Self-energy effects and electron-phonon coupling in Fe-As superconductors.
Doping and temperature dependent studies of optical phonon modes in Fe-122 pnictides are performed using Raman scattering experiments and compared with model calculations to elucidate the role of electron-phonon and spin-phonon interaction in this family of compounds. The frequency and linewidth of the B(1g) mode at around 210 cm(-1) is highlighted as appreciable anomalies at the superconducting and spin density wave transitions are observed that strongly depend on composition. We give estimates of the electron-phonon coupling related to this renormalization and calculate the phonon self-energy on the basis of a four-band model comparing different symmetries of the order parameters. In addition, we observe a pronounced quasi-elastic Raman response for the undoped compound, suggesting persisting magnetic fluctuations in the spin density wave state.


[Adaptation of Leptospira interrograns (sensu stricto) to fresh water].
The contact with polluted waters is one of the main risk factors to catch leptospirosis. A study is presented about the adaptation of Leptospira interrograns to nutrient-lacking water media. For this end, leptospires were incubated in distilled water and tampon saline solution for an undetermined period of time. Leptospires kept viable in water for 98 days whereas the incubated ones in tampon saline solution survived 3 weeks only. Protein cellular and external membrane components were analyzed with electrophoresis in acrylamide gel (SDS-PAGE). When OM protein profiles of leptospires kept in water were compared to those OM profiles of cells cultured in ENJA medium, some differences were observed. A 56 kDa protein was present in leptospires kept in water for a week. This protein was identified as GroEL through Western Blot test.


The effect of flooring on musculoskeletal symptoms in the lower extremities and low back among female nursing assistants.
This study examines the effect of changing the floor from a 2-mm homogenous vinyl floor to a 4-mm heterogeneous vinyl floor (1.5-mm wear layer and 2.5-mm foam layer) on musculoskeletal symptoms in the lower extremities and low back among nursing assistants in a geriatric care centre. A pre-post design with a reference group consisting of nursing assistants from a similar geriatric care centre was used. Follow-up measurements were carried out 12 and 24 months after the intervention by means of questionnaires. At the 1-year follow-up, the pain intensity score in the feet of the intervention group had decreased compared with the baseline value and remained statistically significant at the 2-year follow-up. The decrease in pain intensity score of the feet in the intervention group was statistically significantly different from the reference group, both after 1 and 2 years. The results show the importance of flooring in the workplace with regard to reducing musculoskeletal symptoms. Appropriate flooring is especially important in the female-dominated health care sector, where workers must stand or walk for long periods.


[Secular trends in stature growth in Blumenau-Brazil in relation to human development index (HDI)].
The objective of this study was to analyze the secular trend of growth in height of military recruits enlisted in Blumenau and correlate it with the HDI index. This was a cross-sectional study of recruits aged 18 to 20 enlisted to the 23rd Infantry Battalion in Blumenau between 1963 to 2007. The sample comprised 600 out of a total of 3000 recruits enlisted over the period. Data were collected from individual enlistment files on recruits which had been archived by year. Three years were analyzed from each decade (x3, x5, and x7) and the first forty files were selected systematically from each recruitment year for analysis. Statistical analysis was with descriptive statistics, Student's t test and simple linear regression. There was an increase of the order of 7 cm in the height of recruits in Blumenau over the last 47 years (from 1.7 meters in the 1960s to 1.77 meters in the 2000s) and the increase was most evident between the 1970s and 1980s. The mean heights in years in different decades exhibited a strong and positive correlation with the HDI in Blumenau and Brazil, which both increased progressively during the study period. The secular tendency in growth in height was positive in Blumenau and had a positive correlation with HDI.


An ultrafine platinum-cobalt alloy decorated cobalt nanowire array with superb activity toward alkaline hydrogen evolution.
It is highly desired to design and develop highly efficient electrocatalysts for alkaline hydrogen evolution reactions. Herein, we report the development of ultrafine PtCo alloy nanoparticle decorated one-dimensional Co nanowires grown on Ti mesh (PtCo-Co/TiM). Owing to its favorable composition and structure, the PtCo-Co/TiM can deliver an ultrahigh current density of 46.5 mA cm-2 at an overpotential of 70 mV in 1.0 M KOH, superior to recently reported Pt-based electrocatalysts. This catalyst also provides excellent long-term electrochemical durability with its catalytic activity being maintained for at least 50 h.


Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy.
CNS infection is a nearly constant facet of systemic CNS infection and is generally well controlled by suppressive systemic antiretroviral therapy (ART). However, there are instances when HIV can be detected in the cerebrospinal fluid (CSF) despite suppression of plasma viruses below the clinical limits of measurement. We review three types of CSF viral escape: asymptomatic, neuro-symptomatic, and secondary. The first, asymptomatic CSF escape, is seemingly benign and characterized by lack of discernable neurological deterioration or subsequent CNS disease progression. Neuro-symptomatic CSF escape is an uncommon, but important, entity characterized by new or progressive CNS disease that is critical to recognize clinically because of its management implications. Finally, secondary CSF escape, which may be even more uncommon, is defined by an increase of CSF HIV replication in association with a concomitant non-HIV infection, as a consequence of the local inflammatory response. Understanding these CSF escape settings not only is important for clinical diagnosis and management but also may provide insight into the CNS HIV reservoir.


CTL-promoting effects of CD40 stimulation outweigh B cell-stimulatory effects resulting in B cell elimination and disease improvement in a murine model of lupus.
CD40/CD40L signaling promotes both B cell and CTL responses in vivo, the latter being beneficial in tumor models. Because CTL may also limit autoreactive B cell expansion in lupus, we asked whether an agonist CD40 mAb would exacerbate lupus due to B cell stimulation or would improve lupus due to CTL promotion. These studies used an induced model of lupus, the parent-into-F1 model in which transfer of DBA/2 splenocytes into B6D2F1 mice induces chronic lupus-like graft-vs-host disease (GVHD). Although agonist CD40 mAb treatment of DBA-->F1 mice initially exacerbated B cell expansion, it also strongly promoted donor CD8 T cell engraftment and cytolytic activity such that by 10 days host B cells were eliminated consistent with an accelerated acute GVHD. CD40 stimulation bypassed the requirement for CD4 T cell help for CD8 CTL possibly by licensing dendritic cells (DC) as shown by the following: 1) greater initial activation of donor CD8 T cells, but not CD4 T cells; 2) earlier activation of host DC; 3) host DC expansion that was CD8 dependent and CD4 independent; and 4) induction of acute GVHD using CD4-depleted purified DBA CD8+ T cells. A single dose of CD40 mAb improved lupus-like renal disease at 12 wk, but may not suffice for longer periods consistent with a need for continuing CD8 CTL surveillance. These results demonstrate that in the setting of lupus-like CD4 T cell-driven B cell hyperactivity, CTL promotion is both feasible and beneficial and the CTL-promoting properties of CD40 stimulation outweigh the B cell-stimulatory properties.


IBD-Groupon: an efficient method for detecting group-wise identity-by-descent regions simultaneously in multiple individuals based on pairwise IBD relationships.
Detecting IBD tracts is an important problem in genetics. Most of the existing methods focus on detecting pairwise IBD tracts, which have relatively low power to detect short IBD tracts. Methods to detect IBD tracts among multiple individuals simultaneously, or group-wise IBD tracts, have better performance for short IBD tracts detection. Group-wise IBD tracts can be applied to a wide range of applications, such as disease mapping, pedigree reconstruction and so forth. The existing group-wise IBD tract detection method is computationally inefficient and is only able to handle small datasets, such as 20, 30 individuals with hundreds of SNPs. It also requires a previous specification of the number of IBD groups, or partitions of the individuals where all the individuals in the same partition are IBD with each other, which may not be realistic in many cases. The method can only handle a small number of IBD groups, such as two or three, because of scalability issues. What is more, it does not take LD (linkage disequilibrium) into consideration. In this work, we developed an efficient method IBD-Groupon, which detects group-wise IBD tracts based on pairwise IBD relationships, and it is able to address all the drawbacks aforementioned. To our knowledge, our method is the first practical group-wise IBD tracts detection method that is scalable to very large datasets, for example, hundreds of individuals with thousands of SNPs, and in the meanwhile, it is powerful to detect short IBD tracts. Our method does not need to specify the number of IBD groups, which will be detected automatically. And our method takes LD into consideration, as it is based on pairwise IBD tracts where LD can be easily incorporated.


Analysis of carpal bones on MR images for age estimation: First results of a new forensic approach.
Current multifactorial age estimation methods are based on radiography, however, in the forensic field there is growing interest in using magnetic resonance imaging (MRI). With regard to the carpal region, MRI provides more information for defining the individual ossification nuclei and the cartilage surrounding single bones. During the phase of bone growth, the progressive reduction of the cartilage layer is accompanied by the development of a cartilage-bone interface. The aim of our study was to create a new model for age estimation, based on the ratio between the area occupied by the nucleus of ossification (NO) and the surface of growth (SG) of each carpal bone, the latter derived by adding NO to the area of cartilage-bone interface. We analyzed 57 MRI scans of Italian subjects aged between 12 and 20 years, without growth diseases, endocrine disorders or osteodystrophy. Measurements of NO and SG areas were extracted using ImageJ software, and the ratio between the NO and SG of each bone (NOSG) was calculated. A multiple linear regression model was used to estimate the individual's age as a function of the variables: gender and wrist bone measurements. The results showed that the best model was obtained with 6 predictors (nvmax=6): Gender, and the NOSG of the Trapezoid, Trapezium, Scaphoid, Pisiform, and Capitate. The median of the residuals (observed age minus predicted age) was -0.025 years, with an IQR of 0.19 years. Thus a new forensic approach to age assessment using MRI is introduced in this paper, which gives the preliminary results.


Signal optimization in urban transport: A totally asymmetric simple exclusion process with traffic lights.
We consider the exclusion process on a ring with time-dependent defective bonds at which the hopping rate periodically switches between zero and one. This system models main roads in city traffics, intersecting with perpendicular streets. We explore basic properties of the system, in particular dependence of the vehicular flow on the parameters of signalization as well as the system size and the car density. We investigate various types of the spatial distribution of the vehicular density, and show existence of a shock profile. We also measure waiting time behind traffic lights, and examine its relationship with the traffic flow.


