Social environment alters central distribution of estrogen receptor alpha in juvenile prairie voles.
It is well established that social environment, particularly isolation, has a significant impact on social behaviors and neuroendocrine responses. Estrogen receptor alpha (ERalpha) expression in limbic structures and associated nuclei is related to the display of social behaviors. We hypothesized that the stress of isolation would cause changes in the pattern of ERalpha expression in the brain. Using a highly social (typically monogamous and biparental) rodent species, the prairie vole (Microtus ochrogaster), we housed juvenile voles with a sibling, stranger or in isolation for either 4 days or 21 days. Housing manipulations began following weaning from parents and group housed siblings. Rodents may be especially sensitive to manipulations of their social environment during this juvenile period. In particular, female prairie voles are induced ovulators, reliant upon exposure to an unrelated male (male urine) to become reproductively active. ERalpha immunoreactivity was quantified in the medial preoptic area (MPOA), bed nucleus of the stria terminalis (BST), ventromedial nucleus of the hypothalamus (VMH) and medial amygdala (MeA). Significantly fewer ERalpha immunoreactive (ERalpha-ir) cells were labeled in the MPOA and BST of females isolated for 21 days compared with stranger housed females. Non-significant differences were shown in the VMH and MeA of females. No differences were found in voles isolated for 4 days. These results suggest that female prairie voles may be more sensitive than males to manipulations of their social environment during the juvenile period.


Medical history, lifestyle, family history, and occupational risk factors for sporadic Burkitt lymphoma/leukemia: the Interlymph Non-Hodgkin Lymphoma Subtypes Project.
The etiologic role of medical history, lifestyle, family history, and occupational risk factors in sporadic Burkitt lymphoma (BL) is unknown, but epidemiologic and clinical evidence suggests that risk factors may vary by age. We investigated risk factors for sporadic BL in 295 cases compared with 21818 controls in a pooled analysis of 18 case-control studies in the International Lymphoma Epidemiology Consortium (InterLymph). Cases were defined to include typical BL or Burkitt-like lymphoma. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations were calculated separately for younger (<50 years) and older (≥ 50 years) BL using multivariate logistic regression. Cases included 133 younger BL and 159 older BL (age was missing for three cases) and they were evenly split between typical BL (n = 147) and Burkitt-like lymphoma (n = 148). BL in younger participants was inversely associated with a history of allergy (OR = 0.58; 95% CI = 0.32 to 1.05), and positively associated with a history of eczema among individuals without other atopic conditions (OR = 2.54; 95% CI = 1.20 to 5.40), taller height (OR = 2.17; 95% CI = 1.08 to 4.36), and employment as a cleaner (OR = 3.49; 95% CI = 1.13 to 10.7). BL in older participants was associated with a history of hepatitis C virus seropositivity (OR = 4.19; 95% CI = 1.05 to 16.6) based on three exposed cases. Regardless of age, BL was inversely associated with alcohol consumption and positively associated with height. Our data suggest that BL in younger and older adults may be etiologically distinct.


The long-term impact of early cardiovascular therapy intensification for postoperative troponin elevation after major vascular surgery.
Acute cardiac events are a frequent cause of morbidity after vascular surgery. The impact of early evidence-based treatment for patients with an acute cardiac event after vascular surgery on long-term postoperative outcomes has not been extensively studied. We hypothesized that providing appropriate evidence-based treatment to patients with elevated postoperative cardiac troponin levels may limit long-term mortality. We conducted a study of 667 consecutive major vascular surgery patients with an elevated postoperative troponin I level. We then determined which of these patients received medical therapy as per the 2007 American College of Cardiology/American Heart Association recommendations for the medical management of patients with chronic stable angina. All patients with troponin elevation were then matched with 2 control patients without postoperative troponin elevation. Matching was done using logistic regression and nearest-neighbor matching methods. The primary study end point was 12 months survival without a major cardiac event (i.e., death, myocardial infarction, coronary revascularization, or pulmonary edema requiring hospitalization). Therapy was intensified in 43 of 66 patients (65%) who suffered a troponin I elevation after surgery. Patients with a troponin I elevation not receiving intensified cardiovascular treatment had a hazard ratio (HR) of 1.77 (95% confidence interval (CI), 1.13-2.42; P = 0.004) for the primary study outcome as compared with the control group. In contrast, patients with a troponin I elevation who received intensified cardiovascular treatment had an HR of 0.63 (95% CI, 0.10-1.19; P = 0.45) for the primary outcome as compared with the control group. Patients with a troponin I elevation not receiving treatment intensification likely were at higher risk for a major cardiac event (HR, 2.80; 95% CI, 1.05-24.2; P = 0.04) compared with patients who did receive treatment intensification. The main finding of this study was that in patients with elevated troponin I levels after noncardiac surgery, long-term adverse cardiac outcomes may likely be improved by following evidence-based recommendations for the medical management of acute coronary syndromes.


Control analysis of mammalian serine biosynthesis. Feedback inhibition on the final step.
The flux of serine biosynthesis in the liver of the normal rabbit, and of the rat on a low protein diet, is most sensitive to the activity of phosphoserine phosphatase (flux control coefficient up to 0.97), the last of the three enzymes in the pathway after it branches from glycolysis. The concentration of the pathway product, serine, has a strong controlling influence on the flux (response coefficient up to -0.64) through feedback inhibition at this step. The pathway is therefore controlled primarily by the demand for serine rather than the supply of the pathway precursor, 3-phosphoglycerate. Under conditions where there is a lower biosynthetic flux, the flux control coefficients of the first two enzymes of the pathway are increased, and are probably dominant in the rat on a normal diet. In rabbit liver, when ethanol is used to inhibit serine biosynthesis, control can be distributed between the three enzymes, even though the reactions catalysed by the first two remain close to equilibrium. Apart from their intrinsic value in aiding the understanding of the regulation of mammalian serine metabolism, our findings illustrate the danger of assuming that there are invariant design principles in the regulation of metabolic pathways, such as feedback control on the first step after a branch.


[Adherence to copper and stainless steel metal coupons of common nosocomial bacterial strains].
Copper has a bactericidal activity against a series of bacterial strains. To measure resistance to bacterial adherence of copper (Cu) and stainless steel (SS) metal coupons. Bacterial strains causing nosocomial infections in Chile were analyzed. Bacterial adherence was studied using a previously described method based on a system of metal coupons that are immersed in culture media containing the bacteria of interest at room temperature. Adherence to Cu and SS coupons was different for Methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae and Acinetobacter baumannii strains. For these strains, no adherence to Cu coupons occurred during the 48 h observation period compared to a rapidly increasing adherence to SS coupons, with a final colony count of 1.00 E + 07 cfu/mL. For two different Pseudomonas aeruginosa clinical strains, inhibition of adherence was not observed on Cu coupons, and colony counts were similar for Cu and SS using the standard inoculum (2-3 x lO7 cfu).A partial decrease in adherence was observed for Cu but not for SS coupons, when a lower inoculum was used. Copper surfaces represent an interesting option to reduce bacterial contamination in the hospital environment due to its resistance to bacterial adhesión of most of the common nosocomial bacterial strains.


Screening and management of mental health and substance use disorders in HIV treatment settings in low- and middle-income countries within the global IeDEA consortium.
Integration of services to screen and manage mental health and substance use disorders (MSDs) into HIV care settings has been identified as a promising strategy to improve mental health and HIV treatment outcomes among people living with HIV/AIDS (PLWHA) in low- and middle-income countries (LMICs). Data on the extent to which HIV treatment sites in LMICs screen and manage MSDs are limited. The objective of this study was to assess practices for screening and treatment of MSDs at HIV clinics in LMICs participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We surveyed a stratified random sample of 95 HIV clinics in 29 LMICs in the Caribbean, Central and South America, Asia-Pacific and sub-Saharan Africa. The survey captured information onsite characteristics and screening and treatment practices for depression, post-traumatic stress disorder (PTSD), substance use disorders (SUDs) and other mental health disorders. Most sites (n = 76, 80%) were in urban areas. Mental health screening varied by disorder: 57% of sites surveyed screened for depression, 19% for PTSD, 55% for SUDs and 29% for other mental health disorders. Depression, PTSD, SUDs and other mental health disorders were reported as managed on site (having services provided at the HIV clinic or same health facility) at 70%, 51%, 41% and 47% of sites respectively. Combined availability of screening and on-site management of depression, PTSD, and SUDs, and other mental health disorders was reported by 42%, 14%, 26% and 19% of sites, respectively. On-site management of depression and PTSD was reported significantly less often in rural as compared to urban settings (depression: 33% and 78% respectively; PTSD: 24% and 58% respectively). Screening for depression and SUDs was least commonly reported by HIV programmes that treated only children as compared to HIV programmes that treated only adults or treated both adults and children. Significant gaps exist in the management of MSDs in HIV care settings in LMICs, particularly in rural settings. Identification and evaluation of optimal implementation strategies to scale and sustain integrated MSDs and HIV care is needed.


The microRNA-200 family coordinately regulates cell adhesion and proliferation in hair morphogenesis.
The microRNA (miRNA)-200 (miR-200) family is highly expressed in epithelial cells and frequently lost in metastatic cancer. Despite intensive studies into their roles in cancer, their targets and functions in normal epithelial tissues remain unclear. Importantly, it remains unclear how the two subfamilies of the five-miRNA family, distinguished by a single nucleotide within the seed region, regulate their targets. By directly ligating miRNAs to their targeted mRNA regions, we identify numerous miR-200 targets involved in the regulation of focal adhesion, actin cytoskeleton, cell cycle, and Hippo/Yap signaling. The two subfamilies bind to largely distinct target sites, but many genes are coordinately regulated by both subfamilies. Using inducible and knockout mouse models, we show that the miR-200 family regulates cell adhesion and orientation in the hair germ, contributing to precise cell fate specification and hair morphogenesis. Our findings demonstrate that combinatorial targeting of many genes is critical for miRNA function and provide new insights into miR-200's functions.


[Possibilities of magnetic resonance tomography in cardiac diagnosis].
32 patients with different cardiac lesions underwent examinations by magnetic resonance imaging (MRI). In order to reduce moving artefacts measurements were carried out with ECG-triggering. It was possible to make visible precise anatomical details of the heart in cases of congenital diseases, aneurysms, myocardial infarction etc. Important advantages are contrasted with obvious disadvantages.


