Bone marrow-derived CXCR4+ cells mobilized by macrophage colony-stimulating factor participate in the reduction of infarct area and improvement of cardiac remodeling after myocardial infarction in mice.
The monocyte/macrophage lineage might affect the healing process after myocardial infarction (MI). Because macrophage colony-stimulating factor (M-CSF) stimulates differentiation and proliferation of this lineage, we examined the effect of M-CSF treatment on infarct size and left ventricular (LV) remodeling after MI. MI was induced in C57BL/6J mice by ligation of the left coronary artery. Either recombinant human M-CSF or saline was administered for 5 consecutive days after MI induction. M-CSF treatment significantly reduced the infarct size (P < 0.05) and scar formation (P < 0.05) and improved the LV dysfunction (percent fractional shortening, P < 0.001) after the MI. Immunohistochemistry revealed that M-CSF increased macrophage infiltration (F4/80) and neovascularization (CD31) of the infarct myocardium but did not increase myofibroblast accumulation (alpha-smooth muscle actin). M-CSF mobilized CXCR4(+) cells into peripheral circulation, and the mobilized CXCR4(+) cells were then recruited into the infarct area in which SDF-1 showed marked expression. The CXCR4 antagonist AMD3100 deteriorated the infarction and LV function after the MI in the M-CSF-treated mice. In conclusion, M-CSF reduced infarct area and improved LV remodeling after MI through the recruitment of CXCR4(+) cells into the infarct myocardium by the SDF-1-CXCR4 axis activation; this suggests that the SDF-1-CXCR4 axis is as a potential target for the treatment of MI.


Endodontic length determination--what lengths should we go to?
There is much controversy in the dental literature and among clinicians regarding the ideal length of preparation in endodontic treatment and how this should be determined. The differing opinions are summarized and the methods of length determination described, along with their advantages and disadvantages. Practitioners are encouraged to familiarize themselves with all the available techniques and select the most appropriate for each case.


Differential expression of angiogenesis associated genes in prostate cancer bone, liver and lymph node metastases.
Our objective was to elucidate phenotypic differences between prostate cancer (PCa) liver, lymph node, and bone metastases. PCa metastases were obtained through a rapid tissue acquisition necropsy protocol. We grossly dissected metastatic foci from frozen samples and performed expression analyses using cDNA microarrays. Immunohistochemical analyses using a tissue microarray from thirty individuals with PCa metastases to lymph nodes, liver, and bone was used to confirm the gene expression changes associated with each metastatic site. Transcript alterations statistically-associated with bone metastases included increased expression of IBSP (Bone sialoprotein), F13A1 (factor XIII), and decreased expression of EFNA1 (ephrin-A1) and ANGPT2 (angiopoietin-2) when compared to liver and lymph node metastases. The metastasis-associated changes in proteins involved in coagulation and angiogenesis prompted further analysis of additional factors known to participate in the clotting cascade and blood vessel formation (angiopoitein-1, PAI-1, uPA, PAI-RBP-1 and hepsin). We also assessed tumor-associated microvessel density and distribution in liver, lymph node, and bone metastasis. Intense fibrin(ogen) and fibulin-1 staining was localized to epithelial cells at the periphery of metastatic tumors possibly to facilitate angiogenesis. The expression of hepsin, uPA, PAI-RBP1, PAI-1, and factor XIII may influence fibrinolysis and are regulated by the tumor microenvironment. The expression of angiopoietin-2 and apparent silencing of angiopoietin-1 in PCa bone, liver, and lymph node metastases may be critical for angiogenesis in this tumor type. In addition, the resulting tumor-associated microvessel density and distribution was significantly different between liver and bone metastasis possibly in response to the protein expression changes detailed above.


Repurposing of Cetuximab in antibody-directed chemotherapy-loaded nanoparticles in EGFR therapy-resistant pancreatic tumours.
The anti-Epidermal Growth Factor Receptor (EGFR) antibody Cetuximab (CTX) has demonstrated limited anti-cancer efficacy in cells overexpressing EGFR due to activating mutations in RAS in solid tumours, such as pancreatic cancer. The utilisation of antibodies as targeting components of antibody-drug conjugates, such as trastuzumab emtansine (Kadcyla), demonstrates that antibodies may be repurposed to direct therapeutic agents to antibody-resistant cancers. Here we investigated the use of CTX as a targeting agent for camptothecin (CPT)-loaded polymeric nanoparticles (NPs) directed against KRAS mutant CTX-resistant cancer cells. CPT was encapsulated within poly(lactic-co-glycolic acid) (PLGA) NPs using the solvent evaporation method. CTX conjugation improved NP binding and delivery of CPT to CTX-resistant cancer cell lines. CTX successfully targeted CPT-loaded NPs to mutant KRAS PANC-1 tumours in vivo and reduced tumour growth. This study highlights that CTX can be repurposed as a targeting agent against CTX-resistant cancers and that antibody repositioning may be applicable to other antibodies restricted by resistance.


A comparison of diagnoses obtained from in-person and telephone interviews, using the semi-structured assessment for the genetics of alcoholism (SSAGA).
The aim of this study was to compare the prevalence of psychiatric diagnoses when the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA-II) interview was administered in person with the prevalence when the SSAGA-II was conducted by telephone. As part of the Collaborative Studies on the Genetics of Alcoholism, SSAGAs were administered either by telephone (n = 1,294) or in person (n = 1,484) to adult relatives of probands (42.3% male). The two modes of interview were compared with respect to reported lifetime prevalence of (1) Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol dependence; (2) other DSM-IV substance-dependence diagnoses (nicotine, marijuana, cocaine, opioid, stimulant, sedative); and (3) DSM-IV nonsubstance diagnoses (i.e., antisocial personality disorder, major depressive disorder, mania, panic, social phobia, obsessive-compulsive disorder, and generalized anxiety disorder). These analyses took into account the potential confounds of gender, age, race, education, income, marital status, and potential within-family correlation. Diagnostic prevalence rates for alcohol dependence and major depressive disorder were lower for telephone interviews than for in-person interviews (7% and 2%, respectively); there were no other significant differences. When circumstances dictate (e.g., subject out of area, subject preference), telephone administration of the SSAGA should be considered.


Cases of Pernio-Like Lesions after mRNA-1273 Vaccination with Clinical and Pathological Features: A Single-Center Experience.
The currently available coronavirus disease 2019 (COVID-19) vaccines in South Korea include mRNA (Moderna® and Pfizer®) and adenoviral vector (AstraZeneca® and Janssen®) vaccines. Dermatologic side effects of COVID-19 vaccines range from local injection site reactions to systemic eruptions, including morbilliform rashes or erythema multiforme. Pernio-like lesions, one of the most common cutaneous manifestations of COVID-19, have been rarely reported post-vaccination. Herein, we report four cases of pernio-like lesions, which were detected in a single tertiary hospital within 2 months, after the first dose of mRNA-1273 (Moderna®) vaccination was administered. In this study, we discuss the clinical and pathological features of our cases and compare them with those of previously reported cases of pernio-like lesions after COVID-19 vaccination. It is pivotal to realize that perniolike lesions can be a possible side effect of COVID-19 vaccination and that the number of patients experiencing this side effect is bound to be quite high in real-world clinical settings.


Pathologic nystagmus: a classification based on electro-oculographic recordings.
The widespread availability of eye movement recording systems has added a new dimension to our ability to accurately describe nystagmus. Electrooculography (EOG) is the simplest and most readily available system. With EOG the effect of loss of fixation (either with eyes closed, or eyes open in darkness) can be accurately assessed and quantitative evaluation of nystagmus speed, frequency and amplitude is easily made. Of equal importance, it provides a permanent record that can be compared with nystagmus recorded in other patients. By comparing clinical observation with paper recordings, both students and experienced clinicians can become more efficient in recognizing different varieties of nystagmus.


Muscle ultrasonography for detecting fasciculations in frontotemporal dementia.
Ultrasound detection of muscle fasciculations was recently proposed for assessing lower motor neuron (LMN) dysfunction in ALS patients. Given the continuum between ALS and frontotemporal degeneration (FTD), the aim of the present study was to evaluate muscle ultrasound (MUS) in FTD both for feasibility and prevalence of fasciculations. Twenty-two FTD patients were examined (five muscles bilaterally: biceps brachii, first dorsalis interosseous, T10 paraspinalis, vastus lateralis, tibialis anterior) with a 7-MHz linear array transducer and a fasciculation score (FS) computed. Twenty-two matched cognitively-intact control subjects and six ALS patients were also included. Results showed that MUS was feasible, reliable and well tolerated in all subjects. Two FTD/MND patients displayed very high FS values, similar to those in ALS patients. The remaining 20 FTD patients displayed a mean FS value significantly higher than the control group with six patients (30%) having FS values out of the range of controls. Disease progression rate correlated with the FS. In conclusion, MUS can be easily applied to FTD patients and represents a non-invasive technique for defining LMN involvement in these patients. LMN dysfunction is a frequent condition in FTD and might identify a subset of patients with a different clinical course.


Antithrombotic Treatment in Coronary Artery Disease.
Coronary artery disease exhibits a growing mortality and morbidity worldwide despite the advances in pharmacotherapy and coronary intervention. Coronary artery disease is classified as the acute coronary syndromes and chronic coronary syndromes according to the most recent guidelines of the European Society of Cardiology. Antithrombotic treatment is the cornerstone of therapy in coronary artery disease due to the involvement of atherothrombosis in the pathophysiology of the disease. Administration of antiplatelet agents, anticoagulants and fibrinolytics reduce ischemic risk, which is amplified early post-acute coronary syndromes or post percutaneous coronary intervention; though, antithrombotic treatment increases the risk for bleeding. The balance between ischemic and bleeding risk is difficult to achieve and is affected by patient characteristics, procedural parameters, concomitant medications and pharmacologic characteristics of the antithrombotic agents. Several pharmacological strategies have been evaluated in patients with coronary artery disease, such as the effectiveness and safety of antithrombotic agents, optimal dual antiplatelet treatment schemes and duration, aspirin de-escalation strategies of dual antiplatelet regimens, dual inhibition pathway strategies as well as triple antithrombotic therapy. Future studies are needed in order to shed light on the gaps in our knowledge, including special populations.


