Global variation in the thermal tolerances of plants.
Thermal macrophysiology is an established research field that has led to well-described patterns in the global structuring of climate adaptation and risk. However, since it was developed primarily in animals, we lack information on how general these patterns are across organisms. This is alarming if we are to understand how thermal tolerances are distributed globally, improve predictions of climate change, and mitigate effects. We approached this knowledge gap by compiling a geographically and taxonomically extensive database on plant heat and cold tolerances and used this dataset to test for thermal macrophysiological patterns and processes in plants. We found support for several expected patterns: Cold tolerances are more variable and exhibit steeper latitudinal clines and stronger relationships with local environmental temperatures than heat tolerances overall. Next, we disentangled the importance of local environments and evolutionary and biogeographic histories in generating these patterns. We found that all three processes have significantly contributed to variation in both heat and cold tolerances but that their relative importance differs. We also show that failure to simultaneously account for all three effects overestimates the importance of the included variable, challenging previous conclusions drawn from less comprehensive models. Our results are consistent with rare evolutionary innovations in cold acclimation ability structuring plant distributions across biomes. In contrast, plant heat tolerances vary mainly as a result of biogeographical processes and drift. Our results further highlight that all plants, particularly at mid-to-high latitudes and in their nonhardened state, will become increasingly vulnerable to ongoing climate change.


Microtubule depolymerization induces traction force increase through two distinct pathways.
Traction forces increase after microtubule depolymerization; however, the signaling mechanisms underlying this, in particular the dependence upon myosin II, remain unclear. We investigated the mechanism of traction force increase after nocodazole-induced microtubule depolymerization by applying traction force microscopy to cells cultured on micropatterned polyacrylamide hydrogels to obtain samples of homogeneous shape and size. Control cells and cells treated with a focal adhesion kinase (FAK) inhibitor showed similar increases in traction forces, indicating that the response is independent of FAK. Surprisingly, pharmacological inhibition of myosin II did not prevent the increase of residual traction forces upon nocodazole treatment. This increase was abolished upon pharmacological inhibition of FAK. These results suggest two distinct pathways for the regulation of traction forces. First, microtubule depolymerization activates a myosin-II-dependent mechanism through a FAK-independent pathway. Second, microtubule depolymerization also enhances traction forces through a myosin-II-independent, FAK-regulated pathway. Traction forces are therefore regulated by a complex network of complementary signals and force-generating mechanisms.


Growth Hormone-Releasing Hormone Receptor Antagonist Modulates Lung Inflammation and Fibrosis due to Bleomycin.
Growth hormone-releasing hormone (GHRH) is a 44-amino acid peptide that regulates growth hormone (GH) secretion. We hypothesized that a GHRH receptor (GHRH-R) antagonist, MIA-602, would inhibit bleomycin-induced lung inflammation and/or fibrosis in C57Bl/6J mice. We tested whether MIA-602 (5 μg or vehicle given subcutaneously [SC] on days 1-21) would decrease lung inflammation (at day 14) and/or fibrosis (at day 28) in mice treated with intraperitoneal (IP) bleomycin (0.8 units on days 1, 3, 7, 10, 14, and 21). Bleomycin resulted in inflammation and fibrosis around airways and vessels evident histologically at days 14 and 28. Inflammation (histopathologic scores assessed blindly) was visibly less evident in mice treated with MIA-602 for 14 days. After 28 days, lung hydroxyproline (HP) content increased significantly in mice treated with vehicle; in contrast, lung HP did not increase significantly compared to naïve controls in mice treated with GHRH-R antagonist. GHRH-R antagonist increased basal and maximal oxygen consumption of cultured lung fibroblasts. Multiple genes related to chemotaxis, IL-1, chemokines, regulation of inflammation, and extracellular signal-regulated kinases (ERK) were upregulated in lungs of mice treated with bleomycin and MIA-602. MIA-602 also prominently suppressed multiple genes related to the cellular immune response including those for T-cell differentiation, receptor signaling, activation, and cytokine production. MIA-602 reduced lung inflammation and fibrosis due to bleomycin. Multiple genes related to immune response and T-cell functions were downregulated, supporting the view that MIA-602 can modulate the cellular immune response to bleomycin lung injury.


Enhanced stability and fluidity in droplet on hydrogel bilayers for measuring membrane protein diffusion.
We form artificial lipid bilayers suitable for single-molecule fluorescence microscopy by contacting an aqueous droplet with a hydrogel support immersed in a solution of lipid in oil. Our results show that droplet on hydrogel bilayers (DHBs) have high lipid mobilities, similar to those observed in unsupported lipid bilayers. DHBs are also stable over a period of several weeks. We examine membrane protein diffusion in these bilayers and report a decreased lateral mobility of the heptameric beta-barrel pore-forming toxin alpha-hemolysin versus that of its monomeric precursor. These results corroborate previous models of the alpha-hemolysin insertion mechanism where the monomer binds to the lipid bilayer without insertion.


Combining organotypic tissue culture with light-sheet microscopy (OTCxLSFM) to study glioma invasion.
Glioblastoma is a very aggressive tumor and represents the most common primary brain malignancy. Key characteristics include its high resistance against conventional treatments, such as radio- and chemotherapy and its diffuse tissue infiltration, preventing complete surgical resection. The analysis of migration and invasion processes in a physiological microenvironment allows for enhanced understanding of these phenomena and can lead to improved therapeutic approaches. Here, we combine two state-of-the-art techniques, adult organotypic brain tissue slice culture (OTC) and light-sheet fluorescence microscopy (LSFM) of cleared tissues in a combined method termed OTCxLSFM. Using this methodology, we can show that glioblastoma tissue infiltration can be effectively blocked through treatment with arsenic trioxide or WP1066, as well as genetic depletion of the tetraspanin, transmembrane receptor CD9, or signal transducer and activator of transcription 3 (STAT3). With our analysis pipeline, we gain single-cell level, three-dimensional information, as well as insights into the morphological appearance of the tumor cells.


Induction of adaptive response and enhancement of PC12 cell tolerance by 7-hydroxycholesterol and 15-deoxy-delta(12,14)-prostaglandin J2 through up-regulation of cellular glutathione via different mechanisms.
Increasing evidence suggests an adaptive response induced by reactive oxygen species and other physiologically existing oxidative stimuli. We have recently reported that a variety of lipid peroxidation products at sublethal concentrations could induce adaptive response and enhance PC12 cell tolerance, although the detailed underlying molecular mechanisms have not been clearly clarified. In the present study, we found that both 7-hydroxycholesterol (7-OHCh) and 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) at sublethal concentrations significantly increased the cellular GSH as well as the enzyme activity of glutamate-cysteine ligase (GCL), the rate-limiting enzyme of GSH synthesis. Depletion of cellular GSH by buthionine sulfoximine completely abolished the adaptive response. Interestingly, treatment with 15d-PGJ2 significantly increased the gene expression of both subunits of GCL in an NF-E2-related factor 2 (Nrf2)-dependent manner, whereas neither 7-OHCh induced any considerable changes on the GCL gene expression nor did the Nrf2-small interfering RNA treatment exert any appreciable effects on the GSH elevation and subsequent adaptive response induced by 7-OHCh. These results demonstrate that the adaptive response induced by both 7-OHCh and 15d-PGJ2 is mediated similarly through the up-regulation of GSH but via different mechanisms.


Towards normalization of soybean somatic embryo maturation.
Soybean (Glycine max L. Merrill) somatic embryos have been useful for assaying seed-specific traits prior to plant recovery. Such traits could be assessed more accurately if somatic embryos more closely mimicked seed development. Amino acid supplements, carbon source, and abscisic acid and basal salt formulations were tested in an effort to modify existing soybean embryogenesis histodifferentiation/maturation media to further normalize the development of soybean somatic embryos. The resultant liquid medium, referred to as soybean histodifferentiation and maturation medium (SHaM), consists of FNL basal salts, 3% sucrose, 3% sorbitol, filter-sterilized 30 mM glutamine and 1 mM methionine. SHaM-derived somatic embryos are more similar to seed in terms of protein and fatty acid/lipid composition, and conversion ability, than somatic embryos obtained from traditional soybean histodifferentiation and maturation media.


Characterization of the early inflammatory infiltrate at the feeding site of infected sand flies in mice protected from vector-transmitted Leishmania major by exposure to uninfected bites.
Mice exposed to sand fly saliva are protected against vector-transmitted Leishmania major. Although protection has been related to IFN-γ producing T cells, the early inflammatory response orchestrating this outcome has not been defined. Mice exposed to uninfected P. duboscqi bites and naïve mice were challenged with L. major-infected flies to characterize their early immune response at the bite site. Mostly, chemokine and cytokine transcript expression post-infected bites was amplified in exposed compared to naïve mice. In exposed mice, induced chemokines were mostly involved in leukocyte recruitment and T cell and NK cell activation; IL-4 was expressed at 6 h followed by IFN-γ and iNOS2 as well as IL-5 and IL-10 expression. In naïve animals, the transcript expression following Leishmania-infected sand fly bites was suppressed. Expression profiles translated to an earlier and significantly larger recruitment of leukocytes including neutrophils, macrophages, Gr+ monocytes, NK cells and CD4+ T cells to the bite site of exposed compared to naïve mice post-infected bites. Additionally, up to 48 hours post-infected bites the number of IFN-γ-producing CD4+ T cells and NK cells arriving at the bite site was significantly higher in exposed compared to naïve mice. Thereafter, NK cells become cytolytic and persist at the bite site up to a week post-bite. The quiet environment induced by a Leishmania-infected sand fly bite in naïve mice was significantly altered in animals previously exposed to saliva of uninfected flies. We propose that the enhanced recruitment of Gr+ monocytes, NK cells and CD4 Th1 cells observed at the bite site of exposed mice creates an inhospitable environment that counters the establishment of L. major infection.


