SPARC-thrombospondin-2-double-null mice exhibit enhanced cutaneous wound healing and increased fibrovascular invasion of subcutaneous polyvinyl alcohol sponges.
Secreted protein acidic and rich in cysteine (SPARC) and thrombospondin-2 (TSP-2) are structurally unrelated matricellular proteins that have important roles in cell-extracellular matrix (ECM) interactions and tissue repair. SPARC-null mice exhibit accelerated wound closure, and TSP-2-null mice show an overall enhancement in wound healing. To assess potential compensation of one protein for the other, we examined cutaneous wound healing and fibrovascular invasion of subcutaneous sponges in SPARC-TSP-2 (ST) double-null and wild-type (WT) mice. Epidermal closure of cutaneous wounds was found to occur significantly faster in ST-double-null mice, compared with WT animals: histological analysis of dermal wound repair revealed significantly more mature phases of healing at 1, 4, 7, 10, and 14 days after wounding, and electron microscopy showed disrupted ECM at 14 days in these mice. ST-double-null dermal fibroblasts displayed accelerated migration, relative to WT fibroblasts, in a wounding assay in vitro, as well as enhanced contraction of native collagen gels. Zymography indicated that fibroblasts from ST-double-null mice also produced higher levels of matrix metalloproteinase (MMP)-2. These data are consistent with the increased fibrovascular invasion of subcutaneous sponge implants seen in the double-null mice. The generally accelerated wound healing of ST-double-null mice reflects that described for the single-null animals. Importantly, the absence of both proteins results in elevated MMP-2 levels. SPARC and TSP-2 therefore perform similar functions in the regulation of cutaneous wound healing, but fine-tuning with respect to ECM production and remodeling could account for the enhanced response seen in ST-double-null mice.


First Dark Matter Constraints from a SuperCDMS Single-Charge Sensitive Detector.
We present the first limits on inelastic electron-scattering dark matter and dark photon absorption using a prototype SuperCDMS detector having a charge resolution of 0.1 electron-hole pairs (CDMS HVeV, a 0.93 g CDMS high-voltage device). These electron-recoil limits significantly improve experimental constraints on dark matter particles with masses as low as 1 MeV/c^{2}. We demonstrate a sensitivity to dark photons competitive with other leading approaches but using substantially less exposure (0.49 g d). These results demonstrate the scientific potential of phonon-mediated semiconductor detectors that are sensitive to single electronic excitations.


The first report of a putative "entomoparasitic adult form" in Bursaphelenchus.
A putative "entomoparasitic adult form" of Bursaphelenchus luxuriosae was found in the tracheal system and body cavity of its cerambycid vector beetle, Acalolepta luxuriosa. Morphologically, this form is intermediate between the usual mycophagous adult and the phoretic dauer juvenile, i.e., it shares the primary and secondary reproductive features with the mycophagous phase but shares a degenerate digestive tract with JIV dauer juveniles. In addition, the "parasitic form" has specialized characters relative to the mycophagous phase analogous to dicyclic Hexatylina, e.g., vacuole-like dots (assumed to be sensory organs) at the anterior end, a very long vulval flap, conical female tail, and elongated male spicules. The presence of insect-parasitic juveniles has been reported in several Bursaphelenchus species, but this is the first confirmed report of a putative "entomoparasitic adult form" in the genus. Thus, the "parasitic adult form" of B. luxuriosae is hypothesized to be an autapomorphic character of this species in the genus. The physiological impact of the parasitism on the host beetle is assumed to be weak because no clear symptoms were observed in the infested beetles. Also, no nematode eggs or propagative juveniles were observed in the beetle host, suggesting that more research is needed to confirm the nature of the association (parasitic vs. endophoretic).


[Aortic coarctation. Indications and results of surgical treatment. 16 years of experience].
Eighty-nine patients were treated surgically for coarctation of the aorta in a period of 16 years. In 79, the operative procedure consisted of excision of the coarcted segment and primary anastomosis; in 7 cases of hypoplastic arch and in 3 of aneurysm of the aorta, some form of aortoplasty utilizing the isthmus and the subclavian artery, or the use of a dacron prosthesis were required. In a group of 33 patients under 2 years, 76% had associated cardiac anomalies and 100% heart failure, which made immediate surgical treatment mandatory with a mortality of 42% and a recoarctation rate of 10.5%. Out of 56 cases over 2 years, 46% had other cardiac malformations; however, a less severe clinical conditions allowed for an elective operation, with a mortality of 1.8% and a recoarctation rate of 1.8%. This experience and the review of the literature support the concept of elective surgical treatment for coarctation of the aorta around the age of 4 years, prior to the occurrence of hypertension or its complications. In the neonate and infant, surgery is justified in the presence of heart failure non-responsive to medical treatment within 24 to 48 hours. A deeper understanding of the pathophysiology of the malformation in the very young and a better perioperative management of neonates, have led to a decline in mortality in recent years.


Innovative Approaches Address Aging and Mental Health Needs in LGBTQ Communities.
LGBTQ older adults have higher levels of psychological distress as compared to older adults in general. They also experience multiple barriers to accessing equitable, culturally competent mental health and aging services because of their distinct histories and particular social contexts. This article discusses this lack of access to services, and highlights an innovative way mental health services are being delivered in LGBTQ communities.


Molecular biology of gelsolin, a calcium-regulated actin filament severing protein.
Gelsolin is a Ca2+-binding protein of mammalian leukocytes, platelets and other cells which has multiple and closely regulated powerful effects on actin. In the presence of micromolar Ca2+, gelsolin severs actin filaments, causing profound changes in the consistency of actin polymer networks. A variant of gelsolin containing a 25-amino acid extension at the NH2-terminus is present in plasma where it may be involved in the clearance of actin filaments released during tissue damage. Gelsolin has two sites which bind actin cooperatively. These sites have been localized using proteolytic cleavage and monoclonal antibody mapping techniques. The NH2-terminal half of the molecule contains a Ca2+-insensitive actin severing domain while the COOH-terminal half contains a Ca2+-sensitive actin binding domain which does not sever filaments. These data suggest that the NH2-terminal severing domain in intact gelsolin is influenced by the Ca2+-regulated COOH-terminal half of the molecule. The primary structure of gelsolin, deduced from human plasma gelsolin cDNA clones, supports the existence of actin binding domains and suggests that these may have arisen from a gene duplication event, and diverged subsequently to adopt their respective unique functions. The plasma and cytoplasmic forms of gelsolin are encoded by a single gene, and preliminary results indicate that separate mRNAs code for the two forms. Further application of molecular biological techniques will allow exploration into the structural basis for the multifunctionality of gelsolin, as well as the molecular basis for the genesis of the cytoplasmic and secreted forms of gelsolin.


Matrix metalloproteinases and endometriosis.
Retrograde menstruation represents a plausible explanation for the development of most cases of endometriosis; nevertheless, additional factors must contribute to the development of disease in only 10 to 20% of women. The discriminating factor(s) in determining the development of active endometriosis probably involves a complex array of potentially interactive influences including steroid exposure, immunological disturbances, genetic predisposition, and, perhaps, environmental toxin exposure. Matrix metalloproteinases (MMPs), enzymes that mediate normal tissue turnover including endometrial breakdown at menstruation, appear to be involved in the invasive establishment of the disease. In addition, several MMPs appear to be inappropriately expressed in the endometrium of women with this disease in association with a reduced sensitivity to progesterone. Altered regulation of endometrial MMP expression in response to steroids may represent a mechanism linking the invasive potential of refluxed endometrium to the establishment of this disease only in certain women.


A comparison between the Present State Examination and the Composite International Diagnostic Interview.
Item-by-item interrater agreement, CATEGO syndrome and class agreement, and agreement for Index of Definition were compared for the Present State Examination (PSE) and for the PSE items included in the Composite International Diagnostic Interview. Both interviews were given to 30 subjects representing a wide range of diagnoses, including hospitalized psychotic patients and outpatients with milder neurotic symptoms. Although agreement over individual questions was disappointing, when broader issues, such as syndrome classification, diagnostic class, and severity, were considered, agreement between interviews attained statistical significance.


Adoption of infection prevention and control practices by healthcare workers in Québec: A qualitative study.
To describe barriers and facilitators to the adoption of recommended infection prevention and control (IPC) practices among healthcare workers (HCWs). A qualitative research design was used. Individual semistructured interviews with HCWs and observations of clinical practices were conducted from February to May 2018 in 8 care units of 2 large tertiary-care hospitals in Montreal (Québec, Canada). We interviewed 13 managers, 4 nurses, 2 physicians, 3 housekeepers, and 2 medical laboratory technologists. We conducted 7 observations by following IPC nurses (n = 3), nurses (n = 2), or patient attendants (n = 2) in their work routines. Barriers to IPC adoption were related to the context of care, workplace environment issues, and communication issues. The main facilitator of the IPC adoption by HCWs was the "development of an IPC culture or safety culture." The "IPC culture" relied upon leadership support by managers committed to IPC, shared belief in the importance of IPC measures to limit healthcare-associated infections (HAIs), collaboration and good communication among staff, as well as proactivity and ownership of IPC measures (ie, development of local solutions to reduce HAIs and "working together" toward common goals). Adoption of recommended IPC measures by HCWs is strongly influenced by the "IPC culture." The IPC culture was not uniform within hospital and differences in IPC culture were identified between care units.


Evolutionary history of the land snail Helix aspersa in the Western Mediterranean: preliminary results inferred from mitochondrial DNA sequences.
Intraspecific phylogeographic methods provide a means of examining the history of genetic exchange among populations. As part of a study of the history of Helix aspersa in the Western Mediterranean, we performed a phylogenetic analysis based on partial sequences of the mitochondrial large ribosomal subunit (16S) gene. Our samples include 31 H. a. aspersa populations from North Africa previously investigated for anatomical and biochemical characters. To clarify subspecific relationships, three individuals of the subspecies H. a. maxima were also studied. The molecular phylogeny inferred agrees largely with previous results, in splitting H. a. aspersa haplotypes into an eastern and a western group. H. a. maxima haplotypes form a third lineage arising before the H. a. aspersa groups. Divergence times estimated between the lineages suggest that dispersal during Pleistocene glaciation and vicariance events due to Pliocene geological changes in the western Mediterranean may both have played a significant part in the establishment of the present range of H. aspersa.