Depression Prevalence and Exposure to Organophosphate Esters in Aircraft Maintenance Workers.
Previous studies found that aircraft maintenance workers may be exposed to organophosphates in hydraulic fluid and engine oil. Studies have also illustrated a link between long-term low-level organophosphate pesticide exposure and depression. A questionnaire containing the Patient Health Questionnaire 8 depression screener was e-mailed to 52,080 aircraft maintenance workers (with N = 4801 complete responses) in a cross-sectional study to determine prevalence and severity of depression and descriptions of their occupational exposures. There was no significant difference between reported depression prevalence and severity in similar exposure groups in which aircraft maintenance workers were exposed or may have been exposed to organophosphate esters compared to similar exposure groups in which they were not exposed. However, a dichotomous measure of the prevalence of depression was significantly associated with self-reported exposure levels from low (OR: 1.21) to moderate (OR: 1.68) to high exposure (OR: 2.70) and with each exposure route including contact (OR: 1.68), inhalation (OR: 2.52), and ingestion (OR: 2.55). A self-reported four-level measure of depression severity was also associated with a self-reported four-level measure of exposure. Based on self-reported exposures and outcomes, an association is observed between organophosphate exposure and depression; however, we cannot assume that the associations we observed are causal because some workers may have been more likely to report exposure to organophosphate esters and also more likely to report depression. Future studies should consider using a larger sample size, better methods for characterizing crew chief exposures, and bioassays to measure dose rather than exposure. Hardos JE, Whitehead LW, Han I, Ott DK, Waller DK. Depression prevalence and exposure to organophosphate esters in aircraft maintenance workers. Aerosp Med Hum Perform. 2016; 87(8):712-717.


[ANALYZING THE IMPACT OF HEALTH-SAVING TECHNOLOGIES ON THE LIFE QUALITY OF THE ELDERLY URBAN POPULATION WITH MULTIMORBIDITY (EXEMPLIFIED BY PATIENTS WITH ACUTE LOWER LIMB ISCHEMIA)].
As the population ages, the prevalence of chronic diseases increases and, accordingly, the probability of simultaneous occurrence of many chronic diseases among the elderly population increases, which affects the dynamics and prognoses of the underlying disease. Prevention of complications of concomitant semantics for the underlying disease seems to be a complex medical problem, the solution to which is aimed at improving the quality of life of patients. Based on the data obtained, the effect of polymorbidity on the course of acute lower limb ischemia (ALLI) was studied in the elderly urban population. The purpose of the study is to analyze the effect of multimorbidity on the life quality of the elderly urban population, exemplified by patients with acute lower limb ischemia. 91 patients with ALLI (n=91) were examined, the mean age equaled to 70±1.2 years, with thromboembolism against the background of arterial occlusion. The age of patients is one of the highest risks and must be taken into account when deciding on surgical intervention and further therapy for ALLI. The study had no administrative restrictions. It was found that the value of the comorbidity index in patients with acute lower limb ischemia is associated with the severity of the underlying disease and characterizes the predicted decrease in the probability of a 10-year survival and the risk of death.


Addressing the interaction between food insecurity, depression risk and informal work: findings of a cross-sectional survey among informal women workers with young children in South Africa.
There is a high burden of depression globally, including in South Africa. Maternal depression is associated with poverty, unstable income, food insecurity, and lack of partner support, and may lead to poor outcomes for mothers and children. In South Africa one-third of working women are in informal work, which is associated with socioeconomic vulnerability. A cross sectional survey explored work setting and conditions, food security and risk of depression among informal working women with young children (0-3 years). Depression risk was assessed using the Edinburgh Postnatal Depression Score (EPDS) and Whooley score. Food insecurity was evaluated using Household Food Insecurity Access Scale. Data was analysed using SPSS and Stata. Interviews were conducted with 265 informal women workers. Types of work included domestic work, home-based work, informal employees and own account workers, most of whom were informal traders. Most participants (149/265; 56.2%) earned between US$70-200 per month, but some participants (79/265; 29.8%) earned < US$70 per month, and few earned > US$200 per month (37/265; 14.0%). Many participants experienced mild (38/267; 14.3%), moderate (72/265; 27.2%) or severe (43/265; 16%) food insecurity. Severe food insecurity was significantly higher among participants with the lowest income compared to those with the highest income (p = 0.027). Women who received financial support from the baby's father were less likely to be food insecure (p = 0.03). Using EPDS scores, 22/265 (8.3%) women were designated as being at risk of depression. This was similar among postnatal women and women with older children. Household food insecurity was significantly associated with depression risk (p < 0.001). Informal women workers were shown to be vulnerable with low incomes and high rates of food insecurity, thus increasing the risk for poor maternal health. However, levels of depression risk were low compared to previous estimates in South Africa, suggesting that informal workers may have high levels of resilience. Interventions to improve social protection, access to health services, and support for safe childcare in the workplace could improve the health and wellbeing of these mothers and support them to care for their children.


Geothrix fermentans secretes two different redox-active compounds to utilize electron acceptors across a wide range of redox potentials.
The current understanding of dissimilatory metal reduction is based primarily on isolates from the proteobacterial genera Geobacter and Shewanella. However, environments undergoing active Fe(III) reduction often harbor less-well-studied phyla that are equally abundant. In this work, electrochemical techniques were used to analyze respiratory electron transfer by the only known Fe(III)-reducing representative of the Acidobacteria, Geothrix fermentans. In contrast to previously characterized metal-reducing bacteria, which typically reach maximal rates of respiration at electron acceptor potentials of 0 V versus standard hydrogen electrode (SHE), G. fermentans required potentials as high as 0.55 V to respire at its maximum rate. In addition, G. fermentans secreted two different soluble redox-active electron shuttles with separate redox potentials (-0.2 V and 0.3 V). The compound with the lower midpoint potential, responsible for 20 to 30% of electron transfer activity, was riboflavin. The behavior of the higher-potential compound was consistent with hydrophilic UV-fluorescent molecules previously found in G. fermentans supernatants. Both electron shuttles were also produced when cultures were grown with Fe(III), but not when fumarate was the electron acceptor. This study reveals that Geothrix is able to take advantage of higher-redox-potential environments, demonstrates that secretion of flavin-based shuttles is not confined to Shewanella, and points to the existence of high-potential-redox-active compounds involved in extracellular electron transfer. Based on differences between the respiratory strategies of Geothrix and Geobacter, these two groups of bacteria could exist in distinctive environmental niches defined by redox potential.


Dispersion interactions between neighboring Bi atoms in (BiH3 )2 and Te(BiR2 )2.
Triggered by the observation of a short Bi⋯Bi distance and a BiTeBi bond angle of only 86.6° in the crystal structure of bis(diethylbismuthanyl)tellurane quantum chemical computations on interactions between neighboring Bi atoms in Te(BiR2 )2 molecules (R = H, Me, Et) and in (BiH3 )2 were undertaken. Bi⋯Bi distances atoms were found to significantly shorten upon inclusion of the d shells of the heavy metal atoms into the electron correlation treatment, and it was confirmed that interaction energies from spin component-scaled second-order Møller-Plesset theory (SCS-MP2) agree well with coupled-cluster singles and doubles theory including perturbative triples (CCSD(T)). Density functional theory-based symmetry-adapted perturbation theory (DFT-SAPT) was used to study the anisotropy of the interplay of dispersion attraction and steric repulsion between the Bi atoms. Finally, geometries and relative stabilities of syn-syn and syn-anti conformers of Te(BiR2 )2 (R = H, Me, Et) and interconversion barriers between them were computed. © 2018 Wiley Periodicals, Inc.


"I just stand around and look friendly" - Comparing medical students' and physicians' ward round scripts.
Even though ward rounds are important learning opportunities for medical students, unfavourable ward round scripts of students and physicians may hinder learning in such situations. We investigated medical students' and physicians' ward round scripts with respect to (a) the content focus of ward round activities, and (b) the potential of these activities for knowledge construction. We conducted standardized interviews with 50 medical students and physicians in internal medicine at different expertise stages. Activities participants labelled as typical for ward rounds were coded with respect to their content focus and their potential with regard to knowledge construction. Regarding content focus, especially residents mainly named activities bound to patient care. Teaching- and learning-related activities were very rare, but more frequently mentioned by students and more experienced physicians. With respect to potential for knowledge construction, students regarded significantly more passive activities (= low potential for knowledge construction) as typical for ward rounds, especially when they described their own role. Medical students should be supported in their development of conceiving ward rounds as valuable learning opportunities. Residents should be asked to take their teaching responsibility seriously, for example by demanding an active engagement of the students during ward rounds.


Deformable Face Fitting with Soft Correspondence Constraints.
Despite significant progress in deformable model fitting over the last decade, the problem of efficient and accurate person-independent face fitting remains a challenging problem. In this work, a reformulation of the generative fitting objective is presented, where only soft correspondences between the model and the image are enforced. This has the dual effect of improving robustness to unseen faces as well as affording fitting time which scales linearly with the model's complexity. This approach is compared with three state-of-the-art fitting methods on the problem of person independent face fitting, where it is shown to closely approach the accuracy of the currently best performing method while affording significant computational savings.


The role of intelligence in posttraumatic stress disorder: does it vary by trauma severity?
Only a small minority of trauma victims develops post-traumatic stress disorder (PTSD), suggesting that victims vary in their predispositions to the PTSD response to stressors. It is assumed that the role of predispositions in PTSD varies by trauma severity: when stressors are less severe, predispositions play a bigger role. In this study, we test whether the role of intelligence in PTSD varies by trauma severity. Specifically, does low intelligence plays a bigger part among victims of lower magnitude stressors than among victims of extreme stressors? Data come from a longitudinal study of randomly selected sample in Southeast Michigan (n = 713). IQ was measured at age 6. PTSD was measured at age 17, using the NIMH-DIS for DSM-IV. Stressors were classified as extreme if they involved assaultive violence (e.g. rape, sexual assault, threatened with a weapon); other stressors in the list (e.g. disaster, accidents) were classified as lower magnitude. Assaultive violence victims had experienced assaultive violence plus other event types or only assaultive violence. Victims of other stressors were participants who had never experienced assaultive violence. We compared the influence of age 6 IQ on PTSD among persons exposed to assaultive violence vs. other stressors, using multinomial logistic regression. Relative risk ratio (RRR) for PTSD associated with a one point drop in age 6 IQ among victims of assaultive violence was 1.04 (95% CI 1.01, 1.06); among victims of other stressors, it was 1.03 (95% CI 0.99, 1.06). A comparison of the two RRRs indicates no significant difference between the two estimates (p = 0.652). IQ does not play a bigger role in PTSD among victims of other stressors than it does among victims of assaultive violence. Lower IQ exerts an adverse PTSD effect on trauma victims, with no evidence of variability by the severity of trauma they have experienced.