Ocean acidification promotes otolith growth and calcite deposition in gilthead sea bream (Sparus aurata) larvae.
The effects of ocean acidification on otolith crystallization and growth rates were investigated in gilthead sea bream (Sparus aurata) larvae. Larvae were exposed to three different pH levels: pH8.2, pH7.7 and pH7.3 for a period of 18 days post-fertilization. For the first time, we demonstrate that pH has a significant impact on the carbonate polymorph composition, showing calcite in a significant percentage of individuals at low pH. Around 21% of the larvae exposed to pH7.3 showed irregular calcitic otoliths rather than commonly found round aragonitic otoliths. Calcitic otoliths showed a moderate level of heritability suggesting an important role of genetic factors. We also observed significantly larger otoliths in larvae reared at pH7.7 and pH7.3 compared to pH8.2 in both sagittae and lapilli. Our results demonstrate that otolith growth rates in gilthead sea bream larvae increase at low pH while a significant proportion of larvae are prone to the formation of calcitic otoliths at pH7.3.


GeoSentinel: past, present and future†.
In response to increased concerns about emerging infectious diseases, GeoSentinel, the Global Surveillance Network of the International Society of Travel Medicine in partnership with the US Centers for Disease Control and Prevention (CDC), was established in 1995 in order to serve as a global provider-based emerging infections sentinel network, conduct surveillance for travel-related infections and communicate and assist global public health responses. This review summarizes the history, past achievements and future directions of the GeoSentinel Network. Funded by the US CDC in 1996, GeoSentinel has grown from a group of eight US-based travel and tropical medicine centers to a global network, which currently consists of 68 sites in 28 countries. GeoSentinel has provided important contributions that have enhanced the ability to use destination-specific differences to guide diagnosis and treatment of returning travelers, migrants and refugees. During the last two decades, GeoSentinel has identified a number of sentinel infectious disease events including previously unrecognized outbreaks and occurrence of diseases in locations thought not to harbor certain infectious agents. GeoSentinel has also provided useful insight into illnesses affecting different traveling populations such as migrants, business travelers and students, while characterizing in greater detail the epidemiology of infectious diseases such as typhoid fever, leishmaniasis and Zika virus disease. Surveillance of travel- and migration-related infectious diseases has been the main focus of GeoSentinel for the last 25 years. However, GeoSentinel is now evolving into a network that will conduct both research and surveillance. The large number of participating sites and excellent geographic coverage for identification of both common and illnesses in individuals who have traversed international borders uniquely position GeoSentinel to make important contributions of travel-related infectious diseases in the years to come.


Myeloma neuropathy: passive transfer from man to mouse.
Mice were injected daily, for up to 10 weeks, with purified monoclonal immunoglobulin G from patients with myelomatous polyneuropathy or benign gammopathy. The animals developed a demyelinating polyneuropathy with slowed nerve conduction velocities. The putative antinerve factor may be an antibody since injection of Fab fragments from the monoclonal immunoglobulin G produced a similar demyelination. This provides evidence of a circulating factor in the serum of myeloma patients with polyneuropathy that reproduces typical features of the human disease on passive transfer. This disorder is thus distinguished from other neuropathies that occur as remote effects of malignant disease but have no identified pathogenic factors associated with them.


Stereochemical course of DNA hydrolysis by nuclease S1.
Nuclease S1 hydrolyzes the Sp-diastereomer of 5'-O-(2'-deoxyadenosyl)-3'-O-thymidyl phosphorothioate in H2(18)O to [18O]deoxyadenosine 5'-O-phosphorothioate which can be phosphorylated enzymatically to the Sp-diastereomer of [alpha-18O]deoxyadenosine 5'-O-(1-thiotriphosphate). 31P nmr spectroscopy shows the oxygen-18 in this compound to be in a nonbridging position at the alpha-phosphorus, indicating that the hydrolysis reaction catalyzed by nuclease S1 proceeds with inversion of configuration at phosphorus. This result is compatible with a direct nucleophilic attack of H2O at phosphorus without the involvement of a covalent enzyme intermediate.


Exploring the use and impact of the Australian living guidelines for the clinical care of people with COVID-19: Where to from here?
The Australian National COVID-19 Clinical Evidence Taskforce has been developing, maintaining and disseminating living guidelines and decision support tools (clinical flowcharts) for the care of people with suspected or confirmed COVID-19 since 2020. Living guidelines, a form of living evidence, are a relatively new approach, hence more work is required to determine how to optimise their use to inform practice, policy and decision making and to explore implementation, uptake and impact implications. An update of an earlier impact evaluation was conducted to understand sustained awareness and use of the guidelines; the factors that facilitate the widespread adoption of the guidelines and to explore the perceived strengths and opportunities for improvement of the guidelines. A mixed methods impact evaluation was conducted. Surveys collected both quantitative and qualitative data and were supplemented with qualitative interviews. Participants included Australian healthcare practitioners providing care to individuals with suspected or confirmed COVID-19 and people involved in policy making. Data were collected on awareness, use, impact, strengths and opportunities for improvement of the guidelines and flow charts. A total of 148 participants completed the survey and 21 people were interviewed between January and March 2022. Awareness of the work of the Taskforce was high and over 75% of participants reported that the guidelines were used within their workplace. Participants described the Taskforce website and guidelines as trustworthy, valuable, reliable sources of up-to-date evidence-based information. The evaluation highlighted the varied ways the guidelines were being used across a range of settings and the diverse impacts they have from those at a clinical level to impacts at a policy level. Barriers to and enablers of impact and uptake of the guideline were explored. This evaluation highlights the value of living guidelines during a pandemic when the evidence base is rapidly changing and expanding. It presents useful understanding of the ways clinicians and others use living evidence to inform their clinical practice and decision making and the diverse impacts the guidelines are having around Australia.


The CDRH Helix-I: a physical evaluation.
The use of a resonant helical coil with predominantly axial electric fields for regional hyperthermia in the abdomen and pelvis is addressed. The Helix-I applicator, which consists of a three-turn, 36-cm-long, oval-wound helical coil measuring 60 and 43 cm along its major and minor axes, respectively, is described, and specific absorption rate (SAR) measurements for the device are reported. Measurements of the E-field are also described. Specific absorption patterns for the Helix, determined by transient temperature measurements using a gel phantom, and by E(2)-field scans using a liquid phantom, are in general agreement. The general agreement of electric power intensity distribution, inside and outside the phantom, with corresponding SAR distributions obtained from transient temperature data, ensures reliability of the distribution patterns. The E(2) contours provide a clear picture of hot and cold spots as well as the nature of the general distribution.


Naphthodifuran-based zigzag-type polycyclic arene with conjugated side chains for efficient photovoltaics.
Ladder-type conjugated structures with rigid and coplanar molecular frameworks feature longer effective conjugation, affirmative optoelectronic properties and strong intermolecular π-π interactions, which are ideal characteristics for organic photovoltaics. Here, a new "zigzag" angular-fused naphthodifuran (zNDF) based on alkoxyphenyl side chains was designed and synthesized. The distannylated zNDF building block was copolymerized with 4,7-di(5-bromothiophen-2-yl)-5,6-dioctyloxybenzo[c][1,2,5]thiadiazole and 5,8-bis(5-bromothiophen-2-yl)-2,3-bis(4-(2-ethylhexyloxy)-3-fluorophenyl)-6,7-difloroquinoxaline (Br-BT and Br-ffQx) acceptor units by Stille cross coupling reaction to form two new medium bandgap donor-acceptor polymers PzNDFP-BT and PzNDFP-ffQx, respectively. The photovoltaic properties of the copolymers blended with [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM) as an electron acceptor were investigated. A 6.9% efficiency was achieved from the single device based on the PzNDFP-BT : PC71BM (1 : 1.5, w/w) blend film with a 0.25% 1,8-diiodooctane (DIO) additive, which is among the highest efficiency for zNDF-based polymer solar cells.


Development and Characterization of Somatic Hybrids of Ulva reticulata Forsskål (×) Monostroma oxyspermum (Kutz.)Doty.
Ulvophycean species with diverse trait characteristics provide an opportunity to create novel allelic recombinant variants. The present study reports the development of seaweed variants with improved agronomic traits through protoplast fusion between Monostroma oxyspermum (Kutz.) Doty and Ulva reticulata Forsskål. A total of 12 putative hybrids were screened based on the variations in morphology and total DNA content over the fusion partners. DNA-fingerprinting by inter simple sequence repeat (ISSR) and amplified fragment length polymorphism (AFLP) analysis confirmed genomic introgression in the hybrids. The DNA fingerprint revealed sharing of parental alleles in regenerated hybrids and a few alleles that were unique to hybrids. The epigenetic variations in hybrids estimated in terms of DNA methylation polymorphism also revealed sharing of methylation loci with both the fusion partners. The functional trait analysis for growth showed a hybrid with heterotic trait (DGR% = 36.7 ± 1.55%) over the fusion partners U. reticulata (33.2 ± 2.6%) and M. oxyspermum (17.8 ± 1.77%), while others were superior to the mid-parental value (25.2 ± 2.2%) (p < 0.05). The fatty acid (FA) analysis of hybrids showed notable variations over fusion partners. Most hybrids showed increased polyunsaturated FAs (PUFAs) compared to saturated FAs (SFAs) and mainly includes the nutritionally important linoleic acid, α-linolenic acid, oleic acid, stearidonic acid, and docosahexaenoic acid. The other differences observed include superior cellulose content and antioxidative potential in hybrids over fusion partners. The hybrid varieties with superior traits developed in this study unequivocally demonstrate the significance of protoplast fusion technique in developing improved varients of macroalgae.


Transcriptomine, a web resource for nuclear receptor signaling transcriptomes.
The nuclear receptor (NR) superfamily of ligand-regulated transcription factors directs ligand- and tissue-specific transcriptomes in myriad developmental, metabolic, immunological, and reproductive processes. The NR signaling field has generated a wealth of genome-wide expression data points, but due to deficits in their accessibility, annotation, and integration, the full potential of these studies has not yet been realized. We searched public gene expression databases and MEDLINE for global transcriptomic datasets relevant to NRs, their ligands, and coregulators. We carried out extensive, deep reannotation of the datasets using controlled vocabularies for RNA Source and regulating molecule and resolved disparate gene identifiers to official gene symbols to facilitate comparison of fold changes and their significance across multiple datasets. We assembled these data points into a database, Transcriptomine (http://www.nursa.org/transcriptomine), that allows for multiple, menu-driven querying strategies of this transcriptomic "superdataset," including single and multiple genes, Gene Ontology terms, disease terms, and uploaded custom gene lists. Experimental variables such as regulating molecule, RNA Source, as well as fold-change and P value cutoff values can be modified, and full data records can be either browsed or downloaded for downstream analysis. We demonstrate the utility of Transcriptomine as a hypothesis generation and validation tool using in silico and experimental use cases. Our resource empowers users to instantly and routinely mine the collective biology of millions of previously disparate transcriptomic data points. By incorporating future transcriptome-wide datasets in the NR signaling field, we anticipate Transcriptomine developing into a powerful resource for the NR- and other signal transduction research communities.