Motives and Side-Effects of Microdosing With Psychedelics Among Users.
Microdosing with psychedelics has gained considerable media attention where it is portrayed as a performance enhancer, especially popular on the work floor. While reports are in general positive, scientific evidence about potential negative effects is lacking aside from the prevalence and motives for use. The present study addressed this gap by surveying psychedelic users about their experience with microdosing including their dosing schedule, motivation, and potential experienced negative effects. An online questionnaire was launched on several websites and fora between March and July 2018. Respondents who had consented, were 18 years of age or older, and had experience with microdosing were included in the analyses. In total, 1116 of the respondents were either currently microdosing (79.5%) or microdosed in the past (20.5%). Lysergic acid diethylamide (10 mcg) and psilocybin (0.5 g) were the most commonly used psychedelics with a microdosing frequency between 2 and 4 times per week. The majority of users, however, were oblivious about the consumed dose. Performance enhancement was the main motive to microdose (37%). The most reported negative effects were of psychological nature and occurred acutely while under the influence. In line with media reports and anecdotes, the majority of our respondents microdosed to enhance performance. Negative effects occurred mostly acutely after substance consumption. However, the main reason to have stopped microdosing was that it was not effective. Future experimental placebo-controlled studies are needed to test whether performance enhancement can be quantified and to assess potential negative effects after longer term microdosing.


Precision Health in Disaster Medicine and Global Public Health.
Current debates about precision medicine take different perspectives on its relevance and value in global health. The term has not yet been applied to disaster medicine or humanitarian health, but it may hold significant value. An interpretation of the term for global public health and disaster medicine is presented here for application to vulnerable populations. Embracing the term may drive more efficient use and targeting of limited resources while encouraging innovation and adopting the new approaches advocated in current humanitarian discourse. PatelRB. Precision health in disaster medicine and global public health. Prehosp Disaster Med. 2018;33(6):565-566.


Gap junctional connexin 37 is expressed in sheep ovaries.
The objective of current study was to evaluate the expression of Cx37 in ovarian follicles and in corpora lutea (CL) during the estrous cycle in sheep. Ovine Cx37 was cloned and characterized to design speciesspecific probe and primers. In Exp. 1, ovaries were collected on d 13, 14, 15, and 16 of the estrous cycle, or from FSH-induced ewes at 0, 2, 4, 8, 12, 24, and 48 h after hCG treatment on d 15 of the estrous cycle. In Exps. 2 and 3, CL were collected on d 5, 10, and 15 of the estrous cycle, or at 0, 4, 8, 12, and 24 h after prostaglandin F2alpha (PGF2alpha)-induced luteal regression on d 10 of the estrous cycle, respectively. Ovarian tissues (e.g., granulosa cells, theca cells, ovarian follicles, and /or CL) were used for Cx37 immunostaining followed by image analysis or for determination of Cx37 mRNA expression by real-time RT-PCR. We demonstrated that (1) Cx37 protein was expressed in granulosa and cumulus oocyte complex compartments, ovarian blood vessels, and on the luteal cell borders, (2) expression of Cx37 mRNA was greater in granulosa than in theca cells of preovulatory follicles, (3) Cx37 mRNA expression in granulosa but not theca cells was affected by hCG treatment, (4) Cx37 protein and mRNA expression were dependent on the stage of luteal development, and (5) Cx37 expression changed during PGF2alpha- induced luteal regression. Thus, Cx37 may play a role in follicular development and ovulation as well as in luteal tissue growth, differentiation, and regression.


Moderate ethanol exposure reduces astrocyte-induced neuroinflammatorysignaling and cognitive decline in presymptomatic APP/PS1 mice.
Background Alcohol use disorder (AUD) has been associated with the development of neurodegenerative diseases, including Alzheimer's disease (AD). However, recent studies demonstrate that moderate alcohol consumption may be protective against dementia and cognitive decline. Methods We examined astrocyte function, low-density lipoprotein (LDL) receptor-related protein 1 (LRP1), and the NF-κB p65 and IKK-α/β signaling pathways in modulating neuroinflammation and amyloid beta (Aβ) deposition. We assessed apolipoprotein E (ApoE) in the mouse brain using IHC and ELISA in response to moderate ethanol exposure (MEE). First, to confirm the intracerebral distribution of ApoE, we co-stained with GFAP, a marker for astrocytes that biosynthesize ApoE. We sought to investigate whether the ethanol-induced upregulation of LRP1 could potentially inhibit the activity of IL-1β and TNF-α induced IKK-α/β towards NF-κB p65, resulting in a reduction of pro-inflammatory cytokines. To evaluate the actual Aβ load in the brains of APP/PS1 mice, we performed with a specific antibody Aβ (Thioflavin S) on both air- and ethanol-exposed groups, subsequently analyzing Aβ levels. We also measured glucose uptake activity using 18F-FDG in APP/PS1 mice. Finally, we investigated whether MEE induced cognitive and memory changes using the Y maze, noble objective recognition (NOR) test, and Morris water maze (MWM). Results Our findings demonstrate that MEE reduced astrocytic glial fibrillary acidic protein (GFAP) and ApoE levels in the cortex and hippocampus in presymptomatic APP/PS1 mice. Interestingly, increased LRP1 protein expression is accompanied by dampening the IKK-α/β-NF-κB p65 pathway, resulting in decreased IL-1β and TNF-α levels in male mice. Notably, female mice show reduced anti-inflammatory cytokines, IL-4, and IL-10 levels without altering IL-1β and TNF-α concentrations. In both males and females, Aβ plaques, a hallmark of AD, were reduced in the cortex and hippocampus of ethanol-exposed presymptomatic APP/PS1 mice. Consistently, MEE increased fluorodeoxyglucose (FDG)-positron emission tomography (PET)-based brain activities and normalized cognitive and memory deficits in the APP/PS1 mice. Conclusions Our findings suggest that MEE may benefit AD pathology via modulating LRP1 expression, potentially reducing neuroinflammation and attenuating Aβ deposition. Our study implies that reduced astrocyte derived ApoE and LDL cholesterol levels are critical for attenuating AD pathology.


An Agent-Based Modeling Template for a Cohort of Veterans with Diabetic Retinopathy.
Agent-based models are valuable for examining systems where large numbers of discrete individuals interact with each other, or with some environment. Diabetic Veterans seeking eye care at a Veterans Administration hospital represent one such cohort. The objective of this study was to develop an agent-based template to be used as a model for a patient with diabetic retinopathy (DR). This template may be replicated arbitrarily many times in order to generate a large cohort which is representative of a real-world population, upon which in-silico experimentation may be conducted. Agent-based template development was performed in java-based computer simulation suite AnyLogic Professional 6.6. The model was informed by medical data abstracted from 535 patient records representing a retrospective cohort of current patients of the VA St. Louis Healthcare System Eye clinic. Logistic regression was performed to determine the predictors associated with advancing stages of DR. Predicted probabilities obtained from logistic regression were used to generate the stage of DR in the simulated cohort. The simulated cohort of DR patients exhibited no significant deviation from the test population of real-world patients in proportion of stage of DR, duration of diabetes mellitus (DM), or the other abstracted predictors. Simulated patients after 10 years were significantly more likely to exhibit proliferative DR (P<0.001). Agent-based modeling is an emerging platform, capable of simulating large cohorts of individuals based on manageable data abstraction efforts. The modeling method described may be useful in simulating many different conditions where course of disease is described in categorical stages.


The utility of ultrasound to determine ventricular capture in external cardiac pacing.
Determining electrical capture when using an external cardiac pacemaker is often difficult and confusing, especially when the resulting clinical signs of an effective blood pressure and pulse are inadequate or nondetectable. The objective of this study was to determine the efficacy of using 2-dimensional ultrasound (US) in determining the presence of ventricular capture of an external cardiac pacemaker in a swine model. Five anesthetized swine underwent external cardiac pacing (ECP) at variable levels of energy output while concurrent US images and electrocardiograph monitoring were recorded on videotape. Determinations of capture/no capture were made in the laboratory. Segments of videotape were selected to be reviewed by 2 physicians blinded to these laboratory determinations of capture and to each other. Kappa levels of agreement were determined among the 3 pairs of comparisons. Seventeen segments were reviewed. Kappa levels of agreement were 0.76 for Reviewer A versus Laboratory determination, 0.88 for Reviewer B versus Laboratory determination, and 0.88 for Reviewer A versus Reviewer B. All P values were <.001. These excellent levels of agreement show that 2D US in this animal model is highly effective in determining the presence of ventricular capture in ECP.


Convenient assay for staphylococcal nuclease by the metachromatic well-agar-diffusion technique.
The metachromatic agar-diffusion (MAD) microslide technique was adapted for quantitative assay for staphylococcal thermonuclease in heterogeneous systems, such as milk and broth. When an enzyme-containing solution was placed in a well cut in the agar, a bright pink halo was obtained. The diameter of the pink zone of hydrolysis was related to time and temperature of incubation and to nuclease concentration. Concentrations of nuclease as low as 0.005 mug/ml and as high as 2.0 mug/ml were conveniently determined after 3 hr at 37 C.


DNA methylation episignature in Gabriele-de Vries syndrome.
Gabriele-de Vries syndrome (GADEVS) is a rare genetic disorder characterized by developmental delay and/or intellectual disability, hypotonia, feeding difficulties, and distinct facial features. To refine the phenotype and to better understand the molecular basis of the syndrome, we analyzed clinical data and performed genome-wide DNA methylation analysis of a series of individuals carrying a YY1 variant. Clinical data were collected for 13 individuals not yet reported through an international call for collaboration. DNA was collected for 11 of these individuals and 2 previously reported individuals in an attempt to delineate a specific DNA methylation signature in GADEVS. Phenotype in most individuals overlapped with the previously described features. We described 1 individual with atypical phenotype, heterozygous for a missense variant in a domain usually not involved in individuals with YY1 pathogenic missense variations. We also described a specific peripheral blood DNA methylation profile associated with YY1 variants. We reported a distinct DNA methylation episignature in GADEVS. We expanded the clinical profile of GADEVS to include thin/sparse hair and cryptorchidism. We also highlighted the utility of DNA methylation episignature analysis for classification of variants of unknown clinical significance.