Is ultraviolet light disinfection fit to be the future standard for the disinfection of flexible endoscopes without a working channel?
To investigate colony-forming unit (CFU) reduction on contaminated flexible endoscopes (FEs) without a working channel after UV-C light disinfection, compared to the current disinfection method with the endoscope washer disinfector (EWD). After pharyngolaryngoscopy, a manual pre-cleaning with tap water was performed. A culture was then collected by rolling the distal 8-10 cm of the FE over an Agar plate. The FE was disinfected using the D60 (60-s disinfection process with UV-C light) or the EWD (gold standard reprocessing process with water and chemicals). Another culture was then taken. After incubation, a CFU count was performed. A total of 200 FEs without a working channel were divided equally between the two disinfection groups. After clinical use and manual pre-cleaning, 84 of the 100 (84.0%) (UV-C light group) and 79 of the 100 (79.0%) (EWD) FEs were contaminated with at least 1 CFU. FEs that showed no contamination after use were excluded from further analysis. After disinfection with UV-C light, 72 (85.7%) FEs showed no contamination (i.e., 0 CFUs) versus 66 (83.5%) FEs after reprocessing with the EWD. There is no difference in CFUs reduction on contaminated FEs without a working channel between UV-C light disinfection and the current gold standard, the EWD.


The structure of mononuclear phagocytes differentiating in vivo. I. Sequential fine and histologic studies of the effect of Bacillus Calmette-Guerin (BCG).
Although the differentiation of mononuclear phagocytes is fundamental to their multifarious activities, their differentiation is incompletely understood-particularly in vivo. The development of an epithelioid granuloma may be hypothesized to represent such differentiation in vivo. To test this, the sequential ultrastructure of developing epithelioid granulomas was examined. Viable bacilli Calmette-Guerin (BCG) injected into the subcutaneum of guinea pigs produced epithelioid granulomatous inflammation, which was sampled for light and electron microscopy on alternate days until the 33rd day after injection. Initially, monocytes invaded the tissues and then coalesced, enlarged and formed small granulomas which ultimately evolved into epithelioid granulomas. The monocytes, ultrastructurally very simple cells, developed increased nuclear euchromatin, prominent nucleoli, extensive cytoplasm, free ribosomes, abundant Golgi profiles, many mitochondria and numerous large lysosomes and became macrophages. The macrophages in turn underwent further enlargement and became closely intertwined with one another to form epithelioid cells-large polygonal macrophages, containing euchromatic nuclei, numerous lysosomes, plentiful mitochondria and prominent synthetic apparatus. These changes undergone by monocytes during their development into epithelioid cells, which may be divided into five stages, are interpreted as differentiation in vivo of the mononuclear phagocytes. The observations demonstrate directly the differentiation of these cells in vivo and suggest some, if not all, characteristic features of granulomatous inflammation result from such differentiation.


Decay accelerating factor (CD55)-mediated attenuation of complement: therapeutic implications for age-related macular degeneration.
Sequence variations in complement proteins are associated with age-related macular degeneration (AMD). The terminal pathway of complement results in the formation of the membrane attack complex (MAC) on the cell surface, resulting in their lysis. MAC has been documented on the retinal pigment epithelium (RPE), choroidal blood vessels, and drusen of AMD eyes. Here the investigators test the hypothesis that increasing the expression of decay accelerating factor (CD55) on RPE cells may result in reduced MAC-mediated damage. The investigators constructed a recombinant adenovirus expressing human CD55 (AdCAGCD55). Mouse hepatocytes were infected with AdCAGCD55 or negative controls and subsequently incubated with normal human serum (NHS). Cell lysis and MAC formation were measured by FACS and immunocytochemistry, respectively. Adult mice were injected in the subretinal space with either AdCAGCD55 or controls; after 1 week of CD55 transgene expression, the eyecups were excised, challenged with NHS, and quantified for human MAC formation. Control-infected or uninfected mouse hepatocytes lyse at a rate of 93% and 94%, respectively. AdCAGCD55- infected mouse hepatocytes lyse at a rate of 29%. Lysis was confirmed to occur in the presence of MAC, which was reduced by 67% when cells were infected by AdCAGCD55. Mice injected in the subretinal space with AdCAGCD55 exhibited a 55.7% reduction in MAC formation on the RPE relative to controls. Adenovirus-mediated delivery of hCD55 to murine RPE confers protection against human complement. The investigators propose that the expression of hCD55 on RPE cells warrants investigation as a potential therapy for AMD.


Implementation of an accelerated physical examination course in a doctor of pharmacy program.
To describe the implementation of a 1-day accelerated physical examination course for a doctor of pharmacy program and to evaluate pharmacy students' knowledge, attitudes, and confidence in performing physical examination. Using a flipped teaching approach, course coordinators collaborated with a physician faculty member to design and develop the objectives of the course. Knowledge, attitude, and confidence survey questions were administered before and after the practical laboratory. Following the practical laboratory, knowledge improved by 8.3% (p<0.0001). Students' perceived ability and confidence to perform a physical examination significantly improved (p<0.0001). A majority of students responded that reviewing the training video (81.3%) and reading material (67.4%) prior to the practical laboratory was helpful in learning the physical examination. An accelerated physical examination course using a flipped teaching approach was successful in improving students' knowledge of, attitudes about, and confidence in using physical examination skills in pharmacy practice.


[Morphogenesis and clinical anatomy of the petrotympanic and petrosquamosal fissure].
Petrotympanic and petrosquamosal fissures are located in the temporal bone, in a complex area of the base of the skull, closely related to the evolutionary development of mammals. However, until now we do not have a comprehensive descriptions about how the formation of these fissures were formed. Recent researches have allowed us to determine the factors involved in their development, and consequently how the closure of the middle takes place and its separation of the temporomandibular joint. The mechanisms and structures involved in their morphogenesis determine the variability and anatomoclinical implications.


[Prostatic abscess: report of a case].
To report one case of prostatic abscess which required emergency surgical treatment because of its aggressive evolution. We describe the case of a 61-year-old male patient who was diagnosed of prostatic abscess in the emergency room, and initially underwent conservative treatment with antibiotics and urinary diversion. Due to clinical impairment to septicemia and upper urinary tract involvement we decided to perform a surgical perineal drainage. The septic clinical picture resolved immediately, but he presented a prostatic-perineal fistula in the intermediate postoperative period which resolved with prolonged urinary diversion by cystotomy catheter. HIV serologies were performed considering the aggressiveness of picture; they were positive. We emphasize this case because of the great aggressiveness that presented, possibly due to factors such as diabetes and immunosuppression (HIV). Provided the great variety of presentations of this disease, a high degree of suspicion must be exercised for its diagnosis, and once the diagnosis is got immediate treatment is recommended. We review etiopathogenic factors, clinical findings, diagnosis and therapeutic options.


The melanocyte differentiation program predisposes to metastasis after neoplastic transformation.
The aggressive clinical behavior of melanoma suggests that the developmental origins of melanocytes in the neural crest might be relevant to their metastatic propensity. Here we show that primary human melanocytes, transformed using a specific set of introduced genes, form melanomas that frequently metastasize to multiple secondary sites, whereas human fibroblasts and epithelial cells transformed using an identical set of genes generate primary tumors that rarely do so. Notably, these melanomas have a metastasis spectrum similar to that observed in humans with melanoma. These observations indicate that part of the metastatic proclivity of melanoma is attributable to lineage-specific factors expressed in melanocytes and not in other cell types analyzed. Analysis of microarray data from human nevi shows that the expression pattern of Slug, a master regulator of neural crest cell specification and migration, correlates with those of other genes that are important for neural crest cell migrations during development. Moreover, Slug is required for the metastasis of the transformed melanoma cells. These findings indicate that melanocyte-specific factors present before neoplastic transformation can have a pivotal role in governing melanoma progression.


[Comment on article: "Laboratories as predictors of length of hospital stay in patients with pneumonia"].
Laboratory studies are a useful tool for both diagnosis and prognosis of pathologies, especially in the emergency room. In the article they seek to establish an association between laboratory studies and hospital stay in patients with community-acquired pneumonia. Some suggestions are made to improve the structured review of the article.


Superrepellent Doubly Reentrant Geometry Promotes Antibiofouling and Prevention of Coronavirus Contamination.
The fomite transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has drawn attention because of its highly contagious nature. Therefore, surfaces that can prevent coronavirus contamination are an urgent and unmet need during the coronavirus disease 2019 (COVID-19) pandemic. Conventional surfaces are usually based on superhydrophobic or antiviral coatings. However, these coatings may be dysfunctional because of biofouling, which is the undesired adhesion of biomolecules. A superhydrophobic surface independent of the material content and coating agents may serve the purpose of antibiofouling and preventing viral transmission. Doubly reentrant topology (DRT) is a unique structure that can meet the need. This study demonstrates that the DRT surfaces possess a striking antibiofouling effect that can prevent viral contamination. This effect still exists even if the DRT surface is made of a hydrophilic material such as silicon oxide and copper. To the best of our knowledge, this work first demonstrates that fomite transmission of viruses may be prevented by minimizing the contact area between pathogens and surfaces even made of hydrophilic materials. Furthermore, the DRT geometry per se features excellent antibiofouling ability, which may shed light on the applications of pathogen elimination in alleviating the COVID-19 pandemic.


Economic aspects of quality assurance.
The subject for the Nicholas Research Award 1983 was prompted by the author's earlier involvement in quality assurance and her realization that there was a need to investigate the economic aspects of the subject. In a comparative study, the paper shows that the running costs of a basic quality assurance programme are probably less than 1% of the overall running costs of an 'average' five roomed X-ray department. Future professional implications associated with quality assurance are also discussed.


