Notch signaling as a master regulator of adult neurogenesis.
Neurogenesis ceases in most regions of the mammalian brain before or shortly after birth, however, in a few restricted brain regions, the production of new neurons proceeds into adulthood. Neural stem cells (NSCs) in these neurogenic zones are integrated into niches that control their activity and fate. Most stem cells in the adult brain are mitotically inactive and these cells can remain quiescent for months or even years. One of the key questions is what are the molecular mechanisms that regulate NSC maintenance and differentiation. Notch signaling has been shown to be a critical regulator of stem cell activity and maintenance in many tissues including in the nervous system. In this mini-review we discuss the roles of Notch signaling and the functions of the different Notch receptors and ligands in regulating neurogenesis in the adult murine brain. We review the functions of Notch signaling components in controlling NSC quiescence and entry into cell cycle and neurogenesis.


Normal measurements of size of optic nerve sheath complex using computed tomography.
To establish normal value of optic nerve sheath complex on computed tomography. This prospective study was approved by the institutional ethics committee. Measurement of the optic nerve sheath complex at retrobulbar and waist regions was done on volunteers who came for cranial computed tomography examination at Thammasat University Hospital during May 2013-November 2013. There were 138 volunteers (75 males and 63 females) with average age of 57 years. Volunteers were excluded if they have eye symptoms or known related disease that affected optic nerves such as endocrinopathy, or if they have metallic object or prostheses that might confound the measurement. Size of optic nerve sheath complex was measured at retrobulbar and waist regions on reconstructed orbital CT images in a plane parallel to the optic nerve sheath complex. Two measurements were performed separately at 1-month intervals to evaluate reliability and reproducibility of the measurement. Then normal size and range of the optic nerve sheath complex were evaluated. Correlation between age, gender and size of the optic nerve sheath complex were also evaluated as well as difference in size of the complex between both eyes. Normal value of the optic nerve sheath complex (mean ± 2SDs) at retrobulbar and waist regions are 5.6±1.8 (3.8- 7.4) mm and 3.7± 0.8 (2.9-4.5) mm. There is no correlation between age, gender and size of the optic nerve sheath complex. No difference in size of the optic nerve sheath complex between both eyes was found. Normal value of optic nerve sheath complex at retrobulbar and waist regions in Thai population was established. This information might be useful in diagnosis of some diseases or excluding some conditions.


Phase diagram of a symmetric electron-hole bilayer system: a variational Monte Carlo study.
We study the phase diagram of a symmetric electron-hole bilayer system at absolute zero temperature and in zero magnetic field within the quantum Monte Carlo approach. In particular, we conduct variational Monte Carlo simulations for various phases, i.e. the paramagnetic fluid phase, the ferromagnetic fluid phase, the anti-ferromagnetic Wigner crystal phase, the ferromagnetic Wigner crystal phase and the excitonic phase, to estimate the ground-state energy at different values of in-layer density and inter-layer spacing. Slater-Jastrow style trial wave functions, with single-particle orbitals appropriate for different phases, are used to construct the phase diagram in the (r s , d) plane by finding the relative stability of trial wave functions. At very small layer separations, we find that the fluid phases are stable, with the paramagnetic fluid phase being particularly stable at [Formula: see text] and the ferromagnetic fluid phase being particularly stable at [Formula: see text]. As the layer spacing increases, we first find that there is a phase transition from the ferromagnetic fluid phase to the ferromagnetic Wigner crystal phase when d reaches 0.4 a.u. at r s = 20, and before there is a return to the ferromagnetic fluid phase when d approaches 1 a.u. However, for r s < 20 and [Formula: see text] a.u., the excitonic phase is found to be stable. We do not find that the anti-ferromagnetic Wigner crystal is stable over the considered range of r s and d. We also find that as r s increases, the critical layer separations for Wigner crystallization increase.


[Does exogenous melatonin prove to be effective in the prevention and treatment of pathologies associated with shift and night work?].
The current data concerning the efficacy of exogenous melatonin treatment, especially with respect to night-shift workers, are presented. Therapy of sleep disorders experienced by night-shift workers is not always successful. To assess the results of melatonin therapy in shift workers, it is essential to perform extensive analyses of numerous physiological functions that may be affected by this work system as well as of possible late health effects in this group of workers. It is also necessary to establish indications and conditions for this kind of therapy. We may suspect that both night-shift work tolerance and efficacy of melatonin therapy are different in individual workers, and thus the choice of therapy should be based on a thorough examination of each worker's psycho-somatic conditions.


Clitoral Choristoma: A Rare Case Report.
Clitoral hypertrophy is usually seen as a congenital malformation, specifically during the stages of hormonal expressions in the disorders of sexual development. Acquired clitoral hypertrophy is a relatively rare condition. Clitoris can be the site of neoplastic lesions. Clitoral choristoma has not been reported so far in the literature.


[Chapter 1. From the study of risks to the translation of the ethical issues of Big Data in Health].
Big Data substantially disrupt the medical microcosm up to challenge the paradigms of Medicine Hippocrates as we previously know. Therefore, a reflection on the study of risks associated with ethical issues around personal health data is imposed on us. Our study is based on many field surveys, interviews targeted at different actors, as well as a literature search on the subject. This work led to the realization of an innovative method of alignment of concepts of ontology of the risks to those of ontology of ethical objectives requirements of Big Data in Health. The aim is to make sense and recommendations to realization, implementation and use of personal data in order to better control it.


Some personal comments on the Sydney system for the classification of chronic gastritis.
The Sydney system for the classification of chronic gastritis is a system for describing the histopathological findings of a biopsy specimen. It involves the analysis of two to four biopsies of the gastric mucosa taken from arbitrary sites, which, taken alone, are insufficient for extrapolation to the diagnosis of the whole stomach. The system seems to be useful as a computer-oriented method fo documenting the histopathological analysis of the two to four biopsy specimens obtained from the arbitrary sites in the antrum or corpus. One biopsy specimen is obtained from the anterior wall of the antrum, the other from the posterior wall. They would be better obtained from the lesser and greater curvatures, which areas would provide more accurate data concerning the antrum or body. While this may be invaluable for researchers with particular interests, it is quite valueless for the majority of clinicians who must diagnose and treat their patients. When a classification is made, its purposes should, firstly, be clear and definite. Secondly, the classification should be simple and easy to use. If a classification is effective, it will be widely used. However, in this field, it is almost impossible to achieve a classification that will fully satisfy all practitioners and researchers with different interests. The Sydney system alone is not sufficient for the classification of chronic gastritis. It is merely a system for describing the histopathological findings of biopsy specimens. It does not allow for an integrated diagnosis of chronic gastritis of the entire stomach.


Staff support groups for high-stress medical environments.
Recent changes in health care delivery have added new demands to the already stressful work of medical staff, which makes the benefits of staff support groups all the more cogent. The author describes a conceptual approach to such groups and analyzes the systems issues that need to be understood to penetrate a complex institution successfully. Staff stressors are outlined along with the staff's psychological responses. Specific goals for support groups are considered and the profound technical differences between psychotherapy and support groups are delineated. The developmental stages of staff groups and their associated themes are described in tandem with practical guidelines about starting, maintaining, and terminating such groups. Special requirements of leadership style and related countertransference issues are reviewed.


Process improvement in cardiac surgery: development and implementation of a reoperation for bleeding checklist.
High-performing health care organizations differentiate themselves by focusing on continuous process improvement initiatives aimed at enhancing patient outcomes. Reoperation for bleeding is an event associated with considerable morbidity risk. Hence, our primary objective was to develop and implement a formal operative checklist to reduce technical reasons for postoperative bleeding. From January 1, 2011, through June 30, 2012, 5812 cardiac surgical procedures were performed at Cleveland Clinic (Cleveland, OH). A multidisciplinary team developed a simple, easy-to-perform hemostasis checklist based on the most common sites of bleeding. An extensive educational in-service was performed before limited, then universal, checklist implementation. Geometric charts were used to track the number of cases between consecutive reoperations for bleeding. We compared these before (phase 0) and after the first limited implementation phase (phase 1) and the universal implementation phase (phase 2) of the checklist. The average number of cases between consecutive reoperations for bleeding increased from 32 in phase 0 to 53 in both phase 1 (P = .002) and phase 2 (P = .01). A substantial reduction in reoperation for bleeding cases followed implementation of a formalized hemostasis checklist. Our findings underscore the important influence of memory aids that focus attention on surgical techniques to improve patient outcomes in a complex, operative work environment.


[Causes of death among prostate cancer patients of different ages].
To date, there is no unified approach to evaluating and treating patients with suspected prostate cancer taking into account their age and comorbidities. That was the rationale for conducting this study. To assess the clinical course of prostate cancer in men of all ages with comorbidities. The study included 408 patients aged 50 to 92 years (mean age 74.3 years) with histologically verified prostate cancer. 30 (7.4%) patients had stage T1 disease, 273 (66.9%) - T2, 91 (22.3%) - T3 and 14 (3.4%) - T4. The maximum follow-up was 22 years, the minimum one - 6 months (on average 15.4 years). During the follow-up 159 patients died (39%), 51 of them (32%) of prostate cancer, 108 (68%) - from other diseases. Among the latter the causes of death were cancer (20.4%), cardiovascular and bronchopulmonary diseases (79.6%). Cancer-specific survival rate was 41.4 +/-12,4%, the survival rate for other diseases 23.4 +/-10,6% (p<0.05). We need a differentiated approach to selecting treatment for patients with prostate cancer, especially of old age, including the option for active surveillance of patients with clinically insignificant prostate cancer.


Drude Polarizable Force Field for Molecular Dynamics Simulations of Saturated and Unsaturated Zwitterionic Lipids.
Additive force fields are designed to account for induced electronic polarization in a mean-field average way, using effective empirical fixed charges. The limitation of this approximation is cause for serious concerns, particularly in the case of lipid membranes, where the molecular environment undergoes dramatic variations over microscopic length scales. A polarizable force field based on the classical Drude oscillator offers a practical and computationally efficient framework for an improved representation of electrostatic interactions in molecular simulations. Building on the first-generation Drude polarizable force field for the dipalmitoylphosphatidylcholine 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) molecule, the present effort was undertaken to improve this initial model and expand the force field to a wider range of phospholipid molecules. New lipids parametrized include dimyristoylphosphatidylcholine (DMPC), dilauroylphosphatidylcholine (DLPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), dipalmitoylphosphatidylethanolamine (DPPE), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). The iterative optimization protocol employed in this effort led to lipid models that achieve a good balance between reproducing quantum mechanical data on model compound representative of phospholipids and reproducing a range of experimental condensed phase properties of bilayers. A parametrization strategy based on a restrained ensemble-maximum entropy methodology was used to help accurately match the experimental NMR order parameters in the polar headgroup region. All the parameters were developed to be compatible with the remainder of the Drude polarizable force field, which includes water, ions, proteins, DNA, and selected carbohydrates.


