Climatic niche divergence or conservatism? Environmental niches and range limits in ecologically similar damselflies.
The factors that determine species' range limits are of central interest to biologists. One particularly interesting group comprises odonates (dragonflies and damselflies), which show large differences in secondary sexual traits and respond quickly to climatic factors, but often have minor interspecific niche differences, challenging models of niche-based species coexistence. We quantified the environmental niches at two geographic scales to understand the ecological causes of northern range limits and the coexistence of two congeneric damselflies (Calopteryx splendens and C. virgo). Using environmental niche modeling, we quantified niche divergence first across the whole geographic range in Fennoscandia, and second only in the sympatric part of this range. We found evidence for interspecific divergence along the environmental axes of temperature and precipitation across the northern range in Fennoscandia, suggesting that adaptation to colder and wetter climate might have allowed C. virgo to expand farther north than C. splendens. However, in the sympatric zone in southern Fennoscandia we found only negligible and nonsignificant niche differences. Minor niche differences in sympatry lead to frequent encounters and intense interspecific sexual interactions at the local scale of populations. Nevertheless, niche differences across Fennoscandia suggest that species differences in physiological tolerances limit range expansions northward, and that current and future climate could have large effects on the distributional ranges of these and ecologically similar insects.


ENDOCRINOLOGY IN THE TIME OF COVID-19: Management of hyperthyroidism and hypothyroidism.
This manuscript provides guidance on the management of thyroid dysfunction during the COVID-19 pandemic. Autoimmune thyroid diseases are not linked to increased risks of COVID-19. Uncontrolled thyrotoxicosis may result in more severe complications from SARS-CoV-2 infection, including thyroid storm. The management of patients with a new diagnosis of hyperthyroidism is best undertaken with a block-and-replace regimen due to limited biochemical testing availability. Antithyroid drug (ATD)-induced neutropenia may favour the progression of COVID-19 and symptoms of infection may be confused with SARS-CoV-2 infection. The withdrawal of ATDs and urgent measurement of neutrophils should be considered in case of flu-like manifestations occurring in the initial months of treatment. Urgent surgery or 131-I may be undertaken in selected cases of uncontrolled thyrotoxicosis. Patients with COVID-19 infection may present with conjunctivitis, which could cause diagnostic difficulties in patients with new or existing Graves' ophthalmopathy. Patients who are on replacement treatment with thyroid hormones should ensure they have sufficient supply of medication. The usual advice to increase dosage of levothyroxine during pregnancy should be adhered to. Many newly presenting and previously diagnosed patients with thyroid dysfunction can be managed through virtual telephone or video clinics supported by a dedicated nurse-led service, depending on available facilities.


Relationship of ketamine's plasma metabolites with response, diagnosis, and side effects in major depression.
Ketamine has rapid antidepressant effects lasting as long as 1 week in patients with major depressive disorder (MDD) and bipolar depression (BD). Ketamine is extensively metabolized. This study examined the relationship between ketamine metabolites and response, diagnosis, and psychotomimetic symptoms in MDD and BD patients. Following a 40-minute ketamine infusion (.5 mg/kg), plasma samples were collected at 40, 80, 110, and 230 minutes and day 1 postinfusion in 67 patients currently experiencing a major depressive episode (MDD, n = 45; BD, n = 22). Concentrations of ketamine, norketamine (NK), dehydronorketamine (DHNK), six hydroxynorketamine metabolites (HNK), and hydroxyketamine (HK) were measured. Plasma concentrations were analyzed by diagnostic group and correlated with patients' depressive, psychotic, and dissociative symptoms. The relationship between cytochrome P450 gene polymorphisms and metabolites, response, and diagnosis was also examined. Ketamine, NK, DHNK, four of six HNKs, and HK were present during the first 230 minutes postinfusion. Patients with BD had higher plasma concentrations of DHNK, (2S,6S;2R,6R)-HNK, (2S,6R;2R,6S)-HNK, and (2S,5S;2R,5R)-HNK than patients with MDD, who, in turn, had higher concentrations of (2S,6S;2R,6R)-HK. Higher (2S,5S;2R,5R)-HNK concentrations were associated with nonresponse to ketamine in BD patients. Dehydronorketamine, HNK4c, and HNK4f levels were significantly negatively correlated with psychotic and dissociative symptoms at 40 minutes. No relationship was found between cytochrome P450 genes and any of the parameters examined. A diagnostic difference was observed in the metabolism and disposition of ketamine. Concentrations of (2S,5S;2R,5R)-HNK were related to nonresponse to ketamine in BD. Some hydroxylated metabolites of ketamine correlated with psychotic and dissociative symptoms.


Utilization of deletion bins to anchor and order sequences along the wheat 7B chromosome.
A total of 3,671 sequence contigs and scaffolds were mapped to deletion bins on wheat chromosome 7B providing a foundation for developing high-resolution integrated physical map for this chromosome. Bread wheat (Triticum aestivum L.) has a large, complex and highly repetitive genome which is challenging to assemble into high quality pseudo-chromosomes. As part of the international effort to sequence the hexaploid bread wheat genome by the international wheat genome sequencing consortium (IWGSC) we are focused on assembling a reference sequence for chromosome 7B. The successful completion of the reference chromosome sequence is highly dependent on the integration of genetic and physical maps. To aid the integration of these two types of maps, we have constructed a high-density deletion bin map of chromosome 7B. Using the 270 K Nimblegen comparative genomic hybridization (CGH) array on a set of cv. Chinese spring deletion lines, a total of 3,671 sequence contigs and scaffolds (~7.8 % of chromosome 7B physical length) were mapped into nine deletion bins. Our method of genotyping deletions on chromosome 7B relied on a model-based clustering algorithm (Mclust) to accurately predict the presence or absence of a given genomic sequence in a deletion line. The bin mapping results were validated using three different approaches, viz. (a) PCR-based amplification of randomly selected bin mapped sequences (b) comparison with previously mapped ESTs and (c) comparison with a 7B genetic map developed in the present study. Validation of the bin mapping results suggested a high accuracy of the assignment of 7B sequence contigs and scaffolds to the 7B deletion bins.


Camelimonas abortus sp. nov., isolated from placental tissue of cattle.
A gram-negative, rod-shaped, non-spore-forming bacterium, isolated from placental tissue of a cow, was investigated for its taxonomic position. On the basis of 16S rRNA gene sequence similarities, strain UK34/07-5(T) was shown to belong to the class Alphaproteobacteria, closely related to the type strain of Camelimonas lactis (96.0 % sequence similarity). The polyamine pattern showed the major compound spermidine and moderate amounts of putrescine. The major quinone was ubiquinone Q-10. The polar lipid profile was composed of the major compounds phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol and phosphatidylmonomethylethanolamine and moderate amounts of diphosphatidylglycerol, three unidentified aminolipids and an unidentified phospholipid. The profile of major fatty acids, consisting of C(19 : 0) cyclo ω8c and C(18 : 1)ω7c, with C(18 : 0) 3-OH as the hydroxylated fatty acid, was very similar to that of C. lactis M 2040(T). The results of DNA-DNA hybridization and physiological and biochemical tests allowed both genotypic and phenotypic differentiation of the isolate from C. lactis. The relatively low 16S rRNA gene sequence similarity of 96.0 % to C. lactis M 2040(T) and marked differences in the polar lipid profiles as well as the results of physiological tests and the DNA-DNA hybridization data support the creation of a novel species, for which the name Camelimonas abortus sp. nov. is proposed, with the type strain UK34/07-5(T) ( = CIP 110303(T) = CCUG 61094(T) = DSM 24741(T) = CCM 7941(T)).


Hippo signaling impedes adult heart regeneration.
Heart failure due to cardiomyocyte loss after ischemic heart disease is the leading cause of death in the United States in large part because heart muscle regenerates poorly. The endogenous mechanisms preventing mammalian cardiomyocyte regeneration are poorly understood. Hippo signaling, an ancient organ size control pathway, is a kinase cascade that inhibits developing cardiomyocyte proliferation but it has not been studied postnatally or in fully mature adult cardiomyocytes. Here, we investigated Hippo signaling in adult cardiomyocyte renewal and regeneration. We found that unstressed Hippo-deficient adult mouse cardiomyocytes re-enter the cell cycle and undergo cytokinesis. Moreover, Hippo deficiency enhances cardiomyocyte regeneration with functional recovery after adult myocardial infarction as well as after postnatal day eight (P8) cardiac apex resection and P8 myocardial infarction. In damaged hearts, Hippo mutant cardiomyocytes also have elevated proliferation. Our findings reveal that Hippo signaling is an endogenous repressor of adult cardiomyocyte renewal and regeneration. Targeting the Hippo pathway in human disease might be beneficial for the treatment of heart disease.


Health & demographic surveillance system profile: the Nahuche Health and Demographic Surveillance System, Northern Nigeria (Nahuche HDSS).
The Nahuche Health and Demographic Surveillance System (HDSS) study site, established in 2009 with 137 823 individuals is located in Zamfara State, north western Nigeria. North-West Nigeria is a region with one of the worst maternal and child health indicators in Nigeria. For example, the 2013 Nigeria Demographic and Health Survey estimated an under-five mortality rate of 185 deaths per 1000 live births for the north-west geo-political zone compared with a national average of 128 deaths per 1000 live births. The site comprises over 100 villages under the leadership of six district heads. Virtually all the residents of the catchment population are Hausa by ethnicity. After a baseline census in 2010, regular update rounds of data collection are conducted every 6 months. Data collection on births, deaths, migration events, pregnancies, marriages and marriage termination events are routinely conducted. Verbal autopsy (VA) data are collected on all deaths reported during routine data collection. Annual update data on antenatal care and household characteristics are also collected. Opportunities for collaborations are available at Nahuche HDSS. The Director of Nahuche HDSS, M.O. Oche at [firstname.lastname@example.com] is the contact person for all forms of collaboration.