Effects of roughage source, amount, and particle size on behavior and gastrointestinal health of veal calves.
The European Union 1997 Directive, stipulating that veal calves should be fed a minimum of 50 to 250 g of fibrous feed from 8 to 20 wk of age, is vague. A fibrous feed ration maximum of 250 g has been implicated in welfare issues, namely the occurrence of abnormal oral behaviors and poor gastrointestinal health. Past research suggests that this amount is insufficient to prevent the development of abnormal oral behaviors and enabling good rumen development. Different sources and particle sizes of roughage could lead to very different welfare outcomes. In a 3×2 × 2 factorial design, 240 group-housed calves (10±1 d; 46.1±0.1 kg) were fed different roughage sources (straw, maize silage, or maize cob silage; the latter 2 were dried and provided no extra moisture compared with straw) in 2 amounts (250 or 500 g of dry matter per day), and 2 particle sizes (chopped or ground). Roughage was supplemented to milk replacer (MR) from 2 wk after arrival. In addition, 60 calves were fed 1 of 3 additional control treatments: MR only (n=20), MR plus an iron supplement (n=20), or MR plus ad libitum hay (n=20). Oral behaviors were recorded using instantaneous scan sampling at 2-min intervals for 2 h in 3 periods per day, at 12 and 22 wk of age. Calves were slaughtered at 24 wk of age and rumen and abomasal health parameters were recorded. Limited provision of straw resulted in behavior comparable with that from unlimited provision of hay, with reduced tongue playing and oral manipulation of the environment, as well as increased chewing compared with diets with no roughage supplement. Straw prevented ruminal hairballs, but impaired rumen development and increased abomasal damage. A higher ration of roughage increased chewing (12 wk), decreased oral manipulation of the trough (12 and 22 wk) and the pen (22 wk), and increased rumen weight. However, more roughage led to increased abomasal damage for certain parameters. Longer feed particles had no obvious benefits for behavior, but decreased hairball prevalence. Overall, unlimited hay had the highest benefit for both behavior and gastrointestinal health. Adding iron to the MR did not alter behavior or gastrointestinal health compared with MR without iron supplement. This study demonstrated that different roughage sources, amounts, and particle sizes have different effects on veal calf behavior and gastrointestinal health, and hence on veal calf welfare.


Nucleic acid metabolism of placenta and fetus.
The preceding résumé of placental nucleic acid metabolism indicates considerable changes in RNA and DNA during the course of pregnancy in both human and animal experiments. The presence of an active protein-synthesizing apparatus closely allied with DNA and RNA metabolism has been observed in placental preparations; future studies should reveal even more direct relationships. The specific regulatory role of nucleic acids in normal and abnormal placental function is still unknown. In truth, such specific regulatory or control mechanisms are generally unproved among the entire mammalian (eukaryotype) system. Progress in learning about placental function and control may require more detailed information regarding RNA metabolism from molecular biology. The regulatory control of fetal or intrauterine growth as it relates to nucleic acids remains even more obscure. One of the major drawbacks in this study has been our inability to label fetal tissues adequately during the major portion of the pregnancy. The problem is made even more complex by the many factors involved in intrauterine growth, such as blood volume, uterine blood supply, oxygen flow and transfer, hormonal effects, and nutritional status, in addition to nucleic acids.


Genetic network inference: the effects of preprocessing.
Clustering of gene expression data and gene network inference from such data has been a major research topic in recent years. In clustering, pairwise measurements are performed when calculating the distance matrix upon which the clustering is based. Pairwise measurements can also be used for gene network inference, by deriving potential interactions above a certain correlation or distance threshold. Our experiments show how interaction networks derived by this simple approach exhibit low-but significant-sensitivity and specificity. We also explore the effects that normalization and prefiltering have on the results of methods for identifying interactions from expression data. Before derivation of interactions or clustering, preprocessing is often performed by applying normalization to rescale the expression profiles and prefiltering where genes that do not appear to contribute to regulation are removed. In this paper, different ways of normalizing in combination with different distance measurements are tested on both unfiltered and prefiltered data, different prefiltering criteria are considered.


Anatomic Location of Tissue Expander Placement Is Not Associated With Delay in Adjuvant Therapy in Women With Breast Cancer.
Tissue expanders in breast reconstruction are traditionally placed retropectoral. Increasingly, patients are undergoing prepectoral placement. The impact of this placement on the initiation of adjuvant treatment is unknown. A retrospective review was conducted to identify women diagnosed with breast cancer who underwent mastectomy followed by radiation and/or chemotherapy. Women were divided into 3 groups: prepectoral tissue expander placement, retropectoral tissue expander placement, and no immediate reconstruction. A treatment delay was defined as greater than 8 weeks between tissue expander placement and adjuvant therapy. Of 634 women, 205 (32%) underwent tissue expander placement, and 429 (68%) did not have immediate reconstruction. Of those with tissue expanders placed, 84 (41%) had prepectoral placement, and 121 (59%) had retropectoral placement. The median time to adjuvant therapy was 49 days for the entire cohort: no reconstruction, 47 days; prepectoral, 57 days; and retropectoral, 55 days. Treatment delays were observed in 34% of women: no reconstruction, 28%; prepectoral, 51%; and retropectoral, 46% ( P < 0.001). Tissue expander placement was associated with a delay to adjuvant therapy when compared with no reconstruction ( P < 0.001). The location of the tissue expander did not impact the odds of having a delay. On multivariable analysis, having reconstruction, having postoperative infection, not undergoing chemotherapy treatment, and being a current smoker were associated with a delay to adjuvant therapy. A delay to treatment was not associated with worse survival. Placement of a tissue expander delayed adjuvant therapy. The location of tissue expander placement, retropectoral versus prepectoral, did not impact the time to adjuvant treatment.


Suppression of immunological response against a novel gene product delivered by implants of genetically modified fibroblasts.
We have recently demonstrated the feasibility of genetically modifying autologous primary rat fibroblasts to deliver in vivo a foreign gene product, human growth hormone. However, in this model for gene replacement therapy, all recipient animals developed extremely high titres of antibodies against human growth hormone within two weeks of grafting. We now report on two approaches to suppress this immune-response. First, rats implanted with human growth hormone-secreting rat fibroblasts were treated with an immunosuppressant, cyclosporine A, at 20 mg/kg body weight per day. The production of anti-human growth hormone antibodies in the treated animals was completely blocked during the 12-week course of treatment. Secondly, by using immunologically immature neonatal rats as recipients, the rapid antibody response to the human growth hormone was also avoided. However, after a delay of one month, these rats also developed an extremely high titre of antibodies against the human growth hormone. In comparison, rats in the adolescent, mature and aged groups developed and maintained high titres of antibodies soon after implantation. Therefore, antigenic response against novel gene products can be suppressed either totally by cyclosporine A or temporarily in neonatal animals. The combination of early implantation and subsequent immuno-suppression should be considered in somatic gene therapy for those patients who are negative for cross-reacting-material and may be expected to mount an antigenic response to the replacement gene product.


Pathogens and other symbionts of the Amphipoda: taxonomic diversity and pathological significance.
With over 10000 species of Amphipoda currently described, this order is one of the most diverse groups of freshwater and marine Crustacea. Members of this group are globally distributed, and many are keystone species and ecosystem engineers within their respective ecologies. As with most organisms, disease is a key factor that can alter population size, behaviour, survival, invasion potential and physiology of amphipod hosts. This review explores symbiont diversity and pathology in amphipods by coalescing a range of current and historical literature to provide the first full review of our understanding of amphipod disease. The review is broken into 2 parts. The first half explores amphipod microparasites, which include data pertaining to viruses, bacteria, fungi, oomycetes, microsporidians, dinoflagellates, myxozoans, ascetosporeans, mesomycetozoeans, apicomplexans and ciliophorans. The second half reports the metazoan macroparasites of Amphipoda, including rotifers, trematodes, acanthocephalans, nematodes, cestodes and parasitic Crustacea. In all cases we have endeavoured to provide a complete list of known species that cause disease in amphipods, while also exploring the effects of parasitism. Although our understanding of disease in amphipods requires greater research efforts to better define taxonomic diversity and host effects of amphipod symbionts, research to date has made huge progress in cataloguing and experimentally determining the effects of disease upon amphipods. For the future, we suggest a greater focus on developing model systems that use readily available amphipods and diseases, which can be comparable to the diseases in other Crustacea that are endangered, economically important or difficult to house.


Neighborhood contextual factors and early-starting antisocial pathways.
This paper examines research investigating the effects of neighborhood context on the onset and persistence of early-starting antisocial pathways across middle and late childhood. The review begins by presenting theory and research mapping the early-starting developmental pathway. Next, sociologically and psychologically based investigations linking neighborhood context and early antisocial behavior are examined, in order to posit and evaluate the effects of community economic disadvantage, exposure to neighborhood violence, and involvement with neighborhood-based deviant peer groups on the development of antisocial behavior. It is suggested that middle childhood may represent a critical developmental period during which children are at heightened risk for neighborhood-based effects on antisocial behavior problems. Key methodological issues are addressed, and recommendations for future research integrating developmental pathways and neighborhood theory and research are advanced.


Uracil-DNA glycosylase inhibitor of bacteriophage PBS2: cloning and effects of expression of the inhibitor gene in Escherichia coli.
The uracil-DNA glycosylase inhibitor gene of bacteriophage PBS2 was cloned, and the effects of this inhibitor on Escherichia coli cells that contain uracil-DNA glycosylase activity were determined. A PBS2 genomic library was constructed by inserting EcoRI restriction fragments of PBS2 DNA into a plasmid pUC19 vector. The library was used to transform wild-type (ung+) E. coli, and the presence of the functional inhibitor gene was determined by screening for colonies that supported growth of M13mp19 phage containing uracil-DNA. A clone was identified that carried a 4.1-kilobase EcoRI DNA insert in the vector plasmid. Extracts of cells transformed with this recombinant plasmid lacked detectable uracil-DNA glycosylase activity and contained a protein that inhibited the activity of purified E. coli uracil-DNA glycosylase in vitro. The uracil-DNA glycosylase inhibitor expressed in these E. coli was partially purified and characterized as a heat-stable protein with a native molecular weight of about 18,000. Hence, we conclude that the PBS2 uracil-DNA glycosylase inhibitor gene was cloned and that the gene product has properties similar to those from PBS2-infected Bacillus subtilis cells. Inhibitor gene expression in E. coli resulted in (i) a weak mutator phenotype, (ii) a growth rate similar to that of E. coli containing pUC19 alone, (iii) a sensitivity to the antifolate drug aminopterin similar to that of cells lacking the inhibitor gene, and (iv) an increased resistance to the lethal effects of 5-fluoro-2'-deoxyuridine. These physiological properties are consistent with the phenotypes of other ung mutants.