Characteristics of Adrenal Masses in Familial Adenomatous Polyposis.
Adrenal masses are a known extraintestinal manifestation of familial adenomatous polyposis. However, the literature on this association is largely confined to case reports. This study aimed to determine the characteristics of adrenal masses in familial adenomatous polyposis and their clinical significance, as well as to estimate their prevalence. Mutational analysis was conducted to determine if any potential genotype-phenotype correlations exist. This is a retrospective cohort study. Analysis included all patients meeting the criteria of classic familial adenomatous polyposis who were registered with the Familial Gastrointestinal Cancer Registry, a national Canadian database. Appropriate imaging or autopsy reports were available in 311 registry patients. Patients with adrenal metastases were excluded. Data collection included demographic data, mutation genotype, adrenal mass characteristics, surgical interventions and mortality. The prevalence of adrenal masses was 16% (n = 48/311). The median age at diagnosis of adrenal mass was 45 years. The median diameter of adrenal mass at diagnosis was 1.7 cm (interquartile range, 1.4-3.0) with a median maximal diameter of 2.5 cm (interquartile range, 1.7-4.1) with median imaging follow-up of 48 months. The majority of adrenal masses were benign (97%, n = 61/63). Surgery was performed on 7 patients because of concerns for size, malignancy, or hormonal secretion. One adrenal-related death was due to an adrenocortical carcinoma. Mutation analysis did not identify any specific genotype-phenotype correlations. There were incomplete or insufficient endocrinology data available in the registry to allow for the analysis of hormone secretion patterns. Adrenal masses are approximately twice as prevalent in the familial adenomatous polyposis population as in previous studies of the general population. Nearly all mutations led to truncation of the APC gene; however, there was no genetic signature to help predict those at increased risk. The majority of adrenal lesions identified were of benign etiology; thus, an intensive management or surveillance strategy with imaging screening is likely unwarranted. See Video Abstract at http://links.lww.com/DCR/A507.


[Use of the focus group as evaluation tool of a health education program].
The objective of this study was to identify the possibilities and limitations of the focal group as a tool to evaluation through a case study of a health educational training process. Among the conclusions we emphasize: the maintenance of the same group turns possible to compare results of the groups accomplished before and after the training; the focal group was adequate to reveal the nature of the training deficiencies since it had permitted to analyze the complexity inherent to both the drug field and the training objectives that seek for cultural and affective changes and not only for cognitive changes.


Two new Prenolepis species (Hymenoptera: Formicidae) from Indomalaya and Australasia, with a redescription of P. dugasi from Vietnam.
Prenolepis is a lineage of formicine ants with its center of diversity in the Old World tropics. Three more Prenolepis species are added to the Indomalayan and Australasian fauna and another is synonymized, bringing the total number of Prenolepis species worldwide to 19. Two new species are described: P. nepalensis from Nepal and P. lakekamu from Papua New Guinea, the latter being the first in the genus east of Wallace's Line. Additionally, P. dugasi Forel (comb. rev.) from Vietnam is transferred from Nylanderia and redescribed. Based on morphology, each of the three species appears to be most closely-related to other species found predominantly in or nearest to their respective bioregions: P. nepalensis most resembles P. darlena, P. fisheri, and P. fustinoda; P. lakekamu bears strongest resemblance to P. jacobsoni, P. jerdoni, and P. subopaca; and P. dugasi most resembles P. melanogaster. Descriptions, illustrations and images are provided for all three species. One new synonymy is proposed: P. angulinoda Chen Zhou 2018 = P. fustinoda Williams LaPolla 2016. An updated key for workers of all extant Prenolepis species is also included.


Biological activities and chemical composition of lichens from Serbia.
The aim of this study is to investigate chemical composition of acetone extracts of the lichens Parmelia arseneana and Acarospora fuscata and in vitro antioxidant, antimicrobial, and anticancer activities of these extracts and gyrophoric acid isolated from A. fuscata. The HPLC-UV method was used for the identification of secondary metabolites. Stictic acid, norstictic acid, gyrophoric acid, usnic acid, atranorin and chloroatranorin were identified in the A. fuscata. In P. arseneana, we detected stictic acid, norstictic acid, usnic acid and atranorin, while gyrophoric acid was not identified. Antioxidant activity was evaluated by measuring the scavenging capacity of tested samples on DPPH and superoxide anion radicals, reducing the power of samples and determination of total phenolic compounds in extracts. As a result of the study, gyrophoric acid was found to have the largest DPPH radical scavenging activity with an IC50 value of 105.75 µg/ml. Moreover, the tested samples had an effective superoxide anion radical scavenging and reducing power. The total content of phenol in extracts was determined as pyrocatechol equivalent. The antimicrobial activity was estimated by determination of the minimal inhibitory concentration by the broth microdilution method. The most active was also gyrophoric acid, with minimum inhibitory concentration values ranging from 0.019 to 1.25 mg/ml. Anticancer activity was tested against LS174 (human colon carcinoma cell line), A549 (human lung carcinoma cell line), Fem-x (malignant melanoma cell line), and a chronic myelogeneous leukaemia K562 cell line using the MTT method. Extract of P. arseneana expressed the strongest anticancer activity against all cell lines with IC50 values ranging from 11.61 to 47.06 µg/ml.


Histopathology of pulmonary fibrotic disorders.
Interstitial lung diseases encompass a broad spectrum of disorders that vary greatly in their clinical presentation, natural history, pathology, pathogenesis, prognosis, and treatment. Their correct classification requires integration of clinical, radiological, and pathological findings. Although these disorders may be well defined, interpretation of lung biopsy findings is often difficult, with surprisingly significant interobserver variability. This article reviews the histopathology of the major interstitial lung diseases, including the idiopathic interstitial pneumonias and pulmonary fibrotic disorders associated with collagen vascular diseases and smoking. In addition, the differential diagnosis of each of these disorders is discussed.


Psychological Adjustment To Amputation: Variations On The Bases Of Sex, Age And Cause Of Limb Loss.
Amputation is the removal of a limb or part of a limb by a surgical procedure in order to save the life of a person. The underlying reasons behind the occurrence of this tragic incidence may be varied. However, irrespective of its cause limb loss is associated with wide range of life challenges. The study was done to investigate the psychological sequel of an individual after losing a limb and to know the level of strain and pressure they experience after this traumatic event. It also attempts to examine the moderating role of some demographic traits such as age, sex and cause of limb loss in psychosocial adjustment to amputation. The study includes 100 adult amputees of both genders and the data was collected from major government and private hospitals of Peshawar district. Demographic data sheet was constructed in order to know the demographics traits of amputees and a standardize Psychological Adjustment Scale developed by Sabir (1999) was used to find out the level of psychological adjustment after limb loss. Nearly all the amputees' exhibit signs of psychological maladjustment at varying degrees. Males showed much greater signs of maladjustment than women and young adults were much psychologically shattered and disturbed as a result of limb loss. Amputation caused by planned medical reasons leads to less adjustment issues as compared to unplanned accidental amputation in which patient were not mentally prepare to accept this loss. Psychological aspect of amputation is an important aspect of limb loss which needs to be addressed properly in order to rehabilitate these patients and helps them to adjust successfully to their limb loss.


The Role of PPARγ in the Transcriptional Control by Agonists and Antagonists.
In recent years, peroxisome proliferator-activated receptor gamma (PPARγ) has been reported to be a target for the treatment of type II diabetes. Furthermore, it has received attention for its therapeutic potential in many other human diseases, including atherosclerosis, obesity, and cancers. Recent studies have provided evidence that the endogenously produced PPARγ antagonist, 2,3-cyclic phosphatidic acid (cPA), which is similar in structure to lysophosphatidic acid (LPA), inhibits cancer cell invasion and metastasis in vitro and in vivo. We recently observed that cPA negatively regulates PPARγ function by stabilizing the binding of the corepressor protein, silencing mediator of retinoic acid and thyroid hormone receptor. We also showed that cPA prevents neointima formation, adipocyte differentiation, lipid accumulation, and upregulation of PPARγ target gene transcription. We then analyzed the molecular mechanism of cPA's action on PPARγ. In this paper, we summarize the current knowledge on the mechanism of PPARγ-mediated transcriptional activity and transcriptional repression in response to novel lipid-derived ligands, such as cPA.


Drug-induced hypersensitivity reactions and pharmacogenomics: past, present and future.
Drug-induced hypersensitivity reactions represent a major concern for clinicians, patients, regulators and drug developers. Severe hypersensitivity is associated with high morbidity and mortality, it cannot be predicted from the known pharmacology of the drug and it is usually detected post-marketing when a large number of patients have been exposed to a particular drug. Recent success in developing clinically useful genetic tests that have allowed us to predict the risk of abacavir-induced hypersensitivity has helped to pave the path for a pharmacogenetic approach. However, the loop from identifying a genetic association to improving clinical outcome is still lacking for many drugs. In this commentary, we discuss the progress of hypersensitivity pharmacogenomics over the last decade and point out what remains to be done in the future. The current efforts of the international community are focused on the development of consortia, which aim to standardize disease phenotypes, but also to collect larger numbers of well-phenotyped patients and to pool biological samples through these collaborations. In addition, it is necessary to advance our knowledge of hypersensitivity mechanisms through functional studies, which will lead to the development of predictive and diagnostic tests.


Mutations Designed by Ensemble Defect to Misfold Conserved RNA Structures of Influenza A Segments 7 and 8 Affect Splicing and Attenuate Viral Replication in Cell Culture.
Influenza A virus is a significant public health threat, but little is understood about the viral RNA structure and function. Current vaccines and therapeutic options to control influenza A virus infections are mostly protein-centric and of limited effectiveness. Here, we report using an ensemble defect approach to design mutations to misfold regions of conserved mRNA structures in influenza A virus segments 7 and 8. Influenza A mutant viruses inhibit pre-mRNA splicing and attenuate viral replication in cell culture, thus providing evidence for functions of the targeted regions. Targeting these influenza A viral RNA regions provides new possibilities for designing vaccines and therapeutics against this important human respiratory pathogen. The results also demonstrate that the ensemble defect approach is an efficient way to test for function of RNA sequences.