A suite of 2H NMR spin relaxation experiments for the measurement of RNA dynamics.
A suite of (2)H-based spin relaxation NMR experiments is presented for the measurement of molecular dynamics in a site-specific manner in uniformly (13)C, randomly fractionally deuterated ( approximately 50%) RNA molecules. The experiments quantify (2)H R(1) and R(2) relaxation rates that can subsequently be analyzed to obtain information about dynamics on a pico- to nanosecond time scale. Sensitivity permitting, the consistency of the data can be evaluated by measuring all five rates that are accessible for a spin 1 particle and establishing that the rates obey relations that are predicted from theory. The utility of the methodology is demonstrated with studies of the dynamics of a 14-mer RNA containing the UUCG tetraloop at temperatures of 25 and 5 degrees C. The high quality of the data, even at 5 degrees C, suggests that the experiments will be of use for the study of RNA molecules that are as large as 30 nucleotides.


The intranuclear prolactin/cyclophilin B complex as a transcriptional inducer.
The nuclear translocation of peptide hormones, such as the somatolactogenic hormone prolactin, after receptor internalization has been widely reported. Prolactin has been demonstrated to interact with cyclophilin B, a member of the immunophilin family of proteins. Cyclophilin B interaction with prolactin potentiated prolactin-induced proliferation, cell growth, and the nuclear retrotransport of prolactin. These effects could be abrogated by the removal of the peptidyl-prolyl isomerase activity of cyclophilin B. Our findings indicate that the intranuclear prolactin/cyclophilin B complex acts as a transcriptional inducer by interacting directly with Stat5, resulting in the removal of the Stat-repressor protein inhibitor of activated Stat 3 (PIAS3), thereby enhancing Stat5 DNA-binding activity and prolactin-induced, Stat5-mediated gene expression.


A web tool for the design and management of panels of genes for targeted enrichment and massive sequencing for clinical applications.
Disease targeted sequencing is gaining importance as a powerful and cost-effective application of high throughput sequencing technologies to the diagnosis. However, the lack of proper tools to process the data hinders its extensive adoption. Here we present TEAM, an intuitive and easy-to-use web tool that fills the gap between the predicted mutations and the final diagnostic in targeted enrichment sequencing analysis. The tool searches for known diagnostic mutations, corresponding to a disease panel, among the predicted patient's variants. Diagnostic variants for the disease are taken from four databases of disease-related variants (HGMD-public, HUMSAVAR, ClinVar and COSMIC.) If no primary diagnostic variant is found, then a list of secondary findings that can help to establish a diagnostic is produced. TEAM also provides with an interface for the definition of and customization of panels, by means of which, genes and mutations can be added or discarded to adjust panel definitions. TEAM is freely available at: http://team.babelomics.org.


Comparative assessment of test characteristics of cervical cancer screening methods for implementation in low-resource settings.
Cervical cancer disproportionately affects low-resource settings. Papanicolaou, human papillomavirus (HPV), and visual inspection of cervix with acetic acid (VIA) testing, each with different characteristics, will reduce cervical cancer burden. We conducted a critical literature review using PubMed, Cochrane, WHO, and grey literature from 1994 to 2020. We examined efficacy, harms, and comparative effectiveness of screening methods by age, human immunodeficiency virus, provider characteristics, and assessed implementation challenges in low-resource settings. Comprehensive data on utility and efficacy of screening tests indicates that each screening has strengths and shortcomings but all confer acceptable performance. HPV and VIA appear more promising. Primary HPV test-and-treat, self-testing, and co-testing have been studied but data on triage plans, cost, support system, implementation and sustainability is unclear in low-resource settings. HPV testing could help target subgroups of older or higher risk women. VIA offers local capacity-building and scalability. Quality VIA technique after HPV testing is still required to guide post-screening treatments. VIA competencies decline gradually with current standard trainings. Stationary cervicography improves VIA quality but isn't scalable. Affordable smartphones eliminate this barrier, enhance training through mentorship, and advance continuing education and peer-to-peer training. Smartphone-based VIA facilitates cervical image storage for patient education, health promotion, record-keeping, follow-up care, remote expert support, and quality control to improve VIA reliability and reproducibility and reduce mis-diagnoses and burden to health systems. Rather than ranking screening methods using test characteristics alone in study or higher-resource settings, we advocate for scalable strategies that maximize reliability and access and reduce cost and human resources.


Universality of entropy scaling in one dimensional gapless models.
We consider critical models in one dimension. We study the ground state in the thermodynamic limit (infinite lattice). We are interested in an entropy of a subsystem. We calculate the entropy of a part of the ground state from a space interval (0,x). At zero temperature it describes the entanglement of the part of the ground state from this interval with the rest of the ground state. We obtain an explicit formula for the entropy of the subsystem at any temperature. At zero temperature our formula reproduces a logarithmic formula, discovered by Vidal, Latorre, Rico, and Kitaev for spin chains. We prove our formula by means of conformal field theory and the second law of thermodynamics. Our formula is universal. We illustrate it for a Bose gas with a delta interaction and for the Hubbard model.


Efficiently engineered cell sheet using a complex of polyethylenimine-alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation.
Regeneration of large bone defects is a common clinical problem. Recently, stem cell sheet has been an emerging strategy in bone tissue engineering. To enhance the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic protein 2 (BMP-2) gene-engineered cell sheet using a complex of polyethylenimine-alginate (PEI-al) nanocomposites plus human BMP-2 complementary(c)DNA plasmid, and studied its osteogenesis in vitro and in vivo. PEI-al nanocomposites carrying BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The cell sheet was made by culturing the cells in medium containing vitamin C for 10 days. Assays on the cell culture showed that the genetically engineered cells released the BMP-2 for at least 14 days. The expression of osteogenesis-related gene was increased, which demonstrated that released BMP-2 could effectively induce the cell sheet osteogenic differentiation in vitro. To further test the osteogenic potential of the cell sheet in vivo, enhanced green fluorescent protein or BMP-2-producing cell sheets were treated on the cranial bone defects. The results indicated that the BMP-2-producing cell sheet group was more efficient than other groups in promoting bone formation in the defect area. Our results suggested that PEI-al nanocomposites efficiently deliver the BMP-2 gene to bone marrow mesenchymal stem cells and that BMP-2 gene-engineered cell sheet is an effective way for promoting bone regeneration.


WIPI-1 Positive Autophagosome-Like Vesicles Entrap Pathogenic Staphylococcus aureus for Lysosomal Degradation.
Invading pathogens provoke the autophagic machinery and, in a process termed xenophagy, the host cell survives because autophagy is employed as a safeguard for pathogens that escaped phagosomes. However, some pathogens can manipulate the autophagic pathway and replicate within the niche of generated autophagosome-like vesicles. By automated fluorescence-based high content analyses, we demonstrate that Staphylococcus aureus strains (USA300, HG001, SA113) stimulate autophagy and become entrapped in intracellular PtdIns(3)P-enriched vesicles that are decorated with human WIPI-1, an essential PtdIns(3)P effector of canonical autophagy and membrane protein of both phagophores and autophagosomes. Further, agr-positive S. aureus (USA300, HG001) strains were more efficiently entrapped in WIPI-1 positive autophagosome-like vesicles when compared to agr-negative cells (SA113). By confocal and electron microscopy we provide evidence that single- and multiple-Staphylococci entrapped undergo cell division. Moreover, the number of WIPI-1 positive autophagosome-like vesicles entrapping Staphylococci significantly increased upon (i) lysosomal inhibition by bafilomycin A(1) and (ii) blocking PIKfyve-mediated PtdIns(3,5)P(2) generation by YM201636. In summary, our results provide evidence that the PtdIns(3)P effector function of WIPI-1 is utilized during xenophagy of Staphylococcus aureus. We suggest that invading S. aureus cells become entrapped in autophagosome-like WIPI-1 positive vesicles targeted for lysosomal degradation in nonprofessional host cells.


Differential effects of left and right neuropathy on opioid gene expression in lumbar spinal cord.
The endogenous opioid system (EOS) controls the processing of nociceptive stimuli and is a pharmacological target for opioids. Alterations in expression of the EOS genes under neuropathic pain condition may account for low efficacy of opioid drugs. We here examined whether EOS expression patterns are altered in the lumbar spinal cord of the rats with spinal nerve ligation (SNL) as a neuropathic pain model. Effects of the left- and right-side SNL on expression of EOS genes in the ipsi- and contralateral spinal domains were analysed. The SNL-induced changes were complex and different between the genes; between the dorsal and ventral spinal domains; and between the left and right sides of the spinal cord. Prodynorphin (Pdyn) expression was upregulated in the ipsilateral dorsal domains by each the left and right-side SNL, while changes in expression of μ-opioid receptor (Oprm1) and proenkephalin (Penk) genes were dependent on the SNL side. Changes in expression of the Pdyn and κ-opioid receptor (Oprk1) genes were coordinated between the ipsi- and contralateral sides. Withdrawal response thresholds, indicators of mechanical allodynia correlated negatively with Pdyn expression in the right ventral domain after right side SNL. These findings suggest multiple roles of the EOS gene products in spinal sensitization and changes in motor reflexes, which may differ between the left and right sides.