Methicillin-resistant Staphylococcus aureus colonization among medical residents.
Medical residents may be at risk of becoming colonized by methicillin-resistant Staphylococcus aureus (MRSA) during their training. The occupational risk of this specific population is unknown. Furthermore, there are no data regarding MRSA colonization among health care professionals in Quebec. To determine the MRSA colonization rate in Laval University (Quebec City, Quebec) medical residents and compare it with the MRSA colonization rate of a control group. A controlled cross-sectional study of MRSA prevalence among medical residents of Laval University was performed. The control group consisted of Laval University undergraduate medical students without previous clinical rotations in their curriculum. After informed consent was obtained, participants were screened for MRSA with a nasal swab in both anterior nares. They also completed a questionnaire regarding relevant risk factors and demographic data. A total of 250 residents of all residency levels from medical and surgical specialties and 247 controls were recruited between February and April 2010. One case of MRSA colonization was detected among the residents and none in the control group (prevalence of 0.4% versus 0.0%; P=1.00). MRSA nasal carriage was very low among Laval University residents. This may reflect the decreasing rate of health care-associated MRSA in Quebec City. Young age and good health may also explain this low risk. The strict infection control policies for MRSA patients (including cohorting, use of gloves, gown and patient-dedicated equipment) may also contribute to prevent MRSA transmission. Medical residents in Quebec City appeared to be at very low risk of contracting MRSA through professional activities.


Wound infiltration with Bupivacaine versus Ketorolac for postoperative pain relief in minor to moderate surgeries.
To compare the analgesic efficacy of Bupivacaine 0.25% wound infiltration with Ketorolac incisional infiltration in relieving postoperative pain for first twenty-four hours. Analytical, interventional and comparative study was performed on seventy patients, of both sexes, with varied age groups. Patients underwent minor and moderate surgeries, confined to American Society of Anaesthesiologist ASA category 1-II. Patients were selected by convenience sampling and were divided into two groups i.e. Group I and Group II. Group-I comprised of thirty five patients and were infiltrated with Bupivacaine 0.25% at wound margins postoperatively. Group-II also comprised of thirty-five patients and were infiltrated with Ketorolac at wound margins 60 mg postoperatively. Bupivacaine 0.25% wound infiltration had onset of action within 4 +/- 2 minutes. Percentage pain relief was 80% in minor surgeries and 60% in moderate surgeries. Duration of action lasted for 8 +/- 2 hours regarding minor surgeries while it was 6 +/- 1 hours for moderate surgeries. Ketorolac incisional infiltration had onset of analgesic action within 10 +/- 5 minutes. Duration of action lasted for 6 +/- 1 hours regarding minor surgeries while it was 4 +/- 2 hours regarding moderate surgeries. Percentage pain relief was 60% in minor surgeries and 50% in moderate surgeries. Wound infiltration with Bupivacaine 0.25% was better for postoperative pain relief in comparison with Ketorolac regarding percentage pain relief, onset and duration of action.


An atlas of the protein-coding genes in the human, pig, and mouse brain.
The brain, with its diverse physiology and intricate cellular organization, is the most complex organ of the mammalian body. To expand our basic understanding of the neurobiology of the brain and its diseases, we performed a comprehensive molecular dissection of 10 major brain regions and multiple subregions using a variety of transcriptomics methods and antibody-based mapping. This analysis was carried out in the human, pig, and mouse brain to allow the identification of regional expression profiles, as well as to study similarities and differences in expression levels between the three species. The resulting data have been made available in an open-access Brain Atlas resource, part of the Human Protein Atlas, to allow exploration and comparison of the expression of individual protein-coding genes in various parts of the mammalian brain.


Towards a framework for collective behavior in growth-driven systems, based on plant-inspired allotropic pairwise interactions.
A variety of biological systems are not motile, but sessile in nature, relying on growth as the main driver of their movement. Groups of such growing organisms can form complex structures, such as the functional architecture of growing axons, or the adaptive structure of plant root systems. These processes are not yet understood, however the decentralized growth dynamics bear similarities to the collective behavior observed in groups of motile organisms, such as flocks of birds or schools of fish. Equivalent growth mechanisms make these systems amenable to a theoretical framework inspired by tropic responses of plants, where growth is considered implicitly as the driver of the observed bending towards a stimulus. We introduce two new concepts related to plant tropisms: point tropism, the response of a plant to a nearby point signal source, and allotropism, the growth-driven response of plant organs to neighboring plants. We first analytically and numerically investigate the 2D dynamics of single organs responding to point signals fixed in space. Building on this we study pairs of organs interacting via allotropism, i.e. each organ senses signals emitted at the tip of their neighbor and responds accordingly. In the case of local sensing we find a rich state-space. We describe the different states, as well as the sharp transitions between them. We also find that the form of the state-space depends on initial conditions. This work sets the stage towards a theoretical framework for the investigation and understanding of systems of interacting growth-driven individuals.


Antifeedant activity of botanical crude extracts and their fractions on Bemisia tabaci (Homoptera: Aleyrodidae) adults: I. Gliricidia sepium (Fabaceae).
Bemisia tabaci is an important virus vector on a number of crops worldwide. Therefore, a preventive approach to deal with viral epidemics may be the deployment of repellents or phagodeterrents at earlier stages of plant development (critical period). Thus, the crude extract and four fractions thereof (water, water:methanol, methanol, and diethyl ether) of mother-of-cocoa (Gliricidia sepium, Fabaceae) were tested for phagodeterrence to B. tabaci adults under greenhouse conditions, on tomato plants, in Costa Rica. Both restricted-choice and unrestricted-choice experiments showed that the crude extract and some fractions exerted such effect on the insect. In the former (in sleeve cages), three fractions caused deterrence at doses as low as 0.1% (methanol), 0.5% (water:methanol) and 1.5% (diethyl ether). However, in the latter (plants exposed in a greenhouse) no one of the fractions performed well, suggesting that the deterrent principles somehow decomposed under the experimental conditions.


Oncostatin M, leukemia inhibitory factor, and interleukin 6 induce the proliferation of human plasmacytoma cells via the common signal transducer, gp130.
We analyzed the stimulatory effect of oncostatin M (OSM), leukemia inhibitory factor (LIF), interleukin 6 (IL-6), IL-11, and the inhibitory effect of anti-IL-6 antibody (Ab), anti-IL-6 receptor monoclonal antibody (mAb), and anti-gp130 mAb on the growth of human plasmacytoma cells freshly isolated from a patient with multiple myeloma. The purified cells showed a plasmacytoid morphology and expressed CD38, CD54, and CD56 antigens but no CD3, CD5, CD10, CD19, CD20, or very late antigen 5. IL-6 receptor (IL-6R) and its signal transducer, gp130, were expressed on their cell surface at a low level. Dose-dependent proliferation of the cells in response to OSM, LIF, and IL-6, but not to IL-11, was observed using [3H]TdR incorporation in vitro. Both anti-IL-6 Ab and anti-IL-6R mAb inhibited the growth of the cells in the presence or absence of exogenous IL-6. These cells release IL-6 but not OSM or LIF into the culture supernatant during short-term culture. Therefore, an autocrine growth mechanism mediated by IL-6, but not by OSM or LIF, was confirmed. Furthermore, anti-gp130 mAb completely inhibited the proliferation of the cells induced by OSM, LIF, as well as IL-6. These data indicate that OSM, LIF, and IL-6 can act as growth factors of human plasmacytoma cells through a common signal transducer, gp130, on their cell surface, and also suggest the potential therapeutic application of anti-gp130 mAb, as well as anti-IL-6R mAb against myeloma/plasmacytomas.


Chemically induced skin carcinogenesis in mice and its prevention by Aegle marmelos (an Indian medicinal plant) fruit extract.
This study assessed the chemopreventive potential of the Aegle marmelos plant on mouse skin tumorigenesis initiated by 7,12-dimethylbenz(a)anthracene (DMBA) and promoted by croton oil. A significant reduction in tumor incidence, tumor burden, tumor multiplicity, and the cumulative number of papillomas, along with a significant increase in the average latent period, was recorded in mice treated orally with A. marmelos extract (AME) at peri - and post-initiation phases (i.e., 7 days before DMBA application and continued until the end of the experiment) of papillomagenesis as compared with the carcinogen-treated controls. Furthermore, a significant increase in catalase activity, reduced glutathione and total proteins, and a depleted level of lipid peroxidation were observed in liver and skin of AME-treated animals as compared with the carcinogen-treated controls. Thus, the oral administration of AME, at a dose of 50 mg/kg body wt per day per animal, was found to be significantly effective in reducing skin tumors against chemical carcinogenesis in mice.


Case report: Trabecular juvenile ossifying fibroma presenting as a sellar mass.
A 15-year-old girl presented with left occulomotor nerve palsy and was found to have a space occupying lesion of the sellar region with invasion of the left cavernous sinus. A transsphenoidal approach lead to subtotal removal of a solid tumor with some remnants in the cavernous sinus and revealed the diagnosis of trabecular juvenile ossifying fibroma (JOF). A repeat magnetic resonance imaging was obtained within 1 month that showed intrasellar recurrence and growing tumor in the cavernous sinus. Therefore, a combined transsphenoidal and transcranial approach was performed to more aggressively remove the tumor. Subsequently, adjuvant proton radiotherapy was performed. JOF of the trabecular type is a rare fibro-osseous lesion of the craniofacial skeleton almost exclusively occurring in the maxilla or the mandible. To our knowledge, this is the first case of this tumor entity presenting as a sellar mass.


Focal adhesion kinase is a substrate and downstream effector of SHP-2 complexed with Helicobacter pylori CagA.
Infection with cagA-positive Helicobacter pylori (H. pylori) is associated with atrophic gastritis, peptic ulcer, and gastric adenocarcinoma. The cagA gene product CagA is translocated from H. pylori into gastric epithelial cells and undergoes tyrosine phosphorylation by Src family kinases (SFKs). Tyrosine-phosphorylated CagA binds and activates SHP-2 phosphatase and the C-terminal Src kinase (Csk) while inducing an elongated cell shape termed the "hummingbird phenotype." Here we show that CagA reduces the level of focal adhesion kinase (FAK) tyrosine phosphorylation in gastric epithelial cells. The decrease in phosphorylated FAK is due to SHP-2-mediated dephosphorylation of FAK at the activating phosphorylation sites, not due to Csk-dependent inhibition of SFKs, which phosphorylate FAK. Coexpression of constitutively active FAK with CagA inhibits induction of the hummingbird phenotype, whereas expression of dominant-negative FAK elicits an elongated cell shape characteristic of the hummingbird phenotype. These results indicate that inhibition of FAK by SHP-2 plays a crucial role in the morphogenetic activity of CagA. Impaired cell adhesion and increased motility by CagA may be involved in the development of gastric lesions associated with cagA-positive H. pylori infection.


