Surgical Management of Carotid Body Tumors: Experience of Two Centers.
Carotid body tumors (CBTs) are rare but require surgical resection given their potential for growth and malignancy. For some surgical teams, tumor hypervascularity justifies preoperative embolization to facilitate resection and limit complications. The objective of our study was to evaluate 2 different practices of surgical resection with or without preoperative embolization in a 2-center cohort. A consecutive series of patients who underwent CBT surgery, from January 2011 to June 2019, were divided into 2 groups, as to whether they were (embolized CBT [ECBT]) or not (nonembolized CBT [NECBT]) preoperatively embolized. Both groups were compared specifically according to the duration of operation, postoperative complications, and length of stay. Twenty-two patients with a mean age of 48.5 ± 14.3 years were included. In the series, 23 CBTs were resected: 13 were embolized preoperatively; the mean time between embolization and surgery was 2.62 ± 1.50 days. Both groups were comparable based on characteristics of population and tumor, with a mean size of 33.2 ± 11.9 mm. We noted a significant increase in operation duration in the ECBT group: 151 min (±40.9) vs. 87.0 min (±21); P < 0.01. There was no difference between the 2 groups regarding cranial nerve (50% vs. 46%; P = 1), sympathetic nervous system (20% vs. 23%; P = 1), or vascular nerve (20% vs. 23%; P = 0.18) complications. No cerebrovascular accident was identified. The length of stay was 3.60 days (±1.78) vs. 3.73 days (±1.19; P = 0.44). This study reflects the experience of 2 centers in the management of CBT which is a rare pathology with no standardized treatment. Our series showed no significant difference between the ECBT and NECBT groups regarding postoperative complications and length of hospital stay. The reduction in operating time in the NECBT group remains to be demonstrated.


Regenerative Medicine and Stem Cells in Dermatology.
Clinically relevant regenerative medicine is still in its early stages of development. Difficulties in regenerating large-scale and complex structures, the lack of safety data, and the paucity of clinical trials have slowed the process of technological advance. To familiarize the clinician with techniques available in the laboratory and experimental approaches being tested clinically. In addition, a layout is discussed for how dermatologists can lead the way in bringing regenerative medicine to clinical reality. This article reviews the relevant literature on regenerative medicine for dermatological applications and discusses findings and techniques in a clinically relevant context. Multiple cell-free and cell-based approaches for regenerating dermatologic tissues have been reported in the basic science and clinical literature. These are reviewed in the order of complexity. Incremental steps are needed to apply the principles of regenerative medicine to simple medical problems first. Such a stepwise approach would commence, for example, with creation of single-function tissues that could fill soft-tissue defects and proceed to the development of fully functional skin grafts. Likewise, cell-free approaches can build the foundation for the more technically demanding cell-based strategies that are likely necessary for achieving the ultimate goal of regenerative dermatology.


Dirofilaria immitis in pet dogs from the metropolitan area of the Colombian Caribbean.
A cross-sectional study was carried out to determine the frequency and factors associated with Dirofilaria immitis infection in pet dogs in the metropolitan area of the Colombian Caribbean (northern Colombia). A total of 173 dogs were analyzed by a commercial rapid immunochromatographic test (RIT) and a nested PCR of the cytochrome oxidase subunit I gene, in parallel. Ninety-two (53.2%) of the dogs showed positive results to the RIT, while 59 (34.1%) animals had D. immitis DNA by PCR. Positivity to one or both diagnostic techniques was detected in 104 (60.1%; CI95%: 53.8-67.4) of the sampled dogs. In PCR-positive dogs, phylogenetic analyses evidenced high nucleotide identity (100%) with sequences previously obtained from mosquitoes, dogs and other mammals in different countries. Exercise intolerance (p = 0.002; OR: 2.33; CI95%: 1.37-3.96) and thrombocytopenia (p = < 0.001; OR: 1.95; CI95%: 1.11-3.43) were the main factors associated with D. immitis infection in dogs. The high frequency of D. immitis in dogs indicates a wide distribution of this parasite in the metropolitan area of the Colombian Caribbean, which can be of animal and public health concern. Our results highlight the need to combine different methods to increase the diagnostic accuracy of D. immitis.


Voltage dependence of desensitization. Influence of calcium and activation kinetics.
The voltage dependence of carbachol-induced desensitization has been analyzed in potassium-depolarized frog sartorius muscle preparations with voltage clamp techniques over a wide voltage range (-120 to +40 mV). Desensitization developed exponentially at all voltages with tau, the time constant of desensitization onset, varying as a logarithmic function of membrane voltage. The voltage dependence of tau remained in calcium-deficient solutions and was not altered by elevating either the level of extracellular or intracellular calcium. We have analyzed our results according to a simple sequential kinetic scheme in which the rate-limiting step in the development of desensitization is a transition of the receptor channel complex from the activated conducting state to a desensitized, nonconducting state. We conclude (a) that the observed voltage sensitivity of desensitization primarily resides in the voltage dependence of this transition, and (b) the kinetics of activation appear to have a greater influence on the observed rate of desensitization than on its voltage dependence. The magnitude of the voltage dependence suggests that a greater change in free energy is required for the transition to the desensitized state than for the transition between the open and closed states of the receptor channel complex.


A case series on the development of rest-activity rhythm and quality of sleep in patients hospitalized for treatment of uni- or bipolar depression: a potential role for quetiapine.
Objectives. To assess the development of the rest-activity rhythm and quality of sleep during course of treatment of patients with major depressive episode receiving antidepressant treatment plus quetiapine. Methods. Ten patients with major depressive episode were followed over 4 weeks. Motor activity was measured with actigraphy, sleep with the Pittsburgh Sleep Quality Index (PSQI), and depression was followed with HAM-D-21 and BDI. Correlations and associations were calculated with non-parametric statistical tests. Results. Circadian motor activity improved during the 4 weeks treatment period only for daytime-related motor activity (M10), but not for night-time-related motor activity (L5). Patients with statistically significant higher sleep efficiency scores and sleep fraction on the actigraph after week 1 showed clinical improvement on the HAM-D score after week 4. Patients with good sleep efficiency at week 1 (assessed by PSQI) showed statistically significant clinical improvement of depression after week 4. Conclusions. Various sleep parameters at week 1 of treatment seem to be predictive for treatment outcome of depression after week 4. Actigraphy and subjective sleep assessment with PSQI are useful tools to predict treatment outcome of depression. The positive effects of quetiapine on motor activity and sleep show the clinical significance of our findings.


Noninstitutional births and newborn care practices among adolescent mothers in Bangladesh.
To describe home-based newborn care practices among adolescent mothers in Bangladesh and to identify sociodemographic, antenatal care (ANC), and delivery care factors associated with these practices. The 2007 Bangladesh Demographic Health Survey, conducted from March 24 to August 11, 2007. Selected urban and rural areas of Bangladesh. A total of 580 adolescent women (aged 15-19 years) who had ever been married with noninstitutional births and having at least one child younger than 3 years of age. Outcomes included complete cord care, complete thermal protection, initiation of early breastfeeding, and postnatal care within 24 hours of birth. Descriptive statistics and multivariate logistic regression methods were employed in analyzing the data. Only 42.8% and 5.1% newborns received complete cord care and complete thermal protection. Only 44.6% of newborns were breastfed within 1 hour of birth. The proportion of the newborns that received postnatal care within 24 hours of birth was 9%, and of them 11% received care from medically trained providers (MTP). Higher level of maternal education and richest bands of wealth were associated with complete thermal care and postnatal care within 24 hours of birth but not with complete cord care and early breastfeeding. Use of sufficient ANC and assisted births by MTP were significantly associated with several of the newborn care practices. The association between newborn care practices of the adolescent mothers and sufficient ANC and skilled birth attendance suggest that expanding skilled birth attendance and providing ANC may be an effective strategy to promote essential and preventive newborn care.


Olfactory dysfunction predicts the development of dementia in older patients with type 2 diabetes.
Olfactory dysfunction is associated with the transition from normal cognition to dementia in persons without type 2 diabetes. This study aimed to investigate whether olfactory dysfunction could be an early marker of future dementia in older patients with type 2 diabetes. This exploratory study included 151 older Japanese outpatients with type 2 diabetes who did not have a diagnosis of probable dementia at baseline. A multivariate logistic regression model was used to determine whether Open Essence (OE) test score at baseline is associated with the development of probable dementia. Over 3 years, approximately 9% of the study subjects developed probable dementia. Subjects with olfactory dysfunction at baseline developed probable dementia more frequently than those without. Multivariate logistic regression showed that lower OE test score, higher age, lower Mini-Mental State Examination (MMSE) score, higher total protein concentration, and more frequent use of a sulfonylurea are significantly associated with the development of probable dementia. Stepwise multivariate regression analysis demonstrated that change in OE test score over 3 years is significantly associated with change in MMSE score. Our study suggested that olfactory dysfunction precedes the development of probable dementia in older patients with type 2 diabetes.


Multicentric and diffuse recurrences of meningiomas.
Background: Meningiomas recur with a rate of 10-32% at 10 years. Several features influence the risk of recurrence.Objective: To define the pathological and surgical features at risk of multicentric-diffuse versus local-peripheral recurrence.Methods: Thirty-three patients operated on for intracranial meningiomas who experienced multicentric-diffuse recurrence were retrospectively analyzed. The data of these patients were compared to those of 50 patients who experienced local-peripheral recurrence. The analyzed factors included age and sex, tumor location and shape, brain-tumor interface, entity of resection, WHO grade, Ki67 MIB1, progesterone receptor (PR) expression, number of reoperations, progression of WHO grade, and outcome.Results: Meningiomas which recurred in multicentric-diffuse pattern showed at initial surgery a significantly higher rate of flat-shaped tumors (p = .0008) and of cases with Ki67 Li ≥ 4% (p = .037) than those which recurred in localized-peripheral pattern, whereas other factors did not significantly differ. Among patients with multicentric-diffuse recurrences, 25 underwent one to three reoperations; 17 among them (66%) are alive with local tumor control or slow progression 2-25 years after the initial surgery versus only 2 out of 8 who did not undergo surgery.Conclusions: Flat-shaped meningiomas and those with Ki67 Li ≥ 4% are at higher risk of multicentric-diffuse recurrence. Multiple reoperations over a period of several years may obtain rather long survivals in selected patients with prevalent intradural, not anaplastic tumors and not too extensive dural infiltration.