Immune Checkpoint Therapy in Non-Small Cell Lung Cancer.
Lung cancer remains the number one cause of cancer death in the United States. Even with advances in understanding of tumor histology and mutation status, outcomes remain poor with classic cytotoxic therapies. The development of immune checkpoint inhibitors, designed to optimize a host's own immune response against cancer cells, has led to a new era in the treatment of non-small cell lung cancer (NSCLC). Improved survival in trials have led to rapid US Food and Drug Administration approval for these agents in the advanced-stage NSCLC setting. Many studies are looking at these agents across a variety of patient populations, treatment settings, and in combination with other agents. Because of their unique mechanism of action, tumor response kinetics and patient adverse effect profiles vary greatly from cytotoxic chemotherapy and demand further study. Understanding the optimal use of these agents continues to be elucidated as they shift the NSCLC treatment paradigm.


The ScanHip total hip arthroplasty: radiographic assessment of 72 hips after 10 years.
We analyzed the radiographic and clinical outcome of the ScanHip total hip arthroplasty in 70 patients after 10 years. The Swedish National Hip Register, in which the end-point of the survival analysis is defined as revisions, reported a 10-year survival rate of 94% with the ScanHip, but in the present series 13% of the femoral stems and 29% of the sockets met the criteria for aseptic loosening. Focal osteolysis was found around 8 sockets (11%) and 23 stems (32%) and had occurred significantly oftener around loose sockets, but not around femoral stems. Linear polyethylene wear was significantly increased in loose sockets, but no relationship was noted between polyethylene wear and stem loosening or was there a correlation between clinical symptoms or patients' satisfaction and component loosening. Therefore precise serial long-term radiographic follow-up is the only satisfactory method for detecting aseptic loosening of total hip arthroplasty. It gives the surgeon more detailed information about each case than survival analysis alone.


Association between the dynamics of the COVID-19 epidemic and ABO blood type distribution.
The coronavirus disease 2019 (COVID-19) pandemic is currently the most critical challenge in public health. An understanding of the factors that affect severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection will help fight the COVID-19 pandemic. This study sought to investigate the association between SARS-CoV-2 infection and blood type distribution. The big data provided by the World Health Organization (WHO) and Johns Hopkins University were used to assess the dynamics of the COVID-19 epidemic. The infection data in the early phase of the pandemic from six countries in each of six geographic zones divided according to the WHO were used, representing approximately 5.4 billion people around the globe. We calculated the infection growth factor, doubling times of infection and death cases, reproductive number and infection and death cases in relation to the blood type distribution. The growth factor of infection and death cases significantly and positively correlated with the proportion of the population with blood type A and negatively correlated with the proportion of the population with blood type B. Compared with the lower blood type A population (<30%), the higher blood type A population (⩾30%) showed more infection and death cases, higher growth factors and shorter case doubling times for infections and deaths and thus higher epidemic dynamics. Thus, an association exists between SARS-CoV-2 and the ABO blood group distribution, which might be useful for fighting the COVID-19 pandemic.


Patient counseling detects prescription errors.
Medication errors are part of almost every pharmacist's professional life. They are a consequence of the behavioral habits developed by pharmacists to fill prescriptions efficiently. Outpatient prescription errors at an Indian Health Service pharmacy were reviewed. Mistakes detected after pharmacists had signed off on prescription accuracy were recorded. The errors were separated into two groups: 1) those detected during patient counseling, and 2) those reported after patients left the pharmacy. Patient counseling was the intervening event between the pharmacist's accuracy check and the patient's departure from pharmacy. The review of errors showed that of 323 reported mistakes, 286 (89%) were detected during patient counseling and subsequently corrected. Patient counseling appears to be a valuable tool for intercepting medication errors before they leave the pharmacy. The interactive environment created during the patient encounter probably improves concentration and allows previously overlooked mistakes to be noticed. Pharmacists should be encouraged to develop error detection strategies that are a natural part of the counseling process.


Location of actin, myosin, and microtubular structures during directed locomotion of Dictyostelium amebae.
During their life cycle, amebae of the cellular slime mould Dictyostelium discoideum aggregate to form multicellular structures in which differentiation takes place. Aggregation depends upon the release of chemotactic signals of 3',5'-cAMP from aggregation centers. In response to the signals, aggregating amebae elongate, actively more toward the attractive source, and may be easily identified from the other cells because of their polarized appearance. To examine the role of cytoskeletal components during ameboid locomotion, immunofluorescence microscopy with antibodies to actin, myosin, and to a microtubule-associated component was used. In addition, rhodamine-labeled phallotoxin was employed. Actin and myosin display a rather uniform distribution in rounded unstretched cells. In polarized locomoting cells, actin fluorescence (due to both labeled phallotoxin and specific antibody) is prevalently concentrated in the anterior pseudopod while myosin fluorescence appears to be excluded from the pseudopod. Similarly, microtubules in locomoting cells are excluded from the leading pseudopod. The cell nucleus is attached to the microtubule network by way of a nucleus-associated organelle serving as a microtubule-organizing center and seems to be maintained in a rather fixed position by the microtubules. These findings, together with available morphological and biochemical evidences, are consistent with a mechanism in which polymerized actin is moved into the pseudopod through its interaction with myosin at the base of the pseudopod. Microtubules, apparently, do not actively participate in movement but seem to behave as anchorage structures for the nucleus and possibly other cytoplasmic organelles.


Deep brain stimulation and ablation for obsessive compulsive disorder: evolution of contemporary indications, targets and techniques.
Surgical therapy for treatment-resistant obsessive compulsive disorder (OCD) remains an effective option for well-selected patients managed within a multidisciplinary setting. Historically, lesions within the limbic system have been used to control both obsessive thoughts and repetitive compulsions associated with this disease. We discuss classical targets as well as contemporary neuromodulatory approaches that have been shown to provide symptomatic relief. Recently, deep brain stimulation (DBS) of the anterior limb of the internal capsule/ventral striatum received Conformité Européene (CE) mark and Food and Drug Administration (FDA) approvals for treatment of intractable OCD. Remarkably, this is the first such approval for neurosurgical intervention in a strictly psychiatric indication in modern times. This target is discussed in detail along with alternative targets currently being proposed. We close with a discussion of gamma knife capsulotomy, a modality with deep historical roots. Further directions in the surgical treatment of OCD will require better preoperative predictors of postoperative responses, optimal selection of individualized targets, and rigorous reporting of adverse events and standardized outcomes. To meet these challenges, centers must be equipped with a multidisciplinary team and patient-centered approach to ensure adequate screening and follow up of patients with this difficult-to-treat condition.


Regulation of interleukin-6 in head and neck squamous cell carcinoma is related to papillomavirus infection.
The prevalence of head and neck squamous cell carcinoma (HNSCC) related to human papillomavirus (HPV) is increasing, unlike tobacco- and alcohol-associated cancers. To gain a clearer understanding of the molecular mechanisms implicated in HNSCC, depending on the presence or not of a viral sequence, we investigated the expression of proteins detected in the tumor regions of HNSCC patients. Twenty-two untreated HNSCC patients were selected according to the presence of HPV-16. For six patients, tumor and controlateral healthy tissues were tested for viral detection before quantitative proteomic analysis. After confirmation by Western blot, proteins were connected into a network, leading to investigate interleukin-6 (IL-6) by immunocytochemistry and ELISA. 41 ± 5% of proteins quantified by proteomics were differentially expressed in tumor compared with healthy regions. Among them, 36 proteins were retained as modulated in HPV-16 positive or negative tumors, including cytokeratins, tubulins, annexin A1, and serpin B1. Network analysis suggested a central role of IL-6, confirmed by overexpression of IL-6 in tumor tissues as in sera of HPV-negative HNSCC compared with HPV-16-positive tumors. This modulation may contribute to the survival and proliferation of cancer cells, although it was not related to tumor stage or to the level of HPV-16 DNA.


Cyclic imines in shellfish and ascidians in the northern Adriatic Sea.
The aim of this study was to determine the occurrence of the most representative cyclic imines (CIs) gymnodimine (GYM), pinnatoxin G (PnTX-G), and 13-desmethyl SPX C (SPX1) in Mediterranean mussels (Mytilus galloprovincialis Lamarck, 1819) (n = 416), European oysters (Ostrea edulis Linnaeus, 1758) (n = 104), Queen scallops (Aequipecten opercularis Linnaeus, 1758) (n = 52) and edible ascidians of the Microcosmus spp. (n = 104) originating from nine harvesting and breeding areas in the northern part of the Adriatic Sea using ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). All CI concentrations were far below the guidance level of 400 μg SPXs/kg proposed by the EU Reference Laboratory for Marine Toxins. In contrast to Queen scallops and ascidians, in Mediterranean mussels and European oysters CIs were found throughout the year. Our data reveal the differences between species predisposed for CIs accumulation, as well as seasonal and locational variations in CIs occurrence.


Age-related changes in bone structure and strength in female and male BALB/c mice.
Mice may be useful for studies of skeletal aging, but there are limited data on changes in bone structure and strength over their life span. We obtained bones from female and male BALB/c mice at ages 2, 4, 7, 12, and 20 months and evaluated their structural, densitometric, and mechanical properties. MicroCT of the mid-diaphysis of the femur and radius indicated that during skeletal growth (2-7 months) bone cross-sectional size (area, moment of inertia) increased rapidly; during aging (7-20 months) cortical area was maintained, while moment of inertia continued to increase. Bones from females were smaller than those from males at young ages but not at later ages. Changes in whole-bone stiffness and strength reflected the changes in bone size, with a rapid increase from 2 to 7 months, followed by little or no change. In contrast, energy-to-fracture declined with aging. Cortical tissue mineral density increased during growth and was maintained with aging. MicroCT of trabecular bone revealed age-related changes that were site-dependent. The proximal tibia showed a clear pattern of age-related decline in trabecular BV/TV, with progressive decreases after 4 months in both sexes; lumbar vertebra L5 had more modest age-related declines; in contrast, caudal vertebra Ca7 had increasing BV/TV with aging. Overall, we found no evidence that females had more pronounced age-related deterioration than males. We conclude that bones from aging female and male BALB/c mice exhibit many of the changes seen in humans and are therefore a clinically relevant model for studies of skeletal aging.