Testing wound dressings using an in vitro wound model.
To determine whether or not there are any significant differences in the effects of wound dressings on bacterial bioburden. A selection of non-occlusive, non-adhesive dressings was tested for their effect on bacterial bioburden. The dressings selected included two dressings with antimicrobial properties (one containing silver and one containing PHMB), a cotton-based dressing enclosed in a perforated sleeve of poly(ethylene terephthalate), a carboxymethyl cellulose-based dressing, a fibre-free alginate dressing, and a 12-ply 100% cotton gauze. Using the colony-drip flow reactor (DFR) model, a meticillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa biofilm was grown underneath a dressing sample. Biofilm growth was examined via plate counts, fluorescent microscopy and scanning electron microscopy. The dressings containing antimicrobial agents had the greatest effect on bacterial load. In the MRSA experiments, both antimicrobial dressings produced lower bacteria counts than the other dressings (p<0.001), while in the P. aeruginosa experiments, only the silver-containing sample had fewer bacteria (p<0.0001). However, neither antimicrobial dressing was able to completely eradicate the bacteria when testing with either microorganism. The results presented herein illustrate that bacteria can grow unchallenged within the dressing environment and that an antimicrobial dressing can limit this bacterial growth. None.


Development of the penile urethra in the tammar wallaby.
Hypospadias is increasingly common, and requires surgery to repair, but its aetiology is poorly understood. The marsupial tammar wallaby provides a unique opportunity to study hypospadias because penile differentiation occurs postnatally. Androgens are responsible for penile development in the tammar, but the majority of differentiation, in particular formation and closure of the urethral groove forming the penile urethra in males, occurs when there is no measurable sex difference in the concentrations of testosterone or dihydrotestosterone in either the gonads or the circulation [corrected]. Phalluses were examined morphologically from the sexually indifferent period (when androgens are high) to well after the time that the phallus becomes sexually dimorphic. We show that penile development and critical changes in the positioning of the urethra occur in the male phallus begin during an early window of time when androgens are high. Remodelling of the urethra in the male occurs between days 20-60. The critical period of time for the establishment urethral closure occurs during the earliest phases of penile development. This study suggests that there is an early window of time before day 60 when androgen imprinting must occur for normal penile development and closure of the urethral groove.


Robotic Radiosurgery for Brain Metastases Diagnosed With Either SPACE or MPRAGE Sequence (CYBER-SPACE)-A Single-Center Prospective Randomized Trial.
Stereotactic radiosurgery (SRS) of brain metastases (BM) is recommended in oligometastatic scenarios as a less toxic treatment alternative to whole-brain radiotherapy. Recent findings support SRS for patients with multiple (>3) BM. Furthermore, advances in MR imaging have facilitated the detection of very small BM, as advances in SRS technology have facilitated the highly conformal and simultaneous treatment of multiple target lesions. To compare efficacy and toxicity of repeated frameless robotic SRS of up to 10 simultaneous BM through a single-center prospective randomized trial. Two hundred patients will be randomized and receive imaging and treatment based on either the highly sensitive SPACE (sampling perfection with application optimized contrasts using different flip angle evolution) or the MPRAGE (magnetization-prepared rapid gradient-echo) magnetic resonance imaging sequence. If during follow-up new metastases are detected, treatment is repeated. The primary endpoint is reached when a patient develops more than 10 simultaneous new BM and is thus deemed unsuitable for further SRS. Overall survival will be assessed as secondary endpoint. Quality of life and neurocognition will be evaluated every 3 mo using CANTAB tests and EORTC (European Organisation for Research and Treatment of Cancer) questionnaires. We expect to show that repeated SRS based on sensitive imaging can delay intracranial dissemination while preserving neurocognitive function and quality of life. The present study is the first to prospectively assess the benefit of sensitive imaging and repeated stereotactic irradiation in the treatment of patients with multiple BM. It represents a novel approach, where in a palliative setting advanced technology in treatment and diagnostics is employed to improve tumor control while also reducing toxicity and preserving quality of life.


Does neurotropin-3 have a therapeutic implication in major depression?
Although several classes of antidepressants are used to treat major depression, there is an unmet need in real clinical practice because not all patients treated with an antidepressant fully recover from their functional impairment. Hence, the development of new antidepressants based on a novel therapeutic mechanism may help in the development of more effective and ideal antidepressive agents. There is emerging evidence suggesting that the etiopathogenesis of depression involves transmitters other than the major neurotransmitters such as serotonin, norepinephrine, and dopamine. Therefore, it has consistently been suggested that an alteration in neuroprotection and synaptic plasticity is associated with the pathogenesis and therapeutic mechanism of depression. Neurotropin-3 (NT3) is an interesting protein that regulates neuronal survival, synaptic plasticity, and neurotransmission. It is widely expressed in the hippocampus and facilitates hippocampal plasticity by regulating neurogenesis. It has been also reported that an infusion of NT3 increases the level of brain-derived neurotrophic factor (BDNF) mRNA expression in the cerebral cortex and produces BDNF-like effects that induce cortical tyrosine kinase B phosphorylation. BDNF has been consistently implicated in the pathogenesis of depression and the therapeutic mechanism of antidepressants. It has also been implicated in the treatment effect of mood stabilizers such as lithium. NT3 has demonstrated its possible antidepressant effect in a learned helpless animal model. Animal studies have shown that it also modulates the neurotransmitters, serotonin and noradrenaline, which are essential in the development and treatment of depression. Therefore, further studies on the therapeutic implications of NT3 for depression are warranted and are expected for the development of newer, effective antidepressants.


LIM-Only Protein FHL2 Is a Negative Regulator of Transforming Growth Factor β1 Expression.
Transforming growth factor β1 (TGF-β1) is a master cytokine in many biological processes, including tissue homeostasis, epithelial-to-mesenchymal transition, and wound repair. Here, we report that four and a half LIM-only protein 2 (FHL2) is a critical regulator of TGF-β1 expression. Devoid of a DNA-binding domain, FHL2 is a transcriptional cofactor that plays the role of coactivator or corepressor, depending on the cell and promoter contexts. We detected association of FHL2 with the TGF-β1 promoter, which showed higher activity in Fhl2-/- cells than in wild-type (WT) cells in a reporter assay. Overexpression of FHL2 abrogates the activation of the TGF-β1 promoter, whereas the upregulation of TGF-β1 gene transcription correlates with reduced occupancy of FHL2 on the promoter. Moreover, ablation of FHL2 facilitates recruitment of RNA polymerase II on the TGF-β1 promoter, suggesting that FHL2 may be involved in chromatin remodeling in the control of TGF-β1 gene transcription. Enhanced expression of TGF-β1 mRNA and cytokine was evidenced in the livers of Fhl2-/- mice. We tested the in vivo impact of Fhl2 loss on hepatic fibrogenesis that involves TGF-β1 activation. Fhl2-/- mice developed more severe fibrosis than their WT counterparts. These results demonstrate the repressive function of FHL2 on TGF-β1 expression and contribute to the understanding of the TGF-β-mediated fibrogenic response.


Survey assessing obesity policies for assisted reproductive technology in the United States.
To determine what assisted reproductive technologies (ART) policies, if any, have been instituted in response to an increasingly overweight and obese patient population. Cross-sectional survey. University-affiliated IVF clinic. Women in the overweight and obese body mass index (BMI) categories seeking ART treatments. Anonymous survey sent to medical directors at 395 IVF centers listed in Society for Assisted Reproductive Technology database. Assessment of recommendations, policies, and restrictions for patients who are overweight/obese and who desire treatment for infertility, including in IVF, IUI, and donor egg cycles. Seventy-seven anonymous responses were received (19.5% response rate): 64.9% of centers have a formal policy for obesity, and 84% of those have a maximum BMI at which they will perform IVF, while 38% of those have a maximum BMI for performing IUI; 64.6% of respondents reported anesthesia requirements/concerns as the primary criteria for patient exclusion. Other primary considerations included safety during ongoing pregnancy and ART outcomes. Centers that have policies regarding obesity and access to ART consider efficacy, procedural safety, safety in pregnancy, and overall health status. Policies vary widely. The patient's autonomy must be balanced with nonmaleficence and the avoidance of interventions that may be unsafe both immediately and long term.


Genome Mining and Predictive Functional Profiling of Acidophilic Rhizobacterium Pseudomonas fluorescens Pt14.
Pseudomonas fluorescens Pt14 is a non-pathogenic and acidophilic bacterium isolated from acidic soil (pH 4.65). Genome sequencing of strain Pt14 was performed using Single Molecule Real Time (SMRT) sequencing to get insights into unique existence of this strain in acidic environment. Complete genome sequence of this strain revealed a chromosome of 5,841,722 bp having 5354 CDSs and 88 RNAs. Phylogenomic reconstruction based on 16S rRNA gene, Average Nucleotide Identity (ANI) values and marker proteins revealed that strain Pt14 shared a common clade with P. fluorescens strain A506 and strain SS101. ANI value of strain Pt14 in relation to strain A506 was found 99.23% demonstrating a very close sub-species association at genome level. Further, orthology determination among these three phylogenetic neighbors revealed 4726 core proteins. Functional analysis elucidated significantly higher abundance of sulphur metabolism (>1×) which could be one of the reasons for the survival of strain Pt14 under acidic conditions (pH 4.65). Acidophilic bacteria have capability to oxidize sulphur into sulphuric acid which in turn can make the soil acidic and genome-wide analysis of P. fluorescens Pt14 demonstrated that this strain contributes towards making the soil acidic.