The gamma-subunit governs the susceptibility of recombinant gamma-aminobutyric acid type A receptors to block by the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, 2N).
To identify anesthetic effects that produce the different components of the complex anesthetic state, the so-called nonanesthetics/nonimmobilizer classes of compounds have been introduced. Because ionotropic gamma-aminobutyric acid type A (GABA(A)) receptors play an important role in the mediation of the central nervous system (CNS) effects of general anesthetics, and their susceptibility to modulation by various drugs depends on subunit composition, we have compared the effect of the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6) on GABA(A) receptors expressed in human embryonic kidney 293 cells transfected with alpha1beta2 versus alpha1beta2gamma2s subunits. Using rapid perfusion and whole-cell recording techniques, we found that, like isoflurane, F6 blocked GABA-induced currents through alpha1beta2 receptors but, unlike isoflurane, the presence of the gamma2s subunit conferred complete resistance to block by F6. Also, in contrast to isoflurane, F6 had no effect on deactivation kinetics of GABA-induced currents in either type of receptor. We conclude that modulation of alphabetagamma receptors plays little or no role in the actions of F6, but the block of alphabeta receptors may contribute to its effects on the CNS. Gamma-aminobutyric acidA receptors are the target of numerous drugs affecting the central nervous system. The subunit composition of the GABAA receptors governs their interaction with many drugs. We investigated whether the gamma-subunit influences the interaction with the nonimmobilizer F6.


Off-Label Use of Rituximab in Patients with Different Types of Nephropathies in a Tertiary Hospital: A Retrospective Study.
Off-label use of rituximab is commonly requested for patients with resistant nephropathies. The outcomes and tolerability of rituximab in adult patients with nephropathy treated at our hospital (from 2013 to 2018) were described. Data were retrieved from electronic medical records. Response was classified as complete remission (CR), partial remission (PR), or no response (NR) according to the KDIGO criteria. A total of 89 requests were received for 61 patients. Median age was 58 years (45.9% female). Idiopathic membranous nephropathy (MN) (n = 30) was the most frequent indication, followed by minimal change disease (MCD) (n = 15) and secondary membranoproliferative glomerulonephritis (MPGN) (n = 12). Three patients with focal segmental glomerulosclerosis (FSGS) were included. After most treatment cycles in MN, a CR or PR was observed; median proteinuria levels significantly decreased for these patients (6000 mg/24h (IQR 3584-10,300) vs. 1468.8 (IQR 500-4604.25), p < 0.01). In MPGN, no response was documented after 46.7% of rituximab cycles. A CR or PR was described with the majority of rituximab cycles in MCD, with a significant decrease in proteinuria (6000 mg/24 h (IQR 4007-11,426) vs. 196.8 (IQR 100-1300), p = 0.013). No cycles produced a response in FSGS. Mean CD19+ B-cell decreased in all types of nephropathy (10.44% vs. 0.29%, p < 0.0001). Eleven patients presented infusion-related reactions, and 17 presented infectious complications. The majority of patients with MN and MCD had complete or partial responses; however, neither MPGN nor FSGS had encouraging results.


Differentiation of dementia of the Alzheimer's type from depression with cognitive impairment on the basis of a cortical versus subcortical pattern of cognitive deficit.
This study compared 15 "mildly" cognitively impaired participants with Dementia of the Alzheimer Type (DAT), 15 depressed cognitively impaired participants (DCI), and 15 normal participants. The participants were matched for age, and reading ability, and were tested on a series of cognitive instruments selected on the basis of their ability to distinguish a cortical versus subcortical pattern of deficit. The DAT group demonstrated impaired performances on tests of language, praxis and gnosis. Deficits in these areas were absent from DCI group. There were differences between all of the groups on the California Verbal Learning Test, but after this effect was controlled using an analysis of covariance procedure, the differences in tests of gnosis, praxis and language function between the DCI and the DAT participants still remained. These findings support the clinical usefulness of the cortical-subcortical distinction in differentiating DCI from DAT.


Assessing the impact of cognitive impairment on the usability of an electronic medication delivery unit in an assisted living population.
To examine the relationship between cognitive status and the usability of an integrated medication delivery unit (MDU) in older adults who reside in an Assisted Living Facility (ALF). Subjects were recruited from a single ALF in Pittsburgh, PA. Usability testing sessions required subjects to execute tasks essential to using EMMA(®) (Electronic Medication Management Assistant), a Class II Federal Drug Administration (FDA) approved integrated MDU. Video coding allowed for quantification of usability errors observed during the testing sessions. Each subject's cognitive status was assessed using the Mini Mental State Exam (MMSE(®)) with scores <24 indicating cognitive impairment. Functional status was assessed using the Lawton Instrumental Activities of Daily Living (IADL) questionnaire, and a global assessment of subjective usability was assessed by completing the System Usability Scale (SUS). Non-parametric statistics and correlation analysis were used to determine whether significant differences existed between cognitively impaired and non-impaired subjects. Nineteen subjects were recruited and completed the protocol. The subject pool was primarily white, female, 80+ and in possession of above average education. There was a significant relationship between MMSE(®) scores and the percentage of task success (z=-2.03, p=0.04). Subjects with MMSE(®) scores of 24+ (no cognitive impairment) successfully completed an average of 69.0% of tasks vs. the 34.7% performance for those in the cognitively impaired group (<24). Six of the unimpaired group also succeeded at meeting the 85% (6 out of 7 correct) threshold. No subject with cognitive impairments (<24 MMSE(®)) completed more than 5/7 (71.4%) of their tasks. Two of the impaired subjects failed all of the tasks. Three of the MMSE(®)'s subsections (Date, Location and Spell 'world' backwards) were found to be significantly related (p<0.05) to the percentage of task success. Tasks success rates were related with IADL scores (z=-3.826, p<0.0001), and SUS scores (r=0.467, p=0.0429). Medication delivery units like EMMA(®) have the potential to improve medication management by combining reminder systems with telemedical monitoring and control capabilities. However, subjects judged to be "cognitively impaired" (<24 MMSE(®)) scored a significantly smaller percentage of task success than the "unimpaired" (>=24), suggesting that cognitive screening of patients prior to the use of EMMA(®) may be advisable. Further studies are needed to test the use of EMMA(®) amongst ALF residents without cognitive impairment to see if this technology can improve medication adherence.


Resting and exercise response to altitude in patients with chronic obstructive pulmonary disease.
Exposure to altitude invariably involves some form of physical activity. There are limited data available to help predict the response to activity at altitude in patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the response to acute altitude exposure at rest and during exercise in patients with COPD. Sea level measures of cardio-pulmonary function were compared to the resting and exercise hypoxemic response at the summit of the Mt. Hutt ski field (2086 m), New Zealand, in 18 patients with COPD. Ascent from sea level to altitude caused significant hypoxemia at rest (PaO2: 75 +/- 9 vs. 51 +/- 6 mmHg), and during a walk test (41 +/- 7 mmHg). At altitude, the walk test distance was reduced by 52%. Sea level PaO2 and SaO2 correlated with resting PaO2 (r = 0.69) and SaO2 (r = 0.79) at altitude. Diffusion capacity corrected for alveolar volume (K(CO)) correlated with resting SaO2 (r = 0.74) and exercise PaO2 (r = 0.75) at altitude. Aerobic capacity correlated with the walk test distance at altitude (r = 0.70). Spirometry, lung volumes, and ventilatory reserve did not correlate with the hypoxemic response to altitude. Baseline arterial oxygen levels and K(CO) are key measures in predicting the hypoxemic response to acute altitude exposure in patients with COPD. The impairment in gas exchange associated with COPD is a significant mechanism causing altitude-related hypoxemia in this group.


Spontaneous release of DNA by human blood lymphocytes as shown in an in vitro system.
Human blood lymphocytes released DNA in vitro in the absence of any stimulation. Once purified from the complex appearing in the supernatant, this DNA exhibited typical characteristics as shown by its UV absorption curve, its deoxyribose coloration, and its sensitivity to DNase. Elution patterns on hydroxyapatite columns indicated that the excreted DNA is double stranded. The released DNA was smaller than the cellular DNA; its molecular weight ranged from 3.5 x 10(5) to 3.7 x 10(6) daltons. The DNA appearing in the supernatant does not seem to be due to dead or dying cells since: (a) the same amount of DNA was found in the medium whether the incubation lasted 2 hr or as long as 16 hr; (b) cell death rate had no effect on the amount of extracellular DNA; (c) when the lymphocytes were centrifuged and placed in a new medium several times in a row, a similar amount of extracellular DNA was isolated from each of the successive supernatants, whereas if, after centrifugation, the lymphocytes were put back in their original medium, no increase in the amount of extracellular DNA was observed, suggesting an active regulatory mechanism independent of a mechanical effect; (d) it took more than 1 hr for extracellular DNA to reach its maximum concentration, a fact that also argues against a mechanical effect; (e) the specific activity of the released DNA was different from that of the cellular DNA, depending on the time of labeling; and (f) the cells that had excreted DNA kept their functional integrity, as shown by their fully maintained capacity to increase DNA synthesis after stimulation. The extracellular DNA hybridized specifically with cellular DNA. The hybridization curves indicate that the DNA excreted is highly complex, and they suggest that it is composed of part of the newly synthesized DNA. The higher specific activity of the released DNA, compared with that of the cellular DNA after a long labeling period, can be explained only by a preferential release of the newly synthesized DNA.


