Depression during pregnancy: prevalence and risk factors among women attending a public health clinic in Rio de Janeiro, Brazil.
Depression is the most prevalent psychiatric disorder during pregnancy and is associated with psychosocial and clinical obstetric factors. Despite being an important public health issue, there are few studies about this issue in Brazil. A cross-sectional study was carried out, involving 331 pregnant women attending a public primary health service over a one-year period in Rio de Janeiro city, Brazil. Participants were interviewed about their socio-demographic status, obstetric/medical conditions, life events and violence during pregnancy. Depression was assessed using the Composite International Development Interview. The prevalence of depression during pregnancy was 14.2% (95%CI: 10.7-18.5) and associated factors included: previous history of depression and any psychiatric treatment, unplanned pregnancy, serious physical illness and casual jobs. These data emphasize the need for screening for depression and its risk factors during pregnancy in settings where care is available. Psychosocial interventions and social policies need to be devised for this population.


Associations of conflict and migration on childhood cognitive development in Ethiopia: Evidence from a longitudinal study.
Migration has substantial consequences on the wellness of affected households, thereby exposing children to circumstances that are detrimental for healthy cognitive development. This study evaluates the relationship between conflict and migration during conception or early childhood and childhood cognitive development outcomes among families in Ethiopia. We hypothesized that migration is associated with worse cognitive development outcomes among children and that this association is mediated by educational disparities and caregiver psychological distress. The study used longitudinal data of children enrolled in the Young Lives Study (YLS) conducted in Ethiopia during 2002 (age 1), 2006-2007 (age 5), and 2009-2010 (age 8). We used multivariate linear and logistic regression to analyze the association between migration on cognitive development during middle childhood. Household migration and caregiver psychological distress were measured during round 1, type of education was measured at round 2, and cognitive development was measured at round 3. Results of the multivariate regression analysis showed that migrant children achieved lower scores on a test of verbal intelligence after controlling for sex, ethnicity, religion, and caregiver distress (β: -8.09; 95% CI: -15.33, -0.85). Results of the mediation analysis show that the type of schooling that children attended, but not caregiver psychological distress, mediated the association between migration and cognitive development. Migrant children were more likely to attend private schools, which buffered the association between migration and lower cognitive development. This study suggests that migration is a key determinant of childhood cognitive development among migrated populations. More research is needed to build the evidence base to support interventions for this growing, underserved population.


The disposition and metabolic fate of 14C-cibenzoline in man.
The disposition and metabolic fate of cibenzoline (CBZ) following single oral 153-mg doses of 14C-CBZ succinate were studied in five healthy adult males. The mean maximum plasma radioactivity of 386 ng eq/ml occurred at 2.4 hr after administration. The mean half-life, determined from the 14C plasma concentration and urinary excretion rate data, was 13.1 and 14.8 hr, respectively. The mean maximum CBZ concentration was 196 ng/ml at 1.2 hr post-dose. The mean half-life, determined from the plasma concentration and urinary excretion rate data, was 7.2 and 7.3 hr, respectively. The mean total clearance of radioactivity and CBZ was 300 ml/min and 1224 ml/min, respectively, due to elimination via both renal and nonrenal pathways. The only unconjugated metabolite in the plasma was 4,5-dehydrocibenzoline which, together with other unidentified metabolites, is presumed responsible for the longer observed half-life for total radioactivity. Approximately 75% of the dose was recovered in the urine in the first 24 hr after dosing, 80% of which was present at CBZ and known metabolites. After 6 days, a mean of 85.7% of the dose was excreted in urine and 13.2% in feces. The predominant excreted compound was CBZ (55.7% of the dose) in the 0-72 hr urine. Although several metabolites were identified in urine samples, none were found in substantial amounts relative to the parent drug. Two of these substances showed slight antiarrhythmic activity, whereas the 4,5-dehydro metabolite, representing approximately 4% of radioactivity in urine, was inactive.


Distinct DNA methylation activity of Dnmt3a and Dnmt3b towards naked and nucleosomal DNA.
In mammals, the resetting of DNA methylation patterns in early embryos and germ cells is crucial for development. De novo type DNA methyltransferases Dnmt3a and Dnmt3b are responsible for creating DNA methylation patterns during embryogenesis and in germ cells. Although their in vitro DNA methylation properties are similar, Dnmt3a and Dnmt3b methylate different genomic DNA regions in vivo. In the present study, we have examined the DNA methylation activity of Dnmt3a and Dnmt3b towards nucleosomes reconstituted from recombinant histones and DNAs, and compared it to that of the corresponding naked DNAs. Dnmt3a showed higher DNA methylation activity than Dnmt3b towards naked DNA and the naked part of nucleosomal DNA. On the other hand, Dnmt3a scarcely methylated the DNA within the nucleosome core region, while Dnmt3b significantly did, although the activity was low. We propose that the preferential DNA methylation activity of Dnmt3a towards the naked part of nucleosomal DNA and the significant methylation activity of Dnmt3b towards the nucleosome core region contribute to their distinct methylation of genomic DNA in vivo.


Influence of exogenous factor VIIa on thrombin generation in cord plasma of full-term and pre-term newborns.
Factor (F) VIIa has been used to treat adults and children with a variety of bleeding disorders. The results from these studies cannot be extrapolated to newborns because their hemostatic system differs significantly from adults, which may influence the effects of FVIIa on thrombin (IIa) generation. We compared the effects of FVIIa concentrates on IIa generation in plasmas from adults, full-term newborns and pre-term newborns. Defibrinated plasma (using arvin) from adults, or umbilical cords from full-term or pre-term deliveries was supplemented with FVIIa (Novo Nordisk, Bagsvaerd, Denmark), mixed with dilute thromboplastin reagent, and the resultant reaction mixture subsampled periodically into ethylenediamine tetraacetic acid, followed by measurement of total IIa activity (S-2238). Thrombin-alpha2 macroglobulin complexes, determined as residual activity after neutralization with heparin and antithrombin, were subtracted from total IIa to give free IIa. Prothrombin (FII) and inhibitor complexes were measured by enzyme-linked immunosorbent assays. Addition of FVIIa caused a reduction in the lag phase for the appearance of free IIa and consumption of FII, which was more pronounced in newborn plasma. There was no increase in peak IIa levels regardless of the amount of FVIIa added. Final inhibitor complex concentrations were increased in plasmas from adults compared with newborns, likely reflecting higher plasma concentrations of FII in adults. Generation of IIa was more rapid in pre-term plasma compared with that in adult and full-term cord plasmas due to increased endogenous tissue factor (TF). In summary, FVIIa enhanced IIa generation in plasma from different age groups, with the effect being more pronounced in plasma from pre-term newborns, possibly due to increased levels of plasma TF.


[Frequency of detection of different hepatitis C virus subtypes in the Moscow region].
There is a high degree of the hepatitis C virus (HCV) infection in Moscow region. The analysis of different HCV subtypes is caused by the necessity of prognostic estimation of predominant subtypes for the near future because new schemes of antiviral therapy for several HCV genotypes are developed. It is established that subtype 1b (52.1%) prevails in Moscow region. The increase of subtype 3a (37.2%) against the decrease in subtype 1b is observed. In patients infected before 1990 HCV subtype 1b is predominant and liver cirrhosis is detected in 46.7% of cases. The intergenotypic recombinant 2k/1b is registered with the frequency of 0.8% and about 2% of cases of mixed HCV subtypes are detected.


Being a close relative of a dying person. Development of the concepts "involvement in the light and in the dark".
The current study is based on an earlier article in which relatives' involvement in care was described as "involvement in the light" or "involvement in the dark." Involvement in the light was characterized as the relative being well informed and experiencing a meaningful involvement. The relatives involved in the dark felt uninformed, that they were "grouping around in the dark" when they tried to support the patient. The present study analyzed further the meaning of "involvement in the light" and "involvement in the dark," and investigated whether two different care cultures, the relationship with the staff, and a rapid course of illness influence the involvement of relatives. Relatives of 52 patients who died, 30 at a surgical department and 22 in a hospice ward, were interviewed after the patients' deaths. All the relatives of the patients in the hospice ward and 13 of those in the surgical department were judged to be involved in the light. Of the relatives judged to be involved in the dark, 12 either had a sick relative with a rapid course of illness or felt that the sick relative had died unexpectedly. A pattern was clearly observed: The relatives involved in the light described being met with respect, openness, sincerity, confirmation, and connection, whereas the opposite was experienced by those involved in the dark.


Caregiver distress and quality of life in primary caregivers of oncology patients in active treatment and follow-up.
As the number of informal caregivers and their caregiving responsibilities increase, this study aims at evaluating caregiver distress, quality of life (QoL) and their predictors in informal caregivers of cancer patients during active treatment and follow-up. This cross-sectional descriptive study targeted primary caregivers of patients with different cancer diagnoses. Caregiver-reported outcomes were measured by the Caregiver Risk Screen (CRS), Distress Thermometer (DT) and Caregiver Quality of Life Index-Cancer (CQOLC). Caregivers (n = 1580) experienced a low-to-moderate risk of caregiver distress and a moderate QoL during both treatment and follow-up. About 13% reported a high caregiver risk and 20% reported severe distress. There was a strong and significant correlation between caregiver distress and caregivers' QoL (0.793). Predictive factors for higher distress and poorer QoL were: fewer emotional and practical resources, being female, non-spousal relationship or not living together (p < 0.05). Caregivers of patients with head-and-neck, skin, lung and brain cancers reported the highest distress and lowest QoL. Caregiver distress is highly variable, but a minority of caregivers is at high risk for caregiver distress. Professional caregivers play an important role at supporting caregivers and detecting high-risk caregivers.