A Cohort Study Predicts Better Functional Outcomes and Equivalent Patient Satisfaction Following UKR Compared with TKR.
Total knee replacement (TKR) is considered the gold standard treatment for advanced osteoarthritis of the knee (Choong and Dowsey, Int J Rheum Dis 14:167-74, 2011; Satku, Singapore Med J 44:554-556, 2003). Unicompartmental disease can be treated with unicompartmental knee replacement (UKR) or TKR. Some surgeons prefer the proven track record of TKR, while others prefer the more normal joint kinematics, enhanced proprioception and range of movement achieved with UKR (Hopper and Leach, Knee Surg Sports Traumatol Arthrosc 16:973-9, 2008; Satku, Singapore Med J 44:554-556, 2003). However, there is reported low satisfaction amongst younger patients undergoing UKR (Robertson et al., Acta Orthop Scand 71:262-7, 2000). The purpose of this study is to compare patient-reported outcomes, satisfaction and perception of knee normality in age-matched groups of postoperative TKR and UKR patients aiming to answer the following question: Does UKR have lower patient satisfaction than TKR in younger patients? Sixty-eight patients were recruited from the care of a single surgeon. Patients with isolated medial compartment osteoarthritis, stable ACL and less than grade 3 lateral patellar disease underwent UKR. All other patients underwent TKR. Patients were assessed with validated knee scores. Satisfaction was assessed with a visual analogue scale. There was no statistical difference in patient satisfaction or perception of knee normality scores between the two groups, despite better functional scores including WOMAC, SF-36 and Oxford knee in the UKR group. Patient satisfaction is similar amongst TKR and UKR patients despite better functional outcome in terms of recreation and sport with UKR. This may reflect higher preoperative expectations in patients undergoing UKR. Further work is needed to assess this.


Disease Mechanisms in ALS: Misfolded SOD1 Transferred Through Exosome-Dependent and Exosome-Independent Pathways.
Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neuromuscular degenerative disorder with a poorly defined etiology. ALS patients experience motor weakness, which starts focally and spreads throughout the nervous system, culminating in paralysis and death within a few years of diagnosis. While the vast majority of clinical ALS is sporadic with no known cause, mutations in human copper-zinc superoxide dismutase 1 (SOD1) cause about 20 % of inherited cases of ALS. ALS with SOD1 mutations is caused by a toxic gain of function associated with the propensity of mutant SOD1 to misfold, presenting a non-native structure. The mechanisms responsible for the progressive spreading of ALS pathology have been the focus of intense study. We have shown that misfolded SOD1 protein can seed misfolding and aggregation of endogenous wild-type SOD1 similar to amyloid-β and prion protein seeding. Our recent observations demonstrate a transfer of the misfolded SOD1 species from cell to cell, modeling the intercellular transmission of disease through the neuroaxis. We have shown that both mutant and misfolded wild-type SOD1 can traverse cell-to-cell, either as protein aggregates that are released from dying cells and taken up by neighboring cells via macropinocytosis, or in association with vesicles which are released into the extracellular environment. Furthermore, once misfolding of wild-type SOD1 has been initiated in a human cell culture, it can induce misfolding in naïve cell cultures over multiple passages of media transfer long after the initial misfolding template is degraded. Herein we review the data on mechanisms of intercellular transmission of misfolded SOD1.


Comparison of strictureplasty and endoscopic balloon dilatation for stricturing Crohn's disease--review of the literature.
Stricturing Crohn's disease is accompanied by a high-risk for bowel resection and subsequent short bowel syndrome. Strictureplasty (SP) and endoscopic balloon dilatation (EBD) have been developed to prevent, or at least delay, the requirement for resection. The goal of this study was to compare the outcome of these two procedures with regard to complications and disease recurrence. We conducted a MEDLINE literature search to give a current overview about the safety and efficacy of EBD and SP. The initial search yielded 744 articles. Case reports, reviews and meta-analyses were excluded. Finally, 63 articles (SP, 40 articles; EBD, 23 articles) were used for the review. None of the studies compared the two methods directly. A total of 2,532 patients (SP, n = 1,958; EBD, n = 574) were included. The incidence of perioperative complications after SP was 11% and the incidence of major complications was 5%. The median surgical recurrence rate was 24% after a median follow-up of 46 months. The median technical success for EBD was 90%. Major complications occurred in 3% of the cases. According to an intention-to-treat protocol, the median surgical recurrence rate was 27.6%. Per-protocol analysis revealed a median surgical recurrence rate of 21.4% after a median follow-up of 21 months. Due to the lack of comparable data, there is currently no reliable information on whether one treatment option is superior to the other. Regarding the limited applicability of EBD in strictures of the small bowel, only a controlled trial would provide evidence as a basis for clinical decision making in CD strictures that are potentially treatable by EBD and SP.


Expression of HDAC1 and CBP/p300 in human colorectal carcinomas.
The histone-modifying enzymes histone deacetylase (HDAC) and histone acetyltransferase (HAT) control gene transcriptional activation and repression in human malignancies. To analyse the expression of HDAC/HAT-associated molecules such as HDAC1, CREB-binding protein (CBP) and p300 in human colorectal carcinomas, and investigate the relationship between their expression levels and clinicopathological parameters. Expression levels of HDAC1, CBP, and p300 in human colorectal cancer were investigated by immunohistochemistry. In situ hybridisation (ISH) and reverse transcription (RT)-PCR analyses were also carried out to confirm mRNA expression levels of these genes. Immunoreactivity was evaluated semi-quantitatively using a staining index (SI). The relationships between the SIs and clinicopathological findings were analysed and survival curves were calculated using the Kaplan-Meier method and log-rank tests. The mean SIs for HDAC1, CBP, and p300 in this series of tumours were much higher than those in normal colonic mucosa. The presence of HDAC1 and CBP mRNAs on colorectal carcinoma cells as well as normal epithelial cells was confirmed by ISH analysis. A marked increase in p300 mRNA levels was detected in a majority of cases by RT-PCR. Among the patients with colorectal cancer, overexpression of p300 (SI>11.9) correlated with a poor prognosis, whereas high CBP expression levels (SI>16.6) indicated long-term survival. Results showed the up-regulation of these three histone-modifying molecules in this series of colorectal cancers and suggested that monitoring of CBP and p300 may assist prediction of the prognosis in patients with colorectal adenocarcinoma.


Genome-wide comparative analysis reveals human-mouse regulatory landscape and evolution.
Because species-specific gene expression is driven by species-specific regulation, understanding the relationship between sequence and function of the regulatory regions in different species will help elucidate how differences among species arise. Despite active experimental and computational research, relationships among sequence, conservation, and function are still poorly understood. We compared transcription factor occupied segments (TFos) for 116 human and 35 mouse TFs in 546 human and 125 mouse cell types and tissues from the Human and the Mouse ENCODE projects. We based the map between human and mouse TFos on a one-to-one nucleotide cross-species mapper, bnMapper, that utilizes whole genome alignments (WGA). Our analysis shows that TFos are under evolutionary constraint, but a substantial portion (25.1% of mouse and 25.85% of human on average) of the TFos does not have a homologous sequence on the other species; this portion varies among cell types and TFs. Furthermore, 47.67% and 57.01% of the homologous TFos sequence shows binding activity on the other species for human and mouse respectively. However, 79.87% and 69.22% is repurposed such that it binds the same TF in different cells or different TFs in the same cells. Remarkably, within the set of repurposed TFos, the corresponding genome regions in the other species are preferred locations of novel TFos. These events suggest exaptation of some functional regulatory sequences into new function. Despite TFos repurposing, we did not find substantial changes in their predicted target genes, suggesting that CRMs buffer evolutionary events allowing little or no change in the TFos - target gene associations. Thus, the small portion of TFos with strictly conserved occupancy underestimates the degree of conservation of regulatory interactions. We mapped regulatory sequences from an extensive number of TFs and cell types between human and mouse using WGA. A comparative analysis of this correspondence unveiled the extent of the shared regulatory sequence across TFs and cell types under study. Importantly, a large part of the shared regulatory sequence is repurposed on the other species. This sequence, fueled by turnover events, provides a strong case for exaptation in regulatory elements.


White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities.
White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia.


A family of binuclear dysprosium(III) radical compounds with magnetic relaxation in ON and OFF states.
Four binuclear dysprosium compounds incorporating the radical ligand 2-(4-oxidopyridyl)-4,4,5,5-tetramethylimidazolin-1-oxyl-3-oxide (PyNONIT) have been successfully synthesized under appropriate conditions. Centrosymmetric bimetallic Dy(2)O(2) cores in all of the compounds through double-μ(2)-oxygen atoms of the N-oxide groups are realized in a metal-radical approach for the first time. Dimers 1 and 2, of the same formula {[Dy(hfac)(3)(PyNONIT)](2)}(2) (hfac = hexafluoroacetylacetonate) but obtained by different methods, which contain almost identical local symmetry of D(4d) and Dy-(O)(2)-Dy bridging fashion, however, display no out-of-phase alternating-current (ac) signal for 1 and slow relaxation of the magnetization for 2 corresponding to the difference of the crystal packing mode. The adduct ([Dy(hfac)(3)(PyNONIT)](2)[Dy(0.5)(hfac)(1.5)(H(2)O)](2)) (3) consists of two items, the dimer [Dy(hfac)(3)(PyNONIT)](2) and the monomer [Dy(hfac)(3)(H(2)O)(2)], where the symmetry of Dy(III) ion in Dy(2)O(2) decreases to D(2d), showing slow relaxation of the magnetization at lower temperature. Interestingly, a moisture-mediated reversible solid transformation between 1 and ([Dy(hfac)(3)(H(2)O)(PyNONIT)](2)) (4) has been investigated. Spongelike 1 can undergo a transition from eight to nine coordination at room temperature through hydration. A different coordination field is mostly responsible for no ac signal noticed for 4. The structural diversity of the Dy(2) family provides an opportunity to expand the investigation on 4f single-molecule magnets. Approaches that the relaxation of the supramolecular dimer can be tuned to ON and OFF states modulated by the packing mode and ligand field are presented.