The National Center for Biomedical Ontology.
The National Center for Biomedical Ontology is now in its seventh year. The goals of this National Center for Biomedical Computing are to: create and maintain a repository of biomedical ontologies and terminologies; build tools and web services to enable the use of ontologies and terminologies in clinical and translational research; educate their trainees and the scientific community broadly about biomedical ontology and ontology-based technology and best practices; and collaborate with a variety of groups who develop and use ontologies and terminologies in biomedicine. The centerpiece of the National Center for Biomedical Ontology is a web-based resource known as BioPortal. BioPortal makes available for research in computationally useful forms more than 270 of the world's biomedical ontologies and terminologies, and supports a wide range of web services that enable investigators to use the ontologies to annotate and retrieve data, to generate value sets and special-purpose lexicons, and to perform advanced analytics on a wide range of biomedical data.


Effects of isosorbide-5-mononitrate and isosorbide-2-mononitrate on isolated dog aorta: vascular relaxation and increase in cyclic GMP.
The effects of isosorbide-5-mononitrate (IS-5-MN) and isosorbide-2-mononitrate (IS-2-MN) on vascular smooth muscle tone and on cyclic nucleotide levels were studied in isolated dog aorta. The effects of the mononitrates were compared with that of the relatively well-studied vasorelaxing agent sodium nitroprusside (NP). The substances induced concentration-dependent relaxation of the aortic rings contracted with noradrenaline. The potency order was: NP greater than IS-2-MN greater than IS-5-MN. IS-5-MN and IS-2-MN did not cause significant changes in the cAMP levels in dog aortic preparations. In sharp contrast, definite rises in the cGMP levels were observed in dog aortic rings after treatment with the mononitrates. With respect to both phenomena, IS-2-MN proved to have a stronger effect compared to IS-5-MN. These data support the hypothesis that an increase in cGMP is responsible for the relaxation of vascular smooth muscle by organic nitrates.


Cisapride acts on muscarinic (glandular M2) receptors to induce contraction of isolated gastric myocytes: mediation via a calcium-phosphoinositide pathway.
The effects of cisapride on guinea pig gastric smooth muscle were characterized. Cisapride induced concentration-dependent contraction of isolated myocytes with an EC50 of 10(-11) M, which was antagonized in concentration-dependent fashion by atropine. 4-Diphenylacetoxy-N-methylpiperidine-methiodide (4-DAMP) (10(-6) M), a selective M2 glandular receptor antagonist, inhibited contraction to cisapride (10(-10) M), whereas pirenzepine, an M1 receptor antagonist, had no effect. For comparison, carbachol induced contraction with an EC50 of 5 x 10(-11) M, which was also atropine-sensitive. Cisapride-induced contraction was not blocked by methysergide (10(-6) M), a nonselective serotonin antagonist. Cisapride displaced specific binding of [3H]N-methylscopolamine at a single receptor population with a Ki of 6.51 x 10(-5) M and a Bmax of 351.0 fmol/mg protein. Cisapride (10(-6) M) evoked a 73.8 +/- 7.6% increase in inositol 1,4,5-trisphosphate at 30 sec and a maximal increase of greater than 130% at 2 min, which was significantly reduced by atropine (10(-6) M). In contrast, cisapride did not enhance or inhibit basal levels of cyclic AMP. Thus, cisapride induces contraction via specific interaction at smooth muscle M2 glandular muscarinic receptors, which is associated with inositol trisphosphate generation, but not adenylyl cyclase activation.


The quorum-hindered transcription factor YenR of Yersinia enterocolitica inhibits pheromone production and promotes motility via a small non-coding RNA.
The YenR and YenI proteins of Yersinia enterocolitica resemble the quorum sensing proteins LuxR and LuxI of Vibrio fischeri. Apo-YenR activated a gene, designated yenS, that lies adjacent to and divergent from yenR. YenR-dependent expression of yenS was inhibited by endogenous or exogenous 3-oxohexanoylhomoserine lactone (OHHL) a pheromone made by YenI. Purified apo-YenR bound non-cooperatively to two 20-nucleotide sites that lie upstream of yenS. Binding occurred in the absence of (OHHL), and YenR was largely released from the DNA by this pheromone. yenS encoded two non-translated RNAs 169 and 105 nucleotides long that share the same 5' end but have different 3' ends. One or both RNAs inhibited the translation and accumulation of the yenI mRNA by binding to a region that overlaps the YenI start codon. A mutation in yenI strongly stimulated swarming motility on the surface of semi-solid agar, while exogenous OHHL completely suppressed this phenotype. Hypermotility in yenI mutants was also suppressed by mutations in yenR or yenS, suggesting that YenS plays a direct, stimulatory role in swarming motility.


Pneumomediastinum and soft tissue emphysema in pediatric hanging.
Postmortem computed tomography (CT) is increasingly being used as a tool in forensic pathology. The exact value of postmortem imaging in detecting specific conditions has not yet been established, but in specific cases, it can be used as a diagnostic tool demonstrating findings that remain undetected during autopsy, as in this case. Pneumomediastinum and soft tissue emphysema were detected with postmortem CT in a 3-year-old girl after hanging. It was not found during autopsy. This radiological finding matches 3 adult cases previously described. It is assumed that in this case, the first reported in a child, hanging was the most likely cause as well. In the adult cases, it was interpreted as a vital sign; the person must have been alive to create a pressure gradient causing rupture of the alveoli. This case demonstrates one of the added values of postmortem imaging, the possibility of demonstrating findings that remain undetected during autopsy.


Interval breast cancers in a community screening programme: frequency, radiological classification and prognostic factors.
The frequency of interval cancers (IC) can be an indicator inversely related to the quality of a breast screening programme. The objectives were to estimate the frequency of IC, to classify IC by posterior radiological review, and to describe the prognostic factors of these IC. The setting was the Sabadell-Cerdanyola Breast Cancer Screening Programme, in Northeast Spain. We developed a population-based study of the IC occurring in the first three rounds (1995-2001). The indicators used were the incidence rate of invasive IC per 10 000 women screened and the proportional incidence, stratified by age group, type of screening and the round, and the time elapsed since the last screening mammogram. A radiological informed consensus review was used to classify the IC. No specific pattern of incidence rates was evident with respect to age, type of screening, or round, although screening was generally more sensitive in women aged 60-69 years. The proportional incidence for the period 0-11 months was always under 30%. Twenty-one percent of 38 IC evaluated (95% CI: 8.0-34.0) were attributed to errors in the screening process (false negatives). No major differences in the prognostic factors of the 57 IC were identified on examining the radiological type or the time since the last screening mammogram. We observed a high frequency of IC from 12 months after screening. It is necessary to reach a consensus regarding the definition and the analysis of IC and to establish mechanisms that would allow all the malignant tumours diagnosed in the target population to be identified.


Antimicrobial properties of enzymatically triggered self-assembling aromatic peptide amphiphiles.
The combination of catalysis and self-assembly influences many key processes in living systems. Synthetic analogues of such systems may provide opportunities to direct biological processes. Previously, it has been demonstrated that enzyme triggered assembly of peptide derivatives can influence bacterial cell death by intracellular fibre formation. In this article, we discuss the self-assembly of 9-fluorenylmethyloxycarbonyl (Fmoc) protected dipeptide amphiphiles, FY, YT, YS, YN and YQ, designing phosphorylated precursors to be alkaline phosphatase responsive. We use microscopy techniques, fluorescence and FTIR to demonstrate differences in molecular assembly and nanoscale architecture in vitro- indicating fibre formation of FY, YT, YS and YN, and spherical self-assembled structures of YQ. As the enzyme is naturally occurring in E. coli, we manipulate conditions to over-express the enzyme and demonstrate the conversion of precursors to self-assembling aromatic peptide amphiphiles in vivo. Furthermore, we test whether antimicrobial activity can be differentially controlled by the introduction of varying aromatic peptide amphiphiles, with the results indicating a similar antimicrobial response for each treatment.


Insulin secretion in adult rats after intrauterine exposure to mild hyperglycemia during late gestation.
We investigated the effects of intrauterine mild hyperglycemia during late fetal life on glucose regulation and insulin secretion in adult rats. Unrestrained pregnant rats were continuously infused with glucose during the last week of pregnancy to induce mild hyperglycemia (6.5-8 mM). Control rats were infused with a glucose-free solution. The offspring were studied, as adults, from 1 to 20 mo by performing glucose tolerance and insulin secretion tests. Young-adult rats from hyperglycemic dams showed mild glucose intolerance and impairment of glucose-induced insulin secretion. This situation gradually evolved to basal hyperglycemia and severe impairment of glucose tolerance and insulin secretion. Insulin secretion was also studied in vitro in 20-mo-old rats with the isolated perfused-pancreas technique. Insulin release in response to glucose stimulation from pancreases of hyperglycemic dams was similar to that of controls, and the response to arginine was increased but not significantly. The possible involvement of enhanced sympathetic nervous system activity in the impairment of insulin secretion in adult rats from hyperglycemic mothers was then investigated by performing glucose tolerance and insulin secretion tests in the presence of the alpha 2-blocker idazoxan in 8-mo-old rats. Under these conditions, rats from hyperglycemic dams recovered almost normal glucose tolerance, and glucose-induced insulin secretion was greatly improved. These data show that mild hyperglycemia induced in the fetus during late pregnancy leads to persistent impairment of glucose regulation and insulin secretion. They suggest that the impairment of insulin secretion in vivo results from a perturbation of the neuroregulation of insulin secretion rather than an intrinsic pancreatic beta-cell defect.


Increased behavioral economic demand and craving for alcohol following a laboratory alcohol challenge.
Although increases in subjective alcohol craving have been observed following moderate doses of alcohol (e.g. priming effects), the effects of alcohol consumption on behavioral economic demand for alcohol are largely unstudied. This study examined the effects of alcohol intoxication on alcohol demand and craving. A between-subjects design in which participants were randomly assigned to either an alcohol (n = 31), placebo (n = 29) or control (n = 25) condition. A laboratory setting at the University of Missouri, USA. Eighty-five young adult moderate drinkers were recruited from the University of Missouri and surrounding community. Change in demand for alcohol across time was measured using three single items: alcohol consumption at no cost (i.e. intensity), maximum price paid for a single drink (i.e. breakpoint) and total amount spent on alcohol (i.e. Omax). Alcohol demand at baseline was also assessed using an alcohol purchase task (APT). Craving was assessed using a single visual analog scale item. In the alcohol group compared with the combined non-alcohol groups, intensity, breakpoint and craving increased from baseline to the ascending limb and decreased thereafter (Ps < 0.05; Omax , P = 0.06). Change in craving following alcohol consumption was significantly associated with change in each of the demand indices (Ps < 0.0001). Finally, the demand single items were associated with corresponding indices from the APT (Ps < 0.05). Alcohol demand increases following intoxication, in terms of both the maximum amount people are willing to pay for one drink and the number of drinks people would consume if drinks were free. Behavioral economic measures of alcohol value can complement subjective craving as measures of moment-to-moment fluctuations in drinking motivation following intoxication.