An IoT enabled system for enhanced air quality monitoring and prediction on the edge.
Air pollution is a major issue resulting from the excessive use of conventional energy sources in developing countries and worldwide. Particulate Matter less than 2.5 µm in diameter (PM2.5) is the most dangerous air pollutant invading the human respiratory system and causing lung and heart diseases. Therefore, innovative air pollution forecasting methods and systems are required to reduce such risk. To that end, this paper proposes an Internet of Things (IoT) enabled system for monitoring and predicting PM2.5 concentration on both edge devices and the cloud. This system employs a hybrid prediction architecture using several Machine Learning (ML) algorithms hosted by Nonlinear AutoRegression with eXogenous input (NARX). It uses the past 24 h of PM2.5, cumulated wind speed and cumulated rain hours to predict the next hour of PM2.5. This system was tested on a PC to evaluate cloud prediction and a Raspberry P i to evaluate edge devices' prediction. Such a system is essential, responding quickly to air pollution in remote areas with low bandwidth or no internet connection. The performance of our system was assessed using Root Mean Square Error (RMSE), Normalized Root Mean Square Error (NRMSE), coefficient of determination (R 2), Index of Agreement (IA), and duration in seconds. The obtained results highlighted that NARX/LSTM achieved the highest R 2 and IA and the least RMSE and NRMSE, outperforming other previously proposed deep learning hybrid algorithms. In contrast, NARX/XGBRF achieved the best balance between accuracy and speed on the Raspberry P i .


Rejecting Chaotic Disturbances Using a Super-Exponential-Zeroing Neurodynamic Approach for Synchronization of Chaotic Sensor Systems.
Due to the existence of time-varying chaotic disturbances in complex applications, the chaotic synchronization of sensor systems becomes a tough issue in industry electronics fields. To accelerate the synchronization process of chaotic sensor systems, this paper proposes a super-exponential-zeroing neurodynamic (SEZN) approach and its associated controller. Unlike the conventional zeroing neurodynamic (CZN) approach with exponential convergence property, the controller designed by the proposed SEZN approach inherently possesses the advantage of super-exponential convergence property, which makes the synchronization process faster and more accurate. Theoretical analyses on the stability and convergence advantages in terms of both faster convergence speed and lower error bound within the task duration are rigorously presented. Moreover, three synchronization examples substantiate the validity of the SEZN approach and the related controller for synchronization of chaotic sensor systems. Comparisons with other approaches such as the CZN approach, show the convergence superiority of the proposed SEZN approach. Finally, extensive tests further investigate the impact on convergence performance by choosing different values of design parameter and initial state.


Telophase disc: a new mammalian mitotic organelle that bisects telophase cells with a possible function in cytokinesis.
We have discovered a novel mitosis-specific human autoantigen that arises at the centromeres of prophase chromosomes, but ultimately participates in formation of an organelle that bisects the cell at late anaphase and during telophase. The organelle, discernible as a three-dimensional disc by confocal microscopy, encompasses the entire midzone diameter, and its distribution survives disassembly of interpolar microtubules by cold temperature treatment and detergent lysis of cells. Cytokinetic furrow contraction proceeds normally in dihydrocytochalasin B (DCB)-treated cells, and antigen distribution in the furrow is unaltered. In DCB, the furrow retracts in early interphase, coincident with loss of normal membrane association with the disc, resulting in the formation of binucleate cells. The midzone disc in both drug-treated and normal cells is present at the correct time and position to play a central role in cytokinesis. By immunocytochemistry, the disc appears to contain myosin but not actin. The position of the disc and the possible presence of myosin suggest that cytokinesis may involve the interaction of the disc organelle with actin in the cell cortex to produce cleavage in mammalian cells.


Among-population variation in tolerance to larval herbivory by Anthocharis cardamines in the polyploid herb Cardamine pratensis.
Plants have two principal defense mechanisms to decrease fitness losses to herbivory: tolerance, the ability to compensate fitness after damage, and resistance, the ability to avoid damage. Variation in intensity of herbivory among populations should result in variation in plant defense levels if tolerance and resistance are associated with costs. Yet little is known about how levels of tolerance are related to resistance and attack intensity in the field, and about the costs of tolerance. In this study, we used information about tolerance and resistance against larval herbivory by the butterfly Anthocharis cardamines under controlled conditions together with information about damage in the field for a large set of populations of the perennial plant Cardamine pratensis. Plant tolerance was estimated in a common garden experiment where plants were subjected to a combination of larval herbivory and clipping. We found no evidence of that the proportion of damage that was caused by larval feeding vs. clipping influenced plant responses. Damage treatments had a negative effect on the three measured fitness components and also resulted in an earlier flowering in the year after the attack. Tolerance was related to attack intensity in the population of origin, i.e. plants from populations with higher attack intensity were more likely to flower in the year following damage. However, we found no evidence of a relationship between tolerance and resistance. These results indicate that herbivory drives the evolution for increased tolerance, and that changes in tolerance are not linked to changes in resistance. We suggest that the simultaneous study of tolerance, attack intensity in the field and resistance constitutes a powerful tool to understand how plant strategies to avoid negative effects of herbivore damage evolve.


Induction of immune tolerance during administration of monoclonal antibody to L3T4 does not depend on depletion of L3T4+ cells.
Treatment of mice with mAb to L3T4 profoundly depletes T helper cells. This treatment inhibits humoral and cellular immunity, retards autoimmunity, and permits the induction of Ag-specific tolerance. Treatment of BALB/c mice with F(ab')2 anti-L3T4 inhibits humoral immunity without depleting L3T4+ cells, which is evidence that mAb to L3T4 may inhibit T helper cell function in vivo. In this report, we demonstrate that F(ab')2 anti-L3T4 also permits the induction of immune tolerance in a manner that is independent of T cell depletion. C57BL/6 mice were treated with 1 mg of F(ab')2 anti-L3T4 every other day for 18 days and from the onset were challenged weekly with the immunogen 2C7, a rat mAb to chicken ovalbumin. These mice failed to respond to 2C7 not only during the treatment period but also for at least 5 mo thereafter. This immune tolerance was Ag-specific; the mice rapidly produced antibodies to subsequent challenge with another Ag, human gamma-globulin. Unlike intact anti-L3T4, which immediately depletes L3T4+ cells by greater than 90%, F(ab')2 anti-L3T4 did not initially deplete cells and caused only a partial reduction by the end of the 18-day treatment. This partial reduction of L3T4+ cells did not contribute to the induction of tolerance because mice that were first challenged with 2C7 3 days after stopping the F(ab')2 anti-L3T4 treatment, when L3T4+ cells were lowest, had a normal Ir to 2C7. These findings demonstrate that mAb to L3T4 permits induction of Ag-specific immune tolerance by a mechanism independent of its ability to deplete L3T4+ cells. They also show that F(ab')2 anti-L3T4 treatment does not impair humoral immunity when immunization is initiated after treatment is stopped. Because L3T4 is homologous to CD4 in humans, our findings suggest that F(ab')2 anti-CD4 may offer significant advantages over the use of intact anti-CD4 as an immunosuppressive agent in humans.


Reducing blood glucose variability by use of abdominal insulin injection sites.
Virtually all patients with type I diabetes are familiar with inexplicable fluctuations in blood glucose concentration that expose them to both hypoglycemia and hyperglycemia. It is commonly assumed that such fluctuations are due, in large part, to variations in food intake, physical activities, and emotional state. However, substantial day-to-day variation in blood glucose concentration is observed when diet, exercise, emotional state, insulin dosage, and timing of insulin administration are held constant. This suggests that variation in the rate of absorption of insulin from the subcutaneous injection sites may be an important factor causing those fluctuations. Variations in insulin absorption are increased if the anatomic regions used for injections are rotated. A recent study completed at the University of Minnesota Hospital and Clinic indicates that it is inadvisable for type I diabetic subjects to rotate insulin injection regions; rather, insulin injections should be confined to a single anatomic region (usually the abdomen) as this will decrease day-to-day variability in blood glucose concentration. Such a decrease should allow greater precision in adjusting insulin doses, thereby helping achieve good control.


Poor care and the professional duty of the registered nurse.
Concerns have been raised in recent years about standards of care in the UK. Notable failures have been identified in the care of vulnerable older adults. This article identifies and discusses some logical steps which might be taken to minimise the risk of individual and systemic care failure in settings for older adults. These steps include frank discussion about ageism to promote empowerment and respect for older people; ensuring robust policies are in place that support and encourage the reporting of poor care; and ensuring that registered practitioners are aware of their accountability for their actions and also their omissions should they witness poor care. In addition to reducing the risk of poor care, these steps could contribute to having a more confident, competent and empowered workforce.


Preventing chronic diseases by promoting healthy diet and lifestyle: public policy implications for China.
Fuelled by rapid urbanization and changes in dietary and lifestyle choices, chronic diseases have emerged as a critical public health issue in China. The Healthy China 2020 programme recently announced by the Chinese government has set an overarching goal of promoting public health and making health care accessible and affordable for all Chinese citizens by year 2020. One of important components of the programme is to reduce chronic diseases by promoting healthy eating and active lifestyles. Chronic diseases not only affect health and quality of life, but also have economical and social consequences. With a limited infrastructure for chronic disease care, China is ill-equipped to deal with the escalating chronic disease epidemic, which threatens to reverse the gains of economic development in recent decades. Population-based intervention studies conducted in China and elsewhere have demonstrated the efficacy and effectiveness of several preventive strategies to reduce risk of chronic diseases in high-risk individuals and the general population. However, translating these findings into practice requires changes in health systems and public policies. To achieve the goals set by the Healthy China 2020 programme, prevention of chronic diseases should be elevated to a national public policy priority.


Deciphering the causes of cardiovascular and other complex diseases in populations: achievements, challenges, opportunities, and approaches.
This paper provides an overview of key achievements of the Framingham Heart Study and identifies areas and approaches for future research in cardiovascular disease epidemiology and prevention. There is a need for a range of different studies using diverse designs (i.e. case-control, cohort, multi-community, birth cohort, family-based cohorts and randomized trials) in different settings and involving multiple ethnic groups. Incorporation of a range of new disciplines, such as genetics, behavioural sciences, social epidemiology, measures of the environment, geography, and health policy are required to understand the root determinants of cardiovascular diseases.


Fast and unbiased purification of RNA-protein complexes after UV cross-linking.
Post-transcriptional regulation of gene expression in cells is facilitated by formation of RNA-protein complexes (RNPs). While many methods to study eukaryotic (m)RNPs rely on purification of polyadenylated RNA, other important regulatory RNA classes or bacterial mRNA could not be investigated at the same depth. To overcome this limitation, we developed Phenol Toluol extraction (PTex), a novel and unbiased method for the purification of UV cross-linked RNPs in living cells. PTex is a fast (2-3 h) and simple protocol. The purification principle is solely based on physicochemical properties of cross-linked RNPs, enabling us to interrogate RNA-protein interactions system-wide and beyond poly(A) RNA from a variety of species and source material. Here, we are presenting an introduction of the underlying separation principles and give a detailed discussion of the individual steps as well as incorporation of PTex in high-throughput pipelines.


