The contributing factors to suicide in Italian prisons: An 11-year analysis (2010-2020).
Suicide is a leading cause of death globally, with approximately 800,000 deaths annually and accounting for 1.5% of all deaths. Risk factors are multifaceted, encompassing individual factors (such as genetics, family history and mental illnesses) and environmental factors (such as economic conditions, social support and life events). In prisons, suicide rates are markedly higher than in the general population, particularly in Italy, where the prisoner suicide rate is approximately 20 times that of the non-incarcerated population. There is, however, little research on suicide in Italian prisons. To analyse the characteristics of all people who died by suicide in Italian prisons between 2010 and 2020. We carried out a records-based cohort study analysing official data from the Italian Ministry of Justice on prison suicides between 2010 and 2020. The data were cross-referenced and, when required, supplemented with information from Ristretti Orizzonti, a journal specialising in health and living conditions in prisons, as well as from the website of ISTAT (Italian National Statistical Institute), newspapers, radio broadcasts and news agencies. Factors associated with an increased risk of suicide in prisons were nighttime periods, the months of June, July and October, a relatively brief duration of detention (<6 months), having been convicted of murder, male gender, being about 40 years old, having access to hanging materials and being interned (i.e. subjected to the execution of custodial security measures) or awaiting trial. Prison overcrowding was not a risk factor for suicide. Our findings hold substantial implications for suicide prevention in Italian prisons as they suggest both characteristics of individuals and characteristics of the institutions that could be taken as risk indicators. This knowledge can inform the development of targeted interventions to manage both individual and environmental factors better, leading to improved prison conditions and reduced suicide rates. Furthermore, our research establishes a foundation for more systematic and in-depth investigations that could further improve suicide prevention strategies in Italian prisons, ultimately influencing policy changes in both practice and research, including perhaps establishing a national database on every completed suicide in prisons.


[Irrigation system "Meturakol" in the treatment of dystrophic processes of the posterior eye segment].
An original method for treating degenerative processes in the eye by means of Meturakol irrigation system is described. Studies were performed in 95 patients aged 60-70 years. Use of Meturakol irrigation system ruled out pain associated with frequent administration of drugs, ensured high concentrations of drugs in the posterior segment of the eye, and improved the efficiency of drug therapy in patients with degenerative diseases of the eyes. Good remote results are due to potent drug supply to ocular tissues and to the use of hemostatic sponge Meturakol, containing methyluracil. The method is offered for wide clinical use.


Long-term functional assessment of antegrade colonic enema for combined incontinence and constipation using a modified Marsh and Kiff technique.
Constipation and fecal incontinence can severely affect quality of life for patients, particularly when simultaneously present. Malone antegrade colonic enema enables periodic colonic emptying, thus preventing uncontrolled passage of feces and constipation. Eleven patients with fecal incontinence and severe constipation or perineal colostomy after Miles' operation underwent a modified Marsh and Kiff ileostomy for antegrade colonic enema. Before and after surgery, the patients were fully evaluated for gastrointestinal functions, including gallbladder and stomach emptying time, H(2)-breath test, colonic transit time, dynamic defecography, and anorectal manometry. The severity of incontinence and constipation was scored preoperatively and postoperatively by using the American Medical System score and Cleveland Clinic Constipation scale, respectively, whereas the quality of life was measured by the Gastrointestinal Quality of Life Index. The surgical technique involved division of the terminal ileum 10 to 15 cm from the ileocecal valve, anastomosis and intussusception of the ileum with the cecum, narrowing of the ileal conduit with a linear stapler, and a small, introflexed ileostomy with an advanced skin flap. During the postoperative period, the mean American Medical System score decreased significantly from 77 to 11 (P<0.01) and the mean Cleveland Clinic Constipation score from 23 to 8.5 (P<0.01) with a significant improvement of quality of life. Antegrade colonic enema did not affect gallbladder, gastric, or orocecal transit time, which remained comparable with baseline. Colonic scintigraphy showed that antegrade colonic enema was efficient to clean the whole colon and rectum, leaving only 24 (range, 6-40) percent of the initial radioactivity after 30 minutes. Ileal manometry confirmed the presence of a high-pressure zone, preventing accidental reflux. Modified Marsh and Kiff technique is a safe and effective surgical option to treat patients with combined fecal incontinence and severe constipation and those with perineal colostomy after Miles. It should be recommended as a last option before colostomy.


Measuring quality of life among HIV-infected women using a culturally adapted questionnaire in Rakai district, Uganda.
To examine self-reported quality of life and health status of HIV-infected women and a comparison sample of HIV-uninfected women in rural Uganda, we culturally adapted a Lugandan version of the Medical Outcomes Survey-HIV (MOS-HIV). We administered a cross-sectional survey among 803 women (239 HIV-positive and 564 HIV-negative) enrolled in a community study to evaluate maternal and child health in Rakai District, Uganda. The interview took 20 minutes and was generally well-accepted. Reliability coefficients were >0.70, except for role functioning, energy and cognitive function. MOS-HIV scores for HIV-positive women were correlated with increasing number of physical symptoms and higher HIV viral load. Compared to HIV-negative women, HIV-positive women reported lower scores than HIV-negative women for general health perceptions, physical functioning, pain, energy, role functioning, social functioning, mental health and overall quality of life (p all <0.01). Substantial impairment was noted among women reporting >/=4 symptoms. In summary, HIV-positive women reported significantly poorer functioning and well-being than HIV-negative women. We conclude that patient-reported measures of health status and related concepts may provide a feasible, reliable and valid method to assess the impact of HIV/AIDS and future therapeutic interventions to improve patient outcomes in rural Africa.


Pacing strategy in male elite and age group 100 km ultra-marathoners.
Pacing strategy has been investigated in elite 100 km and elite 161 km (100 mile) ultra-marathoners, but not in age group ultra-marathoners. This study investigated changes in running speed over segments in male elite and age group 100 km ultra-marathoners with the assumption that running speed would decrease over segments with increasing age of the athlete. Running speed during segments in male elite and age group finishers for 5-year age groups (ie, 18-24 to 65-69 years) in the 100 km Lauf Biel in Switzerland was investigated during the 2000-2009 period. Average running speed over segment time station (TS) TS1-TS2 (56.1 km) was compared with running speed Start-TS1 (38 km) and Start-TS3 (76.7 km) and running speed TS2-TS3 was compared with running speed Start-Finish. For the top ten athletes in each edition, running speed decreased from 2000 to 2009 for TS1-TS2 and TS2-TS3 (P<0.0001) but not in TS3-Finish (P>0.05). During TS1-TS2, athletes were running at 98.0%±2.1% of the running speed of Start-TS1. In TS2-TS3, they were running at 94.6%±3.4% of the running speed of TS1-TS2. In TS3-Finish, they were running at 95.5%±3.8% of running speed in TS2-TS3. For age group athletes, running speed decreased in TS1-TS2 and TS2-TS3. In TS3-Finish, running speed remained unchanged with the exception of the age group 40-44 years for which running speed increased. Running speed showed the largest decrease in the age group 18-24 years. To summarize, the top ten athletes in each edition maintained their running speed in the last segment (TS3-Finish) although running speed decreased over the first two segments (TS1-TS2 and TS2-TS3). The best pacers were athletes in the age group 40-44 years, who were able to achieve negative pacing in the last segment (TS3-Finish) of the race. The negative pacing in the last segment (TS3-Finish) was likely due to environmental conditions, such as early dawn and the flat circuit in segment TS3-Finish of the race.


Systematic re-evaluation of genes from candidate gene association studies in migraine using a large genome-wide association data set.
Before the genome-wide association (GWA) era, many hypothesis-driven candidate gene association studies were performed that tested whether DNA variants in genes that had been selected based on prior knowledge about migraine pathophysiology were associated with migraine. Most studies involved small sample sets without robust replication, thereby making the risk of false-positive findings high. Genome-wide marker data of thousands of migraine patients and controls from the International Headache Genetics Consortium provide a unique opportunity to re-evaluate key findings from candidate gene association studies (and other non-GWA genetic studies) in a much larger data set. We selected 21 genes from published candidate gene association studies and six additional genes from other non-GWA genetic studies in migraine. Single nucleotide polymorphisms (SNPs) in these genes, as well as in the regions 500 kb up- and downstream, were inspected in IHGC GWAS data from 5175 clinic-based migraine patients with and without aura and 13,972 controls. None of the SNPs in or near the 27 genes, including the SNPs that were previously found to be associated with migraine, reached the Bonferroni-corrected significance threshold; neither when analyzing all migraine patients together, nor when analyzing the migraine with and without aura patients or males and females separately. The available migraine GWAS data provide no clear evidence for involvement of the previously reported most promising candidate genes in migraine.


Changes in interleukin-1beta mRNA expression in the rat ovary during the estrous cycle in response to lipopolysaccharide.
The changes in interleukin-1 (IL-1) beta mRNA expression and the number of macrophages were studied in the ovary during the estrous cycle in rats and after intraperitoneal injection of lipopolysaccharide (LPS, 2 mg/body) 2 hours before autopsy. IL-1beta mRNA expression was very low in the ovary, and there was no statistically significant change during the estrous cycle. Hybridization signals of IL-1beta mRNA were localized intensely in the thecal layer, moderately in the corpora lutea, and slightly in granulosa cells of the ovary during the cycle. The number of macrophages seen mainly in the hilum and interstitium significantly increased on proestrus compared with other estrous days. LPS significantly increased IL-1beta mRNA expression on each day with the highest response to LPS at 1500 h on proestrus, and caused an increase in the number of macrophages in the ovary within 2 hours. These results indicate that IL-1beta mRNA expressions are low during the estrous cycle in rats, and proestrus is the day of maximal IL-1beta synthesis in response to LPS. The increase in IL-1beta synthesis caused by LPS might be due to at least the influx of macrophages into the ovary.