Choroid plexus, aging of the brain, and Alzheimer's disease.
Choroid plexus tissues are intraventricular structures composed of villi covered by a single layer of ciliated, cuboid epithelium. The plexuses secrete cerebrospinal fluid (CSF), synthesize numerous molecules, carry nutrients from the blood to CSF, reabsorb brain metabolism by-products and participate in brain immunosurveillance. During ageing, atrophy of epithelium occurs along with thickening of basement membranes. Enzymatic activities of epithelial cells decrease significantly. CSF secretion decreases as much as 50%. These modifications are concurrent with subnormal brain activity. In Alzheimer's disease, epithelial atrophy, thickening of basement membrane and stroma fibrosis are even more prominent. Ig and C1q deposition along the basement membrane can be frequently detected, suggesting immunological processes. Synthesis, secretory, and transportation functions are significantly altered resulting in decreased CSF turnover, reduced beta-amyloid clearance, and increased glycation phenomena as well as oxidative stress. Such modifications may favour fibrillary transformation of beta-amyloid protein and tau protein polymerisation.


Differentially expressed genes in response to gamma-irradiation during the vegetative stage in Arabidopsis thaliana.
Biochemical and physiological processes in plants are affected by gamma-irradiation, which causes significant changes in gene transcripts and expression. To identify the differentially expressed Arabidopsis genes in response to gamma-irradiation, we performed a microarray analysis with rosette leaves during the vegetative stage. Arabidopsis plants were exposed to a wide spectrum doses of gamma ray (100, 200, 300, 400, 800, 1200, 1600 or 2000 Gy) for 24 h. At the dose range from 100 to 400 Gy, irradiated plants were found to be shorter than controls after 8 days of irradiation, while doses over 800 Gy caused severe growth retardation. Therefore, 100 and 800 Gy were selected as adequate doses for microarray analysis to identify differentially expressed genes. Among the 20,993 genes used as microarray probes, a total number of 496 and 1,042 genes were up-regulated and down-regulated by gamma-irradiation, respectively (P < 0.05). We identified the characteristics of the genes that were up-and down-regulated fourfold higher genes by gamma irradiation according to The arabidopsis information resource gene ontology. To confirm the microarray results, we performed a northern blot and quantitative real-time PCR with several selected genes that had a large difference in expression after irradiation. In particular, genes associated with lipid transfer proteins, histones and transposons were down-regulated by 100 and/or 800 Gy of gamma irradiation. The expression patterns of selected genes were generally in agreement with the microarray results, although there were quantitative differences in the expression levels.


[Involvement and Handling of Paramedics in Unplanned Out-of-Hospital Births: An Online Survey].
Unplanned out-of-hospital births are very rare in the ambulance service and there is evidence that emergency paramedics do not feel comfortable with this operational picture. At the same time, there is an increased of morbidity and mortality for both the mother and the newborn. The aims of the present cross-sectional study were to identify insecurities of emergency paramedics in connection with unplanned out-of-hospital births, to analyse the reasons for this and to derive possible support measures to be implemented. This study is a quantitative cross-sectional study examining management of unplanned out-of-hospital births by paramedics using a self-designed questionnaire. 65 participants took part in the online survey during the period from April 6, 2022 to April 30, 2022. SPSS was used for statistical data analysis. The central tendency of various influencing variables was examined with the help of the Mann-Whitney U test, the significance level was α<0.05. On average, preparation Median (IQR): 2.0 (1.0) and safety with the measures to be performed 3.0 (01.0), as well as knowledge about unplanned out-of-hospital births 2.0 (1.0) were rated moderately well. The participating paramedics had particular difficulties with the documentation of the birth process 3.0 (1.0). There was a great deal of respect for out-of-hospital birth attendance among participants 1.0 (1.0). Participation in an interdisciplinary simulation session appeared to have had a positive influence on the handling and preparation for safety in the measures to be taken (p=0.016). Insecurites as well as possible reasons for them could be identified. Possible suggestions for improvement for emergency paramedics in unplanned out-of-hospital births were developed. For example, specific birth protocols and participation in a simulation are good ways to help.


Randomized controlled pilot study of B cell-targeted induction therapy in HLA sensitized kidney transplant recipients.
Optimal induction regimens for patients at high risk for antibody and/or cell-mediated rejection have not been established. This pilot, prospective, randomized study evaluated addition of B cell/plasma cell-targeting agents to T cell-based induction with rabbit antithymocyte globulin (rATG) in high immunologic risk renal transplant recipients. Patients were randomized to induction with rATG, rATG + rituximab, rATG + bortezomib or rATG + rituximab + bortezomib. Inclusion criteria were: (1) current cytotoxic panel reactive antibody (PRA) ≥20% or peak cytotoxic PRA ≥50% or (2) T or B cell positive flow crossmatch with donor-specific antibody (DSA) or (3) historical positive serologic or cytotoxic crossmatch or DSA to donor or (4) prior allograft loss with more than one acute rejection. Median overall follow-up was 496 days: 1-year and overall acute rejection were 25% and 27.5%, and 25% of patients developed de novo DSA within 1 year. One-year and overall patient survival were 97.5% and 92.5%, and 1-year and overall death-censored allograft survival were 97.5% and 95%. Renal allograft function posttransplant was similar among all arms. Eight of nine cases of peripheral neuropathy were mild, whereas one case was moderate and required a narcotic prescription. In conclusion, addition of rituximab and/or bortezomib to rATG induction has an acceptable safety/toxicity profile in a high immunologic risk renal transplant population.


Electronic and magnetic structures of coronene-based graphitic nanoribbons.
We study the electronic properties of a series of coronene-derived graphitic nanoribbons recently synthesized in a pre-programmed, nanotube assisted, chemical route [Talyzin et al. Nano Lett., 2011, 11, 4352 and Fujihara et al. J. Phys. Chem. C, 2012, 116, 15141]. We employ a combination of density functional theory and spin-polarized tight-binding methods to show how details of the molecular building blocks and their assembly uniquely determine the electronic structure of the resulting ribbon. We demonstrate the onset of multiple magnetic states for these systems and a non-trivial dependence of the electronic bandgap with both atomic structure and spin configuration, which make these coronene-based ribbons potential candidates for applications in nanoelectronics.


Hospice Staff Perspectives on Caring for People with Dementia: A Multisite, Multistakeholder Study.
Background: In the United States, 45% of people enrolled in hospice have dementia. We know little about how hospice professionals facilitate preference-aligned end-of-life care for people with dementia (PWD) and their families. Objective: To examine hospice stakeholders' perspectives on caring for PWD and their families. Design: Multisite qualitative study using semi-structured interviews with interdisciplinary hospice clinicians, leaders, and administrators. The interdisciplinary team used the constant comparative method to identify, code, and characterize relevant themes. Setting/participants: Four geographically distinct nonprofit U.S. hospice organizations. Fifty-one hospice employees: 61% clinical staff, 25% executive leaders, and 14% administrators. Measurements: Interview domains included participants' practices of engaging patients/families in discussions of preferences for end-of-life care and professional opinions of changes over time. Cross-topic probes focused on delivering hospice care to PWD and their proxies/families. Results: Four themes regarding caring for PWD in hospice. (1) Dementia prevalence in hospice is increasing and some hospices are developing programs to accommodate specific needs. (2) Setting impacts discussions of preferences and care decisions. (3) Caring for PWD on hospice poses unique challenges caused by (i) perceptions that dementia is not terminal, (ii) a lack of advance care planning discussions before hospice admission, and (iii) proxy decision-makers who were inadequately prepared for their role. (4) Hospice regulatory and policy changes disproportionately impact PWD. Conclusions: Hospice professionals perceive increasing demand for, and multilevel challenges to, caring for PWD. Clinicians "upstream" from hospice may help by engaging patients and proxies in discussions of preferences for end-of-life care and providing anticipatory guidance.


Migraine Progression: A Systematic Review.
Migraine is a common and often debilitating neurological disease. It can be divided into episodic and chronic subforms based on the number of monthly headache days. Because only a subset of individuals with episodic migraine (EM) progress to chronic migraine (CM) over any given time period, understanding the factors that predict the new onset of CM or "migraine progression" may provide insights into the mechanisms, pathophysiology, prevention, and treatment of CM. In this review, we identify and summarize studies that report risk factors associated with the new onset of CM or related chronic headache diagnoses, group these risk factors and report the strength of evidence for the identified risk factors. To conduct a systematic review of studies that identify risk factors for the new onset of CM or related chronic headache diagnoses such as transformed migraine (TM) and chronic daily headache (CDH). Herein we summarize the findings of studies of risk factors associated with the new onset of CM/TM, CDH, or related diagnoses from the English language literature published before March 2018. The PubMed database was searched for relevant studies. Longitudinal studies with follow-up data and case-control studies were included in this qualitative synthesis. We report methodology, analytic criteria, and results for each manuscript and for the parent study. Next, we review the strength of evidence for each of the identified risk factors using a modified version of AB Hill's criteria for causation and rank evidence as fair, moderate, or strong. We categorized risk factors as nonmodifiable, modifiable and based on putative mechanisms. We further categorized risk factors into sociodemographics, lifestyle factors and habits, headache features, comorbid and concomitant diseases and conditions and pharmacologic treatment-related. Finally, we review theories of the pathophysiology underlying the development of new onset chronic migraine or increasing attack frequency. The PubMed search yielded 1870 records after duplicates were removed. Nine additional records were identified through expert consultation and other methods (eg, citations found as references in manuscripts identified in the literature review and through communication with the authors of manuscripts included in the review). The 1879 manuscripts were screened against the inclusion and exclusion criteria and 109 were found to be potentially eligible. Of 109 full-text articles, 17 studies were identified as meeting the prespecified criteria based on the consensus of all authors. Of the 17 full texts, 13 were longitudinal cohort studies and 4 were case-controlled studies. We found strength of evidence ranging from fair to strong for the identified risk factors. The strongest data were found for increased headache day frequency, depression, and medication overuse/high-frequency use. Risk factors for new onset CM and CDH in children and adolescents were similar to those identified in adults. A range of risk factors for the new onset of CM/TM, CDH, or related chronic headache diseases were identified with the strongest data supporting increased headache day frequency, acute medication overuse/high-frequency use and depression, which are potentially modifiable risk factors. Modifiable risk factors may provide targets for intervention. The lack of strong evidence or any evidence does not imply that there is not a relationship between a particular risk factor and new onset CM or related disease; but may indicate little or no research or that research did not have sufficient methodological rigor. In addition, it is likely that additional risk factors exist which have not yet been identified. Putative factors include pro-inflammatory states and pro-thrombotic states. Development of central sensitization and increased activation of the trigeminal nociceptive pathways may be drivers of the new onset of CM or CDH. Future research may include the systematic testing of interventions targeting modifiable risk factors to determine if progression can be prevented as well as continued exploration of the benefits of treating these risk factors among people with CM in an effort to increase rates of remission. Future work should also consider the natural fluctuations in headache day frequency and examine progression in terms of continuous definitions rather than or in addition to a dichotomous boundary.


