arms 3q, 17q, 4p, 14q, Xq, 5p, 9q, 8q, 17p, and 20q, whereas shared regional losses were observed at 9p, 3p, 13q, 17p, 11p, 8q, and 18p. Significant loss of 18q was observed only in SCC lesions. Our results demonstrate that numerous chromosomal aberrations are shared by the 2 lesions, suggesting a clonal relationship between SK and SCC. Additionally, the genomic loss of 18q may be a significant event in SK progression to SCC. Finally, the type and frequency of aberrations suggests a common mode of tumorigenesis in SCC-derived tumors.


Course Offerings in the Fourth Year of Medical School: How U.S. Medical Schools Are Preparing Students for Internship.
The fourth year of medical school remains controversial, despite efforts to reform it. A committee from the Clerkship Directors in Internal Medicine and the Association of Program Directors in Internal Medicine examined transitions from medical school to internship with the goal of better academic advising for students. In 2013 and 2014, the committee examined published literature and the Web sites of 136 Liaison Committee on Medical Education-accredited schools for information on current course offerings for the fourth year of medical school. The authors summarized temporal trends and outcomes when available.Subinternships were required by 122 (90%) of the 136 schools and allow students to experience the intern's role. Capstone courses are increasingly used to fill curricular gaps. Revisiting basic sciences in fourth-year rotations helps to reinforce concepts from earlier years. Many schools require rotations in specific settings, like emergency departments, intensive care units, or ambulatory clinics. A growing number of schools require participation in research, including during the fourth year. Students traditionally take fourth-year clinical electives to improve skills, both within their chosen specialties and in other disciplines. Some students work with underserved populations or seek experiences that will be henceforth unavailable, whereas others use electives to "audition" at desired residency sites. Fourth-year requirements vary considerably among medical schools, reflecting different missions and varied student needs. Few objective outcomes data exist to guide students' choices. Nevertheless, both medical students and educators value the fourth year of medical school and feel it can fill diverse functions in preparing for residency.


Influence of Groundwater Hydraulic Gradient on Bank Storage Metrics.
The hydraulic gradient between aquifers and rivers is one of the most variable properties in a river/aquifer system. Detailed process understanding of bank storage under hydraulic gradients is obtained from a two-dimensional numerical model of a variably saturated aquifer slice perpendicular to a river. Exchange between the river and the aquifer occurs first at the interface with the unsaturated zone. The proportion of total water exchanged through the river bank compared to the river bed is a function of aquifer hydraulic conductivity, partial penetration, and hydraulic gradient. Total exchange may be estimated to within 50% using existing analytical solutions provided that unsaturated zone processes do not strongly influence exchange. Model-calculated bank storage is at a maximum when no hydraulic gradient is present and increases as the hydraulic conductivity increases. However, in the presence of a hydraulic gradient, the largest exchange flux or distance of penetration does not necessarily correspond to the highest hydraulic conductivity, as high hydraulic conductivity increases the components of exchange both into and out of an aquifer. Flood wave characteristics do not influence ambient groundwater discharge, and so in large floods, hydraulic gradients must be high to reduce the volume of bank storage. Practical measurement of bank storage metrics is problematic due to the limitations of available measurement technologies and the nested processes of exchange that occur at the river-aquifer interface. Proxies, such as time series concentration data in rivers and groundwater, require further development to be representative and quantitative.


"What the mind does not know, the eyes do not see". Placing food allergy risk in sub-Saharan Africa.
Policy makers and health geographers are increasingly intrigued by the global rise of chronic disease. While current engagement coalesce around cardiovascular disease, cancers, chronic respiratory disease, and diabetes, very little attention has been given to other important chronic conditions: e.g., allergic disease. Concerns about how health is shaped by context and experienced in place can provide important insights to understand the trajectory of allergic disease and inform policy especially in developing countries experiencing an epidemiologic transition. Using Ghana as a case study. this paper draw on theories of political ecology of health to enhance our understanding of how individual (e.g. care seeking behaviours), sociocultural (e.g. lack of education and awareness), health system (e.g. absence of logistics) and policy environments (e.g. absence of policy) influence the ways in which food allergy is perceived, diagnosed and managed. These findings highlight the need for decision makers to target structural factors that impede access to and utilization of healthcare, diagnostic practices, as well as food allergy coping and management strategies. Moreover, the findings highlight the need for a global health agenda that pays critical attention to place-based factors in the construction of emerging health risks.


