In-Depth Quantification of Cell Division and Elongation Dynamics at the Tip of Growing Arabidopsis Roots Using 4D Microscopy, AI-Assisted Image Processing and Data Sonification.
One of the fundamental questions in plant developmental biology is how cell proliferation and cell expansion coordinately determine organ growth and morphology. An amenable system to address this question is the Arabidopsis root tip, where cell proliferation and elongation occur in spatially separated domains, and cell morphologies can easily be observed using a confocal microscope. While past studies revealed numerous elements of root growth regulation including gene regulatory networks, hormone transport and signaling, cell mechanics and environmental perception, how cells divide and elongate under possible constraints from cell lineages and neighboring cell files has not been analyzed quantitatively. This is mainly due to the technical difficulties in capturing cell division and elongation dynamics at the tip of growing roots, as well as an extremely labor-intensive task of tracing the lineages of frequently dividing cells. Here, we developed a motion-tracking confocal microscope and an Artificial Intelligence (AI)-assisted image-processing pipeline that enables semi-automated quantification of cell division and elongation dynamics at the tip of vertically growing Arabidopsis roots. We also implemented a data sonification tool that facilitates human recognition of cell division synchrony. Using these tools, we revealed previously unnoted lineage-constrained dynamics of cell division and elongation, and their contribution to the root zonation boundaries.


Probing microelectromechanical systems in an environmentally controlled chamber using long working distance interferometry.
It is well known that the environment in which micromechanical systems operate significantly affects their performance. It is, therefore, important to characterize micromachine behavior in environments where the humidity, pressure, and chemical composition of the ambient can be precisely controlled. Achieving such a level of environmental control presents significant challenges in view of the required instrumentation. To that end, a custom micromachine characterization system is built that allows for full environmental control (pressure, humidity, and gas composition) while retaining full micromachine characterization techniques (long working distance interferometry, electrical probe connectivity, actuation scripting capability). The system also includes an effective in situ surface cleaning mechanism. As an example of the system's utility, a microcantilever crack healing experiment is conducted and surface adhesion energy measurements are tracked over time after a step change in humidity is applied.


Evolving treatment approaches for the management of metastatic castration-resistant prostate cancer - role of radium-223.
Radium-223 is a first-in-class alpha particle-emitting radiopharmaceutical approved for the treatment of bone metastatic castration-resistant prostate cancer. Radium-223 is administered intravenously with no requirement for complex shielding and specifically targets areas of bone metastasis. In a randomized placebo-controlled Phase III study, treatment with radium-223 was shown to improve overall survival, time to skeletal-related events, and health-related quality of life. Apart from radium-223, the cytotoxic chemotherapy agents docetaxel and cabazitaxel, androgen biosynthesis inhibitor abiraterone acetate, novel anti-androgen enzalutamide, and immunotherapy sipuleucel-T have also been shown to improve survival of men with advanced prostate cancer in Phase III trials. This review will outline current treatment approaches for advanced prostate cancer with a focus on the role of radium-223 in changing treatment paradigms.


Overexpression of PPARγ specifically in pancreatic β-cells exacerbates obesity-induced glucose intolerance, reduces β-cell mass, and alters islet lipid metabolism in male mice.
The contribution of peroxisomal proliferator-activated receptor (PPAR)-γ agonism in pancreatic β-cells to the antidiabetic actions of thiazolidinediones has not been clearly elucidated. Genetic models of pancreatic β-cell PPARγ ablation have revealed a potential role for PPARγ in β-cell expansion in obesity but a limited role in normal β-cell physiology. Here we overexpressed PPARγ1 or PPARγ2 specifically in pancreatic β-cells of mice subjected to high-fat feeding using an associated adenovirus (β-PPARγ1-HFD and β-PPARγ2-HFD mice). We show β-cell-specific PPARγ1 or PPARγ2 overexpression in diet-induced obese mice exacerbated obesity-induced glucose intolerance with decreased β-cell mass, increased islet cell apoptosis, and decreased plasma insulin compared with obese control mice (β-eGFP-HFD mice). Analysis of islet lipid composition in β-PPARγ2-HFD mice revealed no significant changes in islet triglyceride content and an increase in only one of eight ceramide species measured. Interestingly β-PPARγ2-HFD islets had significantly lower levels of lysophosphatidylcholines, lipid species shown to enhance insulin secretion in β-cells. Gene expression profiling revealed increased expression of uncoupling protein 2 and genes involved in fatty acid transport and β-oxidation. In summary, transgenic overexpression of PPARγ in β-cells in diet-induced obesity negatively impacts whole-animal carbohydrate metabolism associated with altered islet lipid content, increased expression of β-oxidative genes, and reduced β-cell mass.


Differences in intergenerational fertility associations by sex and race in Saba, Dutch Caribbean, 1876-2004.
This study examines the intergenerational transmission of fertility behavior in Saba, Dutch Caribbean from 1876 to 2004 using reconstituted genealogies. Pearson product-moment correlation coefficients of several fertility measures and event-history models of age at first birth are used to explore relationships between the fertility of mothers and their children. The strength of intergenerational fertility ties varies by race and gender. Individuals that are better positioned to realize their fertility preferences have the strongest intergenerational associations, while individuals with the most limited reproductive options have the weakest intergenerational associations. This evidence supports hypotheses that posit the intergenerational transmission of attitudes, goals, and behaviors and the ability to act on those preferences as drivers of the presence or magnitude of links between the fertility of parents and their children.


A modified technique for dowel fibular strut graft placement and circumferential fusion in the setting of L5-S1 spondylolisthesis and multilevel degenerative disc disease.
Traditional techniques for the treatment of isthmic spondylolisthesis pass a fibular dowel graft across the L5-S1 disc by using the anterior portion of the L5 body. To introduce a technique for the treatment of isthmic spondylolisthesis in the setting of multilevel degenerative disc disease in adults. Our modified technique allows us to traverse the L5-S1 disc via the L4-5 disc space thereby treating the degenerated disc at L4-5 simultaneously. A standard anterior discectomy was performed on L4-5. Using biplanar fluoroscopy, a Kirschner wire was placed beginning at the anterior third of the L5 superior endplate and ending at S1. An anterior cruciate ligament reamer was used to make a channel for the fibular allograft. Then, a femoral ring allograft was placed in the disc space at L4-5, and standard anterior lumbar interbody fusions were performed at any additional cephalad level(s). Afterward, posterior instrumented fusion was performed to complement the anterior fusion procedure (except at L5), and wide decompression followed. All patients presented with isthmic spondylolisthesis and all had multilevel fusions. The mean slip angle was 32.6 degrees (37.8 degrees preoperatively), and mean lumbar index was 67%. After the procedure, the average endplate-to-dowel angle was 107.1 degrees compared with 134 degrees. All patients had clinical and radiographic evidence of solid fusion without the need for revisions. The proposed advantage of our modified technique is twofold. The graft is placed nearly perpendicular to the L5-S1 interface, as it will behave more efficiently with respect to interfragmental compression. Also, surgeons gain access to fuse L4-5 anteriorly and posteriorly.


Whole-grain consumption and chronic disease: protective mechanisms.
Dietary guidance recommends consumption of whole grains to reduce the risk of chronic diseases including cancer and cardiovascular disease. Epidemiologic studies support the belief that whole grains are protective against cancers, especially gastrointestinal cancers such as gastric and colonic, and cardiovascular disease. Components in whole grains that may be protective are diverse and include compounds that affect the gut environment, i.e., dietary fiber, resistant starch, and other undigestible compounds in whole grains, compounds that function as antioxidants such as trace minerals and phenolic compounds, and compounds that are phytoestrogens with potential hormonal effects. Many of the protective compounds in whole grains are also in fruits and vegetables, but some plant compounds are more concentrated in whole grains, such as phenolic compounds including ferulic and caffeic acid. Other potential mechanistic effects of whole grains include binding of carcinogens and modulation of glycemic index. Clearly, the range of protective substances in whole grains is impressive, and advice to consume additional whole grains is justifiable.


Demonstration of the Rationale for Therapeutic Drug Monitoring of Isavuconazole: A Case Report with a Lung Transplant Recipient.
Mucormycosis is a rare invasive fungal disease diagnosed in immunocompromised patients, including those with diabetes or iron overload, and in patients treated for hematological malignancies or after transplantation. Isavuconazole is a triazole antifungal effective against Mucorales with good tolerability, but with potential for relatively high interindividual variability in pharmacokinetics. This report demonstrates the case of a lung transplant recipient treated with isavuconasole that exhibits a very long elimination half-life of 159 hours, and discusses the practical implications of this finding for dosage adjustment and need for therapeutic drug monitoring.


Concurrent training enhances athletes' strength, muscle endurance, and other measures.
We evaluated the effects of concurrent strength and aerobic endurance training on muscle strength and endurance, body composition, and flexibility in female college athletes and compared two concurrent exercise (CE) protocols. Twenty-eight women (mean age, 19.6 years) were divided into two matched groups and evaluated before and after a vigorous, 11-week, 3-days per week CE training program. One group did serial CE consisting of a warm-up, resistance exercises at low heart rate (HR), aerobics, and a range of motion cool down. The other group did integrated CE consisting of aerobics, the same resistance exercises at high HR achieved by cardioacceleration before each set, and the same range of motion cool down. The two protocols were balanced, differing only in the timing and sequence of exercises. Serial CE produced discernible (p < 0.05) increases in lower- (17.2%) and upper- (19.0%) body muscle strength and fat-free mass (FFM) (1.8%) and trends toward greater lower-body muscle endurance (18.2%) and reduced upper-body flexibility (-160.4%). Integrated CE produced discernible increases in lower- (23.3%) and upper- (17.8%) body muscle strength, lower-body muscle endurance (27.8%), FFM (3.3%), and lower-body flexibility (8.4%) and a decline in fat mass (-4.5%) and percent body fat (-5.7%). Integrated CE produced discernibly larger gains than serial CE for six of nine training adaptations. Effect sizes were generally moderate (44.4% of discernible differences) to large (33.3%). We conclude that serial CE produces adaptations greater than those reported in the literature for single-mode (strength) training in athletes, whereas integrated CE produces discernibly greater gains than serial CE. The results suggest synergy rather than interference between concurrent strength and aerobic endurance training, support prescription of CE under defined conditions, establish the importance of exercise timing and sequence for CE program outcomes, and document a highly effective athletic training protocol.