Epidemiological features and determinants for Chlamydia trachomatis infection among women in Catalonia, Spain.
We determined the prevalence of Chlamydia trachomatis (CT) infection and risk factors for its acquisition by women aged less than 35 years who were attending sexual health centres in the province of Barcelona in 2007. A convenience sample of 397 adolescents and young adult women aged between 16 and 35 years, stratified by age and recruitment site, were tested using realtime polymerase chain reaction by CT DNA. A standardized questionnaire was used to collect epidemiological and behavioural data on the participants, which were analysed in a multivariate logistic regression model. The overall prevalence of CT was 4%, significantly higher in those under 25 years of age (5.8% versus 1.6% over 25). The independent risk factors for CT infection were: foreign origin (odds ratio [OR] 4.7; confidence interval [CI] 1.02-21.8), having had a sexual partner in the last three months (OR 4.59; CI 1.16-18.08) and tobacco use the last 12 months (OR 6.38; CI 1.16-34.93). In conclusion, this is the first study performed in Catalonia showing a high prevalence of CT in young women, consistent with trends in the rest of Europe. Systematic monitoring of CT infection in sentinel populations such as this will inform future targeted screening programmes in our setting.


Thymic microenvironmental factor: a possible chemoattractant for hemopoietic stem cells.
A thymic microenvironmental factor (TMF), distinct from thymic epithelial supernatant, was extracted from membranes of thymic stromal cells. Using a migration-under-agar assay, we showed that hematopoietic stem cells from fetal liver could migrate specifically towards TMF. Fetal thymic rudiments, which are known to attract such cells, can compete for TMF activity in this test. An antibody to TMF inhibited TMF activity. Bone marrow cells and peritoneal macrophages were not specifically attracted towards TMF. We also showed that TMF-attracted cells can colonize embryonic thymic rudiments.


Determination of delay in burn around time (TAT) of stat tests and its causes: an AKUH experience.
To evaluate the delay and reasons of delay of turn around time (TAT) of stat tests in the section of clinical chemistry of the clinical laboratory. Clinical Laboratory, Aga Khan University Hospital, Karachi. In our study turn around time (TAT) of stat tests were analyzed. Turn around time was specified as the time from receipt of the sample till the final verification of results (sample receipt time to result verification time). Delays were categorized into 15 minutes, 16-30 minutes, 31 to 60 minutes and > 60 minutes. It was also noted as to which time of the day was delay in reporting stat results occurred. Reasons for the delay were also looked into. Total 20079 stat samples were received from August 2001 till October 2001. Four hundred eight (2.03%) samples were reported after the acceptable turnaround time. Cumulative analysis of the excess TAT of stat tests showed that 0-15 minutes delay was noted in 68 (16.7%) samples, 16-30 minutes delay in 80(19.6%) samples, 31-60 minutes delay in 76 (18.6%) samples as and more than 60 minutes delay in 185 (45.3%) of samples. Most of the delay in reporting of stat test in three months time was surprisingly noted in the morning shift. Overall delay in reporting in morning shift was found to be of 242 (59.3%) samples. In the evening and night shift 83 (20.3%) and 82 (20.1%) samples respectively were found to be delayed. Reasons for delay in TAT were as follows: n = 163 (40%) due to machine breakdown, n = 147(36%) due to delay in the maintenance of analyzers, n = 73 (18%) due to overlook of the staff during shift change (e.g. night shift to morning shift) and n = 25 (6%) due to computer shutdown. We conclude that most of the delay in TAT of stat tests in our laboratory occurred for more than 60 minutes and was frequently seen in the morning shift. It was also noticed that machine breakdown was the most common reason for this delay. Regular audit of such data helps in the evaluation of the efficiency of the laboratory and hence corrective measures taken accordingly would be helpful in providing better service to the physicians and patients.


Patient satisfaction following dental implant treatment with immediate loading in the edentulous atrophic maxilla.
The present study evaluated patient satisfaction using the Oral Health Impact Profile 49 (OHIP-49) questionnaire for patients who received six implants in the severely resorbed maxilla and an implant-supported prosthesis that was delivered within 24 hours after surgery. Fifty-one edentulous patients with severe atrophy in the maxilla were included in the study, which was performed at two centers. Six implants were placed in the maxilla and loaded within 24 hours with a provisional restoration. The definitive restorations were delivered 20 to 24 weeks later. Patients were asked to complete the OHIP-49 questionnaire (which includes seven domains representing functional limitation, physical pain, psychologic discomfort, physical disability, psychologic disability, social disability, and handicap) prior to implant placement and on three subsequent occasions. The data were collected and analyzed and OHIP scores were compared over time. Baseline satisfaction scores for the two different centers displayed no statistically significant differences. Treatment resulted in improved total OHIP-49 scores in both centers, with no significant difference between centers. Furthermore, no significant differences were observed in any of the individual pretreatment and posttreatment OHIP-49 domains between centers. All seven domains showed a statistically significant improvement posttreatment. Of the seven domains, social disability and handicap showed the least improvement and had the lowest pretreatment scores, indicating lower significance for these domains compared to the other domains during implant treatment. This study also indicated that domains one to five (functional limitation, physical pain, psychologic discomfort, physical disability, and psychologic disability) are the most important domains in patient satisfaction with implant therapy. Measurement with the OHIP-49 questionnaire displayed that patient satisfaction increases after treatment with a fixed restoration on implants loaded within 24 hours.


Soft Printable Electrode Coating for Neural Interfaces.
The mechanical mismatch between implantable interfaces and neural tissues may be reduced by employing soft polymeric materials. Here, we report on a simple strategy to prepare and pattern a soft electrode coating of neural interfacing devices based on a screen-printable conducting hydrogel. The coating formulation, based on polyacrylamide and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate, is suitable to additive manufacturing and exhibits excellent adhesion to polydimethylsiloxane, an elastomer commonly used as a substrate in soft neural interfaces. The soft conductive coating displays a tunable elastic modulus in the 10-100 kPa range and electrochemical properties on a par with stiff conductive inks while supporting good neural cell attachment and proliferation in vitro. Next, the soft printable hydrogel is integrated within a 4 × 4 microelectrode array for electrocorticography with 250 μm-diameter contacts. Acute recording of cortical local field potentials and electrochemical characterization preimplantation and postimplantation highlight the stability of the soft organic conductor. The overall robustness of the soft coating and its patterning method provide a promising route for a range of implantable bioelectronic applications.


Photocatalytic reduction of carbon dioxide over Ag cocatalyst-loaded ALa4Ti4O15 (A = Ca, Sr, and Ba) using water as a reducing reagent.
Ag cocatalyst-loaded ALa(4)Ti(4)O(15) (A = Ca, Sr, and Ba) photocatalysts with 3.79-3.85 eV of band gaps and layered perovskite structures showed activities for CO(2) reduction to form CO and HCOOH by bubbling CO(2) gas into the aqueous suspension of the photocatalyst powder without any sacrificial reagents. Ag cocatalyst-loaded BaLa(4)Ti(4)O(15) was the most active photocatalyst. A liquid-phase chemical reduction method was better than impregnation and in situ photodeposition methods for the loading of the Ag cocatalyst. The Ag cocatalyst prepared by the liquid-phase chemical reduction method was loaded as fine particles with the size smaller than 10 nm on the edge of the BaLa(4)Ti(4)O(15) photocatalyst powder with a plate shape during the CO(2) reduction. CO was the main reduction product rather than H(2) even in an aqueous medium on the optimized Ag/BaLa(4)Ti(4)O(15) photocatalyst. Evolution of O(2) in a stoichiometric ratio (H(2)+CO:O(2) = 2:1 in a molar ratio) indicated that water was consumed as a reducing reagent (an electron donor) for the CO(2) reduction. Thus, an uphill reaction of CO(2) reduction accompanied with water oxidation was achieved using the Ag/BaLa(4)Ti(4)O(15) photocatalyst.


Trends in tuberculosis incidence and mortality coefficients in Brazil, 2011-2019: analysis by inflection points.
To analyze the temporal trend of tuberculosis incidence and mortality rates in Brazil between 2011 and 2019. This was an ecological time series study of tuberculosis incidence and mortality rates in Brazil between 2011 and 2019. Data were extracted from the Notifiable Disease Information System and the Mortality Information System, and population estimates were from the Brazilian Institute of Geography and Statistics. Trends were analyzed by Joinpoint regression, which recognizes inflection points for temporal analysis. The average incidence rate of tuberculosis in Brazil in the period was 35.8 cases per 100 000 population. From 2011 to 2015, this coefficient had an annual percentage change of -1.9% (95% CI [-3.4, -0.5]) followed by an increase of 2.4% (95% CI [0.9, 3.9]) until 2019. The average mortality rate between 2011 and 2019 was 2.2 deaths per 100 000 population, with an average annual percentage change of -0.4% (95% CI [-1.0, 0.2]). Amazonas was the only state with an increase in the annual average percentage variation for the incidence rate (3.2%; 95% CI [1.3, 5.1]) and mortality rate (2.7%; 95% CI [1.0, 4.4]) over the years, while Rio de Janeiro state had an increasing inflection for incidence from 2014 to 2019 (2.4%; 95% CI [1.4, 3.5]) and annual average of decreasing percentage variation (-3.5%; 95% CI [-5.0, -1.9]). During the period analyzed, a decreasing trend in incidence was observed between 2011 and 2015, and an increasing trend for the period from 2015 to 2019. On the other hand, no change in the trend for mortality was found in Brazil.


Lessons from animal models of osteoarthritis.
Animal models of osteoarthritis (OA) provide valuable insight into pathogenetic pathways. Although OA is not an inflammatory disease, synovial activation clearly plays a role. Matrix metalloproteinases 3 (stromelysin) and 13 (collagenase) appear crucial, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5-mediated aggrecan cleavage in the interglobular domain is key in OA cartilage damage. Apart from cytokines, chondrocyte derangement or hypertrophy may contribute. Enhanced discoidin domain receptor-2 expression is found in OA models and human OA. Moreover, deficiency of Runt-related transcription factor-2 ameliorates murine OA. The abundant transforming growth factor-beta prevents chondrocyte hypertrophy. Age-related loss of proper transforming growth factor-beta signaling, with a major drop in SMAD-2 phosphorylation, may contribute to hypertrophy and subsequent development of OA cartilage pathology. Finally, transgenic mice show that osteoprotegerin is protective in OA, and treatment studies with recombinant osteoprotegerin have identified chondrocyte apoptosis blocking as an underlying mechanism.