Hemodynamic significance of internal carotid artery disease.
Neurologic symptoms in the region of an internal carotid artery stenosis are considered to be embolic in most instances. Only in a subgroup has carotid occlusive disease with impairment of the collateral supply, caused a state of hemodynamic failure with marked reduction of perfusion pressure. Though unproven, it is reasonable to assume that without surgical intervention, the risk is higher than average for patients with hemodynamic failure. Equally, should there be any postoperative improvement of cerebral blood flow or neurologic deficits, it should be looked for in this group. Thus, it is necessary to distinguish those with low perfusion pressure from the population of patients with carotid artery disease. Preoperative clinical evaluation and direct visualization of the carotid bifurcation should be supplemented by indirect physiological tests which allow assessment of collateral perfusion. Examination of periorbital flow direction or oculoplethysmography could be used as a screening procedure. Negative tests most certainly rule out any severe pressure gradient across the stenosis, irrespective of the luminal reduction. A positive result, on the other hand, should be further quantified since most indirect tests become positive at relatively small pressure gradients. Studies of cerebral blood flow at rest and during cerebral vasodilation makes it possible to identify patients with severe reduction of cerebral perfusion pressure. Such hemodynamic failure of one hemisphere may be identified in most cases by a conventional non-invasive xenon-133 technique and stationary detectors. Smaller focal regions of hypoperfusion may be identified by computer emission tomography, either by the detection of single-photon emission or by paired detection of annihilation photons. Endarterectomy does improve cerebral hemodynamics in terms of increased flow through the reconstructed vessel and elimination of pressure gradients. The cerebral blood flow, though remains unchanged in the majority of patients, at least when measured at baseline. Only in those patients with a reduction in perfusion pressure can a significant improvement in baseline flow occur. Flow reserve determined by cerebral vasodilation, however, will improve in most patients with hemodynamic failure. In addition, some patients in the low-pressure group develop marked, but temporary, hyperperfusion after reconstruction of very high grade carotid stenosis. This is considered a result of chronic low perfusion pressure with subsequent loss of autoregulation, and autoregulatory control is first regained after some days.(ABSTRACT TRUNCATED AT 400 WORDS)


On the use of ESI-QqTOF-MS/MS for the comparative sequencing of nucleic acids.
The usability of a quadrupole-quadrupole-time-of-flight (QqTOF) instrument for the tandem mass spectrometric sequencing of oligodeoxynuleotides was investigated. The sample set consisted of 21 synthetic oligodeoxynucleotides ranging in length from 5 to 42 nucleotides. The sequences were randomly selected. For the majority of tested oligonucleotides, two or three different charge states were selected as precursor ions. Each precursor ion was fragmented applying several different collision voltages. Overall 282 fragment ion mass spectra were acquired. Computer-aided interpretation of fragment ion mass spectra was accomplished with a recently introduced comparative sequencing algorithm (COMPAS). The applied version of COMPAS was specifically optimized for the interpretation of information-rich spectra obtained on the QqTOF. Sequences of oligodeoxynucleotides as large as 26-mers were correctly verified in >94% of cases (182 of 192 spectra acquired). Fragment ion mass spectra of larger oligonucleotides were not specific enough for sequencing. Because of the occurrence of extensive internal fragmentation causing low sequence coverage paired with a high probability of assigning fragment ions to wrong sequences, tandem mass spectra obtained from oligonucleotides consisting of 30 and more nucleotides could not be used for sequence verification neither manually nor with COMPAS. (c) 2009 Wiley Periodicals, Inc. Biopolymers 91: 401-409, 2009.


Acute and Chronic Toxicity of Sodium Nitrate and Sodium Sulfate to Several Freshwater Organisms in Water-Only Exposures.
Elevated nitrate (NO3 ) and sulfate (SO4 ) in surface water are of global concern, and studies are needed to generate toxicity data to develop environmental guideline values for NO3 and SO4 . The present study was designed to fill existing gaps in toxicity databases by determining the acute and/or chronic toxicity of NO3 (tested as NaNO3 ) to a unionid mussel (Lampsilis siliquoidea), a midge (Chironomus dilutus), a fish (rainbow trout, Oncorhynchus mykiss), and 2 amphibians (Hyla versicolor and Lithobates sylvaticus), and to determine the acute and/or chronic toxicity of SO4 (tested as Na2 SO4 ) to 2 unionid mussels (L. siliquoidea and Villosa iris), an amphipod (Hyalella azteca), and 2 fish species (fathead minnow, Pimephales promelas and O. mykiss). Among the different test species, acute NO3 median effect concentrations (EC50s) ranged from 189 to >883 mg NO3 -N/L, and chronic NO3 20% effect concentrations (EC20s) based on the most sensitive endpoint ranged from 9.6 to 47 mg NO3 -N/L. The midge was the most sensitive species, and the trout was the least sensitive species in both acute and chronic NO3 exposures. Acute SO4 EC50s for the 2 mussel species (2071 and 2064 mg SO4 /L) were similar to the EC50 for the amphipod (2689 mg SO4 /L), whereas chronic EC20s for the 2 mussels (438 and 384 mg SO4 /L) were >2-fold lower than the EC20 of the amphipod (1111 mg SO4 /L), indicating the high sensitivity of mussels in chronic SO4 exposures. However, the fathead minnow, with an EC20 of 374 mg SO4 /L, was the most sensitive species in chronic SO4 exposures whereas the rainbow trout was the least sensitive species (EC20 > 3240 mg SO4 /L). The high sensitivity of fathead minnow was consistent with the finding in a previous chronic Na2 SO4 study. However, the EC20 values from the present study conducted in test water containing a higher potassium concentration (3 mg K/L) were >2-fold greater than those in the previous study at a lower potassium concentration (1 mg K/L), which confirmed the influence of potassium on chronic Na2 SO4 toxicity to the minnow. Environ Toxicol Chem 2020;39:1071-1085. © 2020 SETAC.


Double C-H bond activation of acetylene by atomic boron in forming aromatic cyclic-HBC2BH in solid neon.
The organo-boron species formed from the reactions of boron atoms with acetylene in solid neon are investigated using matrix isolation infrared spectroscopy with isotopic substitutions as well as quantum chemical calculations. Besides the previously reported single C-H bond activation species, a cyclic-HBC2BH diboron species is formed via double C-H bond activation of acetylene. It is characterized to have a closed-shell singlet ground state with planar D2h symmetry. Bonding analysis indicates that it is a doubly aromatic species involving two delocalized σ electrons and two delocalized π electrons. This finding reveals the very first example of double C-H bond activation of acetylene in forming new organo-boron compounds.


Equity in prevention and health care.
There is an increasing body of evidence about socioeconomic inequality in preventive use, mostly for cancer screening. But as far as needs of prevention are unequally distributed, even equal use may not be fair. Moreover, prevention might be unequally used in the same way as health care in general. The objective of the paper is to assess inequity in prevention and to compare socioeconomic inequity in preventive medicine with that in health care. A cross sectional Health Interview Survey was carried out in 1997 by face to face interview and self administered questionnaire. Two types of health care utilisation were considered (contacts with GPs and with specialists) and four preventive care mostly delivered in a GP setting (flu vaccination, cholesterol screening) or in a specialty setting (mammography and pap smear). Belgium. A representative sample of 7378 residents aged 25 years and over (participation rate: 61%). Socioeconomic inequity was measured by the HI(wvp) index, which is the difference between use inequality and needs inequality. Needs was computed as the expected use by the risk factors or target groups. There was significant inequity for all medical contacts and preventive medicine. Medical contacts showed inequity favouring the rich for specialist visits and inequity favouring the poor for contacts with GPs. Regarding preventive medicine, inequity was high and favoured the rich for mammography and cervical screening; inequity was lower for flu immunisation and cholesterol screening but still favoured the higher socioeconomic groups. In the general practice setting, inequity in prevention was higher than inequity in health care; in the specialty setting, inequity in prevention was not statistically different from inequity in health care, although it was higher than in the general practice setting. If inequity in preventive medicine is to be lowered, the role of the GP must be fostered and access to specialty medicine increased, especially for cancer screening.


Prison in-reach mental health nursing.
Surveys have shown that over 90 per cent of the prison population have a diagnosable mental illness, substance abuse problem, or both (ONS 1998). There is general agreement that although there are areas where practice is excellent, practice is not consistent across England and Wales, and often does not equate to standards in the NHS. In 2001 the Department of Health and the prison service set out their joint approach to the modernization of mental health services in prisons (DoH 2001), and proposed mental health in-reach as a means of improving services and achieving the objectives of the NHS Plan (DoH 2000). This article looks at the one of the first prison in-reach services that was launched at HMP Leicester early in 2002, and considers the effect these nurses have had on the care of mentally ill adults at the prison. A case study outlining the in-reach team's approach to one of the prison's greatest challenges, self-harm, is also included.


Can gaze avoidance explain why individuals with Asperger's syndrome can't recognise emotions from facial expressions?
Research has shown that individuals with Autism Spectrum Disorders (ASD) have difficulties recognising emotions from facial expressions. Since eye contact is important for accurate emotion recognition, and individuals with ASD tend to avoid eye contact, this tendency for gaze aversion has been proposed as an explanation for the emotion recognition deficit. This explanation was investigated using a newly developed emotion and mental state recognition task. Individuals with Asperger's Syndrome were less accurate at recognising emotions and mental states, but did not show evidence of gaze avoidance compared to individuals without Asperger's Syndrome. This suggests that the way individuals with Asperger's Syndrome look at faces cannot account for the difficulty they have recognising expressions.


Filtration pressure equilibrium: a statistical analysis.
Statistical analysis of data in published micropuncture studies was applied to determine: a) the number of rats and samples of glomerular capillary pressure (Pg), end-capillary oncotic pressure (COPE), and proximal tubule pressure (Pt), needed in a single study to state with 95% confidence that a measured mean net efferent effective filtration pressure (delta P*E) is within +/- mmHg of any true value, delta PE; b) the effect of intra-animal variation in Pg, COPE, and Pt values on the number of experiments needed; and c) the probability of obtaining a value for delta P*E that meets this criterion in multiple trials. Assuming no intra-animal variation in Pg, Pt, and COPE values and employing published interanimal variances, at least 42 rats should be studied in any series to show that -1 mmHg less than or equal to (delta P*E -- delta PE) less than or equal to 1 mmHg within 95% confidence limits. If intra-animal variances are 60% of the interanimal variances, 67 rats are needed to obtain that degree of confidence when a single measurement of Pt, Pg, and COPE is made in each rat, and 47 animals are required with five measurements per rat. A value for delta P*E within 2-3 mmHg of its true value is, however, attainable with confidence using a far smaller number of animals per series.


Copper extraction from ammoniacal medium in a pulsed sieve-plate column with LIX 84-I.
This article reports on a study of copper removal from ammoniacal aqueous solution (1.0 kg m(-3) Cu, pH 9.5) by liquid-liquid extraction using a pulsed sieve-plate column. The extractant tested was the hydroxyoxime LIX 84-I (2-hydroxy-5-nonylacetophenone oxime) in the aliphatic diluent Shellsol D-70. The results of the pilot plant experiments demonstrated the feasibility of operating the extraction process in this type of column, with efficiencies of copper removal in the range of 90.5-99.5%. Several effects on the column performance were examined, namely the aqueous and organic flow rates and the pulse velocity. The axial dispersion model was applied to simulate the concentration profiles, which reasonably predicted the experimental data. The overall mass transfer coefficient was evaluated from the experimental data and was found to be between 9×10(-6) and 1.2×10(-5) m s(-1). These data were compared with the ones obtained from the resistances in series model, which indicated that the resistance due to chemical reaction was 84-91% of the overall resistance to mass transfer. The extraction using a hollow fiber contactor was also carried out to compare the membrane process performance with the one of conventional process.