Sequential injection immunoassay for environmental measurements.
Sequential injection immunoassay systems for environmental measurements based on the selective immunoreaction between antigen and antibody were described. A sequential injection analysis (SIA) technique is suitable to be applied for the procedure of enzyme-linked immunosorbent assay (ELISA), because the washing and the addition of reagent solutions can be automated by using a computer-controlled syringe pump and switching valve. We selected vitellogenin (Vg), which is a biomarker for evaluating environmental risk caused by endocrine-disrupting chemicals in the hydrosphere, and linear alkylbenzene sulfonates (LAS) and alkylphenol polyethoxylates (APEO), which are versatile surfactants, as target analytes in the flow immunoassay systems. For Vg monitoring, SIA systems based on spectrophotometric, chemiluminescence, and electrochemical determinations were constructed. On the other hand, chemiluminescence determination was applied to the detection of LAS and APEO. For APEO, an SIA system combined with surface plasmon resonance (SPR) sensor was also developed. These new sequential injection immunoassay systems are expected to be useful systems for environmental analysis.


The central serotonin2B receptor as a new pharmacological target for the treatment of dopamine-related neuropsychiatric disorders: Rationale and current status of research.
The serotonin2B receptor (5-HT2BR), which was first cloned and characterized in the rat stomach fundus, is the most recent addition to the 5-HT2R family. While its involvement in the regulation of gastrointestinal, vascular, pulmonary and cardiac physiology has been widely investigated, its functional role within the central nervous system (CNS) has received much less attention. Nevertheless, when considering the data available in the literature with regards to the regulatory control exerted by the central 5-HT2BR on dopamine (DA) and serotonin (5-HT) neuron activity, a very interesting picture emerges and highlights the key role of these receptors for future therapeutic strategies of DA-related neuropsychiatric disorders. Thus, the present review, by compiling molecular, biochemical, electrophysiological and behavioral findings from the literature of the past twenty years, aims at providing a sound analysis of the current knowledge supporting the interest of the central 5-HT2BR for future therapeutic avenues. First, we recall the neuroanatomical and functional data supporting the therapeutic relevance of the 5-HT/DA interaction in the CNS. Thereafter, after a short overview of the central expression and molecular properties of the 5-HT2BR, as well as of the 5-HT2BR agonists and antagonists available in the market, we will focus on the functional role of this receptor in the control of 5-HT, DA and neuroglia activity in the rodent brain. Finally, the therapeutic potential of 5-HT2BR antagonists for improved treatment of schizophrenia and drug addiction will be discussed.


Long-term treatment effectiveness of molding helmet therapy in the correction of posterior deformational plagiocephaly: a five-year follow-up.
To evaluate the long-term effectiveness of helmet therapy in the correction of deformational plagiocephaly and to assess the early occlusal abnormalities seen in these patients. A prospective study with blinded measurements. Twenty-eight patients with deformational plagiocephaly who were treated with molding helmet therapy with at least 5 years of follow-up. The average length of molding helmet treatment was 6.2 months. At the time of this follow-up evaluation, the mean interval since completing the molding helmet therapy was 5.6 years. Anthropometric measurements of cranial asymmetry included cranial vault asymmetry (CVA), orbitotragial depth asymmetry (OTDA), and cranial base asymmetry (CBA). A dental examination was also performed. At the completion of therapy, the most improvement was seen in the measurement of CBA, followed by CVA and OTDA. However, in evaluating the long-term stability of molding treatment, OTDA tended to continue improving after the initial treatment, while CBA and CVA appeared to regress, although none of the changes reached statistically significant levels. In dental measurements, all the dental midline and chin deviations were toward the unaffected side with respect to occipital deformation. This study demonstrated that helmet remodeling with the dynamic orthotic cranioplasty band is effective in the correction of cranial asymmetry, with some nonstatistically significant changes in long-term cranial vault symmetry. Dental observations indicated the possibility of occlusal abnormalities that may affect dental, especially orthodontic, diagnosis and treatment planning.


fastBMA: scalable network inference and transitive reduction.
Inferring genetic networks from genome-wide expression data is extremely demanding computationally. We have developed fastBMA, a distributed, parallel, and scalable implementation of Bayesian model averaging (BMA) for this purpose. fastBMA also includes a computationally efficient module for eliminating redundant indirect edges in the network by mapping the transitive reduction to an easily solved shortest-path problem. We evaluated the performance of fastBMA on synthetic data and experimental genome-wide time series yeast and human datasets. When using a single CPU core, fastBMA is up to 100 times faster than the next fastest method, LASSO, with increased accuracy. It is a memory-efficient, parallel, and distributed application that scales to human genome-wide expression data. A 10 000-gene regulation network can be obtained in a matter of hours using a 32-core cloud cluster (2 nodes of 16 cores). fastBMA is a significant improvement over its predecessor ScanBMA. It is more accurate and orders of magnitude faster than other fast network inference methods such as the 1 based on LASSO. The improved scalability allows it to calculate networks from genome scale data in a reasonable time frame. The transitive reduction method can improve accuracy in denser networks. fastBMA is available as code (M.I.T. license) from GitHub (https://github.com/lhhunghimself/fastBMA), as part of the updated networkBMA Bioconductor package (https://www.bioconductor.org/packages/release/bioc/html/networkBMA.html) and as ready-to-deploy Docker images (https://hub.docker.com/r/biodepot/fastbma/).


Promoting HIV, Hepatitis B Virus, and Hepatitis C Virus Screening Among Migrants With a Language Barrier: Protocol for the Development and Evaluation of an Electronic App (Apidé).
Late diagnoses of HIV, hepatitis B, and hepatitis C are important public health problems that affect the population at large and migrants in particular. Missed opportunities of HIV and hepatitis screening are numerous, with language differences being a significant barrier to testing. Several studies have shown that migrants who do not speak the language of the health provider are less likely to get tested, due to health providers' reluctance to offer a test and to migrants' reluctance to accept testing. The aim of our study is to develop a multilingual electronic tool (app) that assists health providers in offering and explaining HIV and hepatitis screenings to migrants with a language barrier and to evaluate its acceptability and impact in terms of public health. The study will go through 3 stages: (1) concept development, (2) app development, and (3) app evaluation. A qualitative study has been undertaken to explore language barriers during health care encounters and their effect on communication, specifically when a screening test is offered. In parallel, a systematic review of the literature was conducted to have a comprehensive overlook of electronic tools designed to help health care providers communicate with migrants with a language barrier. To generate a list of items to be translated for inclusion in the app, we will conduct a focus group and Delphi survey. The development of the app will include translation and voice recording of items. The electronic development will also include 3 steps of user testing. The acceptability of the app will be evaluated using the System Usability Scale. Evaluation of the app's efficacy will consist of a stepped wedge randomized controlled trial. The study will be carried out in 16 centers that treat migrants and offer them screening tests for infectious diseases. The primary outcome is the percentage of screening tests realized. The secondary outcomes are the rate of screening proposal by health professionals, acceptance rate by migrants, number of positive cases using this app, and frequency of use of the app. The app evaluation study received a 3-year grant from the Agence Nationale de la Recherche contre le SIDA et les hépatites virales (ANRS) and from the Office Français de l'Immigration et Intégration (OFII). At the time of publication of this protocol, the initial qualitative study and systematic literature review were completed. This study will develop an app that assists health providers in offering and explaining HIV and hepatitis screenings to migrants with a language barrier and measure its acceptability and effectiveness in terms of public health. When completed, this app could be distributed to numerous professionals carrying out screening with migrant populations in various health care settings. PRR1-10.2196/22239.


Effect of heavy metals on germination of seeds.
With the expansion of the world population, the environmental pollution and toxicity by chemicals raises concern. Rapid industrialization and urbanization processes has led to the incorporation of pollutants such as pesticides, petroleum products, acids and heavy metals in the natural resources like soil, water and air thus degrading not only the quality of the environment, but also affecting both plants and animals. Heavy metals including lead, nickel, cadmium, copper, cobalt, chromium and mercury are important environmental pollutants that cause toxic effects to plants; thus, lessening productivity and posing dangerous threats to the agro-ecosystems. They act as stress to plants and affect the plant physiology. In this review, we have summarized the effects of heavy metals on seeds of different plants affecting the germination process. Although reports exist on mechanisms by which the heavy metals act as stress and how plants have learnt to overcome, the future scope of this review remains in excavating the signaling mechanisms in germinating seeds in response to heavy metal stress.


Non-technical skills of the operating theatre scrub nurse: literature review.
This paper is a report of a review to identify the non-technical (cognitive and social) skills used by scrub nurses. Recognition that failures in non-technical skills contributed to accidents in high-risk industries led to the development of research programmes to study the role of cognition and social interactions in operational safety. Recently, psychological research in operating theatres has revealed the importance of non-technical skills in safe and efficient performance. Most of the studies to date have focused on anaesthetists and surgeons. On-line sources and university library catalogues, publications of the Association for Perioperative Practice, National Association of Theatre Nurses and Association of Peri-Operative Registered Nurses were searched in 2007. Studies were included in the review if they presented data from scrub nurses on one or more of their non-technical skills. These findings were examined in relation to an existing medical non-technical skills framework with categories of communication, teamwork, leadership, situation awareness and decision-making. Of 424 publications retrieved, 13 were reviewed in detail. Ten concerned communication and eight of those also had data on teamwork. In 11 papers teamwork was examined, and one focused on nurses' situation awareness, teamwork and communication. None of the papers we reviewed examined leadership or decision-making by scrub nurses. Further work is needed to identify formally the non-technical skills which are important to the role of scrub nurse and then to design training in the identified non-technical skills during the education and development of scrub nurses.


Hydrogenation of biofuels with formic acid over a palladium-based ternary catalyst with two types of active sites.
A composite catalyst including palladium nanoparticles on titania (TiO2) and on nitrogen-modified porous carbon (Pd/TiO2@N-C) is synthesized from palladium salts, tetrabutyl titanate, and chitosan. N2 sorption isotherms show that the catalyst has a high BET surface area (229 m(2) g(-1)) and large porosity. XPS and TEM characterization of the catalyst shows that palladium species with different chemical states are well dispersed across the TiO2 and nitrogen-modified porous carbon, respectively. The Pd/TiO2@N-C catalyst is very active and shows excellent stability towards hydrogenation of vanillin to 2-methoxy-4-methylphenol using formic acid as hydrogen source. This activity can be attributed to a synergistic effect between the Pd/TiO2 (a catalyst for dehydrogenation of formic acid) and Pd/N-C (a catalyst for hydrogenation of vanillin) sites.


