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The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.

BACKGROUND & AIMS: Multiple definitions for malnutrition syndromes are found in the literature resulting in confusion. Recent evidence suggests that varying degrees of acute or chronic inflammation are key contributing factors in the pathophysiology of malnutrition that is associated with disease or injury. METHODS: An International Guideline Committee was constituted to develop a consensus approach to defining malnutrition syndromes for adults in the clinical setting. Consensus was achieved through a series of meetings held at the A.S.P.E.N. and ESPEN Congresses. RESULTS: It was agreed that an etiology-based approach that incorporates a current understanding of inflammatory response would be most appropriate. The Committee proposes the following nomenclature for nutrition diagnosis in adults in the clinical practice setting. "Starvation-related malnutrition", when there is chronic starvation without inflammation, "chronic disease-related malnutrition", when inflammation is chronic and of mild to moderate degree, and "acute disease or injury-related malnutrition", when inflammation is acute and of severe degree. CONCLUSIONS: This commentary is intended to present a simple etiology-based construct for the diagnosis of adult malnutrition in the clinical setting. Development of associated laboratory, functional, food intake, and body weight criteria and their application to routine clinical practice will require validation.

INTRODUCTION: The International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the Definition of Premature Ejaculation developed the first evidence-based definition for lifelong premature ejaculation (PE) in 2007 and concluded that there were insufficient published objective data at that time to develop a definition for acquired PE. AIM: The aim of this article is to review and critique the current literature and develop a contemporary, evidence-based definition for acquired PE and/or a unified definition for both lifelong and acquired PE. METHODS: In April 2013, the ISSM convened a second Ad Hoc Committee for the Definition of Premature Ejaculation in Bangalore, India. The same evidence-based systematic approach to literature search, retrieval, and evaluation used by the original committee was adopted. RESULTS: The committee unanimously agreed that men with lifelong and acquired PE appear to share the dimensions of short ejaculatory latency, reduced or absent perceived ejaculatory control, and the presence of negative personal consequences. Men with acquired PE are older, have higher incidences of erectile dysfunction, comorbid disease, and cardiovascular risk factors, and have a longer intravaginal ejaculation latency time (IELT) as compared with men with lifelong PE. A self-estimated or stopwatch IELT of 3 minutes was identified as a valid IELT cut-off for diagnosing acquired PE. On this basis, the committee agreed on a unified definition of both acquired and lifelong PE as a male sexual dysfunction characterized by (i) ejaculation that always or nearly always occurs prior to or within about 1 minute of vaginal penetration from the first sexual experience (lifelong PE) or a clinically significant and bothersome reduction in latency time, often to about 3 minutes or less (acquired PE); (ii) the inability to delay ejaculation on all or nearly all vaginal penetrations; and (iii) negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy. CONCLUSION: The ISSM unified definition of lifelong and acquired PE represents the first evidence-based definition for these conditions. This definition will enable researchers to design methodologically rigorous studies to improve our understanding of acquired PE. Serefoglu EC, McMahon CG, Waldinger MD, Althof SE, Shindel A, Adaikan G, Becher EF, Dean J, Giuliano F, Hellstrom WJG, Giraldi A, Glina S, Incrocci L, Jannini E, McCabe M, Parish S, Rowland D, Segraves RT, Sharlip I, and Torres LO. An evidence-based unified definition of lifelong and acquired premature ejaculation: Report of the second International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation. Sex Med 2014;2:41-59.

Macrophages play essential activities in homeostasis maintenance during different organism's conditions. They may be polarized according to various stimuli, which subsequently subdivide them into distinct populations. Macrophages with inflammatory activity function mainly during pathological context, while those with regulatory activity control inflammation and also remodel the repairing process. Here, we propose to review and to present a concise discuss on the role of different components during tissue repair, including those related to innate immune receptors and metabolic modifications. The scar formation is directly related to the degree of inflammation, but also with the appearance of M2 macrophages. In spite of greater numbers of macrophages in the fibrotic phase, regulatory macrophages present some characteristics related to promotion of fibrosis but also with the control of scar formation. These regulatory macrophages present an oxidative metabolism, and differ from the initial inflammatory macrophages, which in turn, present a glycolytic characteristic, which allow regulatory ones to optimize the oxygen consumption and minimizing their ROS production. We will emphasize the difference in macrophage subpopulations and the origin and plasticity of these cells during fibrotic processes.