Boundary Aware U-Net for Retinal Layers Segmentation in Optical Coherence Tomography Images.
Retinal layers segmentation in optical coherence tomography (OCT) images is a critical step in the diagnosis of numerous ocular diseases. Automatic layers segmentation requires separating each individual layer instance with accurate boundary detection, but remains a challenging task since it suffers from speckle noise, intensity inhomogeneity, and the low contrast around boundary. In this work, we proposed a boundary aware U-Net (BAU-Net) for retinal layers segmentation by detecting accurate boundary. Based on encoder-decoder architecture, we design a dual tasks framework with low-level outputs for boundary detection and high-level outputs for layers segmentation. Specifically, we first use the multi-scale input strategy to enrich the spatial information in the deep features of encoder. For low-level features from encoder, we design an edge aware (EA) module in skip connection to extract the pure edge features. Then, a U-structure feature enhanced (UFE) module is designed in all skip connections to enlarge the features receptive fields from the encoder. Besides, a canny edge fusion (CEF) module is introduced to aforementioned architecture, which can fuse the priory edge information from segmentation task to boundary detection branch for a better predication. Furthermore, we model each boundary as a vertical coordinates distribution for boundary detection. Based on this distribution, a topology guarantee loss with combined A-scan regression loss and structure loss is proposed to make an accurate and guaranteed topological boundary set. The method is evaluated on two public datasets and the results demonstrate that the BAU-Net achieves promising performance than other state-of-the-art methods.


Expression of TLE1 in a Carcinoid Tumor of the Lung With Spindle Cell Morphology-A Potential Diagnostic Pitfall.
Tumors of the lung with a spindle cell morphology require consideration of many entities in the differential diagnosis, including metastases. Ancillary immunohistochemical stains but also molecular studies are typically required to arrive at the proper diagnosis. We present a case of a 71-year-old woman with multiple lung nodules, mediastinal lymphadenopathy, and a history of uterine cancer who underwent endobronchial ultrasound-guided fine needle aspiration and biopsy of the lung and mediastinal lymph nodes. A sampling of the lung lesion showed a cytologically bland neoplasm with spindle cell morphology, lacking necrosis or brisk mitotic activity. In conjunction with the cytomorphology, strong and diffuse Transducin-like enhancer of split 1 (TLE1) reactivity in the tumor cells initially raised the diagnosis of synovial sarcoma; however, subsequent results of additional testing showed strong and diffuse expression with AE1/AE3, CK 8/18, TTF-1, synaptophysin and chromogranin and focal or negative staining with a large number of other antibodies. This warranted a diagnosis of a carcinoid tumor. This is the first report of TLE1 staining in a carcinoid tumor of the lung. Therefore, when evaluating tumors of the lung with spindle cell morphology in which the differential diagnosis may include both carcinoid tumor and synovial sarcoma, TLE1 expression should be interpreted with caution and in conjunction with an expanded immunohistochemical staining panel.


Relation between erectile dysfunction and urinary incontinence after nerve-sparing and non-nerve-sparing radical prostatectomy.
We investigated the status of erectile function and urinary continence after radical prostatectomy to investigate a possible relation between them and then determined whether the status of postoperative urinary continence affected erectile function. Seventy-six patients who had no symptoms of erectile dysfunction or urinary incontinence preoperatively were included in this study. The postoperative status of erectile function and urinary continence was investigated using a self-reported patient questionnaire. Thirteen of 27 patients (48.1%) who underwent nerve-sparing procedures maintained erectile function, while 7 of 49 patients (14.2%) who underwent non-nerve-sparing procedures maintained it postoperatively. None of the 27 patients in the nerve-sparing procedure group reported incontinence, whereas 3 of the 49 patients (6.1%) who underwent non-nerve-sparing procedures reported moderate incontinence. However, no significant correlation between the International Index of Erectile Function-5 score and the Incontinence Impact Questionnaire score was seen. No relation between the status of urinary continence and erectile function was shown, regardless of the nerve-sparing nature of the prostatectomy.


Regulation of the pituitary growth hormone-releasing hormone receptor in ageing male and female LOU rats: new insights into healthy ageing.
Ageing is characterised by a decrease of somatotroph functionality, involving growth hormone-releasing hormone receptor (GHRH-R). The present study was conducted in LOU/C/jall (LOU) rats, a strain described as a model of healthy ageing, which is characterised by a low adiposity and long life expectancy without developing severe pathologies. Effects of age and diet (chow versus self-selection), on levels of anterior pituitary GHRH-R mRNA transcripts, were assessed in male and female LOU rats. The effect of age on pituitary GHRH-R functionality was examined in the anterior pituitary of both males and females fed chow diet. Moreover, serum insulin-like growth factor-I (IGF-I), T4 and leptin were measured because changes in their concentration could affect GHRH-R expression. In the pituitary of 18-month-old male and female LOU/C/jall rats fed standard chow, the level of 2.5-kb GHRH-R mRNA transcript, coding for functional GHRH-R, was significantly decreased. In 24- to 34-month-old males and females, it progressively returned to the level of younger animals, suggesting an enrichment of the group with survivors maintaining functional GHRH-R. In males and females repeatedly submitted to self-selection, this phenomenon was not observed. Studies with the GHRH-R agonist, Fluo-GHRH, revealed that 73% of 16-18-month-old male and female rats studied did not show an increase of fluorescence density characteristic of receptor-mediated internalisation upon incubation at 37 degrees C. In the other 27%, the increase of fluorescence was identical to that observed in pituitaries of young rats, suggesting the presence of an optimal level of functional GHRH-R. Serum levels of leptin, free T4 and total IGF-I decreased more drastically in ageing males and in rats fed a self-selection diet. A positive correlation was demonstrated between leptin and IGF-I levels in ageing males and females fed standard chow and ageing females submitted to a self-selection regimen. In conclusion, healthy ageing in LOU rats fed chow diet appears to be associated with a maintenance of functional pituitary GHRH-R levels found in younger rats but not necessarily with those of serum leptin, T4 and IGF-I.


Evaluation of brivaracetam: a new drug to treat epilepsy.
High prevalence of therapy-resistant epilepsy demands development of anticonvulsants with new mechanisms of action. Brivaracetam is an analogue of levetiracetam which binds to the synaptic vesicle protein 2A (SV2A) and decreases release of excitatory neurotransmitters. Areas covered: Relevant published studies were searched for by predefined strategy in MEDLINE, EBSCO and SCINDEKS electronic databases. Brivaracetam is effective as adjunctive therapy for uncontrolled partial-onset seizures with or without secondary generalization in patients 16 years and older with epilepsy. It reduces baseline-adjusted focal seizure frequency per week from 7.3 to 12.8% over placebo. Adverse events rate in patients with brivaracetam is not higher than in patients with placebo. Expert opinion: Brivaracetam is an important step forward in the treatment of therapy-resistant partial-onset seizures with or without secondary generalization. Its development was systematic and targeted. Due to its efficacy and excellent safety profile, it is likely that brivaracetam will be often prescribed. In future, efficacy and safety of brivaracetam should be tested in monotherapy settings and also in the first-line therapy of partial-onset seizures.


Increases in the density of parvalbumin-immunoreactive neurons in anterior cingulate cortex of amphetamine-withdrawn rats: evidence for corticotropin-releasing factor in sustained elevation.
We previously reported synchronization of pyramidal neurons within prefrontal cortex of rats repeatedly exposed to amphetamine (AMPH). To test the hypothesis that cortical synchronization may be related to changes in local GABA signaling, we used antibodies specific for parvalbumin (PV), calbindin D28k (CB) and calretinin (CR) as selective labels for three distinct GABA interneuron classes in the anterior cingulate cortex (ACC) of similarly treated rats. We observed a selective increase in the density of PV-immunoreactive (ir), but not CB-ir or CR-ir, neurons in the ACC of AMPH-treated rats at both 1 day and 7 day withdrawal. Increased density of PV-ir GABA interneurons in the ACC at 1 day withdrawal was reproduced in rats repeatedly injected with apomorphine or with SKF-38393. Thus, the critical role of DA receptors during AMPH exposure is evident. However, DA receptor activation did not appear to account for the PV up-regulation in AMPH-treated rats at 7 day withdrawal. Significantly higher numbers of pericellular basket-like puncta immunoreactive for corticotropin-releasing factor (CRF) were observed in the ACC of AMPH rats at 7 day withdrawal. Combined dual immunofluorescence and confocal microscopy further revealed that CRF-ir puncta made possible pericellular contacts on PV-ir (not CB-, CR- or glutamate-ir) cell bodies. A potential cellular mechanism seems to emerge that CRF-ir terminals, that may be underdetected under normal conditions due to low activity levels, may be functionally activated during psychostimulant withdrawal, thereby altering local GABAergic signaling.


The Support to Rural India's Public Education System (STRIPES) trial: a cluster randomised controlled trial of supplementary teaching, learning material and material support.
The aim of the STRIPES trial was to assess the effectiveness of providing supplementary, remedial teaching and learning materials (and an additional 'kit' of materials for girls) on a composite of language and mathematics test scores for children in classes two, three and four in public primary schools in villages in the Nagarkurnool division of Andhra Pradesh, India. STRIPES was a cluster randomised trial in which 214 villages were allocated either to the supplementary teaching intervention (n = 107) or to serve as controls (n = 107). 54 of the intervention villages were further randomly allocated to receive additional kit for girls. The study was not blinded. Analysis was conducted on the intention to treat principle, allowing for clustering. Composite test scores were significantly higher in the intervention group (107 villages; 2364 children) than in the control group (106 villages; 2014 children) at the end of the trial (mean difference on a percentage scale 15.8; 95% CI 13.1 to 18.6; p<0.001; 0.75 Standard Deviation (SD) difference). Composite test scores were not significantly different in the 54 villages (614 girls) with the additional kits for girls compared to the 53 villages (636 girls) without these kits at the end of the trial (mean difference on a percentage scale 0.5; 95% CI -4.34 to 5.4; p = 0.84). The cost per 0.1 SD increase in composite test score for intervention without kits is Rs. 382.97 (£4.45, $7.13), and Rs.480.59 (£5.58, $8.94) for the intervention with kits. A 18 month programme of supplementary remedial teaching and learning materials had a substantial impact on language and mathematics scores of primary school students in rural Andhra Pradesh, yet providing a 'kit' of materials to girls in these villages did not lead to any measured additional benefit. Controlled-Trials.com ISRCTN69951502.