Strategies for achieving high sequencing accuracy for low diversity samples and avoiding sample bleeding using illumina platform.
Sequencing microRNA, reduced representation sequencing, Hi-C technology and any method requiring the use of in-house barcodes result in sequencing libraries with low initial sequence diversity. Sequencing such data on the Illumina platform typically produces low quality data due to the limitations of the Illumina cluster calling algorithm. Moreover, even in the case of diverse samples, these limitations are causing substantial inaccuracies in multiplexed sample assignment (sample bleeding). Such inaccuracies are unacceptable in clinical applications, and in some other fields (e.g. detection of rare variants). Here, we discuss how both problems with quality of low-diversity samples and sample bleeding are caused by incorrect detection of clusters on the flowcell during initial sequencing cycles. We propose simple software modifications (Long Template Protocol) that overcome this problem. We present experimental results showing that our Long Template Protocol remarkably increases data quality for low diversity samples, as compared with the standard analysis protocol; it also substantially reduces sample bleeding for all samples. For comprehensiveness, we also discuss and compare experimental results from alternative approaches to sequencing low diversity samples. First, we discuss how the low diversity problem, if caused by barcodes, can be avoided altogether at the barcode design stage. Second and third, we present modified guidelines, which are more stringent than the manufacturer's, for mixing low diversity samples with diverse samples and lowering cluster density, which in our experience consistently produces high quality data from low diversity samples. Fourth and fifth, we present rescue strategies that can be applied when sequencing results in low quality data and when there is no more biological material available. In such cases, we propose that the flowcell be re-hybridized and sequenced again using our Long Template Protocol. Alternatively, we discuss how analysis can be repeated from saved sequencing images using the Long Template Protocol to increase accuracy.


Cysticercus cellulosae Regulates T-Cell Responses and Interacts With the Host Immune System by Excreting and Secreting Antigens.
Cysticercus cellulosae (C. cellulosae) excretes and secretes antigens during the parasitic process to regulate the host immune response; however, resulting immune response and cytokine production in the host during infection still remains unclear. We used C. cellulosae crude antigens (CAs) as controls to explore the effect of excretory secretory antigens (ESAs) on T-cell immune responses in piglets. C. cellulosae ESAs induced imbalanced CD4+/CD8+ T-cell proportions, increased the CD4+Foxp3+ and CD8+Foxp3+ T-cell frequencies, and induced lymphocytes to produce interleukin-10, which was mainly attributed to CD4+ and CD4-CD8- T cells. The ESAs also induced Th2-type immune responses. The results showed that the ability of C. cellulosae to escape the host immune attacks and establish a persistent infection may be related to host immune response regulation by the ESAs.


Cross-resistance to entry inhibitors and lenacapavir resistance through Week 52 in study CAPELLA.
Lenacapavir (LEN) is a first-in-class inhibitor of human immunodeficiency virus type 1 (HIV-1) capsid function for the treatment of heavily treatment-experienced people with HIV (PWH) harbouring multidrug resistance in combination with an optimized background regimen (OBR). Here, we describe in vitro analysis of the interplay between entry inhibitors (EI; enfuvirtide, fostemsavir, ibalizumab, and maraviroc) susceptibility and LEN susceptibility in samples from 72 participants in the phase 2/3 CAPELLA study, as well as the emergence of resistance in CAPELLA through 52 weeks. The phenotypic susceptibility to EIs of screening samples from participants was analysed using entry assays, and susceptibility to LEN was generated. Genotypic and phenotypic resistance to LEN was evaluated for subjects with virological failure through Week 52. Overall, viruses with resistance to EIs showed no cross-resistance to LEN, with a mean fold change from wild type close to 1.0. Of the 22 participants analysed for resistance through Week 52, 9 participants (13%) had emergence of capsid resistance mutation(s) while the remaining 13 participants (18%) had no change in the capsid sequence. The gag sequence from EI-resistant isolates did not affect LEN susceptibility. The lack of cross-resistance to LEN across ARV-resistant isolates supports the use of LEN in PWH regardless of their treatment history. During the second half-year period of the CAPELLA Study, development of LEN resistance was rare and was overall associated with functional LEN monotherapy due to either nonadherence or resistance-driven non-susceptibility to OBR.


Decorated Vesicles as Prebiont Systems (a Hypothesis).
Decorated vesicles in deep, seafloor basalts form abiotically, but show at least four life-analogous features, which makes them a candidate for origin of life research. These features are a physical enclosure, carbon-assimilatory catalysts, semi-permeable boundaries, and a source of usable energy. The nanometer-to-micron-sized spherules on the inner walls of decorated vesicles are proposed to function as mineral proto-enzymes. Chemically, these structures resemble synthetic FeS clusters shown to convert CO2, CO and H2 into methane, formate, and acetate. Secondary phyllosilicate minerals line the vesicles' inner walls and can span openings in the vesicles and thus can act as molecular sieves between the vesicles' interior and the surrounding aquifer. Lastly, basalt glass in the vesicle walls takes up protons, which replace cations in the silicate framework. This results in an inward proton flux, reciprocal outward flux of metal cations, more alkaline pH inside the vesicle than outside, and production of more phyllosilicates. Such life-like features could have been exploited to move decorated vesicles toward protolife systems. Decorated vesicles are proposed as study models of prebiotic systems that are expected to have existed on the early Earth and Earth-like exoplanets. Their analysis can lead to better understanding of changes in planetary geocycles during the origin of life.


Analysis of Ar-ion and X-ray-induced chromatin breakage and repair in V79 plateau-phase cells by the premature chromosome condensation technique.
The premature chromosome condensation technique has been used to compare chromatin breakage and repair in noncycling V79 cells following high and low LET radiation. Plateau-phase V79 cells were exposed to graded doses of low energy Ar ions (LET 1233 keV/microm) and X-rays. Cells were fused to mitotic V79 cells immediately after exposure to examine initial chromatin breakage or after various time intervals of post-irradiation incubation to investigate the kinetics of chromatin break rejoining as well as the fraction of unrejoined fragments. For both radiation qualities an average initial number of about 2.4 excess PCC fragments per cell per Gy was found increasing linearly with dose. The distributions of PCC chromosomes plus excess fragments among cells followed Poisson statistics after X-ray irradiation, while an overdispersion of the frequencies was observed after Ar-irradiation indicating that a single particle traversal through a cell nucleus can produce multiple chromatin lesions. Moreover, for both radiation types the rejoining of excess fragments has been examined. Both data sets could be fitted well to first-order kinetics with a single component. Despite similar rates of rejoining cellular repair was noticeably less effective for Ar ions than for X-rays. While after 10 h of post-irradiation incubation 60% of Ar ion induced excess fragments remained unrejoined, only 14% of X-ray-induced lesions were not rejoined. Furthermore, comparison of the residual number of excess PCC fragments with recently published data on the yield of chromosome aberrations in first post-irradiation metaphases shows that for both radiation types more aberrations are detected in interphase than in metaphase cells. Yet, for comparable doses this difference is more pronounced for Ar ions indicating that scoring of high LET induced aberrations in metaphase cells might result in a significant underestimation of the produced damage.


[Application of the QuavaTAR model to vaccination services in Latium, Italy].
Definition, categorization, and measuring of Quality have become increasingly important concerns in the era of managed care and cost containment. Most attempts to develop quality indicators have been based on outcome measures. The Donabedian model of Structure-Process-Outcome has been universally accepted and used as the basis for much of the work addressing quality and outcomes. Adequate indicators for vaccination services are scant therefore are applied to this setting a new quality measurement process based on a probabilistic approach called MQS (Misure di Qualità in Sanità-Quality Measures in Healthcare), developed by our working group since 2005 in several hospital settings. This new application, called "Quality in Vaccination Theory and Research"(QuaVaTAR), was used to measure the efficiency of the vaccination centers of three Local Health Units (ASL RM B, RM F, RM H) in Lazio Region (Italy). The measure method combines the evidences obtained from the supplied services (objective measurements) and the judgments of the services' stakeholders collected by an "ad hoc" questionnaire (subjective measurements). The subjective evaluations were expressed with a number (between 0-100) representing a personal judgment on the organizational and the communicational efficiency and the comfort of the "ideal" vaccination center. The objective measurements were collected in performance grids on the same points investigated with the questionnaire. Combining objective and subjective measures we obtained "Quality Scores", useful to make improvements in the vaccination centers and to compare different services.


Hemodynamic flow improves rat hepatocyte morphology, function, and metabolic activity in vitro.
In vitro primary hepatocyte systems typically elicit drug induction and toxicity responses at concentrations much higher than corresponding in vivo or clinical plasma C(max) levels, contributing to poor in vitro-in vivo correlations. This may be partly due to the absence of physiological parameters that maintain metabolic phenotype in vivo. We hypothesized that restoring hemodynamics and media transport would improve hepatocyte architecture and metabolic function in vitro compared with nonflow cultures. Rat hepatocytes were cultured for 2 wk either in nonflow collagen gel sandwiches with 48-h media changes or under controlled hemodynamics mimicking sinusoidal circulation within a perfused Transwell device. Phenotypic, functional, and metabolic parameters were assessed at multiple times. Hepatocytes in the devices exhibited polarized morphology, retention of differentiation markers [E-cadherin and hepatocyte nuclear factor-4α (HNF-4α)], the canalicular transporter [multidrug-resistant protein-2 (Mrp-2)], and significantly higher levels of liver function compared with nonflow cultures over 2 wk (albumin ~4-fold and urea ~5-fold). Gene expression of cytochrome P450 (CYP) enzymes was significantly higher (fold increase over nonflow: CYP1A1: 53.5 ± 10.3; CYP1A2: 64.0 ± 15.1; CYP2B1: 15.2 ± 2.9; CYP2B2: 2.7 ± 0.8; CYP3A2: 4.0 ± 1.4) and translated to significantly higher basal enzyme activity (device vs. nonflow: CYP1A: 6.26 ± 2.41 vs. 0.42 ± 0.015; CYP1B: 3.47 ± 1.66 vs. 0.4 ± 0.09; CYP3A: 11.65 ± 4.70 vs. 2.43 ± 0.56) while retaining inducibility by 3-methylcholanthrene and dexamethasone (fold increase over DMSO: CYP1A = 27.33 and CYP3A = 4.94). These responses were observed at concentrations closer to plasma levels documented in vivo in rats. The retention of in vivo-like hepatocyte phenotype and metabolic function coupled with drug response at more physiological concentrations emphasizes the importance of restoring in vivo physiological transport parameters in vitro.