Comparison of motor praxis and performance in children with varying levels of developmental coordination disorder.
The praxis test is a less well-documented method to determine functional manifestations of childhood dyspraxia. For this study, children aged 6-8years were recruited as follows: 17 children with DCD, 18 at risk of DCD and 35 without obvious problems in motor coordination. The Movement Assessment Battery for Children (MABC-2) was used to measure motor performance and identify the motor incoordination. This study developed a battery of tests to assess limb praxis using a praxis imagery questionnaire, gesture representation, and questions about knowledge of object use. In the comparison of subtests within the praxis test, significant differences were observed across groups on the praxis imagery questionnaire and gesture representation tests but not on knowledge of object use. Similar results were observed in the correlation analyses, in which a weak relationship between MABC-2 and praxis tests was observed. The DCD group had lower scores on the praxis imagery questionnaire, whereas the group at risk of DCD had lower scores on most gesture production tests. Our study provides a better understanding of the nature of the childhood dyspraxia and sheds light on its effect on motor coordination to identify praxis tests with specific clinical meanings in children with movement disorders.


Hypotheses and tracking results about the longest migration: The case of the arctic tern.
The arctic tern Sterna paradisaea completes the longest known annual return migration on Earth, traveling between breeding sites in the northern arctic and temperate regions and survival/molt areas in the Antarctic pack-ice zone. Salomonsen (1967, Biologiske Meddelelser, Copenhagen Danske Videnskabernes Selskab, 24, 1) put forward a hypothetical comprehensive interpretation of this global migration pattern, suggesting food distribution, wind patterns, sea ice distribution, and molt habits as key ecological and evolutionary determinants. We used light-level geolocators to record 12 annual journeys by eight individuals of arctic terns breeding in the Baltic Sea. Migration cycles were evaluated in light of Salomonsen's hypotheses and compared with results from geolocator studies of arctic tern populations from Greenland, Netherlands, and Alaska. The Baltic terns completed a 50,000 km annual migration circuit, exploiting ocean regions of high productivity in the North Atlantic, Benguela Current, and the Indian Ocean between southern Africa and Australia (sometimes including the Tasman Sea). They arrived about 1 November in the Antarctic zone at far easterly longitudes (in one case even at the Ross Sea) subsequently moving westward across 120-220 degrees of longitude toward the Weddell Sea region. They departed from here in mid-March on a fast spring migration up the Atlantic Ocean. The geolocator data revealed unexpected segregation in time and space between tern populations in the same flyway. Terns from the Baltic and Netherlands traveled earlier and to significantly more easterly longitudes in the Indian Ocean and Antarctic zone than terns from Greenland. We suggest an adaptive explanation for this pattern. The global migration system of the arctic tern offers an extraordinary possibility to understand adaptive values and constraints in complex pelagic life cycles, as determined by environmental conditions (marine productivity, wind patterns, low-pressure trajectories, pack-ice distribution), inherent factors (flight performance, molt, flocking), and effects of predation/piracy and competition.


Lymphocytes recognize human vascular endothelial and dermal fibroblast Ia antigens induced by recombinant immune interferon.
T-lymphocyte-mediated responses to the cellular components of blood vessels are important in rejection of allografts. The induction of cytolytic T lymphocytes (CTLs) depends on recognition of foreign class II major histocompatibility complex antigens (human HLA-DR, DC/DS, SB and others, collectively referred to as Ia) on the target cells whereas killing by CTLs usually depends on recognition of foreign class I antigens (HLA-A, B), although some alloreactive CTLs recognize foreign Ia instead of HLA-A, B (refs 5-8). The expression of Ia antigens has traditionally been regarded as restricted to immunological cell types, and the presence of class II antigen-bearing 'passenger' leukocytes in rodent organ grafts appears necessary for graft rejection. Recently, Ia antigens have been observed by immunofluorescence microscopy on human renal and dermal capillary endothelium. We have previously shown that human umbilical vein endothelial (HUVE) cells in standard culture conditions do not bear Ia antigens, but may be induced to do so by products of lectin- or alloantigen-activated T lymphocytes. Furthermore, we found that recombinant immune interferon (IFN-gamma), free of other lymphokines, is a potent inducer of Ia expression in HUVE cells. Here we report that IFN-gamma also induces Ia expression on human foreskin capillary endothelial (HFCE) cells, HUVE cells transformed by Simian virus 40 viral DNA (SV-HUVE cells) and human dermal fibroblast (HDF) cells in culture. Further, we present evidence that Ia present on HUVE cells and HDF cells can be functionally recognized by human T cells, resulting in a two-way interaction between T cells and mesenchymal cells that may be important in allograft rejection.


Differentiation induction therapy of acute myelogenous leukaemias.
This article reviews the progress achieved in the field of inducing differentiation in human myeloid leukaemia in vitro and the need for applying this model in leukaemia therapy in vivo. The pre-clinical evaluation of differentiating agents in human myeloid leukaemia is analysed. The clinical experience with differentiation induction therapy in acute myeloid leukaemia is reviewed. This review examines the prospective application of this new form of therapy in patients with acute myeloid leukaemia.


Persistent Müllerian duct syndrome: A novel mutation in the Αnti-Müllerian Ηormone gene.
Persistent Müllerian duct syndrome (PMDS) is a relatively rare form of 46,XY disorder of sex development caused by the failure of formation, release or action of anti-Müllerian hormone (AMH) in intrauterine life. In this report we describe a case diagnosed with PMDS with a novel homozygous mutation in the AMH gene. A 4-month-old male presented with bilateral cryptorchidism and normal external genitalia. The laboratory examination revealed normal gonadotropin levels for his age (FSH: 0.91 mIU/mL, LH: 1.23 mIU/mL, testosteron <0.13 ng/mL, respectively). AMH was undetectable (<0.01 ng/mL). Ultrasonography (USG) revealed absence of the left gonad and an intraabdominally located right gonad. Laparoscopy demonstrated the presence of a rudimentary uterus and fallopian tubes. Karyotyping revealed a normal 46,XY karyotype. Molecular genetic analysis demonstrated a novel homozygous mutation [p.C526F (c.1577G>T)] in the AMH gene. PMDS should be kept in mind in all cases with bilateral crytorchidism. Orchidopexy and resection of Mulletian duct derivates, exercising extra caution with regard to maintaining vascular supply to the testis, is the recommended approach.


Lung mesenchymal expression of Sox9 plays a critical role in tracheal development.
Embryonic lung development is instructed by crosstalk between mesenchyme and epithelia, which results in activation of transcriptional factors, such as Sox9, in a temporospatial manner. Sox9 is expressed in both distal lung epithelium and proximal lung mesenchyme. Here, we investigated the effect of lung mesenchyme-specific inducible deletion of Sox9 during murine lung development. Transgenic mice lacking Sox9 expression were unable to breathe and died at birth, with noticeable tracheal defects. Cartilage rings were missing, and the tracheal lumen was collapsed in the mutant trachea. In situ hybridization showed an altered expression pattern of Tbx4, Tbx5 and Fgf10 genes and marked reduction of Collagen2 expression in the tracheal mesenchyme. The tracheal phenotype was increasingly severe, with longer duration of deletion. Lymphatic vasculature was underdeveloped in the mutant trachea: Prox1, Lyve1, and Vegfr3 were decreased after Sox9 knockout. We also found that compared with normal tracheal epithelium, the mutant tracheal epithelium had an altered morphology with fewer P63-positive cells and more CC10-positive cells, fewer goblet cells, and downregulation of surfactant proteins A and C. The appropriate temporospatial expression of Sox9 in lung mesenchyme is necessary for appropriate tracheal cartilage formation, lymphatic vasculature system development, and epithelial differentiation. We uncovered a novel mechanism of lung epithelium differentiation: tracheal cartilage rings instruct the tracheal epithelium to differentiate properly during embryonic development. Thus, besides having a mechanical function, tracheal cartilage also appears to be a local signaling structure in the embryonic lung.


Extraforaminal ligament attachments of human lumbar nerves.
An anatomic study of the extraforaminal attachments of the lumbar spinal nerves was performed using human lumbar spinal columns. To identify and describe the existence of ligamentous structures at each lumbar level that attach lumbar spinal nerves to structures at the level of the extraforaminal region. During the last 120 years, several mechanisms to protect the spinal nerve against traction have been described. All these structures involved are located in the spinal canal, proximal to the intervertebral foramen. Five embalmed human lumbar spines (T12-S1) were used. Bilaterally, the extraforaminal region was dissected to describe and measure anatomic structures and their relationships. Histology was performed with staining on the sites of attachment and along the ligament. The levels T12-L2 show bilaterally 2 ligaments, a superior extraforaminal ligament and an inferior extraforaminal ligament. The superior extraforaminal ligament emerges from the joint capsule of the facet joints and inserts in both, the intervertebral disc and the ventral crista of the intervertebral foramen, passing the spinal nerve laterally. In one specimen on level L2-L3, the superior extraforaminal ligament is not attached to the spinal nerve. The inferior extraforaminal ligament emerges from the intervertebral disc, passing the nerve medially and attaching the spinal nerve. At the levels L2-L5, the inferior extraforaminal ligaments are only attached to the intervertebral disc, not to the joint capsule. Histologically, the ligaments consisted of mainly collagenous structures. Ligamentous connections exist between lumbar extraforaminal spinal nerves and nearby structures.


Supplementary comments on the standardization of auricular points.
This paper is intended to supplement accurate descriptions concerning auricular point location and provide studies in establishing basic landmarks of the auricle. This paper mainly discusses the medial border of helix, antihelix peak, scapha groove, antihelix scapha border, cymba concha border of the antihelix, deltoid fossa border of the antihelix, cymba concha folding line, cymba concha border of the antitragus, upper line of ear lobe, and the anterior border of tragus.