Antigenic specificity of antibodies in vaginal secretions during infection with Neisseria gonorrhoeae.
Antibodies in genital secretions of patients with gonorrhea have been shown to inhibit the attachment of gonococci to epithelial cells. The gonococcal antigens for which these antibodies are specific were studied by adsorption of the genital secretions from a patient infected with gonorrhea with purified lipopolysaccharide, outer membrane complex, or purified pili of homologous Neisseria gonorrhoeae and measurement of the reduction of inhibition of attachment of the gonococci to epithelial cells. The removal of antibodies was documented with the use of a solid-phase radioimmunoassay in which the amount of antibody in the adsorbed secretions that bound to a specific gonococcal antigen was shown to be reduced as compared with the amount of antibody in unadsorbed secretions. The antibody in the secretions that inhibited attachment was removed primarily by adsorption with the homologous pili, not with homologous lipopolysaccharide. A preparation of the homologous outer membrane complex that contained pili, cell-wall proteins, and lipopolysaccharide also blocked the inhibitory antibody.


hMRAPα, but Not hMRAP2, Enhances hMC4R Constitutive Activity in HEK293 Cells and This Is Not Dependent on hMRAPα Induced Changes in hMC4R Complex N-linked Glycosylation.
MRAP1 but not MRAP2, is essential for melanocortin receptor 2 functional expression. Human MRAP1 splice variant (hMRAPα) and human MRAP2 (hMRAP2) also interact with the other melanocortin receptor subtypes in vitro, although the physiological significance of these interactions is unknown. Previously we showed that HA-hMC4R co-expression with hMRAPα, but not hMRAP2, specifically alters HA-hMC4R complex N-linked glycosylation. hMRAPα-FLAG also enhances hMC4R constitutive activity in vitro. Here we directly compare hMRAPα and hMRAP2 effects on hMC4R constitutive activity in HEK293 cells. In contrast to hMRAPα, co-expression with hMRAP2 had no effect on HA-hMC4R or untagged hMC4R constitutive coupling to adenylyl cyclase. We used fixed and live cell imaging of HA-hMC4R and hMC4R-eGFP respectively, to further characterise effects of hMRAPα on hMC4R subcellular trafficking. hMRAPα-FLAG co-expression did not alter the partitioning of either HA-hMC4R or hMC4R-eGFP into either the ER or the Golgi apparatus, therefore the hMRAPα effect on hMC4R complex N-linked glycosylation is probably not due to hMC4R retention in the ER. We also observed that unlike HA-hMC4R, hMC4R-eGFP lacks complex glycosylation both in the presence and absence of hMRAPα, although both HA-hMC4R and hMC4R-eGFP exhibited increased constitutive coupling to adenylyl cyclase following co-expression with hMRAPα. We conclude that hMRAPα and not hMRAP2 modulates hMC4R constitutive activity. Furthermore, hMRAPα does not increase hMC4R constitutive activity by altering hMC4R complex N-linked glycosylation. Instead we hypothesise that hMRAPα alters hMC4R conformational states leading to increased hMC4R constitutive activity.


Family Presence and Participation: Pediatrics Leading the Way ... And Still Evolving.
Patient- and family-centered care began in pediatrics more than two decades ago, and pediatric care has continued to lead the way in acknowledging and supporting family presence and participation in patient care and decision-making. However, many adult hospitals still have "visiting" policies that restrict the potential for true partnerships with families and other care partners. A national campaign, Better Together: Partnering with Families, developed by the Institute for Patient- and Families-Centered Care (IPFCC), urges all hospitals--pediatric and adult--to welcome families 24/7. Despite the leadership of pediatrics in family-centered care, even in children's hospitals, policy and practice must continue to evolve to strengthen partnerships with families, as described in a profile of C.S. Mott Children's Hospital and the University of Michigan Health System.


Pashto Handwritten Invariant Character Trajectory Prediction Using a Customized Deep Learning Technique.
Before the 19th century, all communication and official records relied on handwritten documents, cherished as valuable artefacts by different ethnic groups. While significant efforts have been made to automate the transcription of major languages like English, French, Arabic, and Chinese, there has been less research on regional and minor languages, despite their importance from geographical and historical perspectives. This research focuses on detecting and recognizing Pashto handwritten characters and ligatures, which is essential for preserving this regional cursive language in Pakistan and its status as the national language of Afghanistan. Deep learning techniques were employed to detect and recognize Pashto characters and ligatures, utilizing a newly developed dataset specific to Pashto. A further enhancement was done on the dataset by implementing data augmentation, i.e., scaling and rotation on Pashto handwritten characters and ligatures, which gave us many variations of a single trajectory. Different morphological operations for minimizing gaps in the trajectories were also performed. The median filter was used for the removal of different noises. This dataset will be combined with the existing PHWD-V2 dataset. Various deep-learning techniques were evaluated, including VGG19, MobileNetV2, MobileNetV3, and a customized CNN. The customized CNN demonstrated the highest accuracy and minimal loss, achieving a training accuracy of 93.98%, validation accuracy of 92.08% and testing accuracy of 92.99%.


[ENDOTHELIAL MONOCYTEACTIVATING FACTOR II CANCELS OXIDATIVE STRESS, CONSTITUTIVE NOS UNCOUPLING AND INDUCED VIOLATIONS OF CARDIAC HEMODYNAMICS IN HYPERTENSION (PART II)].
The purpose of this study was to investigate the effect of EMAP II on free radical state of the heart and blood vessels, to restore cNOS coupling and cardiac hemodynamics in spontaneously hypertensive rats. It was found that, due to the combined inhibition of oxidative and nitrosative stress, EMAP I quickly restores impaired in hypertension constitutive de novo synthesis of NO by restoring cNOS coupling. Restoration by EMAP II of constitutive de novo synthesis NO abolished cardiac and endothelial dysfunction in spontaneously hypertensive rats. In hypertension, the introduction of EMAP II helped to improve the performance of the pumping function of the heart (stroke volume increased by 18.2 %, cardiac output -22 %), an arterial stiffness decreased by 23.2 %, process of relaxation of the left ventricle improved, due to decreased in 4,7 times myocardial end-diastolic stiffness.


Integrating Tobacco Use Treatment Into Practice: Billing and Documentation.
Balancing population-based efforts to modify the social and environmental factors that promote tobacco dependence with efforts to improve the delivery of case-based treatments is necessary for realizing maximum reductions in the cost and consequences of the disease. Public health antismoking campaigns following the 1964 Surgeon General's report on the health risks of smoking have changed social norms, prevented initiation among youth, and promoted abstinence among the addicted. However, the rate of progress enjoyed to date is unlikely to continue into the coming decades, given that current annual unassisted cessation rates among prevalent smokers remains fairly low. With more than 1 billion patient interactions annually, there is an enormous unrealized capacity for health-care systems to have an effect on this problem. Clinicians report a perceived lack of reimbursement as a significant barrier to full integration of tobacco dependence into health care. A more complete understanding of the coding and documentation requirements for successful practice in this critically important area is a prerequisite to increasing engagement. This paper presents several case-based scenarios illustrating important practice management issues related to the treatment of tobacco dependence in health care.


Monastrol, a 3,4-dihydropyrimidin-2(1H)-thione, as structural scaffold for the development of modulators for GHB high-affinity binding sites and α1β2δ GABAA receptors.
The α4βδ subtype of the γ-aminobutyric acid (GABA) type A receptors (GABAARs) has been shown to be implicated in high-affinity binding of the neuromodulator γ-hydroxybutyric acid (GHB), but may not be the only GHB high-affinity binding sites. Monastrol has been identified as a modulator of GHB high-affinity binding and is furthermore reported as an allosteric modulator selective for the α1β2δ GABAARs. Therefore, structural determinants for selectivity at the two targets were investigated. 39 structural diverse monastrol analogues were synthesized by employing the Biginelli cyclocondensation and examined for modulation of GHB high-affinity binding using the GHB-specific ligand [3H]NCS-382 [(E,RS)-6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid] in rat brain homogenate. Only limited modifications were allowed on the monastrol scaffold in order to maintain modulation of GHB high-affinity binding. However, three analogues of monastrol (11, 12 and 24) enhanced the maximal binding of [3H]NCS-382 to a higher maximal level than seen for monastrol itself. Selected compounds were further characterized as modulators at α1β2δ, α1β2γ2s and α1β2 GABAARs. Most of these modulators were shown to have δ-specific GABA-potentiating effects. The dual effect shown for monastrol to modulate the GHB high-affinity binding and α1β2δ GABAAR activity was also shown for the compounds 11, 18 and 24. Compound 29 displayed minimal modulatory effect on GABAARs and therefore appears to be a GHB high-affinity binding preferring modulator. However, compounds 34 and 37 were shown to be α1β2δ GABAAR selective modulators, without modulatory effects on GHB high-affinity binding. Thus, our study shows that minor modifications in the structure of monastrol affects the selectivity profile for the two targets under study enabling separation of the dual activity.


Endothelins stimulate mitogen-activated protein kinase cascade through either ETA or ETB.
Endothelin (ET) has been shown to activate mitogen-activated protein kinase (MAPK). However, it has been unclear which of the ET receptors is coupled to MAPK activation. In the present study, we conducted experiments to determine which ET receptor is linked to MAPK activation. We found that both human ETA and ETB were coupled to the MAPK cascade in ETA or ETB cDNA-transfected Chinese hamster ovary cells. ET-1 was more potent than ET-3 in the activation of p42 MAPK, induction of MAPK kinase (MAPKK) gel retardation and uptake of [3H]thymidine in ETA-transfected cells, whereas sarafotoxin (S6c) showed no stimulatory effect on the kinases and [3H]thymidine uptake. ET-1, ET-3, and S6c had approximately the same potency to activate p42 MAPK, MAPKK gel retardation, and [3H]thymidine uptake in ETB-transfected cells. These data suggest that 1) ET isopeptides, through either ETA or ETB receptors, induce the MAPK cascade as well as cell proliferation; and 2) the different potencies of ET isopeptides for activation of the MAPK cascade and induction of cell growth are mainly due to their different affinities toward ETA and ETB.


MiR-26b regulates 5-FU-resistance in human colorectal cancer via down-regulation of Pgp.
Chemotherapy resistance frequently drives tumor progression. However, the underlying molecular mechanisms remain unclear. In this study, we found that the expression level of miR-26b was down-regulated in the human colorectal cancer tissues and the resistant cells strains: HT-29/5-FU and LOVO/5-FU cells. Meanwhile, we showed that miR-26b improved sensibility of colorectal cancer cells to 5-FU in vitro and enhanced the potency of 5-FU in the inhibition of tumor growth in vivo. We further demonstrated that the tumor suppressive role of miR-26b was mediated by negatively regulating P-glycoprotein (Pgp) protein expression. Furthermore, studies of colorectal cancer specimens indicated that the expression of miR-26b and Pgp had inverse correlation. Importantly, we found that CpG islands in the miR-26b promoter region were hypermethylated in 5-FU resistant cells. Our study is the first to identify the tumor suppressive role of over-expressed miR-26b in chemo-sensitivity. Identification of a novel miRNA-mediated pathway that regulates chemo-sensitivity in colorectal cancer will facilitate the development of novel therapeutic strategies in the future.