Eye-tracking-based experimental paradigm to assess social-emotional abilities in young individuals with profound intellectual and multiple disabilities.
Individuals with Profound Intellectual and Multiple Disabilities (PIMD) experience a combination of severe cognitive and motor impairments frequently associated with additional sensory deficits and numerous medical disorders. The purpose of the present study was to propose an experimental paradigm based on eye-tracking that combines various pre-existing tasks from infancy research as an assessment tool. This would enable the investigation of social-emotional abilities in nine young individuals with PIMD through their visual preferences for different types of stimuli. The first objective was to test the feasibility of this paradigm, by expecting individuals to look more at the tasks' presentation screen than elsewhere during its implementation. The second objective was to investigate whether PIMD individuals exhibit visual preferences for (a) biological (vs. non-biological) motion, (b) socially salient (vs. non-social) scenes, (c) the facial area of the eyes (vs. the mouth), (d) happy (vs. angry) faces, (e) objects of joint attention (vs. non-looked at ones), and for (f) prosocial (vs. anti-social) behaviors similar to those of a control group of typically developing children aged two years on average. Overall, the feasibility of this paradigm proved to be good, resulting in high individual looking rates that were not affected by the presentation or the content of the tasks. Analyses of individual social-emotional abilities, supported by the visual preference patterns of each PIMD individual, firstly revealed strong-but expected-variability both within and between subjects, and secondly highlighted some individual task-specific abilities although few similarities between these individual results and those of the control group were found. These findings underline the great relevance of using this type of paradigm for assessing PIMD individuals and thus contribute to a better understanding of their social and emotional development.


Shear bond strength of stainless steel orthodontic brackets with a moisture-insensitive primer.
The purposes of this study were (1) to evaluate the shear bond strength of stainless steel orthodontic brackets bonded to dry and wet (with water and saliva) etched enamel with the use of the moisture-insensitive primer (MIP; Transbond; 3M Unitek, Monrovia, Calif) and (2) to evaluate the effectiveness of MIP with chemically activated (Concise; 3M Dental Products, St Paul, Minn) and light-activated (Transbond XT; 3M Unitek) resin. One hundred forty-four freshly extracted bovine teeth were divided into 12 groups (n = 12 teeth), and brackets were bonded with either of the 2 resins in combination with the conventional primer or MIP in dry or wet enamel surface conditions. The test specimens were mounted in a screw-driven mechanical testing machine (model 4204; Instron Corp, Canton, Mass) and subjected to a crosshead speed of 0.5 mm/min. The data were analyzed by 2-way analysis of variance. MIP with Concise produced slightly higher bond strengths compared with the conventional primers under wet conditions (MIP vs conventional: saliva, P <.001; water, P =.004). However, MIP in combination with Transbond XT produced comparable bond strengths on both the dry and wet etched enamel (dry, 10.14 MPa; water, 9.69 MPa; saliva, 8.90 MPa). The results of this study suggest that MIP be used only with light-activated composite resins.


Knowledge and Attitudes towards Cervical Cancer Screening amongst University of Botswana Female Students
Background: Cervical cancer is the leading cause of cancer deaths in Botswana. More than two-thirds of cases occur in HIV-infected women, in a nation with a high HIV prevalence of 17%. Even though cancer screening is free in health facilities, cervical cancer screening is low. The objective of this study was to assess the knowledge and attitudes of University of Botswana female students on cervical cancer screening. Methods: A cross-sectional study was conducted among University of Botswana female students to elicit information about their knowledge and attitudes on cervical cancer screening. Results: A total of 335 students completed the questionnaire and all reported that they were aware of cervical cancer. The awareness was mostly through brochures, posters and other printed material. Regarding cervical cancer risk 315 (94%) attributed cervical cancer to smoking and 301 (89.9%) to early sexual debut. The majority of students 329 (98.2 %) were aware of cervical cancer screening. Papanicolaou (Pap) smear was the most popular screening test reported by 160 (47.8%) of the respondents as compared to Human Papilloma Virus testing (HPV) reported by 106 (31.6 %) of the respondents. The overall Pap smear screening rate was 92 of 335 students (27.5%). Those who perceived themselves to be at risk of contracting cervical cancer 203 (60.6%) where 1.8 times more likely to go for Pap smear than those who perceived to be safe, (Adjusted Odds Ratio [AOR] 1.834; 95% Confidence Interval [CI]; 1.094-3.067), (P = 0.02). Conclusions: Pap smear screening uptake is low amongst University of Botswana female students. The likely reason for this could be because students do not perceive themselves to be susceptible to cancer so the lesser the likelihood of engaging in preventive behaviours. There is urgent need for university based cancer education campaign on cervical cancer screening benefits and incorporating these campaigns into the existing university medical services to increase uptake of screening programs offered.


Bilateral simultaneous-onset nongranulomatous acute anterior uveitis: clinical presentation and etiology.
OBJECTIVE To describe the etiology and outcome of patients with simultaneous-onset nongranulomatous bilateral acute anterior uveitis. METHODS The medical records of patients who presented to a single tertiary care center with simultaneous-onset nongranulomatous bilateral acute anterior uveitis between January 1990 and May 2010 were retrospectively reviewed; the clinical presentation, results of diagnostic testing, and outcome data are described. RESULTS A total of 4288 new patients with uveitis were evaluated by the Uveitis Service at the University of Illinois at Chicago Eye and Ear Infirmary between January 1990 and May 2010. Of these new patients, 44 (1%) presented with simultaneous-onset nongranulomatous bilateral acute anterior uveitis. The most common etiologies were postinfectious or drug-induced uveitis (23 of 44 patients [52%]) and idiopathic uveitis (15 patients [34%]). Tubulointerstitial nephritis and uveitis syndrome, HLA-B27-associated uveitis, inflammatory bowel disease, and Kawasaki disease each made up fewer than 5% of diagnoses. Overall, this group of patients was younger than the entire cohort of new patients with uveitis who were evaluated during the same time period (P = .002). For 14 of the 15 patients with at least a year of follow-up (93%), the disease duration was limited (<3 months). Of these 14 patients, 7 (50%) developed recurrent disease, with an average time to first recurrence of 20 months (range, 7.5-40 months) after resolution of the initial inflammatory episode. CONCLUSIONS Simultaneous-onset nongranulomatous bilateral acute anterior uveitis is a rare clinical entity that is more common in younger patients and is most frequently associated with recent infection and/or systemic antibiotic use. Tubulointerstitial nephritis and uveitis syndrome should also be considered as a diagnosis. Diagnostic evaluation should include serum antistreptolysin-O titers, HLA-B27 antigen, and urine β2 microglobulin levels because these may reveal systemic disease that requires therapy.


The mind-body-microbial continuum.
Our understanding of the vast collection of microbes that live on and inside us (microbiota) and their collective genes (microbiome) has been revolutionized by culture-independent "metagenomic" techniques and DNA sequencing technologies. Most of our microbes live in our gut, where they function as a metabolic organ and provide attributes not encoded in our human genome. Metagenomic studies are revealing shared and distinctive features of microbial communities inhabiting different humans. A central question in psychiatry is the relative role of genes and environment in shaping behavior. The human microbiome serves as the interface between our genes and our history of environmental exposures; explorations of our microbiomes thus offer the possibility of providing new insights into our neurodevelopment and our behavioral phenotypes by affecting complex processes such as inter- and intra personal variations in cognition, personality, mood, sleep, and eating behavior, and perhaps even a variety of neuropsychiatric diseases ranging from affective disorders to autism. Better understanding of microbiome-encoded pathways for xenobiotic metabolism also has important implications for improving the efficacy of pharmacologic interventions with neuromodulatory agents.


A potential role for avocado- and soybean-based nutritional supplements in the management of osteoarthritis: a review.
Osteoarthritis (OA) is a common, painful, and debilitating condition that affects approximately 46.4 million individuals in the United States. By 2012, this number is expected to increase to 60 million. In addition, it is the leading cause of activity limitation in adults and represents a widely acknowledged economic burden. Although the ultimate goal is to slow or prevent OA progression, at present, medical management of OA is aimed primarily at controlling symptoms of pain and stiffness and maintaining joint mobility and quality of life. Because of the lack or perceived lack of response to many conventional therapies for OA as well as concerns regarding the long-term administration of drugs (eg, nonsteroidal anti-inflammatory drugs), oral joint health supplements (OJHSs) have become increasingly popular among patients with OA. This article briefly reviews pertinent molecular mechanisms involved in the development of OA and summarizes available in vitro and in vivo evidence supporting the use of avocado and soybean unsaponifiables (ASU) either alone or in combination with glucosamine and chondroitin sulfate in patients with OA. Basic scientific research studies and a systematic review and meta-analysis of the available high-quality randomized clinical trials indicate that 300 mg of ASU per day (with or without glucosamine and chondroitin sulfate) appears to be beneficial for patients with hip or knee OA. There is also some evidence that ASU or ASU/glucosamine/chondroitin sulfate combination products could be used prophylactically in even the earliest stages of OA. Considering concerns regarding inferior-quality OJHSs, consumers and physicians are encouraged to take an evidence-based approach when evaluating OJHSs to identify and recommend safe and effective products that meet label claims when tested independently, and are of the highest quality.


[Ramucirumab-paclitaxel as second-line therapy for advanced gastric cancer: Poliambulanza experience].
We reported the cases of two patients affected by metastatic gastric cancer exposed to second line therapy with ramucirumab plus paclitaxel after progression. Both obtained a fast marker reduction with a very favourable toxicity profile. In the first case, a woman affected by peritoneal carcinomatosis, the disease had been stable for 8 months despite of the chemotherapy suspension after 3 cycles; whereas in the second case, a highly symptomatic man with a heavy tumor load (gastric tumor and multiple bone, node and peritoneal metastases) obtained an immediate clinical benefit even if of relatively short duration with a good tolerability.