[Quantitative changes in piriform neurons of human cerebellar cortex from birth to 20 years].
Age changes of size parameters of piriform (Purkinje) neurons in visual cerebellar cortex (pyramid and lateral areas of right and left digastric lobes) were studied at monthly intervals (during the first postnatal year) and at annual intervals (since birth up to 20 yrs) using computer optic image analyzer. Postnatal development of piriform neurons from human cerebellar visual cortex was found to be periodic (cyclic); each morphological cycle is characterised by certain duration and a series of quantitative and qualitative changes.


Prognostic implications of ventricular ectopy one week, one month, and sixteen months after an acute myocardial infarction. Danish Study Group on Verapamil in Myocardial Infarction.
Ventricular ectopy early after an acute myocardial infarction (AMI) has previously been demonstrated to predict mortality. Less information is available about the prognostic implications of ventricular ectopy occurring late after an AMI, and no information is available about the prognostic implication of the development of ventricular ectopy during the first year after an AMI. The purpose of the present prospectively conducted trial, a part of the Danish Verapamil Infarction Trial II (DAVIT II), was to evaluate the prognostic implication of (1) ventricular premature complexes (VPCs) recorded by 24-h Holter monitoring 1 week, 1 month, and 16 months after an AMI; and (2) development of > 10 VPCs/h or of any complex ventricular ectopy, that is, pairs, more than two types of VPCs, ventricular tachycardia, or > 10 VPCs/h during follow-up after an AMI. Patients were monitored 1 week (n = 250), 1 month (n = 210), and 16 months (n = 201) after AMI. Multivariate analyses based on history, clinical findings, and ventricular ectopy showed the following results: After 1 week, > 10 VPCs/h (p = 0.0006) and heart failure (p < 0.007); after 1 month, > 10 VPCs/h (p = 0.003) and resting heart rate (p < 0.02); and after 16 months, ventricular tachycardia (p = 0.002) independently predicted long-term mortality. Mortality was significantly predicted by the development of > 10 VPCs/h from 1 week to 1 month (p = 0.003) and 16 months (p = 0.03), and from 1 to 16 months (p = 0.007) after AMI, as well as by the development of any complex ventricular ectopy from 1 week to 1 month (p = 0.02) and 16 months (p = 0.01), and from 1 to 16 months (p = 0.04) after AMI. The present study demonstrated that 1 week and 1 month after an AMI the quantity of VPCs, that is, > 10 VPCs/h, predicted mortality, whereas 16 months after an AMI the quality of VPCs, that is, ventricular tachycardia, predicted mortality.


Atypical Clinical presentation of a patient with Monkeypox.
Presentation The Monkeypox virus is spreading in the European continent. A 36-year-old Irish man presented with a cellulitis lesion on the nose, spreading to the cheeks and upper lip. Atypical clinical features of the evolving outbreak are posing a community and healthcare risk to its management. Diagnosis Real-time PCR assay of the lesion swab revealed Monkeypox virus. The biochemical and hematological blood indices were normal, except for C-Reactive Protein, which was higher than normal. Treatment The patient was put on 750 mg intravenous Acyclovir, 15mg/kg twice a day of Vancomycin and 2g/day Ceftriaxone infusion. Discussion Cellulitis lesions are an atypical clinical feature of Monkeypox virus infection. Its management, using antibiotics and antiviral drugs, treated the infection and confined the spread of the virus around the patient's nose.


No evidence for a fundamental visual motion processing deficit in adolescents with autism spectrum disorders.
It has been suggested that atypicalities in low-level visual processing contribute to the expression and development of the unusual cognitive and behavioral profile seen in autism spectrum disorders (ASD). However, previous investigations have yielded mixed results. In the largest study of its kind (ASD n = 89; non-ASD = 52; mean age 15 years 6 months) and testing across the spectrum of IQ (range 52-133), we investigated performance on three measures of basic visual processing: motion coherence, form-from-motion and biological motion (BM). At the group level, we found no evidence of differences between the two groups on any of the tasks, suggesting that there is no fundamental visual motion processing deficit in individuals with an ASD, at least by adolescence. However, we identified a tail of individuals with ASD (18% of the sample) who had exceptionally poor BM processing abilities compared to the non-ASD group, and who were characterized by low IQ. For the entire sample of those both with and without ASD, performance on the BM task uniquely correlated with performance on the Frith-Happé animations, a higher-level task that demands the interpretation of moving, interacting agents in order to understand mental states. We hypothesize that this association reflects the shared social-cognitive characteristics of the two tasks, which have a common neural underpinning in the superior temporal sulcus.


Dicobalt octacarbonyl-catalyzed tandem
Novel 5-5-6 tricyclic compounds containing cyclopentenone have been constructed by the dicobalt octacarbonyl catalyzed tandem [2 + 2 + 1] and [2 + 2 + 2] cycloaddition reaction between a diyne and two phenylacethylene under CO pressure.


Cross-cultural adaptation and reliability of the Italian version of the Foot Function Index (FFI-I) for patients with plantar fasciitis.
The aim of this paper was to translate and cross-culturally adapt the FFI to the Italian language, and to assess the reliability of the Italian version of the FFI (FFI-I) for plantar fasciitis. Fifty symptomatic patients affected by plantar fasciitis completed the FFI-I scale twice, at interval of one week. The translation of the FFI was performed according to international standards for translation of questionnaires. Test-retest reliability was evaluated using intraclass correlation coefficient (ICC). Internal consistency was measured by Cronbach α coefficient. Ceiling and floor effects were assessed. The process resulted in an intelligible version of the questionnaire. The reliability of the FFI-I was adequate, with an ICC ranging from 0.86 to 0.98 for test-retest reliability. The FFI-I showed an excellent internal consistency, ranging from 0.93 to 0.99 for all subscales. Three items involving disability and four items involving activities restrictions had highest proportion of floor score. The FFI-I is a reliable and valid instrument to assess clinical severity in patients with plantar fasciitis and it is suitable for daily practice. We suggest evaluating the total FFI-I score along with the distinct scores of the three subscales of the FFI-I in order to interpret more correctly minor changes in patient status during repetitive outcome assessments.


Hepatitis C virus: Is it time to say goodbye yet? Perspectives and challenges for the next decade.
The majority of individuals exposed to hepatitis C virus (HCV) establish a persistent infection, which is a leading cause of chronic liver disease, cirrhosis and hepatocellular carcinoma. Major progress has been made during the past twenty-five years in understanding the HCV life cycle and immune responses against HCV infection. Increasing evidence indicates that host genetic factors can significantly influence the outcome of HCV infection and the response to interferon alpha-based antiviral therapy. The arrival of highly effective and convenient treatment regimens for patients chronically infected with HCV has improved prospects for the eradication of HCV worldwide. Clinical trials are evaluating the best anti-viral drug combination, treatment doses and duration. The new treatments are better-tolerated and have shown success rates of more than 95%. However, the recent breakthrough in HCV treatment raises new questions and challenges, including the identification of HCV-infected patients and to link them to appropriate health care, the high pricing of HCV drugs, the emergence of drug resistance or naturally occurring polymorphism in HCV sequences which can compromise HCV treatment response. Finally, we still do not have a vaccine against HCV. In this concise review, we will highlight the progress made in understanding HCV infection and therapy. We will focus on the most significant unsolved problems and the key future challenges in the management of HCV infection.


The induction of host resistance to tick infestation with a salivary gland antigen.
Salivary gland antigen, SGA, derived from partially engorged female Dermacentor andersoni was shown to be capable of inducing resistance to tick infestation in guinea pigs never previously exposed to ticks. Immunization regimens involved the administration of SGA by different routes and with or without the use of adjuvants. Induced resistance was expressed by significantly fewer larvae engorging, and the weight of larvae which did engorge was reduced. Salivary gland antigen has been shown to interact with the immune effector elements of animals which acquired and expressed tick resistance due to infestation. These findings demonstrated the potential for an immunologic approach to tick control.


Centromeric SMC1 promotes centromere clustering and stabilizes meiotic homolog pairing.
During meiosis, each chromosome must selectively pair and synapse with its own unique homolog to enable crossover formation and subsequent segregation. How homolog pairing is maintained in early meiosis to ensure synapsis occurs exclusively between homologs is unknown. We aimed to further understand this process by examining the meiotic defects of a unique Drosophila mutant, Mcm5A7. We found that Mcm5A7 mutants are proficient in homolog pairing at meiotic onset yet fail to maintain pairing as meiotic synapsis ensues, causing seemingly normal synapsis between non-homologous loci. This pairing defect corresponds with a reduction of SMC1-dependent centromere clustering at meiotic onset. Overexpressing SMC1 in this mutant significantly restores centromere clustering, homolog pairing, and crossover formation. These data indicate that the initial meiotic pairing of homologs is not sufficient to yield synapsis exclusively between homologs and provide a model in which meiotic homolog pairing must be stabilized by centromeric SMC1 to ensure proper synapsis.


Brief airway occlusion produces prolonged reflex inhibition of inspiratory muscles in obstructive sleep apnea.
The human inspiratory muscles respond to a brief occlusion of the upper airway during inspiration with a profound short-latency reflex inhibition. This inhibition contrasts with the excitatory stretch reflex of limb muscles and may protect the airway from aspiration. It was postulated that this reflex would be altered in subjects with obstructive sleep apnea (OSA) who have repetitive upper airway occlusion. Subjects underwent overnight polysomnography, as well as muscle reflex studies. For the reflex studies (performed during wakefulness), occlusions lasting 250 milliseconds were delivered during inspiration. Surface electromyogram was recorded over the scalenes, parasternal intercostals, and chest wall (overlying diaphragm). Research and sleep laboratories. Nineteen subjects with untreated OSA (9 moderate and 10 severe) and 9 healthy control subjects. In the subjects with severe OSA, the duration of the inhibition was prolonged by at least 25% compared with control subjects. The peak of the inhibitory response for scalenes occurred significantly later for subjects with severe OSA than for control subjects (by 76 +/- 5 ms vs 60 +/- 3 ms [mean +/- SEM], respectively). Onset latencies of the later excitatory response were delayed for scalenes, parasternal intercostals, and chest wall recordings (eg, scalenes: 105 +/- 9 ms for subjects with severe OSA vs 83 +/- 5 ms for control subjects). The latency of peak inhibition and duration of inhibition were positively correlated with the respiratory disturbance index for all muscle groups. These changes may reflect adaptation in central respiratory paths due to repetitive loading during sleep.