Toward Time-Resolved Analysis of RNA Metabolism in Archaea Using 4-Thiouracil.
Archaea are widespread organisms colonizing almost every habitat on Earth. However, the molecular biology of archaea still remains relatively uncharacterized. RNA metabolism is a central cellular process, which has been extensively analyzed in both bacteria and eukarya. In contrast, analysis of RNA metabolism dynamic in archaea has been limited to date. To facilitate analysis of the RNA metabolism dynamic at a system-wide scale in archaea, we have established non-radioactive pulse labeling of RNA, using the nucleotide analog 4-thiouracil (4TU) in two commonly used model archaea: the halophile Euryarchaeota Haloferax volcanii, and the thermo-acidophile Crenarchaeota Sulfolobus acidocaldarius. In this work, we show that 4TU pulse labeling can be efficiently performed in these two organisms in a dose- and time-dependent manner. In addition, our results suggest that uracil prototrophy had no critical impact on the overall 4TU incorporation in RNA molecules. Accordingly, our work suggests that 4TU incorporation can be widely performed in archaea, thereby expanding the molecular toolkit to analyze archaeal gene expression network dynamic in unprecedented detail.


Nanocluster formation and stabilization fundamental studies: investigating "solvent-only" stabilization en route to discovering stabilization by the traditionally weakly coordinating anion BF4- plus high dielectric constant solvents.
The nanocluster literature contains a wide variety of nanocluster stabilizing agents. In addition to the plethora of putative stabilizing additives, 12 claims appear of "solvent-only" stabilization of transition-metal nanoclusters-a hypothesis that is tested for the first time as part of the present studies. When the two main modes of nanocluster stabilization, electrostatic and steric are considered, "solvent-only" stabilization can only be steric (i.e., is not electrostatic). Solvent-only stabilization would, therefore, require that a strongly coordinated, perhaps even kinetically nonlabile, solvent be present on the nanocluster surface. Hence, an investigation has been conducted into potential sources for the stabilization of prototype Ir(0)n transition-metal nanoclusters prepared from [(1,5-COD)Ir(CH3CN)2][BF4] in five different solvents, with a special focus on the formulation and testing of alternative hypotheses regarding the true source of the nanocluster stabilization in putative solvent-only stabilization conditions. Seven total hypotheses are tested with five being initially ruled out; they are, namely, stabilization by (i) trace chloride (ii), surface hydrides, (iii) scavenged charge, (iv) solvent oxidative addition reactions with the nanocluster surface, or (v) polymerized solvent. This led in turn to two additional main alternative hypotheses: (vi) nanocluster surface ligation by high-donor number solvents (i.e., in the absence of anions) and (vii) nanocluster stabilization by surface-coordination of the traditionally weakly coordinating anion BF(4-). Our results reveal a significant contribution to nanocluster stability from the traditionally weakly coordinating BF(4-) in high dielectric constant solvents, such as propylene carbonate. Literature claims of solvent-only nanocluster stabilization are not supported by our findings. Overall, DLVO (Derjaugin-Landau-Verwey-Overbeek) theory of colloidal stability is supported and found to apply to even traditionally weakly coordinating anions.


Intraventricular migration of an ICD patch.
A 42-year-old man presented with fever and weight loss 12 months after ICD replacement. After unsuccessful search for an infected focus and a specific antibiotic treatment ICD pocket was explored and Staphylococcus epidermidis was cultured. Following generator explanation fever recurred and at a second operation one ICD patch was found to have perforated in the right ventricular cavity. Explanation of the patches was performed on cardiopulmonary bypass, the patient survived the operation and infection was eradicated.


Stepwise diagnostic algorithm for high-attenuation pulmonary abnormalities on CT.
High-attenuation pulmonary abnormalities are commonly seen on CT. These findings are increasingly encountered with the growing number of CT examinations and the wide availability of thin-slice images. The abnormalities include benign lesions, such as infectious granulomatous diseases and metabolic diseases, and malignant tumors, such as lung cancers and metastatic tumors. Due to the wide spectrum of diseases, the proper diagnosis of high-attenuation abnormalities can be challenging. The assessment of these abnormal findings requires scrutiny, and the treatment is imperative. Our proposed stepwise diagnostic algorithm consists of five steps. Step 1: Establish the presence or absence of metallic artifacts. Step 2: Identify associated nodular or mass-like soft tissue components. Step 3: Establish the presence of solitary or multiple lesions if identified in Step 2. Step 4: Ascertain the predominant distribution in the upper or lower lungs if not identified in Step 2. Step 5: Identify the morphological pattern, such as linear, consolidation, nodular, or micronodular if not identified in Step 4. These five steps to diagnosing high-attenuation abnormalities subdivide the lesions into nine categories. This stepwise radiologic diagnostic approach could help to narrow the differential diagnosis for various pulmonary high-attenuation abnormalities and to achieve a precise diagnosis.Critical relevance statement Our proposed stepwise diagnostic algorithm for high-attenuation pulmonary abnormalities may help to recognize a variety of those high-attenuation findings, to determine whether the associated diseases require further investigation, and to guide appropriate patient management. Key points • To provide a stepwise diagnostic approach to high-attenuation pulmonary abnormalities.• To familiarize radiologists with the varying cause of high-attenuation pulmonary abnormalities.• To recognize which high-attenuation abnormalities require scrutiny and prompt treatment.


[Effects on secretory function of rat gonad by Erxian decoction and its disassembled prescriptions].
To explain functions, differences and coordination of three divided combinations of the "Erxian decoction", the famous traditional Chinese formula, on the effective sites of gonad gland at the cell level. The effects of Erxian decoction and its main disassembled prescriptions, "Kidney Warming", "Yin Nourishing" and "Chong-ren Adjusting", on the level of testosterone (T) progesterone (P) estradiol (E2), respectively secreted by the primary culture Leydig cell, luteal cell and granulosa cell, were measured by radioimmunoassay. (1) Erxian decoction could stimulate the T secretion while its three main disassembled prescriptions would seem no individual promoting effect on the secretion of T. (2) Erxian decoction and the "Kidney Warming" had the stimulating effect on P secretion, and the action of the whole formula being better than that of the "Kidney Warming". (3) Erxian decoction and its main disassembled prescriptions had the stimulating effect on E2 secretion, especially the whole formula. Erxian decoction can stimulate the secretion of T of the Leydig cell, P of luteal cell and E2 of granulosa cell. It can be seen that the effect of the whole formula is better than that of its main disassembled prescriptions.


Distribution in flowing reaction-diffusion systems.
A power-law distribution is found in the density profile of reacting systems A+B-->C+D and 2A-->2C under a flow in two and three dimensions. Different densities of reactants A and B are fixed at both ends. For the reaction A+B , the concentration of reactants asymptotically decay in space as x-1/2 and x-3/4 in two dimensions and three dimensions, respectively. For 2A , it decays as log(x)/x in two dimensions. The decay of A+B is explained considering the effect of segregation of reactants in the isotropic case. The decay for 2A is explained by the marginal behavior of two-dimensional diffusion. A logarithmic divergence of the diffusion constant with system size is found in two dimensions.


Both an N-terminal 65-kDa domain and a C-terminal 30-kDa domain of SecA cycle into the membrane at SecYEG during translocation.
SecA, a 102-kDa hydrophilic protein, couples the energy of ATP binding to the translocation of preprotein across the bacterial inner membrane. SecA function and topology were studied with metabolically labeled [35S]SecA and with inner membrane vesicles from cells that overexpressed SecYEGDFyajC, the integral domain of preprotein translocase. During translocation in the presence of ATP and preprotein, a 65-kDa N-terminal domain of SecA is protected from proteolytic digestion through insertion into the membrane, as previously reported for a 30-kDa C-terminal domain [Economou, A. & Wickner, W. (1994) Cell 78, 835-843]. Insertion of both domains occurs at saturable SecYEGDFyajC sites and is rapidly followed by deinsertion. SecA also associates nonsaturably and unproductively with lipid. In the presence of ATP, yet without involvement of preprotein or SecYEG, lipid-bound SecA forms domains that are protease-resistant and that remain so even upon subsequent membrane disruption. Unlike the [35S]SecA that inserts into the membrane at SecYEGDFyajC as it promotes preprotein translocation, lipid-associated [35S]SecA does not chase from its protease-resistant state upon the addition of excess SecA. The finding that two domains of SecA (which together represent most regions of the polypeptide chain) cycle into the membrane during preprotein translocation, as well as the distinction between the membrane association of SecA at translocation sites of SecYEGDFyajC and at nonproductive lipid sites, are fundamental to the study of the role of SecA in preprotein movement.


[Attachment Representation and Emotion Regulation in Patients with Burnout Syndrome].
Burnout describes a syndrome of exhaustion resulting from insufficient coping with work-related distress. We investigated if patients that are being clinically treated for burnout show insecure and unresolved attachment representation more often compared with healthy controls. 50 out of 60 consecutive burnout patients participated in the study. Mental representation of attachment was measured by using the Adult Attachment Interview. Additionally, we administered the Self Report Questionnaire to Assess Emotional Experience and Emotion Regulation and several burnout specific questionnaires. A population sample was used as control group. Burnout patients were classified as insecurely attached significantly more often than controls. Unresolved attachment status concerning loss or trauma was found significantly more often within the burnout sample. Patients with insecure attachment representation reported a lower subjective significance of work. Patients with avoidant insecure attachment showed more depersonalisation. Patients with unresolved loss/trauma reported less social support. They showed more passive-negative emotion experience and emotion regulation characterized by externalization. The results of the study suggest that an insecure or unresolved attachment representation might constitute an intrapersonal risk factor for the development of burnout syndrome.