Mechanical Thrombectomy of Carotid Terminus Occlusion Using Direct Aspiration Technique-Video Illustration: 2-Dimensional Operative Video.
Acute carotid terminus occlusion (CTO) is responsible for up to 5% of acute ischemic strokes secondary to emergent large vessel occlusion (ELVO) and up to 20% of acute internal carotid artery (ICA) occlusions.1 The term "CTO" has also been used to describe occlusions in the supra-clinoid segment or at the bifurcation of the ICA. Compared to other ELVOs, patients with CTO present with higher stroke severity and larger infarct volume, likely to be a result of disruption of direct Circle of Willis collaterals across the anterior communicating artery (AComA) and posterior communicating artery (PComA).2,3 Similary, CTO is usually associated with worse prognosis compared to other ELVOs in general. With regard to response to treatment, previous studies have reported significantly lower recanalization rates with intravenous alteplase with CTO compared to M1 segment occlusion. With regard to the safety and efficacy of mechanical thrombectomy, prior reports provide conflicting results with some reporting lower successful recanalization rates with CTO compared to M1 occlusion, and others reporting similar results. In our experience, we have found that successful recanalization of CTO can be achieved with a similar approach to M1 occlusions utilizing a direct aspiration first pass technique (ADAPT).3,4 Herein, we present a case of CTO for which we performed mechanical thrombectomy using ADAPT. This procedure was an emergent standard of care procedure for which a consent was not required and so not obtained.


Greater disorderliness of ACTH and cortisol release accompanies pituitary-dependent Cushing's disease.
We investigated the episodicity of 24-h ACTH and cortisol secretory profiles in 16 patients with Cushing's disease and 25 healthy matched controls, with a recently introduced scale- and model-independent regularity statistic, approximate entropy (ApEn). The mean (+/-S.E.M.) ApEn value for plasma ACTH concentrations in Cushing's disease was 1.3817 +/- 0.033, and in controls 0.8394 +/- 0.049 (P < 10(-10)); for plasma cortisol concentrations the values were 1.4575 +/- 0.052 and 0.8637 +/- 0.020 respectively (P < 10(-10)), implying greater irregularity of release for both hormones in Cushing's subjects. The calculated sensitivity and specificity of ApEn for ACTH profiles were 94% and 100% respectively. For cortisol the sensitivity and specificity were both 100%. ApEn was not correlated with sex, age, or the total 24-h secretion rate of ACTH and cortisol in patients and controls. The increased ApEn in patients with Cushing's disease points to an increased disorderliness of ACTH and cortisol secretion compared with healthy controls. In conjunction with the available literature, we hypothesize more generally that autonomous endocrine tumors may be typified by reduced regularity, orderliness, or synchrony of the time structure of hormone release.


First Year After Stroke: An Integrated Approach Focusing on Participation Goals Aiming to Reduce Depressive Symptoms.
Depression is a common issue after stroke. A focus on assisting people to achieve their personal participation goals may reduce levels of depression. The aim of this study was to investigate the effectiveness of a person-centered, integrated approach on facilitating goal achievement in the first year poststroke on depressive symptoms. This study was a randomized controlled trial that addressed ways to enhance participation in patient-valued activities and intermittently screen for adverse sequelae postdischarge from rehabilitation. Collaborative goal setting was undertaken in both groups at discharge from inpatient rehabilitation. The control group received standard management as determined by the treating team. In addition, the intervention group received a multimodal approach, including telephone contacts, screening for adverse sequelae, written information, home visits, review of goal achievement, and further referral to relevant health services. The main outcome measure was depressed mood, measured by the 15-item Geriatric Depression Scale. One hundred ten participants were recruited. No group differences were identified at baseline on any demographic and clinical variables. Using multiple linear regression analysis, there was a significant difference between the 2 groups with respect to the severity of depressive symptoms at 12 months poststroke (R2=0.366; F (6, 89)=8.57; P<0.005), with the intervention group recording lower depressive scores. This model of community-based rehabilitation proved effective in reducing poststroke depressive symptoms. An integrated approach using pursuit of patient-identified activities should form part of routine poststroke management. URL: http://www.anzctr.org.au. Unique identifier: ACTRN12608000042347.


The alternatively-included 11a sequence modifies the effects of Mena on actin cytoskeletal organization and cell behavior.
During tumor progression, alternative splicing gives rise to different Mena protein isoforms. We analyzed how Mena11a, an isoform enriched in epithelia and epithelial-like cells, affects Mena-dependent regulation of actin dynamics and cell behavior. While other Mena isoforms promote actin polymerization and drive membrane protrusion, we find that Mena11a decreases actin polymerization and growth factor-stimulated membrane protrusion at lamellipodia. Ectopic Mena11a expression slows mesenchymal-like cell motility, while isoform-specific depletion of endogenous Mena11a in epithelial-like tumor cells perturbs cell:cell junctions and increases membrane protrusion and overall cell motility. Mena11a can dampen membrane protrusion and reduce actin polymerization in the absence of other Mena isoforms, indicating that it is not simply an inactive Mena isoform. We identify a phosphorylation site within 11a that is required for some Mena11a-specific functions. RNA-seq data analysis from patient cohorts demonstrates that the difference between mRNAs encoding constitutive Mena sequences and those containing the 11a exon correlates with metastasis in colorectal cancer, suggesting that 11a exon exclusion contributes to invasive phenotypes and leads to poor clinical outcomes.


Margin index is not a reliable tool for predicting residual disease after breast-conserving surgery for DCIS.
We previously introduced the concept of margin index as a method for prediction of residual disease after attempted breast-conserving therapy (BCT). We sought to apply the margin index to patients with ductal carcinoma in situ (DCIS) to determine its reliability in predicting residual disease. We identified all patients with DCIS who were treated with BCT from 2004 to 2010. Margin index was calculated as follows: margin index = closest margin (mm)/tumor size (mm) × 100. A receiver operating curve was created using the derived margin index and the presence or absence of residual disease in the re-excision specimen. Sensitivity and specificity were calculated at various margin indices to identify the optimum margin index. Of 380 patients undergoing attempted BCT, 109 (29%) underwent re-excision. Of 109 patients undergoing re-excision, 46 (42%) had positive margins and were excluded from the study, 15 (14%) were excluded due to inability to determine the size of DCIS on pathology reports, and 48 (44%) met study criteria and were included in the analysis. Of 48 patients undergoing re-excision, 19 (40%) had residual disease. The receiver operating curve c index was 0.65. However, there was no optimum margin index that reliably predicted the presence or absence of residual disease. Margin index is not a reliable method for prediction of residual disease after attempted BCT with close margins in patients with DCIS only. This may be a reflection of the complexities in accurately determining DCIS size and margin status in pathologic specimens.


Sugar transport across lactose permease probed by steered molecular dynamics.
Escherichia coli lactose permease (LacY) transports sugar across the inner membrane of the bacterium using the proton motive force to accumulate sugar in the cytosol. We have probed lactose conduction across LacY using steered molecular dynamics, permitting us to follow molecular and energetic details of lactose interaction with the lumen of LacY during its permeation. Lactose induces a widening of the narrowest parts of the channel during permeation, the widening being largest within the periplasmic half-channel. During permeation, the water-filled lumen of LacY only partially hydrates lactose, forcing it to interact with channel lining residues. Lactose forms a multitude of direct sugar-channel hydrogen bonds, predominantly with residues of the flexible N-domain, which is known to contribute a major part of LacY's affinity for lactose. In the periplasmic half-channel lactose predominantly interacts with hydrophobic channel lining residues, whereas in the cytoplasmic half-channel key protein-substrate interactions are mediated by ionic residues. A major energy barrier against transport is found within a tight segment of the periplasmic half-channel where sugar hydration is minimal and protein-sugar interaction maximal. Upon unbinding from the binding pocket, lactose undergoes a rotation to permeate either half-channel with its long axis aligned parallel to the channel axis. The results hint at the possibility of a transport mechanism, in which lactose permeates LacY through a narrow periplasmic half-channel and a wide cytoplasmic half-channel, the opening of which is controlled by changes in protonation states of key protein side groups.


Is the primitive regulation of pituitary prolactin (tPRL177 and tPRL188) secretion and gene expression in the euryhaline tilapia (Oreochromis mossambicus) hypothalamic or environmental?
We examined the effects of environmental salinity on circulating levels of the two prolactins (tPRL177 and tPRL188) and levels of pituitary tPRL177 and tPRL188 mRNA in the euryhaline tilapia, Oreochromis mossambicus. Fish were sham-operated or hypophysectomized and the rostral pars distalis (RPD) autotransplanted onto the optic nerve. Following post-operative recovery in (1/4) seawater, tilapia were transferred to fresh water (FW), (1/4) seawater (SW) or SW. Serum tPRL177 and tPRL188 levels in sham-operated and RPD-autotransplanted fish were highest in FW and decreased as salinity was increased. tPRL177 and tPRL188 mRNA levels in RPD implants as well as in pituitaries from the sham-operated fish were also highest in FW and decreased with increasing salinity. Serum osmolality increased with salinity, with the highest levels occurring in the seawater groups. We conclude that some plasma factor (probably plasma osmolality), in the absence of hypothalamic innervation, exerts a direct regulatory action on prolactin release and gene expression in the pituitary of O. mossambicus. This regulation is in accord with the actions of the two prolactins in the freshwater osmoregulation of the tilapia.


Clinical review: Exogenous surfactant therapy for acute lung injury/acute respiratory distress syndrome--where do we go from here?
Acute lung injury and acute respiratory distress syndrome (ARDS) are characterised by severe hypoxemic respiratory failure and poor lung compliance. Despite advances in clinical management, morbidity and mortality remains high. Supportive measures including protective lung ventilation confer a survival advantage in patients with ARDS, but management is otherwise limited by the lack of effective pharmacological therapies. Surfactant dysfunction with quantitative and qualitative abnormalities of both phospholipids and proteins are characteristic of patients with ARDS. Exogenous surfactant replacement in animal models of ARDS and neonatal respiratory distress syndrome shows consistent improvements in gas exchange and survival. However, whilst some adult studies have shown improved oxygenation, no survival benefit has been demonstrated to date. This lack of clinical efficacy may be related to disease heterogeneity (where treatment responders may be obscured by nonresponders), limited understanding of surfactant biology in patients or an absence of therapeutic effect in this population. Crucially, the mechanism of lung injury in neonates is different from that in ARDS: surfactant inhibition by plasma constituents is a typical feature of ARDS, whereas the primary pathology in neonates is the deficiency of surfactant material due to reduced synthesis. Absence of phenotypic characterisation of patients, the lack of an ideal natural surfactant material with adequate surfactant proteins, coupled with uncertainty about optimal timing, dosing and delivery method are some of the limitations of published surfactant replacement clinical trials. Recent advances in stable isotope labelling of surfactant phospholipids coupled with analytical methods using electrospray ionisation mass spectrometry enable highly specific molecular assessment of phospholipid subclasses and synthetic rates that can be utilised for phenotypic characterisation and individualisation of exogenous surfactant replacement therapy. Exploring the clinical benefit of such an approach should be a priority for future ARDS research.