Association of kappa-casein glycosylation with milk production and composition in Holsteins.
A total of 545 milk samples were collected from 53 Holstein cows for 1 yr. On test day, morning milk yields were recorded; milk samples were analyzed for N-acetylneuraminic acid, protein, fat, casein, kappa-casein, and SCC. the relationship between the degree of glycosylation of kappa-casein and morning milk yield and composition was investigated. Data were analyzed using least squares procedures with a model that included test day, parity, stage of lactation, SCC, and phenotype for kappa-casein as fixed effects and N-acetylneuraminic acid content of kappa-casein as covariate. After adjustments were made for effects of environmental and genetic factors, the degree of glycosylation of kappa-casein was associated with morning milk yield, protein, and casein content. Milk yield increased linearly with an increase of N-acetylneuraminic content up to approximately 70 micrograms/mg of kappa-casein.


The causes of mutation accumulation in mitochondrial genomes.
A fundamental observation across eukaryotic taxa is that mitochondrial genomes have a higher load of deleterious mutations than nuclear genomes. Identifying the evolutionary forces that drive this difference is important to understanding the rates and patterns of sequence evolution, the efficacy of natural selection, the maintenance of sex and recombination and the mechanisms underlying human ageing and many diseases. Recent studies have implicated the presumed asexuality of mitochondrial genomes as responsible for their high mutational load. We review the current body of knowledge on mitochondrial mutation accumulation and recombination, and conclude that asexuality, per se, may not be the primary determinant of the high mutation load in mitochondrial DNA (mtDNA). Very little recombination is required to counter mutation accumulation, and recent evidence suggests that mitochondrial genomes do experience occasional recombination. Instead, a high rate of accumulation of mildly deleterious mutations in mtDNA may result from the small effective population size associated with effectively haploid inheritance. This type of transmission is nearly ubiquitous among mitochondrial genomes. We also describe an experimental framework using variation in mating system between closely related species to disentangle the root causes of mutation accumulation in mitochondrial genomes.


Neuroglia as targets for drug delivery systems: A review.
Targeted drug delivery within the nervous system is an emerging topic of research that involves designing and developing vehicular delivery systems that have the ability to target specific neuronal and non-neuronal cell types in the central and peripheral nervous system. Drugs, genetic material, or any other payloads can be loaded onto such delivery systems and could be used to treat, prevent or manage various neurological disorders. Currently, majority of studies in this field have been concentrated around targeted delivery to neurons. However, the non-neuronal cells within the nervous system, collectively called neuroglia, have been largely ignored, though it is well known that they play a significant role in the pathophysiology of almost all neurological disorders. In this review, we present current developments in the specific area of neuroglia targeted delivery systems and highlight the use of polymeric, metallic, liposomal and other delivery systems used for this purpose.


Primary and secondary prevention of ventricular arrhythmias in dilated cardiomyopathy: nonsustained, sustained, and incessant.
The occurrence of ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy (DCM) who are treated with an implantable cardioverter-defibrillator (ICD) for primary or secondary prevention is not fully understood. In this nonrandomized, two-centre, observational study we analyzed the occurrence of ventricular arrhythmias in a total of 105 DCM patients (age, 53 +/- 13 years) treated with an ICD. Fifty-one patients with a left ventricular ejection fraction <or= 35% did not have prior sustained ventricular arrhythmias (primary prevention). The secondary prevention group consisted of 54 patients with documented sustained ventricular tachycardia (n = 25) or aborted sudden cardiac death (n = 29). During 32 +/- 7 months follow-up the number of patients with appropriate defibrillator therapies (n = 51) was comparable between the two groups (HR 0.79, 95% CI 0.454 to 1.361, P = 0.389). Importantly, less primary prevention patients experienced appropriate ICD shocks for any arrhythmic event (HR 0.35, 95% CI 0.186 to 0.777, P = 0.008), as well as appropriate ICD shocks for ventricular fibrillation (HR 0.31, 95% CI 0.167 to 0.737, P = 0.006). In contrast, antitachycardia pacing was more often observed in the primary prevention group (HR 2.75, 95% CI 1.031 to 6.238, P = 0.043). Two primary prevention and 6 secondary prevention patients received multiple ICD therapies in consequence of incessant ventricular tachycardia. The characteristics of ventricular arrhythmias in patients with DCM who are treated with an ICD for primary or secondary prevention vary according to the underlying indication. Therefore, different device programming according to the patient's history might improve ventricular tachyarrhythmia management.