[Value and limits of two-dimensional echocardiography in acquired cardiopathies in adults].
Two-dimensional echocardiography is complementary to the unidimensional technique. It offers the possibility of examining a wide area of the heart in real time and obtaining multiple cross-sectional views from several different chest wall transducer positions. Although generally quite accurate this new technique has some limitations, i.e. with regard to resolution of an ultrasonic image. Two-dimensional echocardiography is mainly useful for evaluation of left ventricular function and congenital heart diseases, and for diagnosis of left ventricular and auricular thrombi.


Chemokine CXCL1 dimer is a potent agonist for the CXCR2 receptor.
The CXCL1/CXCR2 axis plays a crucial role in recruiting neutrophils in response to microbial infection and tissue injury, and dysfunction in this process has been implicated in various inflammatory diseases. Chemokines exist as monomers and dimers, and compelling evidence now exists that both forms regulate in vivo function. Therefore, knowledge of the receptor activities of both CXCL1 monomer and dimer is essential to describe the molecular mechanisms by which they orchestrate neutrophil function. The monomer-dimer equilibrium constant (~20 μm) and the CXCR2 binding constant (1 nm) indicate that WT CXCL1 is active as a monomer. To characterize dimer activity, we generated a trapped dimer by introducing a disulfide across the dimer interface. This disulfide-linked CXCL1 dimer binds CXCR2 with nanomolar affinity and shows potent agonist activity in various cellular assays. We also compared the receptor binding mechanism of this dimer with that of a CXCL1 monomer, generated by deleting the C-terminal residues that stabilize the dimer interface. We observe that the binding interactions of the dimer and monomer to the CXCR2 N-terminal domain, which plays an important role in determining affinity and activity, are essentially conserved. The potent activity of the CXCL1 dimer is novel: dimers of the CC chemokines CCL2 and CCL4 are inactive, and the dimer of the CXC chemokine CXCL8 (which is closely related to CXCL1) is marginally active for CXCR1 but shows variable activity for CXCR2. We conclude that large differences in dimer activity among different chemokine-receptor pairs have evolved for fine-tuned leukocyte function.


Trait Openness and serotonin 2A receptors in healthy volunteers: A positron emission tomography study.
Recent research found lasting increases in personality trait Openness in healthy individuals and patients after administration of the serotonin 2A receptor (5-HT2A R) agonist psilocybin. However, no studies have investigated whether 5-HT2A R availability as imaged using positron emission tomography (PET) is associated with this trait. In 159 healthy individuals (53 females), the association between 5-HT2A R binding in neocortex imaged with [18 F]altanserin or [11 C]Cimbi-36 PET and personality trait Openness was investigated using linear regression models. In these models the influence of sex on the association was also investigated. Trait Openness was assessed with the NEO Personality Inventory-Revised. No significant associations between neocortical 5-HT2A R binding and trait Openness were found for [18 F]altanserin (p = 0.5) or [11 C]Cimbi-36 (p = 0.8). Pooling the data in a combined model did not substantially change our results (p = 0.4). No significant interactions with sex were found (p > 0.35). Our results indicate that differences in 5-HT2A R availability are not related to variations in trait Openness in healthy individuals. Although stimulation of the 5-HT2A R with compounds such as psilocybin may contribute to long-term changes in trait Openness, there is no evidence in favor of an association between 5-HT2A R and trait Openness.


Paraganglial cells of urinary bladder and prostate: potential diagnostic problem.
A transurethral prostatic resection for prostatism in a 73 year old man showed a cluster of richly capillarised clear cells originally thought to be indicative of invasive carcinoma. Immunohistochemical studies were carried out on this tissue specimen and three similar cases using a variety of antibodies--Neuron specific enolase, PGP 9.5, chromogranin, synaptophysin, serotonin, somatostatin, substance P, calcitonin, calcitonin gene related peptide, met-enkephalin, VIP, neurofilament, CAM 5.2, S100 protein, prostatic specific antigen and prostatic acid phosphatase. The cellular foci were shown to be composed of paraganglionic cells. The cell clusters were well defined and predominantly comprised clear cells with scanty, fine eosinophilic cytoplasmic granules in three cases. The cell nuclei were round to oval, moderately pleomorphic, with evenly dispersed dense chromatin. It is concluded that the presence of minute foci of paraganglial cells in the bladder wall and prostate gland may be misinterpreted as malignant because of their close association with nerves and their relative rarity. Immunohistochemical staining with neuroendocrine markers should dispel any doubt about their identity.


Balancing sufficiency and impact in reporting standards for mass spectrometry imaging experiments.
Reproducibility, or a lack thereof, is an increasingly important topic across many research fields. A key aspect of reproducibility is accurate reporting of both experiments and the resulting data. Herein, we propose a reporting guideline for mass spectrometry imaging (MSI). Previous standards have laid out guidelines sufficient to guarantee a certain quality of reporting; however, they set a high bar and as a consequence can be exhaustive and broad, thus limiting uptake.To help address this lack of uptake, we propose a reporting supplement-Minimum Information About a Mass Spectrometry Imaging Experiment (MIAMSIE)-and its abbreviated reporting standard version, MSIcheck. MIAMSIE is intended to improve author-driven reporting. It is intentionally not exhaustive, but is rather designed for extensibility and could therefore eventually become analogous to existing standards that aim to guarantee reporting quality. Conversely, its abbreviated form MSIcheck is intended as a diagnostic tool focused on key aspects in MSI reporting.We discuss how existing standards influenced MIAMSIE/MSIcheck and how these new approaches could positively impact reporting quality, followed by test implementation of both standards to demonstrate their use. For MIAMSIE, we report on author reviews of four articles and a dataset. For MSIcheck, we show a snapshot review of a one-month subset of the MSI literature that indicated issues with data provision and the reporting of both data analysis steps and calibration settings for MS systems. Although our contribution is MSI specific, we believe the underlying approach could be considered as a general strategy for improving scientific reporting.


Hidrocystoma: surgical management of cystic lesions of the eyelid.
This report describes the case of a hidrocystoma of the eyelid and the surgical technique used in the therapeutical management of benign cystic lesions of the eyelids. Hidrocystomas are relatively common benign lesions of the eyelids, principally the lower eyelid. They are more common in females over thirty years of age. Diagnosis is clinical and when there is a single lesion, surgery is the treatment of choice. The surgical technique used should be described in greater detail, since it offers good esthetic results and a low risk of recurrence.


Predicting personal self-care in informal caregivers.
Caregiver research often focuses on negative health outcomes, yet little is known about the self-care practices of caregivers. The present study investigates self-care practices among family caregivers and the relationships between personal self-care, perceived stress, and other health variables. Data were collected from informal caregivers through self-administered Internet and paper surveys that included the Medical Outcomes Study Short Form 36-item Health Survey, Perceived Stress Scale, and Self-Care Practices Scale. Personal self-care was most strongly associated with emotional well-being, pain, perceived stress, and general health. The relevance of study findings to strengthening family caregiver programs and future research is discussed.


Systemic disease-induced salivary biomarker profiles in mouse models of melanoma and non-small cell lung cancer.
Saliva (oral fluids) is an emerging biofluid poised for detection of clinical diseases. Although the rationale for oral diseases applications (e.g. oral cancer) is intuitive, the rationale and relationship between systemic diseases and saliva biomarkers are unclear. In this study, we used mouse models of melanoma and non-small cell lung cancer and compared the transcriptome biomarker profiles of tumor-bearing mice to those of control mice. Microarray analysis showed that salivary transcriptomes were significantly altered in tumor-bearing mice vs. controls. Significant overlapping among transcriptomes of mouse tumors, serum, salivary glands and saliva suggests that salivary biomarkers have multiple origins. Furthermore, we identified that the expression of two groups of significantly altered transcription factors (TFs) Runx1, Mlxipl, Trim30 and Egr1, Tbx1, Nr1d1 in salivary gland tissue of melanoma-bearing mice can potentially be responsible for 82.6% of the up-regulated gene expression and 62.5% of the down-regulated gene expression, respectively, in the saliva of melanoma-bearing mice. We also showed that the ectopic production of nerve growth factor (NGF) in the melanoma tumor tissue as a tumor-released mediator can induce expression of the TF Egr-1 in the salivary gland. Taken together, our data support the conclusion that upon systemic disease development, significant changes can occur in the salivary biomarker profile. Although the origins of the disease-induced salivary biomarkers may be both systemic and local, stimulation of salivary gland by mediators released from remote tumors plays an important role in regulating the salivary surrogate biomarker profiles.


Effect of temperature and concentration on the structure of tert-butyl alcohol/water mixtures: near-infrared spectroscopic study.
The effect of temperature and concentration on the structure of tert-butyl alcohol/water binary mixtures in the alcohol-rich region (X(H2O) < 0.3) has been studied by using Fourier transform near-infrared (FT-NIR) spectroscopy. The obtained results demonstrate that the addition of a small amount of water to tert-butyl alcohol (2-methyl-2-propanol, abbreviated as TBA) leads to minor changes in the structure of neat TBA and suggest that molecules of TBA in the mixture are in the same environment as those in pure TBA. The bands of water are red-shifted in the mixture relative to bulk water, implying that the molecules of water in TBA are involved in stronger hydrogen bonding. The present experimental data give no evidence for the existence of nonbonded water in the mixture. Even at a very low content of water, the main NIR bands of water (nu(2) + nu(3) and nu(1) + nu(3)) have two components showing markedly different behavior upon an increase in temperature. From the power spectra, it is seen that the extent of intensity changes due to the free OH groups of TBA is smaller in the mixture relative to pure TBA. All of these results support the model of chain-end bonding of water molecules to TBA associates. An increase in X(H2O) reduces the population of nonbonded OH groups of TBA, yet both processes do not appear at the same rate. The amount of bonded OH groups of water increases faster than that of the nonbonded ones. It seems that the water-water interaction becomes more important as X(H2O) increases. At high alcohol content, the position of the CH alkyl stretching bands is constant, evidencing a negligible role of the hydrophobic hydration in the mixture.