Transcriptome signatures from discordant sibling pairs reveal changes in peripheral blood immune cell composition in Autism Spectrum Disorder.
Notwithstanding several research efforts in the past years, robust and replicable molecular signatures for autism spectrum disorders from peripheral blood remain elusive. The available literature on blood transcriptome in ASD suggests that through accurate experimental design it is possible to extract important information on the disease pathophysiology at the peripheral level. Here we exploit the availability of a resource for molecular biomarkers in ASD, the Italian Autism Network (ITAN) collection, for the investigation of transcriptomic signatures in ASD based on a discordant sibling pair design. Whole blood samples from 75 discordant sibling pairs selected from the ITAN network where submitted to RNASeq analysis and data analyzed by complementary approaches. Overall, differences in gene expression between affected and unaffected siblings were small. In order to assess the contribution of differences in the relative proportion of blood cells between discordant siblings, we have applied two different cell deconvolution algorithms, showing that the observed molecular signatures mainly reflect changes in peripheral blood immune cell composition, in particular NK cells. The results obtained by the cell deconvolution approach are supported by the analysis performed by WGCNA. Our report describes the largest differential gene expression profiling in peripheral blood of ASD subjects and controls conducted by RNASeq. The observed signatures are consistent with the hypothesis of immune alterations in autism and an increased risk of developing autism in subjects exposed to prenatal infections or stress. Our study also points to a potential role of NMUR1, HMGB3, and PTPRN2 in ASD.


Hepatitis C prevalence and quality of health services among HIV-positive mothers in the Democratic Republic of the Congo.
Hepatitis C virus (HCV) contributes to liver-related morbidity and mortality throughout Africa despite effective antivirals. HCV is endemic in the Democratic Republic of the Congo (DRC) but data on HCV/HIV co-infection in pregnancy is limited. We estimated the prevalence of and risk factors for HCV/HIV co-infection among pregnant women in the Kinshasa province of the DRC. This cross-sectional study was conducted as a sub-study of an ongoing randomized trial to assess continuous quality improvement interventions (CQI) for prevention of mother-to-child transmission (PMTCT) of HIV (CQI-PMTCT study, NCT03048669). HIV-infected women in the CQI-PMTCT cohort were tested for HCV, and risk factors were evaluated using logistic regression. The prevalence of HCV/HIV co-infection among Congolese women was 0.83% (95% CI 0.43-1.23). Women who tested positive for HCV were younger, more likely to live in urban areas, and more likely to test positive during pregnancy versus postpartum. HCV-positive women had significantly higher odds of infection with hepatitis B virus (HBV) (aOR 13.87 [3.29,58.6]). An inverse relationship was noted between HCV infection and the overall capacity of the health facility as measured by the service readiness index (SRI) (aOR:0.92 [0.86,0.98] per unit increase). Women who presented to rural, for-profit and PEPFAR-funded health facilities were more likely to test positive for HCV. In summary, this study identified that the prevalence of HCV/HIV co-infection was < 1% among Congolese women. We also identified HBV infection as a major risk factor for HCV/HIV co-infection. Individuals with triple infection should be linked to care and the facility-related differences in HCV prevalence should be addressed in future studies.


Informing policy and programme decisions for scaling up the PMTCT and paediatric HIV response through joint technical missions.
In 2005, due to slow global progress in the scale-up of prevention of mother-to-child transmission (PMTCT) and paediatric HIV programmes, the Inter-agency Task Team (IATT) on the Prevention of HIV infection among Pregnant Women, Mothers, and their Children initiated joint technical missions (JTMs) to countries of high HIV disease burden. The JTMs were intended to galvanize country actions for a more comprehensive response to PMTCT and paediatric HIV by bringing national and global stakeholders together to review national policies and programmes and develop country-specific recommendations for accelerating scale-up. Between 2005 and 2010, the IATT conducted JTMs in 18 low- and middle-income countries. In 2007, to assess the role played by the missions, a review in the first eight countries (Burkina Faso, Cameroon, Côte d'Ivoire, India, Malawi, Rwanda, Tanzania and Zambia) that hosted JTMs was undertaken. Country progress was assessed through desk review and key informant interviews. For each country, documents reviewed included JTM reports, baseline data for PMTCT and paediatric HIV care and treatment, and 2004 to 2007 trend data on key PMTCT and paediatric HIV indicators. Drawing upon the findings, this paper posits that JTMs contributed to national scale-up of PMTCT and paediatric HIV programmes through strengthening governance and co-ordination mechanisms for the programmes, promoting enabling policy environments, and supporting the development of national scale-up plans, which have been critical for leveraging additional financial resources for scale-up. Although the impact of the JTMs could be enhanced through greater follow-up and continued targeted assistance in technical areas such as infant and young child feeding, community-based programming and supply chain management, findings indicate that the JTMs are a useful mechanism for informing policy and programme decisions necessary for scaling up PMTCT and paediatric HIV responses. Moreover, by bringing stakeholders together around unified action plans, the JTMs created a platform for common action-a key tenet of the 'Three Ones' principles for effective HIV/AIDS responses.


COVID-19 Vaccine Mandates and Vaccine Hesitancy among Black People in Canada.
COVID-19 vaccine mandates increased vaccination rates globally. Implemented as a one-size-fits-all policy, these mandates have unintended harmful consequences for many, including Black Canadians. This article reports findings on the interconnectedness of vaccine mandates and vaccine hesitancy by describing a range of responses to mandatory COVID-19 vaccination policies among Black people in Canada. Using qualitative research methods, semi-structured interviews with 36 Black people living in Canada aged 18 years and over across 6 provinces in Canada were conducted. Participants were selected across intersectional categories including migration status, income, religion, education, sex, and Black ethnicity. Thematic analysis informed the identification of key themes using Foucauldian notions of biopower and governmentality. Our results show how the power relations present in the ways many Black people actualize vaccine intentions. Two main themes were identified: acceptance of the COVID-19 vaccine in the context of governmentality and resistance to vaccine mandates driven by oppression, mistrust, and religion. COVID-19 vaccine mandates may have reinforced mistrust of the government and decreased confidence in the COVID-19 vaccine. Policy makers need to consider non-discriminatory public health policies and monitor how these policies are implemented over time and across multiple sectors to better understand vaccine hesitancy.


Simulation Investigation on the Influence Mechanism of Toluene and Heptane on the Aggregation of Asphaltene Molecules.
Asphaltenes are a group of compounds that are soluble in benzene and toluene but insoluble in nonpolar small molecule n-alkanes. The asphaltene aggregation in the asphaltene-heptane-toluene system was studied using molecular dynamics (MD) simulation, and the interaction between asphaltene molecules during this process was also revealed from the evolution of the density field, radial distribution function (RDF), and intermolecular distance of asphaltenes. Three main findings were made: (1) more asphaltene precipitates (heptane) were contained, and more asphaltene dimers or trimers were formed during the MD simulation; (2) asphaltene molecules interacted with each other to form aggregates in the form of π-π or H-bond interaction. The stable distance of the π-π interaction was 3.3-3.5 Å, and the stable distance of the H-bond connection was 1.7-1.9 Å. (3) The asphaltene interaction in the heptane-rich system was dominated by π-π interaction between asphaltene molecules. However, the asphaltene interactions in the toluene-rich system were mainly the π-π interaction between asphaltene molecules and toluene and the H-bond interaction between the side chains of asphaltene molecules. The results of this study can aid in understanding how asphaltene molecules aggregate and self-associate and can also offer theoretical support for flow assurance in systems used to produce crude oil.


HapMap scanning of novel human minor histocompatibility antigens.
Minor histocompatibility antigens (mHags) are molecular targets of allo-immunity associated with hematopoietic stem cell transplantation (HSCT) and involved in graft-versus-host disease, but they also have beneficial antitumor activity. mHags are typically defined by host SNPs that are not shared by the donor and are immunologically recognized by cytotoxic T cells isolated from post-HSCT patients. However, the number of molecularly identified mHags is still too small to allow prospective studies of their clinical importance in transplantation medicine, mostly due to the lack of an efficient method for isolation. Here we show that when combined with conventional immunologic assays, the large data set from the International HapMap Project can be directly used for genetic mapping of novel mHags. Based on the immunologically determined mHag status in HapMap panels, a target mHag locus can be uniquely mapped through whole genome association scanning taking advantage of the unprecedented resolution and power obtained with more than 3 000 000 markers. The feasibility of our approach could be supported by extensive simulations and further confirmed by actually isolating 2 novel mHags as well as 1 previously identified example. The HapMap data set represents an invaluable resource for investigating human variation, with obvious applications in genetic mapping of clinically relevant human traits.


An experimental study on antipersonnel landmine detection using acoustic-to-seismic coupling.
An acoustic-to-seismic system to detect buried antipersonnel mines exploits airborne acoustic waves penetrating the surface of the ground. Acoustic waves radiating from a sound source above the ground excite Biot type I and II compressional waves in the porous soil. The type I wave and type II waves refract toward the normal and cause air and soil particle motion. If a landmine is buried below the surface of the insonified area, these waves are scattered or reflected by the target, resulting in distinct changes to the acoustically coupled ground motion. A scanning laser Doppler vibrometer measures the motion of the ground surface. In the past, this technique has been employed with remarkable success in locating antitank mines during blind field tests [Sabatier and Xiang, IEEE Trans. Geosci. Remote Sens. 39, 1146-1154 (2001)]. The humanitarian demining mission requires an ability to locate antipersonnel mines, requiring a surmounting of additional challenges due to a plethora of shapes and smaller sizes. This paper describes an experimental study on the methods used to locate antipersonnel landmines in recent field measurements.


[Effect of thyroliberin on neurons of the sensorimotor cortex].
The effect of thyroliberin (thyrotropin-releasing hormone) on extracellularly recorded spontaneous activity of sensorimotor cortical neurons was studied in experiments on non-anesthetized rabbits. Thyroliberin injected intravenously in doses of 0.1-7.0 mg/kg had an excitatory effect on the cortical neurons. In contrast, thyroliberin had a depressant effect when applied microiontophoretically to individual neurons. It is concluded that the excitatory effect of thyroliberin on the cortex after systemic application is related to the facilitation of subcortical-cortical activating influences. Extracortical receptors of the excitatory type are likely to be responsible for the main central-stimulating properties of thyroliberin.


Surgical treatment of odontoid fractures with C1 hook and C2 pedicle screw construct.
A number of approaches have been attempted to address the treatment of acute odontoid fractures, spanning from conservative treatment with an external orthotic device to posterior C1-C2 arthrodesis or anterior screw fixation. The current report describes stabilisation of such fractures with a C1 supralaminar hook and a C2 pars interarticularis screw construct. Two patients with odontoid fracture were treated by this technique. Two-year follow-up of both patients revealed complete union without complications. The authors stress that this technique avoids the hazards of C1 lateral mass screws.