Effects of α-blocker 'add on' treatment on blood pressure in symptomatic BPH with or without concomitant hypertension.
We investigated the effects of 'add on' treatment of α-blocker (AB) on blood pressure (BP) and the safety of ABs in men with symptomatic BPH with or without hypertension. We retrospectively reviewed 2,924 BPH outpatients who took ABs at our institution between 2005 and 2009. BPH symptom severity, prostate volume and BP were determined for 953 patients with their baseline data. BP level and International Prostate Symptom Score were measured within 2 months after AB treatment. Patients were assigned to four groups: group 1 had 272 normotensive patients on concomitant hypertensive medication; group 2 had 293 normotensive patients not on the medication; group 3 had 216 hypertensive patients on concomitant medication; and group 4 had 172 hypertensive patients not on the medication. The addition of AB lowered the mean systolic BP by 16.6 mm Hg for group 3 and by 8.6 mm Hg for group 4, and diastolic BP by 18.0 mm Hg for group 3 (P<0.05). However, normotensive groups on entry, irrespective of antihypertensive medication, showed no significant BP changes from baseline after AB medication. In the hypertensive groups on entry, the doxazosin gastrointestinal therapeutic system (GITS) resulted in significant reductions in systolic BP from 142.2 to 134.9 mm Hg and in diastolic BP from 97.6 to 84.6 mm Hg. When analyzed by AB regimen, the incidence of BP-related adverse events was comparable. AB therapy for BPH can have an appropriate and beneficial effect on BP, especially in baseline hypertensive patients. Doxazosin GITS treatment resulted in optimal management of BP within the normal range, especially in pharmacologically or physiologically hypertensive patients.


Estimation of the brain and spinal cord conduction time in man by means of the somatosensory evoked potentials and F and H responses.
Somatosensory evoked potential (SSEP) recordings from the scalp were performed in 17 healthy subjects. In seven of these SSEP was also recorded at the level of the second lumbar spine. In the other ten F and H responses and the corresponding M responses were studied. By means of the SSEP recordings at the level of the second lumbar spine and the F- and H-responses, the conduction time in the brain and spinal cord, that is central latency, was calculated and the following results were obtained: 16.0 ms with standard deviation (SD) +/- 1.1 ms (by means of SSEPs), 9.5 +/- 2.4 ms (by means of F response) and 13.1 +/- 1.5 ms (by means of H response). Of the three methods used the H response method seems to be the best for clinical purposes: it is easy to perform and statistically it is more stable than the F response recording; moreover the recording can be performed reliably even in persons with thick back muscles and subcutaneous fat, unlike the evoked potential procedure which only with difficulty shows detectable responses at the lumbosacral levels in such persons. Three patients are presented to illustrate the technique; in one of these the recording evoked potentials from the epidural space were recorded.


Induction of cytotoxic factors by immunization of mice with Freund's adjuvant components.
Antiidiotypic antibody (AIA) was raised in mice by immunization with MOPC 315 immunoglobulin A emulsified in Freund's adjuvant (FA). The antibody content of mouse serum was assessed by (a) its ability to inhibit rosetting of 2,4,6-trinitro-phenyl-sheep red blood cells around MOPC 315 myeloma cells, and (b) by a solid phase antigen-binding plate assay based on reactivity with 125I-Protein A and inhibition in the presence of dinitrophenyl aminocaproic acid. FA was necessary for the production of AIA to MOPC 315 immunoglobulin A. Some of the AIA-containing mouse sera were cytotoxic for MOPC 315 cells in the presence of guinea pig complement. However, cytotoxicity was not correlated with amount of AIA, as assessed by inhibition of rosette formation, nor was it specific for myeloma cells bearing the MOPC 315 idiotype. Furthermore, cytotoxicity could also be generated by immunization of mice with complete Freund's adjuvant, incomplete Freund's adjuvant, or the muramyl dipeptide portion of mycobacteria, all in the absence of MOPC 315 immunoglobulin A. Therefore, the complement-dependent cytotoxic antibodies in the AIA-containing antisera, which belonged to the immunoglobulin G and M classes, were likely directed against some component of FA. Myeloma cells which were not killed by anti-FA antiserum, as assessed by dye exclusion, were inhibited in their ability to secrete immunoglobulin and to form clones in agar.


Tillage, cropping sequence, and nitrogen fertilization effects on dryland soil carbon dioxide emission and carbon content.
Management practices are needed to reduce dryland soil CO(2) emissions and to increase C sequestration. We evaluated the effects of tillage and cropping sequence combinations and N fertilization on dryland crop biomass (stems + leaves) and soil surface CO(2) flux and C content (0- to 120-cm depth) in a Williams loam from May to October, 2006 to 2008, in eastern Montana. Treatments were no-tilled continuous malt barley (Hordeum vulgaris L.) (NTCB), no-tilled malt barley-pea (Pisum sativum L.) (NTB-P), no-tilled malt barley-fallow (NTB-F), and conventional-tilled malt barley-fallow (CTB-F), each with 0 and 80 kg N ha(-1). Measurements were made both in Phase I (malt barley in NTCB, pea in NTB-P, and fallow in NTB-F and CTB-F) and Phase II (malt barley in all sequences) of each cropping sequence in every year. Crop biomass varied among years, was greater in the barley than in the pea phase of the NTB-P treatment, and greater in NTCB and NTB-P than in NTB-F and CTB-F in 2 out of 3 yr. Similarly, biomass was greater with 80 than with 0 kg N ha(-1) in 1 out of 3 yr. Soil CO(2) flux increased from 8 mg C m(-2) h(-1) in early May to 239 mg C m(-2) h(-1) in mid-June as temperature increased and then declined to 3 mg C m(-2) h(-1) in September-October. Fluxes peaked immediately following substantial precipitation (>10 mm), especially in NTCB and NTB-P. Cumulative CO(2) flux from May to October was greater in 2006 and 2007 than in 2008, greater in cropping than in fallow phases, and greater in NTCB than in NTB-F. Tillage did not influence crop biomass and CO(2) flux but N fertilization had a variable effect on the flux in 2008. Similarly, soil total C content was not influenced by treatments. Annual cropping increased CO(2) flux compared with crop-fallow probably by increasing crop residue returns to soils and root and rhizosphere respiration. Inclusion of peas in the rotation with malt barley in the no-till system, which have been known to reduce N fertilization rates and sustain malt barley yields, resulted in a CO(2) flux similar to that in the CTB-F sequence.


[Construction of replication-deficient recombinant adenoviral vector carrying HBsAg and HSP70 chimeric gene and its expression in vitro].
To construct a recombinant adenoviral vector carrying HBcAg-HSP70 chimeric gene by homologous recombination in bacteria and to detect its expression in vitro. Heat shock protein 70 gene from Mycobacterium tuberculosis were amplified by PCR and were cloned to adenoviral shuttle plasmid pAdTrack-CMV-HBsAg. Then the resultant pAdTrack-CMV-HBsAg-HSP70 was cotransfected into BJ5183 bacteria with the plasmid pAdeasy-1. The adenoviral plasmid carrying HBsAg-HSP70 gene (pAd-HBsAg-HSP70) was generated with homologous recombination in bacteria and the adenoviruses were produced in 293 cells. Several kinds of mammal cells (293 cells and Vero cells) were infected with adenoviruses and the expression of HBsAg-HSP70 was detected by RT-PCR and ELISA in vitro. The adenoviral plasmids pAd-HBsAg-HSP70 were obtained by selection for kanamycin resistance and confirmed by restriction endonuclease Pac analyses. The recombinant adenoviruses Ad-HBsAg-HSP70 were packaged successfully in 293 cells. The titer of Ad-HBsAg-HSP70 was up to 2 x 10(12) pfu/L after the second passage of proliferation in 293 cells. HBsAg and HSP70 were expressed efficiently in mammal cells after infection. The recombinant adenoviruses expressing HBsAg and HSP70 were constructed successfully which can be used further in study of gene therapy for HBV.


The Utility of Arterial Spin Labeling MRI in Medial Temporal Lobe as a Vascular Biomarker in Alzheimer's Disease Spectrum: A Systematic Review and Meta-Analysis.
We sought to systematically review and meta-analy the role of cerebral blood flow (CBF) in the medial temporal lobe (MTL) using arterial spin labeling magnetic resonance imaging (ASL-MRI) and compare this in patients with Alzheimer's disease (AD), individuals with mild cognitive impairment (MCI), and cognitively normal adults (CN). The prevalence of AD is increasing and leading to high healthcare costs. A potential biomarker that can identify people at risk of developing AD, whilst cognition is normal or only mildly affected, will enable risk-stratification and potential therapeutic interventions in the future. All studies investigated the role of CBF in the MTL and compared this among AD, MCI, and CN participants. A total of 26 studies were included in the systematic review and 11 in the meta-analysis. Three separate meta-analyses were conducted. Four studies compared CBF in the hippocampus of AD compared with the CN group and showed that AD participants had 2.8 mL/min/100 g lower perfusion compared with the CN group. Eight studies compared perfusion in the hippocampus of MCI vs. CN group, which showed no difference. Three studies compared perfusion in the MTL of MCI vs. CN participants and showed no statistically significant differences. CBF measured via ASL-MRI showed impairment in AD compared with the CN group in subregions of the MTL. CBF difference was significant in hippocampus between the AD and CN groups. However, MCI and CN group showed no significant difference in subregions of MTL.