Phase I study of combination chemotherapy using sorafenib and transcatheter arterial infusion with cisplatin for advanced hepatocellular carcinoma.
The aims of this study were to evaluate the frequency of dose-limiting toxicities and to find the recommended dose of combination chemotherapy with sorafenib and transcatheter arterial infusion (TAI) using cisplatin for patients with advanced hepatocellular carcinoma (HCC), for whom surgical resection, local ablation therapy, or transcatheter arterial chemoembolization were not indicated. Patients received 800 mg sorafenib daily. Cisplatin was given at one of three dosages (level 1, 35 mg/m(2) /cycle; level 2, 50 mg/m(2) /cycle; and level 3, 65 mg/m(2) /cycle) from feeding arteries to the HCC. The treatment was repeated every 4-6 weeks up to a maximum of six cycles, until there were signs of tumor progression or unacceptable toxicity. The dose-limiting toxicities experienced by the 20 enrolled patients were grade 4 increased aspartate aminotransferase at level 1, grade 3 gastrointestinal hemorrhaging at level 1, and grade 3 hypertension at level 3. The common drug-related adverse events that were of severity grade 3 or 4 included the elevation of aspartate aminotransferase (30%), alanine aminotransferase (20%), amylase (30%), and lipase (30%). Partial response was seen in four patients (20%), and 13 patients (65%) had stable disease. The median overall survival and progression-free survival were 9.1 and 3.3 months, respectively. The combination of sorafenib at 800 mg/day with TAI of cisplatin at 65 mg/m(2) /cycle was determined to be the recommended regimen. A randomized phase II trial of sorafenib alone versus sorafenib plus TAI of cisplatin is currently underway. This study was registered at UMIN as trial number UMIN000001496.


Cloning of the pif region of the F sex factor and identification of a pif protein product.
This paper reports a detailed investigation of the pif region of the F factor responsible for inhibition of development of T7 and related "female-specific" phages. We have mapped a series of pif::Tn5 insertions to a region between 39.6 and 42.8 kilobases on the physical map of F. All pif::Tn5 insertions plated T7 at full efficiency; most were clustered in a 1.8-kilobase interval on both sides of the EcoRI site located at F coordinate 40.3 kilobases. A 5.2-kilobase Pst-I fragment with F coordinates 38.9 to 44.1 has been cloned into a pSC101 vector to create the Pif+ plasmid pGS103. A series of Pif- deletion mutants and nonsense mutants were isolated from pGS103. Using minicells carrying pGS103 or its derivatives, we have identified a 70,000-dalton pif protein.


Slipped upper femoral epiphysis: Outcome after in situ fixation and capital realignment technique.
Slipped upper femoral epiphysis (SUFE) is the gradually acquired malalignment of the upper femoral epiphysis (capital) and the proximal femoral metaphysis. SUFE is uncommon in India, and there are no previous studies on outcome and clinical characteristics of patients with SUFE from India. This study evaluates the presentation, disease associations and outcome of SUFE from a tertiary care centre in India. Twenty six consecutive children with SUFE seen over a period of 4 years were reviewed. The clinical presentations, severity of the slip, surgical interventions (n=30) were assessed. Twenty one boys and five girls with a mean age 13.1 years (range 10-16 years) were included in the study. Four children had bilateral involvement. There were 4 rural and 22 urban children from the eastern and southern states of the country. The presentation was acute in 7, acute on chronic in 5, and chronic in 14, with a mean duration of symptoms of 51 days (range 3-120 days). Slips were stable in 16 and unstable in 10 children. Two children had adiposogenital syndrome. Body mass index was high in 12 out of 23 children. Vitamin D levels were low in 20 out of 21 children, with a mean vitamin D level of 12.61 ± 5 ng/ml. Eighteen children underwent in situ pinning. Eight children underwent capital realignment. Clinical outcome as assessed by Merle d' Aubigne score was excellent in 6, good in 10, fair in 6 and poor in 1. Half of the in situ fixation patients underwent osteoplasty procedure for femoroacetabular impingement and 5 more were symptomatic. The head neck offset and α angle after in situ pinning were -1.12 ± 3 mm and 66.05 ± 9.7°, respectively and this improved to 8.7 mm and 49°, respectively, after osteoplasty. One child in the pinning group had chondrolysis. Eight patients with severe slip underwent capital realignment. Mean followup was 20.15 months. The anterior head neck offset and α angle were corrected to 6.8 ± 1.72 mm and 44.6 ± 7.0° mm, respectively. Two children with unstable slip in the capital realignment group had avascular necrosis which was diagnosed at presentation by bone scan. High BMI, vitamin D deficiency and endocrine disorders are associated with SUFE in India and should be evaluated as some of these are amenable to prevention and treatment. Most patients treated with in situ pinning developed femoroacetabular impingement. The early results after capital realignment procedure are encouraging and help to avoid a second procedure which is needed in a majority of patients who underwent in situ pinning.


Resource availability, utilisation and cost in the provision of critical care in Tanzania: a protocol for a systematic review.
Critical care is essential in saving lives of those that are critically ill, however, provision of critical care can be costly and heterogeneous across lower-resource settings. This paper describes the protocol for a systematic review of the literature that aims to identify the reported costs and resources available for the provision of critical care and the forms of critical care provision in Tanzania. The review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Three databases (MEDLINE, Embase and Global Health) will be searched to identify articles that report the forms of critical care, resources used in the provision of critical care in Tanzania, their availability and the associated costs. The search strategy will be developed from four key concepts; critical care provision, critical illness, resource use, Tanzania. The articles that fulfil the inclusion and exclusion criteria will be assessed for quality using the Reference Case for Estimating the Costs of Global Health Services and Interventions checklist. The extracted data will be summarised using descriptive statistics including frequencies, mean and median of the quantity and costs of resources used in the components of critical care services, depending on the data availability. This study will be carried out between February and November 2021. This study is a review of secondary data and ethical clearance was sought from and granted by the Tanzanian National Institute of Medical Research (reference: NIMR/HQ/R.8a/Vol. IX/3537) and London School of Hygiene and Tropical Medicine (ethics ref: 22866). We will publish the review in a peer-reviewed journal as an open access article in addition to presenting the findings at conferences and public scientific gatherings. The protocol was registered with PROSPERO; registration number: CRD42020221923.


Long-Term Exposure to Ambient Air Pollution and Subclinical Cerebrovascular Disease in NOMAS (the Northern Manhattan Study).
Long-term exposure to ambient air pollution is associated with higher risk of cardiovascular disease and stroke. We hypothesized that long-term exposure to air pollution would be associated with magnetic resonance imaging markers of subclinical cerebrovascular disease. Participants were 1075 stroke-free individuals aged ≥50 years drawn from the magnetic resonance imaging subcohort of the Northern Manhattan Study who had lived at the same residence for at least 2 years before magnetic resonance imaging. Cross-sectional associations between ambient air pollution and subclinical cerebrovascular disease were analyzed. We found an association between distance to roadway, a proxy for residential exposure to traffic pollution, and white matter hyperintensity volume; however, after adjusting for risk factors, this relationship was no longer present. All other associations between pollutant measures and white matter hyperintensity volume were null. There was no clear association between exposure to air pollutants and subclinical brain infarcts or total cerebral brain volume. We found no evidence that long-term exposure to ambient air pollution is independently associated with subclinical cerebrovascular disease in an urban population-based cohort.


In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment.
Mycotoxins found in randomly selected commercial milk thistle dietary supplement were evaluated for their toxicity in silico and in vitro. Using in silico methods, the basic physicochemical, pharmacological, and toxicological properties of the mycotoxins were predicted using ACD/Percepta. The in vitro cytotoxicity of individual mycotoxins was determined in mouse macrophage (RAW 264.7), human hepatoblastoma (HepG2), and human embryonic kidney (HEK 293T) cells. In addition, we studied the bioavailability potential of mycotoxins and silibinin utilizing an in vitro transwell system with differentiated human colon adenocarcinoma cells (Caco-2) simulating mycotoxin transfer through the intestinal epithelial barrier. The IC50 values for individual mycotoxins in studied cells were in the biologically relevant ranges as follows: 3.57-13.37 nM (T-2 toxin), 5.07-47.44 nM (HT-2 toxin), 3.66-17.74 nM (diacetoxyscirpenol). Furthermore, no acute toxicity was obtained for deoxynivalenol, beauvericin, zearalenone, enniatinENN-A, enniatin-A1, enniatin-B, enniatin-B1, alternariol, alternariol-9-methyl ether, tentoxin, and mycophenolic acid up to the 50 nM concentration. The acute toxicity of these mycotoxins in binary combinations exhibited antagonistic effects in the combinations of T-2 with DON, ENN-A1, or ENN-B, while the rest showed synergistic or additive effects. Silibinin had a significant protective effect against both the cytotoxicity of three mycotoxins (T-2 toxin, HT-2 toxin, DAS) and genotoxicity of AME, AOH, DON, and ENNs on HEK 293T. The bioavailability results confirmed that AME, DAS, ENN-B, TEN, T-2, and silibinin are transported through the epithelial cell layer and further metabolized. The bioavailability of silibinin is very similar to mycotoxins poor penetration.


Relative effects of mutability and selection on single nucleotide polymorphisms in transcribed regions of the human genome.
Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation in humans. However, the factors that affect SNP density are poorly understood. The goal of this study was to estimate the relative effects of mutability and selection on SNP density in transcribed regions of human genes. It is important for prediction of the regions that harbor functional polymorphisms. We used frequency-validated SNPs resulting from single-nucleotide substitutions. SNPs were subdivided into five functional categories: (i) 5' untranslated region (UTR) SNPs, (ii) 3' UTR SNPs, (iii) synonymous SNPs, (iv) SNPs producing conservative missense mutations, and (v) SNPs producing radical missense mutations. Each of these categories was further subdivided into nine mutational categories on the basis of the single-nucleotide substitution type. Thus, 45 functional/mutational categories were analyzed. The relative mutation rate in each mutational category was estimated on the basis of published data. The proportion of segregating sites (PSSs) for each functional/mutational category was estimated by dividing the observed number of SNPs by the number of potential sites in the genome for a given functional/mutational category. By analyzing each functional group separately, we found significant positive correlations between PSSs and relative mutation rates (Spearman's correlation coefficient, at least r = 0.96, df = 9, P < 0.001). We adjusted the PSSs for the mutation rate and found that the functional category had a significant effect on SNP density (F = 5.9, df = 4, P = 0.001), suggesting that selection affects SNP density in transcribed regions of the genome. We used analyses of variance and covariance to estimate the relative effects of selection (functional category) and mutability (relative mutation rate) on the PSSs and found that approximately 87% of variation in PSS was due to variation in the mutation rate and approximately 13% was due to selection, suggesting that the probability that a site located in a transcribed region of a gene is polymorphic mostly depends on the mutability of the site.