Shotgun Proteomics Analysis Discards Alkali Labile Phosphate as a Reliable Method To Assess Vitellogenin Levels in Mytilus galloprovincialis.
Vitellogenin, the egg yolk precursor, is a well-known biomarker of endocrine disruption in oviparous vertebrates. In invertebrates, such as bivalves, it has been used in the last 10 years for the same purpose, despite the limited knowledge of invertebrate endocrinology. In bivalves, vitellogenin levels are usually estimated using an indirect technique, alkali labile phosphate (ALP), that assumes that vitellogenin is the most abundant phosphorylated protein in the analyzed tissue. In this study, we applied shotgun proteomics for the identification and quantification of vitellogenin in marine mussel gonads and compared the results with those obtained with the ALP method. The proteomic analysis revealed that vitellogenin is only detected in female gonads with expression levels that are rather variable among female mussels at different stages of gonad development. ALP analysis, on the contrary, detected similar amounts of phosphorylated proteins regardless of sex or gonad development stage. These results show evidence that the ALP method is not providing reliable information about Vtg levels, at least in marine mussel gonads. ALP is not a good proxy to assess Vtg levels in marine mussels, and careful verification of the adequacy of the procedure should be done before ALP is further assumed as a proxy of Vtg in other bivalve mollusks.


Fmoc SPPS using Perloza beaded cellulose.
Perloza beaded cellulose was functionalised by a cyanoethylation/reduction procedure to give aminopropyl Perloza. Fmoc-amino acids were anchored to aminopropyl Perloza beaded cellulose via the TFA labile 4-oxymethylphenoxyacetyl (HMPA) linker. Using Fmoc-aminoacyl-4-oxymethylphenoxyacetyl-2,4-dichloro-phenyl esters, all 20 amino acids were anchored at substitution levels ranging from 0.37 to 0.65 mmol/g. Fmoc-amino acids were also anchored using the peptide-amide linker 4-[(R,S)-1-[1-(9H-fluoren-9-yl)-methoxycarbonylamino - (2',4'-dimethoxybenzyl]phenoxyacetic acid. The Fmoc-aminoacyl resins were used for SPPS using Fmoc chemistry. SPPS was carried out using either an LKB Biolynx 4175 low-pressure pumped column continuous-flow peptide synthesiser or an ABI 430A automated vortexing batchwise instrument. Comparison of peptides made using each synthesiser showed little difference in quality of the crude peptides. Different Fmoc-amino acid activation methods (DIC/HOBt/DMF, HBTU, DIC/HOBt/DCM) were found to be equally useful with Perloza. Peptides were cleaved using TFA plus scavengers; however, the TFA-swollen resin was not readily separated from the TFA/peptide solution by simple filtration. Therefore alternative cleavage workup procedures were used with Perloza. Peptides were purified by HPLC and characterised by HPLC and amino acid analysis, and in some cases by FAB-MS. Successful syntheses ranged from 5 to 34 amino acids in length. Some of the peptides were also synthesized using a polystyrene support and standardised (ABI Fastmoc) SPPS protocols. The crude cleaved peptides from each synthesis were compared by HPLC analysis. The overall aim of our work with Perloza is synthesis of resin-bound peptide ligands for affinity chromatography and antibody generation.(ABSTRACT TRUNCATED AT 250 WORDS)


Hymenobacter siberiensis sp. nov., isolated from a marine sediment of the East Siberian Sea and Hymenobacter psoromatis sp. nov., isolated from an Antarctic lichen.
Gram-stain-negative, strictly aerobic, red-pink-coloured, rod-shaped and non-motile bacterial strains PAMC 29290, PAMC 29294T and PAMC 29296 were isolated from marine surface sediment sampled in the East Siberian Sea and strains PAMC 26553 and PAMC 26554T were obtained from an Antarctic lichen. Strains PAMC 29290, PAMC 29294T and PAMC 29296 were closely related to Hymenobacter artigasi (98.8 % 16S rRNA gene similarity), Hymenobacter antarcticus (97.3 %) and Hymenobacter glaciei (96.9 %), and PAMC 26553 and PAMC 26554T showed high similarity to Hymenobacter ginsengisoli (97.0 %), Hymenobacter rivuli (96.1 %) and Hymenobacter setariae (95.9 %). Genomic relatedness analyses showed that strains PAMC 29290, PAMC 29294T and PAMC 29296 could be distinguished from H. artigasi by average nucleotide identity (ANI; 93.1-93.2 %) and digital DNA-DNA hybridization (dDDH; 50.3-51.0 %) values. Strains PAMC 26553 and PAMC 26554T could be clearly distinguished from H. ginsengisoli with ANI values <79.8 % and dDDH values <23.3 %. The major fatty acids of strains PAMC 29290, PAMC 29294T and PAMC 29296 were C15 : 0 iso (21.0-26.0 %), summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c; 17.4-18.2 %), C15 : 0 anteiso (12.7-19.1 %) and summed feature 4 (C17 : 1 iso I and/or anteiso B; 8.6-16.1 %) and those of strains PAMC 26553 and PAMC 26554T were summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c; 20.7-22.2 %), C15 : 0 anteiso (17.5-19.7 %) and summed feature 4 (C17 : 1 iso I and/or anteiso B; 15.5-18.1 %). The major respiratory quinone was MK-7. The genomic DNA G+C contents were 60.6-60.8 mol%. The polar lipids of PAMC 29294T were found to consist of phosphatidylethanolamine, four unidentified aminolipids, an unidentified aminophospholipid and five unidentified lipids; those of PAMC 26554T were phosphatidylethanolamine, three unidentified aminolipids, four unidentified aminophospholipid and two unidentified lipids. The distinct phylogenetic position and some physiological characteristics distinguished the novel strains from closely related type strains in the genus Hymenobacter. Thus, two novel species are proposed, with the names Hymenobacter siberiensis sp. nov. (type strain, PAMC 29294T=KCTC 82466T=JCM 34574T) and Hymenobacter psoromatis sp. nov. (type strain, PAMC 26554T=KCTC 82464T=JCM 34572T), respectively.


Gold-complexes catalyzed oxidative α-cyanation of tertiary amines.
Oxidative α-cyanation of tertiary amines is catalyzed by gold complexes with trimethylsilyl cyanide to afford the corresponding α-aminonitriles in the presence of tert-butyl hydroperoxide in good to excellent yields under acid-free conditions at room temperature.


Quantifying elasticity and viscosity from measurement of shear wave speed dispersion.
The propagation speed of shear waves is related to frequency and the complex stiffness (shear elasticity and viscosity) of the medium. A method is presented to solve for shear elasticity and viscosity of a homogeneous medium by measuring shear wave speed dispersion. Harmonic radiation force, introduced by modulating the energy density of incident ultrasound, is used to generate cylindrical shear waves of various frequencies in a homogeneous medium. The speed of shear waves is measured from phase shift detected over the distance propagated. Measurements of shear wave speed at multiple frequencies are fit with the theoretical model to solve for the complex stiffness of the medium. Experiments in gelatin phantoms show promising results validated by an independent method. Practical considerations and challenges in possible medical applications are discussed.


Analysis of the Registration Information on Interventions of Acupuncture and Moxibustion Trials in the International Clinical Trials Registry Platform.
To analyze and compare the clinical registration information about acupuncture and moxibustion for intervention characteristics. Clinical trials from the International Clinical Trials Registry Platform of the World Health Organization in acupuncture and moxibustion were comprehensively collected from 2013 to 2015; data were independently screened and extracted by two retrievers, and relevant data involving either basic descriptions or intervention characteristics were analyzed. 425 acupuncture and moxibustion registered clinical trials were included; 88.00% (374/425) were designed as controlled studies, among which 38.59% (164/425) had sham acupuncture as the control group. The most common diseases were pain-related at approximately 19.29% (82/425) of trials. Reports on the intervention information in these acupuncture and moxibustion clinical studies were not sufficiently presented; these reports included the reporting of names of points (39.8%), the method of needle stimulation (32.5%), needle type (29.6%), needle retention time (34.1%), the number of treatment sessions (22.4%), and the frequency and duration of treatment sessions (38.1%). The registration information for the clinical trials of acupuncture and moxibustion was quite low according to this investigational study. Steps should be taken to improve the quality of acupuncture and moxibustion registration information.


Modeling human osteosarcoma in mice through 3AB-OS cancer stem cell xenografts.
Osteosarcoma is the second leading cause of cancer-related death for children and young adults. In this study, we have subcutaneously injected-with and without matrigel-athymic mice (Fox1nu/nu) with human osteosarcoma 3AB-OS pluripotent cancer stem cells (CSCs), which we previously isolated from human osteosarcoma MG63 cells. Engrafted 3AB-OS cells were highly tumorigenic and matrigel greatly accelerated both tumor engraftment and growth rate. 3AB-OS CSC xenografts lacked crucial regulators of beta-catenin levels (E-cadherin, APC, and GSK-3beta), and crucial factors to restrain proliferation, resulting therefore in a strong proliferation potential. During the first weeks of engraftment 3AB-OS-derived tumors expressed high levels of pAKT, beta1-integrin and pFAK, nuclear beta-catenin, c-Myc, cyclin D2, along with high levels of hyperphosphorylated-inactive pRb and anti-apoptotic proteins such as Bcl-2 and XIAP, and matrigel increased the expression of proliferative markers. Thereafter 3AB-OS tumor xenografts obtained with matrigel co-injection showed decreased proliferative potential and AKT levels, and undetectable hyperphosphorylated pRb, whereas beta1-integrin and pFAK levels still increased. Engrafted tumor cells also showed multilineage commitment with matrigel particularly favoring the mesenchymal lineage. Concomitantly, many blood vessels and muscle fibers appeared in the tumor mass. Our findings suggest that matrigel might regulate 3AB-OS cell behavior providing adequate cues for transducing proliferation and differentiation signals triggered by pAKT, beta1-integrin, and pFAK and addressed by pRb protein. Our results provide for the first time a mouse model that recapitulates in vivo crucial features of human osteosarcoma CSCs that could be used to test and predict the efficacy in vivo of novel therapeutic treatments.


Inflammation-mediated hyperexcitability of sensory neurons.
One of the most prominent signs of tissue injury and inflammation is pain and pain continues to be the primary reason people seek medical attention. Inflammatory pain reflects, at least in part, an increase in the excitability, or sensitization, of subpopulations of primary afferent neurons. While the sensitization of high threshold afferents was observed almost 40 years ago, the basis for this phenomenon continues to be an active and fertile area of research today. This review will summarize recent advances in our mechanistic understanding of sensitization, focusing on four general areas where re search has been most active or productive. These include: (1) the characterization of second messenger pathways underlying inflammation-induced changes in afferent excitability; (2) the impact of previous injury on the afferent response to subsequent inflammation; (3) the impact of target of innervation on the specific afferent response to inflammation, and (4) the impact of sex hormones on the sensitization of high threshold afferents. Work in these areas highlights how much has been learned about this process as well as how much there is yet to learn.