INTRODUCTION: In 2009, the International Society for Sexual Medicine (ISSM) convened a select panel of experts to develop an evidence-based set of guidelines for patients suffering from lifelong premature ejaculation (PE). That document reviewed definitions, etiology, impact on the patient and partner, assessment, and pharmacological, psychological, and combined treatments. It concluded by recognizing the continually evolving nature of clinical research and recommended a subsequent guideline review and revision every fourth year. Consistent with that recommendation, the ISSM organized a second multidisciplinary panel of experts in April 2013, which met for 2 days in Bangalore, India. This manuscript updates the previous guidelines and reports on the recommendations of the panel of experts. AIM: The aim of this study was to develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of PE for family practice clinicians as well as sexual medicine experts. METHOD: A comprehensive literature review was performed. RESULTS: This article contains the report of the second ISSM PE Guidelines Committee. It offers a new unified definition of PE and updates the previous treatment recommendations. Brief assessment procedures are delineated, and validated diagnostic and treatment questionnaires are reviewed. Finally, the best practices treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with PE, in facilitating treatment of their patients. CONCLUSION: Development of guidelines is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to a more complete understanding of the pathophysiology as well as new efficacious and safe treatments for this sexual dysfunction. We again recommend that these guidelines be reevaluated and updated by the ISSM in 4 years. Althof SE, McMahon CG, Waldinger MD, Serefoglu EC, Shindel AW, Adaikan PG, Becher E, Dean J, Giuliano F, Hellstrom WJG, Giraldi A, Glina S, Incrocci L, Jannini E, McCabe M, Parish S, Rowland D, Segraves RT, Sharlip I, and Torres LO. An update of the International Society of Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation (PE). Sex Med 2014;2:60-90.

ABSTRACT Introduction Psychological, interpersonal, and sociocultural factors play a significant role in making one vulnerable to developing a sexual concern, in triggering the onset of a sexual difficulty, and in maintaining sexual dysfunction in the long term. Aim To focus on psychological and interpersonal aspects of sexual functioning in women and men after a critical review of the literature from 2010 to the present. Methods This report is part 1 of 2 of our collaborative work during the 2015 International Consultation on Sexual Medicine for Committee 2. Main Outcome Measures Systematic review of the literature with a focus on publications since 2010. Results Our work as sexual medicine clinicians is essentially transdisciplinary, which involves not only the collaboration of multidisciplinary professionals but also the integration and application of new knowledge and evaluation and subsequent revision of our practices to ensure the highest level of care provided. There is scant literature on gender non-conforming children and adolescents to clarify specific developmental factors that shape the development of gender identity, orientation, and sexuality. Conversely, studies consistently have demonstrated the interdependence of sexual function between partners, with dysfunction in one partner often contributing to problems in sexual functioning and/or sexual satisfaction for the other. We recommend that clinicians explore attachment styles of patients, childhood experiences (including sexual abuse), onset of sexual activity, personality, cognitive schemas, infertility concerns, and sexual expectations. Assessment of depression, anxiety, stress, substance use and post-traumatic stress (and their medical treatments) should be carried out as part of the initial evaluation. Clinicians should attempt to ascertain whether the anxiety and/or depression is a consequence or a cause of the sexual complaint, and treatment should be administered accordingly. Cognitive distraction is a significant contributor to sexual response problems in men and women and is observed more consistently for genital arousal than for subjective arousal. Assessment of physical and mental illnesses that commonly occur in later life should be included as part of the initial evaluation in middle-aged and older persons presenting with sexual complaints. Menopausal status has an independent effect on reported changes in sex life and difficulties with intercourse. There is strong support for the use of psychological treatment for sexual desire and orgasm difficulties in women (but not in men). Combination therapies should be provided to men, whenever possible. Conclusion Overall, research strongly supports the routine clinical investigation of psychological factors, partner-related factors, context, and life stressors. A biopsychosocial model to understand how these factors predispose to sexual dysfunction is recommended.