Expression and characterization of the human erythrocyte anion exchanger in a baculovirus/Sf-9 cell system.
The human erythrocyte anion-exchange protein (HAE1) has been expressed in insect Sf-9 cells using a recombinant baculovirus. We subcloned the full-length cDNA encoding HAE1 into the baculovirus expression vector pVL1392 and cotransfected Sf-9 cells with the recombinant vector and wild-type AcMNPV DNA to obtain recombinant baculovirus. The expressed protein was targeted to the Sf-9 plasma membrane at an apparent density of approximately 0.5 x 10(6) copies/cell as determined by quantitative autoradiography using an HAE1-specific monoclonal antibody. Unlike native HAE1, the expressed protein was not glycosylated. Transport studies with HAE1-recombinant-infected Sf-9 cells showed saturable [Km(Cl-) = 44 mM; Vmax(Cl-) = 48 mEq/liter of cell waters min] and H2DIDS-inhibitable (K(O.5) = 34 microM) 36Cl- uptake that was not present in uninfected cells. We also found that extracellular SO4(2-) reduced 36Cl- influx [K(0.5)((SO4)2-) = 26 mM], presumably through substrate competition as in erythrocytes. Finally, we observed that H2DIDS-inhibitable 36Cl- efflux was reduced by 77% in the nominal absence of a suitable counter-anion in the external solution (HCO3(-)-free, all-glucuronate medium), thereby providing strong evidence for an obligatory exchange mechanism. We conclude that there is high-level expression of + ++HAE1 functional activity in recombinant baculovirus-infected Sf-9 cells and that this system will prove useful for kinetic and structural analyses of the HAE1 protein.


Logarithmic sensing in Bacillus subtilis aerotaxis.
Aerotaxis, the directed migration along oxygen gradients, allows many microorganisms to locate favorable oxygen concentrations. Despite oxygen's fundamental role for life, even key aspects of aerotaxis remain poorly understood. In Bacillus subtilis, for example, there is conflicting evidence of whether migration occurs to the maximal oxygen concentration available or to an optimal intermediate one, and how aerotaxis can be maintained over a broad range of conditions. Using precisely controlled oxygen gradients in a microfluidic device, spanning the full spectrum of conditions from quasi-anoxic to oxic (60 n mol/l-1 m mol/l), we resolved B. subtilis' 'oxygen preference conundrum' by demonstrating consistent migration towards maximum oxygen concentrations ('monotonic aerotaxis'). Surprisingly, the strength of aerotaxis was largely unchanged over three decades in oxygen concentration (131 n mol/l-196 μ mol/l). We discovered that in this range B. subtilis responds to the logarithm of the oxygen concentration gradient, a rescaling strategy called 'log-sensing' that affords organisms high sensitivity over a wide range of conditions. In these experiments, high-throughput single-cell imaging yielded the best signal-to-noise ratio of any microbial taxis study to date, enabling the robust identification of the first mathematical model for aerotaxis among a broad class of alternative models. The model passed the stringent test of predicting the transient aerotactic response despite being developed on steady-state data, and quantitatively captures both monotonic aerotaxis and log-sensing. Taken together, these results shed new light on the oxygen-seeking capabilities of B. subtilis and provide a blueprint for the quantitative investigation of the many other forms of microbial taxis.


Detection of inflammation in vivo by surface-enhanced Raman scattering provides higher sensitivity than conventional fluorescence imaging.
The detection of inflammatory changes is a key aim for the early diagnosis and treatment of several autoimmune, infectious, and metastatic diseases. While surface-enhanced Raman scattering (SERS) has the capability to provide noninvasive, in vivo imaging at sufficient depth to achieve this goal, this approach has not been exploited in the study of inflammation. SERS-active nanoparticles were coded with a unique Raman signal that was protected under a wide range of conditions and stimuli. To detect early-stage inflammation, gold nanoparticle clusters containing Raman-active molecules were conjugated to intercellular adhesion molecule 1- (ICAM-1-) specific monoclonal antibodies. SERS allowed noninvasive measurement of ICAM-1 expression in vivo with twice the sensitivity of two-photon fluorescence. This is the first time SERS has been used for in vivo detection of inflammation and is a major advance in the ever-growing toolkit of approaches for use in noninvasive, next-generation in vivo imaging.


Explaining the association between educational level and frailty in older adults: results from a 13-year longitudinal study in the Netherlands.
The aim of this study was to examine the longitudinal association between educational level and frailty prevalence in older adults and to investigate the role of material, biomedical, behavioral, social, and mental factors in explaining this association. Data over a period of 13 years were used from the Longitudinal Aging Study Amsterdam. The study sample consisted of older adults aged 65 years and above at baseline (n = 1205). Frailty was assessed using Fried's frailty criteria. A relative index of inequality was calculated for the level of education. Longitudinal logistic regression analyses based on multilevel modeling were performed. Older adults with a low educational level had higher odds of being frail compared with those with a high educational level (relative index of inequality odds ratio, 2.94; 95% confidence interval, 1.84-4.71). These differences persisted during 13 years of follow-up. Adjustment for all explanatory factors reduced the effect of educational level on frailty by 76%. Income, self-efficacy, cognitive impairment, obesity, and number of chronic diseases had the largest individual contribution in reducing the effect. Social factors had no substantial contribution. Our findings highlight the need for a multidimensional approach in developing interventions aimed at reducing frailty, especially in lower educated groups.


Protein S-acylation in plants (Review).
Membrane resident proteins are a common feature of biology yet many of these proteins are not integral to the membrane. These peripheral membrane proteins are often bound to the membrane by the addition of fatty acyl chains to the protein. This modification, known as S-acylation or palmitoylation, promotes very strong membrane association but is also reversible allowing for a high degree of control over membrane association. Many S-acylated proteins are resident in sterol, sphingolipid and saturated-lipid enriched microdomains indicating an important role for S-acylation in protein partitioning within membranes. This review summarises the current knowledge of S-acylation in plants. S-acylated proteins play a wide variety of roles in plants and affect Ca(2+) signalling, K(+) movement, stress signalling, small and heterotrimeric G-protein membrane association and partitioning, tubulin function as well as pathogenesis. Although the study of S-acylation is in its infancy in plants this review illustrates that S-acylation is extremely important for plant function and that there are many unexplored aspects of S-acylation in plants. A full summary of the techniques and methods available to study S-acylation in plants is also presented.


The sodium-activated potassium channel Slack is required for optimal cognitive flexibility in mice.
Kcnt1 encoded sodium-activated potassium channels (Slack channels) are highly expressed throughout the brain where they modulate the firing patterns and general excitability of many types of neurons. Increasing evidence suggests that Slack channels may be important for higher brain functions such as cognition and normal intellectual development. In particular, recent findings have shown that human Slack mutations produce very severe intellectual disability and that Slack channels interact directly with the Fragile X mental retardation protein (FMRP), a protein that when missing or mutated results in Fragile X syndrome (FXS), the most common form of inherited intellectual disability and autism in humans. We have now analyzed a recently developed Kcnt1 null mouse model in several behavioral tasks to assess which aspects of memory and learning are dependent on Slack. We demonstrate that Slack deficiency results in mildly altered general locomotor activity, but normal working memory, reference memory, as well as cerebellar control of motor functions. In contrast, we find that Slack channels are required for cognitive flexibility, including reversal learning processes and the ability to adapt quickly to unfamiliar situations and environments. Our data reveal that hippocampal-dependent spatial learning capabilities require the proper function of Slack channels.


Research progress on the mechanism of glycolysis in ovarian cancer.
Glycolysis is the preferred energy metabolism pathway in cancer cells even when the oxygen content is sufficient. Through glycolysis, cancer cells convert glucose into pyruvic acid and then lactate to rapidly produce energy and promote cancer progression. Changes in glycolysis activity play a crucial role in the biosynthesis and energy requirements of cancer cells needed to maintain growth and metastasis. This review focuses on ovarian cancer and the significance of key rate-limiting enzymes (hexokinase, phosphofructokinase, and pyruvate kinase, related signaling pathways (PI3K-AKT, Wnt, MAPK, AMPK), transcription regulators (HIF-1a), and non-coding RNA in the glycolytic pathway. Understanding the relationship between glycolysis and these different mechanisms may provide new opportunities for the future treatment of ovarian cancer.


Nobel Prizes and the emerging virus concept.
The existence of infectious agents smaller than bacteria was demonstrated already during the 1890s. After this discovery it took more than 50 years before a resilient definition of viruses could be given. There were separate developments of knowledge concerning plant viruses, bacterial viruses and animal viruses. In the mid-1930s, Wendell Stanley at the Rockefeller Institute for Medical Research at Princeton described the purification and crystallization of tobacco mosaic virus. The finding of an "infectious protein" led to him receiving a Nobel Prize in Chemistry in 1946. In studies initiated at the end of the 1930s, bacteriophages were used as a model for replicating genes. They led to important insights into the unique characteristics of virus-cell interactions. However, an understanding of the chemical nature of animal virus particles and their mode of replication was slow in coming. Not until the early 1950s did tissue culture techniques become available, which allowed studies also of an extended number of animal viruses. This article discusses the emergence of concepts which eventually allowed a description of viruses. The unique real-time analyses of the state of knowledge provided by the Nobel Prize archives were used in the investigation. These archives remain secret for 50 years. Besides all of the underlying documents of the Prize to Stanley, comprehensive investigations made in the mid 1950s of Seymour E. Cohen, Max Delbrück, Alfred D. Hershey and Salvador D. Luria (the latter three received a Prize in Medicine in 1969) and of André Lwoff (he shared a Prize in Medicine with Francois Jacob and Jaques Monod in 1965) were reviewed. The final phase of the evolution of our understanding of the virus concept closely paralleled the eventual insight into the chemical nature of the genetic material. Understanding the principle nature of barriers to the development of new concepts is of timeless value for fostering and facilitating new discoveries in science.