Polyamine metabolism in MRC-5 cells infected with human cytomegalovirus.
The rate of putrescine uptake into MRC-5 cells increased markedly following infection with human cytomegalovirus (HCMV). Enhanced incorporation occurred immediately after infection and the highest levels were attained following the production of infectious, progeny virus. Parallel kinetic changes in the utilization of radio-labelled putrescine were shown by the amounts of spermidine and spermine recovered from infected cells as radioactive derivatives. A temporal correlation was found between these changes in polyamine metabolism and the synthesis of virus DNA. Methylglyoxalbis(guanylhydrazone), an inhibitor of spermidine and spermine synthesis, did not affect virus replication if HCMV-infected cells were exposed to the inhibitor after completion of the eclipse phase of the virus growth cycle. These results show that polyamine metabolism is required only during the initial stages of HCMV replication.


A role for melanopsin in alpha retinal ganglion cells and contrast detection.
Distinct subclasses of retinal ganglion cells (RGCs) mediate vision and nonimage-forming functions such as circadian photoentrainment. This distinction stems from studies that ablated melanopsin-expressing intrinsically photosensitive RGCs (ipRGCs) and showed deficits in nonimage-forming behaviors, but not image vision. However, we show that the ON alpha RGC, a conventional RGC type, is intrinsically photosensitive in mammals. In addition to their classical response to fast changes in contrast through rod/cone signaling, melanopsin expression allows ON alpha RGCs to signal prior light exposure and environmental luminance over long periods of time. Consistent with the high contrast sensitivity of ON alpha RGCs, mice lacking either melanopsin or ON alpha RGCs have behavioral deficits in contrast sensitivity. These findings indicate a surprising role for melanopsin and ipRGCs in vision.


Associations of childhood overweight and obesity with upper-extremity fracture characteristics.
Childhood obesity is a growing epidemic in the United States, and is associated with an increased risk of lower-extremity physeal fractures, and fractures requiring operative intervention. However, no study has assessed the risk upper extremity physeal fractures among overweight children. Our purpose was to compare the following upper-extremity fracture characteristics in overweight and obese children with those of normal-weight/underweight children (herein, "normal weight"): mechanism of injury, anatomical location, fracture pattern, physeal involvement, and treatment types. We hypothesized that overweight and obese children would be higher risk for physeal and complete fractures with low-energy mechanisms and would therefore more frequently require operative intervention compared with normal-weight children.We performed a cross-sectional review of our database of 608 patients aged 2 to 16 years, and included patients who sustained isolated upper-extremity fractures at our level-1 pediatric tertiary care center from January 2014 to August 2017. Excluded were patients who sustained pathologic fractures and those without basic demographic or radiologic information. Using body mass index percentile for age and sex, we categorized patients as obese (≥95th percentile), overweight (85th to <95th percentile), normal weight (5th to <85th percentile), or underweight (<5th percentile). The obese and overweight groups were analyzed both separately and as a combined overweight/obese group. Demographic data included age, sex, height, and weight. Fractures were classified based on fracture location, fracture pattern (transverse, comminuted, buckle, greenstick, avulsion, or oblique), physeal involvement, and treatment type. Of the 608 patients, 58% were normal weight, 23% were overweight, and 19% were obese. There were no differences in the mean ages or sex distributions among the 3 groups.Among patients with low-energy mechanisms of injury, overweight/obese patients had significantly greater proportions of complete fractures compared with normal-weight children (complete: 65% vs 55%, P = .001; transverse: 43% vs 27%, P = .006). In addition, the overweight/obese group sustained significantly more upper-extremity physeal fractures (37%) than did the normal-weight group (23%) (P = .007).Compared with those in normal-weight children, upper-extremity fracture patterns differ in overweight and obese children, who have higher risk of physeal injuries and complete fractures caused by low-energy mechanisms.Level of Evidence: Level III, retrospective comparative study.


Practical antimicrobial periodontal therapy.
Specific pathogenic bacteria play a central role in the etiology and pathogenesis of destructive periodontal disease. Under suitable conditions, periodontal pathogens colonize the subgingival environment and are incorporated into a tenacious biofilm. Successful prevention and treatment of periodontitis is contingent on effective control of the periodontopathic bacteria, which is accomplished with professional treatment of diseased periodontal sites and patient performed plaque control. Subgingival mechanical debridement, with or without surgery, constitutes the basic means of disrupting the subgingival biofilm and controlling pathogens. Appropriate antimicrobial agents that can be administered systemically or via local delivery may enhance eradication or suppression of subgingival pathogens. Microbiological testing may aid the clinician in the selection of the most effective antimicrobial agent or combination of agents. Understanding the benefits and limitations of antibiotics and antiseptics will optimize their usefulness in combating periodontal infections.


'Oh, I don't really want to bother with that:' gay and bisexual young men's perceptions of barriers to PrEP information and uptake.
Pre-exposure prophylaxis (PrEP), a daily oral pill for HIV prevention demonstrated to be effective for adults, was recently approved by the US Food and Drug Administration for use with young people weighing at least 35 kilograms. Given that young people aged 13-19 years account for a disproportionate share of new US HIV infections, PrEP presents an important opportunity. There has been limited effort, however, to increase PrEP awareness and uptake among young people. While prior work has identified barriers young people face in getting PrEP, effective strategies for overcoming these barriers have not yet been identified. This paper presents results from interviews with 15-19 year old gay and bisexual young men about their knowledge and perceptions of PrEP, and the barriers they perceive. Results suggest that participants were aware of PrEP but confused by the details of insurance coverage and out-of-pocket costs. Participants also felt parents and providers would not be knowledgeable or supportive, and were reluctant to share their own use of PrEP on social media. Suggested next steps include online parent and provider education, systemic health care reform to streamline and simplify access to preventative care and awareness campaigns that meet youth where they are on popular platforms.


Dynamics of pH at Santa Catalina Island.
The local expression of ocean acidification may depend on local oceanographic features in addition to global forcings. Our objective is to provide a baseline of pH behavior at Santa Catalina Island, situated within the unique oceanographic characteristics of the Southern California Bight, and to gain insight into ocean acidification at the island. Measurements of the upper water column (to 30-m depth) of pH, temperature, conductivity, chlorophyll and dissolved oxygen at Santa Catalina were made from a fixed mooring and by profiling the water column from a boat and on Self-Contained Underwater Breathing Apparatus (SCUBA). The average pH (8.095 at 18-m depth) was found to be higher than that reported off the nearby mainland and the Northern Channel Islands. The higher value is thought to result from both downwelling produced by internal waves as well as less upwelling at the island compared to other locations. Large modulations in pH at depth corresponded to advection of gradients by internal waves. Within the accuracy of the sensors there was no seasonal dependence detected at near-surface, nor a pH signal associated with the sub-surface chlorophyll and oxygen maxima. We conclude that marine life living at depths affected by internal waves experience significant variation in pH.


Healthcare resource utilization and costs of adverse events among patients with metastatic urothelial cancer in USA.
Aim: To estimate incremental costs and healthcare resource utilization (HRU) associated with select severe adverse events (AEs) and AEs of any severity in patients with metastatic urothelial carcinoma receiving first-line (1L) therapy. Materials & methods: Adults treated with 1L systemic therapy between January 2012 and September 2017 with ≥1 urothelial cancer diagnosis were identified using claims data. Per-patient-per-month cost differences and HRU rate ratios comparing patients with and without select AEs were estimated. Results: Patients with any severe select AEs had higher costs than those without (cost difference = $6130 per-patient-per-month; p < 0.001). Healthcare costs and HRU for patients with select AEs were significantly higher versus those without. Conclusion: Select AEs during 1L therapy for metastatic urothelial carcinoma can result in significant burden to patients and healthcare systems.


Translation and cross-cultural adaptation into Brazilian Portuguese of the Children's Communication Checklist-2.
To translate the Children's Communication Checklist-2 (CCC-2) into Brazilian-Portuguese, to make its cross-cultural adaptation and to assess its internal reliability. The translation and cross-cultural adaptation followed the recommendations of the International Society for Pharmacoeconomics and Outcomes Research. The test was administered to 20 parents or caregivers of individuals with autism in order to investigate the level of understandability of the object under study. After implementing the necessary adjustments, the final version of the Brazilian-Portuguese CCC-2 was achieved. Parents and/or caregivers did not make any suggestion for its adaptation. The final version was certified by the author of the original instrument and by the publisher responsible for marketing the CCC-2. Reliability of the instrument is acceptable, with values of internal consistency of its subscales ranging from 0.75 to 0.90. The instrument can be used in the clinical evaluation of children with autism and developmental language disorder. However, further studies are needed to assess the reliability and validity of the instrument in Brazil.


Splenic pathology in immune thrombocytopenia.
Splenic pathology was analysed in 73 patients with immune thrombocytopenic purpura who underwent splenectomy for bleeding that had been resistant to adrenocorticosteroids. The mean splenic weight was 100 g. The only notable macroscopic feature was the prominence of Malpighian corpuscles in 15 cases. Microscopic examination showed formation of germinal centres in the lymphoid tissue of the white pulp in 40 cases, prominence of the histiocytes in the red pulp in 18 cases, and infiltration with neutrophils in the same area in 49 cases. Myeloid metaplasia throughout the splenic tissue was minimal in 58 cases, moderate in 15, and extreme in two. No distinguishing features were found in the spleen from patients who had not received previous immunosuppressive treatment (n = 3), those treated with prednisone (1 mg/kg/day) for a median of 14 days (n = 62), or those who had received the same dose of prednisone and additional azathioprine or cyclophosphamide (2 mg/kg/day) for a median of four weeks (n = 8). No correlation could be shown between histological features and the age of the patient or titre of antiplatelet antibodies. Similarly, no distinguishing features were found in patients with associated systemic lupus erythematosus (n = 8), hyperthyroidism (n = 6), immune haemolysis (n = 3), or recent viral illness (n = 3).