Importance: Patients with heart failure and preserved ejection fraction (HFpEF) are at high risk of mortality, hospitalizations, and reduced functional capacity and quality of life. Objective: To assess the efficacy of the oral soluble guanylate cyclase stimulator vericiguat on the physical limitation score (PLS) of the Kansas City Cardiomyopathy Questionnaire (KCCQ). Design, Setting, and Participants: Phase 2b randomized, double-blind, placebo-controlled, multicenter trial of 789 patients with chronic HFpEF and left ventricular ejection fraction 45% or higher with New York Heart Association class II-III symptoms, within 6 months of a recent decompensation (HF hospitalization or intravenous diuretics for HF without hospitalization), and with elevated natriuretic peptides, enrolled at 167 sites in 21 countries from June 15, 2018, through March 27, 2019; follow-up was completed on November 4, 2019. Interventions: Patients were randomized to receive vericiguat, up-titrated to 15-mg (n = 264) or 10-mg (n = 263) daily oral dosages, compared with placebo (n = 262) and randomized 1:1:1. Main Outcomes and Measures: The primary outcome was change in the KCCQ PLS (range, 0-100; higher values indicate better functioning) after 24 weeks of treatment. The secondary outcome was 6-minute walking distance from baseline to 24 weeks. Results: Among 789 randomized patients, the mean age was 72.7 (SD, 9.4) years; 385 (49%) were female; mean EF was 56%; and median N-terminal pro-brain natriuretic peptide level was 1403 pg/mL; 761 (96.5%) completed the trial. The baseline and 24-week KCCQ PLS means for the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups were 60.0 and 68.3, 57.3 and 69.0, and 59.0 and 67.1, respectively, and the least-squares mean changes were 5.5, 6.4, and 6.9, respectively. The least-squares mean difference in scores between the 15-mg/d vericiguat and placebo groups was -1.5 (95% CI, -5.5 to 2.5; P = .47) and between the 10-mg/d vericiguat and placebo groups was -0.5 (95% CI, -4.6 to 3.5; P = .80). The baseline and 24-week 6-minute walking distance mean scores in the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups were 295.0 m and 311.8m , 292.1 m and 318.3 m, and 295.8 m and 311.4 m, and the least-squares mean changes were 5.0 m, 8.7 m, and 10.5 m, respectively. The least-squares mean difference between the 15-mg/d vericiguat and placebo groups was -5.5 m (95% CI, -19.7 m to 8.8 m; P = .45) and between the 10-mg/d vericiguat and placebo groups was -1.8 m (95% CI, -16.2 m to 12.6 m; P = .81), respectively. The proportions of patients who experienced symptomatic hypotension were 6.4% in the 15-mg/d vericiguat group, 4.2% in the 10-mg/d vericiguat group, and 3.4% in the placebo group; those with syncope were 1.5%, 0.8%, and 0.4%, respectively. Conclusions and Relevance: Among patients with HFpEF and recent decompensation, 24-week treatment with vericiguat at either 15-mg/d or 10-mg/d dosages compared with placebo did not improve the physical limitation score of the KCCQ. Trial Registration: ClinicalTrials.gov Identifier: NCT03547583.