A signaling-regulated, short-chain dehydrogenase of Stagonospora nodorum regulates asexual development.
The fungus Stagonospora nodorum is a causal agent of leaf and glume blotch disease of wheat. It has been previously shown that inactivation of heterotrimeric G protein signaling in Stagonospora nodorum caused development defects and reduced pathogenicity [P. S. Solomon et al., Mol. Plant-Microbe Interact. 17:456-466, 2004]. In this study, we sought to identify targets of the signaling pathway that may have contributed to phenotypic defects of the signaling mutants. A comparative analysis of Stagonospora nodorum wild-type and Galpha-defective mutant (gna1) intracellular proteomes was performed via two-dimensional polyacrylamide gel electrophoresis. Several proteins showed significantly altered abundances when comparing the two strains. One such protein, the short-chain dehydrogenase Sch1, was 18-fold less abundant in the gna1 strain, implying that it is positively regulated by Galpha signaling. Gene expression and transcriptional enhanced green fluorescent protein fusion analyses of Sch1 indicates strong expression during asexual development. Mutant strains of Stagonospora nodorum lacking Sch1 demonstrated poor growth on minimal media and exhibited a significant reduction in asexual sporulation on all growth media examined. Detailed histological experiments on sch1 pycnidia revealed that the gene is required for the differentiation of the subparietal layers of asexual pycnidia resulting in a significant reduction in both pycnidiospore size and numbers.


Effects of soy isoflavone supplementation on cognitive function in Chinese postmenopausal women: a double-blind, randomized, controlled trial.
To investigate whether soy-derived isoflavone extract improves performance in cognitive function and quality of life in Chinese postmenopausal women. The study was a 6-month double-blind, randomized, placebo-controlled, parallel group trial. Participants were community-dwelling women aged 55 to 76 years; 191 eligible women were randomly assigned to receive a daily oral intake of 80 mg soy-derived isoflavones or an identical-appearing placebo for 6 months. Standardized neuropsychological tests of memory, executive function, attention, motor control, language, and visual perception and a global cognitive function assessment were administered face-to-face individually at baseline and at 6-months posttreatment. The validated Chinese version of the Short Form-36 was used for quality of life measurements. Of the participants, 88% (168 women: 80 among the supplementation group and 88 among the placebo group) completed the trial. Intention-to-treat analysis, conducted for 176 participants with 6-month assessment results, revealed no significant differences in outcome measures between treatment groups. Subgroup analysis among the good compliers only (consumed at least 80% of the supplements or placebo; n = 168) and among the age groups younger or older than 65 years also indicated no significant differences for any outcome measures. Types of complaints of adverse events were similar in both treatment groups and included mainly gastrointestinal and musculoskeletal problems. This 6-month trial indicates that 80-mg soy-derived isoflavone supplementation did not improve performance on standard neuropsychological tests and overall quality of life in generally healthy Chinese postmenopausal women.


Ecology and evolution of viruses infecting uncultivated SUP05 bacteria as revealed by single-cell- and meta-genomics.
Viruses modulate microbial communities and alter ecosystem functions. However, due to cultivation bottlenecks, specific virus-host interaction dynamics remain cryptic. In this study, we examined 127 single-cell amplified genomes (SAGs) from uncultivated SUP05 bacteria isolated from a model marine oxygen minimum zone (OMZ) to identify 69 viral contigs representing five new genera within dsDNA Caudovirales and ssDNA Microviridae. Infection frequencies suggest that ∼1/3 of SUP05 bacteria is viral-infected, with higher infection frequency where oxygen-deficiency was most severe. Observed Microviridae clonality suggests recovery of bloom-terminating viruses, while systematic co-infection between dsDNA and ssDNA viruses posits previously unrecognized cooperation modes. Analyses of 186 microbial and viral metagenomes revealed that SUP05 viruses persisted for years, but remained endemic to the OMZ. Finally, identification of virus-encoded dissimilatory sulfite reductase suggests SUP05 viruses reprogram their host's energy metabolism. Together, these results demonstrate closely coupled SUP05 virus-host co-evolutionary dynamics with the potential to modulate biogeochemical cycling in climate-critical and expanding OMZs.


Idiopathic hypereosinophilic syndrome presenting with liver mass: Report of two cases: Idiopathic hypereosinophilic syndrome and liver mass.
Herein, we report on two cases of hypereosinophilic syndrome presenting as liver mass. One patient was a 22-year-old woman presented with fever, upper abdominal pain, nausea/vomiting and a mass in the right liver lobe. The second patient was a 54-year-old man who presented with nausea and abdominal pain with significant weight loss. He had multiple lesions in both liver lobes. Both patients had eosinophilia that was not attributed to other causes such as allergy or parasites. The patients were treated with glucocorticosteroid and improved clinically. Imaging and laboratory abnormalities resolved.


The molecular mechanism of N-acetylglucosamine side-chain attachment to the Lancefield group A carbohydrate in Streptococcus pyogenes.
In many Lactobacillales species (i.e. lactic acid bacteria), peptidoglycan is decorated by polyrhamnose polysaccharides that are critical for cell envelope integrity and cell shape and also represent key antigenic determinants. Despite the biological importance of these polysaccharides, their biosynthetic pathways have received limited attention. The important human pathogen, Streptococcus pyogenes, synthesizes a key antigenic surface polymer, the Lancefield group A carbohydrate (GAC). GAC is covalently attached to peptidoglycan and consists of a polyrhamnose polymer, with N-acetylglucosamine (GlcNAc) side chains, which is an essential virulence determinant. The molecular details of the mechanism of polyrhamnose modification with GlcNAc are currently unknown. In this report, using molecular genetics, analytical chemistry, and mass spectrometry analysis, we demonstrated that GAC biosynthesis requires two distinct undecaprenol-linked GlcNAc-lipid intermediates: GlcNAc-pyrophosphoryl-undecaprenol (GlcNAc-P-P-Und) produced by the GlcNAc-phosphate transferase GacO and GlcNAc-phosphate-undecaprenol (GlcNAc-P-Und) produced by the glycosyltransferase GacI. Further investigations revealed that the GAC polyrhamnose backbone is assembled on GlcNAc-P-P-Und. Our results also suggested that a GT-C glycosyltransferase, GacL, transfers GlcNAc from GlcNAc-P-Und to polyrhamnose. Moreover, GacJ, a small membrane-associated protein, formed a complex with GacI and significantly stimulated its catalytic activity. Of note, we observed that GacI homologs perform a similar function in Streptococcus agalactiae and Enterococcus faecalis In conclusion, the elucidation of GAC biosynthesis in S. pyogenes reported here enhances our understanding of how other Gram-positive bacteria produce essential components of their cell wall.


Effect of pre-admission "quasi-collective" education on health education for patients with ophthalmic day surgery.
Day surgery is a new surgical model in which patients complete the admission, surgery, and discharge on the same day. The present study aimed to explore the effect of pre-admission "quasi-collective" health education for patients with ophthalmic day surgery. For this study, a total of 200 patients undergoing ophthalmic day surgery from February 2019 to December 2019 were enrolled as the research subjects. The patients were divided randomly into the observation group and the control group, with 100 cases in each group. For the control group, conventional health education was conducted after admission. On the day of admission, the admission education and peri-operative health education were performed. For the observation group, pre-admission health education was provided to the patients, and detailed education on the admission instructions, pre-operative precautions, and simulation of the intra-operative process were given by the medical staff. On the day of admission, the understanding of the education was evaluated, and any weaknesses in the health education were addressed. The anxiety status, method of handwashing, method of administering the drug to the eye, preoperative preparations, intra-operative training, preoperative medication, diet guidance, and postoperative care were compared between the two groups of patients. Before discharge, there were significant differences in the anxiety scores, impact, and satisfaction of health education between the two groups of patients, all of which were statistically significant (P< 0.05). The pre-admission "quasi-collective" health education for patients undergoing day surgery in ophthalmology was better than conventional health education.


Degradation of dental ZrO2-based materials after hydrothermal fatigue. Part I: XRD, XRF, and FESEM analyses.
The aim was to investigate the effect of simulated low-temperature degradation (s-LTD) and hydrothermal fatigue on the degradation of three ZrO(2)-based dental materials. Lava, IPS, and NanoZr discs were randomly assigned to (1) Control-Storage in distilled water at 37°C; (2) Aging at 134°C for 5 h (s-LTD); (3) Thermocycling in saliva for 30,000 cycles (TF). XRD revealed that ZrO(2) m phase was identified in all groups but TF increased the m phase only for Lava. Under the FESEM, Lava showed no alterations under s-LTD, but displayed corrosion areas up to 60 µm wide after TF. We conclude that TF accelerated the degradation of Lava through an increase in the m phase and grain pull-out from the material surface.