[Oto-rhino-laryngological and cervico-maxillofacial pathologies among hospitalized older patients: epidemiological, diagnostical and therapeutical aspects in Lomé, Togo].
In developing countries, 10% of the population is over 60 years old and this proportion is increasing rapidly. The general objective of this study was to describe the profile and management of the elderly subject aged 60 and over, hospitalized in the ENT (Ear, Nose and Throat) and Head/Neck surgery department of the Sylvanus Olympio University Hospital in Lomé, from 2012 to 2021. Retrospective descriptive study. After reviewing the files, selection of patients aged 60 and over, regardless of sex, and hospitalized for an ENT pathology from January 2012 to December 2021. Not included in our study were files of elderly subjects hospitalized but whose age was imprecise, or empty or very incomplete files. A total of 296 cases were included, representing 6.7% of the department's activities. The mean age of the patients was 72 ± 7.3 years with extremes of 60 and 95 years. The age group 6069 years represented 59.5%. The sex ratio M/F was 0.92. Infectious/inflammatory lesions were found in 138 patients (46.6%) including 38.9% of acute cellulitis of dental origin, and tumors were found in 135 patients (45.6%). Tumors were malignant in 59 patients (43.7%) and benign in 76 patients (56.3%). Thyroid was the site of 46 (60.5%) benign lesions and larynx of 29 (49.2%) malignant lesions. Poor oral hygiene, use of non-steroidal anti-inflammatory drugs, diabetes and the combination of smoking and alcohol were the factors favoring the occurrence of acute cellulitis of dental origin in 89.6%, 80.9%, 20.0% and 2.6% of cases respectively (p<0.001). The combination of smoking and alcohol was a factor favoring the occurrence of malignancy in 39% (p<0.001). Surgical treatment was performed in 234 patients (79.1%). With a case lethality rate of 21%, acute cellulitis of dental origin was the leading cause of death (p<0.001). The most frequent pathologies of the ENT sphere in the elderly in our tropical context were infectious and tumoral, largely dominated by acute cellulitis of dental origin, thyroid adenoma and squamous cell carcinoma of the larynx. Despite the tendency to balance infectious and tumoral pathologies, the proportion of acute cellulitis of dental origin remains twice as high as that of malignant tumors. It contrasts with data from other sub-Saharan series where tumoral pathology remains predominant in the elderly. It is important to provide dental care assistance to the elderly and to advocate for the development of geriatrics and access to universal health coverage for the elderly in Togo.


Structure of covalent insulin-receptor complexes (I-S-S-R) in isolated rat adipocytes and human placental membranes.
The structure of naturally-formed covalent disulphide-linked complexes between insulin and its receptor was examined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. To prevent destabilization of disulphide bonds at alkaline pH the standard discontinuous electrophoresis conditions were changed to a continuous buffer system at pH 7.0. 125I-insulin was first bound to either rat adipocytes or human placental membranes for 10 min at 37 degrees C. After washing, non-dissociable radioactivity was extracted from cells or membranes in Triton X-100 and immunoprecipitated with an antiserum (B-2) to the insulin receptor. Electrophoresis of the immune precipitate revealed the two smaller of the three reported species of native insulin receptor (Mr values approx. 350 000, 290 000 and 260 000); in addition, a species of Mr 200 000 was also frequently observed in adipocytes. When non-dissociable 125I-insulin was chemically crosslinked to adipocytes or placental membranes, prior to solubilization and immunoprecipitation, all three species of the native receptor were labelled; after reduction, only a single species of Mr 130000 was observed. These findings indicate that disulphide exchange of insulin occurs with the Mr 130000 (alpha) binding subunit within partially reduced species of the native, oligomeric receptor. The degree of disulphide binding of insulin could therefore depend on the relative abundance of partially reduced receptor species and on the redox state of the cell membrane.


Sex differences in patients' and physicians' communication during primary care medical visits.
This study reports on the analysis of audiotapes of 537 adult, chronic disease patients and their 127 physicians (101 men and 26 women) in a variety of primary care practice settings to explore differences attributable to the effects of the patient's and the physician's sex on the process of communication during medical visits. Compared to male physicians, women conducted longer medical visits (22.9 vs 20.3 minutes; F(1,515) = 7.9, P less than .005), with substantially more talk F(1,518) = 19.5, P less than .000. Differences were especially evident during the history segment of the visit when female physicians talked 40% more than male physicians (F(1,518) = 20.1, P less than .000) and when patients of female physicians talked 58% more than male physicians' patients (F(1,448) = 24.4, P less than .000). Compared to male physicians, female physicians engaged in more positive talk, partnership-building, question-asking, and information-giving. Similarly, when with female compared to male physicians, patients engaged in more positive talk, more partnership-building, question-asking, and information-giving related to both biomedical and psychosocial topics.


Diesel exhaust exposure enhances venoconstriction via uncoupling of eNOS.
Environmental air pollution is associated with adverse cardiovascular events, including increased hospital admissions due to heart failure and myocardial infarction. The exact mechanism(s) by which air pollution affects the heart and vasculature is currently unknown. Recent studies have found that exposure to air pollution enhances arterial vasoconstriction in humans and animal models. Work in our laboratory has shown that diesel emissions (DE) enhance vasoconstriction of mouse coronary arteries. Thus, we hypothesized that DE could enhance vasoconstriction in arteries and veins through uncoupling of endothelial nitric oxide synthase (eNOS). To test this hypothesis, we first bubbled DE through a physiological saline solution and exposed isolated mesenteric veins. Second, we exposed animals, whole body, to DE at 350 microg/m(3) for 4 h, after which mesenteric arteries and veins were isolated. Results from these experiments show that saline bubbled with DE as well as inhaled DE enhances vasoconstriction in veins but not arteries. Exposure to several representative volatile organic compounds found in the DE-exposed saline did not enhance arterial constriction. L-nitro-arginine-methyl-ester (L-NAME), an eNOS inhibitor, normalized the control vessels to the DE-exposed vessels implicating an uncoupling of eNOS as a mechanism for enhanced vasoconstriction. The principal conclusions of this research are 1) veins exhibit endothelial dysfunction following in vivo and ex vivo exposures to DE, 2) veins appear to be more sensitive to DE effects than arteries, and 3) DE components most likely induce endothelial dysfunction through the uncoupling of eNOS.


Quantitative cell and matrix changes in human humeral head osteoarthritic cartilage.
A new quantitative method was devised both to establish an objective standard for morphometric diagnosis and to determine the extent of degeneration in osteoarthritic cartilage. Eight normal and forty-eight osteoarthritic humeral heads, subsequently confirmed by light microscopy, were obtained at necropsy. The articular cartilage was observed in situ with a laser scanning confocal microscope (LSCM) and morphometric measurements determined cell density (cells/mm), cell volume fraction (%) and mean cell volume (microm3). The osteoarthritic cartilages were classified according to the following four characteristics: increase in thickness, increase in cell volume fraction, decrease in cell volume fraction, and fibrous pannus. Deviations in cell density and cell volume fraction from normal means were calculated as extent of degeneration. Our present approach aims to provide valuable clues, such as objective stereological information and a unique reference for biochemical and traditional morphological analyses, that clinicians will be able to use in combination with other methods in order to establish a reliable diagnosis.


Persistent disparities over time in the distribution of sugar-sweetened beverage intake among children in the United States.
Recent research suggests that sugar-sweetened beverage (SSB) consumption has been declining among US children aged 2-18 y. However, most studies focused on changes in mean intake, ignore high SSB consumers and do not examine intake among vulnerable groups and, including adolescents, low-income households, and several racial/ethnic minorities. The aim was to estimate usual SSB intake from NHANES surveys from 2003-2004 to 2013-2014 to examine shifts at both the median and 90th percentile among US children, evaluating the extent to which intake disparities in total SSBs and subtypes have persisted. Children 2-18 y from NHANES 2003, 2005, 2007, 2009, 2011 and 2013. SSBs were all non-diet beverages sweetened with sugars including revising all beverages to as consumed status and excluding soy and dairy based beverages. The NCI usual intake method was used to estimate usual intake from two 24-hour recalls. A 2-part correlated model accounted for nonconsumers. Quantile regression was then used to examine differences in SSB usual intakes at the 50th and 90th percentiles by race-ethnicity, and examine interactions indicating whether racial-ethnic disparities in intake were modified by income. Despite considerable declines, children's SSB intake remains high, particularly among heavy consumers. Among adolescents, median SSB intake in 2013-2014 was on the order of 150-200 kcal/d, and heavy intake at the 90th percentile was on the order of 250-300 kcal/d. There were important disparities in intake that persisted over time. Although high household income was associated with lower SSB intake in non-Hispanic white (NHW) children, intakes of non-Hispanic black (NHB) and Mexican-American (MA) children from these households were similar to or higher than those from poor households. There were also large racial/ethnic differences in the types of SSBs consumed. The consumption of regular sodas by NHB children was somewhat lower than among MA and NHW children, whereas fruit drink intake was markedly higher. Overall, these findings suggest that, despite recent declines, strategies are needed to further reduce SSB consumption, and particularly heavy intake, especially among NHB children where fruit drinks also are key source of SSBs.


Evaluating the bone-regenerative role of the decellularized porcine bone xenograft in a canine extraction socket model.
To evaluate the efficacy of a novel decellularized porcine bone xenograft, produced by supercritical carbon dioxide extraction technology, on alveolar socket healing after tooth extraction compared to a commercially available deproteinized bovine bone (Bio-Oss®). Nine dogs (about 18 months old and weighing between 20 kg and 30 kg) underwent extractions of lower second to fourth premolars, bilaterally. The dogs were randomly selected and allocated to the following groups: Group 1: control unfilled socket; Group 2: socket filled with decellularized porcine bone xenograft (ABCcolla®) and covered by a commercially available porcine collagen membrane (Bio-Gide®); Group 3: socket filled with Bio-Oss® and covered by Bio-Gide® membrane. One dogs from each group was sacrificed at 4-, 12-, and 24-week to evaluate the socket healing after tooth extraction. The mandible bone blocks were processed without decalcification and specimens were embedded in methyl methacrylate and subjected to histopathology analyses to evaluate the bone regeneration in the extraction sockets. At 24-week after socket healing, ABCcolla® treated defects demonstrated significantly higher histopathology score in new bone formation and bone bridging, but significantly lower score in fluorescent labeling than those of the Bio-Oss®. In the microphotographic examination, decellularized porcine bone xenograft showed similar characteristics of new bone formation to that of Bio-Oss®. However, there was significantly less remnant implant materials in the decellularized porcine bone xenograft compared to the Bio-Oss® group at 24-week. Thus, the decellularized porcine bone graft seems to have promising bone regeneration properties similar to that of Bio-Oss® with less remnant grafted material in a canine tooth extraction socket model. Within the limits of the study, we concluded that ABCcolla® treated defects demonstrated significantly more new bone formation and better bone bridging, but less amount of fluorescent labeling than those of the Bio-Oss® group. However, clinical studies in humans are recommended to confirm these findings.