Mannan-binding lectin in asthma and allergy.
Mannan-binding lectin (MBL) is a vital and versatile component of innate immunity. It is present in serum and may bind to a plethora of microbial pathogens and mediate opsonization of these by complement-dependent and/or independent mechanisms. Low-MBL levels in serum, attributed to certain genetic polymorphisms, constitute a major factor predisposing to several infectious diseases. However, recent studies propose that MBL extends beyond its classic role as a first-line host-defense molecule to a modulator of inflammation. In this review, we summarize and explore this potential and a possible novel role of MBL in asthma and allergy.


Purification and composition of a novel gastrointestinal tumor-associated glycoprotein expressing sialylated lacto-N-fucopentaose II (CA 19-9).
Monoclonal antibody 1116NS 19-9 (Mab 19-9) exhibits selective reactivity with human gastrointestinal carcinomas and recognizes a carbohydrate determinant (CA 19-9) defined as a sialylated lacto-N-fucopentaose II. A scheme was devised for the purification of a human gastrointestinal tumor-associated glycoprotein antigen expressing CA 19-9 from colorectal carcinoma cell line SW1116 culture media in high yield. The key steps in the purification were immunoaffinity column chromatography with Mab 19-9 followed by reduction and alkylation of the specifically bound proteins in the presence of 6 M guanidine hydrochloride and a second Mab 19-9 immunoaffinity fractionation. The purified CA 19-9 containing glycoprotein ran as a single band on sodium dodecyl sulfate-polyacrylamide gradient gels with an apparent molecular mass of 210 kilodaltons. In the absence of detergents, this purified glycoprotein apparently reassociated to form aggregates of 600-2000 kilodaltons molecular mass as determined by size-exclusion chromatography. Amino acid analysis of CA 19-9 containing glycoprotein revealed that serine, threonine, and proline together accounted for greater than 35% of the amino acid residues, consistent with a mucin-like structure for the protein. Carbohydrate compositional analysis, however, was in contrast to a typical mucin with a fucose:mannose:galactose:N-acetylgalactosamine: N-acetylglucosamine:N-acetylneuraminic acid molar ratio of 4:1:12:2.5:5:5. The presence of both N-acetylgalactosamine and mannose suggested that both O- and N-linked oligosaccharides may exist on CA 19-9 containing glycoprotein. Protein and carbohydrate analyses indicated that this novel tumor-associated glycoprotein was 85% carbohydrate by weight. This purification procedure may be applicable to the isolation of other epithelial tumor-associated antigens.


digit-a tool for detection and identification of genomic interchromosomal translocations.
Structural variations (SVs) in genomic DNA can have profound effects on the evolution of living organisms, on phenotypic variations and on disease processes. A critical step in discovering the full extent of structural variations is the development of tools to characterize these variations accurately in next generation sequencing data. Toward this goal, we developed a software pipeline named digit that implements a novel measure of mapping ambiguity to discover interchromosomal SVs from mate-pair and pair-end sequencing data. The workflow robustly handles the high numbers of artifacts present in mate-pair sequencing and reduces the false positive rate while maintaining sensitivity. In the simulated data set, our workflow recovered 96% of simulated SVs. It generates a self-updating library of common translocations and allows for the investigation of patient- or group-specific events, making it suitable for discovering and cataloging chromosomal translocations associated with specific groups, traits, diseases or population structures.


Lower urinary tract obstruction: fetal intervention based on prenatal staging.
The authors present an overview of lower urinary tract obstruction (LUTO) in the fetus with a particular focus on the insult to the developing renal system. Diagnostic criteria along with the challenges in estimating long-term prognosis are reviewed. A proposed prenatal LUTO disease severity classification to guide management decisions with fetal intervention to maintain or salvage in utero and neonatal pulmonary and renal function is also discussed. Stage I LUTO (mild form) is characterized by normal amniotic fluid index after 18 weeks, normal kidney echogenicity, no renal cortical cysts, no evidence of renal dysplasia, and favorable urinary biochemistries when sampled between 18 and 30 weeks; prenatal surveillance is recommended. Stage II LUTO is characterized by oligohydramnios/anhydramnios, hyperechogenic kidneys but absent renal cortical cysts or apparent signs of renal dysplasia and favorable fetal urinary biochemistry; fetal vesicoamniotic shunting (VAS) or fetal cystoscopy is indicated to prevent pulmonary hypoplasia and renal failure. Stage III LUTO is oligohydramnios/anhydramnios, hyperechogenic kidneys with cortical cysts and renal dysplasia and unfavorable fetal urinary biochemistry after serial evaluation; fetal vesicoamniotic shunt may prevent severe pulmonary hypoplasia but not renal failure. Stage IV is characterized by intrauterine fetal renal failure, defined by anhydramnios and ultrasound (US) findings suggestive of severe renal dysplasia, and is associated with death in 24 h of life or end-stage renal disease (ESRD) within the first week of life; fetal vesicoamniotic shunt and fetal cystoscopy are not indicated.


[Psychological manifestations of epilepsy in childhood].
Epilepsy in infancy, far from being a condition in which only convulsive phenomena occur, also has important cognitive and behavioral components, which may be more important than the epileptic seizures itself. The psychological repercussions of epilepsy are the sum of various factors due to the epilepsy itself, the treatment given, the side-effects of drugs given and the manner in which the patient copes with his illness. The epilepsy itself shows the effect of the causal lesion, lesions associated with this causal lesion and the immediate and long-term effects of the resulting paroxystic discharges. The most significant manifestations are: attention disorders, problems of social relationships and problems of conduct. Treatment and diagnosis should not be limited to treatment of the crises. In all epileptic children neuropsychological assessment should be directed towards the detection and surveillance of the most common problems. This has a considerable effect on the quality of life of the epileptic patient. In cases of benign idiopathic epilepsies, which occur most frequently in childhood, evaluation of conduct using Achenbach's questionnaire (CBCL) may be sufficient, together with assessment of the ability to pay attention on Continuous Performance Test (CPT) and a quantitative and qualitative evaluation of intellectual capacity using the WISC-R or K-ABC scales.


Tendency to being bitten by insects among patients with eczema and with other dermatoses.
In order to ascertain whether patients with eczema are more prone to being bitten by insects than those with other dermatoses, data were collected by interview and questionnaire from 496 patients attending the outpatient department of a hospital in Sydney and a general dermatological practice in Geelong, Australia. Of the 93 patients with eczema 65% claimed they were prone to insect bite and that they were bitten in preference to other people when in a group, compared with 17% of the 403 patients with other chronic dermatoses. Similar proportions of both groups (approximately 50%) had used insect repellents. Excluding those with eczema 30% of the 149 patients with a family history of atopy claimed they were prone to being bitten by insects compared with 8% of the 254 patients without a family history of atopy. There was no difference in the prevalence of eczema or family history of atopy between men and women, but more women felt themselves to be susceptible to insect bites than men. There is evidence that patients with eczema and those with a family history of atopy are prone to being bitten by insects. Further confirmatory work, perhaps using volunteers and mosquitoes, is indicated. However, patients with severe eczema or a family history of atopy should take care when travelling to areas where disease-carrying insects are prevalent.


Synthesis of two diastereoisomeric p-nitrophenyl phosphodiesters of 2',3'-secouridine and their affinity for phosphodiesterases.
The synthesis of the p-nitrophenyl esters of the 5'- and 3'-phosphates of the nucleoside analogue 2',3'-secouridine are described. Unlike the corresponding diesters of thymidine, these two compounds are diastereoisomers. Their affinity for phosphodiesterases types I and II were investigated. Both analogues were hydrolysed very slowly by snake venom phosphodiesterase but their affinity for the enzyme was similar to that of the p-nitrophenyl ester of thymidine 5'-monophosphate of which they were both competitive inhibitors with Ki approximately Km. Neither compound was hydrolysed by spleen phosphodiesterase but both competitively inhibited the p-nitrophenyl ester of thymidine 3'-monophosphate, with Ki's slightly higher than the Km. Although for each enzyme the Ki of the correct analogue phosphodiester (i.e. the 5'-derivative for snake venom and the 3'-derivative for spleen) was the lower, the absolute specificity seen for the normal substrates had been lost.


The significance of transferrin for intestinal iron absorption.
A mechanism is proposed by which apotransferrin is secreted from mucosal cells, loaded with iron in the intestinal lumen, and then the intact complex is taken into the cell. Within the cell, iron is released and transferred to the blood stream, whereas iron-free transferrin returns to the brush border to be recycled. We have investigated this hypothesis by measuring intestinal absorption of radioiron and 125I-labeled plasma transferrin using tied-off gut segments in normal and iron-deficient rats. There was no absorption of diferric transferrin from the ileum, but high absorption from the duodenum and jejunum segments. Jejunal absorption occurred as a function of the dose offered and showed saturation kinetics. In normal animals, 4 micrograms of the 50 micrograms of transferrin iron was absorbed over 1 hr. In iron-deficient animals, mean values as high as 13 micrograms were observed. Radioiron content of the jejunal mucosa bore a linear relationship to the dose administered and was inversely proportional to the amount of iron entering the plasma. Recycling of transferrin was indicated by the presence of labeled apotransferrin in the lumen, first observed between 15 and 60 min after the injection of diferric transferrin. A high resistance of diferric and apotransferrin to proteolytic degradation within the gut lumen was demonstrated. Comparative studies with lactoferrin and ferritin disclosed poor availability of their iron for absorption. The small amount that was absorbed did not relate to the iron status of the recipient animal. These studies support the role of mucosal transferrin as a shuttle protein for iron absorption.