Effects of Dinotefuran on Brain miRNA Expression Profiles in Young Adult Honey Bees (Hymenopptera: Apidae).
Honey bees are important pollinators of wild plants and crops. MicroRNAs (miRNAs) are endogenous regulators of gene expression. In this study, we initially determined that the lethal concentration 50 (LC50) of dinotefuran was 0.773 mg/l. Then, the expression profiles and differentially expressed miRNAs (DE miRNAs) in honey bee brains after 1, 5, and 10 d of treatment with the lethal concentration 10 (LC10) of dinotefuran were explored via deep small-RNA sequencing and bioinformatics. In total, 2, 23, and 27 DE miRNAs were identified after persistent exposure to the LC10 of dinotefuran for 1, 5, and 10 d, respectively. Some abundant miRNAs, such as ame-miR-375-3p, ame-miR-281-5p, ame-miR-3786-3p, ame-miR-10-5p, and ame-miR-6037-3p, were extremely significantly differentially expressed. Enrichment analysis suggested that the candidate target genes of the DE miRNAs are involved in the regulation of biological processes, cellular processes, and behaviors. These results expand our understanding of the regulatory roles of miRNAs in honey bee Apis mellifera (Hymenopptera: Apidae) responses to neonicotinoid insecticides and facilitate further studies on the functions of miRNAs in honey bees.


Delaying corn rootworm resistance to Bt corn.
Transgenic crops producing Bacillus thuringiensis (Bt) toxins for insect control have been successful, but their efficacy is reduced when pests evolve resistance. To delay pest resistance to Bt crops, the U.S. Environmental Protection Agency (EPA) has required refuges of host plants that do not produce Bt toxins to promote survival of susceptible pests. Such refuges are expected to be most effective if the Bt plants deliver a dose of toxin high enough to kill nearly all hybrid progeny produced by matings between resistant and susceptible pests. In 2003, the EPA first registered corn, Zea mays L., producing a Bt toxin (Cry3Bb1) that kills western corn rootworm, Diabrotica virgifera virgifera LeConte, one of the most economically important crop pests in the United States. The EPA requires minimum refuges of 20% for Cry3Bb1 corn and 5% for corn producing two Bt toxins active against corn rootworms. We conclude that the current refuge requirements are not adequate, because Bt corn hybrids active against corn rootworms do not meet the high-dose standard, and western corn rootworm has rapidly evolved resistance to Cry3Bb1 corn in the laboratory, greenhouse, and field. Accordingly, we recommend increasing the minimum refuge for Bt corn targeting corn rootworms to 50% for plants producing one toxin active against these pests and to 20% for plants producing two toxins active against these pests. Increasing the minimum refuge percentage can help to delay pest resistance, encourage integrated pest management, and promote more sustainable crop protection.


Early experience with the gamma interlocking nail for peritrochanteric fractures of the proximal femur.
Surgical fixation, early weight-bearing, and bony union remain a challenge in the treatment of peritrochanteric femur fractures, especially if the fractures are comminuted or unstable. Preliminary experience with the Gamma locking nail, a short intramedullary nail connected to a sliding compression screw augmented with distal locking screws, is presented. In a consecutive series of 29 patients, all fractures were adequately reduced and immediate weight-bearing was begun regardless of fracture configuration (13/27 fractures classified as unstable). Twenty-seven patients were reviewed at 6 months. At follow-up, all patients continued to be ambulatory and all fractures healed. Major complications included screw migration in the femoral head (two patients), difficulty in securely placing the distal screws (eight patients), and a femoral shaft fracture through the distal locking screws following a fall. The technical problems inherent in the device and its instrumentation are discussed. In this early experience, the Gamma nail appears to allow for early patient ambulation regardless of the fracture configuration with excellent clinical results.


Sample size and predictive performance of machine learning methods with survival data: A simulation study.
Prediction models are increasingly developed and used in diagnostic and prognostic studies, where the use of machine learning (ML) methods is becoming more and more popular over traditional regression techniques. For survival outcomes the Cox proportional hazards model is generally used and it has been proven to achieve good prediction performances with few strong covariates. The possibility to improve the model performance by including nonlinearities, covariate interactions and time-varying effects while controlling for overfitting must be carefully considered during the model building phase. On the other hand, ML techniques are able to learn complexities from data at the cost of hyper-parameter tuning and interpretability. One aspect of special interest is the sample size needed for developing a survival prediction model. While there is guidance when using traditional statistical models, the same does not apply when using ML techniques. This work develops a time-to-event simulation framework to evaluate performances of Cox regression compared, among others, to tuned random survival forest, gradient boosting, and neural networks at varying sample sizes. Simulations were based on replications of subjects from publicly available databases, where event times were simulated according to a Cox model with nonlinearities on continuous variables and time-varying effects and on the SEER registry data.


Epigenetic inheritance mediated by coupling of RNAi and histone H3K9 methylation.
Histone post-translational modifications (PTMs) are associated with epigenetic states that form the basis for cell-type-specific gene expression1,2. Once established, histone PTMs can be maintained by positive feedback involving enzymes that recognize a pre-existing histone modification and catalyse the same modification on newly deposited histones. Recent studies suggest that in wild-type cells, histone PTM-based positive feedback is too weak to mediate epigenetic inheritance in the absence of other inputs3-7. RNA interference (RNAi)-mediated histone H3 lysine 9 methylation (H3K9me) and heterochromatin formation define a potential epigenetic inheritance mechanism in which positive feedback involving short interfering RNA (siRNA) amplification can be directly coupled to histone PTM positive feedback8-14. However, it is not known whether the coupling of these two feedback loops can maintain epigenetic silencing independently of DNA sequence and in the absence of enabling mutations that disrupt genome-wide chromatin structure or transcription15-17. Here, using the fission yeast Schizosaccharomyces pombe, we show that siRNA-induced H3K9me and silencing of a euchromatic gene can be epigenetically inherited in cis during multiple mitotic and meiotic cell divisions in wild-type cells. This inheritance involves the spreading of secondary siRNAs and H3K9me3 to the targeted gene and surrounding areas, and requires both RNAi and H3K9me, suggesting that the siRNA and H3K9me positive-feedback loops act synergistically to maintain silencing. By contrast, when maintained solely by histone PTM positive feedback, silencing is erased by H3K9 demethylation promoted by Epe1, or by interallelic interactions that occur after mating to cells containing an expressed allele even in the absence of Epe1. These findings demonstrate that the RNAi machinery can mediate transgenerational epigenetic inheritance independently of DNA sequence or enabling mutations, and reveal a role for the coupling of the siRNA and H3K9me positive-feedback loops in the protection of epigenetic alleles from erasure.


Protein kinase activity immunoprecipitated from adenovirus infected cells by sera from tumor-bearing hamsters.
Earlier, we reported (N. J. Lassam, S. T. Bayley, F. L. Graham, and P. E. Branton, Nature (London) 277:241-243, 1979) detecting protein kinase activity when cytoplasmic extracts of human adenovirus type 5 (Ad5)-infected KB cells immunoprecipitated with 14b antitumor serum directed against the transforming proteins of Ad5, were incubated with [gamma-32P]ATP. Here we show that in the in vitro assay this kinase phosphorylated both the heavy chain of immunoglobulin G and polypeptide than comigrated on sodium dodecyl sulfate gels with the 58,000-dalton Ad5 antigen. It also phosphorylated added histone H3. Evidence is presented that the protein kinase activity found with extracts from Ad5-infected cells is not due to nonspecific trapping of cellular enzymes in immune complexes, but to an enzyme which is distinct from kinases detected at background levels in controls. Serine and threonine were the major phosphorylated amino acids, and essentially no phosphotyrosine was detected. Protein kinase activity detected in Ad12-infected cells immunoprecipitated by an antiserum derived from hamsters bearing Ad12-induced tumors appeared to be immunologically distinct from that immunoprecipitated from Ad5-infected cells by 14b serum.


ACOG committee opinion. Air travel during pregnancy.
In the absence of obstetric or medical complications, pregnant women can observe the same general precautions for air travel as the general population and can fly safely up to 36 weeks of gestation. In-craft environmental conditions, such as low cabin humidity and changes in cabin pressure, coupled with the physiologic changes of pregnancy, do result in maternal adaptations, which could have transient effects on the fetus. Pregnant air travelers with medical problems that may be exacerbated by a hypoxic environment, but who must travel by air, should be prescribed supplemental oxygen during air travel. Pregnant women at significant risk for preterm labor or with placental abnormalities should avoid air travel. Because air turbulence cannot be predicted and the risk for trauma is significant, pregnant women should be instructed to continuously use their seat belts while seated, as should all air travelers. Pregnant air travelers may take precautions to ease in-flight discomfort, and although no hard evidence exists, preventive measures can be employed to minimize risks.


Inhibitory effect of glyceollins on vasculogenesis through suppression of endothelial progenitor cell function.
Endothelial progenitor cells (EPCs) are derived from hematopoietic stem cells, and have the ability to differentiate into mature endothelial cells and contribute to neovascularization. Glyceollins are a type of phytoalexin produced in soybeans under stress conditions. The aim of this study is to determine the effect of glyceollin treatment on EPCs during early tumor vasculogenesis. We found that glyceollin treatment significantly decreased the number of EPC colony-forming units in human cord blood-derived AC133⁺ cells and mouse bone-marrow-derived c-Kit⁺/Sca-1⁺/Lin⁻ cells. Glyceollin treatment diminished the number of lineage-committed EPC cells in a dose-dependent manner (1-20 μM). Glyceollin treatment inhibited EPC migration, tube formation and the mRNA expression of angiopoietin-1 (Ang-1), Tie-2, stromal-derived factor-1 (SDF-1), C-X-C-chemokine receptor-4 (CXCR4), and endothelial nitric oxide synthase (eNOS) in cultured EPCs. Glyceollin treatment suppressed activation of Akt, Erk, and eNOS induced by SDF-1α or vascular endothelial growth factor (VEGF). Treatment with 10 mg/kg glyceollins significantly reduced the number of tumor-induced circulating EPCs and the incorporation of EPCs into neovessels in bone marrow transplanted mice. These results suggest that glyceollins inhibit the function of EPCs in tumor neovascularization. Glyceollins from soybean elicitation could be beneficial in prevention of cancer development via vasculogenesis.