[Spatial and temporal distribution and predictive value of chest CT scoring in patients with COVID-19].
Objective: To explore a modified CT scoring system, its feasibility for disease severity evaluation and its predictive value in coronavirus disease 2019 (COVID-19) patients. Methods: This study was a multi-center retrospective cohort study. Patients confirmed with COVID-19 were recruited in three medical centers located in Beijing, Wuhan and Nanchang from January 27, 2020 to March 8, 2020. Demographics, clinical data, and CT images were collected. CT were analyzed by two emergency physicians of more than ten years' work experience independently through a modified scoring system. Final score was determined by average score from the two reviewers if consensus was not reached. The lung was divided into 6 zones (upper, middle, and lower on both sides) by the level of trachea carina and the level of lower pulmonary veins. The target lesion types included ground-glass opacity (GGO), consolidation, overall lung involvement, and crazy-paving pattern. Bronchiectasis, cavity, pleural effusion, etc., were not included in CT reading and analysis because of low incidence. The reviewers evaluated the extent of the targeted patterns (GGO, consolidation) and overall affected lung parenchyma for each zone, using Likert scale, ranging from 0-4 (0=absent; 1=1%-25%; 2=26%-50%; 3=51%-75%; 4=76%-100%). Thus, GGO score, consolidation score, and overall lung involvement score were sum of 6 zones ranging from 0-24. For crazy-paving pattern, it was only coded as absent or present (0 or 1) for each zone and therefore ranging from 0-6. Results: A total of 197 patients from 3 medical centers and 522 CT scans entered final analysis. The median age of the patients was 64 years, and 54.8% were male. There were 76(38.8%) patients had hypertension and 30(15.3%) patients had diabetes mellitus. There were 75 of the patients classified as moderate cases, as well as 95 severe cases and 27 critical cases. As initial symptom, dry cough occurred in 170 patients, 134 patients had fever, and 125 patients had dyspnea. Reparatory rate, oxygen saturation, lymphocyte count and CURB 65 score on admission day varied among patients with different disease severity scale. There were 50 of the patients suffered from deterioration during hospital stay. The median time consumed for each CT by clinicians was 86.5 seconds. Cronbach's alpha for GGO, consolidation, crazy-paving pattern, and overall lung involvement between two clinicians were 0.809, 0.712, 0.678, and 0.906, respectively, showing good or excellent inter-rater correlation. There were 193 (98.0%) patients had GGO, 147 (74.6%) had consolidation, and 126(64.0%) had crazy-paving pattern throughout clinical course. Bilateral lung involvement was observed in 183(92.9%) patients. Median time of interval for CT scan in our study was 7 days so that the whole clinical course was divided into stages by week for further analysis. From the second week on, the CT scores of various types of lesions in severe or critically patients were higher than those of moderate cases. After the fifth week, the course of disease entered the recovery period. The CT score of the upper lung zones was lower than that of other zones in moderate and severe cases. Similar distribution was not observed in critical patients. For moderate cases, the ground glass opacity score at the second week had predictive value for the escalation of the severity classification during hospitalization. The area under the receiver operating characteristic curve was 0.849, the best cut-off value was 5 points, with sensitivity of 84.2% and specificity of 75.0%. Conclusions: It is feasible for clinicians to use the modified semi-quantitative CT scoring system to evaluate patients with COVID-19. Severe/critical patients had higher scores for ground glass opacity, consolidation, crazy-paving pattern, and overall lung involvement than moderate cases. The ground glass opacity score in the second week had an optimal predictive value for escalation of disease severity during hospitalization in moderate patients on admission. The frequency of CT scan should be reduced after entering the recovery stage.


The effect of radial keratotomy on ocular integrity in an animal model.
The safety of deep corneal incisions in radial keratotomy was evaluated in a porcine model of blunt trauma. One eye of each enucleated pair (right and left) of porcine eyes was subjected to a variation of radial keratotomy; the fellow eyes served as unoperated-on controls. All eyes were subjected to a standard injury. Control eyes ruptured at the equatorial sclera. Eyes with radial incisions cut through approximately 70% of corneal thickness also ruptured at the equator. When incisions of this depth (70%) were extended across the limbus (rather than to the corneal-scleral junction), all ruptures occurred at the limbal incisions. Eyes cut 95% to 100% of corneal thickness tended to rupture at the incisions. The safety of deep radial keratotomy incisions with respect to ocular integrity is discussed.


Pharmacokinetics of the analgesic and anti-inflammatory drug meloxicam after administration of multiple doses to nursehound sharks (Scyliorhinus stellaris).
To determine the pharmacokinetics of meloxicam in the nursehound shark (Scyliorhinus stellaris) during multiple dose administration. Prospective experimental trial. A total of eight clinically healthy adult nursehounds (four males, four females). Meloxicam was administered intramuscularly at a dose of 1.5 mg kg-1 once daily for 7 days. Blood samples were collected from the caudal vein for pharmacokinetic analysis at 2.5 hours and 24 hours after drug administration. After a 4 week washout period, meloxicam was administered orally at the same dose at 12 hour intervals for three repeated doses. Blood samples were collected at 1, 2, 4, 6, 8, 12, 24, 36 and 48 hours after the first administration. Sharks were visually monitored during each study and 4 weeks afterwards for side effects or signs of toxicity. Time required to achieve steady state was assessed by visual inspection and statistical comparison of peak and trough concentrations using a Friedman test; comparison between sexes was performed using a Mann-Whitney U test and p-value was set at 0.05. No animal died or showed clinical signs of toxicity during the study. Meloxicam administered orally did not produce detectable concentrations in plasma. After intramuscular administration, steady state was achieved after five doses, and mean trough and peak plasma concentrations at steady state were 1.76 ± 0.21 μg mL-1 and 3.02 ± 0.23 μg mL-1, respectively. Mean peak concentration accumulation ratio was 2.50 ± 0.22. This study shows that intramuscular posology produces plasma concentrations considered therapeutic for other species. However, meloxicam was not detected in plasma after oral administration. These results suggest that meloxicam administered intramuscularly may be a useful non-steroid anti-inflammatory drug in nursehound sharks. Further pharmacodynamic studies are needed to fully evaluate its clinical use in this species.


A review of the effects of nuts on appetite, food intake, metabolism, and body weight.
Tree nuts and peanuts are good sources of many nutrients and antioxidants, but they are also energy dense. The latter often limits intake because of concerns about their possible contribution to positive energy balance. However, evidence to date suggests that nuts are not associated with predicted weight gain. This is largely due to their high satiety value, leading to strong compensatory dietary responses, inefficiency in absorption of the energy they contain, a possible increment in resting energy expenditure, and an augmentation of fat oxidation. Preliminary evidence suggests that these properties are especially evident when they are consumed as snacks.


Genistein induces breast cancer-associated aromatase and stimulates estrogen-dependent tumor cell growth in in vitro breast cancer model.
In breast cancer, the interaction between estrogen-producing breast adipose fibroblasts (BAFs) and estrogen-dependent epithelial tumor cells is pivotal. Local estrogen production is catalyzed by aromatase, which is differentially regulated in disease-free and tumorigenic breast tissue. The use of aromatase inhibitors to block local estrogen production has proven effective in treatment of estrogen-dependent breast cancer. However, a major problem during breast cancer treatment is the sudden onset of menopause and many women seek for alternative medicines, such as the soy isoflavone genistein. In this study, we show that genistein can induce estrogen-dependent MCF-7 tumor cell growth and increase breast cancer-associated aromatase expression and activity in vitro. We have previously developed an in vitro breast cancer model where the positive feedback loop between primary BAFs and estrogen-dependent MCF-7 tumor cells is operational, thereby representing a more natural in vitro model for breast cancer. In this model, genistein could negate the growth inhibitory action of the aromatase inhibitor fadrozole at physiologically relevant concentrations. These data suggest that soy-based supplements might affect the efficacy of breast cancer treatment with aromatase inhibitors. Considering the high number of breast cancer patients using soy supplements to treat menopausal symptoms, the increasing risk for adverse interactions with breast cancer treatment is of major concern and should be considered with care.


SAR studies on curcumin's pro-inflammatory targets: discovery of prenylated pyrazolocurcuminoids as potent and selective novel inhibitors of 5-lipoxygenase.
The anticarcinogenic and anti-inflammatory properties of curcumin have been extensively investigated, identifying prostaglandin E2 synthase (mPGES)-1 and 5-lipoxygenase (5-LO), key enzymes linking inflammation with cancer, as high affinity targets. A comparative structure-activity study revealed three modifications dissecting mPGES-1/5-LO inhibition, namely (i) truncation of the acidic, enolized dicarbonyl moiety and/or replacement by pyrazole, (ii) hydrogenation of the interaryl linker, and (iii) (dihydro)prenylation. The prenylated pyrazole analogue 11 selectively inhibited 5-LO, outperforming curcumin by a factor of up to 50, and impaired zymosan-induced mouse peritonitis along with reduced 5-LO product levels. Other pro-inflammatory targets of curcumin (i.e., mPGES-1, cyclooxygenases, 12/15-LOs, nuclear factor-κB, nuclear factor-erythroid 2-related factor-2, and signal transducer and activator of transcription 3) were hardly affected by 11. The strict structural requirements for mPGES-1 and 5-LO inhibition strongly suggest that specific interactions rather than redox or membrane effects underlie the inhibition of mPGES-1 and 5-LO by curcumin.


Testing a Moderated Mediation Model of Mindfulness, Psychosocial Stress, and Alcohol Use among African American Smokers.
Mindfulness-based strategies have received empirical support for improving coping with stress and reducing alcohol use. The present study presents a moderated mediation model to explain how mindfulness might promote healthier drinking patterns. This model posits that mindfulness reduces perceived stress, leading to less alcohol use, and also weakens the linkage between stress and alcohol use. African American smokers (N = 399, 51% female, Mage = 42) completed measures of dispositional mindfulness, perceived stress, quantity of alcohol use, frequency of binge drinking, and alcohol use disorder symptoms. Participants with higher levels of dispositional mindfulness reported less psychosocial stress and lower alcohol use on all measures. Furthermore, mindfulness moderated the relationship between perceived stress and quantity of alcohol consumption. Specifically, higher perceived stress was associated with increased alcohol use among participants low, but not high, in mindfulness. Mindfulness may be one strategy to reduce perceived stress and associated alcohol use among African American smokers.


Quantification of Gaussian quantum steering.
Einstein-Podolsky-Rosen steering incarnates a useful nonclassical correlation which sits between entanglement and Bell nonlocality. While a number of qualitative steering criteria exist, very little has been achieved for what concerns quantifying steerability. We introduce a computable measure of steering for arbitrary bipartite Gaussian states of continuous variable systems. For two-mode Gaussian states, the measure reduces to a form of coherent information, which is proven never to exceed entanglement, and to reduce to it on pure states. We provide an operational connection between our measure and the key rate in one-sided device-independent quantum key distribution. We further prove that Peres' conjecture holds in its stronger form within the fully Gaussian regime: namely, steering bound entangled Gaussian states by Gaussian measurements is impossible.


Vaccinia viral/retroviral chimeric vectors.
Retroviral vectors have become important tools in gene therapy due to a number of desirable properties, including efficient gene delivery and stable genomic integration. Some shortcomings, however, still remain to be solved. Retroviral vectors cannot be grown to as high titers as for example adenoviruses or vaccinia viruses, they tend to be unstable and are sensitive to lysis by complement when transfused into patients. The search for more robust retroviral delivery systems has led to the development of hybrid viral vectors trying to combine the broadly estimated features of retroviral vectors with advantageous properties of a second viral vector system. Chimeric systems with retroviruses and adeno-alphavirus and herpesviruses have been reported. This review is dedicated to vaccinia virus, a widely used vector in molecular and cell biology, as a chimeric carrier for retroviral vector units. In the first poxviral/retroviral constructs, retroviral vector units integrated into a defective vaccinia vector, gave rise to transduction competent particles. Due to the high insertion capacity of the vaccinia system, also the packaging components could be inserted into the carrier virus resulting in a system that is independent of retroviral packaging cell lines. Moreover, since vaccinia is a cytoplasmic virus that does not recognize nuclear transcription and processing signals, retroviral vectors with introns and internal transcription stops could be constructed that transduce complex gene cassettes. The topic of this review is the vaccinia viral / retroviral vector system and possible applications to gene therapy.