The Landscape of Movement Control in Locomotion: Cost, Strategy, and Solution.
Features of gait are determined at multiple levels, from the selection of the gait itself (e.g., walk or run) through the specific parameters utilized (stride length, frequency, etc.) to the pattern of muscular excitation. The ultimate choices are determined neurally, but what is involved with deciding on the appropriate strategy? Human locomotion appears stereotyped not so much because the pattern is predetermined, but because these movement patterns are good solutions for providing movement utilizing the machinery available to the individual (the legs and their requisite components). Under different circumstances the appropriate solution may differ broadly (different gait) or subtly (different parameters). Interpretation of the neural decision making process would benefit from understanding the influences that are utilized in the selection of the appropriate solution in any set of circumstances, including normal conditions. In this review we survey an array of studies that point to energetic cost as a key input to the gait coordination system, and not just an outcome of the gait pattern implemented. We then use that information to rigorously define the construct proposed by Sparrow and Newell (1998) where the effects of environment, organism, and task act as constraints determining the solution set available, and the coordination pattern is then implemented under pressure for energetic economy. The fit between the environment and the organism define affordances that can be actualized. We rely on a novel conceptualization of task that recognizes that the task goal needs to be separated from the mechanisms that achieve it so that the selection of a particular implementation strategy can be exposed and understood. This reformulation of the Sparrow and Newell construct is then linked to the proposed pressure for economy by considering it as an optimization problem, where the most readily selected gait strategy will be the one that achieves the task goal at (or near) the energetic minimum.


Effect of socioeconomic status on the relationship between atmospheric pollution and mortality.
Current knowledge about potential interactions between socioeconomic status and the short- and long-term effects of air pollution on mortality was reviewed. A systematic search of the Medline database through April 2006 extracted detailed information about exposure measures, socioeconomic indicators, subjects' characteristics and principal results. Fifteen articles (time series, case-crossover, cohort) examined short-term effects. The variety of socioeconomic indicators studied made formal comparisons difficult. One striking fact emerged: studies using socioeconomic characteristics measured at coarser geographic resolutions (city- or county-wide) found no effect modification, but those using finer geographic resolutions found mixed results, and five of six studies using individually-measured socioeconomic characteristics found that pollution affected disadvantaged subjects more. This finding was echoed by the six studies of long-term effects (cohorts) identified; these had substantial methodological differences, which we discuss extensively. Current evidence does not yet justify a definitive conclusion that socioeconomic characteristics modify the effects of air pollution on mortality. Nevertheless, existing results, most tending to show greater effects among the more deprived, emphasise the importance of continuing to investigate this topic.


FRESCO-2: a global Phase III study investigating the efficacy and safety of fruquintinib in metastatic colorectal cancer.
Fruquintinib, a novel, highly selective, small-molecule tyrosine kinase inhibitor of VEGF receptors (VEGFRs)-1, -2 and -3, is approved in China for the treatment of metastatic colorectal cancer. FRESCO-2, a global, randomized, double-blind, placebo-controlled, Phase III study, is investigating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer. Key inclusion criteria include: progression on or intolerance to TAS-102 and/or regorafenib; and prior treatment with approved chemotherapy, anti-VEGF therapy, and, if RAS wild-type, anti-EGFR therapy. Approximately 687 patients will be randomized 2:1 to fruquintinib plus best supportive care or placebo plus best supportive care. Primary and key secondary end points are overall survival and progression-free survival, respectively. FRESCO-2 is enrolling in the USA, Europe, Australia and Japan.


Nonsecretory myelomatosis without intracellular immunoglobulin. Immunofluorescent and ultramicroscopic studies.
A patient with multiple myeloma is reported with severe hypogammaglobulinaemia but without monoclonal immunoglobulin (M-component) in the serum or Bence Jones protein in the urine. In May-Grünwald-Giemsa stained bone marrow film 45% of the cells resembled plasma cells. Marrow immunofluorescent studies showed no increase of immunoglobulin containing cells. Ultrastructural studies showed a large number of cells with a well developed rough endoplasmic reticulum and other morphological features characteristic for plasma cells.


Mirroring in the analysis of an artist.
A patient, a young woman artist, once remarked, 'I am always looking in the mirror and that's why I can't paint'. Miranda in W. H. Auden's The Sea and the Mirror said, 'My dear one is mine as mirrors are lonely'. Both these quotations refer to the wish to be free from the residual derivations of infantile mirroring which Winnicott defined by saying that the mother's face is the child's natural mirror; a young girl, when she has recourse to the glass mirror, is reassuring herself that the mother-image is there. The paper traces the connexions between mirroring and a painter's stated personal dilemma of knowing that looking in the mirror was an alternative to being able to paint and yet of needing to look in the mirror to reassure herself. To have framed that dilemma had involved work to effect a shift from narcissism to reflective self-awareness. The theme of mirroring, as previously described by other clinicians, is enlarged upon to show how the painter's dilemma could be reconstructed in terms of the early mother-child-mirror dissonances. The patient's experience of her self-image through painting began to become more accessible as an accompaniment to a move 'through the looking glass' into the mirror dialogue with her infantile mother-image.


[Characteristics of body constitution and their relations to success in learning].
Somatotype, finger dermatoglyphic pattern type, emotional stability level and foreign languages learning successfulness have been analyzed in 297 male cadets (aged 17-20 years) of the Military Institute of Physical Training. The cadets studied most frequently belonged to macrosomal and mesosomal somatotypes. In the study of finger patterns, loops were found to be most common (61.5% of all the patterns), while ringlets (33.4%) and arc patterns (5.1%) were less frequent. The amount of ulnar loops increased, while that of ringlets became less in the direction from micro- to macrosomal type. Almost half (46.9%) of the cadets appeared to be ambiverts, 30.8% were intraverts and the rest were extraverts. Loop patterns on all the fingers to a greater extent were found in cadets with high level of neuroticism; the cadets having lower neuroticism level were characterized by a combinations of loops with arcs on the left hand and arcs with ringlets on the right one. The cadets differing in foreign language learning successfulness level were different in their dermatoglyphic patterns and, especially in the prevalence of pattern combinations. So, among the excellent pupils the loop-arc combinations were 2.7 times more common and combinations of all three types of patterns (arcs, loops, ringlets) were 1.4 times more common.


A Statewide Nested Case-Control Study of Preterm Birth and Air Pollution by Source and Composition: California, 2001-2008.
Preterm birth (PTB) has been associated with exposure to air pollution, but it is unclear whether effects might vary among air pollution sources and components. We studied the relationships between PTB and exposure to different components of air pollution, including gases and particulate matter (PM) by size fraction, chemical composition, and sources. Fine and ultrafine PM (respectively, PM2.5 and PM0.1) by source and composition were modeled across California over 2000-2008. Measured PM2.5, nitrogen dioxide, and ozone concentrations were spatially interpolated using empirical Bayesian kriging. Primary traffic emissions at fine scale were modeled using CALINE4 and traffic indices. Data on maternal characteristics, pregnancies, and birth outcomes were obtained from birth certificates. Associations between PTB (n = 442,314) and air pollution exposures defined according to the maternal residence at birth were examined using a nested matched case-control approach. Analyses were adjusted for maternal age, race/ethnicity, education and neighborhood income. Adjusted odds ratios for PTB in association with interquartile range (IQR) increases in average exposure during pregnancy were 1.133 (95% CI: 1.118, 1.148) for total PM2.5, 1.096 (95% CI: 1.085, 1.108) for ozone, and 1.079 (95% CI: 1.065, 1.093) for nitrogen dioxide. For primary PM, the strongest associations per IQR by source were estimated for onroad gasoline (9-11% increase), followed by onroad diesel (6-8%) and commercial meat cooking (4-7%). For PM2.5 composition, the strongest positive associations per IQR were estimated for nitrate, ammonium, and secondary organic aerosols (11-14%), followed by elemental and organic carbon (2-4%). Associations with local traffic emissions were positive only when analyses were restricted to births with residences geocoded at the tax parcel level. In our statewide nested case-control study population, exposures to both primary and secondary pollutants were associated with an increase in PTB. Laurent O, Hu J, Li L, Kleeman MJ, Bartell SM, Cockburn M, Escobedo L, Wu J. 2016. A statewide nested case-control study of preterm birth and air pollution by source and composition: California, 2001-2008. Environ Health Perspect 124:1479-1486; http://dx.doi.org/10.1289/ehp.1510133.


Inhibitory effects of urine on the polymerase chain reaction for cytomegalovirus DNA.
The inhibitory effects of urine samples taken from neonates and older children, some of which were known to be infected with cytomegalovirus, on the polymerase chain reaction (PCR) were investigated. Urea was the major inhibitory component of urine and inhibited the PCR at a concentration of more than 50 mM. Urine samples from older children were more inhibitory than those from neonates. This correlated with the higher concentration of urea generally found in urine samples from older children compared with neonatal urines. Two of 13 neonatal urine samples, however, were inhibitory despite low urea concentrations--presumably due to metabolites derived from parenteral nutrition. The inhibitory effects of urine were effectively removed by simple dialysis or ultrafiltration. The sensitivity and specificity of PCR for detecting cytomegalovirus DNA in urine were further improved by using "nested" primers and a modified PCR protocol entailing the use of reduced reactants in the first 20 cycles of a two-stage 50 cycle PCR.


Structural consequences of cyclophilin A binding on maturational refolding in human immunodeficiency virus type 1 capsid protein.
While several cellular proteins are incorporated in the human immunodeficiency virus type 1 virion, cyclophilin (CyP) A is the only one whose absence has been demonstrated to impair infectivity. Incorporation of the cytosolic protein results from interaction with a highly exposed Pro-rich loop in the N-terminal region of the capsid (CA) domain of the precursor polyprotein, Pr55(Gag). Even when prevented from interacting with CyP A, Pr55Gag still forms particles that proceed to mature into morphologically wild-type virions, suggesting that CyP A influences a postassembly event. The nature of this CyP A influence has yet to be elucidated. Here, we show that while CyP A binds both Gag and mature CA proteins, the two binding interactions are actually different. Tryptophan 121 (W121) in CyP A distinguished the two proteins: a phenylalanine substitution (W121F) impaired binding of mature CA protein but not of Gag. This indicates the occurrence of a maturation-dependent switch in the conformation of the Pro-rich loop. A structural consequence of Gag binding to CyP A was to block this maturational refolding, resulting in a 24-kDa CA protein retaining the immature Pro-rich loop conformation. Using trypsin as a structure probe, we demonstrate that the conformation of the C-terminal region in mature CA is also a product of maturational refolding. Binding to wild-type CyP A altered this conformation, as indicated by a reduction in the accessibility of Cys residue(s) in the region to chemical modification. Hence, the end result of binding to CyP A, whether the Pro-rich loop is in the context of Gag or mature CA protein, is a structurally modified mature CA protein. The postassembly role of CyP A may be mediated through these modified mature CA proteins.