A technique for assessing the effects of olfaction on feed preference in lactating Holstein cows.
Our objective was to develop a method for assessing the effects of olfaction on feed preference. Two multiparous lactating Holstein cows were offered a totally mixed ration consisting of corn silage, alfalfa haylage, and a ground corn and soybean meal-based concentrate mixture (25:25:50 on a DM basis) for their ad libitum consumption in four consecutive 2.5-h periods daily for 5 d. An apparatus was developed that allowed odorants to be distributed at a set rate over two feeding containers with limited possibility of odor carryover. Four odorants and a control (no odorant) were compared against each other. All possible comparisons were conducted on the left and right feeding sides to avoid potential lateral-preference effects. Rank values of 0 or .5 were assigned to each odorant based on the percentage of total feed consumed in a period. A test of overall equality based on the sums of squares of ranks was used to determine whether odors affected preference. The limited results indicated that inhalation of odorants did not affect preference. Rank values were doubled for several odorants when compared with others, which suggested that the sample size limited experimental sensitivity. To attain reasonable power, we estimated that at least six cows were needed per study. Large effects of odorants on feed preference would have been required to reach statistical significance in this trial; however, the method provides a practical technique for testing the effects of olfaction on feed preference in cattle when the suggested number of cows is used.


Effects of a monoclonal antibody to P-selectin on recovery of neonatal lamb hearts after cold cardioplegic ischemia.
The interaction between endothelium and leukocytes plays a crucial role in ischemia-reperfusion injury. P-selectin, which is expressed on activated endothelium, mediates the first step in leukocyte adherence to the endothelium. This study examined the effects of a monoclonal antibody (mAb) against P-selectin on the recovery of cardiac function and myocardial neutrophil infiltration after ischemia. Thirteen blood-perfused, isolated neonatal lamb hearts underwent 2 hours of hypothermic cardioplegic arrest and 2 hours of reperfusion. Immediately before reperfusion, mAb to P-selectin was administered to the perfusate (15 micrograms/mL) in 6 hearts (group P-sel). In control (n = 7), the same volume of saline was added. Isovolumic left ventricular function and coronary blood flow were measured. At 2 hours after reperfusion, myocardial myeloperoxidase activity, an index of neutrophil accumulation, was assayed. At 30 minutes of reperfusion, hearts treated with mAb to P-selectin achieved significantly greater recovery of maximum developed pressure (70 +/- 4% in control versus 77 +/- 2% in group P-sel, P < 0.01), maximum positive first derivative of pressure (dP/dt) (64 +/- 7% in control versus 73 +/- 5% in group P-sel, P < 0.05), and maximum negative dP/dt (61 +/- 6% in control versus 70 +/- 6% in group P-sel, P < 0.05) compared with control. Percent baseline of coronary blood flow was also significantly increased in group P-sel (135 +/- 40% in control versus 205 +/- 43% in group P-sel, P < 0.05). Myocardial myeloperoxidase activity was significantly lower (P < 0.05) in group P-sel (4.7 +/- 3.2) versus control (16.0 +/- 10.1). (Units are change in absorbance/min/g tissue.) The functional blockade of P-selectin resulted in better recovery of cardiac function and attenuated neutrophil accumulation during early reperfusion. Strategies to block P-selectin mediated neutrophil adherence may have clinical application in improving myocardial function at early reperfusion.


Upper and lower extremity motor function and cognitive impairment in multiple sclerosis.
Motor impairments and cognitive dysfunction are common in multiple sclerosis (MS). We aimed to delineate the relationship between cognitive capacity and upper and lower motor function in 211 MS patients, and 120 healthy volunteers. Lower and upper motor function were assessed with the Timed 25 Foot Walk (T25FW) and the Nine Hole Peg Test (NHPT) as implemented in the Multiple Sclerosis Functional Composite (MSFC). Subjects also underwent neuropsychological evaluation. Hierarchical linear regression analysis was conducted separately for the MS and healthy groups with the T25FW and NHPT serving as the outcome measures. Cognitive performance indices served as predictors. As expected, healthy subjects performed better than the MS group on all measures. Processing speed and executive function tests were significant predictors of lower and upper motor function in both groups. Correlations were more robust in the MS group, where cognitive tests predicted variability in motor function after controlling for disease duration and physical disability. In conclusion, we find evidence of higher order cognitive control of motor function that appears to be particularly salient in this large and representative MS sample. The findings may have implications for risk assessment and treatment of mobility dysfunction in MS.


Objectively measured physical activity and depressive symptoms in adult outpatients diagnosed with major depression. Clinical perspectives.
Physical activity (PA) is linked to reduced risk of depression, but research on the objectively measured PA in clinically diagnosed adult outpatients with major depressive disorder (MDD) is scarce. This study aimed to examine relationships of objectively measured PA with depression and mood. A total of 19 outpatients (6 males) with MDD, a mean age of 47.79 ± 11.67 years and mild-moderate depression participated in the study. To record PA, participants wore a triaxial accelerometer device on the right hip during waking hours for seven consecutive days. Depression and mood were assessed with self-reports immediately after day seven. Participants wore the accelerometers for a high number of days (M = 6.26 ± 1.24 days) and hours per day (13.40 ± 2.61 h), recording light (266.01 ± 100.74 min/day) or moderate (31.19 ± 24.90 min/day) PA, and sedentary time (515.33 ± 155.71 min/day). Stepwise regression analysis yield a significant prediction (p < .05) with only moderate PA contributing to the prediction of depression (Beta = -0.47, p < .05). The model explained 22% of the variance of depression. Our findings provide valuable preliminary evidence regarding the relationship between objectively measured PA and lower depression in clinically diagnosed outpatients with MDD, suggesting moderate PA may help alleviating depressive symptoms.


An exploratory study of the individual determinants of students' sexual risk behaviour at a South African university.
The prevalence of sexual risk behaviour is high on campuses at South African universities, putting many students at risk of HIV infection. This study explores individual influences on students' sexual risk-taking behaviour at the University of KwaZulu-Natal. The study collected cross-sectional data obtained between late 2008 and early 2010. A total of 80 in-depth interviews and four focus group discussions were conducted, allowing for an equal representation of males and females and a mix of different races (black, white, Indian and coloured) among students at two campuses (Howard College and Pietermaritzburg) and at different levels of study (undergraduate and postgraduate). The data were analysed using thematic analysis to identify factors associated with the students' sexual risk behaviour. Sexual risk behaviour was found to be influenced by a range of individual factors, especially: personal beliefs about long-term relationships; attitudes towards sex for variety; a drive for material wealth; a lack of satisfaction in relationships; levels of trust and attention; pursuit of the long-term goal of marriage; and HIV denialism. As young adults, university students lack experience in assessing influences on their risk-taking behaviour, thus they require education on the individual risk factors that put them at risk of acquiring HIV infection. Likewise, the nature of these factors pose significant challenges to reducing sexual risk behaviour among university students.


Predictors of family communication of one's organ donation intention in Switzerland.
Family members continue to play a prominent role in decisions to donate organs at the time of death. Prior knowledge of the deceased's intention to donate was identified as an important influential factor in the donation decision-making process. This study examined what factors lead to family communication of a person's wish regarding organ donation. A population-based survey was used to identify the prevalence of people who had informed family members of their intention to donate. Associated factors were evaluated using bivariate and multivariate analyses. Multivariate analysis revealed that communication to a family member of the intention to donate organs was more likely if the respondent had a signed donor card (OR = 10.23, CI = 5.25-19.93), had a family discussion on organ donation or transplantation (OR = 7.12, CI = 4.91-10.34), had a partner and knew his or her attitude to organ donation (OR = 5.76, CI = 4.20-7.90), had previously personally had a good look at the issue of organ donation (OR = 2.59, CI = 1.79-3.75), was rather younger (OR = 0.98, CI = 0.97-0.99), was of Swiss nationality (OR = 2.21, CI = 1.25-3.91), felt that he or she was sufficiently informed (OR = 2.10, CI = 1.50-2.94), had the information necessary to come to an appropriate decision on organ donation and-although this relation may be weaker-were (rather) willing to become an organ donor after death (OR = 1.41, CI = 1.01-1.97). Our findings highlight the need for public education and community campaigns to promote the need to share with others, the intention to donate and to increase people's knowledge on this issue.


Taxonomic implications of synthesis of poly-beta-hydroxybutyrate and other poly-beta-hydroxyalkanoates by aerobic pseudomonads.
Whereas poly-beta-hydroxybutyrate (PHB) production by Pseudomonas species is rare, synthesis of medium-chain-length poly-beta-hydroxyalkanoates (mcl-PHAs) other than PHB, has been observed in fluorescent and non-fluorescent species. Contrary to original reports, Pseudomonas corrugata and Pseudomonas ficuserectae accumulate mcl-PHAs and not PHB. The taxonomic implications of these characteristics are discussed.


Venous thrombosis at unusual sites and the role of thrombophilia.
Thrombophilia includes multiple inherited and acquired risk factors that determine a shift in the balance of procoagulant and anticoagulant factors promoting hypercoagulability, which is associated with an increased risk of venous thromboembolism (VTE). VTE is characterized by more common clinical manifestations, such as deep vein thrombosis of the lower limbs or pulmonary embolism, and less common clinical manifestations affecting cerebral, splanchnic, upper limbs, and retinal veins. The role of inherited thrombophilia in the pathogenesis of VTE at unusual sites is better established in cerebral vein thrombosis, but its role is less clear in splanchnic, upper limbs, and retinal vein thrombosis, in which acquired risk factors such as malignancy, central venous catheters, or systemic diseases also are frequently involved. The complex interactions between different inherited and acquired thrombophilic risk factors and their relationship with endothelium may be considered the pathophysiologic key of underlying phenotypic manifestations of thrombosis. The understanding of these mechanisms might facilitate diagnosis with appropriate investigations and improve therapeutic decision making.