Regulation of E2F Transcription Factor 3 by microRNA-152 Modulates Gastric Cancer Invasion and Metastasis.
The transcription factor, E2F transcription factor 3 (E2F3), has been proved to modulate metastasis in multiple human cancers. The present study was aimed to expound the function and specific mechanism of E2F3 in gastric cancer (GC) progression. The expression of E2F3, microRNA-152 (miR-152) and PLK1 (polo-like kinase 1) in GC cell lines was detected by quantitative RT-PCR and Western blot. The roles of E2F3 and miR-152 in GC metastasis were classified using gain-of-function and loss-of-function assays. The miRNAs directly targeting E2F3 were identified by bioinformatics analysis and luciferase reporter experiment. Chromatin immunoprecipitation was carried out to reveal the correlation between E2F3 and PLK1. E2F3 expression was frequently up-regulated in GC tissues, and its high expression might imply poor prognosis. Downregulation of E2F3 restrained GC migration and invasion in vitro and in vivo. Interestingly, we proved that miR-152 was an upstream regulator of E2F3. Moreover, miR-152 reduced E2F3 expression by directly targeting its 3'-UTR, and then modulated GC metastasis via polo-like kinase 1 (PLK1) mediated protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) signals. E2F3 plays a crucial role in GC progression and the newly discovered miR-152/E2F3/PLK1 axis provides a new underlying target for therapy of metastasis in GC patients.


Gut Microbiota in Alzheimer's Disease, Depression, and Type 2 Diabetes Mellitus: The Role of Oxidative Stress.
Gut microbiota consists of over 100 trillion microorganisms including at least 1000 different species of bacteria and is crucially involved in physiological and pathophysiological processes occurring in the host. An imbalanced gastrointestinal ecosystem (dysbiosis) seems to be a contributor to the development and maintenance of several diseases, such as Alzheimer's disease, depression, and type 2 diabetes mellitus. Interestingly, the three disorders are frequently associated as demonstrated by the high comorbidity rates. In this review, we introduce gut microbiota and its role in both normal and pathological processes; then, we discuss the importance of the gut-brain axis as well as the role of oxidative stress and inflammation as mediators of the pathological processes in which dysbiosis is involved. Specific sections pertain the role of the altered gut microbiota in the pathogenesis of Alzheimer's disease, depression, and type 2 diabetes mellitus. The therapeutic implications of microbiota manipulation are briefly discussed. Finally, a conclusion comments on the possible role of dysbiosis as a common pathogenetic contributor (via oxidative stress and inflammation) shared by the three disorders.


High-level expression in Escherichia coli of enzymatically active Harvey murine sarcoma virus p21ras protein.
The gene for the Harvey murine sarcoma virus (Ha-MuSV) p21ras protein was fused to the amino-terminal portion of the bacteriophage lambda cII gene on the expression vector pJL6. The fusion was such that transcription was controlled by the well-regulated phage lambda pL promoter, and translation initiated in the cII gene continued in frame into the ras gene sequences that code for p21. When the pL promoter was derepressed, the Escherichia coli cells harboring the fusion plasmid synthesized 23,000-dalton protein, which represented more than 10 percent of the total cellular protein. This protein was chimeric and contained 14 residues, which were specified by the vector; these residues were followed by all of the amino acids that make up Ha-MuSV p21ras except for four residues at the amino-terminal end. The protein appears similar to Ha-MuSV p21ras in that it undergoes immunoprecipitation by monoclonal antibodies directed toward that protein, binds guanosine diphosphate, and is capable of autophosphorylation.


Epigenetic repolarization of T lymphocytes from chronic lymphocytic leukemia patients using 5-aza-2'-deoxycytidine.
T cell immune dysfunction has an important role in the profound immune suppression that characterizes chronic lymphocytic leukemia (CLL). Improper polarization of T cells has been proposed as one of the mechanism involved. Mounting data implicates chromatin regulation, namely promoter methylation, in the plasticity of naïve human T cells. Recent in vitro evidence indicates that this plasticity may be phenotypically altered by using methylation inhibitors which are approved for clinical use in certain types of cancer. These results beg the question: can the ineffective polarization of T lymphocytes in the context of CLL be effectively modulated using methylation inhibitors in a sustainable therapeutic fashion? To answer this question our laboratory has studied the effects of 5-aza-2'-deoxycytidine (5A2) in helper and cytotoxic T lymphocytes from healthy donors and CLL patients in well characterized molecular and epigenetic signaling pathways involved in effective polarization. Moreover, we sought to investigate the consequences of methylation inhibitor treatment on lymphocyte survival, activation intensity, and naïve cell polarization. Our data indicates that 5A2 treatment can depolarize Th2 cells to effectively secrete interferon gamma, signal via T-bet, and achieve demethylation of critical Th1 specific promoters. Moreover, we demonstrate that 5A2 can force Th1 polarization of naïve T cells despite a strong IL-4 stimuli and a lack of IL-12. In conclusion our data seeks to define a modality in which improper or ineffective T cell polarization can be altered by 5AZA and could be incorporated in future therapeutic interventions.


Thrombolytic therapy for the treatment of prosthetic heart valve thrombosis in pregnancy with low-dose, slow infusion of tissue-type plasminogen activator.
Prosthetic valve thrombosis during pregnancy is life-threatening for mother and fetus, and the treatment of this complication is unclear. Cardiac surgery in pregnancy is associated with very high maternal and fetal mortality and morbidity. Thrombolytic therapy has rarely been used in these patients. The aim of this study is to evaluate the safety and efficacy of low-dose (25 mg), slow infusion (6 hours) of tissue-type plasminogen activator for the treatment of prosthetic valve thrombosis in pregnant women. Between 2004 and 2012, tissue-type plasminogen activator was administered to 24 consecutive women in 25 pregnancies with 28 prosthetic valve thrombosis episodes (obstructive, n=15; nonobstructive, n=13). Mean age of the patients was 29±6 years. Thrombolytic therapy sessions were performed under transesophageal echocardiography guidance. The mean dose of tissue-type plasminogen activator used was 48.7±29.5 mg (range, 25-100 mg). All episodes resulted in complete thrombus lysis after thrombolytic therapy. One patient had placental hemorrhage with preterm live birth at the 30th week, and 1 patient had minor bleeding. Low-dose, slow infusion of tissue-type plasminogen activator with repeated doses as needed is an effective therapy with an excellent thrombolytic success rate for the treatment of prosthetic valve thrombosis in pregnant women. This protocol also seems to be safer than cardiac surgery or any alternative medical strategies published to date. Thrombolytic therapy should be considered first-line therapy in pregnant patients with prosthetic valve thrombosis.


Hepatic drug metabolizing enzyme activity and tumorigenesis in mice following perinatal exposure to benzo(a)pyrene.
It is known that in utero exposure to polycyclic aromatic hydrocarbon carcinogens (PAH) results in a high incidence of pulmonary and other tumors in the offspring, usually after a long latency period. The present study tested the hypothesis that perinatal exposure to benzo(a)pyrene (BP) produces alterations in microsomal mixed-function oxidase (MFO) activity that modify the response to postnatal challenge with a PAH in such a way as to render the offspring to be more susceptible to tumorigenesis, and to determine whether the gestational age at which BP exposure occurred was a determinant of the proposed alterations. Swiss mice were treated with BP on day 3, 8, 10, 12, 14, or 18 of gestation. Subgroups from each gestational-age treatment group and appropriate controls were studied for enzyme activity or were challenged with 3-methylcholanthrene (3-MC) when three months old. Female offspring of BP-treated mice had significantly elevated hepatic microsomal aminopyrine demethylase activity; cytochrome P-450 concentrations were significantly lower in male offspring. The most striking finding was the increased susceptibility to tumorigenesis of female offspring. Latency for local tumors was decreased by two weeks; tumors were more frequent and grew more rapidly. Significantly more female offspring had both local and pulmonary lesions, and the total number of pulmonary adenomas was also significantly higher. Further studies are required to determine if the developmental alterations in hepatic (MFO) activity resulting from perinatal exposure to PAH relate in a causative way to the enhanced susceptibility of female offspring to tumorigenesis.


Ginger Extract Loaded into Chitosan Nanoparticles Enhances Cytotoxicity and Reduces Cardiotoxicity of Doxorubicin in Hepatocellular Carcinoma in Mice.
This study aimed to investigate the impact of ginger extract (GE) loaded into chitosan nanoparticles (CNPs) in enhancing cytotoxicity and reducing cardiotoxicity of doxorubicin (DXN) in hepatocellular carcinoma (HCC) induced mice. DXN and GE were loaded into CNPs and cytotoxicity of loaded and unloaded drugs against HepG2 cells was evaluated. HCC was induced in male albino mice by injection of diethylnitrosamine (DINA). Mice were divided into eight groups (n = 15): (1) normal control, (2) DINA, (3) CNPs, (4) free DXN, (5) CNPs DXN, (6) free GE, (7) CNPs GE, and (8) CNPs DXN + CNPs GE. Both GE and DXN loaded into CNPs showed a greater decline in cell viability of HepG2 cells than the unloaded forms. GE CNPs displayed pronounced anticancer activity In Vivo through apoptosis, greater down-regulation of multidrug resistance 1, enhancement of anti-oxidant activity and depletion of vascular endothelial growth factor content in liver tissues. GE CNPs in combination with DXN CNPs showed nearly normal hepatic lobule architecture and the greatest increase in apoptotic cell count. Co-treatment group had decreased cardiac malondialdehyde, tumor necrosis factor-α and serum activity of creatine kinase and lactate dehydrogenase. Combination of GE CNPs and DXN CNPs might be a potentially effective therapeutic approach for HCC.