Marine toxins.
Seafood products are important both nutritionally and economically. Within Europe, some 12 billion Pounds of fishery products are consumed annually and an enormous variety of species are available. Although seafood is rarely implicated in food poisoning, compared to other food sources, it does provide some specific human health hazards unique to this particular resource. Generally, these are toxins from toxic microscopic algae which accumulate through the food-chain. The toxins can cause various neurological and gastrointestinal illnesses and, potentially, consumers are exposed from seafood produced within Europe, from imported products, or from seafood eaten while travelling abroad. The symptoms of illness which may be encountered, the source and mode of action of the toxins, and some emerging problems are described. European legislation aims to ensure the quality and safety of seafood products by prohibiting sale of some toxic species, setting toxin limits, requiring monitoring and controlling imports.


The use of unirradiated and γ-irradiated zinc oxide nanoparticles as a preservative in cosmetic preparations.
Microbial contamination of different cosmetic preparations, as a result of preservative failure, presents a major public health threat. Also, most of the known preservatives have serious consumer side effects. The antimicrobial activity of zinc oxide nanoparticles (ZnO NP) is well documented. Therefore, we aimed to determine the possible use of unirradiated and γ-irradiated ZnO NP as a cosmetic preservative. The possible use of ZnO NP as a preservative was tested and compared to commonly used preservatives using a challenge test. Their activity was tested in six different types of preparations. The effect of γ radiation on the antimicrobial activity of ZnO NP was tested through determination of the obtained zone diameters against different microorganisms and the total aerobic microbial count in tested preparations. The antimicrobial activity, of unirradiated and γ-irradiated ZnO NP during storage was also determined. ZnO NP were superior to other commonly used preservatives in all tested cosmetic preparations. They pass the challenge test in all types of tested preparations. γ irradiation enhanced their antimicrobial activity in all tested preparations. The irradiation causes a reduction in NP sizes that is directly proportional to the applied radiation dose. Upon storage, ZnO NP were effective in maintaining the microbial count of the product within the acceptable range. Their activity in stored products was enhanced by γ irradiation. Unirradiated and γ-irradiated ZnO NP can be used as effective preservatives. They are compatible with the components of all tested products. γ irradiation enhanced the antimicrobial activity of ZnO NP.


Retinal "Caratopathy": Diamond Dust Residuals after Surgeries.
Diamond dust particles were identified within patients' eyes both during vitrectomy procedures using diamond-dusted membrane scrapers and in postoperative clinical examinations. The particles had no impact on the patients' vision and caused no apparent sequelae. Scanning electron microscopy analysis showed the average particle size to be 23.4 μm and an unequal surface area for particle adhesion onto the soft tip. It was determined that diamond dust particles can dislodge from the silicone tip of the Tano diamond-dusted membrane scrapers during the insertion into valve trocars throughout vitrectomy operations and deposit on the retinal surface or within macular holes. Ophthalmologists should be aware of residual diamond particles during procedures and consider diamond dust retinopathy in the differential diagnosis of crystalline retinopathies. Understanding the appearance of residual particles on the retina allows for future studies revealing the long-term impact on patient's visual performance.


Identifying adolescent protective factors that disrupt the intergenerational transmission of cannabis use and disorder.
Adolescent cannabis use is common, has been associated with several deleterious outcomes, and is often associated with previous parent cannabis use. Therefore, identifying protective factors that prevent this intergenerational transmission of cannabis use is increasingly important given shifting contemporary policies around cannabis use. The present study examines 3 protective factors in adolescence (active coping, positive activity involvement, and school grades) that may disrupt patterns of intergenerational cannabis use. The present study uses data from a high-risk longitudinal sample followed for over 30 years that includes Generation 1 (G1) parents (54.19% with lifetime alcohol use disorder, 8.15% with lifetime cannabis use disorder), their Generation 2 (G2) children, and their Generation 3 (G3) grandchildren and therefore provides the opportunity to replicate effects across 2 intergenerational cohorts (a G1-G2 cohort and a G2-G3 cohort). Results from ordered logistic regression models reveal that in both intergenerational cohorts, greater midadolescent active coping, higher positive activity involvement, and higher grades prospectively predict lower late adolescent cannabis use at significant (p < .05) or marginal (p < .10) levels, even after powerful control variables, such as parent cannabis use and alcohol use, as well as previous early adolescent cannabis use, are accounted for. Additionally, in both intergenerational cohorts, midadolescent high levels of active coping disrupt intergenerational transmission of cannabis use. Results indicate replication in the intergenerational transmission of cannabis use and in the protective effects of coping, grades, and, to a lesser extent, positive activity involvement across generational cohorts. Implications for prevention programming are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Cytodiagnosis of rheumatoid pleural effusions.
The stained smears of the deposits from one pericardial and 19 pleural effusions complicating rheumatoid arthritis were examined. On the basis of clinical and biochemical evidence it was considered that in six cases the effusions were due to the rheumatoid disease while in a further nine cases the association was considered likely. In the remaining five cases the association was considered to be due to chance as other causes for the effusions were diagnosed. On cytological examination, seven cases showed a characteristic picture of degenerating polymorphs with amorphous extracellular material and epithelioid cells many of which were multinucleate. Five others contained similar amorphous material without epithelioid cells; of these two had many plasma cells and a third numerous macrophages probably containing ;droplets' of rheumatoid factor complex. Thus in 12 of 15 cases a definite diagnosis of rheumatoid effusion could be made. In the remaining five cases cytological examination confirmed that the effusions were unrelated to the rheumatoid disease.The extracellular material gave a non-specific fluorescence with labelled anti-gamma globulin antisera, and since this reaction was not seen in control pleural fluid deposits, or with preparations of fibrin, it may have a confirmatory value. It is concluded that in many cases reliable cytological evidence can be found to confirm or refute a diagnosis of rheumatoid pleural or pericardial effusion. This may be helpful in the management of the rheumatoid disease.


Multiplexing of multicolor bioluminescence resonance energy transfer.
Bioluminescence resonance energy transfer (BRET) is increasingly being used to monitor protein-protein interactions and cellular events in cells. However, the ability to monitor multiple events simultaneously is limited by the spectral properties of the existing BRET partners. Taking advantage of newly developed Renilla luciferases and blue-shifted fluorescent proteins (FPs), we explored the possibility of creating novel BRET configurations using a single luciferase substrate and distinct FPs. Three new (to our knowledge) BRET assays leading to distinct color bioluminescence emission were generated and validated. The spectral properties of two of the FPs used (enhanced blue (EB) FP2 and mAmetrine) and the selection of appropriate detection filters permitted the concomitant detection of two independent BRET signals, without cross-interference, in the same cells after addition of a unique substrate for Renilla luciferase-II, coelentrazine-400a. Using individual BRET-based biosensors to monitor the interaction between G-protein-coupled receptors and G-protein subunits or activation of different G-proteins along with the production of a second messenger, we established the proof of principle that two new BRET configurations can be multiplexed to simultaneously monitor two dependent or independent cellular events. The development of this new multiplexed BRET configuration opens the way for concomitant monitoring of various independent biological processes in living cells.


Discontinuation and nonpublication of pediatric otolaryngology clinical trials.
Randomized controlled trial (RCT) discontinuation and nonpublication are potential mechanisms of waste in resources and lead to decreased advancement of medical science and compromised ethical issues in all specialties. However, the prevalence of discontinued or unpublished RCTs regarding common pediatric otolaryngology disorders and interventions remains unclear. Cross-sectional analysis. Retrospective analysis of common pediatric otolaryngology RCTs registered in ClinicalTrials.gov up until November 2, 2018. Data were collected from the registry, and publication status was identified. If a reason for trial discontinuation or nonpublication was not identified through a systematic search, corresponding trialists were contacted through email. After exclusion, 260 RCTs were included for analysis. Analysis found 198 (76%) RCTs were completed, and 62 (24%) trials were discontinued. The most commonly reported reasons for RCT discontinuation were program termination by sponsor or management (7/24; 29.2%), lack of participant enrollment, difficulty recruiting, or slow accrual (7/24; 29.2%). A total of 192 (192/260; 73.8%) published RCTs and 68 (68/260; 26.2%) unpublished RCTs were identified. Twenty-six (26/62; 42%) of the discontinued RCTs reached publication, while 36 (58%) remained unpublished. Regarding the completed RCTs, 166 of 198 (83.8%) completed trials reached publication, while 32 (32/198; 16.2%) remained unpublished after trial completion. Approximately 1 in 4 of included RCTs were discontinued or did not reach publication. Findings suggest further guidance is needed for RCTs regarding common pediatric otolaryngology disorders and interventions. NA.


Acquisition of mental state language in Spanish children: a longitudinal study of the relationship between the production of mental verbs and linguistic development.
The development of language indicating the emergence of thinking about the thoughts of self and others has been scarcely studied in Spanish-speaking children. For this reason, we studied the development of mental state language and various indicators of language development in 25 Spanish-speaking children assessed at 3, 3 1/2, 4, 4 1/2, and 5 years of age. We coded and categorized the 40,250 utterances children produced during the five time points, 1202 (3.01%) of which had mental terms. In this sample, mental state language in Spanish children developed with a similar timeline and patterns as described in English-speaking children. However, several findings were novel for studies of mental state language. The general indexes of syntactic development did not correlate with the production of mental terms. The Index of Lexical Diversity was associated with the frequency of references to verbs of desire. The results of regression analyses suggest that not only the development of subordinate sentences with complement is associated with genuine mental references to desires and beliefs, but the development of lexical skills as well.


Electroconvulsive Therapy in Depression: Improvement in Quality of Life Depending on Age and Sex.
It is uncertain if there are variations in the improvement of quality in life between sexes and age groups after electroconvulsive therapy (ECT). The aim of this study was to investigate how health-related quality of life changed after treatment and to examine differences in the results between sex and age groups. This register-based study used data from the Swedish national quality register for ECT. The study population was patients diagnosed with depression who had received ECT. Health-related quality of life was quantified using the 3-level version the EuroQol 5-dimensional questionnaire (EQ-5D 3 L). Analysis of variance was used to compare change in EQ-5D score from pretreatment to posttreatment between sex and age groups. There was a statistically significant improvement in EQ-5D index score and EQ visual analog scale (VAS) score in all patient groups after ECT. The mean improvement in EQ-5D index score and EQ-VAS score ranged from 0.31 to 0.46 and 28.29 to 39.79, respectively. Elderly patients had greater improvement in EQ-5D index score and EQ-VAS score than younger patients. There was no significant difference in improvement between the sexes. The mean improvement in EQ-5D index score was 0.40 for male patients and 0.41 for female patients. Electroconvulsive therapy had a considerable effect on health-related quality of life in patients with depression of both sexes and all age groups. The improvement was greatest in elderly patients, who more often had psychotic features. More studies are needed to investigate the long-term effects of ECT and to further explain the varying treatment results between elderly and younger patients.