Course of neuropsychiatric symptoms in residents with dementia in long-term care institutions: a systematic review.
Neuropsychiatric symptoms (NPS) occur frequently in residents of long-term care institutions. The aim of this study was to review the literature systematically on the course of NPS in residents with dementia in long-term care institutions. A systematic literature search was conducted using Medline, PsychInfo, Embase and Cinahl. Search terms included "dementia", "long-term care institutions", "NPS", "longitudinal", and additional related terms. All titles and abstracts were independently assessed for inclusion and for methodological quality by two researchers, and the full texts of relevant papers were retrieved. Inclusion criteria were: dementia diagnosis, long-term care institutions, NPS, and longitudinal design. The literature search revealed 1982 papers of which 18 met the inclusion criteria. The patients were predominately female and aged 75 years and over. The follow-up period ranged from three months to one year. The number of assessments ranged from two to five, and 12 different assessment instruments were used to study NPS. Aberrant motor behavior, depression, anxiety, and euphoria showed decline over time, and psychosis remained constant whereas apathy, agitation, irritability, and disinhibition increased over time. All symptoms showed specific intermittent courses. The methodological quality of the literature was limited by the small sample sizes, short follow-up periods, and lack of comprehensive neuropsychiatric assessment instruments. In the reviewed studies, NPS in institutionalized residents with dementia showed a heterogeneous course, although methodological limitations and the diversity of the studies call for caution in interpretation. Future research should focus on large prospective cohort studies with institutionalized residents with dementia, examining a wide range of NPS.


Taxonomic distinctness and conservation of a new high biodiversity subterranean area in Brazil.
Subterranean environments, even though they do not possess a primary production (photosynthesis), may present high biodiversity, faunistic originality, endemism, phylogenetic isolations and unique ecological and/or evolution events, in addition to rare taxa. Studies investigating the biological diversity in Neotropical caves are relatively rare and recent, and most of them have been conducted in Brazil. We sampled caves from the state of Bahia, northeastern Brazil, and through sampling sufficiency tests and richness estimators, we demonstrate that the normatization for the Brazilian cave laws is not adequate for its conservation and that only α diversity index is not enough to verify faunistic patterns. We suggest that a phylogenetic diversity index be more robust and accurate for conservation purposes, particularly the Taxonomic Distinctness index. Moreover, we propose that the sandstone complex caves from Chapada Diamantina National Park need to be classified as being of high subterranean biodiversity in a global scope.


Mistaken identity: Reporting two cases of rare forms of extrapulmonary tuberculosis in Solomon Islands.
Extrapulmonary tuberculosis (EPTB) is a relatively rare and difficult-to-diagnose manifestation of Myobacterium tuberculosis (TB) infection. This study reports the cases of a 47-year-old male and a 35-year old female with rare forms of EPTB who sought medical care in Solomon Islands. Both patients presented with nondescript symptoms and a chief complaint of pain. Initial diagnosis for the male and female patient was an abacterial colon polypoid mass and a urinary tract infection (UTI) respectively. Following unsuccessful treatment for UTI and further investigation, the surgical team diagnosed the female patient with a tuberculosis spondylitis and a bilateral psoas abscess. The male patient was subsequently diagnosed with isolated colonic tuberculosis. After starting medication, the patients were discharged and prescribed 9-month treatment regimens. During outpatient treatment both patients reported suboptimal adherence. The female patient resumed treatment and showed improvement while the male patient discontinued treatment, experienced worsening symptoms, and ultimately died. The nonspecific symptoms of extrapulmonary TB infection make it difficult to diagnose. Cases of rare forms of EPTB are particularly challenging to identify. Misdiagnosis may further increase the likelihood of mortality and morbidity in these cases. Intensive medication counseling, patient outreach, and regularly scheduled follow-up visits may reduce the incidence of poor adherence and reduce the risk of developing drug-resistant TB. Medical practitioners in tuberculosis-endemic countries like Solomon Islands should maintain a high clinical index of suspicion in diagnosing EPTB. Future research should investigate the prevalence of TB and EPTB in the Solomon Islands.


Integrative Metabolome and Transcriptome Analyses Provide Insights into Carotenoid Variation in Different-Colored Peppers.
Carotenoids are important pigments in pepper fruits. The colors of each pepper are mainly determined by the composition and content of carotenoid. The 'ZY' variety, which has yellow fruit, is a natural mutant derived from a branch mutant of 'ZR' with different colors. ZY and ZR exhibit obvious differences in fruit color, but no other obvious differences in other traits. To investigate the main reasons for the formation of different colored pepper fruits, transcriptome and metabolome analyses were performed in three developmental stages (S1-S3) in two cultivars. The results revealed that these structural genes (PSY1, CRTISO, CCD1, CYP97C1, VDE1, CCS, NCED1 and NCED2) related to carotenoid biosynthesis were expressed differentially in the two cultivars. Capsanthin and capsorubin mainly accumulated in ZR and were almost non-existent in ZY. S2 is the fruit color-changing stage; this may be a critical period for the development of different color formation of ZY and ZR. A combination of transcriptome and metabolome analyses indicated that CCS, NCED2, AAO4, VDE1 and CYP97C1 genes were key to the differences in the total carotenoid content. These new insights into pepper fruit coloration may help to improve fruit breeding strategies.


Control of virulence by small RNAs in Streptococcus pneumoniae.
Small noncoding RNAs (sRNAs) play important roles in gene regulation in both prokaryotes and eukaryotes. Thus far, no sRNA has been assigned a definitive role in virulence in the major human pathogen Streptococcus pneumoniae. Based on the potential coding capacity of intergenic regions, we hypothesized that the pneumococcus produces many sRNAs and that they would play an important role in pathogenesis. We describe the application of whole-genome transcriptional sequencing to systematically identify the sRNAs of Streptococcus pneumoniae. Using this approach, we have identified 89 putative sRNAs, 56 of which are newly identified. Furthermore, using targeted genetic approaches and Tn-seq transposon screening, we demonstrate that many of the identified sRNAs have important global and niche-specific roles in virulence. These data constitute the most comprehensive analysis of pneumococcal sRNAs and provide the first evidence of the extensive roles of sRNAs in pneumococcal pathogenesis.


The Coupled Photothermal Reaction and Transport in a Laser Additive Metal Nanolayer Simultaneous Synthesis and Pattering for Flexible Electronics.
The Laser Direct Synthesis and Patterning (LDSP) technology has advantages in terms of processing time and cost compared to nanomaterials-based laser additive microfabrication processes. In LDSP, a scanning laser on the substrate surface induces chemical reactions in the reactive liquid solution and selectively deposits target material in a preselected pattern on the substrate. In this study, we experimentally investigated the effect of the processing parameters and type and concentration of the additive solvent on the properties and growth rate of the resulting metal film fabricated by this LDSP technology. It was shown that reactive metal ion solutions with substantial viscosity yield metal films with superior physical properties. A numerical analysis was also carried out the first time to investigate the coupled opto-thermo-fluidic transport phenomena and the effects on the metal film growth rate. To complete the simulation, the optical properties of the LDSP deposited metal film with a variety of thicknesses were measured. The characteristics of the temperature field and the thermally induced flow associated with the moving heat source are discussed. It was shown that the processing temperature range of the LDSP is from 330 to 390 K. A semi-empirical model for estimating the metal film growth rate using this process was developed based on these results. From the experimental and numerical results, it is seen that, owing to the increased reflectivity of the silver film as its thickness increases, the growth rate decreases gradually from about 40 nm at initial to 10 nm per laser scan after ten scans. This self-controlling effect of LDSP process controls the thickness and improves the uniformity of the fabricated metal film. The growth rate and resulting thickness of the metal film can also be regulated by adjustment of the processing parameters, and thus can be utilized for controllable additive nano/microfabrication.


Axon regeneration genes identified by RNAi screening in C. elegans.
Axons of the mammalian CNS lose the ability to regenerate soon after development due to both an inhibitory CNS environment and the loss of cell-intrinsic factors necessary for regeneration. The complex molecular events required for robust regeneration of mature neurons are not fully understood, particularly in vivo. To identify genes affecting axon regeneration in Caenorhabditis elegans, we performed both an RNAi-based screen for defective motor axon regeneration in unc-70/β-spectrin mutants and a candidate gene screen. From these screens, we identified at least 50 conserved genes with growth-promoting or growth-inhibiting functions. Through our analysis of mutants, we shed new light on certain aspects of regeneration, including the role of β-spectrin and membrane dynamics, the antagonistic activity of MAP kinase signaling pathways, and the role of stress in promoting axon regeneration. Many gene candidates had not previously been associated with axon regeneration and implicate new pathways of interest for therapeutic intervention.


Advanced fibrosis: Correlation between pharmacokinetic parameters at dynamic gadoxetate-enhanced MR imaging and hepatocyte organic anion transporter expression in rat liver.
To compare the value of enhancement and pharmacokinetic parameters measured at dynamic gadoxetate-enhanced magnetic resonance (MR) imaging in determining hepatic organic anion transporter expression in control rats and rats with advanced liver fibrosis. Institutional animal review board approval was received before the study began. Advanced liver fibrosis was created in rats by means of carbon tetrachloride injections over an 8-week period. In 17 rats with liver fibrosis and eight control rats, dynamic gadoxetate-enhanced MR images of the liver were obtained during 1 hour after injection of 0.025 mmol gadoxetate per kilogram of body weight. Enhancement parameters (maximum enhancement [Emax], time to peak [Tmax], and elimination half-life) were measured on enhancement-versus-time curves, and pharmacokinetic parameters (hepatic extraction fraction [HEF] and mean residence time [MRT]) were obtained by means of deconvolution analysis of the concentration-versus-time curves in the liver and the portal vein. The parameters were correlated at simple and multiple regression analysis with the expression of the hepatic anion uptake transporter organic anion-transporting polypeptide 1A1 (Oatp1a1), the hepatobiliary transporter multidrug resistance-associated protein 2 (Mrp2), and the backflux transporter Mrp4, as determined with reverse transcription polymerase chain reaction. In rats with advanced liver fibrosis, the Emax, Tmax, HEF, and MRT decreased significantly relative to those in control rats, whereas the elimination half-life increased significantly. The enhancement and pharmacokinetic parameters correlated significantly with the expression of the transporters at simple regression analysis. At multiple regression analysis, HEF was the only parameter that was significantly associated with the expression of Oatp1a1 and Mrp2 (P < .001, r = 0.74 and P < .001, r = 0.70, respectively). The pharmacokinetic parameter HEF at dynamic gadoxetate-enhanced MR imaging is independently correlated with hepatic organic anion transporter expression.