INTRODUCTION: In 2009, the International Society for Sexual Medicine (ISSM) convened a select panel of experts to develop an evidence-based set of guidelines for patients suffering from lifelong premature ejaculation (PE). That document reviewed definitions, etiology, impact on the patient and partner, assessment, and pharmacological, psychological, and combined treatments. It concluded by recognizing the continually evolving nature of clinical research and recommended a subsequent guideline review and revision every fourth year. Consistent with that recommendation, the ISSM organized a second multidisciplinary panel of experts in April 2013, which met for 2 days in Bangalore, India. This manuscript updates the previous guidelines and reports on the recommendations of the panel of experts. AIM: The aim of this study was to develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of PE for family practice clinicians as well as sexual medicine experts. METHOD: A comprehensive literature review was performed. RESULTS: This article contains the report of the second ISSM PE Guidelines Committee. It offers a new unified definition of PE and updates the previous treatment recommendations. Brief assessment procedures are delineated, and validated diagnostic and treatment questionnaires are reviewed. Finally, the best practices treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with PE, in facilitating treatment of their patients. CONCLUSION: Development of guidelines is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to a more complete understanding of the pathophysiology as well as new efficacious and safe treatments for this sexual dysfunction. We again recommend that these guidelines be reevaluated and updated by the ISSM in 4 years.

OBJECTIVE: To investigate whether the recent repetitive transcranial magnetic stimulation (rTMS) studies on depression using new parameters of stimulation have shown improved clinical results. METHOD: We performed a systematic review and a meta-analysis of the rTMS studies on depression published in the past 12 months comparing these results with an earlier meta-analysis that analyzed the results of the initial rTMS studies on depression. RESULTS: Using our inclusion criteria, we selected the meta-analysis of Martin [Br J Psychiatry (2003) Vol. 182, 480-491] that included 13 studies (324 patients) and five studies for the recent meta-analysis (274 patients). The pooled effect size (standardized mean difference between pretreatment vs. post-treatment) from the random effects model was -0.76 (95% confidence interval, CI, -1.01 to -0.51). This result was significantly larger than that of the earlier meta-analysis (-0.35, 95% CI -0.66 to -0.04). CONCLUSION: Our findings suggest that recent rTMS clinical trials have shown larger antidepressant effects when compared with the earlier studies.

Abstract Introduction The International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the Definition of Premature Ejaculation developed the first evidence-based definition for lifelong premature ejaculation (PE) in 2007 and concluded that there were insufficient published objective data at that time to develop a definition for acquired PE. Aim The aim of this article is to review and critique the current literature and develop a contemporary, evidence-based definition for acquired PE and/or a unified definition for both lifelong and acquired PE. Methods In April 2013, the ISSM convened a second Ad Hoc Committee for the Definition of Premature Ejaculation in Bangalore, India. The same evidence-based systematic approach to literature search, retrieval, and evaluation used by the original committee was adopted. Results The committee unanimously agreed that men with lifelong and acquired PE appear to share the dimensions of short ejaculatory latency, reduced or absent perceived ejaculatory control, and the presence of negative personal consequences. Men with acquired PE are older, have higher incidences of erectile dysfunction, comorbid disease, and cardiovascular risk factors, and have a longer intravaginal ejaculation latency time (IELT) as compared with men with lifelong PE. A self-estimated or stopwatch IELT of 3 minutes was identified as a valid IELT cut-off for diagnosing acquired PE. On this basis, the committee agreed on a unified definition of both acquired and lifelong PE as a male sexual dysfunction characterized by (i) ejaculation that always or nearly always occurs prior to or within about 1 minute of vaginal penetration from the first sexual experience (lifelong PE) or a clinically significant and bothersome reduction in latency time, often to about 3 minutes or less (acquired PE); (ii) the inability to delay ejaculation on all or nearly all vaginal penetrations; and (iii) negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy. Conclusion The ISSM unified definition of lifelong and acquired PE represents the first evidence-based definition for these conditions. This definition will enable researchers to design methodologically rigorous studies to improve our understanding of acquired PE.