Defining accelerometer thresholds for activity intensities in adolescent girls.
To derive a regression equation that estimates metabolic equivalent (MET) from accelerometer counts, and to define thresholds of accelerometer counts that can be used to delineate sedentary, light, moderate, and vigorous activity in adolescent girls. Seventy-four healthy 8th grade girls, age 13 - 14 yr, were recruited from urban areas of Baltimore, MD, Minneapolis/St. Paul, MN, and Columbia, SC, to participate in the study. Accelerometer and oxygen consumption (.-)VO(2)) data for 10 activities that varied in intensity from sedentary (e.g., TV watching) to vigorous (e.g., running) were collected. While performing these activities, the girls wore two accelerometers, a heart rate monitor and a Cosmed K4b2 portable metabolic unit for measurement of (.-)VO(2). A random-coefficients model was used to estimate the relationship between accelerometer counts and (.-)VO(2). Activity thresholds were defined by minimizing the false positive and false negative classifications. The activities provided a wide range in (.-)VO(2) (3 - 36 mL x kg x min) with a correspondingly wide range in accelerometer counts (1- 3928 counts x 30 s). The regression line for MET score versus counts was MET = 2.01 +/- 0.00171 (counts x 30 s) (mixed model R = 0.84, SEE = 1.36). A threshold of 1500 counts x 30 s defined the lower end of the moderate intensity (approximately 4.6 METs) range of physical activity. That cutpoint distinguished between slow and brisk walking, and gave the lowest number of false positive and false negative classifications. The threshold ranges for sedentary, light, moderate, and vigorous physical activity were found to be 0 - 50, 51- 1499, 1500 - 2600, and >2600 counts x 30 s, respectively. The developed equation and these activity thresholds can be used for prediction of MET score from accelerometer counts and participation in various intensities of physical activity in adolescent girls.


[Temporal cochlear changes evoked by prolonged exposure to low intensity noise. Electrophysiological study in guinea pigs].
Behavioral temporal threshold shifts (TTS) have been shown in the chinchilla, to be correlated with cochlear microphonic (CM) and whole-nerve action potential (AP) losses in the sensitivity as well as in maximum voltage. The Guinea-pig's ear differs significantly both anatomically and physiologically from the chinchilla's; as a result, it does not seem to be as susceptible to TTS at non-injurious noise levels, except at those frequency bands were middle-ear impedance and other factors are more favorable. At times varying from 2 hrs to 48 hrs after termination of noise exposures of 48 hrs duration to an octave-band of noise (7-14 KHz) with a sound-pressure level of 95 dB, the CM from the first three cochlear turns as well as the whole-nerve AP were measured in Guinea pigs. Losses in sensitivity as well as in maximum voltage were found in the CM recorded from the first turn. CM recovered gradually with time, reaching normal levels at about 40 hrs after termination of noise exposures. The AP +showed similar losses. Microscopic examination of the organ of Corti showed no loss of hair cells.


Casein kinase 1γ1 inhibits the RIG-I/TLR signaling pathway through phosphorylating p65 and promoting its degradation.
The casein kinase 1 (CK1) plays an important role in various biological processes by phosphorylating its target proteins. In this study, we demonstrate that CK1γ1 inhibits RNA virus-mediated activation of retinoic acid-inducible gene I (RIG-I) signaling by affecting the stability of NF-κB subunit p65. First, we found that ectopic expression of CK1γ1 inhibits RIG-I pathway-mediated activation of IFN-β, whereas knockdown of CK1γ1 potentiates the activation of IFN-β and NF-κB induced by Sendai virus (SeV). We then revealed that CK1γ1 interacts with p65 and specifically enhances its phosphorylation at Ser(536) induced by SeV. By using an in vitro kinase assay, we confirmed that CK1γ1 can phosphorylate p65 at Ser(536). We also showed that the kinase dead mutants CK1γ1K73A and CK1γ1N169A did not inhibit SeV-induced activation of IFN-β and NF-κB, suggesting that the kinase activity of CK1γ1 is critical for its inhibitory effect on RIG-I signaling. Additionally, we found that CK1γ1 also has the similar effect on TLR signaling. Further analysis indicated that CK1γ1 phosphorylates p65 and consequently promotes its degradation by ubiquitin E3 ligases CUL2 and COMMD1. These results revealed a novel negative regulatory manner of CK1γ1 on innate immune signaling.