Multiomics of HER2-low triple-negative breast cancer identifies a receptor tyrosine kinase-relevant subgroup with therapeutic prospects.
To provide complementary information and reveal the molecular characteristics and therapeutic insights of HER2-low breast cancer, we performed this multiomics study of hormone receptor-negative (HR-) and HER2-low breast cancer, also known as HER2-low triple-negative breast cancer (TNBC), and identified 3 subgroups: basal-like, receptor tyrosine kinase-relevant (TKR), and mesenchymal stem-like. These 3 subgroups had distinct features and potential therapeutic targets and were validated in external data sets. Interestingly, the TKR subgroup (which exists in both HR+ and HR- breast cancer) had activated HER2 and downstream MAPK signaling. In vitro and in vivo patient-derived xenograft experiments revealed that pretreatment of the TKR subgroup with a tyrosine kinase inhibitor (lapatinib or tucatinib) could inhibit HER2 signaling and induce accumulated expression of nonfunctional HER2, resulting in increased sensitivity to the sequential HER2-targeting, Ab-drug conjugate DS-8201. Our findings identify clinically relevant subgroups and provide potential therapeutic strategies for HER2-low TNBC subtypes.


Estimating the duration of speciation from phylogenies.
Speciation is not instantaneous but takes time. The protracted birth-death diversification model incorporates this fact and predicts the often observed slowdown of lineage accumulation toward the present. The mathematical complexity of the protracted speciation model has barred estimation of its parameters until recently a method to compute the likelihood of phylogenetic branching times under this model was outlined (Lambert et al. ). Here, we implement this method and study using simulated phylogenies of extant species how well we can estimate the model parameters (rate of initiation of speciation, rate of extinction of incipient and good species, and rate of completion of speciation) as well as the duration of speciation, which is a combination of the aforementioned parameters. We illustrate our approach by applying it to a primate phylogeny. The simulations show that phylogenies often do not contain enough information to provide unbiased estimates of the speciation-initiation rate and the extinction rate, but the duration of speciation can be estimated without much bias. The estimate of the duration of speciation for the primate clade is consistent with literature estimates. We conclude that phylogenies combined with the protracted speciation model provide a promising way to estimate the duration of speciation.


A great earthquake doublet and seismic stress transfer cycle in the central Kuril islands.
Temporal variations of the frictional resistance on subduction-zone plate boundary faults associated with the stick-slip cycle of large interplate earthquakes are thought to modulate the stress regime and earthquake activity within the subducting oceanic plate. Here we report on two great earthquakes that occurred near the Kuril islands, which shed light on this process and demonstrate the enhanced seismic hazard accompanying triggered faulting. On 15 November 2006, an event of moment magnitude 8.3 ruptured the shallow-dipping plate boundary along which the Pacific plate descends beneath the central Kuril arc. The thrust ruptured a seismic gap that previously had uncertain seismogenic potential, although the earlier occurrence of outer-rise compressional events had suggested the presence of frictional resistance. Within minutes of this large underthrusting event, intraplate extensional earthquakes commenced in the outer rise region seaward of the Kuril trench, and on 13 January 2007, an event of moment magnitude 8.1 ruptured a normal fault extending through the upper portion of the Pacific plate, producing one of the largest recorded shallow extensional earthquakes. This energetic earthquake sequence demonstrates the stress transfer process within the subducting lithosphere, and the distinct rupture characteristics of these great earthquakes illuminate differences in seismogenic properties and seismic hazard of such interplate and intraplate faults.


Prospective phase II trial of regional hyperthermia and whole liver irradiation for numerous chemorefractory liver metastases from colorectal cancer.
A prospective phase II trial was conducted to evaluate the effectiveness and toxicity of regional hyperthermia and whole liver irradiation (WLI) for numerous chemorefractory liver metastases from colorectal cancer. Enrolled patients had numerous chemorefractory hepatic metastases from colorectal cancer. Five sessions of hyperthermia and seven fractions of 3-gray WLI were planned. Health-related quality of life (HRQoL) was determined using the Korean version of the European Organization for Research and Treatment of Cancer quality of life questionnaire C-30 and the Functional Assessment of Cancer Therapy-Hepatobiliary version 4.0. Objective and pain response was evaluated. A total of 12 patients consented to the study and the 10 who received WLI and hyperthermia were analyzed. WLI was completed as planned in nine patients and hyperthermia in eight. Pain response was partial in four patients and stable in four. Partial objective response was achieved in three patients (30.0%) and stable disease was seen in four patients at the 1-month follow-up. One patient died 1 month after treatment because of respiratory failure related to pleural metastasis progression. Other grade III or higher toxicities were detected in three patients; however, all severe toxicities were related to disease progression rather than treatment. No significant difference in HRQoL was noted at the time of assessment for patients who were available for questionnaires. Combined WLI and hyperthermia were well tolerated without severe treatment-related toxicity with a promising response from numerous chemorefractory hepatic metastases from colorectal cancer.


Anaesthetic considerations for the hiv positive parturient.
The HIV epidemic in children parallels that among women on account of perinatal transmission. A combination of antiretroviral therapy and elective caesarean section reduces the rate of vertical transmission to <2%. Elective caesarean section independent of antiretroviral therapy decreases the risk of HIV vertical transmission from mother to baby. However, a caesarean section is a major surgical intervention that has well-reported complications. Women infected with HIV have been reported to be more susceptible to such complications. The multi-organ nature of HIV poses challenges at the time of surgery and anesthesia. Preoperative evaluation will allow a good prediction for the perioperative risk of the HIV-patient. The anesthesiologist should be aware of the possible toxic side effects or the possible interaction of antiretroviral drugs with the anesthetics. Some of these adverse effects may mimic signs and symptoms of the HIV disease itself. Regional anesthesia has been shown to be associated with reduced morbidity and mortality in a wide range of patients, including HIV positive parturients. Finally, the possibility of transmission in the health care setting highlights the need for anesthetists to enforce rigorous infection control policies to protect themselves, other health workers and their patients.


The promise of CCR5 antagonists as new therapies for HIV-1.
The chemokine receptors CCR5 and CXCR4 were identified as HIV-1 co-receptors in 1996. Since then, a range of agents that bind these receptors and potently block HIV-1 infection have been described, including monoclonal antibodies, peptides and modified chemokines. However, small organic molecules that bind CCR5 are currently the most promising of the co-receptor antagonists for the potential treatment of HIV. These agents are now in advanced stages of clinical development and should soon augment current therapies, as well as being candidates for inclusion in microbicides. Unlike existing drugs that target HIV proteins (eg, reverse transcriptase and protease), co-receptor antagonists bind receptors encoded by the host. As a consequence, blockade of these receptors may result in immunosuppressive effects or other disorders. Furthermore, co-receptor inhibitors may also be more toxic than currently available HIV therapies, and it is not yet clear whether they will become candidates for first-line therapy. Nonetheless, safer, less toxic versions of such inhibitors may be achievable in the future. The use of CCR5 inhibitors as a second-line treatment increases the possibility that these reagents will select for more pathogenic CXCR4-using variants. The development of effective CXCR4 antagonists for dual treatment would be beneficial; however, whether long-term treatment with antagonists of the widely expressed CXCR4 receptor is feasible without toxicity is unknown. This review discusses the current status of CCR5 antagonists, their modes of action and their development for therapeutic use.


Role of growth factor synthesis in the acquisition of insulin/insulin-like growth factor I independence in rat mammary carcinoma cells.
In previous work, we demonstrated that a subset of carcinogen-induced rat mammary carcinomas consists of cells that are independent of growth factors strictly required by normal rat mammary epithelial (RME) cells for long-term growth in serum-free medium. Furthermore, only those tumors that expressed growth factor independence in vitro were serially transplantable in vivo. The present studies were aimed at determining if the independence of insulin (IN)/insulin-like growth factor I (IGF-I) is mediated by autocrine factors synthesized by the rat mammary tumor (RMT) cells. The results of these experiments indicate that IN/IGF-I-independent RMT cells do not synthesize IGF-I that is detectable at the message or peptide level. Both normal and neoplastic cells do, however, secrete IGF-I-binding activity. Conditioned medium, cell lysates, and cell extracts obtained from growth factor-independent cells do not contain growth factor activity that can substitute for IN for growth of IN-dependent RMT cells. Growth factor-independent cells do not express a density dependence for growth in IN-free medium nor do they respond to exogenous IN or IGF-I in low density growth assays. By contrast, growth factor-dependent cells that were rendered IN/IGF-I independent by transfection with an expression vector containing the IGF-I gene secrete IGF-I-like biological activity that is readily detectable and maintain responsiveness to exogenous IN at low densities. Taken together, these results suggest that growth factor-independent RMT cells are truly autonomous of IN/IGF-I for growth and are not synthesizing a growth factor that satisfies their IN/IGF-I requirement in an autocrine manner.


Ictal and interictal brain activation in episodic migraine: Neural basis for extent of allodynia.
In some patients, migraine attacks are associated with symptoms of allodynia which can be localized (cephalic) or generalized (extracephalic). Using functional neuroimaging and cutaneous thermal stimulation, we aimed to investigate the differences in brain activation of patients with episodic migraine (n = 19) based on their allodynic status defined by changes between ictal and interictal pain tolerance threshold for each subject at the time of imaging. In this prospective imaging study, differences were found in brain activity between the ictal and interictal visits in the brainstem/pons, thalamus, insula, cerebellum and cingulate cortex. Significant differences were also observed in the pattern of activation along the trigeminal pathway to noxious heat stimuli in no allodynia vs. generalized allodynia in the thalamus and the trigeminal nucleus but there were no activation differences in the trigeminal ganglion. The functional magnetic resonance imaging (fMRI) findings provide direct evidence for the view that in migraine patients who are allodynic during the ictal phase of their attacks, the spinal trigeminal nucleus and posterior thalamus become hyper-responsive (sensitized)-to the extent that they mediate cephalic and extracephalic allodynia, respectively. In addition, descending analgesic systems seem as "switched off" in generalized allodynia.