Ursolic Acid Enhances Cytotoxicity of Doxorubicin-Resistant Triple-Negative Breast Cancer Cells via ZEB1-AS1/miR-186-5p/ABCC1 Axis.
Background: Triple-negative breast cancer (TNBC) is the most serious subtype of breast cancer (BC) and has been a great health threat to females. Although chemotherapeutic agent contributes a lot to TNBC treatment, drug resistance has been a great obstacle for chemotherapies. Ursolic acid (UA), a pentacyclic triterpenoid compound, was reported to reverse paclitaxel resistance in BC. However, whether UA could affect the resistance of TNBC cells to other drugs such as doxorubicin (DOX) remains to be discovered. Materials and Methods: MTT assay, EdU assay, colony formation assay, and flow cytometry analysis were implemented to detect the viability, proliferation, and apoptosis of DOX-resistant MDA-MB-468 and MDA-MB-436 cells with or without UA treatment. Mechanism assays including RIP, RNA pull-down, and luciferase reporter assays verified the interaction between RNAs. Results: UA treatment hindered the growth and mitigated the DOX resistance of DOX-resistant MDA-MB-468 and MDA-MB-436 cells. Mechanistically, multidrug resistance-associated protein 1 (ABCC1) expression was downregulated by UA treatment. MiR-186-5p was verified to target ABCC1. Further, UA-inhibited ZEB1-AS1 (zinc finger E-box binding homeobox 1 antisense RNA 1) was verified as a competitive endogenous RNA (ceRNA) to upregulate ABCC1 through sponging miR-186-5p. Importantly, UA treatment impaired the malignant phenotypes of DOX-resistant MDA-MB-468 and MDA-MB-436 cells through ZEB1-AS1/ABCC1 axis. Conclusion: UA promotes TNBC cell sensitivity to DOX through inactivating ZEB1-AS1/miR-186-5p/ABCC1 signaling.


BRAIN Initiative: Cutting-Edge Tools and Resources for the Community.
The overarching goal of the NIH BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative is to advance the understanding of healthy and diseased brain circuit function through technological innovation. Core principles for this goal include the validation and dissemination of the myriad innovative technologies, tools, methods, and resources emerging from BRAIN-funded research. Innovators, BRAIN funding agencies, and non-Federal partners are working together to develop strategies for making these products usable, available, and accessible to the scientific community. Here, we describe several early strategies for supporting the dissemination of BRAIN technologies. We aim to invigorate a dialogue with the neuroscience research and funding community, interdisciplinary collaborators, and trainees about the existing and future opportunities for cultivating groundbreaking research products into mature, integrated, and adaptable research systems. Along with the accompanying Society for Neuroscience 2019 Mini-Symposium, "BRAIN Initiative: Cutting-Edge Tools and Resources for the Community," we spotlight the work of several BRAIN investigator teams who are making progress toward providing tools, technologies, and services for the neuroscience community. These tools access neural circuits at multiple levels of analysis, from subcellular composition to brain-wide network connectivity, including the following: integrated systems for EM- and florescence-based connectomics, advances in immunolabeling capabilities, and resources for recording and analyzing functional connectivity. Investigators describe how the resources they provide to the community will contribute to achieving the goals of the NIH BRAIN Initiative. Finally, in addition to celebrating the contributions of these BRAIN-funded investigators, the Mini-Symposium will illustrate the broader diversity of BRAIN Initiative investments in cutting-edge technologies and resources.


Exposure to and Attitudes Regarding Transgender Education Among Urology Residents.
Transgender individuals are underserved within the health care system but might increasingly seek urologic care as insurers expand coverage for medical and surgical gender transition. To evaluate urology residents' exposure to transgender patient care and their perceived importance of transgender surgical education. Urology residents from a representative sample of U.S. training programs were asked to complete a cross-sectional survey from January through March 2016. Respondents were queried regarding demographics, transgender curricular exposure (didactic vs clinical), and perceived importance of training opportunities in transgender patient care. In total, 289 urology residents completed the survey (72% response rate). Fifty-four percent of residents reported exposure to transgender patient care, with more residents from Western (74%) and North Central (72%) sections reporting exposure (P ≤ .01). Exposure occurred more frequently through direct patient interaction rather than through didactic education (psychiatric, 23% vs 7%, P < .001; medical, 17% vs 6%, P < .001; surgical, 33% vs 11%, P < .001). Female residents placed greater importance on gender-confirming surgical training than did their male colleagues (91% vs 70%, P < .001). Compared with Western section residents (88%), those from South Central (60%, P = .002), Southeastern (63%, P = .002), and Mid-Atlantic (63%, P = .003) sections less frequently viewed transgender-related surgical training as important. Most residents (77%) stated transgender-related surgical training should be offered in fellowships. Urology resident exposure to transgender patient care is regionally dependent. Perceived importance of gender-confirming surgical training varies by sex and geography. A gap exists between the direct transgender patient care urology residencies provide and the didactic transgender education they receive.


Prevalence of pathogenicity island IICFT073 genes among extraintestinal clinical isolates of Escherichia coli.
Uropathogenic Escherichia coli is the most common cause of urinary tract infection (UTI). Cystitis in women is by far the most common UTI; pyelonephritis in both sexes and prostatitis in men are more severe but are less frequent complaints. The ability of E. coli to cause UTI is associated with specific virulence determinants, some of which are encoded on pathogenicity islands (PAI). One such PAI (PAI IICFT073), of the prototypical uropathogenic E. coli strain CFT073, contains 116 open reading frames, including iron-regulated genes, carbohydrate biosynthetic genes, the serine protease autotransporter picU, a two-partner secretion system, a type I secretion system, mobility genes, and a large number of hypothetical genes. To determine the association of PAI IICFT073 with UTI, PCR was used to examine the prevalence of the five virulence-associated loci among the ECOR collection and a collection of E. coli isolated from patients with cystitis, pyelonephritis, prostatitis, or septicemia. All PAI IICFT073 loci were found to be more prevalent among the B2 phylogenetic group than any other group within the ECOR collection and among invasive prostatitis strains than were cystitis or pyelonephritis strains. These data support the theory that clinical isolates causing prostatitis are more virulent than those producing cystitis or pyelonephritis in women.


[Analysis of mitochondrial DNA haplotypes in yakut population].
To study the mitochondrial gene pool structure in Yakuts, polymorphism of mtDNA hypervariable segment I (16,024-16,390) was analyzed in 191 people sampled from the indigenous population of the Sakha Republic. In total, 67 haplotypes of 14 haplogroups were detected. Most (91.6%) haplotypes belonged to haplogroups A, B, C, D, F, G, M*, and Y, which are specific for East Eurasian ethnic groups; 8.4% haplotypes represented Caucasian haplogroups H, HV1, J, T, U, and W. A high frequency of mtDNA types belonging to Asian supercluster M was peculiar for Yakuts: mtDNA types belonging to haplogroup C, D, or G and undifferentiated mtDNA types of haplogroup M (M*) accounted for 81% of all haplotypes. The highest diversity was observed for haplogroups C and D, which comprised respectively 22 (44%) and 18 (30%) haplotypes. Yakuts showed the lowest genetic diversity (H = 0.964) among all Turkic ethnic groups. Phylogenetic analysis testified to a common genetic substrate of Yakuts, Mongols, and Central Asian (Kazakh, Kyrgyz, Uigur) populations. Yakuts proved to share 21 (55.5%) mtDNA haplogroups with the Central Asian ethnic groups and Mongols. Comparisons with modern paleo-Asian populations (Chukcha, Itelmen, Koryaks) revealed three (8.9%) haplotypes common for Yakuts and Koryaks. The results of mtDNA analysis disagree with the hypothesis of an appreciable paleo-Asian contribution to the modern Yakut gene pool.


A Comprehensive Transcriptomic Analysis of Arsenic-Induced Bladder Carcinogenesis.
Arsenic (sodium arsenite: NaAsO2) is a potent carcinogen and a known risk factor for the onset of bladder carcinogenesis. The molecular mechanisms that govern arsenic-induced bladder carcinogenesis remain unclear. We used a physiological concentration of NaAsO2 (250 nM: 33 µg/L) for the malignant transformation of normal bladder epithelial cells (TRT-HU1), exposed for over 12 months. The increased proliferation and colony-forming abilities of arsenic-exposed cells were seen after arsenic exposure from 4 months onwards. Differential gene expression (DEG) analysis revealed that a total of 1558 and 1943 (padj < 0.05) genes were deregulated in 6-month and 12-month arsenic-exposed TRT-HU1 cells. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that cell proliferation and survival pathways, such as the MAPK, PI3K/AKT, and Hippo signaling pathways, were significantly altered. Pathway analysis revealed that the enrichment of stem cell activators such as ALDH1A1, HNF1b, MAL, NR1H4, and CDH1 (p < 0.001) was significantly induced during the transformation compared to respective vehicle controls. Further, these results were validated by qPCR analysis, which corroborated the transcriptomic analysis. Overall, the results suggested that stem cell activators may play a significant role in facilitating the arsenic-exposed cells to gain a survival advantage, enabling the healthy epithelial cells to reprogram into a cancer stem cell phenotype, leading to malignant transformation.


Insect Odorscapes: From Plant Volatiles to Natural Olfactory Scenes.
Olfaction is an essential sensory modality for insects and their olfactory environment is mostly made up of plant-emitted volatiles. The terrestrial vegetation produces an amazing diversity of volatile compounds, which are then transported, mixed, and degraded in the atmosphere. Each insect species expresses a set of olfactory receptors that bind part of the volatile compounds present in its habitat. Insect odorscapes are thus defined as species-specific olfactory spaces, dependent on the local habitat, and dynamic in time. Manipulations of pest-insect odorscapes are a promising approach to answer the strong demand for pesticide-free plant-protection strategies. Moreover, understanding their olfactory environment becomes a major concern in the context of global change and environmental stresses to insect populations. A considerable amount of information is available on the identity of volatiles mediating biotic interactions that involve insects. However, in the large body of research devoted to understanding how insects use olfaction to locate resources, an integrative vision of the olfactory environment has rarely been reached. This article aims to better apprehend the nature of the insect odorscape and its importance to insect behavioral ecology by reviewing the literature specific to different disciplines from plant ecophysiology to insect neuroethology. First, we discuss the determinants of odorscape composition, from the production of volatiles by plants (section "Plant Metabolism and Volatile Emissions") to their filtering during detection by the olfactory system of insects (section "Insect Olfaction: How Volatile Plant Compounds Are Encoded and Integrated by the Olfactory System"). We then summarize the physical and chemical processes by which volatile chemicals distribute in space (section "Transportation of Volatile Plant Compounds and Spatial Aspects of the Odorscape") and time (section "Temporal Aspects: The Dynamics of the Odorscape") in the atmosphere. The following sections consider the ecological importance of background odors in odorscapes and how insects adapt to their olfactory environment. Habitat provides an odor background and a sensory context that modulate the responses of insects to pheromones and other olfactory signals (section "Ecological Importance of Odorscapes"). In addition, insects do not respond inflexibly to single elements in their odorscape but integrate several components of their environment (section "Plasticity and Adaptation to Complex and Variable Odorscapes"). We finally discuss existing methods of odorscape manipulation for sustainable pest insect control and potential future developments in the context of agroecology (section "Odorscapes in Plant Protection and Agroecology").