Maternal pre-pregnancy body mass index, gestational weight gain and breastfeeding outcomes: a cross-sectional analysis.
It is well established that mothers with above-normal pre-pregnancy BMI are at increased risk of breastfeeding cessation; however, the impact of pregnancy weight-gain (PWG) is less well-defined. Excess PWG may alter the hormonal preparation of breast tissue for lactation, increase the risk of complications that negatively impact breastfeeding (e.g. Cesarean-section, gestational diabetes), and may make effective latch more difficult to achieve. Our objective was to determine the impact of PWG and pre-pregnancy BMI on the risk of breastfeeding cessation utilizing the Institute of Medicine's 2009 recommendations. Cox proportional hazards models were utilized to estimate the risk of cessation of exclusive breastfeeding, and cessation of any breastfeeding among women who initiated exclusive and any breastfeeding, respectively, in a cross sectional sample of survey respondents from a New York county (N = 1207). PWG category was interacted with pre-pregnancy BMI (3 levels of pre-pregnancy BMI, 3 levels of PWG). Confounders of the relationship of interest were evaluated using directed acyclic graphs and bivariate analyses; variables not on the proposed causal pathway and associated with the exposure and outcome were included in multivariate models. After adjustment, women of normal and obese pre-pregnancy BMI with greater-than-recommended PWG had 1.39 (1.03-1.86) and 1.48 (1.06-2.07) times the risk of any breastfeeding cessation within the first 3 months postpartum compared to women with normal pre-pregnancy BMI who gained within PWG recommendations. Overweight women with greater-than-recommended PWG were at increased risk of cessation, although not significantly (aHR [95% CI]: 1.29 [0.95-1.75]). No significant relationship was observed for exclusive breastfeeding cessation. Pre-pregnancy BMI and PWG may be modifiable risk factors for early breastfeeding cessation. Understanding the mechanism behind this risk should be ascertained by additional studies aimed at understanding the physiological, social, logistical (positioning) and other issues that may lead to early breastfeeding cessation.


Phenotypic changes of human aortic smooth muscle cells during development and in the adult vessel.
To characterize phenotypic expression of human aortic smooth muscle cells (SMCs), we have studied the content of cytodifferentiation-related cytoskeletal proteins, and of fibronectin (FN) variants in the samples of media from the fetal, child, and adult aorta and in the subendothelial intima of the normal and atherosclerotic aorta. Mature SMCs from the adult aortic media contained high amounts of alpha-SM-actin, SM-myosin heavy chains, meta-vinculin, and 150 kDa caldesmon. Cytokeratin 8 and extra domain-containing variants of FN (A-FN and B-FN) were not found in these cells. The SMCs from the aortic media of 10-wk-old fetus contained low amounts of the SM markers, expressed cytokeratin 8, A-FN, and B-FN. In 25-wk-old fetus, as well as in 2- and 6-mo-old child, aortic medial SMCs expressed an intermediate phenotype, and only in 18-mo-old child were the cells found to be similar to those from adult media. SMCs from the normal adult subendothelial intima contained reduced amounts of meta-vinculin and of 150 kDa caldesmon, and they expressed A-FN. In addition, the SMCs from atherosclerotic fibrous plaque contained a decreased proportion of alpha-SM-actin and of SM-myosin heavy chains, whereas cytokeratin 8 was found. Therefore we conclude that the SMCs from intimal thickenings appear to express a less mature phenotype than that of the medial cells from adult aorta. Rather, these SMCs contain reduced amounts of the SM markers and express proteins typical of the fetal SMC phenotype, A-FN and cytokeratin 8.


Periarticular Injection and Peripheral Nerve Blocks With Standard Agents.
The block of sensory nerves in the ipsilateral limb or locally is an integral part of the multimodal pain management protocol after primary total knee arthroplasty. The 2022 clinical practice guidelines published by the American Association of Hip and Knee Surgeons, the American Society of Regional Anesthesia and Pain Medicine, and the American Academy of Orthopaedic Surgeons describe various strengths of recommendations concerning the use of nerve blocks and periarticular injection. There is also experimental and clinical evidence to support a technique for the surgeon to perform both the periarticular injection and an intra-articular saphenous nerve block. High-dose bupivacaine injection has been shown to be effective and safe. The value of adductor canal block is currently uncertain. Future studies are needed concerning longer-lasting local anesthetic agents and techniques.


Feasibility and safety of on table extubation after corrective surgical repair of tetralogy of Fallot in a developing country: a case series.
Fast-track extubation is an established safe practice in pediatric congenital heart disease (CHD) surgical patients. On table extubation (OTE) in acyanotic CHD surgical patients is well established with validated safety profile. This practice is not yet reported in tetralogy of Fallot (TOF) cardiac surgical repair patients in developing countries. Evidence suggests that TOF total correction patients should be extubated early, as positive pressure ventilation has a negative impact on right ventricular function and the overall increase in post-TOF repair complications such as low cardiac output state and arrhythmias. The objective of the case series was to determine the safety and feasibility of OTE in elective TOF total correction cardiac surgical patients with an integrated team approach. To the best of our knowledge, this is the first reported case series. A total of 8 elective male and female TOF patients were included. Standard anesthetic, surgical and perfusion techniques were used in these procedures. All patients were extubated in the operating room safely without any complications with the exception of one patient who continued to bleed for 3 h of postextubation at 2-3 ml/kg/h which was managed with transfusion of fresh frozen plasma at 15 mL/kg, packed red blood cells 10 mL/kg and bolus of transamine at 20 mg/kg. Apart from better surgical and bypass techniques, the most important factor leading to successful OTE was an excellent analgesia. On the basis of the case series, it is suggested to extubate selected TOF cardiac surgery repair patients on table safely with integrated multidisciplinary approach.


Risk factors for the development of necrotizing enterocolitis: a case-control study.
To determine risk or protective factors for the development of necrotizing enterocolitis in very low birth weight infants. This retrospective case-control study was conducted at La Paz University Hospital including infants with a birth weight of <1500 g for three years. Cases with confirmed diagnosis of necrotizing enterocolitis were evaluated; each one was paired with a control infant of the same gestational age. Statistical analysis included unadjusted and multivariable analyses. A total of 576 very low birth weight infants were admitted; of them 30 infants (5.2%) developed necrotizing enterocolitis. The main clinical and demographic characteristics did not differ between the two groups. The frequency of infants transfused with packed red blood cells was similar in cases (63%) and control patients (77%). However, a greater number of transfusions increased the odds of necrotizing enterocolitis [OR 1.5, 95%CI (1.01 to 2.24)]. A greater number of transfusions of packed red blood cells are associated with an increased risk of necrotizing enterocolitis in very low birth weight infants. The other analyzed variables in this study do not identify the infants at risk. Caution is advocated in using transfusions in newborns.


RNA-Seq reveals virus-virus and virus-plant interactions in nature.
As research on plant viruses has focused mainly on crop diseases, little is known about these viruses in natural environments. To understand the ecology of viruses in natural systems, comprehensive information on virus-virus and virus-host interactions is required. We applied RNA-Seq to plants from a natural population of Arabidopsis halleri subsp. gemmifera to simultaneously determine the presence/absence of all sequence-reported viruses, identify novel viruses and quantify the host transcriptome. By introducing the criteria of read number and genome coverage, we detected infections by Turnip mosaic virus (TuMV), Cucumber mosaic virus and Brassica yellows virus Active TuMV replication was observed by ultramicroscopy. De novo assembly further identified a novel partitivirus, Arabidopsis halleri partitivirus 1 Interestingly, virus reads reached a maximum level that was equivalent to that of the host's total mRNA, although asymptomatic infection was common. AhgAGO2, a key gene in host defence systems, was upregulated in TuMV-infected plants. Multiple infection was frequent in TuMV-infected leaves, suggesting that TuMV facilitates multiple infection, probably by suppressing host RNA silencing. Revealing hidden plant-virus interactions in nature can enhance our understanding of biological interactions and may have agricultural applications.


Sexual Health Care, Sexual Behaviors and Functioning, and Female Genital Cutting: Perspectives From Somali Women Living in the United States.
We investigated the sexual values, attitudes, and behaviors of 30 Somali female refugees living in a large metropolitan area of Minnesota by collecting exploratory sexual health information based on the components of the sexual health model-components posited to be essential aspects of healthy human sexuality. A Somali-born bilingual interviewer conducted the semistructured interviews in English or Somali; 22 participants chose to be interviewed in Somali. Interviews were translated, transcribed, and analyzed using descriptive statistics and thematic analyses. Our study findings highlighted a sexually conservative culture that values sexual intimacy, female and male sexual pleasure, and privacy in marriage; vaginal sexual intercourse as the only sanctioned sexual behavior; and the importance of Islamic religion in guiding sexual practices. Findings related to human immunodeficiency virus (HIV) revealed HIV testing at immigration, mixed attitudes toward condom use, and moderate knowledge about HIV transmission modes. Female genital cutting (FGC) was a pervasive factor affecting sexual functioning in Somali women, with attitudes about the controversial practice in transition. We recommend that health professionals take the initiative to discuss sexual health care and safer sex, sexual behaviors/functioning, and likely challenges to sexual health with Somali women--as they may be unlikely to broach these subjects without permission and considerable encouragement.


Aripiprazole differentially affects mesolimbic and nigrostriatal dopaminergic transmission: implications for long-term drug efficacy and low extrapyramidal side-effects.
Aripiprazole has been used effectively to treat schizophrenia in the clinic; however, its mechanisms of action are not clear. This study examined how short- and long-term aripiprazole treatment affects dopaminergic transmission in mesolimbic and nigrostriatal pathways. For comparison, the effects of haloperidol and olanzapine treatment were also examined. Aripiprazole significantly increased D2 receptor mRNA expression and decreased tyrosine hydroxylase (TH) mRNA expression in the ventral tegmental area (VTA) after 1- and 12-wk treatment, but had no effect in substantia nigra (SN) and nucleus accumbens (NAc). Aripiprazole also decreased dopamine transporter (DAT) binding density in NAc (for 1- and 12-wk treatment) and VTA (1-wk treatment). In contrast, haloperidol significantly increased D2 receptor binding density and decreased DAT binding density in NAc and caudate putamen (CPu) after 1- and 12-wk treatment, and it also decreases DAT binding in VTA after 12-wk treatment. Olanzapine had less widespread effects, namely an increase in D2 receptor mRNA in VTA after 12-wk treatment and decreased DAT binding in NAc after 1-wk treatment. These results suggest that aripiprazole has selective effects on the mesolimbic dopaminergic pathway. Selectively reducing dopamine synthesis in VTA is a possible therapeutic mechanism for the long-term efficacy of aripiprazole in controlling schizophrenia symptoms with reduced extrapyramidal side-effects.