Rapid Differentiation of Unfrozen and Frozen-Thawed Tuna with Non-Destructive Methods and Classification Models: Bioelectrical Impedance Analysis (BIA), Near-Infrared Spectroscopy (NIR) and Time Domain Reflectometry (TDR).
The performances of three non-destructive sensors, based on different principles, bioelectrical impedance analysis (BIA), near-infrared spectroscopy (NIR) and time domain reflectometry (TDR), were studied to discriminate between unfrozen and frozen-thawed fish. Bigeye tuna (Thunnus obesus) was selected as a model to evaluate these technologies. The addition of water and additives is usual in the fish industry, thus, in order to have a wide range of possible commercial conditions, some samples were injected with different water solutions (based on different concentrations of salt, polyphosphates and a protein hydrolysate solution). Three different models, based on partial least squares discriminant analysis (PLS-DA), were developed for each technology. This is a linear classification method that combines the properties of partial least squares (PLS) regression with the classification power of a discriminant technique. The results obtained in the evaluation of the test set were satisfactory for all the sensors, giving NIR the best performance (accuracy = 0.91, error rate = 0.10). Nevertheless, the classification accomplished with BIA and TDR data resulted also satisfactory and almost equally as good, with accuracies of 0.88 and 0.86 and error rates of 0.14 and 0.15, respectively. This work opens new possibilities to discriminate between unfrozen and frozen-thawed fish samples with different non-destructive alternatives, regardless of whether or not they have added water.


Age-dependent alterations in the assembly of signal transduction complexes at the site of T cell/APC interaction.
TCR interaction with peptide-MHC complexes triggers migration of protein kinases, actin-binding proteins, and other accessory molecules to the T cell/APC synapse. We used confocal immunofluorescence methods to show that the adapter protein LAT (linker for activation of T cells) and the guanine nucleotide exchange factor Vav also move to the APC interface in mouse CD4 T cells conjugated to anti-CD3 hybridoma cells, and in TCR-transgenic CD4 cells conjugated to APC bearing agonist (but not closely related nonagonist) peptides. The proportion of CD4+ T cells able to relocalize LAT or Vav, or to relocate cytoplasmic NT-AT (NF-ATc) from cytoplasm to nucleus, declines about 2-fold in aged mice. The decline in LAT relocalization is accompanied by a similar decline in tyrosine phosphorylation of LAT in CD4 cells stimulated by CD3/CD4 cross-linking. Two-color experiments show that LAT redistribution is strongly associated with relocalization of both NF-ATc and protein kinase C-theta among individual cells. LAT migration to the immunological synapse depends on actin polymerization as well as on activity of Src family kinases, but aging leads to only a small change in the percentage of CD4 cells that redistribute F-actin to the site of APC contact. These results suggest that defects in the ability of T cells from aged donors to move kinase substrates and coupling factors, including LAT and Vav, into the T cell/APC contact region may contribute to the decline with age in NF-ATc-dependent gene expression, and thus to defects in T cell clonal expansion.


[Characterization of new chemoattractant agents in leukocytes].
G protein-coupled receptors constitute one of the largest gene families in mammals. About a hundred orphan receptors still exist, for which the ligands and functions are unknown. We have recently identified the natural ligands of two orphan receptors expressed in dendritic cells and monocytes/macrophages. Chemerin, product of the gene Tig-2, was characterized as the ligand of the chemR23 receptor. The protein is synthesized as an inactive precursor, prochemerin, which requires the proteolytic removal of the last 6 or 7 amino acids, in order to generate a high affinity ligand of chemR23. Two neutrophil proteases, elastase and cathepsin G, are able to mediate this conversion. Besides, a peptide derived from the intracellular protein heme-binding protein (HBP) has been characterized as the first specific ligand of the FPRL2 receptor. The role of these two new systems in the control of physiological and pathological inflammatory reactions is presently being studied.


The treatment of acute gout with naproxen.
The effectiveness of naproxen in the management of acute gouty arthritis was assessed in an open study of 20 patients. These patients were selected on the basis of their clinical presentation of characteristic acute arthritis associated in 19 with concomitant hyperuricemia. There were 17 men and three women varying in age from 35 to 89 years. The first 12 patients were treated with 600 mg naproxen initially, followed by 300 mg every 8 hours for the first 48 hours and then tapered or discontinued depending upon their clinical response. The last eight patients received a loading dose of 750 mg naproxen, followed by 250 mg every 8 hours for a duration of 72 hours before tapering the drug. The response of 15 of the 20 was either excellent or good, while the response was fair in three and poor in two. Poor responders had been failures in other regimens or were treated late in the course of their attack. The higher loading dose was associated with more rapid and satisfactory remission. No significant undesirable side effects were observed. On the basis of this study, naproxen was found effective in alleviating the inflammation of acute gout.