Environmental effects of ozone depletion and its interactions with climate change: Progress report, 2016.
The Parties to the Montreal Protocol are informed by three Panels of experts. One of these is the Environmental Effects Assessment Panel (EEAP), which deals with two focal issues. The first focus is the effects of UV radiation on human health, animals, plants, biogeochemistry, air quality, and materials. The second focus is on interactions between UV radiation and global climate change and how these may affect humans and the environment. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than previously believed. As a result of this, human health and environmental issues will be longer-lasting and more regionally variable. Like the other Panels, the EEAP produces a detailed report every four years; the most recent was published as a series of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1-184). In the years in between, the EEAP produces less detailed and shorter Progress Reports of the relevant scientific findings. The most recent of these was for 2015 (Photochem. Photobiol. Sci., 2016, 15, 141-147). The present Progress Report for 2016 assesses some of the highlights and new insights with regard to the interactive nature of the direct and indirect effects of UV radiation, atmospheric processes, and climate change. The more detailed Quadrennial Assessment will be made available in 2018.


A Comprehensive Investigation of Risk Association Between the -786 T > C, + 884 G > A, VNTR, rs743506, rs3918226 of eNOS and Susceptibility of Migraine: A Updated Meta-Analysis Utilizing Trial Sequential Analysis.
With a feature of complex pathogenic mechanisms, migraine is a well-known common neurovascular disorder. Multiple genes are responsible for hindering the susceptibility of pain threshold one of which is the eNOS gene and its variants. Multiple independent observational studies with case-control design produced conflicting findings, which can be attributed to a variety of factors including varying sample sizes, demographic stratification, technique application, etc. Therefore, in the present study we aimed to find out the precise risk between the selected variant of eNOS and the risk of migraine and its clinical subtypes using a meta-analysis approach. To find the association between the risk variants of the eNOS gene and migraine, a PRISMA-based systematic literature review strategy was utilized to search via online resources including PubMed and Google Scholar. Using several genetic models, odds ratios with 95% confidence intervals were computed to pool the data. To access heterogeneity, Cochran's Q Test and I2 statistics were utilized, while Begg's and Egger's tests were used to determine publication bias. A p-value of 0.05 or below was deemed statistically significant for all two-sided tests. The present meta-analysis was able to find out the significant protective association between rs743506 and migraine after using dominant (OR: 0.66, CI [0.49-0.86]), over-dominant (OR: 0.56, CI [0.42-0.75]), codominant model (OR: 0.58, CI[0.43-0.77]). Only significant risk association was found between rs1799983, rs3918226, and risk of migraine with aura after utilizing recessive and codominant models i.e., HR vs HW and HR vs HT. The present meta-analysis showed that rs743506 showed a protective association in comparison to rs1799983, rs3918226 which showed significant risk in the MA group. Also, TSA showed non-significant results and therefore, in conclusion, more studies are required to establish risk.


Determining protein complex structures based on a Bayesian model of in vivo Förster resonance energy transfer (FRET) data.
The use of in vivo Förster resonance energy transfer (FRET) data to determine the molecular architecture of a protein complex in living cells is challenging due to data sparseness, sample heterogeneity, signal contributions from multiple donors and acceptors, unequal fluorophore brightness, photobleaching, flexibility of the linker connecting the fluorophore to the tagged protein, and spectral cross-talk. We addressed these challenges by using a Bayesian approach that produces the posterior probability of a model, given the input data. The posterior probability is defined as a function of the dependence of our FRET metric FRETR on a structure (forward model), a model of noise in the data, as well as prior information about the structure, relative populations of distinct states in the sample, forward model parameters, and data noise. The forward model was validated against kinetic Monte Carlo simulations and in vivo experimental data collected on nine systems of known structure. In addition, our Bayesian approach was validated by a benchmark of 16 protein complexes of known structure. Given the structures of each subunit of the complexes, models were computed from synthetic FRETR data with a distance root-mean-squared deviation error of 14 to 17 Å. The approach is implemented in the open-source Integrative Modeling Platform, allowing us to determine macromolecular structures through a combination of in vivo FRETR data and data from other sources, such as electron microscopy and chemical cross-linking.


Human myosin Vc is a low duty ratio nonprocessive motor.
There are three distinct members of the myosin V family in vertebrates, and each isoform is involved in different membrane trafficking pathways. Both myosin Va and Vb have demonstrated that they are high duty ratio motors that are consistent with the processive nature of these motors. Here we report that the ATPase cycle mechanism of the single-headed construct of myosin Vc is quite different from those of other vertebrate myosin V isoforms. K(ATPase) of the actin-activated ATPase was 62 microm, which is much higher than that of myosin Va ( approximately 1 mum). The rate of ADP release from actomyosin Vc was 12.7 s(-1), which was 2 times greater than the entire ATPase cycle rate, 6.5 s(-1). P(i) burst size was 0.31, indicating that the equilibrium of the ATP hydrolysis step is shifted to the prehydrolysis form. Our kinetic model, based on all kinetic data we determined in this study, suggests that myosin Vc spends the majority of the ATPase cycle time in the weak actin binding state in contrast to myosin Va and Vb. Consistently, the two-headed myosin Vc construct did not show processive movement in total internal reflection fluorescence microscope analysis, demonstrating that myosin Vc is a nonprocessive motor. Our findings suggest that myosin Vc fulfills its function as a cargo transporter by different mechanisms from other myosin V isoforms.


Programmed cell death in host-symbiont associations, viewed through the Gene Ontology.
Manipulation of programmed cell death (PCD) is central to many host microbe interactions. Both plant and animal cells use PCD as a powerful weapon against biotrophic pathogens, including viruses, which draw their nutrition from living tissue. Thus, diverse biotrophic pathogens have evolved many mechanisms to suppress programmed cell death, and mutualistic and commensal microbes may employ similar mechanisms. Necrotrophic pathogens derive their nutrition from dead tissue, and many produce toxins specifically to trigger programmed cell death in their hosts. Hemibiotrophic pathogens manipulate PCD in a most exquisite way, suppressing PCD during the biotrophic phase and stimulating it during the necrotrophic phase. This mini-review will summarize the mechanisms that have evolved in diverse microbes and hosts for controlling PCD and the Gene Ontology terms developed by the Plant-Associated Microbe Gene Ontology (PAMGO) Consortium for describing those mechanisms.


Hypercalcaemia of malignancy: evidence for a nonparathyroid humoral agent with an effect on renal tubular handling of calcium.
The renal handling of calcium was examined in 31 patients with hypercalcaemia of malignancy. Results were compared with those from patients with primary hyperparathyroidism, and normal controls rendered hypercalcaemic by calcium infusion. On relating the urinary calcium excretion indices to serum calcium values, inappropriately low rates of urinary calcium excretion were generally found in patients with malignancy associated hypercalcaemia. Further, the pattern of urinary calcium excretion in these subjects was similar to that found in patients with primary hyperparathyroidism. These observations suggest that, in many solid tumours, the development of hypercalcaemia may be attributable to a humoral mediator with a parathyroid hormone-like effect on renal tubular calcium reabsorption. The relatively frequent occurrence of hypercalcaemia in malignant disease thus may be partially explained by the presence of this humoral agent, which may impair the renal excretion of an increase in filtered calcium load, whether due to bone metastases, or humorally mediated osteolysis.


Detailed analysis of RNA-protein interactions within the bacterial ribosomal protein L5/5S rRNA complex.
The crystal structure of ribosomal protein L5 from Thermus thermophilus complexed with a 34-nt fragment comprising helix III and loop C of Escherichia coli 5S rRNA has been determined at 2.5 A resolution. The protein specifically interacts with the bulged nucleotides at the top of loop C of 5S rRNA. The rRNA and protein contact surfaces are strongly stabilized by intramolecular interactions. Charged and polar atoms forming the network of conserved intermolecular hydrogen bonds are located in two narrow planar parallel layers belonging to the protein and rRNA, respectively. The regions, including these atoms conserved in Bacteria and Archaea, can be considered an RNA-protein recognition module. Comparison of the T. thermophilus L5 structure in the RNA-bound form with the isolated Bacillus stearothermophilus L5 structure shows that the RNA-recognition module on the protein surface does not undergo significant changes upon RNA binding. In the crystal of the complex, the protein interacts with another RNA molecule in the asymmetric unit through the beta-sheet concave surface. This protein/RNA interface simulates the interaction of L5 with 23S rRNA observed in the Haloarcula marismortui 50S ribosomal subunit.


Self-Reported Illicit Drug Use Among Norwegian University and College Students. Associations With Age, Gender, and Geography.
Background and Aims: Several studies have pointed to relatively high levels of illicit drug use among students in higher education compared to the general population. The aim of the present study was to provide an updated examination of self-reported illicit drug use among Norwegian University and college students. Methods: Data stem from the SHoT study (Students' Health and Well-being Study), a nationwide cross-sectional survey for higher education in Norway including Norwegian full-time students aged 18-35. Self-reported illicit drug use across a range of specified drugs comprised the outcome variables. Information on gender, age, and study location (geographical area) was also collected and used as stratification variables. The SHoT-survey from 2018 (N = 50,054) was used for the analyses of associations between demographical variables and illicit drug use, while trends in illicit drug use were estimated by comparing the 2018-results with data from the SHoT-surveys conducted in 2010 and 2014. Results: The proportion of students reporting having ever tried illicit drugs increased from 2014 to 2018, for both males (30.8 vs. 36.7%) and females (17.5 vs. 24.0%, both p < 0.001), while only minimal changes occurred between 2010 and 2014. The most commonly used illicit drugs during the past 12 months in 2018 were cannabis (15.2%), followed by MDMA (4.0%), cocaine (3.0%), and LSD/psilocybin (2.1%). Illicit drug use showed both linear increase with age, and inverted U-shaped relationships that peaked in the age span from 23 to 28 years of age. Males reported higher illicit drug use compared with females for all drugs. Proportions of illicit drug use varied across geographical areas within the country, with the highest use being reported in the Oslo area (the largest city and capital of Norway). Conclusions: The present study reports an increase from 2010 to 2018 among Norwegian University and college students in the proportion of those reporting to have tried illicit drugs. Despite varying proportions of use across type of drug, age, gender, and geographical location, the overall high levels of illicit drug use past 12 months confirm the need to address illicit drug use in this population.