Alcohol use patterns predict high-risk HIV behaviors among active injection drug users.
The purpose of this study was to determine if alcohol use is independently associated with needle-sharing behavior. Participants were 196 active injection drug users recruited into the Providence, Rhode Island Needle Exchange program between July 1997 and March 1998. All subjects were administered a 45-minute questionnaire that included questions on quantity/frequency of alcohol use and the alcohol abuse section of the Structured Clinical Interview for DSM-III-R (SCID; Spitzer, Williams, Gibbon, & First, 1992). Drug risk behaviors, including needle sharing were assessed using the HIV Risk Assessment Battery (RAB; Navaline et al., 1994). Of 196 IDUs, 60% had used alcohol in the last month. Twenty-eight percent met criteria from the Diagnostic and Statistical Manual for Mental Disorders, 3rd ed., rev. (DSM-III-R; American Psychiatric Association, 1987) for alcohol abuse over the last 6 months. One half of IDUs had shared needles in the last 6 months. Increasing levels of alcohol ingestion were associated with greater RAB drug risk scores and greater needle sharing. Using multiple logistic regression, high-level "at-risk" alcohol use (odds ratio [OR], 2.5) and alcohol abuse (OR, 2.3) were significantly associated with needle sharing when controlling for other demographic and behavioral factors previously found to be associated with sharing. The results of this study showed that prevalence of alcohol abuse is high in this population and is associated with needle sharing. HIV prevention effects in needle exchange programs should address alcohol use.


Photo-induced radical thiol-ene chemistry: a versatile toolbox for peptide-based drug design.
While the global market for peptide/protein-based therapeutics is witnessing significant growth, the development of peptide drugs remains challenging due to their low oral bioavailability, poor membrane permeability, and reduced metabolic stability. However, a toolbox of chemical approaches has been explored for peptide modification to overcome these obstacles. In recent years, there has been a revival of interest in photoinduced radical thiol-ene chemistry as a powerful tool for the construction of therapeutic peptides.


Cement line staining in undecalcified thin sections of cortical bone.
A technique for demonstrating cement lines in thin, undecalcified transverse sections of cortical bone has been developed. Cortical bone samples are processed and embedded undecalcified in methyl methacrylate plastic. After sectioning at 3-5 microns, cross-sections are transferred to a glass slide and flattened for 10 min. Sections of cortical bone are stained for 20 sec free-floating in a fresh solution of 1% toluidine blue dissolved in 0.1% formic acid. The section is dehydrated in t-butyl alcohol, cleared in xylene, and mounted with Eukitt's medium. Reversal lines appear as thin, scalloped, dark blue lines against a light blue matrix, whereas bone formation arrest lines are thicker with a smooth contour. With this technique cellular detail, osteoid differentiation, and fluorochrome labels are retained. Results demonstrate the applicability of a one-step staining method for cement lines which will facilitate the assessment of bone remodeling activity in thin sections of undecalcified cortical bone.


Priority service needs and receipt across the lifespan for individuals with autism spectrum disorder.
Individuals with Autism Spectrum Disorder (ASD) have a range of health, community, and social support needs across the lifespan that create age-specific challenges in navigating service sectors. In this study, we set out to identify the priority needs of individuals with ASD across the lifespan, and the factors that predict receiving priority services. Participants included 3,317 individuals with ASD from a Canada-wide online caregiver survey, stratified into five age groups (preschool, elementary school age, adolescence, emerging adulthood, adulthood). Priority receipt was calculated as a ratio of current services that corresponded to individualized priority need. Age-stratified Poisson regression analyses were used to identify the sociodemographic, clinical and systemic predictors of priority receipt. Results indicate that the distribution of priority need varied by age, except for social skills programming, which was a high across all groups. The number of high and moderate priority needs diversified with age. Overall, 30% of individuals had none of their priority needs met and priority receipt decreased with age. Systemic factors were most consistently related to priority receipt across the lifespan. Understanding patterns and correlates of priority needs and use that currently exist in different age groups can inform policies to improve service access. Autism Res 2017, 10: 1436-1447. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.


The potential impact of compositional changes in farmed fish on its health-giving properties: is it time to reconsider current dietary recommendations?
Assessment of national dietary guidelines in a number of European countries reveals that some are based on cohort studies, focusing on total seafood consumption, while others are based on the content of EPA and DHA, distinguishing between oily and other fish. The mean actual intake of fish in most countries is around or below the recommended intake, with differences in intake of fish being present between sex and age groups. Many people do not reach the national recommendation for total fish intake. Dietary recommendations for fish and EPA/DHA are based mainly on data collected more than 10 years ago. However, methods of farmed fish production have changed considerably since then. The actual content of EPA and DHA in farmed salmon has nearly halved as the traditional finite marine ingredients fish meal and fish oil in salmon diets have been replaced with sustainable alternatives of terrestrial origin. As farmed salmon is an important source of EPA and DHA in many Western countries, our intake of these fatty acids is likely to have decreased. In addition, levels of vitamin D and Se are also found to have declined in farmed fish in the past decade. Significant changes in the EPA and DHA, vitamin D and Se content of farmed fish means that average intakes of these nutrients in Western populations are probably lower than before. This may have consequences for the health-giving properties of fish as well as future dietary recommendations for fish intake.


A new algorithm for computational image analysis of deformable motion at high spatial and temporal resolution applied to root growth. Roughly uniform elongation in the meristem and also, after an abrupt acceleration, in the elongation zone.
A requirement for understanding morphogenesis is being able to quantify expansion at the cellular scale. Here, we present new software (RootflowRT) for measuring the expansion profile of a growing root at high spatial and temporal resolution. The software implements an image processing algorithm using a novel combination of optical flow methods for deformable motion. The algorithm operates on a stack of nine images with a given time interval between each (usually 10 s) and quantifies velocity confidently at most pixels of the image. The root does not need to be marked. The software calculates components of motion parallel and perpendicular to the local tangent of the root's midline. A variation of the software has been developed that reports the overall root growth rate versus time. Using this software, we find that the growth zone of the root can be divided into two distinct regions, an apical region where the rate of motion, i.e. velocity, rises gradually with position and a subapical region where velocity rises steeply with position. In both zones, velocity increases almost linearly with position, and the transition between zones is abrupt. We observed this pattern for roots of Arabidopsis, tomato (Lycopersicon lycopersicum), lettuce (Lactuca sativa), alyssum (Aurinia saxatilis), and timothy (Phleum pratense). These velocity profiles imply that relative elongation rate is regulated in a step-wise fashion, being low but roughly uniform within the meristem and then becoming high, but again roughly uniform, within the zone of elongation. The executable code for RootflowRT is available from the corresponding author on request.


Effects of β2-adrenergic receptor gene polymorphisms on ritodrine therapy in pregnant women with preterm labor: prospective follow-up study.
This study aimed to evaluate the effects of β2-adrenergic receptor (ADRB2) gene polymorphisms on ritodrine therapy outcomes in patients with preterm labor. Genotyping analysis of ADRB2 gene (rs1042713, rs1042714, rs1042717, rs1042718, and rs1042719) was performed on 137 patients with preterm labor. Survival analysis was conducted for the effects of SNPs on the median time to delivery as a primary outcome. The median time to delivery in the study patients was 349.3 h. Gestational age at admission and modified Bishop scores revealed significant effects on time to delivery (p<0.001). Among studied SNPs, rs1042717 and rs1042718 showed linkage disequilibrium in this population, and their effects on time to delivery were marginally significant (p<0.1). Patients with variant-homozygotes in the rs1042713 showed considerably shortened time to delivery compared to wild-allele carriers. The rs1042719 polymorphism significantly affected time to delivery in both univariate and multivariate analysis; the GC and CC carriers showed 64% decrease in time to delivery compared to the wild-type homozygote carriers. Based on the results, it was concluded that the gene polymorphisms of ADRB2 could affect ritodrine therapy in patients with preterm labor. However, given the single-center and the relatively small sample size, our hypothesis requires further independent validation using multi-center and large sample size.


Generation of accelerating Airy and accelerating parabolic beams using phase-only patterns.
We generate both accelerated Airy and accelerated parabolic beams using phase-only patterns encoded onto a liquid crystal display (LCD). The usual system length is 2f, where f is the focal length of the Fourier transform lens. We develop a compact optical system having a total system length of f. However, the mask must now incorporate the Fresnel diffraction that is not provided by the reduced optical system length. Finally we incorporate the Fourier transform lens onto the mask. We obtain excellent experimental results with a phase-only pattern and a shorter optical system. This approach makes these beams much easier to implement.


Clinical applications of restriction endonuclease analysis.
These are exciting times in human genetics. Recombinant DNA technology has enabled investigators to sequence human genes so that the structure and organization of some genes is now known. These observations led to studies of "natural mutations," such as the hemoglobinopathies and thalassemias. This information in turn provided insight so that many mutations affecting the alpha- or beta-globin genes can now be detected prenatally. It seems probable that these techniques will be applicable to many other human genetic diseases. In the future, however, the greatest impact of these advances may be through their applications to produce proteins, such as hormones and vaccines, which can be used to treat deficient patients.


Effect of aqueous extract of Crocus sativus L. (saffron) stigma against subacute effect of diazinon on specific biomarkers in rats.
In this study, the effect of aqueous extract of Crocus sativus L. (saffron) stigma was studied against subacute toxicity of diazinon (DZN) on specific biochemical markers in rats. Vitamin E (200 IU/kg) and the aqueous extract of saffron at doses 50, 100 and 200 mg/kg were injected intraperitoneally three times per week alone or with DZN (20 mg/kg/day, orally) for 4 weeks. Red blood cell (RBC) cholinesterase activity was inhibited by DZN and this effect was not affected by vitamin E or saffron plus DZN. The levels of serum tumor necrosis factor-α (inflammation marker), direct 8-iso-prostaglandin F(2α) (oxidative stress marker) and soluble protein-100 β (S100β, neuronal damage marker) were increased significantly by DZN. The saffron extract inhibited the effect of DZN on these biomarkers levels. However, vitamin E was able to only reduce 8-iso-prostaglandin F(2α) and S100β levels. This study showed that the aqueous extract of saffron prevents DZN-induced rise of several specific inflammation, oxidative stress and neuronal damage biomarkers.