The development and use of radiolabeled antitumor antibodies.
The use of radioactive tumor-localizing antibodies is developed historically, starting with the demonstration that antibodies can be radioiodinated without destroying antibody activity. Then, antibodies against normal organs were shown to contain antibodies which localize in the normal organ. Subsequently, antibodies capable of localizing in tumors were demonstrated, and these localized well enough to permit their use diagnostically by scanning for radioactivity and their use therapeutically by localizing sufficient radioiodine. Various relevant problems are discussed.


Epigenome variation in severe asthma.
Asthma is a complex heterogeneous disease process with mild, moderate, and severe classifications. Although the science of genomics has opened our understanding of the molecular underpinnings of asthma, epigenetics is emerging as a mechanism whereby the expression of disease-risk genes may be influenced by environmental exposure. The purpose of this article is to discuss the methodology of data collection and evaluation involved in genome-wide methylation profiling (epigenomic) through presentation of data generated for a population presenting with severe asthma. Over 14,000 gene promoter sites were analyzed for methylation status among six subjects with severe asthma and four normal controls in this pilot study. Two duplicate samples were used as technical replicates. Nonsmoking case/control subjects were chosen based on similar gender and age. Blood samples were used for DNA extraction, and methylation data were collected utilizing the Illumina Infinium HumanMethylation27BeadChip platform. Technical replicates were highly concordant, and statistically significant differences were found in methylation profiles between subjects with severe asthma and normal controls (p < 10(-8)), some previously reported with pulmonary function and others never before reported. After correction for multiple testing, three gene promoter regions remained statistically different: FAM181A, ZNF718, and MRI1. This research supports the internal validity of the Illumina platform in methylation analysis of DNA from stored blood samples. Although significant differences in methylation were noted between subjects with severe asthma and controls, the small sample size warrants further investigation into these results.


A new method for treating weeping canals: clinical and histopathologic study.
In this study the effect of Nd:YAG laser on the apical oozing of the weeping canals was evaluated both clinically and histopathologically. It was noticed that application of the laser beam at energy 15 pps/1.50 w for 2-2.5 minutes to the apical position of these canals resulted in complete dryness of the canals in 82-23% of the cases. On the other hand most of the lased teeth become relatively asymptomatic after laser application. Histopathologic examination of the periapical lesion related to weeping canals showed marked improvement in the inflammatory condition. Sixty percent of lased cases showed grade 1 inflammation where 70% cases showed grade 3 inflammation in unlased cases.


Synthesis and characterization of Zr- and Hf-doped nano-TiO2 as internal standards for analytical quantification of nanomaterials in complex matrices.
The reliable quantification of nanomaterials (NMs) in complex matrices such as food, cosmetics and biological and environmental compartments can be challenging due to interactions with matrix components and analytical equipment (vials and tubing). The resulting losses along the analytical process (sampling, extraction, clean-up, separation and detection) hamper the quantification of the target NMs in these matrices as well as the compatibility of results and meaningful interpretations in safety assessments. These issues can be overcome by the addition of known amounts of internal/recovery standards to the sample prior to analysis. These standards need to replicate the behaviour of target analytes in the analytical process, which is mainly defined by the surface properties. Moreover, they need to carry a tag that can be quantified independently of the target analyte. As inductively coupled plasma mass spectrometry is used for the identification and quantification of NMs, doping with isotopes, target analytes or with chemically related rare elements is a promising approach. We present the synthesis of a library of TiO2 NMs doped with hafnium (Hf) and zirconium (Zr) (both low in environmental abundance). Zirconia NMs doped with Hf were also synthesized to complement the library. NMs were synthesized with morphological and size properties similar to commercially available TiO2. Characterization included: transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy, X-ray diffraction spectroscopy, Brunauer-Emmett-Teller total specific surface area analysis, cryofixation scanning electron microscopy, inductively coupled plasma optical emission spectroscopy and UV-visible spectrometry. The Ti : Hf and Ti : Zr ratios were verified and calculated using Rietveld refinement. The labelled NMs can serve as internal standards to track the extraction efficiency from complex matrices, and increase method robustness and traceability of characterization/quantification.


Polymer-Assisted Synthesis of Single and Fused Diketomorpholines.
The synthesis of different diketomorpholines via N-acyl-3,4-dihydro-2 H-1,4-oxazine-3-carboxylic acids is reported in this article. The key intermediates were prepared using a convenient solid-phase synthesis starting from polymer-supported Ser( tBu)-OH. After subsequent sulfonylation with 4-nitrobenzenesulfonyl chloride (4-Nos-Cl), alkylation with an α-bromoketone, cleavage of the 4-Nos group and acylation with an α-halocarboxylic acids, acid-mediated cleavage from the resin yielded dihydrooxazine-3-carboxylic acids in high crude purities. Depending on the reaction conditions, exposure to base resulted in cyclization to either oxazino[3,4- c][1,4]oxazine-diones or 3-methylidenemorpholine-2,5-diones. Further reaction with triethylsilane-trifluoroacetic acid (TES/TFA) led to olefin reduction, in the case of oxazino[3,4- c][1,4]oxazine-dione with full control of the newly formed stereocenter.


Position of the American Dietetic Association: functional foods.
It is the position of The American Dietetic Association that functional foods, including whole foods and fortified, enriched, or enhanced foods, have a potentially beneficial effect on health when consumed as part of a varied diet on a regular basis, at effective levels. The Association supports research to further define the health benefits and risks of individual functional foods and their physiologically active components. Dietetics professionals will continue to work with the food industry, government, the scientific community, and the media to ensure that the public has accurate information regarding this emerging area of food and nutrition science. Knowledge of the role of physiologically active food components, both from phytochemicals and zoochemicals, has changed the role of diet in health. Functional foods have evolved as food and nutrition science has advanced beyond the treatment of deficiency syndromes to reduction of disease risk. This position reviews the definition of functional foods, their regulation, and the scientific evidence supporting this emerging area of food and nutrition. Foods can no longer be evaluated only in terms of macronurtrient and micronutrient intake. Analyzing the content, of other physiologically active components will be necessary. The availability of health-promoting functional foods in the US diet has the potential to help ensure a healthier population. However, each functional food should be evaluated on the basis of scientific evidence to ensure appropriate integration into a varied diet.


Effects of acoustical stimuli delivered through hearing aids on tinnitus.
The use of acoustic signals to mask, mix with, or ease the distress associated with tinnitus has been clinically employed for decades. It has been proposed that expanding acoustic options for tinnitus sufferers due to personal preferences is desirable. Fractal tones incorporate many useful characteristics of music while avoiding certain features that could be distracting to some individuals. To assess the effects on relaxation, tinnitus annoyance, tinnitus handicap, and tinnitus reaction from the use of a hearing aid that incorporates combinations of amplification, fractal tones, and white noise. Participants listened to experimental hearing aids containing several acoustic options and were asked to rate the signals in terms of their effect on relaxation and tinnitus annoyance. They subsequently wore the hearing aids for 6 mo and completed tinnitus handicap and reaction scales. Fourteen hearing-impaired adults with primary complaints of subjective tinnitus. Participants were tested wearing hearing aids containing several programs including amplification only, fractal tones only, and a combination of amplification, noise, and/or fractal tones. The fractal tones (now commercially available as the "Zen" feature) were generated by the Widex Mind hearing aid. Rating procedures were conducted in the laboratory, and tinnitus reaction and handicap were assessed during and following a 6 mo field trial. Data were collected at the initial visit, one week, 1 mo, 3 mo, and 6 mo. Nonparametric statistics included Wilcoxon matched-pairs signed-rank, chi(2), and repeated-measures analyses of variance. Thirteen of 14 participants reported that their tinnitus annoyance, as measured by the Tinnitus Annoyance Scale, was reduced for at least one of the amplified conditions (with or without fractal tones or noise), relative to the unaided condition. Nine assigned a lower tinnitus annoyance rating when listening to fractal tones alone versus the amplification-alone condition. There was a range of preferences observed for fractal settings, with most participants preferring fractals with a slow or medium tempo and restricted dynamic range. The majority (86%) indicated that it was easier to relax while listening to fractal signals. Participants had preferences for certain programs and fractal characteristics. Although seven participants rated the noise-only condition as providing the least tinnitus annoyance, only two opted to have noise only as a program during the field trial, and none selected the noise-only condition as the preferred setting. Furthermore, while all four of the experienced hearing aid users selected noise as producing the least annoying tinnitus in the laboratory, only one selected it for field wear. Tinnitus Handicap Inventory and Tinnitus Reaction Questionnaire scores were improved over the course of the 6 mo trial, with clinically significant improvements occurring for over half of the participants on at least one of the measures. The results suggest that use of acoustic stimuli, particularly fractal tones, delivered though hearing aids can provide amplification while allowing for relief for some tinnitus sufferers. It is important to recognize, however, that tinnitus management procedures need to be supplemented with appropriate counseling.


Mortality from occupational accidents to United Kingdom fishermen 1961-80.
After the catastrophic losses of three Hull deep sea trawlers in 1968, the Committee of Inquiry into Trawler Safety (CITS) was established. Fourteen months later, CITS reported on factors affecting the safety of deep sea trawlers and their crews. Pre-CITS (1961-70) and post-CITS (1971-80) crude mortality rates for accidents at work are compared for "deep sea" fishermen (those working on vessels greater than or equal to 24.4 m (80 feet) registered length) and "inshore" fishermen (those working on vessels less than 24.4 m). The ratio of deep sea to inshore fishermen had changed from 1:1.5 (1961) to 1:7.0 (1980), reflecting the radical restructuring of the fishing fleet that began in the early 1970s. Between 1961 and 1980, there were 909 recorded deaths at sea of United Kingdom fishermen. Of these, 711 (78%) were due to accidents (either from vessel losses or personal accidents) and 198 (22%) were due to unspecified disease, homicide, and suicide. Comparison of pre-CITS and post-CITS mean death rates showed an increase (+39%) for deep sea fishermen, a decrease (-4%) for inshore fisherman, and an increase (+2%) for both combined. For deep sea fishermen, there were synchronous increases in mortality from vessel losses (+32%) and from personal accidents (+49%, p less than 0.05) whereas the overall rate for inshore fishermen reflected a decrease (-33%, p less than 0.01) in deaths from personal accidents but an increase (+52%) in deaths from vessel losses. Although pre-CITS mortality rates exhibited no statistically significant difference between deep sea fisherman was significantly greater (p< 0.02). Compared with coal miners, fishermen were, on average, four times more likely to die from accidents at work. If CITS had reasonable cause for concern in 1969, the grounds for similar concern did not diminish because the evidence suggests that deep sea fishermen were at no lesser risk of death from accidents after CITS reported than before. Overall, both groups of fishermen experienced an accident mortality rate between 1961 and 1980 that showed no indication of improvement.