Monoclinic guanidinoacetate methyltransferase and gadolinium ion-binding characteristics.
Guanidinoacetate methyltransferase (GAMT) is the enzyme that catalyzes the last step of creatine biosynthesis. The enzyme is found in abundance in the livers of all vertebrates. Recombinant rat liver GAMT truncated at amino acid 37 from the N-terminus has been crystallized with S-adenosylhomocysteine (SAH) in a monoclinic modification and the crystal structure has been determined at 2.8 A resolution. There are two dimers in the crystallographic asymmetric unit. Each dimer has non-crystallographic twofold symmetry and is related to the other dimer by pseudo-4(3) symmetry along the crystallographic b axis. The overall structure of GAMT crystallized in the monoclinic modification is quite similar to the structure observed in the tetragonal modification [Komoto et al. (2002), J. Mol. Biol. 320, 223-235], with the exception of the loop containing Tyr136. In the monoclinic modification, the loops in three of the four subunits have a catalytically unfavorable conformation and the loop of the fourth subunit has a catalytically favorable conformation as observed in the crystals of the tetragonal modification. From the structures in the monoclinic and tetragonal modifications, we can explain why the Y136F mutant enzyme retains considerable catalytic activity while the Y136V mutant enzyme loses the catalytic activity. The crystal structure of a Gd derivative of the tetragonal modification has also been determined. By comparing the Gd-derivative structure with the native structures in the tetragonal and the monoclinic modifications, useful characteristic features of Gd-ion binding for application in protein crystallography have been observed. Gd ions can bind to proteins without changing the native protein structures and Gd atoms produce strong anomalous dispersion signals from Cu Kalpha radiation; however, Gd-ion binding to protein requires a relatively specific geometry.


Sequence-specific effects of ara-5-aza-CTP and ara-CTP on DNA synthesis by purified human DNA polymerases in vitro: visualization of chain elongation on a defined template.
1-beta-D-arabinofuranosyl-5-aza-cytosine (ara-5-aza-Cyd) is an analog of 1-beta-D-arabinofuranosylcytosine (ara-C), which resembles ara-C in anabolic metabolism, incorporation into DNA, and inhibition of DNA replication. Human T-lymphoblastic cells (Molt-4) incorporate three- to fivefold more ara-5-aza-Cyd than ara-C into DNA during 5-8 hr exposure. Although ara-5-aza-Cyd and its triphosphate metabolite are unstable in aqueous solution, the aza-analog was much more stable in solution when incorporated into native DNA isolated from Molt-4 cells. By using gapped duplex DNA as a substrate for purified human DNA polymerases alpha and beta, inhibition of [3H]-dCTP incorporation by ara-5-aza-CTP and ara-CTP was competitive, with Ki values for alpha of 11 and 1.5 microM, respectively. Ki values for polymerase beta were 39 and 7.6 microM, respectively. A DNA elongation assay was adapted from DNA sequencing technology, using singly primed bacteriophage M13mp19 or M13mp9 (+)-DNA. Elongation of 5'-[32P]-labeled primer by polymerase alpha is slowed considerably by incorporation of one ara-CMP and to a lesser extent after incorporation of one ara-5-aza-CMP. Neither analog significantly affected elongation by polymerase beta after a single incorporation. However, neither polymerase alone could appreciably extend the growing chain if two consecutive ara-5-aza-CMP or ara-CMP analogs were incorporated. Thus, if similar mechanisms are operant in intact cells, the greater incorporation of ara-5-aza-Cyd than ara-C into DNA may be due to a more facile elongation of the nascent DNA strand by polymerase alpha after incorporation of a single analog. The effect in vitro of incorporation of either analog on DNA chain elongation is widely variable, depending on the identity of the polymerase involved and the sequence of the DNA template being copied.


Raman and IR Spectroscopy Studies on Propane at Pressures of Up to 40 GPa.
Raman and IR spectroscopy studies on propane were performed at pressures of up to 40 GPa at ambient temperatures using the diamond anvil cell technique. Propane undergoes three phase transitions at 6.4(5), 14.5(5), and 26.5(5) GPa in Raman spectroscopy and at 7.0(5), 14.0(5), and 27.0(5) GPa in IR spectroscopy. The phase transitions were identified using the Raman and IR splitting modes and the appearance or disappearance of peaks, which clearly corresponded to the changes in the frequencies of the modes as the pressure changed. Our results demonstrate the complex high-pressure behavior of solid propane.


Nasal Epistaxis Balloons: A Comprehensive MAUDE Database Analysis.
While nasal epistaxis balloons are generally seen as safe and routinely utilized by both surgical and nonsurgical providers, the complication profile related to this type of device has not been well defined. The objective of this study was to utilize the FDA MAUDE (Manufacturer and User Facility Device Experience) database to better assess adverse events (AE) related to use of nasal epistaxis balloons. Reports were individually tabulated and events were categorized with special attention to AEs. The FDA MAUDE database was queried for all medical device reports (MDR) related to nasal epistaxis balloon devices from January 2012 to November 2022. 19 MDRs met inclusion criteria. 5 MDRs were classified as device related (26.3 %); two events were reported for balloon leak and deflation, two events were reported for device breakage, and one device related event was unknown. 14 MDRs (73.7 %) were classified as patient related. Two documented MDRs were patient deaths due to exsanguination. Additional serious AEs included balloon ingestion and subsequent small bowel perforation (n = 1), cerebrospinal fluid leak (n = 1), skull base violation and intracranial placement of the device (n = 1), and respiratory distress (n = 3). Though epistaxis control with nasal balloons is generally seen as a safe procedure, there have been several concerning AEs reported. While two reports of death due to exsanguination were the most severe AEs, multiple other life-threatening AEs were also documented. Increased awareness of associated complications can be used to better counsel patients during the informed consent process as well as providers in their clinical decision making.


Prognostic model based on nailfold capillaroscopy for identifying Raynaud's phenomenon patients at high risk for the development of a scleroderma spectrum disorder: PRINCE (prognostic index for nailfold capillaroscopic examination).
To construct a prognostic index based on nailfold capillaroscopic examinations that is capable of predicting the 5-year transition from isolated Raynaud's phenomenon (RP) to RP secondary to scleroderma spectrum disorders (SSDs). The study involved 104 consecutive adult patients with a clinical history of isolated RP, and the index was externally validated in another cohort of 100 patients with the same characteristics. Both groups were followed up for 1-8 years. Six variables were examined because of their potential prognostic relevance (branching, enlarged and giant loops, capillary disorganization, microhemorrhages, and the number of capillaries). The only factors that played a significant prognostic role were the presence of giant loops (hazard ratio [HR] 2.64, P = 0.008) and microhemorrhages (HR 2.33, P = 0.01), and the number of capillaries (analyzed as a continuous variable). The adjusted prognostic role of these factors was evaluated by means of multivariate regression analysis, and the results were used to construct an algorithm-based prognostic index. The model was internally and externally validated. Our prognostic capillaroscopic index identifies RP patients in whom the risk of developing SSDs is high. This model is a weighted combination of different capillaroscopy parameters that allows physicians to stratify RP patients easily, using a relatively simple diagram to deduce the prognosis. Our results suggest that this index could be used in clinical practice, and its further inclusion in prospective studies will undoubtedly help in exploring its potential in predicting treatment response.


The development of asymmetry: the sidedness of drug-induced limb abnormalities is reversed in situs inversus mice.
We are studying the development of handedness, in particular the relationships between handed structures with bilateral symmetry, for example the limbs, and those with lateral asymmetry, such as the heart, lungs and gut. Asymmetric (unilateral) developmental limb abnormalities can be induced by chemical treatment of mouse embryos, either in utero by acetazolamide, or in culture by misonidazole. We have examined these effects in mice homozygous for the iv gene. The development of bilateral symmetry in iv/iv mice is normal, but the control of asymmetry appears to be random, that is 50% develop normally (situs solitus), 50% with laterally inverted viscera (situs inversus). We find that the handedness of induced asymmetric limb defects is highly correlated with embryonic visceral situs. Right limb defects are induced in situs solitus embryos, left-sided defects in situs inversus. This suggests that the mechanism of induction of asymmetric defects is not related to any intrinsic difference between the development of left and right limbs, but is connected to visceral asymmetry. In addition, the high correlation of limb defects with situs was observed in culture as well as in utero suggesting that the maternal environment plays no role in the development of asymmetry.


Responses of the hypothalamopituitary adrenal axis and the sympathoadrenal system to isolation/restraint stress in sheep of different adiposity.
There is evidence that levels of adipose tissue can influence responses of the hypothalamopituitary-adrenal (HPA) axis to stress in humans and rats but this has not been explored in sheep. Also, little is known about the sympathoadrenal responses to stress in individuals with relatively different levels of adipose tissue. We tested the hypothesis that the stress-induced activation of the HPA axis and sympathoadrenal system is lower in ovariectomized ewes with low levels of body fat (lean) than ovariectomized ewes with high levels of body fat (fat). Ewes underwent dietary manipulation for 3 months to yield a group of lean ewes (n = 7) with a mean (+/-SEM) live weight of 39.1 +/- 0.9 kg and body fat of 8.9 +/- 0.6% and fat ewes (n = 7) with a mean (+/-SEM) live weight of 69.0 +/- 1.8 kg and body fat of 31.7 +/- 3.4%. Fat ewes also had higher circulating concentrations of leptin than lean ewes. Blood samples were collected every 15 min over 8 h when no stress was imposed (control day) and on a separate day when 4 h of isolation/restraint was imposed after 4 h of pretreatment sampling (stress day). Plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, epinephrine and norepinephrine did not change significantly over the control day and did not differ between lean and fat ewes. Stress did not affect plasma leptin levels. All stress hormones increased significantly during isolation/restraint stress. The ACTH, cortisol and epinephrine responses were greater in fat ewes than lean ewes but norepinephrine responses were similar. Our results suggest that relative levels of adipose tissue influence the stress-induced activity of the hypothalamopituitary-adrenal axis and some aspects of the sympathoadrenal system with fat animals having higher responses than lean animals.