Mental Health and Burnout Syndrome Among Postgraduate Students in Medical and Multidisciplinary Residencies During the COVID-19 Pandemic in Brazil: Protocol for a Prospective Cohort Study.
The COVID-19 pandemic has led to high levels of physical, psychological, and social stress among health care professionals, including postgraduate students in medical and multidisciplinary residencies. This stress is associated with the intense fear of occupational exposure to SARS-CoV-2, the virus known to cause COVID-19. These professionals are at risk of developing physical and mental illnesses not only due to the infection but also due to prolonged exposure to multidimensional stress and continued work overload. This study aims to evaluate the prevalence of symptoms suggestive of mental disorders and burnout syndrome and determine the risk factors for burnout among postgraduate students in medical and multidisciplinary residencies in Brazil during the COVID-19 pandemic. For this prospective cohort study with parallel groups, participants were recruited between July and September 2020 to achieve a sample size of at least 1144 participants. Research instruments such as Depression, Anxiety, and Stress Scale; Patient Health Questionnaire; Brief Resilient Coping Scale; and Oldenburg Burnout Inventory will be used to collect data. Data will be collected in 2 waves: the first wave will include data related to sample characterization and psychosocial evaluation, and the second wave will be launched 12 weeks later and will include an evaluation of the incidence of burnout as well as correlations with the potential predictive factors collected in the first wave. Additionally, we will collect data regarding participants' withdrawal from work. The recruitment took place from July 29 to September 5, 2020. Data analyses for this phase is already in progress. The second phase of the study is also in progress. The final data collection began on December 1, 2020, and it will be completed by December 31, 2020. We believe the findings of this study will help evaluate the impact of the COVID-19 pandemic on the mental health conditions of health professionals in Brazil as well as contribute to the planning and implementation of appropriate measures that can alleviate these mental health challenges. DERR1-10.2196/24298.


Changes in incisor third-order inclination resulting from vertical variation in lingual bracket placement.
To test the null hypothesis that third-order measurements are not correlated to lingual incisor features seen on radiographs. The lateral headfilms of 38 untreated, norm-occlusion subjects without incisor abrasions or restorations were used for third-order measurements of upper and lower central incisors and assessment of the inclination of four sites suitable for lingual bracket placement with reference to the occlusal plane perpendicular. Lingual sections were determined by the tangents at the incisal fossa (S1), at the transition plateau between incisal fossa and the cingulum (S2), by a constructed line reaching from the incisal tip to the cingulum (S3), and by a tangent at the cingulum convexity (S4). Third-order angles were also assessed on corresponding dental casts using an incisor inclination gauge. Regression analysis was performed using the third-order measurements of both methods as the dependent variables and the inclination of the lingual enamel sections (S1, S2, S3, S4) as the independent variables. The null hypothesis was rejected. For the most common bracket application sites located on the lingual shovel (S1 and S2), third-order inclination changes of 0.4-0.7 degrees are expected for each degree of change in the inclination of the lingual surface. The impact of bracket placement errors on third-order angulation is similar between sections S1 and S2 and the cingulum convexity (S4). Section S3 proved to be least affected by interindividual variation. The third-order measurements are correlated to lingual incisor features. Accordingly, third-order changes resulting from variation in lingual bracket placement can be individually predicted from radiographic assessments.


Genetic secrets of long-term glioblastoma survivors.
Glioblastomas are the most aggressive and lethal primary astrocytic tumors of the central nervous system. They account for 60% to 70% of all gliomas and the majority are diagnosed in Caucasian male patients at advanced age. Genetic analyses of glioblastoma show a great intra- and inter-tumor heterogeneity, which opens up a debate about its cellular origin. Different types of brain cells, including astrocytes, neural stem cells, oligodendrocyte precursor cells and glioblastoma stem cells are proposed to have a role in tumor initiation and spreading; however, data is still inconclusive. Due to short life expectancy, long-term glioblastoma survivors are defined as patients who live longer than two years post-diagnosis. Extreme survivors, living 10 years or more after diagnosis, comprise less than 1% of all patients. Molecular testing indicates genetic differences between short- and long-term survivors with glioblastoma. The most informative are IDH1/2 gene mutations and MGMT promoter methylation, which are associated with a better response to standard clinical care. Moreover, a decreased expression of the CHI3L1, FBLN4, EMP3, IGFBP2, IGFBP3, LGALS3, MAOB, PDPN, SERPING1 and TIMP1 genes has been associated with prolonged survival. In addition, emerging evidence suggests the role of different microRNAs in predicting patient survival. Other factors that may affect the survival of glioblastoma patients include clinical/demographic characteristics such as seizures at presentation, age at diagnosis, and the extent of surgical resection. Because of the small number of long-term survivors with glioblastoma, comparative studies on genetic differences between short- and long-term survivors are challenging. To improve patient management and clinical outcomes, a thorough "omics" approach is necessary for identifying differences between short- and long-term survivors with glioblastoma.


Killing of Histoplasma capsulatum by macrophage colony stimulating factor-treated human monocyte-derived macrophages: role for reactive oxygen intermediates.
The interaction of human macrophages with the yeast-form of Histoplasma capsulatum was studied. The use of culture and a short-term assay period instead of microscopy gave direct evidence of the fungicidal activity of human macrophages. The present study reports the novel finding of fungicidal activity of macrophages derived from monocytes in the presence of macrophage colony-stimulating-factor (MCSF). The induction of fungicidal activity by this cytokine was dose dependent. MCSF at 10,000 U/ml was optimal with 73(SD3)% killing. Inhibition of macrophage killing by superoxide dismutase (SOD), but not catalase (CAT) or N-monomethyl-L-arginine (NMMA), established the role of the superoxide anion in the killing mechanism. The fungistatic activity of MCSF-derived human macrophages in a 24-h assay was also dose dependent and was not inhibited by SOD, CAT or NMMA. MCSF at 10,000 U/ml produced optimal macrophage fungistatic activity, 34.6(SD4)%.


Organizational learning in hospitals: A realist review.
To establish a middle-range theory of organizational learning in hospitals. A realist review of the literature, conducted according to established standards for realist and meta-narrative evidence syntheses. Middle-range theory development was performed according to Smith and Liehr's recommendations. Two comprehensive scientific databases and six discipline-focused databases spanning health care, life sciences, business, sociology, and psychology were searched from inception to 12 May 2016. Citations meeting the inclusion criteria were appraised using the Mixed Methods Appraisal Tool. Data extraction was guided by a focus on the contextual factors, mechanisms, and outcomes associated with organizational learning. The initial search yielded 2,332 citations, 147 of which were ultimately included in the review. The included citations were generally of high quality. Reviewed evidence indicates certain aspects of organizational context can be conducive to mechanisms of organizational learning, leading to a range of positive organizational outcomes. This review updates and expands on a previous review of the literature on organizational learning in hospitals, refines the concept of organizational learning in hospitals, and provides a middle-range theory of organizational learning in hospitals. This updated review provides a strong evidence base for future work on the topic of organizational learning in hospitals. The refined concept of organizational learning makes it possible to develop reliable, valid research instruments that better reflect of the full scope of organizational learning. Finally, the middle-range theory guides researchers and clinical leaders as they advance the science and practice of organizational learning.


The risk of adverse outcomes in extra-articular distal radius fractures is increased with malalignment in patients of all ages but mitigated in older patients.
The purpose of this study was to determine if malalignment after extra-articular distal radius fractures influenced patient-reported pain and disability at 1 year and to investigate how this relationship changes with age. Two hundred sixteen subjects with extra-articular distal radius fractures were followed. The influence of specific radiographic parameters and the overall "acceptability" of alignment on Patient-Rated Wrist Evaluation (PRWE) and Disabilities of Arm, Shoulder and Hand (DASH) scores were assessed. The relative risk (RR) of a poor outcome in the presence of malalignment of the distal radius at various ages was calculated; the RR was then used to calculate a number needed to harm. Malalignment of the distal radius was associated with higher reports of pain and disability in patients <65 years of age. In patients aged > or =65 years, no isolated radiography parameter was found to affect PRWE or DASH scores significanly; however, there was an increased risk of a poor outcome in fractures with malalignment when compared with fractures with acceptable alignment in all age groups. The RR of a poor outcome with malalignment showed a decreasing trend with increasing age, with a significant reduction after 65 years. In patients > or =65 years of age, 8 malaligned fractures would require correction to prevent 1 poor outcome (based on DASH, or 9 based on PRWE); in younger patients, only 2 malaligned fractures would need correction to avoid 1 poor outcome (based on DASH, or 3 based on PRWE). Patients > or =65 years of age showed no statistically significant relationship between malalignment of the distal radius and PRWE or DASH scores when the radiography parameters were examined in isolation and when clustered together. The relative risk data demonstrates, however, that patients at all ages have a higher risk of a poor outcome with malalignment of the distal radius when compared with those with acceptable alignment. Therefore, we conclude that the relationship between outcome and alignment of the radius should not be considered as an all-or-none phenomenon but rather considered as a decreasing gradient of risk, with the most significant change seen after patients reach 65 years of age.


Influence of formulation and preparation process on ambroxol hydrochloride dry powder inhalation characteristics and aerosolization properties.
The objective of this study is to evaluate the influence of formulation and preparation process on ambroxol hydrochloride (AH) dry powder inhalation (DPI) characteristics and aerosolization properties. Spray-dried samples of AH, AH/leucine, and AH/leucine/mannitol were prepared from their corresponding water solutions under the same conditions to study the influence of the composition, and the AH/leucine/mannitol (2.5/0.5/1 by weight) formulation was used for investigation of the effect of the preparation process. Following spray-drying, the resulting powders were characterized using scanning electron microscopy, laser diffraction, tapped density, and angle of repose measurements, and the aerosolization performance was determined using a twin-stage liquid impinger. AH/leucine/mannitol (2.5/0.5/1 by weight) obtained by cospray-drying improved the AH aerosolization properties. The AH/leucine/mannitol (2.5/0.5/1 by weight) preparation exhibited the following properties: 62.34% yield, 0.34 g/cm(3) tap density, 2.71 microm d(ae), 33.45 degrees angle of repose, and 30.93% respirable fraction. The influence of the preparation process on DPI characteristics and aerosolization properties was relatively small, but the influence of the composition was relatively large. Optimization of DPI can be achieved by selecting the most appropriate formulation and preparation process.