JMJD1C-mediated metabolic dysregulation contributes to HOXA9-dependent leukemogenesis.
Abnormal metabolism is a fundamental hallmark of cancer and represents a therapeutic opportunity, yet its regulation by oncogenes remains poorly understood. Here, we uncover that JMJD1C, a jumonji C (JmjC)-containing H3K9 demethylase, is a critical regulator of aberrant metabolic processes in homeobox A9 (HOXA9)-dependent acute myeloid leukemia (AML). JMJD1C overexpression increases in vivo cell proliferation and tumorigenicity through demethylase-independent upregulation of a glycolytic and oxidative program, which sustains leukemic cell bioenergetics and contributes to an aggressive AML phenotype in vivo. Targeting JMJD1C-mediated metabolism via pharmacologic inhibition of glycolysis and oxidative phosphorylation led to ATP depletion, induced necrosis/apoptosis and decreased tumor growth in vivo in leukemias co-expressing JMJD1C and HOXA9. The anti-metabolic therapy effectively diminished AML stem/progenitor cells and reduced tumor burden in a primary AML patient-derived xenograft. Our data establish a direct link between drug responses and endogenous expression of JMJD1C and HOXA9 in human AML cell line- and patient-derived xenografts. These findings demonstrate a previously unappreciated role for JMJD1C in counteracting adverse metabolic changes and retaining the metabolic integrity during tumorigenesis, which can be exploited therapeutically.


Recommendations for Reopening Endoscopy Units in Turkey: A Set-up Plan from a Tertiary Center in Istanbul.
In the midst of Coronavirus-19 (COVID-19) pandemic, endoscopic procedures have been separated for only urgent and semi-urgent cases for the last few months to prevent transmission in endoscopy units. This approach will perhaps resolve the burden of elective procedures in the months ahead of us. As we observe a downtrend in new cases of COVID-19 in Turkey, a strategy for reopening endoscopy units is required. We are stepping into a time period where we should not only re-provide the essential services to our patients but also maintain the safety of healthcare workers and preserve the valuable personal protective equipment as well. Herein, we aim to share the available knowledge in performing endoscopy during the pandemic and the set-up plan of a tertiary center in Istanbul for reopening the endoscopy unit in the era of the COVID-19 pandemic.


Once upon a time ... how west discovered east.
One of the most critical advances in modern burns care stemmed from the realisation that morbidity and mortality were significantly reduced if the burn tissue was surgically removed and the resulting surgical wound was closed with autologous skin grafts. This observation derived from the pioneering work of Zora Janzekovic who introduced the burns world to the practice of tangential excision. Working in the most challenging of circumstances in 1960, behind the then 'Iron Curtain' Zora Janzekovic began to explore and develop the role of early tangential burn wound excision. This paper is a personal account of this revolutionary era of burns care. It was presented by Zora Janzekovic herself at the 10th Workshop of the European Club for Paediatric Burns held in Graz, Austria, in the autumn of 2007.


Functional characterizations of effector protein BipC, a type III secretion system protein, in Burkholderia pseudomallei pathogenesis.
The bsa locus of Burkholderia pseudomallei encodes several proteins that are components of the type III secretion system (TTSS). BipC was postulated as one of the TTSS-3 effector proteins, but its role in the pathogenesis of B. pseudomallei infection is not well understood. Thus, the aim of this study was to determine its role(s) in the virulence of B. pseudomallei pathogenesis. A bipC TTSS-3-deficient strain of B. pseudomallei and complemented strains were generated to assess the role of BipC as a type III translocation apparatus. Human cell lines and a mouse model of melioidosis were used for in vitro and in vivo assays, respectively. A significant 2-fold reduction was demonstrated in the percentage of adherence, invasion, intracellular survival, and phagosomal escape of the bipC mutant. Interestingly, microscopic studies have shown that BipC was capable of delayed B. pseudomallei actin-based motility. The virulence of the mutant strain in a murine model of melioidosis demonstrated that the bipC mutant was less virulent, compared with the wild type. The results suggested that BipC possesses virulence determinants that play significant roles in host cell invasion and immune evasion.


Evaluation of limit feeding corn and distillers dried grains with solubles in non-feed-withdrawal molt programs for laying hens.
An experiment was conducted using 504 Hy-Line W-36 Single Comb White Leghorn hens (69 wk of age) randomly assigned to 1 of 7 treatments. These treatments consisted of a 47% corn:47% soy hulls diet (C:SH) fed ad libitum; a 94% corn diet fed at a rate of 36.3, 45.4, or 54.5 g/hen per day (CORN 36, CORN 45, and CORN 54, respectively); and a 94% corn distillers dried grains with solubles (DDGS) diet fed at the same rates as the previous corn diets (DDGS 36, DDGS 45, and DDGS 54, respectively) during the molt period of 28 d. The intent was to feed the DDGS diets for 28 d; however, all hens on these diets had very low feed intakes and greater than anticipated BW loss. Thus, they were switched to a 16% CP corn-soybean meal layer diet on d 19 of the molt period. At d 28, hens on all treatments were fed the same corn-soybean meal layer diet for 39 wk (73 to 112 wk of age). All DDGS diets and the CORN 36 diet resulted in total cessation of egg production during the molt period and egg production of hens fed the CORN 45, CORN 54, and C:SH diets had decreased to 3 and 4%, respectively, by d 28. Body weight loss during the 28-d molt period ranged from 14% for the CORN 54 diet to approximately 23% for the 3 DDGS diets. Postmolt egg production (5 to 43 wk) was higher for hens fed the DDGS molt diets than those fed the corn diets. There were no consistent differences in egg mass, egg-specific gravity, feed efficiency, or layer feed consumption among molt treatments for the postmolt period. These results indicate that limit feeding corn diet and DDGS diet in non-feed-withdrawal molt programs will yield long-term postmolt performance that is comparable to that observed by ad libitum feeding a C:SH diet.


Improving physician-patient communication about cancer pain with a tailored education-coaching intervention.
This study examined the effect of a theoretically grounded, tailored education-coaching intervention to help patients more effectively discuss their pain-related questions, concerns, and preferences with physicians. Grounded in social-cognitive and communication theory, a tailored education-coaching (TEC) intervention was developed to help patients learn pain management and communication skills. In a RCT, 148 cancer patients agreed to have their consultations audio-recorded and were assigned to the intervention or a control group. The recordings were used to code for patients' questions, acts of assertiveness, and expressed concerns and to rate the quality of physicians' communication. Patients in the TEC group discussed their pain concerns more than did patients in the control group. More active patients also had more baseline pain and interacted with physicians using participatory decision-making. Ratings of physicians' information about pain were higher when patients talked more about their pain concerns. The study demonstrates the efficacy of a theoretically grounded, coaching intervention to help cancer patients talk about pain control. Coaching interventions can be effective resources for helping cancer patients communicate about their pain concerns if they are theoretically grounded, can be integrated within clinical routines, and lead to improve health outcomes.


A biomechanical comparison of lateral and posterior approaches to sacroplasty.
Biomechanical cadaveric bench study. To measure the augmentation effect and extravasation risk of posterior and lateral approaches to sacroplasty. The biomechanical stabilizing effect of sacroplasty is unknown. Using a sacral insufficiency fracture model, we performed sacroplasty in 15 osteoporotic cadaveric pelves. Five served as controls, and 10 were each injected with 4 mL of a polymethylmethacrylate cement (5 via a posterior approach, 5 via a lateral approach). Cement extravasation was assessed using computed tomography. Restored strength and stiffness were defined as the ratios of treatment to initial strength and to stiffness, respectively. Between-group differences in restoration parameters were checked for significance (P < 0.05) using an analysis of variance followed by Tukey's test. We found no significant differences between groups in terms of restored strength ( approximately 61%) and stiffness ( approximately 77%). Both injection methods produced extravasation into the anterior sacrum, the posterior sacrum, the sacroiliac joint, and the neural foramens. Sacroplasty with 4 mL of cement does not restore the strength or stiffness of the sacrum in a cadaveric model, regardless of the approach used.


A technique for repeated sampling of the blood of individual resting fish.
A dorsal cannulation technique is described. It has been employed for repeated blood sampling in unanaesthetized rainbow trout (Salmo gairdneri) kept singly in special receptacles described in the paper. The level of the studied haematological parameters (Haematocrit, Hb, glucose, lactate, K+, Na+, Ca2+) differed between fish kept in receptacles for 1 week and free-swimming fish, most probably owing to differences in the motility of the fish. The receptacle seems to minimize visual and handling disturbances, and permits both the standardization of experimental conditions and quick and easy sampling via the dorsal aorta cannula. The general variation in the blood parameter values was very small compared with the previously reported variation in such values for rainbow trout.


Tradeoff between Stem Hydraulic Efficiency and Mechanical Strength Affects Leaf-Stem Allometry in 28 Ficus Tree Species.
Leaf-stem allometry is an important spectrum that linked to biomass allocation and life history strategy in plants, although the determinants and evolutionary significance of leaf-stem allometry remain poorly understood. Leaf and stem architectures - including stem area/mass, petiole area/mass, lamina area/mass, leaf number, specific leaf area (LA), and mass-based leafing intensity (LI) - were measured on the current-year branches for 28 Ficus species growing in a common garden in SW China. The leaf anatomical traits, stem wood density (WD), and stem anatomical and mechanical properties of these species were also measured. We analyzed leaf-stem allometric relationships and their associations with stem hydraulic ad mechanical properties using species-level data and phylogenetically independent contrasts. We found isometric relationship between leaf lamina area/mass and stem area/mass, suggesting that the biomass allocation to leaf was independent to stem size. However, allometric relationship between LA/mass and petiole mass was found, indicating large leaves invest a higher fractional of biomass in petiole than small ones. LI, i.e., leaf numbers per unit of stem mass, was negatively related with leaf and stem size. Species with larger terminal branches tend to have larger vessels and theoretical hydraulic conductivity, but lower WD and mechanical strength. The size of leaf lamina, petiole, and stem was correlated positively with stem theoretical hydraulic conductivity, but negatively with stem WD and mechanical strength. Our results suggest that leaf-stem allometry in Ficus species was shaped by the trade-off between stem hydraulic efficiency and mechanical stability, supporting a functional interpretation of the relationship between leaf and stem dimensions.