Effect of visceral manipulation on menstrual complaints in women with polycystic ovarian syndrome.
Research is lacking regarding osteopathic approaches in treating polycystic ovary syndrome (PCOS), one of the prevailing endocrine abnormalities in reproductive-aged women. Limited movement of pelvic organs can result in functional and structural deficits, which can be resolved by applying visceral manipulation (VM). This study aims to analyze the effect of VM on dysmenorrhea, irregular, delayed, and/or absent menses, and premenstrual symptoms in PCOS patients. Thirty Egyptian women with PCOS, with menstruation-related complaints and free from systematic diseases and/or adrenal gland abnormalities, prospectively participated in a single-blinded, randomized controlled trial. They were recruited from the women's health outpatient clinic in the faculty of physical therapy at Cairo University, with an age of 20-34 years, and a body mass index (BMI) ≥25, <30 kg/m2. Patients were randomly allocated into two equal groups (15 patients); the control group received a low-calorie diet for 3 months, and the study group that received the same hypocaloric diet added to VM to the pelvic organs and their related structures, according to assessment findings, for eight sessions over 3 months. Evaluations for body weight, BMI, and menstrual problems were done by weight-height scale, and menstruation-domain of Polycystic Ovary Syndrome Health-Related Quality of Life Questionnaire (PCOSQ), respectively, at baseline and after 3 months from interventions. Data were described as mean, standard deviation, range, and percentage whenever applicable. Of 60 Egyptian women with PCOS, 30 patients were included, with baseline mean age, weight, BMI, and menstruation domain score of 27.5 ± 2.2 years, 77.7 ± 4.3 kg, 28.6 ± 0.7 kg/m2, and 3.4 ± 1.0, respectively, for the control group, and 26.2 ± 4.7 years, 74.6 ± 3.5 kg, 28.2 ± 1.1 kg/m2, and 2.9 ± 1.0, respectively, for the study group. Out of the 15 patients in the study group, uterine adhesions were found in 14 patients (93.3%), followed by restricted uterine mobility in 13 patients (86.7%), restricted ovarian/broad ligament mobility (9, 60%), and restricted motility (6, 40%). At baseline, there was no significant difference (p>0.05) in any of demographics (age, height), or dependent variables (weight, BMI, menstruation domain score) among both groups. Poststudy, there was a statistically significant reduction (p=0.000) in weight, and BMI mean values for the diet group (71.2 ± 4.2 kg, and 26.4 ± 0.8 kg/m2, respectively) and the diet + VM group (69.2 ± 3.7 kg; 26.1 ± 0.9 kg/m2, respectively). For the improvement in the menstrual complaints, a significant increase (p<0.05) in the menstruation domain mean score was shown in diet group (3.9 ± 1.0), and the diet + VM group (4.6 ± 0.5). On comparing both groups poststudy, there was a statistically significant improvement (p=0.024) in the severity of menstruation-related problems in favor of the diet + VM group. VM yielded greater improvement in menstrual pain, irregularities, and premenstrual symptoms in PCOS patients when added to caloric restriction than utilizing the low-calorie diet alone in treating that condition.


Cochlear potentials in the study of cochlear physiology.
Cochlear potentials have been used for many years as probes of cochlear mechanics. Early studies of cochlear microphonics addressed the pattern of wave motion and linearity of the basilar membrane motion. Since the development of techniques to record from single receptor cells and sensory neurons, these potentials have also been used in studies of the mechanics. Although techniques exist for recording cochlear mechanical motion directly, cochlear potentials can be powerful supplements, since the methods used cause minimal damage to the cochlea and can be applied throughout the cochlear spiral. Unlike existing direct methods, cochlear potentials can be used to characterize the micromechanics of the organ of Corti.


[The study of infrared absorption spectrum of diamond during growth by FTIR].
The diamond thin films were deposited on silicon substrates under invariable conditions of process pressure, substrate temperature negative direct-current (dc) bias of substrate and microwave power while the rations of methane (CH4) to hydrogen (H2) changing from 3% to 5% and 9% using electron-cyclotron-resonance microwave plasma-assisted chemical vapor deposition technique (ECRCVD). In situ Fourier transform infrared spectroscopy (FTIR) have been used to study the plasma species absorbed on the substrate surfaces as well as the species above the substrates surfaces both before and during the nucleation and film growth. It is demonstrated that these techniques can provide useful information on the early stages of diamond growth. When correlated with film properties measured by Raman spectroscopy and scanning electron microscopy, the results from FTIR indicate that the absorption of the graphitic and diamond phases are related to the ratio of CH4 to H2 and can be identified at the early stages of film growth.


Analysis of the Chromosomal Localization of Yeast SMC Complexes by Chromatin Immunoprecipitation.
A plethora of biological processes like gene transcription, DNA replication, DNA recombination, and chromosome segregation are mediated through protein-DNA interactions. A powerful method for investigating proteins within a native chromatin environment in the cell is chromatin immunoprecipitation (ChIP). Combined with the recent technological advancement in next generation sequencing, the ChIP assay can map the exact binding sites of a protein of interest across the entire genome. Here we describe a-step-by step protocol for ChIP followed by library preparation for ChIP-seq from yeast cells.