Risk of early, intermediate, and late rejection following heart transplantation: Trends over the past 25 years and relation to changes in medical management. Tertiary center experience: The Sheba Heart Transplantation Registry.
To explore the trends in the risk for rejection following heart transplantation (HT) over the past 25 years, and their relation to changes in medical management. The study population comprised 216 HT patients. Rejection periods were defined as follows: 0-3 months (early), 3-12 months (intermediate), and 12+ months (late). HT era was dichotomized as follows: 1991-1999 (remote era) and 2000-2016 (recent era). Medication combination was categorized as newer (TAC, MMF, and everolimus) vs older therapies (AZA, CSA). Multivariate analysis showed that patients who underwent HT during the recent era experienced a significant reduction in the risk for major rejection. These findings were consistent for early (OR = 0.44 [95% CI 0.22-0.88]), intermediate (OR = 0.02 [95% CI 0.003-0.11]), and late rejections (OR = 0.18 [95% CI 0.05-0.52]). Using the year of HT as a continuous measure showed that each 1-year increment was independently associated with a significant reduction in the risk for early, intermediate, and late rejections (5%, 21%, 18%, respectively). In contrast, the risk reduction associated with newer types of immunosuppressive therapies was not statistically significant after adjustment for the treatment period. Major rejection rates following HT have significantly declined over the past 2 decades even after adjustment for changes in immunosuppressive therapies, suggesting that other factors may also play a role in the improved outcomes of HT recipients.


Impaired recruitment of the small GTPase rab7 correlates with the inhibition of phagosome maturation by Leishmania donovani promastigotes.
We have shown recently that one of the survival strategies used by Leishmania donovani promastigotes during the establishment of infection in macrophages consists in inhibiting phagosome-endosome fusion. This inhibition requires the expression of lipophosphoglycan (LPG), the predominant surface glycoconjugate of promastigotes, as parasites expressing truncated forms of LPG reside in phagosomes that fuse extensively with endocytic organelles. In the present study, we developed a single-organelle fluorescence analysis approach to study and analyse the intracellular trafficking of 'fusogenic' and 'low-fusogenic' phagosomes induced by an LPG repeating unit-defective mutant (Ipg2 KO) or by wild-type L. donovani promastigotes respectively. The results obtained indicate that phagosomes containing mutant parasites fuse extensively with endocytic organelles and transform into phagolysosomes by losing the early endosome markers EEA1 and transferrin receptor, and acquiring the late endocytic and lysosomal markers rab7 and LAMP1. In contrast, a majority of 'low-fusogenic' phagosomes containing wild-type L. donovani promastigotes do not acquire rab7, wheres they acquire LAMP1 with slower kinetics. These results suggest that L. donovani parasites use LPG to restrict phagosome-endosome fusion at the onset of infection in order to prevent phagosome maturation. This is likely to permit the transformation of hydrolase-sensitive promastigotes into hydrolase-resistant amastigotes within a hospitable vacuole not displaying the harsh environment of phagolysosomes.


The effects of biofeedback on rectal sensation and distal colonic motility in patients with disorders of rectal evacuation: evidence of an inhibitory rectocolonic reflex in humans?
Abnormalities of descending colon motility reported in a subset of patients with rectal evacuation disorders are consistent with a rectocolonic inhibitory reflex. Our aims were to evaluate distal colon motor function and rectal sensation in such patients and assess effects of biofeedback (BF) training on these functions. Seven patients (five women, two men; mean age 36 yr) with rectal evacuation disorders were studied before and after 10-days biofeedback training; six healthy volunteers (five women, one man; mean age 30 yr) were studied once. Colonic compliance, motility, sensation thresholds, and perception scores during standardized rectal distentions were measured using two barostat-manometry assemblies inserted into the cleansed colon with the aid of flexible sigmoidoscopy. Sigmoid compliance, fasting, and postprandial motility index, and perception thresholds were similar in controls and patients before and after biofeedback training. Postprandial sigmoid tone tended (p = 0.09) to be lower in patients than controls; after biofeedback, postprandial tone was comparable to that in controls. Rectal urgency scores at 24 mm Hg distention were greater in patients than in controls (p = 0.02 for both). After biofeedback, there were trends for lower perceptions of urgency to defecate (7.6 +/- 1.1 cm pre- vs 5.3 +/- 1.5 post-; p = 0.04) at 24 mm Hg; conversely, gas sensation at 12 mm Hg was higher (1.2 +/- 0.5 cm pre- vs 3.3 +/- 0.6 post-; p = 0.05). Normalization of rectal evacuation and postprandial sigmoid tone in patients with evacuation disorders by biofeedback training supports the presence of a rectocolonic inhibitory reflex. Effect of biofeedback on rectal sensation in these patients requires further study.


A DGGE Marker-Mediated Fast Monitoring of Bacterial Diversity and Comprehensive Identification of High-Temperature Daqu Starter.
Bacteria play an essential role in Daqu starter (Daqu) fermentation. The identification of Daqu bacteria was investigated by polymerase chain reaction (PCR) based denaturing gradient gel electrophoresis (DGGE) analysis of the highly variable V3 region of the 16S rRNA gene. Here, we define a novel DGGE marker for the quick identification of Daqu bacteria. A dynamic alteration of the bacterial populations at different stages of fermentation was determined through a 2-y continuous monitoring. The physicochemical parameters of Daqu at different fermentation stages were investigated by weighing, NaOH titration, and HCl hydrolysis together with Fehling reagent methods. Furthermore, infrared spectral analysis using Fourier Transformed Infrared Spectroscopy was performed to determine physicochemical changes of Daqu. Therefore, our studies provide key insight for a comprehensive quality control of Daqu at different fermentation stages using the PCR-DGGE analysis combined with the physicochemical measurement. Chinese liquor is one of the 6 well-known distilled spirits in the world. High-temperature Daqu acts as an important source of nutrients and of microorganisms in the solid-state fermentation of Chinese Moutai-flavor liquor, which has a critical impact on the final flavor of the liquor. The study identifies a novel DGGE marker and provides an efficient way to identify bacterial diversity in Daqu from different fermentation stages. Importantly, the study defines dynamic changes of the physicochemical parameters and the infrared spectra analysis of Daqu during the fermentation process. These studies will help to (1) establish a standard operation procedure for Daqu production; (2) stabilize manufacturing process for Daqu fermentation and even for liquor brewing.


Detection of an Anaplasma marginale common surface protein present in all stages of infection.
The establishment and maintenance of anaplasmosis-free cattle herds is impaired due to the lack of a rapid, sensitive, and specific serologic test to detect persistently infected cattle which serve as carriers for the organism. To develop an improved diagnostic test for anaplasmosis we screened Anaplasma marginale initial body proteins to identify a protein common to antigenically different isolates that is recognized by the host immune system at all stages of infection. Seronegative cattle were infected with either the Florida, Virginia, or North Texas isolate of A. marginale and monitored for infection by daily examination of Wright-stained blood smears for parasitized erythrocytes. Sera from cattle at different stages of infection, from acute through persistent, were used to immunoprecipitate A. marginale proteins that were metabolically radiolabeled with [35S]methionine or surface radiolabeled with 125I. Multiple A. marginale proteins were recognized by using sera either undiluted or at 1:10; however, only four or five proteins were sufficiently antigenic to elicit antibody reactive with a 1:1,000 serum dilution. A single protein with an apparent molecular mass of 86 kilodaltons was consistently recognized at all stages of infection regardless of the isolate used to infect the cattle. This protein was demonstrated to be on the surface of the A. marginale initial body and to be water soluble. We propose use of this 86-kilodalton protein to develop an improved serologic test for diagnosis of bovine anaplasmosis.


Neoadjuvant Chemotherapy versus Chemoradiation Prior to Esophagectomy: Impact on Rate of Complete Pathologic Response and Survival in Esophageal Cancer Patients.
The aim of this study was to evaluate differences in pathologic complete response (pCR) rates and overall survival among patients receiving either neoadjuvant chemotherapy or chemoradiation before esophagectomy for locally advanced esophageal cancer. Patients with esophageal cancer receiving either neoadjuvant chemotherapy or chemoradiation before esophagectomy were identified using the National Cancer Database. Univariate analysis compared patient, tumor, and postoperative outcome characteristics. Logistic regression was performed to identify variables associated with achieving pCR. Kaplan-Meier analysis was performed to compare overall median survival by neoadjuvant therapy type and pCR status. Finally, a Cox proportional hazards model was fitted to identify variables associated with increased mortality hazard. From 2006 to 2012, a total of 916 of 7338 of patients (12.5%) received neoadjuvant chemotherapy whereas 6422 (87.5%) received neoadjuvant chemoradiation. Patients who received neoadjuvant chemoradiation were more likely to achieve a pCR (17.2% versus 6.4%, p < 0.001) and less likely to have positive margins (5.6% versus 11.5%, p < 0.001) than were patients who received neoadjuvant chemotherapy, with no difference in 30- or 90-day mortality. Achieving a pCR was associated with improved overall median survival (59.5 ± 4.0 months versus 30.1 ± 0.76 months for those with persistent disease, p < 0.001). On logistic regression, neoadjuvant chemoradiation therapy was independently associated with achieving a pCR (OR = 2.75, 95% confidence interval: 2.01-3.77, p < 0.001). Despite improvement in the pCR rate with neoadjuvant chemoradiation, neoadjuvant therapy type was not independently associated with long-term survival (hazard ratio = 1.12; 95% confidence interval: 0.97-1.30, p = 0.12). Although neoadjuvant chemoradiation is more successful in downstaging esophageal cancer before esophagectomy, it was not independently prognostic for improved long-term survival. Other factors affecting long-term survival among pathologic complete responders and among patients with persistent disease should be investigated to clarify this association.