Competitive sport and aging: the need for qualitative sociological research.
The number of older athletes is growing with the aging of populations across the developed world. This article reviews studies from a variety of disciplines that focus specifically on the motives and experiences of older adults competing in physically demanding sports at events such as masters and veterans competitions in Australia or the Senior Olympics in North America. It is shown that the majority of research into this phenomenon has taken a quantitative approach or failed to consider older athletes' experiences in the context of broader sociocultural discourses. Therefore, using the author's research into the experiences of older Australian masters athletes as a catalyst, the need for and strength of sociological qualitative research in this area is discussed. The use of qualitative methods, such as in-depth interviews and observations, and interpretive analysis provided alternative ways of making sense of older adults and their relationship with competitive sport to what is typically found in the sport and aging literature.


Computer-assisted design and manufacture of implants in the late reconstruction of extensive orbital fractures.
To evaluate the use of computer-assisted designed and manufactured (CAD/CAM) orbital wall and floor implants for late reconstruction of extensive orbital fractures. We performed a retrospective data review on 29 patients treated for extensive orbital fractures from January 1, 1997, through December 31, 2007, at the University College London Hospitals. The use of a CAD/CAM technique based on cross-sectional computed tomographic scans, generating an accurate stereolithographic model, enabled surgeons and technicians to plan and create the best dimension and position of the implant. Sheet titanium was then pressed to shape from a design outlined on a counterdie of the new reconstructed model. Twenty-nine patients with late enophthalmos due to complex orbital fractures underwent successful reconstruction surgery. Enophthalmos was corrected in all patients. Diplopia was improved in 14 patients, and extraocular movement was improved in 13. The CAD/CAM implants represent a financially viable method for secondary reconstruction of the orbit. This method enables the surgeon to plan the operation in detail, facilitates the surgical procedure, and can help to improve the outcome.


Visual exploration of big spatio-temporal urban data: a study of New York City taxi trips.
As increasing volumes of urban data are captured and become available, new opportunities arise for data-driven analysis that can lead to improvements in the lives of citizens through evidence-based decision making and policies. In this paper, we focus on a particularly important urban data set: taxi trips. Taxis are valuable sensors and information associated with taxi trips can provide unprecedented insight into many different aspects of city life, from economic activity and human behavior to mobility patterns. But analyzing these data presents many challenges. The data are complex, containing geographical and temporal components in addition to multiple variables associated with each trip. Consequently, it is hard to specify exploratory queries and to perform comparative analyses (e.g., compare different regions over time). This problem is compounded due to the size of the data-there are on average 500,000 taxi trips each day in NYC. We propose a new model that allows users to visually query taxi trips. Besides standard analytics queries, the model supports origin-destination queries that enable the study of mobility across the city. We show that this model is able to express a wide range of spatio-temporal queries, and it is also flexible in that not only can queries be composed but also different aggregations and visual representations can be applied, allowing users to explore and compare results. We have built a scalable system that implements this model which supports interactive response times; makes use of an adaptive level-of-detail rendering strategy to generate clutter-free visualization for large results; and shows hidden details to the users in a summary through the use of overlay heat maps. We present a series of case studies motivated by traffic engineers and economists that show how our model and system enable domain experts to perform tasks that were previously unattainable for them.


PEGylation improves the receptor-mediated transfection efficiency of peptide-targeted, self-assembling, anionic nanocomplexes.
Non-viral vector formulations comprise typically complexes of nucleic acids with cationic polymers or lipids. However, for in vivo applications cationic formulations suffer from problems of poor tissue penetration, non-specific binding to cells, interaction with serum proteins and cell adhesion molecules and can lead to inflammatory responses. Anionic formulations may provide a solution to these problems but they have not been developed to the same extent as cationic formulations due to difficulties of nucleic acid packaging and poor transfection efficiency. We have developed novel PEGylated, anionic nanocomplexes containing cationic targeting peptides that act as a bridge between PEGylated anionic liposomes and plasmid DNA. At optimized ratios, the components self-assemble into anionic nanocomplexes with a high packaging efficiency of plasmid DNA. Anionic PEGylated nanocomplexes were resistant to aggregation in serum and transfected cells with a far higher degree of receptor-targeted specificity than their homologous non-PEGylated anionic and cationic counterparts. Gadolinium-labeled, anionic nanoparticles, administered directly to the brain by convection-enhanced delivery displayed improved tissue penetration and dispersal as well as more widespread cellular transfection than cationic formulations. Anionic PEGylated nanocomplexes have widespread potential for in vivo gene therapy due to their targeted transfection efficiency and ability to penetrate tissues.


Efficacy of psychosocial group intervention for children with chronic illness and their parents.
To investigate the efficacy of a cognitive-behavioral group intervention for children with chronic illnesses and to test the effect of an added parent component. Children (n = 194) and their parents participated in a multicenter randomized clinical trial comparing a child-only intervention and a parent-child intervention to a wait-list control group. Primary outcomes were parent- and self-reported internalizing and externalizing problems; secondary outcomes were child disease-related coping skills (information seeking, relaxation, social competence, medical compliance, and positive thinking). Assessments took place at baseline and at 6- and 12-month follow-ups. Intention-to-treat mixed-model analyses were performed to test the difference in change in outcomes. The intervention had a positive effect on changes in parent-reported internalizing problems, child-reported externalizing problems, information seeking, social competence, and positive thinking. The additional effect of parental involvement was observed on parent-reported internalizing problems, child-reported externalizing problems, information seeking, and social competence. Illness severity and illness type did not moderate the effects. There were no intervention effects on child-reported internalizing problems, parent-reported externalizing problems, relaxation, or medical compliance. Of the families in the wait-list control group, 74% sought alternative psychological support during the intervention period. This RCT supports the efficacy of a protocol-based group intervention for children with chronic illnesses and their parents. Adding a parental component to the intervention contributed to the persistence of the effects. Future research should focus on moderating and mediating effects of the intervention.


Systematic review of illness uncertainty management interventions for cancer patients and their family caregivers.
Illness uncertainty pervades individuals' experiences of cancer across the illness trajectory and is associated with poor psychological adjustment. This review systematically examined the characteristics and outcomes of interventions promoting illness uncertainty management among cancer patients and/or their family caregivers. PubMed, Scopus, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, and Cochrane Database of Systematic Reviews were systematically searched for relevant literature. We included randomized controlled trials (RCTs) and quasi-experimental studies focusing on interventions for uncertainty management in cancer patients and/or their family caregivers. Our database searches yielded 26 studies. Twenty interventions were only offered to cancer patients, who were mostly elder, female, and White. All interventions included informational support. Other intervention components included emotional support, appraisal support, and instrumental support. Most interventions were delivered in person and via telephone (n = 8) or exclusively in person (n = 7). Overall, 18 studies identified positive intervention effects on illness uncertainty outcomes. This systematic review foregrounds the promising potential of several interventions-and especially multi-component interventions-to promote uncertainty management among cancer patients and their family caregivers. To further improve these interventions' effectiveness and expand their potential impact, future uncertainty management interventions should be tested among more diverse populations using rigorous methodologies.


Sharing a Playbook: Integrated Care in Community Health Centers in the United States.
We investigated basic measures used to assess collaboration between colocated providers and to gauge the extent to which health centers practice integrated care. We used the Assessment of Behavioral Health Services survey and the 2010 Uniform Data System to explore the elements of integrated care for behavioral health conditions. We used multivariable regression models to examine the correlates of integrated care. More than 85% of health centers provided mental health services in 2010, and almost half offered substance use treatment. Health centers commonly reported shared access to information among behavioral health and medical providers and joint care planning. A higher degree of integrated care involving joint case conferences was less common. Health centers without electronic health records and those with lower percentages of total staff composed of behavioral health workers were less likely to provide integrated care. A 2-pronged strategy involving financial incentives and technical assistance to spread best practices might increase integrated care, particularly among health centers that are not maximizing the potential of electronic health records and health centers with low behavioral health staffing levels.


Al-Air Batteries: Fundamental Thermodynamic Limitations from First-Principles Theory.
The Al-air battery possesses high theoretical specific energy (4140 W h/kg) and is therefore an attractive candidate for vehicle propulsion. However, the experimentally observed open-circuit potential is much lower than what bulk thermodynamics predicts, and this potential loss is typically attributed to corrosion. Similarly, large Tafel slopes associated with the battery are assumed to be due to film formation. We present a detailed thermodynamic study of the Al-air battery using density functional theory. The results suggest that the maximum open-circuit potential of the Al anode is only -1.87 V versus the standard hydrogen electrode at pH 14.6 instead of the traditionally assumed -2.34 V and that large Tafel slopes are inherent in the electrochemistry. These deviations from the bulk thermodynamics are intrinsic to the electrochemical surface processes that define Al anodic dissolution. This has contributions from both asymmetry in multielectron transfers and, more importantly, a large chemical stabilization inherent to the formation of bulk Al(OH)3 from surface intermediates. These are fundamental limitations that cannot be improved even if corrosion and film effects are completely suppressed.


Structural and Functional Alterations of Skeletal Muscle Microvasculature in Dystrophin-Deficient mdx Mice.
Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease, caused by an absence of dystrophin, inevitably leading to death. Although muscle lesions are well characterized, blood vessel alterations that may have a major impact on muscle regeneration remain poorly understood. Our aim was to elucidate alterations of the vascular network organization, taking advantage of Flk1(GFP/+) crossed with mdx mice (model for human DMD where all blood vessels express green fluorescent protein) and functional repercussions using in vivo nuclear magnetic resonance, combining arterial spin-labeling imaging of perfusion, and (31)P-spectroscopy of phosphocreatine kinetics. For the first time, our study focused on old (12-month-old) mdx mice, displaying marked chronic muscle lesions, similar to the lesions observed in human DMD, in comparison to young-adult (3-month-old) mdx mice displaying only mild muscle lesions with no fibrosis. By using an original approach combining a specific animal model, state-of-the-art histology/morphometry techniques, and functional nuclear magnetic resonance, we demonstrated that the microvascular system is almost normal in young-adult in contrast to old mdx mice, displaying marked microvessel alterations, and the functional repercussions on muscle perfusion and bioenergetics after a hypoxic stress vary depending on stage of pathology. This original approach clarifies disease evolution and paves the way for setting up new diagnostic markers or therapeutic strategies.