Online Porn Addiction: What We Know and What We Don't-A Systematic Review.
In the last few years, there has been a wave of articles related to behavioral addictions; some of them have a focus on online pornography addiction. However, despite all efforts, we are still unable to profile when engaging in this behavior becomes pathological. Common problems include: sample bias, the search for diagnostic instrumentals, opposing approximations to the matter, and the fact that this entity may be encompassed inside a greater pathology (i.e., sex addiction) that may present itself with very diverse symptomatology. Behavioral addictions form a largely unexplored field of study, and usually exhibit a problematic consumption model: loss of control, impairment, and risky use. Hypersexual disorder fits this model and may be composed of several sexual behaviors, like problematic use of online pornography (POPU). Online pornography use is on the rise, with a potential for addiction considering the "triple A" influence (accessibility, affordability, anonymity). This problematic use might have adverse effects in sexual development and sexual functioning, especially among the young population. We aim to gather existing knowledge on problematic online pornography use as a pathological entity. Here we try to summarize what we know about this entity and outline some areas worthy of further research.


[Clinical characteristics and risk factors for feeding intolerance in preterm infants].
To investigate the clinical characteristics and risk factors for feeding intolerance (FI) in preterm infants and to provide evidence for early identification, effective prevention and treatment of FI. Methods: A total of 116 preterm infants were recruited in the Department of Neonatology, West China Second Hospital, Sichuan University, from July 2016 to December 2016. Self-designed "the clinical observation table for feeding intolerance of preterm infant" was used to find out the main risk factors of FI in preterm infants. Results: 1) There were 62 cases of FI. The incidence of FI in preterm infants was 53.45% (62/116). It was 44.93% (31/69) and 65.96% (31/47) for males and females, respectively, with significant difference between them (P<0.05). The incidence of FI in very low birth weight infants was 48.57% (34/70), and in the extremely low birth weight infant was 88.89% (8/9). FI in preterm infants mainly occurred in the period of being fed within 48-72 h. The symptoms included abdominal distension, gastric retention, vomiting and stomach brown color for clinical manifestations. Among them, abdominal distension was the main clinical manifestation. 2) The logistic multivariate regression analysis showed that birth weight <1 000 g (P<0.05), the use of caffeine citrate (P<0.05) and the formula feeding (P<0.05) were the main risk factors for FI. Conclusion: The incidence of FI is very high in preterm infants. Birth weight <1 000 g, the use of caffeine citrate, and formula feeding are main risk factors for FI.


An investigation of cannabis use for insomnia in depression and anxiety in a naturalistic sample.
Little is known about cannabis use for insomnia in individuals with depression, anxiety, and comorbid depression and anxiety. To develop a better understanding of distinct profiles of cannabis use for insomnia management, a retrospective cohort study was conducted on a large naturalistic sample. Data were collected using the medicinal cannabis tracking app, Strainprint®, which allows users to monitor and track cannabis use for therapeutic purposes. The current study examined users managing insomnia symptoms in depression (n = 100), anxiety (n = 463), and comorbid depression and anxiety (n = 114), for a total of 8476 recorded sessions. Inferential analyses used linear mixed effects modeling to examine self-perceived improvement across demographic variables and cannabis product variables. Overall, cannabis was perceived to be efficacious across all groups, regardless of age and gender. Dried flower and oral oil were reported as the most used and most efficacious product forms. In the depression group, all strains were perceived to be efficacious and comparisons between strains revealed indica-dominant (Mdiff = 1.81, 95% CI 1.26-2.36, Padj < .001), indica hybrid (Mdiff = 1.34, 95% CI 0.46-2.22, Padj = .045), and sativa-dominant (Mdiff = 1.83, 95% CI 0.68-2.99, Padj = .028) strains were significantly more efficacious than CBD-dominant strains. In anxiety and comorbid conditions, all strain categories were perceived to be efficacious with no significant differences between strains. In terms of perceptions, individuals with depression, anxiety, and both conditions who use cannabis for insomnia report significant improvements in symptom severity after cannabis use. The current study highlights the need for placebo-controlled trials investigating symptom improvement and the safety of cannabinoids for sleep in individuals with mood and anxiety disorders.


[The state of carotid arteries in young men with arterial hypertension].
To study elastic properties of carotid arteries in young men with arterial hypertension (AH). We examined men aged 18-25 years (mean 21.1+/-0.14 years): 36 with normal blood pressure (BP), 123 with stable and 51 with unstable AH. Parameters studied comprised intima-media thickness (IMT) of carotid arteries, their M-mode measured maximal systolic and minimal diastolic diameters (Ds and Dd), stiffness of common carotid artery (CCA) wall determined on the basis of analysis of elasticity and distensibility coefficients (CC and DC), Peterson's and Young's modules of elasticity (Ep and E), and index of flow deformation (CS). Compared with young men with normal BP and unstable AH patients with stable AH had abnormal elastic properties of CCA and increased IMT. Stable AH in young men is associated with signs of remodeling of CCA walls and increase of their rigidity.


Heterospin biradicals provide insight into molecular conductance and rectification.
The correlation of electron transfer with molecular conductance (g: electron transport through single molecules) by Nitzan and others has contributed to a fundamental understanding of single-molecule electronic materials. When an unsymmetric, dipolar molecule spans two electrodes, the possibility exists for different conductance values at equal, but opposite electrode biases. In the device configuration, these molecules serve as rectifiers of the current and the efficiency of the device is given by the rectification ratio (RR = gforward/greverse). Experimental determination of the RR is challenging since the orientation of the rectifying molecule with respect to the electrodes and with respect to the electrode bias direction is difficult to establish. Thus, while two different values of g can be measured and a RR calculated, one cannot easily assign each conductance value as being aligned with or opposed to the molecular dipole, and calculations are often required to resolve the uncertainty. Herein, we describe the properties of two isomeric, triplet ground state biradical molecules that serve as constant-bias analogs of single-molecule electronic devices. Through established theoretical relationships between g and electronic coupling, H2, and between H2 and magnetic exchange coupling, J (g ∝ H2 ∝ J), we use the ratio of experimental J-values for our two isomers to calculate a RR for an unsymmetric bridge molecule with known geometry relative to the two radical fragments of the molecule and at a spectroscopically-defined potential bias. Our experimental results are compared with device transport calculations.


[Soroka University Medical Center marks its 50th anniversary--a celebration for Israel's health services].
In December 2009, the Soroka University Medical Center celebrated its 50th anniversary. Following a difficult struggle, Soroka was established in 1959 as a small community hospital. Today, it is difficult to imagine the health services in Israel without a major hospital in the Negev. Soroka is presently providing quality primary, secondary and tertiary medical care to a diverse population of one million people from Kiryat Gat to Eilat. Soroka is the second largest hospital in Israel with over 200,000 emergency visits, 90,000 admissions, 32,000 surgeries and a birth rate of over 13,000 annually. in 1974, the Ben-Gurion University Medical School was opened adjacent to the hospital, with the vision and mission of training humane and skilled physicians and pursuing advanced medical education and research. Within the faculty's framework and the infrastructure of Soroka, the largest Department of Family Physicians in Israel was developed in the Negev. Graduates serve in most of the Negev clinics and have had a tremendous impact on health in the Negev. Many of the graduates are currently serving in key positions in Israel's health services. A third of the School's graduates are annually accepted for training at Soroka. This special edition includes 11 articles representing the clinical research carried out in the hospital's various divisions. They all expose clinical implications of general medical science and some are related to special health problems in the Negev with its diverse population--old native and new immigrants, Jews and Arab Bedouin.We salute Soroka on its outstanding achievements.


Structural classification of alphabetabeta and betabetaalpha supersecondary structure units in proteins.
We present a fully automatic structural classification of supersecondary structure units, consisting of two hydrogen-bonded beta strands, preceded or followed by an alpha helix. The classification is performed on the spatial arrangement of the secondary structure elements, irrespective of the length and conformation of the intervening loops. The similarity of the arrangements is estimated by a structure alignment procedure that uses as similarity measure the root mean square deviation of superimposed backbone atoms. Applied to a set of 141 well-resolved nonhomologous protein structures, the classification yields 11 families of recurrent arrangements. In addition, fragments that are structurally intermediate between the families are found; they reveal the continuity of the classification. The analysis of the families shows that the alpha helix and beta hairpin axes can adopt virtually all relative orientations, with, however, some preferable orientations; moreover, according to the orientation, preferences in the left/right handedness of the alpha-beta connection are observed. These preferences can be explained by favorable side by side packing of the alpha helix and the beta hairpin, local interactions in the region of the alpha-beta connection or stabilizing environments in the parent protein. Furthermore, fold recognition procedures and structure prediction algorithms coupled to database-derived potentials suggest that the preferable nature of these arrangements does not imply their intrinsic stability. They usually accommodate a large number of sequences, of which only a subset is predicted to stabilize the motif. The motifs predicted as stable could correspond to nuclei formed at the very beginning of the folding process.


Quantitative planar temperature imaging in turbulent non-premixed flames using filtered Rayleigh scattering.
The paper presents results demonstrating the application of filtered Rayleigh scattering (FRS) for quantitative temperature measurements within turbulent non-premixed jet flames. Through targeted fuel tailoring, i.e., the selection of a specific fuel mixture, temperature measurements are made under non-premixed fueling conditions with a single FRS measurement. For this to be feasible, the instantaneous measured FRS signal is uniquely proportional to the local temperature for all thermo-chemical states of the targeted fuel-oxidizer system. Simulated results using laminar, counterflow flame calculations show that for select CH4/H2/Ar fuel mixtures issuing into air, a unique relationship between the local FRS signal and temperature is achieved for all mixture fraction values over a full range of operating conditions from near-equilibrium to near-extinction flames. Furthermore, for the selected FRS-optimized fuel, the local mixture-averaged Rayleigh scattering cross section is nearly constant from fuel to oxidizer to products. Thus, traditional laser Rayleigh scattering (LRS) can be used to determine the temperature as a "standard" to which to compare and assess the FRS-based temperature results. Simultaneous LRS-FRS temperature measurements from Re=10,000, 20,000, and 30,000 turbulent non-premixed jet flames are presented that show good agreement between the two techniques in terms of instantaneous temperature fields and statistical quantities at various spatial locations within the flame. These results provide confidence that the current approach of FRS thermometry allows for accurate temperature measurements within the selected set of turbulent non-premixed flames.