Mixed-dimensional MXene-hydrogel heterostructures for electronic skin sensors with ultrabroad working range.
Skin-mountable microelectronics are garnering substantial interest for various promising applications including human-machine interfaces, biointegrated devices, and personalized medicine. However, it remains a critical challenge to develop e-skins to mimic the human somatosensory system in full working range. Here, we present a multifunctional e-skin system with a heterostructured configuration that couples vinyl-hybrid-silica nanoparticle (VSNP)-modified polyacrylamide (PAM) hydrogel with two-dimensional (2D) MXene through nano-bridging layers of polypyrrole nanowires (PpyNWs) at the interfaces, featuring high toughness and low hysteresis, in tandem with controlled crack generation and distribution. The multidimensional configurations endow the e-skin with an extraordinary working range (2800%), ultrafast responsiveness (90 ms) and resilience (240 ms), good linearity (800%), tunable sensing mechanisms, and excellent reproducibility. In parallel, this e-skin platform is capable of detecting, quantifying, and remotely monitoring stretching motions in multiple dimensions, tactile pressure, proximity sensing, and variations in temperature and light, establishing a promising platform for next-generation smart flexible electronics.


The fall of cardiac output in endotoxemic rats cannot explain all changes in organ blood flow: a comparison between endotoxin and low venous return shock.
During endotoxin shock mean arterial pressure (MAP) and cardiac output (CO) fall, and the latter is redistributed. To evaluate whether these changes are solely caused by the low output, or are also based on endotoxin itself, we compared regional hemodynamic changes during endotoxemia with those in a nonendotoxemic state of decreased CO in anesthetized rats. In group E (n = 10) endotoxin Escherichia coli O127:B8 (8 mg.kg-1) was infused from t = 0 till t = 60 min. In group B (n = 10) the same decrease of CO and MAP was obtained as in group E by inflating a balloon in the inferior caval vein, distal to the renal veins, from t = 0 till t = 60 min. We measured MAP, CO (thermodilution), central venous pressure, heart rate, organ blood flow, and redistribution of CO (microspheres), arterial lactate and glucose, and hematocrit. MAP and CO decreased (p < .05) in both groups (by 30 and 50%, respectively at t = 60). Heart rate, hematocrit, arterial lactate, and arterial glucose were significantly higher (p < .05) in group E (by 17, 12, 180, and 55%, respectively). Blood flow to most organs had similarly decreased in both groups. The decreased intestinal blood flow lead to macroscopic damage only in group E. Blood flows (absolute or as percentage of CO) to heart, hepatic artery, and diaphragm, however, had significantly increased in group E while blood flows to skin, skeletal muscle, and stomach had decreased more in group E. Except for the heart these differences could be explained by increased work load (detoxification: liver; hyperventilation: diaphragm, muscle) and thus to a more pronounced redistribution at the expense of skin and muscle blood flow. Regional hemodynamic changes during endotoxemia thus could largely be attributed to decrease of CO and redistribution of the circulating blood volume. In the heart, endotoxin seemed to exert effects independent of the hypodynamic state. This was also true for the intestinal damage and the rise in hematocrit and arterial lactate.


Mechanically unloading the left ventricle before coronary reperfusion reduces left ventricular wall stress and myocardial infarct size.
Ischemia/reperfusion injury worsens infarct size, a major determinant of morbidity and mortality after acute myocardial infarction (MI). We tested the hypothesis that reducing left ventricular wall stress with a percutaneous left atrial-to-femoral artery centrifugal bypass system while delaying coronary reperfusion limits myocardial injury in a model of acute MI. MI was induced by balloon occlusion of the left anterior descending artery in adult male swine. In the MI group (n=4), 120 minutes of left anterior descending artery occlusion was followed by 120 minutes of reperfusion without mechanical support. In the mechanically supported group (MI+unload; n=4), percutaneous left atrial-to-femoral artery bypass was initiated after 120 minutes of ischemia, and left anterior descending artery occlusion was prolonged for an additional 30 minutes, followed by 120 minutes of reperfusion with device support. All animals were euthanized after reperfusion, and infarct size was quantified by triphenyltetrazolium chloride staining. Compared with baseline, mean left ventricular wall stress and stroke work were not changed at any point in the MI group but were decreased after reperfusion in the MI+unload group (mean left ventricular wall stress, 44 658 versus 22 963 dynes/cm(2); stroke work, 2823 versus 655 mm Hg·mL, MI versus MI+unload). Phosphorylation of reperfusion injury salvage kinase pathway proteins from noninfarcted left ventricular tissue was unchanged in the MI group but was increased in the MI+unload group. Compared with the MI group, total infarct size was reduced in the MI+unload group (49% versus 28%, MI versus MI+unload). These data support that first unloading the left ventricle despite delaying coronary reperfusion during an acute MI reduces myocardial injury.


Comparing Performance During Morning vs. Afternoon Training Sessions in Intercollegiate Basketball Players.
Time of day is a key factor that influences the optimization of athletic performance. Intercollegiate coaches oftentimes hold early morning strength training sessions for a variety of factors including convenience. However, few studies have specifically investigated the effect of early morning vs. late afternoon strength training on performance indices of fatigue. This is athletically important because circadian and/or ultradian rhythms and alterations in sleep patterns can affect training ability. Therefore, the purpose of the present study was to examine the effects of morning vs. afternoon strength training on an acute performance index of fatigue (countermovement jump height, CMJ), player readiness (Omegawave), and self-reported sleep quantity. We hypothesized that afternoon training sessions would be associated with increased levels of performance, readiness, and self-reported sleep. A retrospective analysis was performed on data collected over the course of the preseason on 10 elite National Collegiate Athletic Association Division 1 male basketball players. All basketball-related activities were performed in the afternoon with strength and conditioning activities performed either in the morning or in the afternoon. The average values for CMJ, power output (Power), self-reported sleep quantity (sleep), and player readiness were examined. When player load and duration were matched, CMJ (58.8 ± 1.3 vs. 61.9 ± 1.6 cm, p = 0.009), Power (6,378.0 ± 131.2 vs. 6,622.1 ± 172.0 W, p = 0.009), and self-reported sleep duration (6.6 ± 0.4 vs. 7.4 ± 0.25 p = 0.016) were significantly higher with afternoon strength and conditioning training, with no differences observed in player readiness values. We conclude that performance is suppressed with morning training and is associated with a decrease in self-reported quantity of sleep.


Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis.
Since its discovery in 2007, the encephalitis associated with antibodies against the N-methyl-D-aspartate receptor (NMDAR) has entered the mainstream of neurology and other disciplines. Most patients with anti-NMDAR encephalitis develop a multistage illness that progresses from psychosis, memory deficits, seizures, and language disintegration into a state of unresponsiveness with catatonic features often associated with abnormal movements, and autonomic and breathing instability. The disorder predominantly affects children and young adults, occurs with or without tumour association, and responds to treatment but can relapse. The presence of a tumour (usually an ovarian teratoma) is dependent on age, sex, and ethnicity, being more frequent in women older than 18 years, and slightly more predominant in black women than it is in white women. Patients treated with tumour resection and immunotherapy (corticosteroids, intravenous immunoglobulin, or plasma exchange) respond faster to treatment and less frequently need second-line immunotherapy (cyclophosphamide or rituximab, or both) than do patients without a tumour who receive similar initial immunotherapy. More than 75% of all patients have substantial recovery that occurs in inverse order of symptom development and is associated with a decline of antibody titres. Patients' antibodies cause a titre-dependent, reversible decrease of synaptic NMDAR by a mechanism of crosslinking and internalisation. On the basis of models of pharmacological or genetic disruption of NMDAR, these antibody effects reveal a probable pathogenic relation between the depletion of receptors and the clinical features of anti-NMDAR encephalitis.


Aging Q3: an initiative to improve internal medicine residents' geriatrics knowledge, skills, and clinical performance.
A growing number of older adults coupled with a limited number of physicians trained in geriatrics presents a major challenge to ensuring quality medical care for this population. Innovations to incorporate geriatrics education into internal medicine residency programs are needed. To meet this need, in 2009, faculty at the Medical University of South Carolina developed Aging Q(3)-Quality Education, Quality Care, and Quality of Life. This multicomponent initiative recognizes the need for improved geriatrics educational tools and faculty development as well as systems changes to improve the knowledge and clinical performance of residents. To achieve these goals, faculty employ multiple intervention strategies, including lectures, rounds, academic detailing, visual cues, and electronic medical record prompts and decision support. The authors present examples from specific projects, based on care areas including vision screening, fall prevention, and caring for patients with dementia, all of which are based on the Assessing Care of Vulnerable Elders quality indicators. The authors describe the principles driving the design, implementation, and evaluation of the Aging Q(3) program. They present data from multiple sources that illustrate the effectiveness of the interventions to meet the knowledge, skill level, and behavior goals. The authors also address major challenges, including the maintenance of the teaching and modeling interventions over time within the context of demanding primary care and inpatient settings. This organized, evidence-based approach to quality improvement in resident education, as well as faculty leadership development, holds promise for successfully incorporating geriatrics education into internal medicine residencies.


Posterior urethral valves and adult sexual function.
To evaluate sexual function and fertility in adult patients treated for posterior urethral valves (PUV) in childhood and to compare these patients with the normal population. To examine if patient characteristics such as chronic renal failure (CRF), history of cryptorchidism and bladder neck incision in childhood have an impact on sexual function. Information on sexual function was assessed using questions from the International Index of Erectile Function (IIEF). In addition, the patients were asked if they had had children or been treated for CRF. Out of 108 adult patients with PUV, 67 (62%) returned the questionnaires. Sexual function in these patients was compared with 201 controls and paternity rates were compared with a national database. The mean (sd) age of the patients and controls was 38 (9) and 38 (7) years, respectively. Six percent of the patients and 9% of the controls reported problems in achieving erection during sexual stimulation and 9% of the patients and 10% of the controls reported problems with the hardness of erection (P = nonsignificant). Ejaculation was absent in 1/61 sexually active patients (2%). The only significant risk factor in patients for erectile dysfunction (ED) was increasing age. Thirty-three (49%) of all 67 patients and four (57%) of the seven patients with kidney transplantation had had children. The paternity rates were similar to those in corresponding age groups of the general Finnish population. Eight patients (12%) had attempted to have children without success. Men treated for PUV have a similar prevalence of ED and similar paternity rates to men without PUV. Erectile function and paternity rates can be satisfactory in spite of CRF.