Affects and affect consciousness : initial experiences with the assessment of affect integration.
Affect consciousness (AC) was operationalized as degrees of awareness, tolerance, nonverbal expression, and conceptual expression of nine specific affects. A semistructured interview (ACI) and separate scales were developed to assess these aspects of affect integration. Their psychometric properties were preliminarily explored by having 20 former psychiatric outpatients complete the interview. Concurrent validity was assessed by using DSM-III-R Axis I and II diagnoses, the Health-Sickness Rating Scale, SCL-90-R, and several indexes from the Minnesota Multiphasic Personality Inventory. Satisfactory interrater reliability and high levels of internal consistency supported the construct validity of the measure. Results suggest the most meaningful use of this instrument is in measuring specific affect and overall AC. Clinically, the ACI has provided highly specific and relevant qualitative data for use in planning psychotherapeutic interventions.


Risk and resilience among Asian American youth: Ramifications of discrimination and low authenticity in self-presentations.
This study examines adjustment patterns among a group neglected in developmental science-Asian American students in high-achieving schools. National reports have declared such schools to connote risk for elevated problems among teens. Asian American students are commonly referred to as model minorities, but little is known about adjustment issues within academically competitive settings, specifically. Guided by past research on culturally salient issues, multiple U.S. high schools were examined to (a) determine areas of relative strength versus weakness in adjustment of Asian Americans compared with Whites, and (b) more importantly, to illuminate salient within-group processes related to Asian Americans' well-being. Risk modifiers examined were perceptions of ethnic discrimination, parent perfectionism, internalized achievement pressure, authenticity in self-presentation, and closeness to school adults. Outcome variables included depression, anxiety, and isolation at school. Results demonstrated that Asian Americans fared better than Whites on anxiety and school isolation, but with low effect sizes. By contrast, they fared more poorly on almost all risk modifiers, with a large effect size on discrimination. Regression results showed that among Asian Americans the most consistent associations, across cohorts and outcomes, were for discrimination and authenticity. Findings underscore the need for greater recognition that discrimination could be inimical for students not typically thought of as vulnerable-Asian Americans in high-achieving schools; these issues are especially pressing in light of increased racism following coronavirus disease 2019 (COVID-19). Results also suggest that feelings of inauthenticity could be a marker of generalized vulnerability to internalizing symptoms. Implications for future theory and interventions are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


S-7 inhibition of Herpes simplex virus type 1 infectivity and replication in cultured cells.
The effect of ethyl 2-methylthio-4-methyl-5-pyrimidine, carboxylate (S-7) on the infectivity and replication of herpes simplex virus type 1 in Vero cells was studied. S-7, at the highest concentration lacking toxic effect on cells (40 microg/ml), produced, at various inocula, a 40% inhibition of HSV-1 infectivity with respect to the plaque formation detected in control infected cultures. This inhibitory activity was substantiated by studies on progeny production. We cannot conclude that the inhibition of viral cytopathic effect resides in a specific inhibition of viral enzymes, however, the possibility of a more specific antiviral effect cannot be totally ruled out.


Albumin Cobalt Binding or Ischaemia Modified Albumin: a Test of Great Prognostic Value in Malaria.
We evaluated albumin cobalt binding (ACB) assay also known as Ischaemia Modified Albumin (IMA) assay as a prognostic marker for severe malaria in a medical college setting. Consecutive adult patients admitted with both vivax and falciparum malaria were evaluated with ACB assay at the time of admission. Detailed work up and individual patient directed management were instituted in addition to immediate artemisin based antimalarial therapy. 100 consecutive patients (50 with vivax and 50 with falciparum malaria) were evaluated. The reference range for ACB assay was established using 50 adult healthy (25 male and 25 female) individuals. 16 out of 50 p. Falciparum-Infected developed complicated malaria. None of the P Vivax patients developed complicated malaria. All malaria infected patients had high ACB levels (P<0.0001). There was a stepwise increase in ACB levels from healthy volunteers to different categories of malaria (P<0.0001) without any overlap. ACB has the potential to be used as a robust simple and inexpensive prognostic marker for organ dysfunction in severe malaria even if an evaluation at multiple sites with a bigger number of patients should be initiated for final recommendation.


Percutaneous dilation of ureteral strictures in renal transplant patients.
Percutaneous dilation of benign ureteral strictures was performed as an alternative to surgical therapy in 14 patients with renal transplants. Dilations were performed with balloon catheters in 13 patients and with a tapered angiographic catheter in one patient. Eleven strictures were successfully dilated (79%). There were three recurrences (21%). Follow-up in nine of the 11 successful cases ranged from 12 to 61 months (mean, 29 months; median, 24 months). There were no complications directly related to balloon dilation. The high success rate in this series may be related to the early diagnosis of strictures in these closely followed patients.


Next-generation sequencing identifies HOXA6 as a novel oncogenic gene in low grade glioma.
Low grade glioma is one of the most common lethal cancers in the human nervous system. Emerging evidence has demonstrated that homeobox A cluster (HOXA) gene family plays a critical role in the transcriptional regulation as well as cancer initiation and progression. However, the expression, biological functions and upstream regulatory mechanism of 11 HOXAs in low grade glioma are not yet clear. In this study, we utilized various public databases and bioinformatics analyzed, including TCGA, CGGA, Rembrandt, HPA, LinkedOmics, cBioPortal, TISDIB, single-sample GSEA (ssGSEA), TIMER, LnCeVar, LASSO regression, Cox regression, Kaplan-Meier plot, and receiver operating, characteristic (ROC) analyses, GDSC and CTRP databases to analyzed the mRNA and protein expression profiles, gene mutation, clinical features, diagnosis, prognosis, signaling pathway, TMB, immune subtype, immune cell infiltration, immune modulator, ceRNA network and drug sensitivity of 11 HOXAs. Growth curve and transwell assays were utilized to study the biological characteristics of HOXA6 in LGG progression. In the present study, we found that 11 HOXAs (HOXA1, HOXA2, HOXA3, HOXA4, HOXA5, HOXA6, HOXA7, HOXA9, HOXA10, HOXA11 and HOXA3) were consistently up-regulated in LGG tissues and GBM tissues. Up-regulated of the HOXAs expression were significantly correlated with higher tumor stage, IDH mutation status, 1p/19q co-deletion, histological type and primary therapy outcome. Survival analyses showed that higher expression of HOXA1, HOXA2, HOXA3, HOXA4, HOXA5, HOXA7, HOXA9, HOXA10, HOXA11 and HOXA13 were correlated with shorter overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS) in LGG patients. Univariate and multivariate analyses revealed that HOXA1, HOXA6 expression and tumor grade, age, primary therapy outcome and age were independent factors affecting the prognosis of LGG patients. ROC curve analysis of HOXAs showed that HOXAs had a high accuracy (AUC > 0.80) in predicting LGG. Furthermore, gene functional enrichment analysis indicated that HOXAs mainly involved in the inflammatory response and immune regulation signaling pathway. CNV and DNA methylation significantly affect the expression of HOXAs. Finally, we uncover that HOXAs expression are highly correlated with immune cells infiltrate, immune modulator and drug sensitivity. We also uncover that the HOXAs related ceRNA network in LGG. More importantly, we found that HOXA6 was highly expressed in LGG cells lines and significantly affected their proliferation and migration abilities. In conclusion, our data demonstrated that HOXA was correlated with progression and immune infiltration, and could serve as a prognostic biomarker for LGG.


Tildrakizumab for treating psoriasis.
Agents that block inflammatory pathways other than tumor necrosis factor (TNF) have represented new options for treating psoriasis in recent years. IL-23 is involved in regulating Th17 cells and is a potent activator of keratinocyte proliferation. Targeting IL-23p19 alone may be a promising treatment approach in patients with moderate-to-severe chronic plaque psoriasis, with a downregulation of Th17 and Th22 cell responses, while IL-12 blockade is not required to achieve efficacy in these patients. Areas covered: The authors review and provide an update on tildrakizumab, a humanized IgG1 monoclonal antibody that blocks the p19 subunit of IL-23. Expert opinion: Total skin clearance is an important treatment goal that has both measurable and clinically meaningful benefits. Meeting patient needs about total clearance, IL-23p19 inhibitors will obtain a specific position in the crowded psoriasis market. On the other hand, PASI 75 and PASI 90 response achieved by tildrakizumab in the phase II and III trials are less than the response achieved by the IL-17A inhibitors and other p19 competitors, possibly due to a less intensive dosing regimen, although direct comparisons cannot be made without a head-to-head randomized clinical trial. The main advantage of tildrakizumab is that it is dosed in a maintenance regimen of 12 weeks, and similar to ustekinumab, this is likely to encourage adherence and aid persistence to the drug.


Large-Scale Analysis of Drug Side Effects via Complex Regulatory Modules Composed of microRNAs, Transcription Factors and Gene Sets.
Identifying the occurrence mechanism of drug-induced side effects (SEs) is critical for design of drug target and new drug development. The expression of genes in biological processes is regulated by transcription factors(TFs) and/or microRNAs. Most of previous studies were focused on a single level of gene or gene sets, while studies about regulatory relationships of TFs, miRNAs and biological processes are very rare. Discovering the complex regulating relations among TFs, gene sets and miRNAs will be helpful for researchers to get a more comprehensive understanding about the mechanism of side reaction. In this study, a framework was proposed to construct the relationship network of gene sets, miRNAs and TFs involved in side effects. Through the construction of this network, the potential complex regulatory relationship in the occurrence process of the side effects was reproduced. The SE-gene set network was employed to characterize the significant regulatory SE-gene set interaction and molecular basis of accompanied side effects. A total of 117 side effects complex modules including four types of regulating patterns were obtained from the SE-gene sets-miRNA/TF complex regulatory network. In addition, two cases were used to validate the complex regulatory modules which could more comprehensively interpret occurrence mechanism of side effects.


Injury patterns in competitive and recreational surfing: a systematic review.
Despite the growing evidence regarding surf-related injuries, investigation seems to overlook the differences between professional and recreational surfers' injuries and their specific risk factors. This review aimed at identifying differences in injuries sustained by recreational and competitive surfers. It also presents research gaps and suggests recommendations for future injury research and prevention. Study search was conducted on MEDLINE/PubMed, SportDiscus and Web of Science databases. To be included studies needed to report original data, clearly specify if recreational and/or competitive surfers were included, provide information regarding acute surfing injuries and/or analyse data concerning those injuries. 17 studies were included in the analysis. All included studies had at least Oxford Centre for Evidence-Based Medicine level of evidence 3. The percentage of recreational surfers sustaining at least one injury ranged from 31% to 35% in the 12 months prior to data collection and from 88% to 100% in lifetime while 42% to 49% and 81% to 100% of competitors were injured over the same periods. Competitive surfers appear to have a higher injury risk. Both recreational and competitive surfers appear to sustain more frequently skin, joint/ligament and muscle/tendon injuries affecting the lower limbs and caused by contact with their own equipment. Competitive status, less surfing experience, older age and prior surgical injuries are risk factors for sustaining injuries while surfing. The most common types, anatomical locations and mechanisms of injury seem to be similar between recreational and competitive surfers.