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Abstract. The Tropical Forest and Fire Emissions Experiment (TROFFEE) used laboratory measurements followed by airborne and ground based field campaigns during the 2004 Amazon dry season to quantify the emissions from pristine tropical forest and several plantations as well as the emissions, fuel consumption, and fire ecology of tropical deforestation fires. The airborne campaign used an Embraer 110B aircraft outfitted with whole air sampling in canisters, mass-calibrated nephelometry, ozone by UV absorbance, Fourier transform infrared spectroscopy (FTIR), and proton-transfer mass spectrometry (PTR-MS) to measure PM10, O3, CO2, CO, NO, NO2, HONO, HCN, NH3, OCS, DMS, CH4, and up to 48 non-methane organic compounds (NMOC). The Brazilian smoke/haze layers extended to 2–3 km altitude, which is much lower than the 5–6 km observed at the same latitude, time of year, and local time in Africa in 2000. Emission factors (EF) were computed for the 19 tropical deforestation fires sampled and they largely compare well to previous work. However, the TROFFEE EF are mostly based on a much larger number of samples than previously available and they also include results for significant emissions not previously reported such as: nitrous acid, acrylonitrile, pyrrole, methylvinylketone, methacrolein, crotonaldehyde, methylethylketone, methylpropanal, "acetol plus methylacetate," furaldehydes, dimethylsulfide, and C1-C4 alkyl nitrates. Thus, we recommend these EF for all tropical deforestation fires. The NMOC emissions were ~80% reactive, oxygenated volatile organic compounds (OVOC). Our EF for PM10 (17.8±4 g/kg) is ~25% higher than previously reported for tropical forest fires and may reflect a trend towards, and sampling of, larger fires than in earlier studies. A large fraction of the total burning for 2004 likely occurred during a two-week period of very low humidity. The combined output of these fires created a massive "mega-plume" >500 km across that we sampled on 8 September. The mega-plume contained high PM10 and 10–50 ppbv of many reactive species such as O3, NH3, NO2, CH3OH, and organic acids. This is an intense and globally important chemical processing environment that is still poorly understood. The mega-plume or "white ocean" of smoke covered a large area in Brazil, Bolivia, and Paraguay for about one month. The smoke was transported >2000 km to the southeast while remaining concentrated enough to cause a 3–4-fold increase in aerosol loading in the São Paulo area for several days.

Autosomal recessive polycystic kidney disease (ARPKD/PKHD1) is an important cause of renal-related and liver-related morbidity and mortality in childhood. Recently mutations in the PKHD1 gene on chromosome 6p21.1-p12 have been identified as the molecular cause of ARPKD. The longest continuous open reading frame (ORF) is encoded by a 67-exon transcript and predicted to yield a 4074-amino acid protein ("polyductin") of thus far unknown function. By now, a total of 29 different PKHD1 mutations have been described. This study reports mutation screening in 90 ARPKD patients and identifies mutations in 110 alleles making up a detection rate of 61%. Thirty-four of the detected mutations have not been reported previously. Two underlying mutations in 40 patients and one mutation in 30 cases are disclosed, and no mutation was detected on the remaining chromosomes. Mutations were found to be scattered throughout the gene without evidence of clustering at specific sites. About 45% of the changes were predicted to truncate the protein. All missense mutations were nonconservative, with the affected amino acid residues found to be conserved in the murine polyductin orthologue. One recurrent missense mutation (T36M) likely represents a mutational hotspot and occurs in a variety of populations. Two founder mutations (R496X and V3471G) make up about 60% of PKHD1 mutations in the Finnish population. Preliminary genotype-phenotype correlations could be established for the type of mutation rather than for the site of the individual mutation. All patients carrying two truncating mutations displayed a severe phenotype with perinatal or neonatal demise. PKHD1 mutation analysis is a powerful tool to establish the molecular cause of ARPKD in a given family. Direct identification of mutations allows an unequivocal diagnosis and accurate genetic counseling even in families displaying diagnostic challenges.