Population studies of Plasmodium vivax. 1. The theory of polymorphism of sporozoites and epidemiological phenomena of tertian malaria.
The understanding of clinico-epidemiological phenomena of tertian malaria has been the subject of controversy. The authors suggest a system of postulates which give a non-contradictory explanation of the phenomena of relapses and long incubation. The main idea is that the duration of exoerythrocytic development of Plasmodium vivax is a polymorphic characteristic controlled by a set of genes. According to these postulates sporozoites may be subdivided into two groups designated as tachysporozoites and bradysporozoites, responsible for early and late manifestations, respectively. The logical analysis of the system suggests that it does not contradict the experimental facts. Moreover, the theory of polymorphic sporozoites permits an explanation and quantification of interrelations between different phenomena. The authors stress that the variation of genes is much greater in natural populations of parasites than in individual isolates and strains and therefore that the features of strains do not fully reflect the features of populations. Classical laboratory experiments should be combined with epidemiological experiments which allow a study of the population as a whole. The methodology of experiments to be undertaken in further investigations of the long latency period is discussed.


Estrogen-dependent regulation of ornithine decarboxylase in breast cancer cells through activation of nongenomic cAMP-dependent pathways.
17beta-estradiol (E2) induces ornithine decarboxylase (ODC) activity in several E2-responsive tissues/cells, and this study investigated the mechanism of hormone-induced transactivation in MCF-7 human breast cancer cells. E2-induced reporter gene (luciferase) activity in MCF-7 cells transfected with a construct (pODC1) containing the -164 to +29 region of the human ODC gene promoter linked to bacterial luciferase. This promoter sequence contains GC-rich Sp1 binding sites, CAAT, LSF, cAMP response element (CRE), and TATA motifs. Deletion and mutational analysis of the ODC promoter showed that both CAAT and LSF sites were required for hormone-induced transactivation. Gel mobility shift and DNA footprinting assays indicated that NFYA and LSF bound the CAAT and LSF motifs, respectively, and GAL4-NFYA/GAL4-LSF chimeras were also activated by E2, 8-bromo-cAMP, and protein kinase A (PKA) expression plasmid. However, E2-induced transactivation of GAL4-NFYA and GAL4-LSF was blocked by the PKA inhibitor SQ22356 indicating that the mechanism of ODC induction by E2 involves upregulation of cAMP/PKA through nongenomic pathways of estrogen action.


Effects of Exogenous Dopamine on the Uptake, Transport, and Resorption of Apple Ionome Under Moderate Drought.
The frequency and intensity of water deficits is expected to increase because of global warming. Drought stress is often one of the most limiting factors for plant growth. We conducted greenhouse pot experiments to address how dopamine affects the drought-resistance traits of apple trees at the physiological and molecular levels. Our factorial design consisted of dopamine and no-dopamine applications combined with well-watered and moderate-drought conditions. Seedling biomass, photosynthesis rates, chlorophyll concentrations, and stomatal apertures were markedly reduced under stress but dopamine treatment mitigated the inhibiting effects of drought on plant growth and helped maintain strong photosynthesis, chlorophyll levels, and stomatal functioning. Concentrations of most macro-, micro-, and trace elements decreased in response to drought. This stress also diminished the uptake and transport of elements in the leaves and stems, but increased the partitioning of elements in the roots. Nutrient resorption proficiency decreased while nutrient resorption efficiency increased for most analyzed elements. Exogenous dopamine significantly increased the concentrations, uptake, and transport of nutrients under drought stress, and also altered their distribution within the whole plant. However, this molecule had a negative effect on nutrient resorption. Although transcript levels of a key chlorophyll degradation gene, pheide a oxygenase, and senescence-associate gene 12 were elevated upon drought treatment, dopamine significantly suppressed the upregulation of those genes under such stress conditions. These observations indicate that dopamine has an important anti-senescence effect that might be helpful for regulating nutrient uptake, transport, and resorption, and ultimately influencing overall plant growth. Thus, understanding the role of dopamine in drought tolerance introduces new possibilities to use this compound for agricultural purposes.


Diagnosis of vitamin B12 deficiency in patients with myeloproliferative disorders.
Myeloproliferative disorders are characterized by proliferation of 1 or more lineage of hematologic cells. Rapid proliferation of cells may lead to depletion of vitamin B12, which may be falsely elevated by conventional assays in these disorders. We evaluated vitamin B12 status with conventional vitamin B12 assay and levels of serum methylmalonic acid (MMA), serum holotranscobalamin (holoTC), and plasma homocysteine in myeloproliferative disorders. In 58 patients who had myeloproliferative disorders and normal serum creatinine levels, we measured levels of vitamin B12, MMA, holoTC, and homocysteine. Correlations were evaluated between these tests, with MMA as the reference standard for vitamin B12 deficiency. Prevalence of vitamin B12 deficiency was 69%, despite high serum vitamin B12 levels. Levels of holoTC of 40.6 pmol/L or less and homocysteine of greater than 14 mol/L were the best cutoff levels with sensitivity values of 75% and 70%, specificity values of 80% and 68%, and positive predictive values of 88% and 80%. Logistic regression showed that cutoff values of holoTC of 40.6 pmol/L or less and homocysteine of greater than 14 mol/L resulted in odds ratio 15.5 for low versus high holoTC, and odds ratio 5.4 for high versus low homocysteine, to confirm vitamin B12 deficiency. Patients who had myeloproliferative disorders had a high prevalence of vitamin B12 deficiency, despite high serum vitamin B12 levels. Therefore, vitamin B12 status should be evaluated in patients with myeloproliferative disorders. Holotranscobalamin level may be the best initial test and may replace vitamin B12 assay to accompany MMA and homocysteine levels.


Critical consciousness, racial and gender discrimination, and HIV disease markers in African American women with HIV.
Critical consciousness, the awareness of social oppression, is important to investigate as a buffer against HIV disease progression in HIV-infected African American women in the context of experiences with discrimination. Critical consciousness comprises several dimensions, including social group identification, discontent with distribution of social power, rejection of social system legitimacy, and a collective action orientation. The current study investigated self-reported critical consciousness as a moderator of perceived gender and racial discrimination on HIV viral load and CD4+ cell count in 67 African American HIV-infected women. Higher critical consciousness was found to be related to higher likelihood of having CD4+ counts over 350 and lower likelihood of detectable viral load when perceived racial discrimination was high, as revealed by multiple logistic regressions that controlled for highly active antiretroviral therapy (HAART) adherence. Multiple linear regressions showed that at higher levels of perceived gender and racial discrimination, women endorsing high critical consciousness had a larger positive difference between nadir CD4+ (lowest pre-HAART) and current CD4+ count than women endorsing low critical consciousness. These findings suggest that raising awareness of social oppression to promote joining with others to enact social change may be an important intervention strategy to improve HIV outcomes in African American HIV-infected women who report experiencing high levels of gender and racial discrimination.


Excess mortality among children discharged from hospital after treatment for diarrhoea in rural Bangladesh.
Five hundred and fifty one children aged between 3 months and 3 years were followed up at home for 12 months after treatment of diarrhoea in a rural treatment centre of the International Centre for Diarrhoeal Disease Research, Bangladesh. During follow up the children were found to have a significantly higher mortality than generally observed in the community. The first three months after discharge appeared to be crucial, some 70% of the deaths occurring in that period. Severely malnourished children (nutritional state below 56% of the American National Center for Health Statistics (NCHS) standard of weight for age ratio) had a risk of death 14 times that of their well nourished counterparts (nutritional state 66% or more of the NCHS standard). The highest mortality occurred in 2 year olds, one in three of the severely malnourished children dying compared with one in 10 of the moderately malnourished. This pattern was not seen in children aged under 2 years. Immediate priority should be given to providing nutritional rehabilitation for malnourished children who contract diarrhoea.


Telerehabilitation for aphasia - protocol of a pragmatic, exploratory, pilot randomized controlled trial.
The Cochrane review on the effectiveness of speech and language therapy for aphasia following stroke suggests intensity of therapy is a key predictor for outcome. Current aphasia services cannot provide intervention at the intensity observed within trial contexts because of resource limitations. Telerehabilitation could widen access to speech-language pathologists (SLPs) in geographically remote contexts and reduce the time spent on travel by the therapist and patient. The current academic literature within this field is in its infancy, with few trials of speech and language therapy (SLT) delivered by videoconference. Our pilot randomized controlled trial (RCT) will explore feasibility aspects and effectiveness of telerehabilitation for aphasia in addition to standard SLT. Our study is a pragmatic, exploratory, pilot randomized controlled trial, where participants will be randomized to a telerehabilitation group or a control group. Both groups receive standard SLT (usual care) but the telerehabilitation group receives an additional 5 h of telerehabilitation per week over 4 weeks through videoconference. This additional telerehabilitation focuses on spoken language with an emphasis on word naming. We aim to include 40 patients in each group, with inclusion criteria being aphasia any time post stroke. Participants will be assessed blindly at pre-randomization (baseline), and 4 weeks and 4 months after randomization. The primary endpoint is naming ability 3 months after the completed intervention, measured by the Norwegian Basic Aphasia Assessment (NGA) naming subtest. Secondary endpoints include other subtests of the NGA, the VAST (Verb and Sentence Test) subtest sentence production, Communicative Effectiveness Index (CETI) and the Stroke and Aphasia Quality of Life scale (SAQOL-39). Experiences of patients and SLPs with telerehabilitation are assessed using questionnaires and semi-structured interviews. Statistical between group comparisons will be in line with an intention-to-treat analysis. This pilot RCT of intensive language training by videoconference will contribute new scientific evidence to the field of aphasia telerehabilitation. Here, we describe our trial which will explore the feasibility of telerehabilitation for aphasia as an intervention, our choice of primary and secondary outcome measures and proposed analyses. Our trial will provide information for the development and delivery of future definitive RCTs. ClinicalTrials.gov, ID: NCT02768922 . Registered on 11 May 2016. Last updated on 17 November 2017.