Characterization of the aerosol vertical distributions and their impacts on warm clouds based on multi-year ARM observations.
Aerosol vertical distribution plays a crucial role in cloud development and thus precipitation since both aerosol indirect and semi-direct effects significantly depend on the relative position of aerosol layer in reference to cloud, but its precise influence on cloud remains unclear. In this study, we integrated multi-year Raman Lidar measurements of aerosol vertical profiles from the U.S. Department of Energy Atmospheric Radiation Measurement (ARM) facility with available Value-Added Products of cloud features to characterize aerosol vertical distributions and their impacts on warm clouds over the continental and marine ARM atmospheric observatories, i.e., Southern Great Plains (SGP) and Eastern North Atlantic (ENA). A unimodal seasonal distribution of aerosol optical depths (AODs) with a peak in summer is found at upper boundary layer over SGP, while a bimodal distribution is observed at ENA for the AODs at lower levels with a major winter-spring maximum. The diurnal mean of upper-level AOD at SGP shows a maximum in the early evening. According to the relative positions of aerosol layers to clouds we further identify three primary types of aerosol vertical distribution, including Random, Decreasing, and Bottom. It is found that the impacts of aerosols on cloud may or may not vary with aerosol vertical distribution depending on environmental conditions, as reflected by the wide variations of the relations between AOD and cloud properties. For example, as AOD increases, the liquid water paths (LWPs) tend to be reduced at SGP but enhanced at ENA. The relations of cloud droplet effective radius with AOD largely depend on aerosol vertical distributions, particularly showing positive values in the Random type under low-LWP condition (<50 g m-2). The distinct features of aerosol-cloud interactions in relation to aerosol vertical distribution are likely attributed to the continental-marine contrast in thermodynamic environments and aerosol conditions between SGP and ENA.


[Interaction of H+ and K+ transport systems in E. coli growing under anaerobic and aerobic conditions].
The interaction of H+-ATPase complex F1 X F0 with the Trk system of K+ accumulation in E. coli grown quasi-anaerobically in pepton media with glucose (anaerobia) and aerobically in the salt medium with succinate (aerobia) treated with cyanide was studied. The ratio of H+ fluxes via F1 X F0 and K+ fluxes via the Trk system is stable and equals 2 in anaerobia and is changed from 0.5 to 5.0 in aerobia treated with cyanide in response to pH variation, K+ activity and temperature variations. Q10 is about 2.8 both for F1 X F0 and the Trk system in anaerobia, but 2.4 and 1.0 respectively in aerobia. K+ distribution in anaerobia reaches high values, K+ equilibrium potential is much higher than the measured membrane potential. K+ distribution in aerobia is smaller, which is in conformity with the measured membrane potential. Structural association of F1 X F0 and the Trk system with the formation of H+--K+-pump is assumed to take place in anaerobia, and separate operation of these systems occurs in aerobia, transfer of K+ via Trk system being energized by the electric field on the membrane.


Molecular properties of lupin and serradella leghaemoglobins.
1. Leghaemoglobins were extracted from the root nodules of lupin (Lupinus luteus L.) and serradella (Ornithopus sativus Brot.) plants and fractionated into different leghaemoglobin components on DEAE-cellulose-acetate columns. 2. The first two fractions eluted from columns loaded with either lupin or serradella leghaemoglobins were in the Fe(3+) oxidation state. 3. These components have protohaem IX as the prosthetic group and glycine as the N-terminal amino acid. 4. Other properties are: lupin component I, pI5.08, molecular weight 19000; lupin component II, pI5.13, molecular weight 20600; serradella component I, pI5.00, molecular weight 17500; serradella component II, pI5.05, molecular weight 19100. 5. Leghaemoglobins are thus heterogeneous with respect to size and charge.


Reliability of quantifying foot and ankle muscle strength in very young children.
Preschool-age children with neuromuscular disorders are often excluded from clinical trials due to the lack of reliable and objective strength measures. We evaluated the reliability of measuring foot and ankle muscle strength in 60 healthy children age 2-4 years. The strength of foot inversion and eversion, ankle plantarflexion, and dorsiflexion was measured using a hand-held dynamometer. Intrarater and interrater reliability of two assessors was determined for each muscle group using intraclass correlation coefficients (ICCs), 95% confidence intervals (CIs), and standard error of measurement (SEM). For all muscle groups intrarater (ICC(2,2) = 0.85-0.94, 95% CI = 0.75-0.96, SEM = 1.5-4.7 N) and interrater (ICC(2,1) = 0.88-0.96, 95% CI = 0.81-0.98, SEM = 1.2-4.6 N) reliability was high for all children. As expected, reliability was generally highest in 3- and 4-year-old children and lowest in 2-year-old children. Hand-held dynamometry can reliably measure foot and ankle strength in very young children and may help aid in diagnosis and in characterizing disease progression in disorders affecting the foot and ankle.


Professional dietetic education in the U.S. Historical notes.
Since its founding in 1917, The American Dietetic Association has been concerned with the development and improvement of educational programs for the professional dietitian. This article traces the evolution of professional dietetic educational programs from its beginning in the early cooking schools in the nineteenth century through the development of educational standards, the requirement for training beyond the bachelor's degree, and the establishment of academic requirements. The continued importance of educating the professional dietitian is evidenced by the inclusion of academic requirements as a prerequisite to membership in the Association.


Multi-Gram Scale Synthesis and Characterization of Mometasone Furoate EP Impurity C.
Mometasone furoate is a synthetic corticosteroid used in the treatment of skin inflammatory conditions, hay fever and asthma. The industrial manufacturing routes to mometasone furoate are generally accompanied by the formation of numerous process impurities that need to be detected and quantified, as requested by regulatory authorities. The ready availability of such impurities in the required quantity and purity is therefore essential for toxicological studies, analytical method development and process validation. Herein, we report the multi-gram scale preparation of 21'-chloro-(16'α-methyl-3',11',20'-trioxo-pregna-1',4'-dien-17'-yl)-furan-2-carboxylate (mometasone furoate EP impurity C), one of the known impurities of mometasone furoate. This study also includes the systematic investigation of the final acylation step, as well as the characterization of the difuroate enol ether intermediate and its conversion to the target impurity C.


Ultrafast mass spectrometry based bioanalytical method for digoxin supporting an in vitro P-glycoprotein (P-gp) inhibition screen.
The evaluation of interactions between drug candidates and transporters such as P-glycoprotein (P-gp) has gained considerable interest in drug discovery and development. Inhibition of P-gp can be assessed by performing bi-directional permeability studies with in vitro P-gp-expressing cellular model systems such as Caco-2 (human colon carcinoma) cells, using digoxin as a substrate probe. Existing methodologies include either assaying (3)H-digoxin with liquid scintillation counting (LSC) detection or assaying non-labeled digoxin with liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis at a speed of several minutes per sample. However, it is not feasible to achieve a throughput high enough using these approaches to sustain an early liability screen that generates more than a thousand samples on a daily basis. To address this challenge, we developed an ultrafast (9 s per sample) bioanalytical method for digoxin analysis using RapidFire™, an on-line solid-phase extraction (SPE) system, with MS/MS detection. A stable isotope labeled analog, d3-digoxin, was used as internal standard to minimize potential ionization matrix effect during the RF-MS/MS analysis. The RF-MS/MS method was more than 16 times faster than the LC-MS/MS method but demonstrated similar sensitivity, selectivity, reproducibility, linearity and robustness. P-gp inhibition results of multiple validation compounds obtained with this RF-MS/MS method were in agreement with those generated by both the LC-MS/MS method and the (3)H-radiolabel assay. This method has been successfully deployed to assess P-gp inhibition potential as an important early liability screen for drug-transporter interaction.


Molecular homology and incompatibility in the IncFI plasmid Group.
The usual grounds for the inclusion of a plasmid in a particular incompatibility group are its mutual incompatibility with a type plasmid of that group, and, in some cases, the demonstration of shared regions of specific homology, presumed to be related to DNA replication. We have found that some plasmids classified as IncFI on genetical grounds share no homology with the previously described incompatibility regions of F on the basis of hybridization of specific radioactive probes to restriction enzyme digests of DNA from these plasmids. Others show homology with some or all of the regions of the F plasmid that can express incompatibility. The incompatibility behaviour of these plasmids has been examined to determine the relationship between the possession of regions of homology and the expression of incompatibility. Three plasmids, ColV3-K30, pHH507 and Entp307, show homology only with the secondary replicon of F and appear to use sequences homologous with the secondary F replicon in their replication. The results are consistent with the propositions that some contemporary IncFI plasmids arose by the integration of several replicons, and, in general, the replicon not being used for replicon expresses its incompatibility, as does the replicon being used for replication. We conclude that incompatibility of two plasmids with F does not necessarily demonstrate relatedness of the plasmids to each other, and that inclusion within the IncFI group can result from the possession of any of several combinations of inc sequences.


Antagonism between bacteriostatic and bactericidal antibiotics is prevalent.
Combination therapy is rarely used to counter the evolution of resistance in bacterial infections. Expansion of the use of combination therapy requires knowledge of how drugs interact at inhibitory concentrations. More than 50 years ago, it was noted that, if bactericidal drugs are most potent with actively dividing cells, then the inhibition of growth induced by a bacteriostatic drug should result in an overall reduction of efficacy when the drug is used in combination with a bactericidal drug. Our goal here was to investigate this hypothesis systematically. We first constructed time-kill curves using five different antibiotics at clinically relevant concentrations, and we observed antagonism between bactericidal and bacteriostatic drugs. We extended our investigation by performing a screen of pairwise combinations of 21 different antibiotics at subinhibitory concentrations, and we found that strong antagonistic interactions were enriched significantly among combinations of bacteriostatic and bactericidal drugs. Finally, since our hypothesis relies on phenotypic effects produced by different drug classes, we recreated these experiments in a microfluidic device and performed time-lapse microscopy to directly observe and quantify the growth and division of individual cells with controlled antibiotic concentrations. While our single-cell observations supported the antagonism between bacteriostatic and bactericidal drugs, they revealed an unexpected variety of cellular responses to antagonistic drug combinations, suggesting that multiple mechanisms underlie the interactions.


What is the canonical theory of assimilation?
Throughout the past century, assimilation has been the hegemonic theory of ethnic group relations in sociology, and Robert E. Park is generally considered to be the key figure associated with the articulation of assimilation's canonical formulation. Based on a careful reading of Park's main essays on assimilation, this article argues that those who associate his position with the melting pot (with its assumption of the eradication of ethnic traits and ties), the race-relations cycle, or a straight-line process of incorporation misconstrue his views. This article is in part corrective and in part revisionist insofar as it is intended to indicate aspects of Park's theory that have particular relevance to current sociological efforts to understand the implications of assimilation in multiethnic liberal democracies.