High-Throughput Sequencing to Investigate Associations Between HLA Genes and Metamizole-Induced Agranulocytosis.
Background and Objective: Agranulocytosis is a rare and potentially life-threatening complication of metamizole (dipyrone) intake that is characterized by a loss of circulating neutrophil granulocytes. While the mechanism underlying this adverse drug reaction is not well understood, involvement of the immune system has been suggested. In addition, associations between genetic variants in the Human Leukocyte Antigen (HLA) region and agranulocytosis induced by other drugs have been reported. The aim of the present study was to assess whether genetic variants in classical HLA genes are associated with the susceptibility to metamizole-induced agranulocytosis (MIA) in a European population by targeted resequencing of eight HLA genes. Design: A case-control cohort of Swiss patients with a history of neutropenia or agranulocytosis associated with metamizole exposure (n = 53), metamizole-tolerant (n = 39) and unexposed controls (n = 161) was recruited for this study. A high-throughput resequencing (HTS) and high-resolution typing method was used to sequence and analyze eight HLA loci in a discovery subset of this cohort (n = 31 cases, n = 38 controls). Identified candidate alleles were investigated in the full Swiss cohort as well as in two independent cohorts from Germany and Spain using HLA imputation from genome-wide SNP array data. In addition, variant calling based on HTS data was performed in the discovery subset for the class I genes HLA-A, -B, and -C using the HLA-specific mapper hla-mapper. Results: Eight candidate alleles (p < 0.05) were identified in the discovery subset, of which HLA-C∗04:01 was associated with MIA in the full Swiss cohort (p < 0.01) restricted to agranulocytosis (ANC < 0.5 × 109/L) cases. However, no candidate allele showed a consistent association in the Swiss, German and Spanish cohorts. Analysis of individual sequence variants in class I genes produced consistent results with HLA typing but did not reveal additional small nucleotide variants associated with MIA. Conclusion: Our results do not support an HLA-restricted T cell-mediated immune mechanism for MIA. However, we established an efficient high-resolution (three-field) eight-locus HTS HLA resequencing method to interrogate the HLA region and demonstrated the feasibility of its application to pharmacogenetic studies.


Leber's hereditary optic neuropathy (LHON)-related mitochondrial DNA sequence changes in italian patients presenting with sporadic bilateral optic neuritis.
Eighteen Italian patients presenting with sporadic, bilateral, simultaneous, or sequential optic neuritis (ON) were evaluated for 14 base changes in mitochondrial DNA (mtDNA) previously found associated with Leber's hereditary optic neuropathy (LHON), aiming to identify at a molecular level LHON cases with nontypical phenotypes. During a 36-month follow-up, 11 ON patients developed clinical or laboratory features allowing diagnosis of clinically definite multiple sclerosis (MS). None was positive for any of the "primary" LHON-associated mutations. However, single or multiple "secondary" LHON-associated sequence changes at 4216/ND1, 4917/ND2, and 13708/ND5 were detected in ON and ON-MS patients. MS controls without visual failure as well as healthy control subjects harbored the same base changes at similar frequencies. In addition, coexistence of three sequence changes was found in two cases (1 ON-MS patient and 1 MS control patient). We also report finding two new neutral sequence base changes in the ND-4 gene which were identified by SSCP and confirmed by automated DNA sequence analysis. The results suggests that these secondary mutations do not contribute to MS susceptibility in these patients, but rather represent neutral mitochondrial DNA polymorphisms. In addition, whether there are biochemical abnormalities related to single and multiple secondary mtDNA sequence changes remain to be demonstrated.


Analysis of the combined effect of two linear inhibitors on a single enzyme.
Different methods for studying the concurrent effects of two linear inhibitors on a single enzyme have been published, including the fractional product of Webb, the Yonetani-Theorell plot or the method of Chou and Talalay. Recently the use of combination plots has also been advocated for this purpose. We have evaluated the applicability of these methods and found that most of them depend on assumptions about the mechanism of action of the inhibitors. If the mechanism of action is not completely understood, or if some assumptions about the mechanism are unfounded, the parameters obtained may be meaningless. Even if these assumptions are correct, the interaction can be advantageously measured using an alternative representation that does not require a knowledge of the inhibition constants and allows experimental data to be retrieved from the plot. In other cases it is the interpretation of the results rather than the validity of the method that is misleading. A common mistake is to take the exclusivity of the effects of two inhibitors as exclusivity of their binding. We show that this assumption is seldom justified. In any case, it is possible to decide whether the combination of two or more inhibitors is more effective than their individual use by means of isobolographic analysis, even when no information about their mechanism of action is available.