[Oral pathology in children. Part I. Diseases of the oral mucosa].
An overview is present of diseases of the oral mucosa that are more or less limited to occurrence in children or that are more difficult to recognize in children. An example of the latter is geographic tongue.


Cross-cultural differences in risk perceptions of disasters.
Public risk perceptions of mass disasters carry considerable influences, both psychologically and economically, despite their oft-times imprecise nature. Prior research has identified the presence of an optimistic bias that affects risk perception, but there is a dearth of literature examining how these perceptions differ among cultures-particularly with regard to mass disasters. The present study explores differences among Japanese, Argentinean, and North American mental health workers in their rates of the optimistic bias in risk perceptions as contrasted between natural disasters and terrorist events. The results indicate a significant difference among cultures in levels of perceived risk that do not correspond to actual exposure rates. Japanese groups had the highest risk perceptions for both types of hazards and North Americans and Argentineans had the lowest risk perceptions for terrorism. Additionally, participants across all cultures rated risk to self as lower than risk to others (optimistic bias) across all disaster types. These findings suggest that cultural factors may have a greater influence on risk perception than social exposure, and that the belief that one is more immune to disasters compared to others may be a cross-cultural phenomenon.


Reconstitution of T-cell compartment after in utero stem cell transplantation: analysis of T-cell repertoire and thymic output.
In utero transplantation of hematopoietic stem cells allows immune reconstitution of fetuses with severe combined immunodeficiency. The objective of this work was to study the quality of T-cell reconstitution following this procedure. We evaluated the kinetics and extent of T-cell reconstitution in five infants with severe combined immune deficiency (SCID), three with a B+ and two with a B- phenotype, who received haploidentical stem cell transplantation before birth. To this end, we measured the frequency of T-cell receptor excision circles (TREC) and the diversity of the T-cell repertoire. In utero transplantation led to engraftment of donor-derived T lymphocytes which attained normal numbers in four infants, who are in good health. In the three patients with a B+ phenotype, generation of a heterogeneous T-cell repertoire was associated with development of TREC levels comparable to those of SCID patients treated by post-natal transplantation and of healthy babies. Of the two patients with a B- phenotype, one developed mixed T-cell chimerism and a substantial number of circulating T cells, associated with a variable heterogeneity of the T-cell repertoire; TREC levels were normal soon after birth, but declined thereafter. The remaining B- patient remained lymphopenic with a skewed T-cell repertoire and very low TREC levels. This patient eventually required transplantation from a matched unrelated donor at 5 years of age, but died of EBV-related lymphoproliferative disease. These data indicate that in utero transplantation of fetuses with B+ SCID allows generation of newly diversified T lymphocytes and ensures long-term reconstitution of cell-mediated immunity.


Nanotechnological approaches for the treatment of placental dysfunction: recent trends and future perspectives.
The transitory placenta develops during pregnancy and mediates the blood flow between the mother and the developing baby. Placental dysfunction, including but not limited to placenta accreta spectrum, fetal growth restriction, preeclampsia and gestational trophoblastic disease, arises from abnormal placental development and can result in significant adverse maternal and fetal health outcomes. Unfortunately, there is a lack of treatment alternatives for these disorders. Nanocarriers offer versatility, including extended circulation, organ-specific targeting and intracellular transport, finely tuning therapeutic placental interactions. This thorough review explores nanotechnological strategies for addressing placental disorders, encompassing dysfunction insights, potential drug delivery targets and recent strides in placenta-targeted nanoparticle (NP)therapies, instilling hope for effective placental malfunction treatment.


Achieving solubility alteration with functionalized polydimethylsiloxane for improving the viscosity of supercritical CO2 fracturing fluids.
Supercritical carbon dioxide (SC-CO2) fracturing technology has the characteristics of a large amount of fixed CO2 and anhydrous fracturing. It has great application potential for developing unconventional oil and gas resources and mitigating the greenhouse effect. However, the low viscosity of SC-CO2 limits the development of this technology. In this work, HS series thickeners were prepared via a ring-opening polymerization and hydrosilylation reaction by a molecular simulation-aided design method. The simulation results of cohesive energy density, interaction energy, and radial distribution function are consistent with the visualization experimental results, which proves that HS (hyperbranched siloxane) series thickeners have excellent solubility in SC-CO2. HS-3 is the best thickener in the HS series. At 305.15 K and 10 MPa, 5 wt% HS-3 (60 s-1) increases the viscosity of SC-CO2 by 151 times, and the apparent viscosity is 3.024 mPa s. The apparent viscosity of SC-CO2 was positively correlated with the pressure and concentration but negatively correlated with the temperature and shear rate. The results indicate that it is feasible to introduce an aliphatic group and polysiloxane into a SC-CO2 thickener by hydrosilylation.


What's new in multifocal motor neuropathy in 2007-2008?
Several articles on multifocal motor neuropathy (MMN) have appeared in 2007 and 2008, broadening the boundaries of this neuropathy and improving its diagnosis. A number of retrospective studies confirmed the prolonged efficacy of high-dose intravenous immunoglobulins (IVIg) in this neuropathy. The efficacy of other immune therapies was not however, confirmed in other studies in MMN including a randomized controlled trial on mycophenolate mofetil as adjunctive therapy to IVIg. These negative results and the lack of new other studies on the cause of MMN should lead to some reconsideration on its pathogenesis.


Cardiac asthma: new insights into an old disease.
Cardiac asthma has been defined as wheezing, coughing and orthopnea due to congestive heart failure. The clinical distinction between bronchial asthma and cardiac asthma can be straight forward, except in patients with chronic lung disease coexisting with left heart disease. Pulmonary edema and pulmonary vascular congestion have been thought to be the primary causes of cardiac asthma but most patients have a poor response to diuretics. There appears to be limited effectiveness of classical asthma medications like bronchodilators or corticosteroids in treating cardiac asthma. Evidence suggests that circulating inflammatory factors and tissue growth factors also lead to airway obstruction suggesting the possibility of developing novel therapies.


Activin A induces Langerhans cell differentiation in vitro and in human skin explants.
Langerhans cells (LC) represent a well characterized subset of dendritic cells located in the epidermis of skin and mucosae. In vivo, they originate from resident and blood-borne precursors in the presence of keratinocyte-derived TGFbeta. In vitro, LC can be generated from monocytes in the presence of GM-CSF, IL-4 and TGFbeta. However, the signals that induce LC during an inflammatory reaction are not fully investigated. Here we report that Activin A, a TGFbeta family member induced by pro-inflammatory cytokines and involved in skin morphogenesis and wound healing, induces the differentiation of human monocytes into LC in the absence of TGFbeta. Activin A-induced LC are Langerin+, Birbeck granules+, E-cadherin+, CLA+ and CCR6+ and possess typical APC functions. In human skin explants, intradermal injection of Activin A increased the number of CD1a+ and Langerin+ cells in both the epidermis and dermis by promoting the differentiation of resident precursor cells. High levels of Activin A were present in the upper epidermal layers and in the dermis of Lichen Planus biopsies in association with a marked infiltration of CD1a+ and Langerin+ cells. This study reports that Activin A induces the differentiation of circulating CD14+ cells into LC. Since Activin A is abundantly produced during inflammatory conditions which are also characterized by increased numbers of LC, we propose that this cytokine represents a new pathway, alternative to TGFbeta, responsible for LC differentiation during inflammatory/autoimmune conditions.


Optical coherence tomography image in gelatinous drop-like corneal dystrophy: case report.
Gelatinous drop-like corneal dystrophy is a rare disorder with few cases described in the present literature. The following report will show how difficult it is to diagnose this disease in early stages. Modern image exams, such as optical coherence tomography helps to diagnose and can be crucial to establish the best treatment. We will present the histopathological changes and clinical features in this unusual dystrophy.


Prophylactic Appendectomy during Laparoscopic Surgery for Other Conditions.
Acute appendicitis remains the most common surgical emergency. Laparoscopy has gained increasing favor as a method of both investigating right iliac fossa pain and treating the finding of appendicitis. A question arises: what to do with an apparent healthy appendix discovered during laparoscopic surgery for other pathology. We present a case of unilateral hydroureteronephrosis complicated with rupture of the renal pelvis, due to gangrenous appendicitis with abscess of the right iliopsoas muscle and periappendicular inflammation in a 67-year-old woman, who underwent laparoscopic right annessiectomy for right ovarian cyst few years earlier, in which a healthy appendix was left inside. There is a lack of consensus in the literature about what to do with a normal appendix. The main argument for removing an apparently normal appendix is that endoluminal appendicitis may not be recognized during surgery, leading to concern that an abnormal appendix is left in place. Because of a lack of evidence from randomized trials, it remains unclear whether the benefits of routine elective coincidental appendectomy outweigh the costs and risks of morbidity associated with this prophylactic procedure. Nevertheless, it appears, from limited data, that women aged 35 years and under benefit most from elective coincidental appendectomy.


Compliance with therapeutic regimens: a follow-up study for patients with affective disorders.
The purpose of this study was to assess the impact of patient education on patient compliance to psychotropic medication after discharge from the hospital. A sample of 36 patients discharged from an in-patient care facility and receiving an oral form of psychotropic drug were the subjects of this study. All subjects were patients of affective disorders. Subjects were randomly assigned to two groups: a control group; and a directive patient-education group. The subjects were followed up after discharge for a 6-month period. In analyzing the data, results indicated that the difference in percentage of compliance between the two groups was statistically significant. Findings imply that patient education did have an effect on patient compliance to medication. The findings of the study support a technique that can be incorporated in both in-patient and out-patient programmes in psychiatric-mental health nursing. It would increase patient compliance to medication and hence decrease chances of rehospitalization.