Hospital readmission among people experiencing homelessness in England: a cohort study of 2772 matched homeless and housed inpatients.
Inpatients experiencing homelessness are often discharged to unstable accommodation or the street, which may increase the risk of readmission. We conducted a cohort study of 2772 homeless patients discharged after an emergency admission at 78 hospitals across England between November 2013 and November 2016. For each individual, we selected a housed patient who lived in a socioeconomically deprived area, matched on age, sex, hospital, and year of discharge. Counts of emergency readmissions, planned readmissions, and Accident and Emergency (A&E) visits post-discharge were derived from national hospital databases, with a median of 2.8 years of follow-up. We estimated the cumulative incidence of readmission over 12 months, and used negative binomial regression to estimate rate ratios. After adjusting for health measured at the index admission, homeless patients had 2.49 (95% CI 2.29 to 2.70) times the rate of emergency readmission, 0.60 (95% CI 0.53 to 0.68) times the rate of planned readmission and 2.57 (95% CI 2.41 to 2.73) times the rate of A&E visits compared with housed patients. The 12-month risk of emergency readmission was higher for homeless patients (61%, 95% CI 59% to 64%) than housed patients (33%, 95% CI 30% to 36%); and the risk of planned readmission was lower for homeless patients (17%, 95% CI 14% to 19%) than for housed patients (30%, 95% CI 28% to 32%). While the risk of emergency readmission varied with the reason for admission for housed patients, for example being higher for admissions due to cancers than for those due to accidents, the risk was high across all causes for homeless patients. Hospital patients experiencing homelessness have high rates of emergency readmission that are not explained by health. This highlights the need for discharge arrangements that address their health, housing and social care needs.


[Acute abdomen at onset of incomplete and atypical Kawasaki disease: case report].
Kawasaki disease is one of the most common systemic vasculitis in children and the most common cause of acquired heart disease in developed countries. Diagnosis relies on clinical findings and there is no specific test. Diagnosis and treatment decisions are very difficult in incomplete or atypical cases and questions inevitably arise during the care of these patients. In children with atypical or incomplete disease, the option in favor of therapy with gamma globulin seems currently to be the most suitable one. A patient with acute abdomen is presented as the initial symptom of Kawasaki disease.


[Overall trypsin-like, elastase-like and antitryptic activity in patients with eye contusion].
The investigations of tear fluid of eye after contusion injury revealed on increase of trypsin-like activity in 1-3 day and 10-19 day after trauma, the progressively elevation of elastase-like activity and lowering of inhibitory potential along 2-3 week. It was detected indirect correlation between the elastase-like activity and severity of the contusion injury of the eye, the grade of corneal edema, corneal erosion and conjunctival wound, hyphema. This results was shown the participation and the role of proteolytic and inflammatory processes in pathogenesis of eye blunt trauma. It was establish that the during of local inflammation is 2 week end more and is necessary antiinflammatory therapy with use the proteases inhibitors.


Myoglobin diffusion in bovine heart muscle.
The rotational mobility of myoglobin in situ was determined by proton nuclear magnetic resonance line width measurements of a characteristic myoglobin resonance observed in bovine heart muscle spectra. The protein diffuses intracellularly at nearly half the rate observed in dilute solution. This high mobility allows the oxygenated form of myoglobin to contribute significantly to the overall diffusive flux of oxygen in respiring heart muscle.


Acetylation and cleavage of purine nucleosides. Synthesis of 6-azauridine, 5-fluorouridine, and 5-methyluridine.
Inosine (I) when acetylated with acetic anhydride in the presence of acetyl chloride in acetic acid solution (the so called "acid acetylation"), affords an acetylated nucleoside III (75%) along with cleavage products of the nucleoside (hypoxanthine, 19%). The reaction of I with acetyl chloride (7 days) results in the formation of hypoxanthine (95%) and triacetylribofuranosyl chloride (IV) isolated in the form of tetraacetylribofuranose (47%). The acetylated purine nucleoside affords a similar result by reaction with acetyl chloride or acetyl bromide. 2'-Deoxyuridine gives a diacetyl derivative (80%) by reaction with acetyl bromide. On treatment with acetyl bromide, the nucleoside bond of purine nucleosides is quantitatively cleavaged (4 h, 20 degrees C) with the formation of tri-O-acetyl-D-ribofuranosyl bromide (X). The halogenose X affords pure beta-anomers, namely, 1,2,3,5-tetra-O-acetyl-beta-D-ribofuranose (75%), the triacetyl derivatives of 5-methyluridine (XVIIa; 75%, referred to guanosine), 6-azauridine (XVIII; 71%), and 5-fluorouridine (XIXa; 75%).


The barn owls' Minimum Audible Angle.
Interaural time differences (ITD) and interaural level differences (ILD) are physical cues that enable the auditory system to pinpoint the position of a sound source in space. This ability is crucial for animal communication and predator-prey interactions. The barn owl has evolved an exceptional sense of hearing and shows abilities of sound localisation that outperform most other species. So far, behavioural studies in the barn owl often used reflexive responses to investigate aspects of sound localisation. Furthermore, they predominately probed the higher frequencies of the owl's hearing range (> 3 kHz). In the present study we used a Go/NoGo paradigm to measure the barn owl's behavioural sound localisation acuity (expressed as the Minimum Audible Angle, MAA) as a function of stimulus type (narrow-band noise centred at 500, 1000, 2000, 4000 and 8000 Hz, and broad-band noise) and sound source position. We found significant effects of both stimulus type and sound source position on the barn owls' MAA. The MAA improved with increasing stimulus frequency, from 14° at 500 Hz to 6° at 8000 Hz. The smallest MAA of 4° was found for broadband noise stimuli. Comparing different sound source positions revealed smaller MAAs for frontal compared to lateral stimulus presentation, irrespective of stimulus type. These results are consistent with both the known variations in physical ITDs and variation in the width of neural ITD tuning curves with azimuth and frequency. Physical and neural characteristics combine to result in better spatial acuity for frontal compared to lateral sounds and reduced localisation acuity at lower frequencies.


Zika Virus Advice for Mountaineers: A UIAA Medcom Consensus Advice Sheet.
Hillebrandt, David, Paul Richards, Andy Clark, and Dominique Jean. Zika virus advice for mountaineers: A UIAA Medcom consensus advice sheet. High Alt Med Biol. 17:70-71, 2016.-With the current media coverage of the spread of Zika virus from Africa and Asia to Central and South America and its possible relationship with fetal abnormalities, UIAA Medcom has produced an advice sheet for mountaineers visiting risk areas.


Psychological symptoms and health-related quality of life in idiopathic environmental intolerance attributed to electromagnetic fields.
Need for better understanding of the etiology of idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF) motivated the present study of psychological symptoms and health-related quality of life (HRQoL) in person who attribute health problems to electromagnetic fields. Participants with IEI-EMF (n=114) and a population-based sample of referents (n=104) were investigated with six subscales of the Symptom Checklist 90 (SCL-90) to assess psychological symptoms, and with eight subscales of the Short Form (36) Health Survey (SF-36) to assess HRQoL. Significantly higher scores were found on obsessive/compulsive behavior, interpersonal hypersensitivity, hostility, phobic anxiety, paranoid thoughts in the IEI-EMF group compared to referents, whereas only a tendency of such a difference was found for psychotism. Furthermore, poorer HRQoL in the IEI-EMF group, compared to referents, were found regarding physical and social functioning, physical and emotional role limitations, general health, vitality, bodily pain, and mental health. Significant correlation with moderate to strong effect sizes were found between several of the SCL-90 and SF-36 subscales. The results suggest that IEI-EMF is associated with various types of psychological symptoms and with poor HRQoL. Clinical implications include theoretical support for cognitive behavioral therapy, and, although further research is needed, that attention should be directed towards feelings of inferiority and uneasiness in relationships as well as anger, hostility and resentment towards other people.


Genes encoding the T-cell antigen receptor.
The search for the elusive and controversial T-cell antigen receptor is over. It is now clear that gene complexes for both alpha and beta chains are distinct from those for immunoglobulin genes. They are, however, related to Ig genes as well as to other class I and class II major histocompatibility complex (MHC) gene products. Therefore, they belong to the immunoglobulin super gene family.


Moving from laboratory to real life conditions: Influence on the assessment of variability and stability of gait.
The availability of wearable sensors allows shifting gait analysis from the traditional laboratory settings, to daily life conditions. However, limited knowledge is available about whether alterations associated to different testing environment (e.g. indoor or outdoor) and walking protocols (e.g. free or controlled), result from actual differences in the motor behaviour of the tested subjects or from the sensitivity to these changes of the indexes adopted for the assessment. In this context, it was hypothesized that testing environment and walking protocols would not modify motor control stability in the gait of young healthy adults, who have a mature and structured gait pattern, but rather the variability of their motor pattern. To test this hypothesis, data from trunk and shank inertial sensors were collected from 19 young healthy participants during four walking tasks in different environments (indoor and outdoor) and in both controlled (i.e. following a predefined straight path) and free conditions. Results confirmed what hypothesized: variability indexes (Standard deviation, Coefficient of variation and Poincaré plots) were significantly influenced by both environment and walking conditions. Stability indexes (Harmonic ratio, Short term Lyapunov exponents, Recurrence quantification analysis and Sample entropy), on the contrary, did not highlight any change in the motor control. In conclusion, this study highlighted an influence of environment and testing condition on the assessment of specific characteristics of gait (i.e. variability and stability). In particular, for young healthy adults, both environment and testing conditions affect gait variability indexes, whereas neither affect gait stability indexes.