An epidemiological evaluation of 1098 acute poisoning cases from Turkey.
This study evaluated the characteristics of orally poisoned patients admitted to our emergency department (ED) between January 1, 1998 and February 28, 2002. This study included 1098 patients. Poisoning cases annualy accounted for 0.5-1.3% of total patient admission during this period. The average age of the patients was 26y old. Poisoning was particulary common in students and housewives. Poisoning cases presented to the ED most commonly between 6 pm and 12 am (38%). More than half of study patients (52%) were admitted to the ED within 2 h of exposure. The incidence of concomitant alcohol intake with another intoxicant was 11%. The ingested drugs were 32% various antidepressants, 23% paracetamol, 20% analgesics (excluding paracetamol and salicylates), 10% antibiotics, 9% benzodiazepines, 7% salicylates and 7% cardiovascular drugs. Most patients received at least 1 of the following treatments: gastric lavage, oral activated charcoal, iv hydration, or diuresis. Thirty-two percent of patients were hospitalized beyond 24 h and 68% of were discharged within 24 h. The mortality rate of the overall cohort was < 1%. Psychiatric consultation was obtained for 55% of patients.


Impact of Local Flavored Tobacco Sales Restrictions on Policy-Related Attitudes and Tobacco Product Access.
As of September 2020, more than 300 state and local jurisdictions restrict the sales of flavored tobacco, with some including menthol. To evaluate the impact of local ordinances restricting the sale of flavored tobacco, we surveyed Californians regarding policy support and perceived access to flavored tobacco. In 2019, we conducted an online survey of 3,075 California youth and young adults recruited via social media, about half of whom lived in a policy jurisdiction. Logistic regressions assessed differences on propensity score-weighted outcomes, policy support, and perceived access. Most respondents indicated agreement with almost all policy support statements. Although policy respondents were less likely than rest-of-California respondents to report perceived difficulty in buying flavored cigars, flavored vape users in policy jurisdictions were more likely than those in the rest of California to report perceived difficulty in buying flavored e-liquid. Regardless of jurisdiction, certain priority subgroups were significantly more likely to report perceived difficulty in accessing flavored cigars, flavored vaping products, flavored e-liquid, and menthol cigarettes. With some exceptions, these findings demonstrate that among vape users in policy jurisdictions and priority subgroups, there is a higher likelihood of reporting perceived difficulty to access flavored tobacco products. Findings might be an early indication of shifts in social norms about flavored tobacco products in California, which could gain traction as local sales restriction ordinances proliferate throughout the state and a statewide flavored-tobacco sales restriction goes into effect.


"We are in this together" - Polish midwives' reflections on perinatal care for Ukrainian women after the outbreak of war.
February 24, 2022, the beginning of Russia's invasion of Ukraine, was also the beginning of an exceptional situation and a challenge for the Polish health care system, the health care workers and Polish citizens. This study aims to conduct a qualitative analysis of midwives' experiences of maternity care for Ukrainian women after the outbreak of war. Eight midwives with experience working with both Ukrainian patients and Ukrainian war refugees (who came to Poland after February 24, 2022) participated in a semi-structured interview. The interview data were transcribed and thematically analysed to identify the observations, challenges and medical personnel needs. The most frequently observed reactions in Ukrainian patients included crying, increased anxiety and irritability, fear, withdrawal, and constant information seeking about the current situation. Breastfeeding problems understood as a consequence of chronic stress were also observed and assisted by the midwives. All respondents pointed out the language barrier and their involvement, showing empathy and attentiveness to the patients' situation. No hospital introduced additional support for midwives. A high level of emotional burden on midwives was observed. The midwives were eager to help Ukrainian patients - they emphasized the more frequent need to make themselves available for them. However, the emotional involvement of the midwives is accompanied by the risk of traumatization and burnout, which are associated with exposure to the difficult experiences of patients. Implementation of training in trauma-informed care and supervision could support midwives in their work and prevent the consequences of long-term stress. Systemic solutions concerning translators' presence and hospital documents' translation are also essential.