Cadmium and high temperature effects on brain and behaviour of Lymantria dispar L. caterpillars originating from polluted and less-polluted forests.
Insects brain as a part of nervous system is the first-line of fast stress response that integrate stress signals to regulate all aspects of insect physiology and behaviour. The cadmium (Cd) bioaccumulation factor (BF), activity of the neurotoxicity biomarker acetylcholinesterase (AChE), dopamine content, expression and amount of Hsp70 in the brain and locomotor activity were evaluated in the 4th instar of Lymantria dispar L. caterpillars fed a Cd supplemented diet and reared in an optimal temperature regime (23 °C) and/or exposed to high temperature (28 °C). The insects originated from two forests, one close to "Nikola Tesla" thermoelectric power plant, Obrenovac (polluted population), and the other Kosmaj mountain (less-polluted population, far from any industrial region). The Cd BF was higher in the less-polluted than in the polluted population especially at the high ambient temperature. AChE activity and dopamine content were changed in the brains of L. dispar from both populations in the same manner. Hsp70 concentration in caterpillar brains showed opposite trends, a decrease in the less-polluted and an increase in the polluted population. Locomotor activity was modified in both Lymantria dispar populations, but the pattern of changes depended on the stressors and their combined effect. ACh activity and dopamine content are sensitive parameters to Cd exposure, regardless of pollutant experience, and might be promising biomarkers in monitoring forest ecosystems.


An unusual presentation and way to diagnose hepatocellular carcinoma.
A 67-year-old man with a history of chronic obstructive pulmonary disease (COPD) was admitted with acute progression of dyspnoea, productive cough, fever, elevated central venous pressure, oedema and liver enzyme abnormalities. Pneumonia with secondary right-sided congestive heart failure was considered. Additional abdominal ultrasound examination confirmed by a CT scan showed a mass in the inferior vena cava (VCI) extending into the right atrium. The central liver location and impaired haemostasis rendered liver biopsy impossible. An alternative approach was discussed and guided by two-dimensional transoesophageal electrocardiography accessing the right internal jugular vein, biopsies were taken from the atrial mass with histology suggesting the presence of a hepatocellular carcinoma as the cause of acute dyspnoea.


Peroxisomes in adrenal steroidogenesis.
Peroxisomes, cytoplasmic organelles limited by a single membrane and with a matrix of moderate electron density, are present in a great number of cells, namely in adrenal cortex and other steroid-secreting organs. Presently peroxisomes are considered to be involved in important metabolic processes. They intervene in: (1) the production and degradation of H2O2; (2) biosynthesis of ether-phospholipids, cholesterol, dolichol, and bile acids; (3) oxidation of very long chain fatty acids, purines, polyamines, and prostaglandins; (4) catabolism of pipecolic, phythanic and glyoxylic acids; and (5) gluconeogenesis. Recent studies demonstrated that the experimental alterations in the normal steroidogenesis, produce significant morphological and biochemical changes in peroxisomes. Besides this, the presence of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (the key enzyme in the de novo cholesterol synthesis from acetate) and of sterol carrier protein-2 (SCP2), which is involved in the cholesterol metabolism and steroid metabolic pathways, are located in peroxisomes of steroid-secreting cells. In addition, patients with peroxisome diseases present deficiency in steroidogenesis, as well as reduced levels of SCP2. These data pointed out the important role of peroxisomes in steroid biosynthesis.


The Risk of Posterior Capsule Rupture during Phacoemulsification Cataract Surgery in Eyes with Previous Intravitreal Anti Vascular Endothelial Growth Factor Injections.
To investigate if previous intravitreal anti vascular endothelial growth factor (VEGF) injections are a predictor for posterior capsule rupture (PCR) during phacoemulsification cataract surgery. National Health Service: Whipps Cross University Hospital Eye Treatment Centre. District General, London, United Kingdom DESIGN:: Single centre, retrospective, electronic medical record (EMR) database study with univariate analysis. EMR (Medisoft) was used to extract data for eyes undergoing phacoemulsification surgery between 01.08.16 to 01.01.18. Patient demographics, indication for intravitreal therapy, treatment type, number of previous intravitreal injections (IVI), diabetic status, surgeon grade and operative complications were included as variables for analysis. Data was available for 4047 cataract operations. Of these, 108 had undergone previous anti-VEGF IVI treatment. Three eyes were noted to have pre-operative PC trauma and were excluded from the final analysis. The logistic regression analysis after exclusion of the eyes with pre-existing damage to the PC confirmed that prior anti-VEGF IVI treatment was associated with an increased risk of PCR when compared to the non IVI group (9.26% vs 1.88%, p<0.0001). There is a dose dependent relationship between the number of anti-VEGF injections and the likelihood of PCR. Previous intravitreal anti-VEGF injections are significantly correlated with an increased risk of surgical PCR despite the absence of visible structural damage to the PC pre-operatively.


Murimonas intestini gen. nov., sp. nov., an acetate-producing bacterium of the family Lachnospiraceae isolated from the mouse gut.
Three strains of an anaerobic, Gram-stain-positive coccobacillus were isolated from the intestines of mice. These strains shared 100 % similarity in their 16S rRNA gene sequences, but were distantly related to any described members of the family Lachnospiraceae (<94 %). The most closely related species with names that have standing in nomenclature were Robinsoniella peoriensis, Ruminococcus gnavus, Blautia producta and Clostridium xylanolyticum. Phylogenetic relationships based on 16S rRNA gene sequence analysis were confirmed by partial sequencing of hsp60 genes. The use of an in-house database search pipeline revealed that the new isolates are most prevalent in bovine gut samples when compared with human and mouse samples for Ruminococcus gnavus and B. producta. All three isolated strains shared similar cellular fatty acid patterns dominated by C16 : 0 methyl ester. Differences in the proportions of C12 : 0 methyl ester, C14 : 0 methyl ester and C18 : 1 cis-11 dimethyl acetal were observed when compared with phylogenetically neighbouring species. The major short-chain fatty acid produced by strain SRB-530-5-H(T) was acetic acid. This strain tested positive for utilization of d-fructose, d-galacturonic acid, d-malic acid, l-alanyl l-threonine and l-glutamic acid but was negative for utilization of amygdalin, arbutin, α-d-glucose, 3-methyl d-glucose and salicin, in contrast to the type strain of the closest related species Robinsoniella peoriensis. The isolates were not able to use mannitol for growth. Based on genotypic, phenotypic and chemotaxonomic characteristics, we propose to create the new genus and species Murimonas intestini gen. nov., sp. nov. to accommodate the three strains SRB-530-5-H(T) ( = DSM 26524(T) = CCUG 63391(T)) (the type strain of Murimonas intestini), SRB-509-4-S-H ( = DSM 27577 = CCUG 64595) and SRB-524-4-S-H ( = DSM 27578 = CCUG 64594).


Moral Breakdowns and Ethical Dilemmas of Perioperative Nurses during COVID-19: COREQ-Compliant Study.
(1) Background: The COVID-19 pandemic has led to an increase in the complexity of caregiving, resulting in challenging situations for perioperative nurses. These situations have prompted nurses to assess their personal and professional lives. The aim of this study was to explore the experiences of perioperative nurses during the first wave of the COVID-19 pandemic, with a specific focus on analyzing moral breakdowns and ethical dilemmas triggered by this situation. (2) Methods: A qualitative design guided by a hermeneutical approach was employed. Semi-structured interviews were conducted with 24 perioperative nurses. The interviews were transcribed and thematically analysed following the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. (3) Results: The findings revealed three main categories and ten subcategories. These categories included the context in which moral breakdowns emerged, the ethical dilemmas triggered by these breakdowns, and the consequences of facing these dilemmas. (4) Conclusions: During the first wave of COVID-19, perioperative nurses encountered moral and ethical challenges, referred to as moral breakdowns, in critical settings. These challenges presented significant obstacles and negatively impacted professional responsibility and well-being. Future studies should focus on identifying ethical dilemmas during critical periods and developing strategies to enhance collaboration among colleagues and provide comprehensive support.


Modulation of a constitutive transcriptional block at exon-1 controls human c-myc oncogene expression.
C-myc gene down-regulation is known to be mediated by a transcriptional block at the end of exon-1 (Bentley & Groudine, 1986; Siebenlist et al., 1988). When transcription is initiated normally, this block is expected to produce a truncated RNA, but to date, this product has escaped direct detection in somatic cells. We have been able to detect a 0.38 kb c-myc exon-1 specific RNA species by northern blot analysis. This RNA appeared not only in dimethyl sulfoxide (DMSO)-induced HL-60 cells, but also in uninduced HL-60 cells, the NALM-6, REH, RPMI-8392 and TALL-1 cell lines, and in human T-cell acute lymphocytic leukemia (T-ALL) and normal peripheral blood lymphocytes (PBL), indicating that the transcriptional block producing it is constitutive. In HL-60 cells, the 0.38 kb RNA level increased on DMSO induction while the 2.3 kb c-myc mRNA was down-regulated. Upon DMSO removal, as the 2.3 kb mRNA was made again, the 0.38 kb RNA fell to preinduction levels, Thus, modulation of this constitutive block regulates the relative amounts of c-myc message available for translation in response to specific growth stimuli. This mechanism for c-myc gene regulation may be common within the hematologic system.


An unusual case of schwannomatosis with bilateral maxillary sinus schwannomas and a novel SMARCB1 gene mutation.
Schwannomas are benign tumors that arise from Schwann cells in the peripheral nervous system. Patients with multiple schwannomas without signs and symptoms of neurofibromatosis Type 1 or 2 have the rare disease schwannomatosis. Tumors in these patients occur along peripheral nerves throughout the body. Mutations of the SMARCB1 gene have been described as one of the predisposing genetic factors in the development of this disease. This report describes a patient who was observed for 6 years after having undergone removal of 7 schwannomas, including bilateral maxillary sinus schwannomas, a tumor that has not been previously reported. Genetic analysis revealed a novel mutation of c.93G>A in exon 1 of the SMARCB1 gene.