Choice of Hemodialysis Access in Older Adults: A Cost-Effectiveness Analysis.
Although arteriovenous fistulas have been found to be the most cost-effective form of hemodialysis access, the relative benefits of placing an arteriovenous fistula versus an arteriovenous graft seem to be least certain for older adults and when placed preemptively. However, older adults' life expectancy is heterogeneous, and most patients do not undergo permanent access creation until after dialysis initiation. We evaluated cost-effectiveness of arteriovenous fistula placement after dialysis initiation in older adults as a function of age and life expectancy. Using a hypothetical cohort of patients on incident hemodialysis with central venous catheters, we constructed Markov models of three treatment options: (1) arteriovenous fistula placement, (2) arteriovenous graft placement, or (3) continued catheter use. Costs, utilities, and transitional probabilities were derived from existing literature. Probabilistic sensitivity analyses were performed by age group (65-69, 70-74, 75-79, 80-84, and 85-89 years old) and quartile of life expectancy. Costs, quality-adjusted life-months, and incremental cost-effectiveness ratios were evaluated for up to 5 years. The arteriovenous fistula option was cost effective compared with continued catheter use for all age and life expectancy groups, except for 85-89 year olds in the lowest life expectancy quartile. The arteriovenous fistula option was more cost effective than the arteriovenous graft option for all quartiles of life expectancy among the 65- to 69-year-old age group. For older age groups, differences in cost-effectiveness between the strategies were attenuated, and the arteriovenous fistula option tended to only be cost effective in patients with life expectancy >2 years. For groups for which the arteriovenous fistula option was not cost saving, the cost to gain one quality-adjusted life-month ranged from $2294 to $14,042. Among older adults, the cost-effectiveness of an arteriovenous fistula placed within the first month of dialysis diminishes with increasing age and lower life expectancy and is not the most cost-effective option for those with the most limited life expectancy.


Statistical analysis of tracheal breath sounds during wakefulness for screening obstructive sleep apnea.
Obstructive sleep apnea (OSA) is a prevalent disorder. The accepted method of diagnosis in widespread clinical practice, polysomnography (PSG), is costly and very time consuming; therefore, quick screening methods, especially when there is a need for quick diagnosis, is of great interest. Diagnostic methods which exploit subtle differences in breath sounds recorded during wakefulness, such as our group's Awake-OSA technology, have shown their capability to diagnose OSA at the research stage. Simplifying the breath sound recording procedure employed in the Awake-OSA diagnostic method would increase its efficiency when used in a clinical setting. In this study, we adopted breath sound data collected during wakefulness in two positions (sitting upright and supine) and two breathing maneuvers (nose and mouth breathing) from our previous study, and ran hypothesis tests on a wide variety of sound features to select the most significant features correlated with OSA. The goal was to investigate which combinations of patient position and breathing maneuver contribute the least to the significant features amongst groups of people with differing OSA severity, thus permitting simplification of the recording protocol. The results show that all signals recorded by a combination of the two breathing maneuvers and two positions result in features significantly correlated with OSA severity; this makes it impossible to confidently recommend that a combination be omitted from the recording protocol. Nevertheless, the results show that the majority of significant features originated from recordings made in the supine position. Therefore, as a step toward simplification of the Awake-OSA diagnostic algorithm, we may use breath sound signals recorded only in the supine position and further investigate the accuracy of the algorithm in distinguishing amongst groups with differing OSA severity.


Lithic technological responses to Late Pleistocene glacial cycling at Pinnacle Point Site 5-6, South Africa.
There are multiple hypotheses for human responses to glacial cycling in the Late Pleistocene, including changes in population size, interconnectedness, and mobility. Lithic technological analysis informs us of human responses to environmental change because lithic assemblage characteristics are a reflection of raw material transport, reduction, and discard behaviors that depend on hunter-gatherer social and economic decisions. Pinnacle Point Site 5-6 (PP5-6), Western Cape, South Africa is an ideal locality for examining the influence of glacial cycling on early modern human behaviors because it preserves a long sequence spanning marine isotope stages (MIS) 5, 4, and 3 and is associated with robust records of paleoenvironmental change. The analysis presented here addresses the question, what, if any, lithic assemblage traits at PP5-6 represent changing behavioral responses to the MIS 5-4-3 interglacial-glacial cycle? It statistically evaluates changes in 93 traits with no a priori assumptions about which traits may significantly associate with MIS. In contrast to other studies that claim that there is little relationship between broad-scale patterns of climate change and lithic technology, we identified the following characteristics that are associated with MIS 4: increased use of quartz, increased evidence for outcrop sources of quartzite and silcrete, increased evidence for earlier stages of reduction in silcrete, evidence for increased flaking efficiency in all raw material types, and changes in tool types and function for silcrete. Based on these results, we suggest that foragers responded to MIS 4 glacial environmental conditions at PP5-6 with increased population or group sizes, 'place provisioning', longer and/or more intense site occupations, and decreased residential mobility. Several other traits, including silcrete frequency, do not exhibit an association with MIS. Backed pieces, once they appear in the PP5-6 record during MIS 4, persist through MIS 3. Changing paleoenvironments explain some, but not all temporal technological variability at PP5-6.


Activity of fluoro and deoxy analogues of glycerol as substrates and inhibitors of glycerol kinase.
Analogues of glycerol in which each of the three hydroxy groups is successively replaced by fluorine or hydrogen have been examined as substrates or inhibitors of glycerol kinase (Candida mycoderma) to assess the ability of fluorine to mimic a substrate hydroxy group in enzyme-analogue interactions. The four diols resulting from replacement of the hydroxy groups at C-1 or C-2 of sn-glycerol by fluorine or hydrogen are weak substrates. Similar substitution of the C-3 hydroxy group gives compounds which act as competitive inhibitors of glycerol or dihydroxyacetone phosphorylation but show no activity as substrates. Comparison of the steady-state kinetic parameters of the corresponding analogues shows that replacement of a hydroxy group by either fluorine or hydrogen leads to compounds with similar activity in this system. A convenient synthesis of (+)-propane-1,2-diol is described.


[Creole dyschromia or idiopathic macular hypomelanosis of the melanodermic halfcast of Guillet-Hélénon].
Melanodermic halfcasts may develop an original cutaneous dyschromia known as "progressive and extensive hypomelanosis" (Guillet-Helenon 1988). This disease is characterized by hypochromic and coalescent macules on the back and abdomen with possible spontaneous improvement within five years, favoured by UV exposure. The disease is not restricted to a limited geographic group: eight observations were collected in melanodermic patients leaving in temperate area. The pathogenesis of the disorder involves a variation in melanosome size and distribution with decrease in production of type IV melanosomes featuring a change of ultrastructural phenotype of melanogenesis. Since it may be misdiagnosed as fungal disease, leprosy or achromic eczema leading to useless laboratory examinations, this specific and frequent disease deserves to be known and recognized.


Genome-wide microsatellite identification in the fungus Anisogramma anomala using Illumina sequencing and genome assembly.
High-throughput sequencing has been dramatically accelerating the discovery of microsatellite markers (also known as Simple Sequence Repeats). Both 454 and Illumina reads have been used directly in microsatellite discovery and primer design (the "Seq-to-SSR" approach). However, constraints of this approach include: 1) many microsatellite-containing reads do not have sufficient flanking sequences to allow primer design, and 2) difficulties in removing microsatellite loci residing in longer, repetitive regions. In the current study, we applied the novel "Seq-Assembly-SSR" approach to overcome these constraints in Anisogramma anomala. In our approach, Illumina reads were first assembled into a draft genome, and the latter was then used in microsatellite discovery. A. anomala is an obligate biotrophic ascomycete that causes eastern filbert blight disease of commercial European hazelnut. Little is known about its population structure or diversity. Approximately 26 M 146 bp Illumina reads were generated from a paired-end library of a fungal strain from Oregon. The reads were assembled into a draft genome of 333 Mb (excluding gaps), with contig N50 of 10,384 bp and scaffold N50 of 32,987 bp. A bioinformatics pipeline identified 46,677 microsatellite motifs at 44,247 loci, including 2,430 compound loci. Primers were successfully designed for 42,923 loci (97%). After removing 2,886 loci close to assembly gaps and 676 loci in repetitive regions, a genome-wide microsatellite database of 39,361 loci was generated for the fungus. In experimental screening of 236 loci using four geographically representative strains, 228 (96.6%) were successfully amplified and 214 (90.7%) produced single PCR products. Twenty-three (9.7%) were found to be perfect polymorphic loci. A small-scale population study using 11 polymorphic loci revealed considerable gene diversity. Clustering analysis grouped isolates of this fungus into two clades in accordance with their geographic origins. Thus, the "Seq-Assembly-SSR" approach has proven to be a successful one for microsatellite discovery.


Language-related hemispheric asymmetry in healthy subjects and patients with temporal lobe epilepsy as studied by event-related brain potentials and intracarotid amobarbital test.
There are current attempts to replace the WADA test for pre-surgical evaluation of hemispheric language capabilities by one of the methods of functional brain imaging. Recent PET and fMRI studies using verbal cognitive tasks like verb generation, semantic monitoring or semantic ('deep') encoding of words showed asymmetries of activation in the fronto-lateral cortex. In a previous ERP study subjects were required to indicate whether pronounceable non-words and abstract geometric figures were presented for the first time ('new item') or whether they had been shown before ('old item'). Group analyses of this study showed significant material-specific hemispheric asymmetries with ERPs being more negative-going in recordings of the posterior part of the left hemisphere with verbal material (CP5/6) but more negative-going in recordings of the right hemisphere with the spatial material (P7/8). The aim of the present study was to test statistically ERP lateralization effects in individual healthy subjects as well as WADA-tested patients suffering from seizures of the mesio-temporal lobe (MTL). In all subjects ERP lateralization with verbal material was tested in the electrode pair CP5/6, and ERP lateralization with figures in the electrode pair P7/8. Statistical analyses of single trials showed that in 20 out of 24 subjects ERPs with verbal material started to be more negative-going in CP5 as compared to CP6 in the period between 100 and 200 ms after stimulus onset or the subsequent time epoch (200-300 ms). In one subject not CP5/6 but the closely adjacent electrode pair P7/P8 showed this verbal material-related hemispheric effect. In patients language dominance as indicated by ERPs was not always consistent with the data of the WADA test. In one patient with left MTL seizures ERPs with verbal material and figures were found to be significantly lateralized to the right hemisphere although the WADA test assigned this patient to have a language-dominant left hemisphere.