Patterns of Tumor Vasculogenesis on a Chick Embryo Chorioallantoic Membrane In Vivo Model of Breast Cancer.
Understanding tumor vasculogenesis is a cornerstone for the inhibition of tumor progression. This study aimed to generate an in vivo breast cancer environment to analyze the patterns of tumor vasculogenesis. Human mesenchymal stem cells (hMSC) and breast cancer MCF-7 cells (MCF-7) were seeded onto a chorioallantoic membrane (CAM) and, after a 7-day incubation, we performed a morphological and immunohistochemical analysis of CAM. hMSC and MCF-7 activated vasculogenesis and hematopoiesis on CAM. They stimulated the development of cord/capillary-like structures (CLS), formed by endothelial-like cells and hematopoietic cells. CLS presented a polygonal pattern, evolving towards a clearly visible plexus. Immunohistochemically, CLS were CD105+/AC133+/Oct3/4+, and the intensity was weak-moderate in the endothelial-like cells (inconstant) and weak in the hematopoietic cells. Tumor and embryonic vasculogenesis share a common paradigm, while CD105, AC133, and Oct3/4 were found to play a role in establishing the vasculogenic and hematopoietic stage.


Structure and topographic distribution of oral denticles in elasmobranch fishes.
The placoid scales, or denticles, of the external epidermis of elasmobranchs are well known as a hard protective coat over the skin to reduce abrasion or as elements to reduce hydrodynamic drag. However, the structure and function of denticles within the oral cavity is uncertain. Using stereological and scanning electron microscopy, this study examines the structure and distribution of oral denticles in a range of elasmobranchs. Of the batoids analyzed, only members of the Rhinobatidae possessed oral denticles, with no denticles found in the members sampled in the Gymnuridae or Dasyatidae. In contrast, oral denticles were located in all the selachians examined, except for members of the Orectolobidae. Within the selachians, the denticles of the Carcharhinidae have a grooved surface and a central spine, which is angled toward the posterior of the mouth. These denticular adaptations are beneficial to reduce hydrodynamic drag, an advantage for these free-swimming species with ram ventilation. Alternatively, members of the Hemiscyllidae have broad bulbous denticles that often overlap, providing a hard surface to protect the epithelium from abrasion during the consumption of hard-bodied prey. The distribution and high number of oral denticles appears to spatially compromise the capacity for oral (taste) papillae to populate the oropharyngeal cavity but provides increased friction and grip on prey items as they are manipulated within the mouth.


Try Before You Buy: Are There Benefits to a Random Trial Period before Students Choose Their Collaborative Teams?
The cognitive and performance benefits of group work in undergraduate courses depend on understanding how to structure groups to promote communication and comfort while also promoting diversity and reducing conflict. The current study utilized social network analysis combined with self-reported survey data from 555 students in 155 groups to understand how students identified group members whom they wished to work with. Students' willingness to work with their peers was positively associated with behavioral traits pertaining to attention, participation, and preparedness in class. We tested whether preventing students from choosing their group members until completing a multiweek period of random assignment to different groups each week influenced group selection criteria, and we found little effect. Students continued to depend on demographic similarities such as gender and ethnicity when selecting groupmates and enforcing random interactions before the group formation did not influence group satisfaction and/or grades. Random interactions before group formation did influence the willingness of students to continue working with peers who were persistently poorly rated based on behavioral attributes and contribution to the group work. Thus, the effort of random assignment could be beneficial to identify struggling students and improve collaboration.


Preanesthesia medical evaluation for electroconvulsive therapy: a review of the literature.
Electroconvulsive therapy (ECT) is widely used for the treatment of psychiatric disorders, yet there is few published literature to guide the practitioner in the preprocedural evaluation of patients. Based on a review of the literature, we sought to develop a concise, algorithmic approach to be used when evaluating patients for ECT, including those with underlying conditions, such as cardiovascular and neurological disorders. The databases of Ovid MEDLINE, PubMed, the Web of Knowledge, and PsychINFO were searched from January 2000 through December 2011. All abstracts were reviewed for relevancy to preprocedural ECT evaluation, and full articles of selected abstracts were reviewed in full, along with bibliographies of each. Algorithms were then constructed using the clinical information obtained from the selected articles. Our review of the literature located 275 articles using the search criteria. After review, 38 articles were selected. A total of 167 articles were excluded because they did not pertain to medical comorbidities in patients undergoing ECT, and an additional 70 were excluded because they did not pertain to ECT. Bibliography review of the selected articles located an additional 10 articles. Although ECT is generally a safe and effective therapy, some patient subgroups, such as those with certain cardiac conditions or history of cerebrovascular disease, require additional evaluation or, rarely, postponement of ECT. Chronic medical conditions should be optimized before undergoing ECT. Most patient populations are able to undergo ECT safely and effectively.


Outcomes in type 1 diabetic pregnancies: a nationwide, population-based study.
The aim of this study was to compare pregnancy outcomes in type 1 diabetic pregnancies with the background population. This nationwide prospective multicenter study took place in eight Danish centers treating pregnant women with type 1 diabetes during 1993-1999. A total of 990 women with 1,218 pregnancies and delivery after 24 weeks (n=1,215) or early termination due to severe congenital malformations (n=3) were included. Data were collected prospectively by one to three caregivers in each center and reported to a central registry. The perinatal mortality rate was 3.1% in type 1 diabetic pregnancies compared with 0.75% in the background population (RR 4.1 [95% CI 2.9-5.6]), and the stillbirth rate was 2.1% compared with 0.45 (4.7 [3.2-7.0]). The congenital malformation rate was 5.0% in the study population and 2.8% (1.7 [1.3-2.2]) in the background population. Six of the perinatal deaths (16%) were related to congenital malformations. Only 34% of women performed daily home monitoring of blood glucose at conception, and 58% received preconceptional guidance. Pregnancies with serious adverse outcomes (perinatal death and/or congenital malformations) were characterized by higher HbA1c values before and during pregnancy and a lesser degree of maternal self-care and preconceptional guidance. Women who performed daily self-monitoring of blood glucose at any time during pregnancy had lower HbA1c values than women who did not measure their daily profile. Likewise, daily self-monitoring was associated with a reduction in serious adverse outcomes. The caesarean section rate was 55.9 and 12.6%, respectively, and the risk of preterm delivery was 41.7 and 6.0%, respectively. Type 1 diabetic pregnancies are still complicated by considerably higher rates of severe perinatal complications compared with the background population, and women with poor self-care are at the highest risk. Adequate glycemic control using daily glucose monitoring before and during pregnancy is a crucial step toward reaching the goals of the St. Vincent declaration.


The Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders: recruitment, assessment instruments, methods for the development of multicenter collaborative studies and preliminary results.
To describe the recruitment of patients, assessment instruments, implementation, methods and preliminary results of The Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders, which includes seven university sites. This cross-sectional study included a comprehensive clinical assessment including semi-structured interviews (sociodemographic data, medical and psychiatric history, disease course and comorbid psychiatric diagnoses), and instruments to assess obsessive-compulsive (Yale-Brown Obsessive-Compulsive Scale and Dimensional Yale-Brown Obsessive-Compulsive Scale), depressive (Beck Depression Inventory) and anxious (Beck Anxiety Inventory) symptoms, sensory phenomena (Universidade de São Paulo Sensory Phenomena Scale), insight (Brown Assessment Beliefs Scale), tics (Yale Global Tics Severity Scale) and quality of life (Medical Outcome Quality of Life Scale Short-form-36 and Social Assessment Scale). The raters' training consisted of watching at least five videotaped interviews and interviewing five patients with an expert researcher before interviewing patients alone. The reliability between all leaders for the most important instruments (Structured Clinical Interview for DSM-IV, Dimensional Yale-Brown Obsessive-Compulsive Scale, Universidade de São Paulo Sensory Phenomena Scale) was measured after six complete interviews. Inter-rater reliability was 96%. By March 2008, 630 obsessive-compulsive disorder patients had been systematically evaluated. Mean age (+/-SE) was 34.7 (+/-0.51), 56.3% were female, and 84.6% Caucasian. The most prevalent obsessive compulsive symptom dimensions were symmetry and contamination. The most common comorbidities were major depression, generalized anxiety and social anxiety disorder. The most common DSM-IV impulsive control disorder was skin picking. The sample was composed mainly by Caucasian individuals, unmarried, with some kind of occupational activity, mean age of 35 years, onset of obsessive-compulsive symptoms at 13 years of age, mild to moderate severity, mostly of symmetry, contamination/cleaning and comorbidity with depressive disorders. The Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders has established an important network for standardized collaborative clinical research in obsessive-compulsive disorder and may pave the way to similar projects aimed at integrating other research groups in Brazil and throughout the world.


Inferring pointwise diffusion properties of single trajectories with deep learning.
To characterize the mechanisms governing the diffusion of particles in biological scenarios, it is essential to accurately determine their diffusive properties. To do so, we propose a machine-learning method to characterize diffusion processes with time-dependent properties at the experimental time resolution. Our approach operates at the single-trajectory level predicting the properties of interest, such as the diffusion coefficient or the anomalous diffusion exponent, at every time step of the trajectory. In this way, changes in the diffusive properties occurring along the trajectory emerge naturally in the prediction and thus allow the characterization without any prior knowledge or assumption about the system. We first benchmark the method on synthetic trajectories simulated under several conditions. We show that our approach can successfully characterize both abrupt and continuous changes in the diffusion coefficient or the anomalous diffusion exponent. Finally, we leverage the method to analyze experiments of single-molecule diffusion of two membrane proteins in living cells: the pathogen-recognition receptor DC-SIGN and the integrin α5β1. The analysis allows us to characterize physical parameters and diffusive states with unprecedented accuracy, shedding new light on the underlying mechanisms.