Global prevalence and associated risk factors of posttraumatic stress disorder during COVID-19 pandemic: A meta-analysis.
The COVID-19 pandemic has negatively impacted the psychological well-being of individuals and society. Previous studies conducted on coronavirus outbreaks including Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome pandemic found that posttraumatic stress disorder (PTSD), depression, and anxiety were the most common mental health problems and long-term consequences of these outbreaks. Currently, comprehensive and integrated information on the global prevalence of PTSD due to the COVID-19 pandemic is lacking. In the present meta-analysis, we examined the global prevalence and associated risk factors of PTSD in patients/survivors of COVID-19, health professionals, and the population at large. Meta-analysis. Cochrane, CINAHL, Embase, MEDLINE, PubMed, Scopus, Web of Science, and manual search up to June 2021. We included studies evaluating the prevalence of PTSD during the COVID-19 pandemic in either patients/survivors, health professionals, and the population at large. The data were analyzed using logit transformation with the random-effects model. Risk of bias assessment was conducted using Hoy and colleagues. A total of 63 studies (n = 124,952) from 24 different countries were involved. The overall pooled estimate of PTSD prevalence was 17.52% (95% CI 13.89 to 21.86), with no evidence of publication bias (t=-0.22, p-value=0.83). This study found a high prevalence of PTSD among patients with COVID-19 (15.45%; 95% CI 10.59 to 21.99), health professionals (17.23%; 95% CI 11.78 to 24.50), and the population at large (17.34%; 95% CI 12.21 to 24.03). Subgroup analyses showed that those working in COVID-19 units (30.98%; 95% CI, 16.85 to 49.86), nurses (28.22%; 95% CI, 15.83 to 45.10), those living in European countries (25.05%; 95% CI 19.14 to 32.06), and studies that used Clinician-Administered PTSD Scale for DSM-5 (30.18%, 95% CI 25.78 to 34.98) demonstrated to have the highest PTSD prevalence compared to other subgroups. Meta-regression analyses revealed that the elderly (above age 65) had lower PTSD prevalence (-1.75, 95% CI -3.16 to -0.34) than the adult population. Substantial PTSD prevalence was found in patients with COVID-19, health professionals, and the population at large. Moderator analysis revealed that age, unit of work, health profession, continent, and assessment tools as significant moderators. Mental health services are needed for everyone, especially adults under the age of 65, those who work in COVID-19 units, nurses, and people in the European continent. The study protocol was registered with the International database of prospective registered systematic reviews (PROSPERO): CRD42020218762. Tweetable abstract: The pooled PTSD prevalence during COVID-19 pandemic for patients with COVID-19, health professionals, and the population at large was 17.52%.


Association between experience of stressful life events and muscle-related temporomandibular disorders in patients seeking free treatment in a dental hospital.
Psychological factors are known to play an important role in the etiology and maintenance of temporomandibular disorders. Since there have been very few studies on this issue in Asian countries, the study was aimed to investigate the relationship between various stressful life events and temporomandibular disorders in patients seeking free treatment in a Dental Hospital, Bangladesh. Five hundred and twenty Bangladeshi adults (370 males and 150 females; mean age, 30.9 +/- 8.2 years) participated in this study. The subjects were given a questionnaire to evaluate their stress status in the last 12 months. The Research Diagnostic Criteria for TMD (RDC/TMD) was used as TMD diagnostic system by three standardized examiners. Two hundred and thirty-six patients were RDC/TMD-defined TMD-positive and were subsequently classified into 7 groups: group I, myofacial pain only; group II, disk displacement only; group III, joint pain only; group IV, myofacial pain and disc displacement; group V, myofacial pain and joint pain; group VI, disc displacement and joint pain; and group VII, myofacial pain, disk displacement and joint pain. Two hundred and eighty-four subjects were RDC/TMD-defined TMD-negative subjects (controls). Adjusted odds ratios were calculated by multiple logistic regression analysis. Logistic regression analysis revealed that patients diagnosed with myofacial pain (group I) and a combination of myofacial and joint pain (group V) had significantly higher levels of financial and job stress than did the controls. Self-health-related stress and stress related to a spouse or deaths of a relative were also identified as predisposing factors for myofacial pain (group I). This study suggests that myofacial pain is more common in individuals with various types of psychological stress. When treating patients with facial pain, dentists should consider the possible presence of psychological factors.


Sustainable prevention of obesity through integrated strategies: The SPOTLIGHT project's conceptual framework and design.
The prevalence of overweight and obesity in Europe is high. It is a major cause of the overall rates of many of the main chronic (or non communicable) diseases in this region and is characterized by an unequal socio-economic distribution within the population. Obesity is largely determined by modifiable lifestyle behaviours such as low physical activity levels, sedentary behaviour and consumption of energy dense diets. It is increasingly being recognised that effective responses must go beyond interventions that only focus on a specific individual, social or environmental level and instead embrace system-based multi-level intervention approaches that address both the individual and environment. The EU-funded project "sustainable prevention of obesity through integrated strategies" (SPOTLIGHT) aims to increase and combine knowledge on the wide range of determinants of obesity in a systematic way, and to identify multi-level intervention approaches that are strong in terms of Reach, Efficacy, Adoption, Implementation and Maintenance (RE-AIM). SPOTLIGHT comprises a series of systematic reviews on: individual-level predictors of success in behaviour change obesity interventions; social and physical environmental determinants of obesity; and on the RE-AIM of multi-level interventions. An interactive web-atlas of currently running multi-level interventions will be developed, and enhancing and impeding factors for implementation will be described. At the neighbourhood level, these elements will inform the development of methods to assess obesogenicity of diverse environments, using remote imaging techniques linked to geographic information systems. The validity of these methods will be evaluated using data from surveys of health and lifestyles of adults residing in the neighbourhoods surveyed. At both the micro- and macro-levels (national and international) the different physical, economical, political and socio-cultural elements will be assessed. SPOTLIGHT offers the potential to develop approaches that combine an understanding of the obesogenicity of environments in Europe, and thus how they can be improved, with an appreciation of the individual factors that explain why people respond differently to such environments. Its findings will inform governmental authorities and professionals, academics, NGOs and private sector stakeholders engaged in the development and implementation of policies to tackle the obesity epidemic in Europe.


Treatment of ADHD with French maritime pine bark extract, Pycnogenol.
Attention Deficit/Hyperactivity Disorder (ADHD) is the most common psychiatric disorder in children. Pycnogenol, an extract from the bark of the French maritime pine, consisting of phenolic acids, catechin, taxifolin and procyanidins, has shown improvement of ADHD in case reports and in an open study. Aim of the present study was to evaluate the effect of Pycnogenol on ADHD symptoms. Sixty-one children were supplemented with 1 mg/kg/day Pycnogenol or placebo over a period of 4 weeks in a randomised, placebo-controlled, doubleblind study. Patients were examined at start of trial, 1 month after treatment and 1 month after end of treatment period by standard questionnaires: CAP (Child Attention Problems) teacher rating scale, Conner's Teacher Rating Scale (CTRS), the Conner's Parent Rating Scale (CPRS) and a modified Wechsler Intelligence Scale for children. Results show that 1-month Pycnogenol administration caused a significant reduction of hyperactivity, improves attention and visual-motoric coordination and concentration of children with ADHD. In the placebo group no positive effects were found. One month after termination of Pycnogenol administration a relapse of symptoms was noted. Our results point to an option to use Pycnogenol as a natural supplement to relieve ADHD symptoms of children.


An App for Detecting Bullying of Nurses Using Convolutional Neural Networks and Web-Based Computerized Adaptive Testing: Development and Usability Study.
Workplace bullying has been measured in many studies to investigate its effects on mental health issues. However, none have used web-based computerized adaptive testing (CAT) with bully classifications and convolutional neural networks (CNN) for reporting the extent of individual bullying in the workplace. This study aims to build a model using CNN to develop an app for automatic detection and classification of nurse bullying-levels, incorporated with online Rasch computerized adaptive testing, to help assess nurse bullying at an earlier stage. We recruited 960 nurses working in a Taiwan Ch-Mei hospital group to fill out the 22-item Negative Acts Questionnaire-Revised (NAQ-R) in August 2012. The k-mean and the CNN were used as unsupervised and supervised learnings, respectively, for: (1) dividing nurses into three classes (n=918, 29, and 13 with suspicious mild, moderate, and severe extent of being bullied, respectively); and (2) building a bully prediction model to estimate 69 different parameters. Finally, data were separated into training and testing sets in a proportion of 70:30, where the former was used to predict the latter. We calculated the sensitivity, specificity, and receiver operating characteristic curve (area under the curve [AUC]), along with the accuracy across studies for comparison. An app predicting the respondent bullying-level was developed, involving the model's 69 estimated parameters and the online Rasch CAT module as a website assessment. We observed that: (1) the 22-item model yields higher accuracy rates for three categories, with an accuracy of 94% for the total 960 cases, and accuracies of 99% (AUC 0.99; 95% CI 0.99-1.00) and 83% (AUC 0.94; 95% CI 0.82-0.99) for the lower and upper groups (cutoff points at 49 and 66 points) based on the 947 cases and 42 cases, respectively; and (2) the 700-case training set, with 95% accuracy, predicts the 260-case testing set reaching an accuracy of 97. Thus, a NAQ-R app for nurses that predicts bullying-level was successfully developed and demonstrated in this study. The 22-item CNN model, combined with the Rasch online CAT, is recommended for improving the accuracy of the nurse NAQ-R assessment. An app developed for helping nurses self-assess workplace bullying at an early stage is required for application in the future.