Role of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community-acquired lower respiratory tract infections.
In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae, we studied 613 children aged 2-14 years who were hospitalized for community-acquired lower respiratory tract infections (LRTIs). The patients were enrolled in the study by 21 centers in different regions of Italy from May 1998 through April 1999. Paired serum samples were obtained on admission and after 4-6 weeks to assay the titers of M. pneumoniae and C. pneumoniae antibodies. Nasopharyngeal aspirates for the detection of M. pneumoniae and C. pneumoniae were obtained on admission. Acute M. pneumoniae infections in 210 patients (34.3%) and acute C. pneumoniae infections in 87 (14.1%) were diagnosed. Fifteen of the 18 children with M. pneumoniae and/or C. pneumoniae infections whose treatments were considered clinical failures 4-6 weeks after enrollment had not been treated with macrolides. Our study confirms that M. pneumoniae and/or C. pneumoniae plays a significant role in community-acquired LRTIs in children of all ages and that such infections have a more complicated course when not treated with adequate antimicrobial agents.


Protein corona affects the relaxivity and MRI contrast efficiency of magnetic nanoparticles.
Magnetic nanoparticles (NPs) are increasingly being considered for use in biomedical applications such as biosensors, imaging contrast agents and drug delivery vehicles. In a biological fluid, proteins associate in a preferential manner with NPs. The small sizes and high curvature angles of NPs influence the types and amounts of proteins present on their surfaces. This differential display of proteins bound to the surface of NPs can influence the tissue distribution, cellular uptake and biological effects of NPs. To date, the effects of adsorption of a protein corona (PC) on the magnetic properties of NPs have not been considered, despite the fact that some of their potential applications require their use in human blood. Here, to investigate the effects of a PC (using fetal bovine serum) on the MRI contrast efficiency of superparamagnetic iron oxide NPs (SPIONs), we have synthesized two series of SPIONs with variation in the thickness and functional groups (i.e. surface charges) of the dextran surface coating. We have observed that different physico-chemical characteristics of the dextran coatings on the SPIONs lead to the formation of PCs of different compositions. (1)H relaxometry was used to obtain the longitudinal, r1, and transverse, r2, relaxivities of the SPIONs without and with a PC, as a function of the Larmor frequency. The transverse relaxivity, which determines the efficiency of negative contrast agents (CAs), is very much dependent on the functional group and the surface charge of the SPIONs' coating. The presence of the PC did not alter the relaxivity of plain SPIONs, while it slightly increased the relaxivity of the negatively charged SPIONs and dramatically decreased the relaxivity of the positively charged ones, which was coupled with particle agglomeration in the presence of the proteins. To confirm the effect of the PC on the MRI contrast efficiency, in vitro MRI experiments at ν = 8.5 MHz were performed using a low-field MRI scanner. The MRI contrasts, produced by different samples, were fully in agreement with the relaxometry findings.


[Outstanding contribution of prof. Henryk M. Wisniewski (1931-1999) to the world neuropathology in 20th century].
Born in Poland in 1931, Henryk Miroslaw Wisniewski, obtained MD at the Medical School in Gdansk (1955), where he continued his neuropathological research awarded with Ph. D. in 1960. During 1961-1962 a worked as a Visiting Scientist at NIH (Institute of Neurology and Communicative Diseases and Stroke). In Medical School in Warsaw he was promoted to Docent degree (an associate professor). In 1966 he emigrated with his family to New York, where he was a Research Associate and Professor at Albert Einstein College of Medicine (1966-1975) Subsequently he became a Director of the State Institute for Basic Research in Developmental Disabilities Staten Island. In New York he remained till his early death at the age of 68. Prof. Wisniewski advanced pathological research concerning the development of dementia, including Alzheimer disease. His investigations proved that presentile dementia (Alzheimer disease) is almost identical with senile dementia. That is why he is called the pioneer of modern Alzheimers research. The comments about his scientific contribution were generously published in scientific journals and daily press. The New York Times cited Dr Mony de Leon Prof. of Psychiatry statement reflecting so well Prof. Wisniewski's achievements "He taught us what the lesions for Alzheimers looked like, what they were made of and how they worked".


Cu-Catalyzed Pyridine Synthesis via Oxidative Annulation of Cyclic Ketones with Propargylamine.
A Cu-catalyzed, easily scalable one-pot synthesis of fused pyridines by the reaction of cyclic ketones with propargylamine is described. The protocol was optimized based on the results of more than 30 experiments. The highest product yields were achieved in i-PrOH as a solvent in the presence of 5.0 mol % CuCl2 in air. In contrast to the well-known Au-catalyzed protocol, our procedure is "laboratory friendly", cost-effective, and suitable for preparing dozens of grams of fused pyridine-based building blocks and does not require a high-pressure autoclave technique. Decreasing the catalyst amount in the reaction to 1.25 mol % CuCl2 provided a yield comparable to that achieved with 5 mol % catalyst, though a longer reaction time was required. A plausible reaction mechanism was proposed. The scope and limitation of the reaction were studied using 24 different cyclic ketones as starting materials. The fused pyridine yield decreased among cyclic ketones in the following order: six-membered ≫ eight-membered > five-membered ∼ seven-membered. The elaborated reaction conditions demonstrated tolerance to a number of protective functional groups in ketone such as ester, tert-butoxycarbonyl (Boc)-protected amine, and acetal moieties.


Ultrastructural and cytochemical studies of the spermatozoa of Acrosternum aseadum (Hemiptera: Pentatomidae) after copulation.
Beside the morphofunctional modifications undergone during spermiogenesis, the spermatozoon could undergo other modifications after copulation. Since no structural modification occurs in the spermatozoon of Acrosternum aseadum after copulation, we used cytochemical studies to show the enzymatic activities variations of acid phosphatase, thiamine pyrophosphatase, glucose-6-phosphatase and cytochrome C oxidase, when the spermatozoon passes through the spermatheca. The enzymatic activity, few hours after copulation, is strong and specifically located. However, 40 h after copulation, there is considerable loss of enzymatic activity, with the exception of thiamine pyrophosphatase, which shows the same activity. This result indicates that the spermatozoon of A. aseadum undergoes physiological modifications when passing through the spermatheca and that these modifications may be involved with survival in this organ as well as with the fertilization process.


Genetic Polymorphism of Angiotensin II Type 1 Receptors and Their Effect on the Clinical Outcome of Captopril Treatment in Arab Iraqi Patients with Acute Coronary Syndrome (Mid Euphrates).
Genetic variation in the angiotensin II type 1 receptor (AT1R) has an important effect on the outcome of acute coronary syndrome (ACS) initiated treatment with captopril. This study aims to investigate the impact of genetic polymorphism of AT1R (rs5186 and rs275651) on the ACS outcome in Iraqi patients treated with captopril. A total of 250 Iraqi individuals with ACS were included in this case-control study and they were divided into two study groups; Study group 1 included 125 participants who were prescribed captopril, 25 mg twice daily and study group 2 included 125 participants who received no captopril as part of their ACS treatment (control study). The AT1R gene (rs5186) CC genotype was found to be associated with ST-elevation myocardial infarction (STEMI) (Odd's ratio (O.R) = 1.2, P = 0.7), while AC was associated with Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina (UA) (O.R = 1.2, P = 0.8). AC genotype is more prone to have Percutaneous coronary intervention (PCI) after ACS attack (O.R = 1.2, P = 0.6). CC genotype had a risk to get less improvement (O.R = 1.6, P = 0.5), so might require higher doses of captopril during acute coronary insult. The AT1R gene (rs275651) AA genotype was associated with UA (O.R = 1.3, P = 0.9). AA and AT genotypes were more prone to have PCI after ACS attack (O.R = 3.9 P = 0.2, O.R = 3.5, P = 0.3 respectively) and thus requiring higher doses of captopril. We conclude that the AT1R rs5186, rs275651 genetic polymorphisms might partially affect the clinical outcome of ACS patients treated with captopril and might have captopril resistance which requires higher doses.


Myelinating glia differentiation is regulated by extracellular matrix elasticity.
The mechanical properties of living tissues have a significant impact on cell differentiation, but remain unexplored in the context of myelin formation and repair. In the PNS, the extracellular matrix (ECM) incorporates a basal lamina significantly denser than the loosely organized CNS matrix. Inhibition of non-muscle myosin II (NMII) enhances central but impairs peripheral myelination and NMII has been implicated in cellular responses to changes in the elasticity of the ECM. To directly evaluate whether mechanotransduction plays a role in glial cell differentiation, we cultured Schwann cells (SC) and oligodendrocytes (OL) on matrices of variable elastic modulus, mimicking either their native environment or conditions found in injured tissue. We found that a rigid, lesion-like matrix inhibited branching and differentiation of OL in NMII-dependent manner. By contrast, SC developed normally in both soft and stiffer matrices. Although SC differentiation was not significantly affected by changes in matrix stiffness alone, we found that expression of Krox-20 was potentiated on rigid matrices at high laminin concentration. These findings are relevant to the design of biomaterials to promote healing and regeneration in both CNS and PNS, via transplantation of glial progenitors or the implantation of tissue scaffolds.


Angioseal VIP® vs. StarClose SE® closure devices: a comparative analysis in non-cardiological procedures.
The aim of this paper was to compare the use of two different commercially available vascular closure devices (VCD), Angioseal VIP® (St. Jude Medical, St. Paul, MN, USA) and StarClose SE (Abbott Laboratories, Abbott Park, IL, USA). From January 2010 to January 2012, 347 patient underwent retrograde femoral arterial puncture for different interventional procedures (angioplasty, stenting, embolization for bleeding, fibrinolysis for ischemia and chemoembolization). Hemostasis was achieved by deployment of an Angioseal VIP® (N.=184) or StarClose SE® (N.=163). In 94 cases, the retrograde femoral access was bilateral and managed with two StarClose SE devices (N.=53) or an Angioseal VIP® plus a StarClose SE® (N.=41). Technical success was obtained in 95.1% (330/347) of patients. Overall time to hemostasis (TTH) and time to ambulation (TTA) were 5,5±1,5 min (range 3-8 min) and 6±2.5 hr (range 2-9 hours) respectively. No statistical significative difference (P>0.05) were appreciable between to groups for both TTH and TTA: Angioseal VIP® TTH was 5.3±1.4 min and StarClose SE® TTH was 5.6±1.6 min; Angioseal VIP® TTA was 5.9±1.8 hr and StarClose SE® TTA was 6.1±1.9 hr. VAS scores result underline a mild difference between two devices. Angioseal VIP® patients experience a mild to moderate pain within the first 3 minutes from the deployment. Whereas StarClose SE® patients still experience pain at 5 minutes from deployment. The device failure rate was 4.9% (17 cases) and included 13 minor complications and 4 major complications. Minor complications (3.75%) occurred during the initial phase and consisted in recurrent wound bleeding (N.=5 StarClose SE®; N.=4 Angioseal VIP®) treated with manual compression, and hematoma (N.=2 StarClose SE®; N.=2 Angioseal VIP®) that solved spontaneously. The 4 major complications (1,15%) were: 1 Angioseal-related common femoral artery (CFA) obstruction treated with surgical bypass from the CFA to the superficial femoral artery; 1 Angioseal-related CFA dissection solved with surgery; 1 Angioseal-related embolization of the deep femoral artery partially treated with localized fibrinolysis; 1 StarClose-related pseudoaneurysm treated with manual compression. Both Angioseal VIP® and StarClose SE® systems can be considered safe and effective in providing hemostasis following a variety of interventional vascular procedures.