[Neuropsychiatric symptoms in dementia syndrome].
The aim of this study was to describe the neuropsychiatric disorders that present in dementia and the differences they show at each stage as the disease progresses. The study involved a total of 175 patients from a psychogeriatric clinic who had been diagnosed as suffering from dementia at distinct stages of the disease: 66 had mild dementia, 56 were with moderate dementia and 53 were suffering from severe dementia. The following instruments were used to collect both socio demographic and clinical data: the Spanish version of the Mini Mental State Examination (miniexamen cognitivo: MEC) for cognitive impairment, the Barthel index for functional deterioration and the neuropsychiatric inventory (NPI) for the non cognitive symptoms. There were no significant differences in the NPI according to the degree of cognitive impairment and the most frequently seen symptoms were anomalous motor activity, apathy and irritability; the neuropsychiatric disorder that was least often present was euphoria. The presence of disinhibition, irritability, depression, hallucinations and anomalous motor activity varied significantly in the different phases of dementia. Thus, disinhibition, irritability and depression were more frequent in the initial stages of the disease whereas hallucinations and anomalous motor activity were seen more often when the cognitive impairment was severe. Neuropsychiatric disorders appear throughout the whole course of dementia and symptoms vary according to the stage of the disease.


Effects of phenylbutazone, indomethacin, prostaglandin E2, butyrate, and glutamine on restitution of oxidant-injured right dorsal colon of horses in vitro.
To study the effects of phenylbutazone, indomethacin, prostaglandin E2 (PGE2), glutamine, and butyrate on restitution of oxidant-injured right dorsal colon of horses in vitro. Right dorsal colon from 9 adult horses euthanatized for reasons other than gastrointestinal tract disease. Mucosal segments from the right dorsal colon were injured via exposure to HOCl and incubated in Ussing chambers in solutions containing phenylbutazone, indomethacin, indomethacin and PGE2, glutamine, and butyrate. Transepithelial resistance and mucosal permeability to mannitol were measured, and all mucosal segments were examined histologically. The HOCl-injured mucosa had lower resistance and higher permeability to mannitol, compared with control tissue. Histologic changes were also evident. Resistance of HOCl-injured mucosa recovered partially during the incubation period, and glutamine improved recovery. Phenylbutazone and indomethacin increased resistance, but these increases were not significant. Butyrate and PGE2 had no effects, compared with nontreated HOCl-injured tissues. Mucosal permeability to mannitol was lower in glutamine-treated tissue, compared with nontreated tissue. Histologic changes reflected the resistance and permeability changes. According to our findings, phenylbutazone and indomethacin do not seem to interfere with restitution of oxidant-injured mucosa of equine colon in vitro, and glutamine could facilitate mucosal restitution.


Suitability of Mycorrhiza-Defective Rice and Its Progenitor for Studies on the Control of Nitrogen Loss in Paddy Fields via Arbuscular Mycorrhiza.
Employing mycorrhiza-defective mutants and their progenitors does not require inoculation or elimination of the resident microbial community in the experimental study of mycorrhizal soil ecology. We aimed to examine the suitability of mycorrhiza-defective rice (non-mycorrhizal, Oryza sativa L., cv. Nipponbare) and its progenitor (mycorrhizal) to evaluate nitrogen (N) loss control from paddy fields via arbuscular mycorrhizal (AM) fungi. We grew the two rice lines in soils with the full community of AM fungi and investigated root AM colonization. In the absence of AM fungi, we estimated rice N content, soil N concentration and microbial community on the basis of phospholipid fatty acids; we also quantified N loss via NH3 volatilization, N2O emission, runoff and leaching. In the presence of AM fungi, we did not find any evidence of AM colonization for non-mycorrhizal rice while mycorrhizal rice was colonized and percentage of root colonization was 17-24%. In the absence of AM fungi, the two rice lines had similar N content, soil N concentration and microbial community. Importantly, there was no significant difference in N loss via all the four pathways between mycorrhizal and non-mycorrhizal systems. This mycorrhizal/non-mycorrhizal rice pair is suitable for further research on the role of AM fungi in the control of soil N loss in paddy fields.


Unintended events following immunization with MMR: a systematic review.
Public debate over the safety of the trivalent measles, mumps and rubella (MMR) vaccine and the drop in vaccination rates in several countries persists despite its almost universal use and accepted effectiveness. We carried out a systematic review to assess the evidence of unintended effects (beneficial or harmful) associated with MMR and the applicability of systematic reviewing methods to the field of safety evaluation. Eligible studies were comparative prospective or retrospective on healthy individuals up to 15 years of age, carried out or published by 2003. We identified 120 articles satisfying our inclusion criteria and included 22. MMR is associated with a lower incidence of upper respiratory tract infections, a higher incidence of irritability, similar incidence of other adverse effects compared to placebo and is likely to be associated with benign thrombocytopenic purpura (TP), parotitis, joint and limb complaints and aseptic meningitis (mumps Urabe strain-containing MMR). Exposure to MMR is unlikely to be associated with Crohn's disease, ulcerative colitis, autism or aseptic meningitis (mumps Jeryl-Lynn strain-containing MMR). The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunization with MMR cannot be separated from its role in preventing the target diseases.