A Narrative Review of Psychological Cannabis Use Treatments with And Without Pharmaceutical Adjunct.
As policy responses to cannabis use and availability change internationally, levels of cannabis use disorder rise and treatment seeking increases. Diversion to cannabis treatment from the criminal justice system also increases demand in the system. At a time of developing treatment systems in response to this demand, an understanding of the evidence is increasingly important. To provide a narrative review of the developing evidence-base for psycho-social interventions for cannabis use disorder, including adjunctive cannabinoid agonist therapy. Two researchers independently conducted a literature search for articles published prior to February 2016, located through online search of four electronic databases (Google Scholar, CINAHL, Medline, and PsycINFO). Only randomised controlled trials describing treatment(s) for cannabis use or cannabis use disorder with a measure of either cannabis use frequency or cannabis use disorder severity were included. Non-English papers, review papers, posters, opinion pieces, letters or editorials, case studies (N<10) and published abstracts were excluded. The cannabis treatment most likely to be effective for adolescents and adults is based on the combination of Motivational Enhancement Therapy (MET) and Cognitive Behavioural Therapy (CBT) with the inclusion of contingency management and agonist replacement therapy showing promise. A more concrete and robust evidence base is required for these interventions. Replication of treatment studies is needed using standardised interventions, methods and measures to minimise conflicting findings, inconsistent follow-up periods and relatively poor treatment effects over time.


[Application of the navigation system in endoscopic surgery of paranasal sinuses and base of the skull].
The intraoperative navigation computer system Stealth Station is an effective technique of stereotactic guidance during endoscopic endonasal interventions. Use of navigation allows performance of a radical operation without damaging basic anatomical structures of the base of the skull (vision nerve, cribriform lamina, internal carotid arteries, cavernous sonus, etc.). In rhinosurgery, Stealth Station is indicated in borderline pathology of the paranasal sinuses and base of the skull. Ten cases of patients with combined pathology of the paranasal sinuses and base of the skull, cases of endoscopic endonasal removal of the lesions of the base of the skull and foreign bodies with application of the navigation system are reported.


Growth hormone: current and future therapeutic applications.
The increased availability of growth hormone (GH) in the mid-1980s, as a result of advances in recombinant DNA techniques, has allowed research into the use of this hormone at physiological dosage, as replacement therapy for adults with GH deficiency (GHD) and at pharmacological dosages as a possible therapeutic agent, for a number of disease states. GHD adults have increased body fat and reduced muscle mass and consequently, reduced strength and exercise tolerance. In addition, they are osteopenic, have unfavourable cardiac risk factors and impaired quality of life. In these individuals, replacing GH reverses these anomalies, although it may not alter the reduced insulin-sensitivity. A proportion of adults with GHD perceive a dramatic improvement in their well-being, energy levels and mood following replacement. GH has protein and osteoanabolic, lipolytic and antinatriuretic properties. GH has been considered for the therapeutic treatment of frailty associated with ageing, osteoporosis, morbid obesity, cardiac failure, major thermal injury and various acute and chronic catabolic conditions. Initial small, uncontrolled studies for many of these clinical problems suggested a beneficial effect of GH, although, later placebo-controlled studies have not observed such dramatic effects. Furthermore, with a recent publication demonstrating an approximate 2-fold increase in mortality in critically ill patients receiving large doses of GH, the use of GH should remain in the realms of replacement therapy and research, until there are significant advances in our understanding.


Liquid chromatographic detector for organosulphur compounds based on a ligand-exchange reaction.
A method is described for the post-column reaction detection of organosulphur compounds in liquid chromatography, which is based on a ligand-exchange reaction between the palladium(II)-calcein complex and the sulphur-containing compounds. The release of free calcein provides an indirect measure of the amount of organosulphur compounds via fluorescence detection. The kinetics of the reaction and the signal intensity have been studied as a function of the structure of selected organosulphur compounds and of parameters such as carrier- and reagent-stream composition and temperature. Optimal conditions are as follows: an aqueous mobile phase of pH 5-7, to which may be added up to 20% of methanol; an elevated reaction temperature of around 60 degrees C and a palladium(II)-calcein reagent solution of ca. 10(-5) M, which should contain some zinc(II) to enhance the fluorescence intensity. Detection limits, which are dependent on the structure of the compounds, typically are between 0.5 and 1.0 ng. Good linearity is observed over a two- to three-order concentration range. The method has been applied to the determination of ethylene thiourea in e.g. wash-water of apples and tomatoes, and to the detection of penicillamine in spiked serum and urine.


Detection of Astronaut's Stress Levels During 240-Day Confinement using EEG Signals and Machine Learning.
Early detection of mental stress is particularly important in prolonged space missions. In this study, we propose utilizing electroencephalography (EEG) with multiple machine learning models to detect elevated stress levels during a 240-day confinement. We quantified the levels of stress using alpha amylase levels, reaction time (RT) to stimuli, accuracy of target detection, and functional connectivity of EEG estimated by Phase Locking Value (PLV). Our results show that, alpha amylase level increased every 60-days (with 0.76 correlation) In-mission resulting in four elevated levels of stress. The RT and accuracy of target detection did not show any significant difference with time In-mission. The functional connectivity network showed different patterns between the frontal/occipital with other regions, and parietal to central region. The machine learning classifiers differentiate between four levels of stress with classification accuracy of 91.8%, 91.4%, 90.2%, 87.8, and 81% using linear discriminate analysis (LDA), Support Vector Machine (SVM), k-nearest neighbor (KNN), Naïve bayes (NB) and decision trees (DT). Our results suggest that EEG and machine learning can be used to detect elevated levels of mental stress in isolation and confined environments.


Oxidative remobilization of technetium sequestered by sulfide-transformed nano zerovalent iron.
Our previous study showed that formation of TcS2-like phases is favored over TcO2 under sulfidic conditions stimulated by nano zerovalent iron. This study further investigates the stability of Tc(IV) sulfide upon reoxidation by solution chemistry, solid phase characterization, and X-ray absorption spectroscopy. Tc dissolution data showed that Tc(VII) reduced by sulfide-transformed nZVI has substantially slower reoxidation kinetics than Tc(VII) reduced by nZVI only. The initial inhibition of Tc(IV) dissolution at S/Fe = 0.112 is due to the redox buffer capacity of FeS, which is evidenced by the parallel trends in oxidation-reduction potentials (ORP) and Tc dissolution kinetics. The role of FeS in inhibiting Tc oxidation is further supported by the Mössbauer spectroscopy and micro X-ray diffraction data at S/Fe = 0.112, showing persistence of FeS after 24-h oxidation but complete oxidation after 120-h oxidation. X-ray absorption spectroscopy data for S/Fe = 0.011 showed significantly increasing percentages of TcS2 in the solid phase after 24-h oxidation, indicating stronger resistance of TcS2 to oxidation. At S/Fe = 0.112, the XAS results revealed significant transformation of Tc speciation from TcS2 to TcO2 after 120-h oxidation. Given that no apparent Tc dissolution occurred during this period, the speciation transformation might play a secondary role in hindering Tc oxidation. Collectively, the results indicate that sequestrating Tc as TcS2 under stimulated sulfate reduction is a promising strategy to improve the long-term stability of reduced Tc in subsurface remediation.


Systematics and ecology of the Australasian genus Empodisma (Restionaceae) and description of a new species from peatlands in northern New Zealand.
The genus Empodisma comprises two species that are ecologically important in wetland habitats. Empodisma gracillimum is restricted to south-western Australia, whereas Empodisma minus is found in Tasmania, eastern Australia and New Zealand. We sequenced three cpDNA genes for 15 individuals of Empodisma sampled from throughout the range of the species. The results support an Australian origin for Empodisma sometime during the late Oligocene to early Miocene with more recent dispersal, colonization and diversification in New Zealand. We recovered six genetically distinct maternal lineages: three Empodisma gracillimum haplotypes corresponding to the three accessions in our analysis, a wide-ranging Empodisma minus haplotype found in eastern Australia and Tasmania, an Empodisma minus haplotype found in New Zealand from Stewart Island to approximately 38° S latitude on the North Island, and a distinct haplotype restricted to the North Island of New Zealand north of 38° S latitude. The Eastern Australian and New Zealand haplotypes of Empodisma minus were supported by only one cpDNA gene, and we felt the relatively minor morphological differences and the small amount of genetic divergence did not warrant taxonomic recognition. However, we recommend that the northern New Zealand haplotype should be recognized as the new species Empodisma robustum and provide descriptions and a key to the species of Empodisma. Monophyly of Empodisma robustum is supported by all three cpDNA genes. Empodisma robustum can be distinguished from Empodisma gracillimum and Empodisma minus by its robust growth stature and distinct ecology. It is typically eliminated by fire and re-establishes by seed (seeder strategy), whereas Empodisma minus and Empodisma gracillimum regrow after fire (sprouter strategy).


The (re)generation of splenic tissue.
A 48-year-old man with a history of a traumatic splenic rupture followed by splenectomy at the age of 5 years was referred to the outpatient clinic with markedly elevated liver enzymes. He was diagnosed with alcoholic liver cirrhosis. Ultrasound of the upper abdomen revealed hepatomegaly and suggested a central mass in the liver. Subsequent MRI of the abdomen did not show a hepatic mass, but revealed multiple intraperitoneal and retroperitoneal ovoid structures with a maximum diameter of 3 cm. A peripheral blood smear did not reveal Howell-Jolly bodies suggesting intact splenic function. The diagnosis splenosis-that is, autotransplantation of splenic tissue after iatrogenic/traumatic rupture of the spleen-was considered and confirmed by SPECT-CT with technetium-99m ((99m)Tc) labelled heat-denatured autologous red blood cells.


A comparison of contractile properties in human arm and leg muscles.
Isometric twitch properties have been compared in two pairs of opposing human limb muscles; these were the brachial biceps and triceps, and the anterior tibial and plantarflexor muscles. All four muscles were examined in each of 24 healthy subjects (16 men and 8 women). The brachial triceps had the shortest contraction and half-relaxation times and the greatest twitch potentiation, while the plantarflexors had the most prolonged twitches and least potentiation; the anterior tibial and brachial biceps muscles had similar characteristics. Susceptibility to fatigue was less in the plantarflexors than in the other three muscles. When muscles were assessed without reference to their anatomical sites, a significant relationship was noted between contraction time and potentiation, but not between either of these features and fatiguability. There was no evidence that muscles were uniformly 'faster' or 'slower' in some subjects than in others.