Variability is common on construction projects and must be managed effectively. New management thinking, like that of lean production, has suggested that better labor and cost performance can be achieved by reducing output variability. Efforts to utilize lean thinking in construction, so far, have generated limited evidence to support this claim. This paper investigates the relationship between variability and project performance to test the notion that reducing output variability will result in improved labor performance. Using productivity data from concrete formwork activities on multiple projects, various measures of output variability are tested against construction performance. It is shown that variability in output is inevitable and that there is little correlation between output variability and project performance, but that variability in labor productivity is closely correlated to project performance. It is concluded that lean improvement initiatives should be redirected to adaptable workforce management capabilities to reduce variability in labor productivity instead of output in order to improve project performance.

AIMS: This study aimed to highlight the salient sociocultural factors contributing to sexual health and dysfunction and to offer recommendations for culturally sensitive clinical management and research as well for an ethically sound sexual health care, counseling and medical decision-making. BACKGROUND: There are limited data on the impact of sociocultural factors on male and female sexual function as well as on ethical principles to follow when clinical care falls outside of traditional realms of medically indicated interventions. METHODS: This study reviewed the current literature on sociocultural and ethical considerations with regard to male and female sexual dysfunction as well as cultural and cosmetic female and male genital modification procedures. RESULTS: It is recommended that clinicians evaluate their patients and their partners in the context of culture and assess distressing sexual symptoms regardless of whether they are a recognized dysfunction. Both clinicians and researchers should develop culturally sensitive assessment skills and instruments. There are a number of practices with complex ethical issues (eg, female genital cutting, female and male cosmetic genital surgery). Future International Committee of Sexual Medicine meetings should seek to develop guidelines and associated recommendations for a separate, broader chapter on ethics.

INTRODUCTION: The frequent recolonization of treated sites by periodontopathogens and the emergence of antibiotic resistance have led to a call for new therapeutic approaches for managing periodontal diseases. As probiotics are considered a new tool for combating infectious diseases, we systematically reviewed the evidences for their effectiveness in the management of periodontitis. AREAS COVERED: An electronic search was performed in the MEDLINE, SCOPUS and Cochrane Library databases up to March 2016 using the terms 'periodontitis', 'chronic periodontitis', 'probiotic(s)', 'prebiotic(s)', 'symbiotic(s)', 'Bifidobacterium and 'Lactobacillus'. Only randomized controlled trials (RCTs) were included in the present study. Analysis of 12 RCTs revealed that in general, oral administration of probiotics improved the recognized clinical signs of chronic and aggressive periodontitis such as probing pocket depth, bleeding on probing, and attachment loss, with a concomitant reduction in the levels of major periodontal pathogens. Continuous probiotic administration, laced mainly with Lactobacillus species, was necessary to maintain these benefits. Expert commentary: Oral administration of probiotics is a safe and effective adjunct to conventional mechanical treatment (scaling) in the management of periodontitis, specially the chronic disease entity. Their adjunctive use is likely to improve disease indices and reduce the need for antibiotics.

Autosomal recessive polycystic kidney disease (ARPKD; MIM 263200) is a hereditary and severe form of polycystic disease affecting the kidneys and biliary tract with an estimated incidence of 1 in 20,000 live births. The clinical spectrum is widely variable: up to 50% of affected neonates die shortly after birth, whereas others survive to adulthood. Mutations at a single locus, polycystic kidney and hepatic disease 1 (PKHD1), are responsible for all typical forms of ARPKD. Mutation detection was performed in PKHD1 by DHPLC in 85 affected, unrelated individuals. Seventy-four amplicons were amplified and analyzed from the PKHD1 genomic locus. Sequence variants were considered pathogenic when they were not observed in 160 control individuals (320 chromosomes). For purposes of genotype-phenotype comparisons, families were stratified by clinical presentation into two groups: the severe perinatal group, in which at least one affected child presented with perinatal disease and neonatal demise, and the less severe, nonperinatal group, in which none of the affected children died in the neonatal period. Forty-one mutations were found in 55 affected disease chromosomes; 32 of these mutations have not been reported previously. Mutations were distributed throughout the portions of gene encoding the predicted extracellular portion of the protein product. The most commonly encountered mutation, T36M, was found in 8 of 55 disease chromosomes. Amino acid substitutions were found to be more commonly associated with a nonlethal presentation, whereas chain terminating mutations were more commonly associated with neonatal demise (chi(2) = 11.54, P = 0.003). All patients who survive the neonatal period have at least one amino acid substitution mutation, suggesting that such substitutions produce milder disease through production of partially functional protein products. The nature of the germline mutations in ARPKD plays a significant role in determining clinical outcome.