Case managers' roles and functions: Commission for Case Manager Certification's 2004 research, part II.
The Commission for Case Manager Certification (CCMC) conducted its third case managers' role and functions study in 2004 for the purpose of validating the currency and relevancy of the certified case manager examination. The results of this study are shared in an article of 2 parts. Part I, which was published in the previous issue of this journal, discussed the process the CCMC used for the development of the Case Managers' Role and Functions Survey Instrument and the identification of new 6 essential functions and 6 knowledge areas that describe case management practice. These findings were based on the survey of a large national sample of practicing case managers. Part II continues the analysis of the results and focuses on identifying the empirical (statistically derived) activity and knowledge domains of case management practice, using exploratory factor analysis. It discusses the similarities and differences found among various subgroups of case managers who were compared on the basis of certain demographic variables. In addition, Part II summarizes future changes in the field of case management as perceived by those who participated in the study.


[Embryologic and pathogenetic aspects of the common atrioventricular canal development].
Atrioventricular canal (AVC) is an inherited defect the embryological basis of which is deficiency of the affluent part of the interventricular septum (IVS). Folds of the atrioventricular (AV) valves are formed from the myocardium and not from the endocardial thickening but much later than the IVS formation. Under the conditions of the affluent part of IVS the mode of connection of the anterior fold of the left AV valve creates the narrowing of the left ventricular effluent part. Endocardial thickenings play a role of a glue fixing corresponding structural components of AV valves and primary heart partitions. The degree of sticking together determines great variants of the defect anatomy. Important deficiency of the affluent part of IVS is possible this making the function difficult due to space change of the endocardial thickenings. The common valve ring with freely floating bridge-like folds is frequently revealed in such case. The notion "deficiency of the endocardial thickenings" has the only manifestation as an isolated splitting of the anterior fold of the mitral valve and exhibits main features of AVC.


Indocyanine Green-Loaded Liposomes for Light-Triggered Drug Release.
Light-triggered drug delivery systems enable site-specific and time-controlled drug release. In previous work, we have achieved this with liposomes containing gold nanoparticles in the aqueous core. Gold nanoparticles absorb near-infrared light and release the energy as heat that increases the permeability of the liposomal bilayer, thus releasing the contents of the liposome. In this work, we replaced the gold nanoparticles with the clinically approved imaging agent indocyanine green (ICG). The ICG liposomes were stable at storage conditions (4-22 °C) and at body temperature, and fast near-infrared (IR) light-triggered drug release was achieved with optimized phospholipid composition and a 1:50 ICG-to-lipid molar ratio. Encapsulated small molecular calcein and FITC-dextran (up to 20 kDa) were completely released from the liposomes after light exposure for 15 s. Location of ICG in the PEG layer of the liposomes was simulated with molecular dynamics. ICG has important benefits as a light-triggering agent in liposomes: fast content release, improved stability, improved possibility of liposomal size control, regulatory approval to use in humans, and the possibility of imaging the in vivo location of the liposomes based on the fluorescence of ICG. Near-infrared light used as a triggering mechanism has good tissue penetration and safety. Thus, ICG liposomes are an attractive option for light-controlled and efficient delivery of small and large drug molecules.


Prevalence of knee bursitis in the workforce.
Knee bursitis (KB) is a common disorder in specific occupations requiring frequent and/or sustained kneeling postures. To assess the prevalence of KB in the general working population. Between 2002 and 2005, a total of 3710 workers of a French region were randomly included in the study. A standardized physical examination of the knee was performed when knee pain was reported by the worker during the preceding 12 months. The criteria for diagnosis of KB were (i) the presence of pain and/or tenderness in the anterior face of the knee at the date of the examination (or for at least 4 days in the preceding week) and (ii) the presence of swelling and/or pressure-induced pain of the pre- or infra-patellar bursa. Occupational risk factors were assessed by a self-administered questionnaire. The prevalence of uni- or bilateral cases of knee bursitis was low: 0.6% [0.2-0.9] in men and 0.2% [0.0-0.6] in women. The highest prevalence was observed in the construction sector (2.3% [0.8-5.4]) and in the food and meat processing industries (1.4% [0.4-3.5)]. More blue-collar workers were affected than other occupation categories (0.8% [0.3-1.2] versus 0.1% [0.0-0.4]). The study showed a concentration of cases among male workers exposed to heavy workloads and frequent kneeling.


Posterior spinal artery infarct.
Acute medullary syndrome developed in a patient in whom glue had been inadvertently injected into the right posterior radiculomedullary artery during endovascular occlusion of a spinal dural arteriovenous fistula at T-11. MR imaging 40 days after the procedure showed signal changes and contrast enhancement in the posterior and right lateral column at T10-11. Circumscribed signal changes in the same areas without contrast enhancement were seen 4 months later. MR imaging was able to show this posterior spinal artery infarct.


Analysis of the diffractional properties of dual-period apodizing gratings: theoretical and experimental results.
We present an analysis of the diffractional properties of dual-period apodizing gratings. In a previous paper we used these components to obtain single-lateral-mode and dual-longitudinal-mode emission from a broad-area diode laser. We now calculate the diffracted field for a monochromatic beam incident on the grating by using an analytical model. Predictions of the model are compared with experimental measurements made with several dual-period gratings. We also discuss the situation in which a dual-period grating is used as an external coupler of a diode laser in a two-wavelength emission regime.


Phosphorylation status of pyruvate dehydrogenase distinguishes metabolic phenotypes of cultured rat brain astrocytes and neurons.
Glucose metabolism in nervous tissue has been proposed to occur in a compartmentalized manner with astrocytes contributing largely to glycolysis and neurons being the primary site of glucose oxidation. However, mammalian astrocytes and neurons both contain mitochondria, and it remains unclear why in culture neurons oxidize glucose, lactate, and pyruvate to a much larger extent than astrocytes. The objective of this study was to determine whether pyruvate metabolism is differentially regulated in cultured neurons versus astrocytes. Expression of all components of the pyruvate dehydrogenase complex (PDC), the rate-limiting step for pyruvate entry into the Krebs cycle, was determined in cultured astrocytes and neurons. In addition, regulation of PDC enzymatic activity in the two cell types via protein phosphorylation was examined. We show that all components of the PDC are expressed in both cell types in culture, but that PDC activity is kept strongly inhibited in astrocytes through phosphorylation of the pyruvate dehydrogenase alpha subunit (PDH alpha). In contrast, neuronal PDC operates close to maximal levels with much lower levels of phosphorylated PDH alpha. Dephosphorylation of astrocytic PDH alpha restores PDC activity and lowers lactate production. Our findings suggest that the glucose metabolism of astrocytes and neurons may be far more flexible than previously believed.


Maternity care monitoring in Ibadan, Nigeria.
During this hospital stay, 993 women delivered 1008 infants at University College Hospital in Ibadan, Nigeria from January through June 1977. The stillbirth rate was 45.4 per 1000 deliveries; the neonatal mortality rate was 20.2 per 1000 deliveries. Significant differences occurred in patient characteristics, antenatal care, and complications of labour/delivery between those patients with favourable and unfavourable birth outcomes. As expected from all previous reports, the rate of multiple births was very high: 37 sets of twins and 3 sets of triplets. Contraceptive acceptance rose after delivery from 17.1% to 63.5% accepting some method. Orals were the most popular choice both antepartum and postpartum.


TDAG8 is a proton-sensing and psychosine-sensitive G-protein-coupled receptor.
T cell death-associated gene 8 (TDAG8) has been reported to be a receptor for psychosine. Ovarian cancer G-protein-coupled receptor 1 (OGR1) and GPR4, G-protein-coupled receptors (GPCRs) closely related to TDAG8, however, have recently been identified as proton-sensing or extracellular pH-responsive GPCRs that stimulate inositol phosphate and cAMP production, respectively. In the present study, we examined whether TDAG8 senses extracellular pH change. In the several cell types that were transfected with TDAG8 cDNA, cAMP was markedly accumulated in response to neutral to acidic extracellular pH, with a peak response at approximately pH 7.0-6.5. The pH effect was inhibited by copper ions and was reduced or lost in cells expressing mutated TDAG8 in which histidine residues were changed to phenylalanine. In the membrane fractions prepared from TDAG8-transfected cells, guanosine 5'-O-(3-thiotriphosphate) binding activity and adenylyl cyclase activity were remarkably stimulated in response to neutral and acidic pH. The concentration-dependent effect of extracellular protons on cAMP accumulation was shifted to the right in the presence of psychosine. The inhibitory psychosine effect was also observed for pH-dependent actions in OGR1- and GPR4-expressing cells but not for prostaglandin E(2)- and sphingosine 1-phosphate-induced actions in any pH in native and sphingosine 1-phosphate receptor-expressing cells. Glucosylsphingosine and sphingosylphosphorylcholine similarly inhibited the pH-dependent action, although to a lesser extent. Psychosine-sensitive and pH-dependent cAMP accumulation was also observed in mouse thymocytes. We concluded that TDAG8 is one of the proton-sensing GPCRs coupling to adenylyl cyclase and psychosine, and its related lysosphingolipids behave as if they were antagonists against protein-sensing receptors, including TDAG8, GPR4, and OGR1.