Whole grain intakes in the diets of Irish children and teenagers.
A growing body of evidence supports the inclusion of whole grain foods in the diet to help prevent certain chronic diseases. Although much of the research has been conducted in adult cohorts, it is thought that younger populations may also benefit from whole-grain-rich diets. The aim of the present study was to quantify the intake of whole grain in Irish children and teenagers, and assess the major sources of intake. Data used in the present study were from the National Children's Food Survey and the National Teens' Food Survey, which used 7 d food diaries to collect data on habitual food and beverage consumption in representative samples of Irish children and teenagers. Results showed that over 90 % of children (5-12 years) and over 86 % of teenagers (13-17 years) are consumers of whole grain, with mean daily intakes of 18·5 and 23·2 g/d, respectively. Ready-to-eat breakfast cereals made the greatest contribution to whole grain intakes for both children and teenagers (59·3 and 44·3 %), followed by bread (14·4 and 26·5 %), with wheat being the major source of intake, accounting for over 65 % of all whole grains consumed. Whole grain consumers had significantly higher intakes of fibre, P and Mg in comparison with non-consumers of whole grain, even though whole grain intakes in this sample were well below the recommendation of three servings or 48 g/d. The present study characterises, for the first time, the patterns of whole grain consumption in Irish children and teenagers and shows whole grain intake to be low.


[Effect of immunization with live tularemia vaccine on the growth of various tumor strains in rats].
The paper deals with a study of the effect of a single challenge with living tularemia vaccine on the growth of such transplantable tumors as Zajdela's hepatoma, Pliss' lymphosarcoma, Walker's carcinosarcoma, Schwetz' erythromyelosis and sarcoma 45 in Wistar rats. Immunization was followed by a significant (37.2-86%) inhibition of the rate of growth of the said tumors. Ascites was detected in half the vaccinated animals of Zajdela's hepatoma series, this being matched by 100% in controls.


Effects of GNA transgenic sugarcane on life history parameters of Parallorhogas pyralophagus (Marsh) (Hymenoptera: Braconidae), a parasitoid of Mexican rice borer.
Parallorhogas pyralophagus (Marsh) is the principal parasitoid of the Mexican rice borer [Eoreuma loftini (Dyar)], the primary pest of sugarcane in south Texas. Insect resistant transgenic sugarcane producing Galanthus nivalis agglutinin (GNA) was developed to improve control of E. loftini. The present laboratory study addressed whether over two consecutive generations transgenic sugarcane delivered via artificial diet has adverse host-mediated effects on P. pyralophagus life history parameters. The results of this study showed that a number of life history parameters were affected by transgenic sugarcane, whereas others were not affected, and that effects varied between generations. In the first generation, adult longevity was increased by approximately 2 d, and cocoon to adult and egg to adult developmental times were prolonged by approximately 1 d in parasitoids exposed to transgenic sugarcane, whereas effects were not evident on adult size; egg load; egg to cocoon developmental time; rates of gain of longevity and egg load with adult size; and egg, larval, and pupal mortality. However, in the second generation, adult longevity was reduced by approximately 3 d, adult size by approximately 5%, egg load by approximately 24%, and rate of gain of longevity with adult size by approximately 21%, whereas effects were not evident on the rate of gain of egg load with adult size. It was concluded that although GNA transgenic sugarcane, ingested via E. loftini tissues, was not acutely toxic to P. pyralophagus, the sublethal effects on life history parameters measured in this study must be considered in a broader context to determine their possible ecological significance.


Self-cleaning and mechanical properties of modified white cement with nanostructured TiO2.
In the present study, self-cleaning and mechanical properties of white Portland cement by addition of commercial available TiO2 nanoparticles with the average particle size of 80 nm were investigated. X-ray diffraction (XRD), transmission electron microscopy (TEM) and BET were used to characterize TiO2 nanoparticles. For determination of self-cleaning properties of TiO2-modified white cement, colorimetric tests in decolorization of C.I. Basic Red 46 (BR46) in comparison to unmodified cement samples was applied. The results indicated that with increasing the amount of TiO2 nanoparticles in modified cement, self-cleaning property of the samples increased. The mechanical properties of TiO2-modified and unmodified cement samples, such as time of setting of hydraulic cement, compressive strength of hydraulic cement mortar and flexural strength of hydraulic cement mortar were examined. The results indicated that addition of TiO2 nanoparticles up to maximum replacement level of 1.0% improved compressive and flexural strength and decreased its setting time.


Calprotectin and lactoferrin faecal levels in patients with Clostridium difficile infection (CDI): a prospective cohort study.
Measurement of both calprotectin and lactoferrin in faeces has successfully been used to discriminate between functional and inflammatory bowel conditions, but evidence is limited for Clostridium difficile infection (CDI). We prospectively recruited a cohort of 164 CDI cases and 52 controls with antibiotic-associated diarrhoea (AAD). Information on disease severity, duration of symptoms, 30-day mortality and 90-day recurrence as markers of complicated CDI were recorded. Specimens were subject to microbiological culture and PCR-ribotyping. Levels of faecal calprotectin (FC) and lactoferrin (FL) were measured by ELISA. Statistical analysis was conducted using percentile categorisation. ROC curve analysis was employed to determine optimal cut-off values. Both markers were highly correlated with each other (r2 = 0.74) and elevated in cases compared to controls (p<0.0001; ROC>0.85), although we observed a large amount of variability across both groups. The optimal case-control cut-off point was 148 mg/kg for FC and 8.1 ng/µl for FL. Median values for FL in CDI cases were significantly greater in patients suffering from severe disease compared to non-severe disease (104.6 vs. 40.1 ng/µl, p = 0.02), but were not significant for FC (969.3 vs. 512.7 mg/kg, p = 0.09). Neither marker was associated with 90-day recurrence, prolonged CDI symptoms, positive culture results and colonisation by ribotype 027. Both FC and FL distinguished between CDI cases and AAD controls. Although FL was associated with disease severity in CDI patients, this showed high inter-individual variability and was an isolated finding. Thus, FC and FL are unlikely to be useful as biomarkers of complicated CDI disease.


A Comprehensive, Ethnically Diverse Library of Sickle Cell Disease-Specific Induced Pluripotent Stem Cells.
Sickle cell anemia affects millions of people worldwide and is an emerging global health burden. As part of a large NIH-funded NextGen Consortium, we generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs) from patients of different ethnicities, β-globin gene (HBB) haplotypes, and fetal hemoglobin (HbF) levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients. Here, we describe this unique resource for the study of sickle cell disease, including novel haplotype-specific polymorphisms that affect disease severity, as well as for the development of patient-specific therapeutics for this phenotypically diverse disorder. As a complement to this library, and as proof of principle for future cell- and gene-based therapies, we also designed and employed CRISPR/Cas gene editing tools to correct the sickle hemoglobin (HbS) mutation.


H-ras oncogene mutation in dedifferentiated liposarcoma. Polymerase chain reaction-restriction fragment length polymorphism analysis.
Point mutations of the ras gene family (K-ras, H-ras, and N-ras) are thought to be involved in the development of a variety of human tumors. Dedifferentiated liposarcoma is characterized by the coexistence of well-differentiated (WD) and high-grade anaplastic (HG) components. The presence of point mutations at codons 12 and 13 of the H-ras gene was studied in 34 liposarcomas, comprising 15 well-differentiated liposarcomas and 19 dedifferentiated liposarcomas, and in 8 storiform-pleomorphic type malignant fibrous histiocytomas (MFHs) using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing analysis. The 2 components of dedifferentiated liposarcoma were analyzed independently. H-ras mutations were seen only in dedifferentiated liposarcomas (4/19 [21%]), 1 in WD components and 3 in HG components. The mutation was not seen in any of 15 cases of well-differentiated liposarcoma. MFHs showed an H-ras mutation in 1 (12%) of 8 cases. Our results seem to suggest that the H-ras mutation is a relatively uncommon event in dedifferentiated liposarcoma, which may demonstrate an epiphenomenon of dedifferentiation in dedifferentiated liposarcoma.


Lighting conditions alter Candida albicans-induced sleep responses in rabbits.
To evaluate the influence of light on sleep patterns after microbial challenge, we studied rabbits housed in 12:12-h light-dark (LD), constant light (LL), or constant darkness (DD) before and after intravenous Candida albicans inoculation. Compared with the LD group, uninoculated LL rabbits sporadically increased slow-wave sleep and delta-wave amplitudes during the circadian period previously associated with the dark phase. In contrast, uninfected DD rabbits showed reduced sleep during the circadian period previously associated with the light phase. Inoculation of LD rabbits with Candida approximately 2 h after light onset increased slow-wave sleep and delta-wave amplitudes during hours 4-8 postinoculation and reduced these parameters during hours 20-46. In contrast, Candida-inoculated LL rabbits demonstrated increased slow-wave sleep for up to 28 h after inoculation, with little subsequent reduction; delta-wave amplitudes were similar to those of LD rabbits. Candida-inoculated DD rabbits demonstrated attenuated increases in slow-wave sleep and delta-wave amplitudes, but the suppression phase was not altered. We conclude that lighting conditions modulate microbially induced sleep alterations.


A culture of care: the French approach to cardiovascular risk factor management.
The objective of this study was to describe French primary care physicians' beliefs about cardiovascular disease (CVD) risk factors and best practices for managing CVD. This study comprised a purposive convenience sample of 656 primary care physicians in France, recruited from contacts made through the French Society of General Medicine. We compiled the physicians' responses to free text questions taken from an Internet-based survey and analyzed them using a qualitative approach. Physician's responses were inductively analyzed using content analysis. Responses were thematically coded, tabulated, and computed for frequencies. Overall themes and verbatim examples are presented in this article. The French physicians in our study are generally happy with their country's health care system and cite equity as the primary reason. Interestingly, along with food and lifestyle differences, they also cite equity of their health system as the reason for the lower CVD death rate in France, Japan, and Israel compared with the United States. The physicians believe that they are successful at managing CVD risk factors by emphasizing aspects of the doctor-patient relationship, including spending more time with patients and focusing on education. Physicians who are on the front line of care and management offer a fresh perspective on best practices for CVD prevention and management. The equity of the French health care system supports a "culture of care" in France that might lead to better outcomes for CVD risk factor patients than in the United States.