Abstract. Real-time mass spectra of the non-refractory species in submicron aerosol particles were recorded in a tropical rainforest in the central Amazon Basin during the wet season from February to March 2008, as a part of the Amazonian Aerosol Characterization Experiment (AMAZE-08). Organic material accounted on average for more than 80% of the non-refractory submicron particle mass concentrations during the period of measurements. There was insufficient ammonium to neutralize sulfate. In this acidic, isoprene-rich, HO2-dominant environment, positive-matrix factorization of the time series of particle mass spectra identified four statistical factors to account for the 99% of the variance in the signal intensities of the organic constituents. The first factor was identified as associated with regional and local pollution and labeled "HOA" for its hydrocarbon-like characteristics. A second factor was associated with long-range transport and labeled "OOA-1" for its oxygenated characteristics. A third factor, labeled "OOA-2," was implicated as associated with the reactive uptake of isoprene oxidation products, especially of epoxydiols to acidic haze, fog, or cloud droplets. A fourth factor, labeled "OOA-3," was consistent with an association with the fresh production of secondary organic material (SOM) by the mechanism of gas-phase oxidation of biogenic volatile organic precursors followed by gas-to-particle conversion of the oxidation products. The suffixes 1, 2, and 3 on the OOA labels signify ordinal ranking with respect to the extent of oxidation represented by the factor. The process of aqueous-phase oxidation of water-soluble products of gas-phase photochemistry might also have been associated to some extent with the OOA-2 factor. The campaign-average factor loadings had a ratio of 1.4:1 for OOA-2 : OOA-3, suggesting the comparable importance of particle-phase compared to gas-phase pathways for the production of SOM during the study period.

This article is published as part of a supplement sponsored by Kidney Disease: Improving Global Outcomes (KDIGO). The opinions or views expressed in this supplement are those of the authors and do not necessarily reflect the opinions or recommendations of the International Society of Nephrology or Elsevier. Dosages, indications, and methods of use for products that are referred to in the supplement by the authors may reflect their clinical experience or may be derived from the professional literature or other clinical sources.

OBJECTIVE: A cross-sectional study was conducted to investigate if anxiety, depression and hopelessness symptoms are associated with periodontal disease. METHOD: A total of 160 subjects took part in this study. Probing depth and clinical attachment level were recorded at six sites per tooth and the gingival and plaque indices were also recorded. The instruments used to assess the psychological variables (anxiety, depression, stress, psychiatric symptoms and hopelessness) were: the State-Trait Anxiety Inventory, the Beck Depression Inventory, the Life Events Scale modified by Savoia, the Self-Report Screening Questionnaire-20 and the Beck Hopelessness Scale. RESULTS: There was no difference in scale score means between patients with and without established periodontitis. Results of the Ordinal Logistic Regression Analysis model that included age, plaque index, smoking and psychological factors showed that patients with psychiatric symptoms (odds ratio (OR) 1.24, 95% confidence interval (CI) 0.33-4.78), depression symptoms (OR 0.57, 95% CI 0.15-2.21) and with hopelessness (OR 0.70, 95% CI 0.13-3.84) were not at a greater risk of developing established periodontitis. CONCLUSION: In this sample, no evidence was found for an association between depression, hopelessness, psychiatric symptoms and established periodontitis. The association of periodontal disease to depression, anxiety and stress should be investigated in psychiatric populations, especially in those with depression and anxiety disorders.