Cellular and molecular assessment of rose bengal photodynamic antimicrobial therapy on keratocytes, corneal endothelium and limbal stem cell niche.
Rose Bengal Photodynamic Antimicrobial Therapy (RB-PDAT) is a novel potential treatment for progressive infectious keratitis. The principle behind this therapy is using Rose Bengal as a photosensitizer that can be activated by green light and results in the production of oxygen free radicals which in turn eradicate the microorganism. Given RB-PDAT's mechanism of action and the potential cytotoxic effects, concerns regarding the safety of this technique have arisen. The purpose of this study was to evaluate the effect of RB-PDAT on keratocytes, while focusing on the safety profile that the photo-chemical reaction has on the limbal stem cell (LSC) niche and endothelial cell layer of the treated cornea. To perform RB-PDAT, Rose Bengal solution (0.1% RB in BSS) was applied to the right cornea of rabbits for 30 min and then irradiated by a custom-made green LED light source (525 nm, 6 mW/cm2) for 15 min (5.4 J/cm2). Three rabbits were sacrificed and enucleated after 24 h for evaluation. TUNEL assay and immunohistochemistry for endothelium and limbal stem cell viability were performed on whole mounts and frozen sections in treated and control eyes. LSC of both eyes were isolated and cultured to perform MTT viability and proliferation, and scratch wound healing assays under time-lapse microscopy. Interestingly, while Rose Bengal dye penetration was superficial, yet associated cellular apoptosis was evidenced in up to 1/3 of the stromal thickness on frozen sections. TUNEL assay on whole mounts showed no endothelial cell death following treatment. Immunohistochemistry on frozen sections of LSC displayed no structural difference between treated and non-treated eyes. There was no difference in LSC proliferation rates and scratch wound healing assay demonstrated adequate cell migration from treated and non-treated eyes. The current study suggests that even though penetration of the RB dye has been shown to be limited, oxidative stress produced by RB-PDAT can reach deeper into the corneal stroma. Nevertheless, our results show that performing RB-PDAT is safe on the corneal endothelium and has no effect on LSC viability or function.


Developmental variations of plasma gamma-glutamyltransferase fractions in humans and in laboratory mammalians.
Plasma samples from human cord blood, and fetuses, newborns, and adults of different mammalians species were analyzed by gel-filtration chromatography, to ascertain whether gamma-glutamyltransferase (GGT) fractions reflect liver maturation. Human cord blood plasma showed higher b-, m-, and s-GGT fraction as compared to adult women. In rat and mouse fetuses and in newborns, b-GGT was the most abundant fraction. As in adult humans, in adult rats, mice, rabbits, sheep, and mini pigs, f-GGT was the most abundant fraction. GGT fractions are a common feature of all mammalian species tested. Their pattern changes seem to reflect liver postnatal maturation, function.


Co-axial Endotracheal Tube Technique for Achieving One Lung Ventilation in a Toddler With a Space Occupying Malignant Tumor of the Right Lung.
Achieving one-lung ventilation in pediatrics is often challenging. In caring for these patients, the anesthesiologist must consider the child's age and size, underlying tracheobronchial anatomy, equipment availability, urgency of procedure, and as well as the experience level of the anesthesiologist. This report describes a "tube-inside-tube" technique that was adopted for providing one-lung ventilation in a toddler. The method described here involved railroading a smaller endotracheal tube over a flexible intubation video endoscope into the left mainstem bronchus coaxially through a larger endotracheal tube placed in the trachea. The technique achieved effective left-lung ventilation and isolation of the operative right lung during surgical resection of a malignant mesenchymal tumor. On completion of the procedure, double-lung ventilation could be established through the endotracheal tube in the trachea after the retraction of the video endobronchial tube.


Energetics of radical transfer in DNA photolyase.
Charge separation and radical transfer in DNA photolyase from Escherichia coli is investigated by computing electrostatic free energies from a solution of the Poisson-Boltzmann equation. For the initial charge separation 450 meV are available. According to recent experiments [Aubert et al. Nature 2000, 405, 586-590] the flavin receives an electron from the proximal tryptophan W382, which consequently forms a cationic radical WH(*)(+)382. The radical state is subsequently transferred along the triad W382-W359-W306 of conserved tryptophans. The radical transfer to the intermediate tryptophan W359 is nearly isoenergetic (58 meV uphill); the radical transfer from the intermediate W359 to the distal W306 is 200 meV downhill in energy, funneling and stabilizing the radical state at W306. The resulting cationic radical WH(*)(+)306 is further stabilized by deprotonation, yielding the neutral radical W(*)306, which is 214 meV below WH(*)(+)306. The time scale of the charge recombination process yielding back the resting enzyme with FADH(*) is governed by reprotonation of W306, with a calculated lifetime of 1.2 ms that correlates well with the measured lifetime of 17 ms. In photolyase from Anacystis nidulans the radical state is partially transferred to a tyrosine [Aubert et al. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 5423-5427]. In photolyase from Escherichia coli, there is a tyrosine (Y464) close to the distal tryptophan W306 that could play this role. We show that this tyrosine cannot be involved in radical transfer, because the electron transfer from tyrosine to W306 is much too endergonic (750 meV) and a direct hydrogen transfer is likely too slow. Coupling of specific charge states of the tryptophan triad with protonation patterns of titratable residues of photolyase is small.


[Diagnostic problems in pulmonary miliary tuberculosis, an analysis of 125 cases].
From Dec. 1984 to Dec. 1985, 4805 cases of various types of pulmonary tuberculosis were admitted to our hospital. Among them, there were 125 cases of pulmonary miliary tuberculosis, accounted for 2.6% of total cases. The rate of delayed diagnosis was 92%. The rate of delayed diagnosis patients of rural areas was higher than that of city (96.9%, versus 82.8%, P less than 0.05). Only 33.6% showed typical miliary changes on chest radiographs. The complication of enlargement of peripheral lymph nodes and extrapulmonary tuberculosis were much higher in miliary tuberculosis patients than that of total cases (36%, 45/125; 4.9%, 236/4805; P less than 0.01. 71.2%, 89/125; 5.8%, 278/4805; P less than 0.01 respectively).


The ruthenium-catalyzed meta-selective C-H nitration of various azole ring-substituted arenes.
The efficient ruthenium-catalyzed meta-selective CAr-H nitration of azole ring substituted arenes has been developed. In this work, Ru3(CO)12 was used as the catalyst, AgNO2 as the nitro source, HPcy3+·BF4- as the ligand, pivalic acid as the additive, and DCE as the solvent, and a wide spectrum of arenes bearing thiazole, pyrazolyl or removable oxazoline directing groups were tolerated in this meta-selective CAr-H nitration, affording the nitrated products in moderate to good yields. Moreover, this study reveals a gentler and environmentally friendly way to access meta-nitration arenes compared to the traditional process.


Hereditary erythrocyte adenylate kinase deficiency: a defect of multiple phosphotransferases?
Adenylate kinase (AK) modulates the interconversion of adenine nucleotides (AMP + adenosine triphosphate----2 ADP). We evaluated the fifth kindred with hereditary erythrocyte (RBC) AK deficiency. The proband had chronic hemolytic anemia. Her RBC had undetectable AK activity when measured spectrophotometrically, whereas those of her parents had half-normal AK activity. AK electrophoresis showed only AK-1 in the parents. The activities of pyruvate kinase and phosphoribosylpyrophosphate synthetase were decreased given the young age of the proband's RBC. Despite the absence of spectrophotometric AK activity, the proband's RBC were able to incorporate 14C-adenine into 14C-adenine nucleotides at 50% of the rate expected for her young RBC population, suggesting the possibility of an alternative pathway for the formation of ADP from AMP. Normal hemolysate had AMP:guanosine triphosphate (GTP) phosphotransferase activity, which produced ADP at 8% to 9% of the rate of AK (6.8 +/- 0.8 IU/mL RBC). AMP:GTP phosphotransferase activity was not detectable in the proband's or parent's hemolysates. These additional biochemical defects in the AK-deficient RBC further support the concept that AK deficiency per se may not cause hemolytic anemia. We propose that defects occur in multiple phosphotransferases in the AK-deficient RBC and that these other biochemical defects may produce deleterious lesions that promote the shortened RBC survival in AK deficiency.


The embryotoxicity of gossypol.
In utero development was analyzed in pregnancies that resulted from matings between gossypol-treated male rats and untreated female rats and in pregnancies in which gossypol was administered to the pregnant rat only. Gossypol treatment of males had no effect on the outcome of pregnancy. There was no significant effect on resorption, fetal growth, or malformation rate. Similarly, gossypol administered to pregnant dams at stages during organogenesis had no observable effect on pregnancy. Under the conditions of this experiment, gossypol administered to either the breeding male rat or the pregnant female rat had no demonstrable adverse effect on development in utero.


Assessing the relationship between ad volume and awareness of a tobacco education media campaign.
The relation between aided ad recall and level of television ad placement in a public health setting is not well established. We examine this association by looking back at 8 years of the California's Tobacco Control Program's (CTCP) media campaign. Starting in July 2001, California's campaign was continuously monitored using five telephone series of surveys and six web-based series of surveys immediately following a media flight. We used population-based statewide surveys to measure aided recall for advertisements that were placed in each of these media flights. Targeted rating points (TRPs) were used to measure ad placement intensity throughout the state. Cumulative TRPs exhibited a stronger relation with aided ad recall than flight TRPs or TRP density. This association increased after log-transforming cumulative TRP values. We found that a one-unit increase in log-cumulative TRPs led to a 13.6% increase in aided ad recall using web-based survey data, compared to a 5.3% increase in aided ad recall using telephone survey data. In California, the relation between aided ad recall and cumulative TRPs showed a diminishing return after a large volume of ad placements These findings may be useful in planning future ad placement for CTCP's media campaign.