New paradigm old thinking: The case for emergency obstetric care in the prevention of maternal mortality in Nigeria.
The continuing burden of maternal mortality, especially in developing countries has prompted a shift in paradigm from the traditional risk assessment approach to the provision of access to emergency obstetric care services for all women who are pregnant. This study assessed the knowledge of maternity unit operatives at the primary and secondary levels of care about the concept of emergency obstetric care (EmOC) and investigated the contents of antenatal care (ANC) counseling services they delivered to clients. It also described the operatives' preferred strategies and practices for promoting safe motherhood and averting maternal mortality in South-west Nigeria. The study population included all the 152 health workers (doctors, midwives, nurses and community health extension workers) employed in the maternity units of all the public health facilities (n = 22) offering maternity care in five cities of 2 states. Data were collected with the aid of a self-administered, semi-structured questionnaire and non-participant observation checklist. Results were presented using descriptive statistics. Ninety one percent of the maternity unit staff had poor knowledge concerning the concept of EmOC, with no difference in knowledge of respondents across age groups. While consistently more than 60% of staff reported the inclusion of specific client-centered messages such as birth preparedness and warning/danger signs of pregnancy and delivery in the (ANC) delivered to clients, structured observations revealed that less than a quarter of staff actually did this. Furthermore, only 40% of staff reported counseling clients on complication readiness, but structured observations revealed that no staff did. Only 9% of staff had ever been trained in lifesaving skills (LSS). Concerning strategies for averting maternal deaths, 70% of respondents still preferred the strengthening of routine ANC services in the health facilities to the provision of access to EmOC services for all pregnant women who need it. We concluded that maternity unit operatives at the primary and secondary care levels in South-west Nigeria were poorly knowledgeable about the concept of emergency obstetric care services and they still prioritized the strengthening of routine antenatal care services based on the risk approach over other interventions for promoting safe motherhood despite a global current shift in paradigm. There is an urgent need to reorientate/retrain the staff in line with global best practices.


Regulatory T cells in HIV-infected immunological nonresponders are increased in blood but depleted in lymphoid tissue and predict immunological reconstitution.
HIV-infected immunological nonresponders fail to immune reconstitute despite optimal treatment. We hypothesized that regulatory T cells (Tregs) are involved in immunological reconstitution. Tregs and Treg subpopulations were measured in blood and Foxp3 cells in lymphoid tissue, and the impact of Tregs on immunological reconstitution was determined. HIV-infected individuals on combination antiretroviral therapy for a minimum of 2 years were included. The study population included 14 immunological nonresponders (INR; CD4 T-cell count <200 cells/μL), 33 intermediate responders (CD4 T-cell count 200-500 cells/μL), 30 responders (CD4 T-cell count >500 cells/μL), and 34 healthy controls. Tregs, Treg subpopulations, and intracellular staining for interleukin 10 in peripheral blood were measured using flow cytometry. Foxp3 cells in lymphoid tissue were evaluated using immunolabeling. The CD4 T-cell count was determined at inclusion and after 1 year of follow-up. INR displayed high percentage of Tregs and activated Tregs in peripheral blood accompanied by a high percentage of Tregs expressing interleukin 10, whereas numbers of Foxp3 cells in lymphoid tissue were low. In contrast, responders resembled healthy controls. Finally, in INR, high level of Tregs in blood and Foxp3 cells in lymphoid tissue were associated with higher level of immunological reconstitution after 1 year of follow-up. In conclusion, altered distribution of Tregs was found in INR. Interestingly, high level of Tregs predicted higher level of immunological reconstitution suggesting a role for Tregs in immunological reconstitution.


Performance of multi-city land use regression models for nitrogen dioxide and fine particles.
Land use regression (LUR) models have been developed mostly to explain intraurban variations in air pollution based on often small local monitoring campaigns. Transferability of LUR models from city to city has been investigated, but little is known about the performance of models based on large numbers of monitoring sites covering a large area. We aimed to develop European and regional LUR models and to examine their transferability to areas not used for model development. We evaluated LUR models for nitrogen dioxide (NO2) and particulate matter (PM; PM2.5, PM2.5 absorbance) by combining standardized measurement data from 17 (PM) and 23 (NO2) ESCAPE (European Study of Cohorts for Air Pollution Effects) study areas across 14 European countries for PM and NO2. Models were evaluated with cross-validation (CV) and hold-out validation (HV). We investigated the transferability of the models by successively excluding each study area from model building. The European model explained 56% of the concentration variability across all sites for NO2, 86% for PM2.5, and 70% for PM2.5 absorbance. The HV R2s were only slightly lower than the model R2 (NO2, 54%; PM2.5, 80%; PM2.5 absorbance, 70%). The European NO2, PM2.5, and PM2.5 absorbance models explained a median of 59%, 48%, and 70% of within-area variability in individual areas. The transferred models predicted a modest-to-large fraction of variability in areas that were excluded from model building (median R2: NO2, 59%; PM2.5, 42%; PM2.5 absorbance, 67%). Using a large data set from 23 European study areas, we were able to develop LUR models for NO2 and PM metrics that predicted measurements made at independent sites and areas reasonably well. This finding is useful for assessing exposure in health studies conducted in areas where no measurements were conducted.


Microemulsions, nanoemulsions and emulgels as carriers for antifungal antibiotics.
According to estimates, up to 25% of the world's population has fungal skin diseases, making them the most prevalent infectious disease. Several chemical classes of antifungal drugs are available to treat fungal infections. However, the major challenges of conventional formulations of antifungal drugs include poor pharmacokinetic profiles like solubility, low permeability, side effects and decreased efficacy. Novel drug delivery is a promising approach for overcoming pharmacokinetic limitations and increasing the effectiveness of antibiotics. In this review, we have shed light on microemulsions, nanoemulsions, and emulgels as novel drug delivery approaches for the topical delivery of antifungal antibiotics. We believe these formulations have potential translational value and could be developed for treating fungal infections in humans.


[The influence of grade 1 stress urinary incontinence on the physical activity of women depending on nutritional status as defined by the Body Mass Index].
Stress urinary incontinence (SUI) and obesity are problems recognized by the World Health Organization as social diseases. The International Continence Society has estimated that about 10–40% of women have problems with urinary incontinence. Overweight states and obesity are among the biggest health problems in perimenopausal women. The aim of the study was to analyze the impact of SUI on the physical activity (PA) of women in relation to their body weight. The study comprised 54 women aged 41–67 years with SUI. Anthropometric measurements were taken. Physical activity was examined by specially designed questionnaires. The statistical significance was calculated in the Statistica 12 software using normality tests, correlation coefficient, nonparametric tests, and a post -hoc test. The mean age of subjects was 55 ±7 years. Body Mass Index (BMI) in subjects was normal (N1) – 11 (20.4%), or indicated the state of being overweight (N2) – 33 (59.2%) or obese (N3) – 11 (20.4%); 94% (51) patients had the android body type and 6% (3) had the gynoidal body type. PA before the onset of problems with SUI was assessed by patients as a sedentary lifestyle – 12 (22.2%), active – 23 (42.6%) or mixed – 19 (35.2%). Subjects, when asked how strong the impact of SUI on their PA was, answered: minor 13 (24.1%), moderate – 14 (25.9%), very strong – 27 (50%). No statistically signi􀏐icant differences between PA and SUI were found in N1, N2 and N3 groups. Overweight patients reported the strongest impact of SUI on their PA, but the differences between the analysed groups were not signi􀏐icant. Most subjects had the android body type, which was assessed by means of WHR.


Guillain-Barré Syndrome During Platinum-Based Chemotherapy: A Case Series and Review of the Literature.
Platinum-based chemotherapy is commonly associated with toxic sensory neuropathies, but also, although rarely, with Guillain-Barré syndrome (GBS). We describe five patients who developed GBS while receiving platinum-based chemotherapy for a solid tumor and report the five cases published so far. Most patients had received cumulative platinum doses below known neurotoxic levels, and all of them had an optimal outcome after platinum discontinuation, associated in most cases with administration of intravenous immunoglobulin. Clinical presentation, electroneuromyography, and cerebrospinal fluid analysis help clinicians to differentiate GBS from toxic neuropathy. Platinum compounds are the only chemotherapeutic agents used for solid tumors that have been associated to GBS. Thus, we propose that GBS may constitute a non-dose-dependent side effect of platinum drugs and that awareness needs to be raised among oncologists on this rare but potentially life-threatening complication of platinum chemotherapy. IMPLICATIONS FOR PRACTICE: Many patients on platinum-based chemotherapy for solid tumors develop sensory neuropathy, a common dose-dependent side effect. The authors propose that Guillain-Barré syndrome may constitute an immune-mediated, non-dose-related side effect of platinum-based chemotherapy. Prompt diagnosis of Guillain-Barré syndrome and distinction from classical toxic neuropathy are crucial for optimal treatment. Platinum discontinuation, associated if needed to intravenous immunoglobulin administration, radically changes the course of the disease and minimizes neurological sequelae.


Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophies.
Nonsyndromic recessive retinal dystrophies cause severe visual impairment due to the death of photoreceptor and retinal pigment epithelium cells. These diseases until recently have been considered to be incurable. Molecular genetic studies in the last two decades have revealed the underlying molecular causes in approximately two-thirds of patients. The mammalian eye has been at the forefront of therapeutic trials based on gene augmentation in humans with an early-onset nonsyndromic recessive retinal dystrophy due to mutations in the retinal pigment epithelium-specific protein 65kDa (RPE65) gene. Tremendous challenges still lie ahead to extrapolate these studies to other retinal disease-causing genes, as human gene augmentation studies require testing in animal models for each individual gene and sufficiently large patient cohorts for clinical trials remain to be identified through cost-effective mutation screening protocols.