Long-Distance Transport of Finisher Pigs in the Iberian Peninsula: Effects of Season on Thermal and Enthalpy Conditions, Welfare Indicators and Meat pH.
Current legislation in the European Union places limits on live pig transport according to outside temperature, but less is known about the effects of sudden changes in the thermal microenvironment in trailers, particularly during long-distance transport. In this study, we measured the temperature and relative humidity inside livestock vehicles carrying 1920 Spanish finisher pigs (live weight 100 kg and 240 animals per journey) during eight long-distance (>15 h) commercial journeys to slaughter from northern Spain to Portugal in the summer and winter. Here, we report the rate of change in the air temperature (°C × min-1) and air enthalpies in the transport vehicle (kg water kg dry air-1). At sticking, blood samples were taken for to measure cortisol, glucose, and creatine kinase (CK) as stress response indicators, and the meat pH after 45 min and the pH after 24 h were also determined. The rate of change in the air temperature and enthalpy was higher inside the livestock vehicle during the winter months and was positively related with higher cortisol and glucose levels and lower pH after 45 min (p < 0.05). It is proposed that the rate of temperature change and air enthalpy represent useful integrated indices of thermal stress for pigs during transport.


[Sagittal split osteotomy of the mandibular ramus].
The sagittal ramus osteotomy is a versatile procedure, routinely performed for the correction of various dentofacial deformities. Despite the popularity of this operative approach some problems may occur related to several technical and anatomic aspects of this technique. Complications are in a large part avoidable with some tricks and little modifications of the original procedure.


Shape-diversified silver nanostructures uniformly covered on aluminium micro-powders as effective SERS substrates.
Highly-sensitive, reliable and reproducible Raman-active substrates via a facile and organic-free method are reported. These intriguing hierarchical structures are formed through the uniform incorporation of silver (Ag) nanoflowers with aluminium (Al) micro-supporters. The underlying mechanism is systematically investigated, visualizing that the solvents used in galvanic displacement have a major effect on diversifying the reaction kinetics of Ag deposition. Moreover, the exploration of AgNO3 concentrations reveals a drastic transition of Ag morphologies, driven by the elimination of high-energy surfaces of Ag. In addition, the surface-modified Al@Ag structures with octadecyltrichlorosilane demonstrate both the non-wetting (contact angle = 157.2°), as well as easy droplet roll-off (contact angle hysteresis = 5.4°) characteristics, which further enables the tested targets to avoid being pinned at a static position upon detection. Finally, we find that the Ag nanoflower surfaces are corrugated with numerous nanogaps at interparticle sites, in such a way that allows the abundant active sites (referred to as "hot spots") to amplify the Raman signal, and simultaneously maintain the sound reliability and reproducibility of Raman detection. These designs along with the fabrication strategy are anticipated to benefit versatile optical, optoelectronic and energy devices.


Allergy to iguana.
Furry animals produce allergens that can cause allergic rhinitis and asthma. In contrast, scaly animals, such as lizards, are assumed not to be allergenic. We sought to evaluate a 32-year-old man who complained of allergic rhinitis and asthma symptoms that occurred exclusively in his own home. He had dogs and cats at home but denied any increase in symptoms specifically associated with these pets. Skin prick testing initially performed to 42 common aeroallergens, including cat, dog, and house dust mite, elicited negative results. He later reported that the symptoms were worse on exposure to his pet iguanas. Skin prick tests were subsequently performed to an extract made from scales from his pet iguana. Extracts were also prepared from several zoo reptiles. Immunoassays for IgE antibody, as well as IgE immunoblots, were performed by using these extracts and the patient's serum. The skin prick test result with the pet iguana scale extract was positive. The patient's serum contained IgE antibody to his own pet iguana and to a zoo iguana. Our patient's history, skin test results, and in vitro studies clearly demonstrate that he is allergic to iguana. Physicians should be aware that such allergy to scaly pets may occur and should not restrict history taking to questions about furry pets.


Chemical and clinical studies of endogenous digitalis-like factor in hypertension.
Endogenous digitalis-like factor (endalin) was investigated by measuring the ability of rat and human plasma and urine to inhibit [3H]ouabain-specific binding, digoxin-antidigoxin antibodies interaction, and renal Na+, K+-ATPase activity. Endalin was detected in plasma (and urine) of one third of 112 patients with sustained and moderate hypertension (Na+ intake = 110 mmol/l). Endalin tended to be increased in the more pronounced hypertensives. No correlation with any other clinical and biological parameter could be detected. An activity to inhibit Na+, K+-ATPase was also detected in the rat after acute and chronic Na+ loading, in reduced renal mass-type hypertension and in SHRs as compared to WKY rats. Comparison of the plasma and urine inhibitory effects in the different tests revealed some chemical heterogeneity. However, a compound possessing the biochemical and pharmacological characteristics of digitaline was extracted from human urine. Chromatographic and spectral analysis of about 1,000 liters revealed a compound with apparent chemical homogeneity, molecular weight around 500, devoid of peptidic bound and of aliphatic structure.


Intracellular SPIO labeling of microglia: high field considerations and limitations for MR microscopy.
The purpose of this study is to investigate MRI contrast as a function of magnetic field strength for microglia labeled with superparamagnetic iron oxide (SPIO) nanoparticles. A rat microglia cell line, Bv2, was incubated with SPIOs for 6 h. In two separate experiments conducted at 11.75 and 21.1 T, the impact of SPIO loading and cell count on T(1) , T(2) and T(2) * contrast were evaluated: (a) cells were incubated with 1, 2 or 5 µl of Feridex; and (b) cells incubated with 5 µl of Feridex were used to form layers of 25 000, 50 000, 100 000 or 200 000 cells. Intracellular iron was analyzed with ICP-MS and histological staining while cell viability was evaluated by Trypan blue dye exclusion. Bv2 cells displayed increases in intracellular iron concentration with SPIO exposure, with the highest labeling yielding 0.83 pg of Fe per cell. Although no differences were identified for T(1) mechanisms, both fields displayed trends toward increasing T(2) and T(2) * contrast with increasing SPIO loading or cell count, with few differences evident between fields. Bv2 cells can be labeled readily with commercially available SPIOs, with the potential of increasing the intracellular iron content over short incubation times without impacting viability. This phagocytotic cell line not only provides direct SPIO uptake but also plays a critical role in inflammation after brain injury, providing a possible neurodegeneration biomarker. With few differences between field strengths and limited ability to quantify intracellular iron content and cell count, this study demonstrates only a slight benefit of SPIO-based contrast agent at high fields based on susceptibility-based contrast and detection, necessitating unique agents for such applications.


Genetics and heart failure: a concise guide for the clinician.
The pathogenesis of heart failure involves a complex interaction between genetic and environmental factors. Genetic factors may influence the susceptibility to the underlying etiology of heart failure, the rapidity of disease progression, or the response to pharmacologic therapy. The genetic contribution to heart failure is relatively minor in most multifactorial cases, but more direct and profound in the case of familial dilated cardiomyopathy. Early studies of genetic risk for heart failure focused on polymorphisms in genes integral to the adrenergic and renin-angiotensin-aldosterone system. Some of these variants were found to increase the risk of developing heart failure, and others appeared to affect the therapeutic response to neurohormonal antagonists. Regardless, each variant individually confers a relatively modest increase in risk and likely requires complex interaction with other variants and the environment for heart failure to develop. Dilated cardiomyopathy frequently leads to heart failure, and a genetic etiology increasingly has been recognized in cases previously considered to be "idiopathic". Up to 50% of dilated cardiomyopathy cases without other cause likely are due to a heritable genetic mutation. Such mutations typically are found in genes encoding sarcomeric proteins and are inherited in an autosomal dominant fashion. In recent years, rapid advances in sequencing technology have improved our ability to diagnose familial dilated cardiomyopathy and those diagnostic tests are available widely. Optimal care for the expanding population of patients with heritable heart failure involves counselors and physicians with specialized training in genetics, but numerous online genetics resources are available to practicing clinicians.


Is topical vitamin C an effective post-Fraxel laser regimen for asians?
The Fraxel laser has been a useful method for skin resurfacing. According to recent reports, vitamin C has beneficial effects for the skin. However, there is a paucity of data about the effect of vitamin C associated with the Fraxel laser. This study aimed to assess the effect of topical vitamin C as a post-Fraxel regimen. The study involved 44 Koreans, who wished to improve their facial skin aesthetics. All the patients were treated by Fraxel laser twice, with a 4-week interval between treatments. Beginning on day 1, the treatment group used a topical vitamin C agent as a post-Fraxel regimen for 12 weeks. The control group was told not to apply any topical agents. At every visit (0, 4, 8, and 12 weeks after the first Fraxel), colorimetric status, stratum corneum hydration, skin surface lipids, skin pH, and transepidermal water loss (TEWL) were measured. The parameters showing significant differences were TEWL and pH. Stratum corneum hydration, skin surface lipids, and colorimetric status showed no statistically significant differences between the two groups. Topical vitamin C application reduces the injury of the skin's surface barrier after Fraxel laser and promotes restoration of skin pH. However, there is a limit with increasing skin lightness or decreasing skin redness. This journal requires that authors assign a level of evidence to each article.


Comparison of the use of H1N1 and seasonal influenza vaccinations between veterans and non-veterans in the United States, 2010.
Veterans of the U.S. armed forces tend to be older and have more chronic health problems than the general adult population, which may place them at greater risk of complications from influenza. Despite Centers for Disease Control and Prevention (CDC) recommendations, seasonal influenza vaccination rates for the general adult population remain well below the national goal of 80%. Achieving this goal would be facilitated by a clearer understanding of which factors influence vaccination. Using the 2010 U.S. National Health Interview Survey (NHIS), this study estimates models of two types of vaccinations (H1N1 and seasonal flu), assesses if the correlates differ for these vaccinations, and analyses the distribution of the correlates by veteran status. Veterans, women, non-Hispanic whites, non-smokers, those at high risk, educated, with health insurance, and who use clinics as a usual source of care were more likely to receive both types of vaccinations. Those who were older, married, and with higher income were more likely to get vaccinated for seasonal flu, but not for H1N1. Age and number of children living in the household were found to have different effects for H1N1 compared to seasonal flu. Veterans are more likely to get vaccinated for seasonal influenza and H1N1 compared to the general population. This might be due to Veterans having better access to care or Veterans participating in better health care practices. Future studies should examine potential differences in flu vaccination use among Veterans using Veterans Affairs (VA) health care system vs. non-VA users.