Nicotinamide Adenine Dinucleotide Deficiency and Its Impact on Mammalian Development.
Significance: Nicotinamide adenine dinucleotide (NAD) is an important molecule synthesized from tryptophan or vitamin B3 and involved in numerous cellular reactions. NAD deficiency during pregnancy causes congenital NAD deficiency disorder (CNDD) characterized by multiple congenital malformations and/or miscarriage. Studies in genetically engineered mice replicating mutations found in human patient cases show that CNDD can be prevented by dietary supplements. Recent Advances: A growing number of patient reports show that biallelic loss-of-function of genes involved in NAD de novo synthesis (KYNU, HAAO, NADSYN1) cause CNDD. Other factors that limit the availability of NAD precursors, for example, limited dietary precursor supply or absorption, can cause or contribute to NAD deficiency and result in CNDD in mice. Molecular flux experiments allow quantitative understanding of NAD precursor concentrations in the circulation and their usage by different cells. Studies of NAD-consuming enzymes and contributors to NAD homeostasis help better understand how perturbed NAD levels are implicated in various diseases and adverse pregnancy outcomes. Critical Issues: NAD deficiency is one of the many known causes of adverse pregnancy outcomes, but its prevalence in the human population and among pregnant women is unknown. Since NAD is involved in hundreds of diverse cellular reactions, determining how NAD deficiency disrupts embryogenesis is an important challenge. Future Directions: Furthering our understanding of the molecular fluxes between the maternal and embryonic circulation during pregnancy, the NAD-dependent pathways active in the developing embryo, and the molecular mechanisms by which NAD deficiency causes adverse pregnancy outcomes will provide direction for future prevention strategies. Antioxid. Redox Signal. 39, 1108-1132.


Differential evolution of the Saccharomyces cerevisiae DUP240 paralogs and implication of recombination in phylogeny.
Multigene families are observed in all genomes sequenced so far and are the reflection of key evolutionary mechanisms. The DUP240 family, identified in Saccharomyces cerevisiae strain S288C, is composed of 10 paralogs: seven are organized as two tandem repeats and three are solo ORFs. To investigate the evolution of the three solo paralogs, YAR023c, YCR007c and YHL044w, we performed a comparative analysis between 15 S.cerevisiae strains. These three ORFs are present in all strains and the conservation of synteny indicates that they are not frequently involved in chromosomal reshaping, in contrast to the DUP240 ORFs organized in tandem repeats. Our analysis of nucleotide and amino acid variations indicates that YAR023c and YHL044w fix mutations more easily than YCR007c, although they all belong to the same multigene family. This comparative analysis was also conducted with five arbitrarily chosen Ascomycetes-specific genes and five arbitrarily chosen common genes (genes that have a homolog in at least one non-Ascomycetes organism). Ascomycetes-specific genes appear to be diverging faster than common genes in the S.cerevisiae species, a situation that was previously described between different yeast species. Our results point to the strong contribution, during DNA sequence evolution, of allelic recombination besides nucleotide substitution.


[The effect of Tween-80 on the differentiation of Trichophyton mentagrophytes and Trichophyton rubrum strains with FT-IR spectroscopy].
Trichophyton mentagrophytes and Trichophyton rubrum, are two of the frequently identified dermatophyte species in routine microbiology laboratories. Although newer technologies may assist in species-level identification, direct application of these methods usually require improvement in order to obtain reliable identification of these species. Earlier data have shown that dermatophytes may be identified with FT-IR spectroscopy although there are some limitations. In particular, the organic bond ranges in FT-IR spectra showed more irregularity because of the eucaryotic complexity of the molds. In this study, Tween-80 which is an inorganic molecule, was added to the dermatophyte growth medium in order to investigate its effect on FT-IR spectroscopy analysis of dermatophytes. Nine reference dermatophyte strains [5 T.mentagrophytes complex (T.asteroides CBS 424.63, T.erinacei CBS 344.79, CBS 511.73, CBS 677.86, T.mentagrophytes CBS 110.65) and 4 T.rubrum complex strains with different morphotypes (T.fluviomuniense CBS 592.68, T.kuryangei CBS 422.67, T.raubitschekii CBS 102856, T.rubrum CBS 392.58)] were included in the study. All strains were cultured on Sabouraud glucose agar either with or without 1% Tween-80 for three weeks. After the incubation period, superficial scrapings from each dermatophyte colony were analyzed using FT-IR spectroscopy. All measurements were performed in transmission mode between 4400 and 400 cm-1. Numerous spectral window data were analyzed by principal component analysis and hierarchical clustering was performed. The second derivations of spectral ranges revealed clear grouping of T.mentagrophytes complex and T.rubrum complex in association over five separate spectral ranges. The findings also showed that while all of the T.mentagrophytes strains contained lipid compounds in their mold structure after Tween-80 incubation (p< 0.025), T.rubrum strains did not. Based on these results, it was concluded that culture medium containing Tween-80 was sufficient to enable differentiation of T.mentagrophytes complex from T.rubrum complex by FT-IR spectroscopy. This effect might be attributed to the possible transfer of lipid compounds from culture to cell structure during growth. Further studies with the use of large number of reference strains and clinical isolates exposed to different environmental factors, such as antifungal agents and inorganic ions, are needed to support these data indicating favorable effect of Tween-80 on the differentiation of T.mentagrophytes and T.rubrum complexes by FT-IR spectroscopy.


Proposing a syllabus for the operation room B.S. courses in Iran.
Education is based upon the knowledge, skills, and attitudes that are required for an occupation, and the changes occurring in the occupations and duties as well as in the ideals and values necessitate constant needs analysis. Furthermore, owing to the transformations in sciences, especially medical sciences, the current syllabus for the operation room courses at associate level will not meet the requirements for operation room personnel in future. Therefore, the syllabus for operation room B.S. was developed and proposed in a research project entitled "Study of the international syllabus for the operation room courses and proposing an appropriate syllabus for the courses in Iran." Since the operation room courses at B.S. level are supposed to be introduced in Iranian universities, we intended to learn about the opinions of other people related to this subject in Iran. In this research, a questionnaire was used that contained the syllabus proposed for the operation room B.S. courses, which was the result of a research project entitled "Study of the international syllabus for the operation room courses and proposing an appropriate syllabus for the courses in Iran." To develop this syllabus, 12 heads of the operation room departments in universities across Iran in which the subject matter was being taught at associate level were consulted. The study showed that 14 out of the 53 courses proposed in the syllabus had a desirability level of 100%, 22 courses were desirable at levels of 91-100%, 19 were 75-90% desirable, and no courses had a desirability level less than 75%. After carrying out some modifications to the syllabus, the problems were resolved and the opinions were again asked. When a consensus of greater than 70% was reached, the syllabus for the operation room courses at B.S. level was finalized and proposed. The regulations from the Development, Planning, and Evaluation Office of the Ministry of Health were also followed. Although all the courses showed a desirability level of greater than 70%, receiving appropriate suggestions about some courses led the research team to carry out major or minor modifications to some of the courses.


Enhanced detection of hyperactivity after drug withdrawal with a simple modification of the open-field apparatus.
The open-field apparatus has been used to study withdrawal reactions from chronic treatments with central nervous system depressant drugs. To study the behavior of the same animal after drug withdrawal, the rats are introduced into the open field on consecutive days. Because the open field is a novel environment, the repetition could lead to false-negative results with regard to drug withdrawal. To overcome this problem, we sought a modification of the open field, using different floor-painting patterns every time the animal is observed. The most frequently observed withdrawal manifestation was hyperactivity. We verified that long-term treatment withdrawal reactions from barbital, clonazepam, and ethanol were seen more often if the rats were introduced in the modified open field. In addition, fewer animals were used here than in other trials and hyperactivity was detected more frequently in the modified open field than was sound-induced convulsions. We propose that the modified open field is more useful than the classic one for screening of drug withdrawal reactions.


Video. Laparoscopic splenic-preserving distal pancreatectomy for trauma in a child.
To reduce the risks associated with splenectomy, there has been a trend toward splenic preservation when performing distal pancreatectomy. Although laparoscopy has gained almost universal acceptance, it is still not utilized often for pancreatic surgery in children. In fact, review of the literature shows only a few case series of splenic-preserving laparoscopic distal pancreatectomy, and even less reported experience in the pediatric population. To our knowledge, there has been only one other report of laparoscopic spleen-preserving distal pancreatectomy in the setting of trauma in a child. A 13-year-old boy suffered a handlebar injury to the abdomen secondary to a dirt bike accident. He did not report loss of consciousness but complained of abdominal pain. CT scan revealed a grade II splenic laceration with a transected distal pancreas. He was hemodynamically stable with a large contusion in the left upper quadrant. Laboratory evaluation showed that his hematocrit was stable but was significant for elevated amylase and lipase. During his hospitalization, he developed significant abdominal distension and his amylase and lipase continued to rise. He was taken to the operating room for definitive management of his pancreatic injury 72 hours after his initial injury. In the operating room, a central line was placed so that he could receive total parenteral nutrition postoperatively. The video demonstrates the performance of a laparoscopic spleen-preserving distal pancreatectomy. There was a fair amount of old blood seen in the left upper quadrant and behind the pancreas. There was no evidence of active bleeding. The operation was performed without complication and with preservation of the splenic vessels. The postoperative course was very smooth with the child resuming diet by postoperative day (POD) 4. He was sent home on POD 7. This video demonstrates that in the proper trauma patient, a minimally invasive approach to a spleen-preserving distal pancreatectomy can still be performed.


Aortic intima-media thickness in nicotine-exposed rat pups during gestation and lactation period.
There have been several studies confirming an association between maternal smoking during pregnancy and low birth weight. The detrimental effect of nicotine exposure beginning in fetal life continues during lactation, in infancy and in the early childhood period. In our previous studies, we found increased aortic intima-media thickness (aIMT) as a preatherosclerotic lesion in neonates with intrauterine growth restriction and in infants of smoking mothers. We aimed to evaluate histopathologically the effect of nicotine exposure during pregnancy and lactation period on fetal growth and aIMT at postnatal 45 days of age (end of the mid-adolescent period) in rat pups living in the same conditions. Gravid rats were assigned into three groups. In nicotine A, pregnant rats received 6 mg/kg/day nicotine intraperitoneally during pregnancy from 1 to 21 days of gestation and lactation (until postnatal day 21). Nicotine B received 3 mg/kg/day nicotine for the same period. Control pregnant rats received only saline intraperitoneally. Abdominal aIMT was studied histopathologically at postnatal 45 days of age. Nicotine exposure resulted in decreased birth weight and pregnancy weight gain. The mean aIMT values of the rat pups exposed to nicotine in both nicotine A and B groups were higher than those of the control group (103.78 ± 21.33 μm, 99.11 ± 30.12 μm, and 62.56 ± 7.18 μm, respectively). In conclusion, the detrimental effect on birth weight of nicotine exposure that began in fetal life is dose dependent. Nicotine exposure during intrauterine life and the lactation period causes increased aIMT in rat pups.