Dinosaur ichnology and sedimentology of the Chignik Formation (Upper Cretaceous), Aniakchak National Monument, southwestern Alaska; Further insights on habitat preferences of high-latitude hadrosaurs.
While there are now numerous records of dinosaurs from Cretaceous rocks around the state of Alaska, very few fossil records of terrestrial vertebrates are known from the Mesozoic rocks of the southwestern part of the state. Here we report the new discovery of extensive occurrences of dinosaur tracks from Aniakchak National Monument of the Alaska Peninsula. These tracks are in the Late Cretaceous (Maastrichtian) Chignik Formation, a cyclic sequence of rocks, approximately 500-600 m thick, representing shallow marine to nearshore marine environments in the lower part and continental alluvial coastal plain environments in the upper part of the section. These rocks are part of the Peninsular Terrane and paleomagnetic reconstructions based on the volcanic rocks of this terrane suggest that the Chignik Formation was deposited at approximately its current latitude which is almost 57° N. Recent field work in Aniakchak National Monument has revealed over 75 new track sites, dramatically increasing the dinosaur record from the Alaska Peninsula. Most of the combined record of tracks can be attributed to hadrosaurs, the plant-eating duck-billed dinosaurs. Tracks range in size from those made by full-grown adults to juveniles. Other tracks can be attributed to armored dinosaurs, meat-eating dinosaurs, and two kinds of fossil birds. The track size of the predatory dinosaur suggests a body approximately 6-7 m long, about the estimated size of the North Slope tyrannosaurid Nanuqsaurus. The larger bird tracks resemble Magnoavipes denaliensis previously described from Denali National Park, while the smaller bird tracks were made by a bird about the size of a modern Willet. Previous interdisciplinary sedimentologic and paleontologic work in the correlative and well-known dinosaur bonebeds of the Prince Creek Formation 1400km-1500km further north in Alaska suggested that high-latitude hadrosaurs preferred distal coastal plain or lower delta plain habitats. The ichnological record being uncovered in the Chignik Formation of southwestern Alaska is showing that the hadrosaur tracks here were also made in distal coastal and delta plain conditions. This similarity may corroborate the habitat preference model for Cretaceous high-latitude dinosaurs proposed for the data gathered from the Prince Creek Formation, and may indicate that at least Beringian hadrosaurids had similar habitat preferences regardless of latitude.


Mesothelioma among brake mechanics: an expanded analysis of a case-control study.
The U.S. Environmental Protection Agency has begun discussions to consider its assessment of asbestos toxicity related to mineral form and fiber size. Brake workers are typically exposed to short chrysotile fibers. To explore the mesothelioma risk among brake workers, considering other occupational exposures to asbestos, data from a study that was published previously were obtained and the analysis was extended. The National Cancer Institute provided data from a case-control study of mesothelioma. Because many participants with a history of brake work also had employment in other asbestos-related occupations, mesothelioma cases and controls were compared for a history of brake work, controlling for employment in eight occupations with potential asbestos exposure. A stratified analysis was also performed excluding those with any of the eight occupations. Possible interactions between brake work and other occupational exposures related to risk of mesothelioma were also examined. The odds ratio (OR) for employment in brake installation or repair was 0.71 (95% CI: 0.30-1.60) when controlled for insulation or shipbuilding. When a history of employment in any of the eight occupations with potential asbestos exposure was controlled, the OR was 0.82 (95% CI: 0.36-1.80). ORs did not increase with increasing duration of brake work. Exclusion of those with any of the eight exposures resulted in an OR of 0.62 (95% CI: 0.01-4.71) for occupational brake work. There was no evidence of an interaction between brake work and other occupational exposures. These latter analyses were based on small numbers of exposed cases. The results are consistent with the existing literature indicating that brake work does not increase the risk of mesothelioma and adds to the evidence that fiber type and size are important determinants of mesothelioma risk.


The palearctic oystercatcher Haematopus ostralegus, a natural definitive host for Gymnophalloides seoi.
In order to verify the role of migrating birds as natural definitive hosts for Gymnophalloides seoi (Gymnophallidae), Palearctic oystercatchers, Haematopus ostralegus, were caught from several western coastal areas in the Republic of Korea and examined for intestinal flukes. Five (71.4%) of 7 oystercatchers were infected with 302-1,660 (mean 892) adult G. seoi. In intestinal sections of the host, worms were found in the intervillous space of the mucosal layer. We conclude that the oystercatcher is a natural definitive host for G. seoi.


Atraumatic lateral collateral ligament complex signal abnormalities by magnetic resonance imaging in patients with osteoarthrosis of the knee.
To determine the prevalence of atraumatic lateral collateral ligament complex (LCLC) abnormalities by magnetic resonance imaging (MRI) in patients with osteoarthrosis (OA) of the knee. Magnetic resonance imaging scans in 96 subjects (25 with OA and 71 without OA) were retrospectively reviewed for the presence and severity of LCLC signal abnormalities. Abnormalities in the MRI scans of subjects with OA were compared with those of subjects without OA using chi2 test and the Mantel-Haenszel test for trend. Lateral compartment OA (23 of 25) was associated with abnormalities of the LCLC in 96% (22 of 23 subjects had fibular collateral ligament abnormalities, P < 0.0001). Medial compartment OA (25 of 25) was associated with abnormalities of the LCLC in 88% (22 of 25 subjects had fibular collateral ligament abnormalities, P < 0.0001). There was a positive trend for severity of MRI abnormalities with severity of OA (P < 0.0001 to P = 0.04). Lateral collateral ligament complex MRI signal abnormalities are common in patients with OA, in the absence of trauma.


TDP-43 dysfunction results in R-loop accumulation and DNA replication defects.
TAR DNA-binding protein 43 (TDP-43; also known as TARDBP) is an RNA-binding protein whose aggregation is a hallmark of the neurodegenerative disorders amyotrophic lateral sclerosis and frontotemporal dementia. TDP-43 loss increases DNA damage and compromises cell viability, but the actual function of TDP-43 in preventing genome instability remains unclear. Here, we show that loss of TDP-43 increases R-loop formation in a transcription-dependent manner and results in DNA replication stress. TDP-43 nucleic-acid-binding and self-assembly activities are important in inhibiting R-loop accumulation and preserving normal DNA replication. We also found that TDP-43 cytoplasmic aggregation impairs TDP-43 function in R-loop regulation. Furthermore, increased R-loop accumulation and DNA damage is observed in neurons upon loss of TDP-43. Together, our findings indicate that TDP-43 function and normal protein homeostasis are crucial in maintaining genomic stability through a co-transcriptional process that prevents aberrant R-loop accumulation. We propose that the increased R-loop formation and genomic instability associated with TDP-43 loss are linked to the pathogenesis of TDP-43 proteinopathies.This article has an associated First Person interview with the first author of the paper.


Problematic prescription opioid use in an HIV-infected cohort: the importance of universal toxicology testing.
Providers treating chronic pain must attempt to relieve suffering, while minimizing problematic prescription opioid use, including addiction and diversion. Previously described risk factors for problematic use include history of substance use, younger age, male sex, psychiatric comorbidity, and lower education level. We examined these risk factors in HIV-infected individuals, using cross-sectional and longitudinal data from the Manhattan HIV Brain Bank. Problematic use was defined as illicit substance use (documented by urine toxicology or structured psychiatric interview), while receiving prescription opioids. Among 173 participants prescribed opioids, 62% had problematic use, the majority of which was discovered by urine toxicology. Problematic use was associated with past substance use, current psychiatric disorder, and poorer adherence to antiretrovirals. However, when participants without problematic use at baseline were followed longitudinally, these factors were not predictive. Furthermore, the cumulative incidence of problematic use behaviors was no greater than in a similar group of participants who were not prescribed opioids. Problematic prescription opioid use is common among HIV-infected individuals and is associated with history of substance use, current psychiatric disorder, and poor adherence to antiretrovirals. However, these factors do not predict future problematic use in those who are not currently using illicit substances, and the prescription of an opioid does not seem to predispose patients toward a future substance use disorder. Rather than attempting to assess risk for problematic prescription opioid use in HIV-infected individuals, we recommend baseline and follow-up urine toxicology.


The rise and fall of dental therapy in Canada: a policy analysis and assessment of equity of access to oral health care for Inuit and First Nations communities.
Inequality between most Canadians and those from Inuit and First Nations communities, in terms of both access to oral health care services and related health outcomes, has been a long-standing problem. Efforts to close this equity gap led to the creation of dental therapy training programs. These programs were designed to produce graduates who would provide services in rural and northern communities. The closure of the last dental therapy program in late 2011 has ended the supply of dental therapists and governments do not appear to have any alternative solutions to the growing gap in access to oral health care services between most Canadians and those from Inuit and First Nations communities. A policy analysis of the rise and fall of the dental therapy profession in Canada was conducted using historical and policy documents. The analysis is framed within Kingdon's agenda-setting framework and considers why dental therapy was originally pursued as an option to ensure equitable access to oral health care for Inuit and First Nations communities and why this policy has now been abandoned with the closure of Canada's last dental therapy training school. The closure of the last dental therapy program in Canada has the potential to further reduce access to dental care in some Inuit and First Nations communities. Overlaps between federal and provincial jurisdiction have contributed to the absence of a coordinated policy approach to address the equity gap in access to dental care which will exacerbate the inequalities in comparison to the general population. The analysis suggests that while a technically feasible policy solution is available there continues to be no politically acceptable solution and thus it remains unlikely that a window of opportunity for policy change will open any time soon. In the absence of federal government leadership, the most viable option forward may be incremental policy change. Provincial governments could expand the scope of practice for dental hygienists in the hope that it may support enhanced access, consumer choice, and efficiency in the delivery of oral health care to Inuit and First Nations communities in Canada.


Causal Evaluation of Post-Marketing Drugs for Drug-induced Liver Injury from Electronic Health Records.
Drug-induced liver injury (DILI) is one of the most common and serious adverse drug reactions that can lead to acute liver failure and death. Detection of DILI and causal estimation of drug-hepatotoxicity association are of great importance for patient safety. This paper proposes a framework for causal estimation of post-marketing drugs for DILI from real-world electronic health record (EHR) data. Randomized clinical trials were replicated at scale by automatically generating different user and non-user cohorts for each potential drug, and average treatment effects (ATEs) of drugs were estimated using targeted maximum likelihood estimation. Ten years of real-world EHRs were used to validate the framework. Of all 1199 single-ingredient drugs analyzed, 7 novel and 7 known drug-hepatotoxicity associations were found to be causal.