Reduction in opioid use with perioperative non-pharmacologic analgesia in total knee arthroplasty and ACL reconstruction: a systematic review.
The world's opioid epidemic has gotten increasingly severe over the last several decades and projects to continue worsening. Orthopedic surgery is the largest contributor to this epidemic, accounting for 8.8% of postoperative opioid dependence cases. Total knee arthroplasty (TKA) and anterior cruciate ligament (ACL) reconstruction are commonly performed orthopedic operations heavily reliant on opioids as the primary analgesic in the peri- and immediate postoperative period. These downfalls highlight the pressing need for an alternate, non-pharmacologic analgesic to reduce postoperative opioid use in orthopedic patients. The presented systematic review aimed to analyze and compare the most promising non-pharmacologic analgesic interventions in the available literature to guide future research in such a novel field. A systematic search of PubMed, MEDLINE, Embase, Cochrane, and Web of Science was performed for studies published before July 2020 based on the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines, and the obtained manuscripts were evaluated for inclusion or exclusion against strict, pre-determined criteria. Risk-of-bias and GRADE (grades of recommendation, assessment, development, and evaluation) assessments were then performed on all included studies. Six studies were deemed fit for inclusion, investigating three non-pharmacologic analgesics: percutaneous peripheral nerve stimulation, cryoneurolysis, and auricular acupressure. All three successfully reduced postoperative opioid use while simultaneously maintaining the safety and efficacy of the procedure. The results indicate that all three presented non-pharmacologic analgesic interventions are viable and warrant future research. That said, because of its slight advantages in postoperative pain control and operational outcomes, cryoneurolysis seems to be the most promising. Further research and eventual clinical implementation of these analgesics is not only warranted but should be a priority because of their vast potential to reduce orthopedics surgeries' contribution to the opioid epidemic.


Rat as an animal model for male erectile function evaluation in sexual medicine research.
Animal models have contributed, to a great extent, to our understanding and advancement in the field of sexual medicine. Many current medical and surgical therapies in sexual medicine are the direct result of the development of such animal models. Over the past 15-20 years, rodents have become the premier models for such studies. In particular, the rat model provided the most valuable and reproducible investigations that significantly contributed to our knowledge of male sexual dysfunction as well as in the development of various treatment modalities. In addition, such in vivo animal models helped us develop the latest biotechnological tools that allowed numerous investigations at the cellular and molecular levels. Review the most common laboratory techniques that employ rat model for the evaluation of male erectile function and erectile tissue end-organ analyses. Review of peer-reviewed literature. Pathophysiology and laboratory research outcome correlation. The review suggests that rat is a versatile model in sexual medicine research. This versatile model should help in the further development of research tools, characterize additional signaling target molecules and pathways, and help in our understanding of male sexual dysfunction.


Self-assembling α,γ-cyclic peptides that generate cavities with tunable properties.
The design and synthesis of β-sheet-based self-assembling cyclic peptides with tunable cavities is described. The incorporation of a γ-amino acid with a hydroxyl group at C2 allows the incorporation of different groups that modify the internal properties of the resulting dimeric ensemble. These dimers can entrap different guests depending on the properties of the group at C2. The guest defines the geometry of the resulting aggregate.


Gene expression in the phenotypically plastic Arctic charr (Salvelinus alpinus): A focus on growth and ossification at early stages of development.
Gene expression during development shapes the phenotypes of individuals. Although embryonic gene expression can have lasting effects on developmental trajectories, few studies consider the role of maternal effects, such as egg size, on gene expression. Using qPCR, we characterize relative expression of 14 growth and/or skeletal promoting genes across embryonic development in Arctic charr (Salvelinus alpinus). We test to what extent their relative expression is correlated with egg size and size at early life-stages within the study population. We predict smaller individuals to have higher expression of growth and skeletal promoting genes, due to less maternal resources (i.e., yolk) and prioritization of energy toward ossification. We found expression levels to vary across developmental stages and only three genes (Mmp9, Star, and Sgk1) correlated with individual size at a given developmental stage. Contrary to our hypothesis, expression of Mmp9 and Star showed a non-linear relationship with size (at post fertilization and hatching, respectively), whilst Sgk1 was higher in larger embryos at hatching. Interestingly, these genes are also associated with craniofacial divergence of Arctic charr morphs. Our results indicate that early life-stage variation in gene expression, concomitant to maternal effects, can influence developmental plasticity and potentially the evolution of resource polymorphism in fishes.


Inward cholesterol gradient of the membrane system in P. falciparum-infected erythrocytes involves a dilution effect from parasite-produced lipids.
Plasmodium falciparum (Pf) infection remodels the human erythrocyte with new membrane systems, including a modified host erythrocyte membrane (EM), a parasitophorous vacuole membrane (PVM), a tubulovesicular network (TVN), and Maurer's clefts (MC). Here we report on the relative cholesterol contents of these membranes in parasitized normal (HbAA) and hemoglobin S-containing (HbAS, HbAS) erythrocytes. Results from fluorescence lifetime imaging microscopy (FLIM) experiments with a cholesterol-sensitive fluorophore show that membrane cholesterol levels in parasitized erythrocytes (pRBC) decrease inwardly from the EM, to the MC/TVN, to the PVM, and finally to the parasite membrane (PM). Cholesterol depletion of pRBC by methyl-β-cyclodextrin treatment caused a collapse of this gradient. Lipid and cholesterol exchange data suggest that the cholesterol gradient involves a dilution effect from non-sterol lipids produced by the parasite. FLIM signals from the PVM or PM showed little or no difference between parasitized HbAA vs HbS-containing erythrocytes that differed in lipid content, suggesting that malaria parasites may regulate the cholesterol contents of the PVM and PM independently of levels in the host cell membrane. Cholesterol levels may affect raft structures and the membrane trafficking and sorting functions that support Pf survival in HbAA, HbAS and HbSS erythrocytes.


Robotic-assisted laparoscopic prostatectomy in overweight and obese patients.
To assess outcomes of robotic laparoscopic radical prostatectomy (RLRP) in overweight and obese patients, defined as those with a body mass index (BMI) of 25 to 30 kg/m2 and greater than 30 kg/m2, respectively. This was a nonrandomized study evaluating all of our RLRP patients. Patients were divided into three groups: BMI of 25 kg/m2 or less (group 1), BMI greater than 25 kg/m2 and less than 30 kg/m2 (group 2), and BMI of 30 kg/m2 or more (group 3). Patients were evaluated prospectively with the validated Rand 36-Item Health Survey (version 2) and with the University of California, Los Angeles Prostate Cancer Index questionnaire. Between February 2003 and November 2004, 150 RLRPs were performed at our center. Average follow-up was 8 months. Groups 1, 2, and 3 had 39, 65, and 46 patients, respectively. Average BMIs for all three groups were statistically different (P < 0.01). When compared with group 1, open conversion rates, hospital stay, positive margin, and complication rates were not statistically different for groups 2 or 3. Operative time (P < 0.004) and estimated blood loss (P < 0.03), however, were statistically greater for group 3 compared with group 1. Transfusion rate was highest in group 2 (P = 0.04 compared with group 1). Prostate weights were also statistically greater in groups 2 (P = 0.003) and 3 (P = 0.02) compared with group 1. Overall, BMI did not increase perioperative and postoperative morbidity. Robotic laparoscopic radical prostatectomy is safe in overweight and obese patients and might be the surgical management of choice in this subset of patients. Further long-term follow-up with more patients is required to verify this initial observation.


Efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component monotherapy in patients with type 2 diabetes.
The aim of this study was to compare efficacy and tolerability of initial combination therapy with vildagliptin/pioglitazone to component monotherapy. This 24-week, multicentre, randomized, double-blind, active-controlled study assessed the effects of the dipeptidyl peptidase-4 inhibitor vildagliptin (100 mg q.d.), pioglitazone (30 mg q.d.) and vildagliptin combined with pioglitazone (100/30 mg q.d. or 50/15 mg q.d.) in 607 drug-naive patients with type 2 diabetes (T2DM). The primary outcome measure was change from baseline in HbA(1c) in patients receiving initial combination therapy compared with pioglitazone monotherapy. After 24-week treatment, adjusted mean changes in HbA(1c) from baseline (approximately 8.7%) in patients receiving pioglitazone monotherapy, 50/15 mg combination, 100/30 mg combination and vildagliptin monotherapy were -1.4 +/- 0.1%, -1.7 +/- 0.1%, -1.9 +/- 0.1% and -1.1 +/- 0.1% respectively. Both low-dose and high-dose combinations were significantly more efficacious than pioglitazone alone (p = 0.039 and p < 0.001 respectively). Adjusted mean changes in fasting plasma glucose were -1.9 +/- 0.2, -2.4 +/- 0.2, -2.8 +/- 0.2 and -1.3 +/- 0.2 mmol/l respectively, and both combination groups were significantly more effective than pioglitazone monotherapy (p = 0.022 and p < 0.001 respectively). The overall incidence of adverse events ranged from 45.8% in the low-dose combination to 51.6% in the pioglitazone monotherapy group. The incidence of peripheral oedema was highest in patients receiving pioglitazone monotherapy (9.3%) and lowest in those receiving low-dose combination (3.5%). One mild hypoglycaemic event was reported by one patient receiving high-dose combination and one patient receiving vildagliptin monotherapy. First-line treatment with vildagliptin/pioglitazone combination in patients with T2DM provides better glycaemic control than either monotherapy component yet has minimal risk of hypoglycaemia and a tolerability profile comparable with component monotherapy.