Clustering of mutations affecting alginic acid biosynthesis in mucoid Pseudomonas aeruginosa.
A 10-kilobase DNA fragment previously shown to contain the phosphomannose isomerase gene (pmi) of Pseudomonas aeruginosa was used to construct a pBR325-based hybrid that can be propagated in P. aeruginosa only by the formation of a chromosomal-plasmid cointegrate. This plasmid, designated pAD4008, was inserted into the P. aeruginosa chromosome by recombination at a site of homology between the cloned P. aeruginosa DNA and the chromosome. Mobilization of pAD4008 into P. aeruginosa PAO and 8830 and selection for the stable acquisition of tetracycline resistance resulted in specific and predictable changes in the pattern of endonuclease restriction sites in the phosphomannose isomerase gene region of the chromosomes. Chromosomal DNA from the tetracycline-resistant transformants was used to clone the drug resistance determinant with Bg/II or XbaI, thereby allowing the "walking" of the P. aeruginosa chromosome in the vicinity of the pmi gene. Analysis of overlapping tetracycline-resistant clones indicated the presence of sequences homologous to the DNA insert of plasmid pAD2, a recombinant clone of P. aeruginosa origin previously shown to complement several alginate-negative mutants. Restriction mapping, subcloning, and complementation analysis of a 30-kilobase DNA region demonstrated the tight clustering of several genetic loci involved in alginate biosynthesis. Furthermore, the tetracycline resistance determinant in PAO strain transformed by pAD4008 was mapped on the chromosome by plasmid FP2-mediated conjugation and was found to be located near 45 min.


Proteomic identification of secreted proteins of Propionibacterium acnes.
The anaerobic Gram-positive bacterium Propionibacterium acnes is a human skin commensal that resides preferentially within sebaceous follicles; however, it also exhibits many traits of an opportunistic pathogen, playing roles in a variety of inflammatory diseases such as acne vulgaris. To date, the underlying disease-causing mechanisms remain ill-defined and knowledge of P. acnes virulence factors remains scarce. Here, we identified proteins secreted during anaerobic cultivation of a range of skin and clinical P. acnes isolates, spanning the four known phylogenetic groups. Culture supernatant proteins of P. acnes were separated by two-dimensional electrophoresis (2-DE) and all Coomassie-stained spots were subsequently identified by MALDI mass spectrometry (MALDI-MS). A set of 20 proteins was secreted in the mid-exponential growth phase by the majority of strains tested. Functional annotation revealed that many of these common proteins possess degrading activities, including glycoside hydrolases with similarities to endoglycoceramidase, β-N-acetylglucosaminidase and muramidase; esterases such as lysophospholipase and triacylglycerol lipase; and several proteases. Other secreted factors included Christie-Atkins-Munch-Petersen (CAMP) factors, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and several hypothetical proteins, a few of which are unique to P. acnes. Strain-specific differences were apparent, mostly in the secretion of putative adhesins, whose genes exhibit variable phase variation-like sequence signatures. Our proteomic investigations have revealed that the P. acnes secretome harbors several proteins likely to play a role in host-tissue degradation and inflammation. Despite a large overlap between the secretomes of all four P. acnes phylotypes, distinct differences between predicted host-tissue interacting proteins were identified, providing potential insight into the differential virulence properties of P. acnes isolates. Thus, our data presents a rich resource for guiding much-needed investigations on P. acnes virulence factors and host interacting properties.


Carvedilol-Afforded Protection against Daunorubicin-Induced Cardiomyopathic Rats In Vivo: Effects on Cardiac Fibrosis and Hypertrophy.
Anthracyclines, most powerful anticancer agents, suffer from their cardiotoxic effects, which may be due to the induction of oxidative stress. Carvedilol, a third-generation, nonselective β-adrenoreceptor antagonist, possesses both reactive oxygen species (ROS) scavenging and ROS suppressive effects. It showed protective effects against daunorubicin- (DNR-) induced cardiac toxicity by reducing oxidative stress and apoptosis. This study therefore was designed to examine the effects of carvedilol on DNR-induced cardiomyopathic rats, focused on the changes of left ventricular function, cardiac fibrosis, and hypertrophy. Carvedilol increased survival rate, prevented systolic and diastolic dysfunction, and attenuated myocardial fibrosis and hypertrophy. DNR alone treated rats showed upregulated myocardial expression of ANP, PKC-α, OPN, and TGF-β1 and downregulation of GATA-4 in comparison with control, and treatment with carvedilol significantly reversed these changes. The results of the present study add the available evidences on the cardioprotection by carvedilol when associated with anthracyclines and explain the mechanisms underlying the benefits of their coadministration.


Spatio-temporal distribution and sources identifications of polycyclic aromatic hydrocarbons and their alkyl homolog in surface sediments in the central Arabian Gulf.
The quantitative analysis of 18 parents and their alkyl homologs was performed in sediment samples from the central Arabian Gulf (Gulf) around Qatar Peninsula in six sequential seasons, winter 2014 to spring 2015, at 21 locations with a water depth range of 1.5-60 m. PAHs distribution was patchy with higher concentrations found inside semi-enclosed coastal areas like harbors and bays. The mean PAHs concentration was 112 ng·g-1 dry weight with a range of 0.6 to 1560 ng·g-1 and a variability coefficient of 2.4. The PAHs mean concentration was highest in the winter by a factor of 5 compared to mean summer concentration. A significant seasonal variability in the concentrations of ∑PAHs is mainly attributed to variability in the concentrations of the low molecular weight PAHs fraction and the less alkylated PAHs. Alkylated-PAHs were the most dominant PAHs comprising about 50% of the ∑PAHs, and with about 6 times higher than the mean concentrations in the winter compared to the mean summer concentration. The LPAHs concentrations correlated negatively with temperature and ∑PAHs correlated positively with % clay. Principal component analysis was used to identify sources of PAHs. PAHs in the Gulf have mixed sources with an estimated 57% from petroleum and 43% from pyrogenic sources. Coastal water hydrodynamics and lateral transport processes affect the distribution and composition of PAHs in the central Gulf.


Lumbar puncture: it is time to change the needle.
Lumbar puncture is a frequent procedure performed by physicians from several disciplines to help establish a diagnosis and treatment for several diseases. Post-lumbar puncture headache (PLPH) is a frequent complication that typically lasts for a couple of days and can be severe enough to immobilize the patient and to require therapy. There are several risk factors identified, pain characteristics, and characteristic findings on spinal and head magnetic resonance imaging. There are several procedural factors that have been identified to be of consequence in attenuating the PLPH incidence, specifically the needle type and size used for this procedure. Once PLPH occurs, the clinician should treat it conservatively with bed rest, analgesics and increased fluids intake, especially caffeine-containing beverages, as it can dramatically affect the patient's wellness. If the pain is severe and disabling and does not respond to conservative treatment, a blood patch should be considered at least 24-48 h following the LP. Epidural blood patch is a safe and rapidly effective treatment in experienced hands. Furthermore, patients who developed PLPH should be advised to contact the medical staff in case of changes in the characteristics of headaches. When a patient who was diagnosed with PLPH has a change in the pain character, or additional neurological manifestations appear, an urgent brain CT/head MRI should be performed to exclude rarer life-threatening intracranial complications.


[Current potentials of endoscopic rhinosinusosurgery].
Information on current potentials of endoscopic rhinosinusosurgery are presented in this review. Potentials of miniinvasive endoscopic procedures as an alternative or adjuvant treatment option in surgery of ophthalmologic patients are discussed.


A review of the first year of Medicare coverage of erythropoietin.
Recombinant human erythropoietin (rHuEPO) is a new drug for treating anemia associated with end stage renal disease (ESRD). In a study of rHuEPO diffusion, costs, and effectiveness, we analyze ESRD program data and all claims submitted to Medicare for reimbursement of rHuEPO administered to ESRD dialysis patients. Access to rHuEPO was rapid and extensive during the first year of Medicare coverage. Dosing of rHuEPO and achieved hematocrit were lower than expected based on the results of clinical trials. rHuEPO cost Medicare $144 million in its first year. The analysis of insurance claims data allowed effective monitoring of access, costs, and effectiveness of this new biotechnology.


Episiotomy pain relief: Use of Lavender oil essence in primiparous Iranian women.
Post-episiotomy discomfort and its consequences can affect maternal quality of life and mental health as well as the mother and baby relationship. Complementary medicine is increasingly used and Lavender oil is frequently prescribed due to its antiseptic and healing properties. This clinical trial involved 60 qualified primiparous women admitted for labor in Kamali Hospital in Karaj, Iran. They were randomly categorized into two groups: case (using Lavender oil) and control (usual hospital protocol). Participants pain and discomfort were recorded using a Visual Analogue Scale (VAS) and a Redness, Edema, Ecchymosis, Discharge Scale (REEDA). Pain was evaluated at 4 h, 12 h and 5 days following episiotomy. Collected data was analyzed in SPSS 14 using an independent t-test and chi-square. There was a statistical difference in pain intensity scores between the 2 groups after 4 h (p = 0.002, and 5 days (p = 0.000) after episiotomy. However, differences in pain intensity between the two groups, at 12 h post-surgery, were not significant (p = 0.066). The REEDA score was significantly lower in the experimental group (Lavender oil group) 5 days after episiotomy (p = 0.000). According to these findings, use of Lavender oil essence can be effective in reducing perineal discomfort following episiotomy. It is suggested that Lavender oil essence may be preferably to the use of Betadine for episiotomy wound care.