[Investigation of cutaneous leishmaniasis by active screening in primary schools in Sanliurfa, Turkey].
Cutaneous leishmaniasis (CL) is endemic in Sanliurfa, a province located at southestern part of Turkey. The aims of this study were to determine CL cases among children aged 7-15 years attending primary schools and evaluate the demographical and clinical characteristics by active screening method. In our study, a total of 163.464 children attending to 123 primary schools have been evaluated in terms of CL prevalence between 2010 to 2012 period. Accordingly, 67.585, 72.279 and 23.600 students studying in 74, 37 and 12 primary schools were actively screened, respectively. Children suspected with CL were invited to the Center for Diagnosis and Treatment of Oriental Sore, Sanlıurfa Division of Turkish Public Health Institute. Two slides were prepared from bloodless, serous fluid of the skin lesions and stained with Giemsa for the microscopic examination to identify Leishmania amastigotes. The lesions were also evaluated according to their clinical manifestations, size, duration and number. In the study, 455 (%0.3) of the children were diagnosed as CL. The incidence of CL cases was 0.41%, 0.14%, and 0.31% in 2010, 2011 and 2012, respectively. Of the CL cases, 250 (54.9%) were female and 205 (45.1%) were male with a mean age of 10.54 ± 2.42 years. Most of the cases (64.2%) were in 7-11 years old group, while 35.8% were in 12-15 years old group. The average number of the CL lesions was 1.78±0.7, ranging from one to fifteen. Single lesions were detected in 281 cases (61.8%), whereas double, triple and multiple lesions (≥ 4) were detected in 87 (19.1%), 51 (11.2%) and 36 (7.9%) of the CL cases, respectively. The lesions were mostly involved on face (n= 280, 61.5%) and especially cheeks (133/280, 47.5%), followed by upper (n= 127, 27.9%) and lower (n=39, 8.6%) extremities. The average duration of lesions was 13.40 ± 0.47 months (range: 4-104 weeks) and the average size of lesions was 10.32 ± 0.4 mm (range: 3-10 mm). Among all, mostly nodular (n= 211, 46.4%) and ulcerative (n=204, 44.8%) lesions were recorded. Of the cases 330 (72.5%) were diagnosed as acute CL (duration of lesions were ≤ 24 months), while 125 (27.5%) were chronic CL (duration of lesions were > 24 months). Leishmaniasis recidivans were identified in a total of five (1.1%) cases, of them one was acute and four was chronic CL cases. Twenty-five relatives of the children with CL were diagnosed as new CL cases in the 2011-2012 period. Most of the patients (n= 437, 96%) were successfully treated with topical pentavalent antimonials, however 18 (4%) who were unresponsive to local therapy were treated systemically. Our findings showed that local transmission is ongoing in terms of CL. It should be kept in mind that, primary school aged children might be responsible for the ongoing local transmission in endemic regions and the local transmission may be decreased with the early diagnosis and treatment of CL cases.


The adaptations of a quality of life questionnaire for routine use in clinical practice: the Chronic Respiratory Disease Questionnaire in cystic fibrosis.
The assessment of quality of life (QoL) is necessary to monitor the course of disease and to assess the effect of new and existing interventions in clinical practice. This will only be achieved if QoL can be measured accurately and routinely. The aim of this study was to demonstrate the methodology involved in the adaptation and shortening of the Chronic Respiratory Disease Questionnaire (CRDQ) in a population of adults with cystic fibrosis (CF). A single interviewer administered the CRDQ to a sample of 45 adult patients (32 males) with CF prior to assessment of spirometric measures of lung function. Those patients whose lung function was stable at the time of study and who could attend for a retest within 14 days were asked to complete the questionnaire at a subsequent visit (n = 10). The mean interval between visits was 7 days (range 5-14 days). Correlations between spirometry and CRDQ dimensions ranged from -0.003 to 0.426. The fatigue, emotion and mastery dimensions showed high internal consistency and adequate construct validity. In the small number of patients suitable for retest, the results indicated that the dimensions exhibited adequate test-retest reliability. In contrast, low internal consistency was demonstrated for the dyspnoea dimension. The fatigue, emotion and mastery dimensions could be reduced, in terms of their number of items, without a substantial loss in explanatory power. This study suggests that QoL measurement can be made convenient and, thus, more easily accessible for routine clinical assessment.


A comparison of airway responsiveness in smokers with chronic bronchitis and in asthmatic subjects.
Fifty-two of 95 smokers with a forced expiratory volume in one second (FEV1) above 70% predicted and with chronic bronchitis were found to have increased bronchial responsiveness, expressed as PC20FEV1, upon challenge with inhaled histamine. The degree of responsiveness was significantly below that found in matched asthmatics, but substantially higher than that reported in normals. The degree of responsiveness was significantly correlated to prechallenge ventilatory capacity, age and tobacco consumption but not to sex. PC40MEF50 showed the same distribution as PC20FEV1, but did not add further information. The slope of the dose response curve expressing the maximum expiratory flow at 50% of vital capacity expired (MEF50) did not correlate with any of the parameters measured. The slope of the FEV1 dose-response curves showed significant correlation with tobacco consumption. The degree of bronchial responsiveness as an indication for future disability needs to be investigated.


When a neglected tropical disease goes global: early estimates from the Monkeypox outbreak, the first 1,054 cases.
Monkeypox virus (MPXV), genus Orthopoxvirus, is a large double-stranded DNA virus (200-250 nm), that is evolutionarily related to human variola virus (VARV) (1), and causes a clinical syndrome quite similar to smallpox, with a generally less severe outcome (1,2). MPXV has a wide range of hosts and reservoirs in wild animals, and since 1970 has been commonly acknowledged as a human pathogen, endemic to Central and Western African countries through two distinctive clades (2,3). Central African clade (CAC) is responsible of the majority of 20,000 incident cases of the last decade, with a case-fatality-ratio of 7-10%, compared to < 4% for Western African clade (WAC) (4). In 2003, the importation of infected pests (Cynomys spp, i.e. "prairie dogs") to United Stated resulted in the first MPXV-WAC outbreak out of Africa, involving a total of 81 human cases, with no documented deaths (5). In the next decade, the spreading of the MPVX-WAC to Nigeria, has then resulted in multiple travel-related cases in non-endemic countries (4,6). Since May 7th, 2022, an unprecedented outbreak of MPXV-WAC infections with around 1,051 documented cases (Table 1) is occurring across Europe (89.7% of cases), Americas (10.7%), and Australia (0.6%), mostly occurring in subjects with no established travel link to endemic areas (7-13). Reported cases are mostly characterized by mild clinical features (Table 2) (7,9,10,12,13), with no deaths and some specificities. First of all, skin lesions are inconsistently pronounced in number, size and density, being possibly confounded with chickenpox (7,13). Similarly, cervical lymphadenopathy, previously acknowledged as a nearly constant clinical sign, has been reported by less than 20% of incident cases (7,9,13), with an increased prevalence of inguinal lymph node involvement (35.3% to 48.1%) (7,9,13), anal and genital ulcers (18.5% to 57%) (9,10,13). As some cases have been initially reported in men having sex with men (9,14), with a relatively high prevalence of HIV seropositivity (9,10), reporting risky sexual behaviors and multiple sexual partners (9,10,12), and having a documented epidemiologic link with high-risk settings in Madrid and Lisbon areas, and mass gatherings in Antwerp (Belgium), and Gran Canaria (Canary Islands, Spain) (8,9,12,14), such specificities have been initially explained through a presumptive sextually-related transmission. However, labelling the current outbreak as a sort of "gay" disease is not only improper and discriminating, but also scientifically inaccurate (9). First, most of reported cases remain outside a clear and well-defined chain of transmission (9,10,12). Second, the earliest symptom onset clearly ranged between April 20th and April 29th, anticipating all of the aforementioned mass gatherings (9,12). Third, 3 of recent US cases were linked to travel-associated cases from Nigeria reported in 2018 and 2019 (15). In other words, the current MPXV-WAC outbreak has been introduced in Western Hemisphere by several, distinctive episodes that have largely anticipated the initial hypotheses. As its containment of appears, to date, particularly difficult to achieve MPXV-WAC could profit of this outbreak to eventually evolve into a global pathogen (3,14), corroborating a decade of disregarded warning from International Health authorities (2,3).


The effect of storage temperatures and packaging methods on properties of Motal cheese.
The effects of storage temperature (+4 degrees C and -18 degrees C) and packaging method (nonvacuum and vacuum) on biogenic amines in Motal cheese during storage periods were investigated. In addition, dry matter, titratable acidity, total nitrogen, water-soluble nitrogen, trichloroacetic acid-soluble nitrogen, phosphotungstic acid-soluble nitrogen, free amino group (proteolysis), electrophoretic patterns of casein, and amounts of lactic acid bacteria and coliforms were determined. Storage period had a significant effect on all of the biogenic amines. When compared with vacuum packaging, normal packaging had higher amounts of putrescine, cadaverine, histamine, and tyramine. Coliforms were not found at detectable levels (<100cfu/g) in all cheese samples. Results of urea-PAGE analysis of cheese samples were in good agreement with biogenic amine results and other proteolysis parameters.


The everyday experience of psychiatric hospitalization: the users' viewpoint.
Using 38 focussed accounts the author reports on the hospitalization experiences of patients 18 to 38 years old in the psychiatric ward. The sample comes from the psychiatric wards of two general hospitals in the Montréal area (Canada). The data were analyzed using a qualitative method. Empirical categories were inferred from the respondents' discourse based on the broad themes which make up the psychiatric experience: admission; hospital environment and rules; daily life; medication; relations with the staff and leaving the hospital. The results shed light on the suffering, dissatisfaction and ambivalent feelings surrounding the patients' hospital experience. Based on the experience of psychiatric patients, the author identified five processes at work during psychiatric hospitalization.


The chicken frizzle feather is due to an α-keratin (KRT75) mutation that causes a defective rachis.
Feathers have complex forms and are an excellent model to study the development and evolution of morphologies. Existing chicken feather mutants are especially useful for identifying genetic determinants of feather formation. This study focused on the gene F, underlying the frizzle feather trait that has a characteristic curled feather rachis and barbs in domestic chickens. Our developmental biology studies identified defects in feather medulla formation, and physical studies revealed that the frizzle feather curls in a stepwise manner. The frizzle gene is transmitted in an autosomal incomplete dominant mode. A whole-genome linkage scan of five pedigrees with 2678 SNPs revealed association of the frizzle locus with a keratin gene-enriched region within the linkage group E22C19W28_E50C23. Sequence analyses of the keratin gene cluster identified a 69 bp in-frame deletion in a conserved region of KRT75, an α-keratin gene. Retroviral-mediated expression of the mutated F cDNA in the wild-type rectrix qualitatively changed the bending of the rachis with some features of frizzle feathers including irregular kinks, severe bending near their distal ends, and substantially higher variations among samples in comparison to normal feathers. These results confirmed KRT75 as the F gene. This study demonstrates the potential of our approach for identifying genetic determinants of feather forms.