Dissolved Organic Matter Composition Determines Its Susceptibility to Complete and Partial Photooxidation within Lakes.

Dissolved organic matter (DOM) plays an important role in carbon cycling within inland surface waters. Under sunlight irradiation, DOM undergoes complete photooxidation to produce carbon dioxide (CO2) and partial photooxidation that alters the molecular composition of DOM. However, a mechanistic understanding of the relationship between DOM composition and its susceptibility to partial and complete photooxidation in surface waters is currently lacking. This work combines light exposure experiments with high-resolution mass spectrometry to investigate DOM photooxidation using two DOM isolates and DOM from 16 lakes that vary in trophic status and size. High ratios of oxygen consumption to dissolved inorganic carbon (DIC) production demonstrate that all samples undergo extensive partial photooxidation. At the molecular level, more oxidized, aromatic DOM formulas are associated with oxygen consumption and DIC production. Bulk level measurements indicate that DOM becomes less aromatic and lower in apparent molecular weight following partial photooxidation, and there is molecular level evidence of oxygen addition and loss of CO2 in all samples. However, formulas most susceptible to photooxidation vary depending on the initial DOM composition. Collectively, this work provides insights into the relationship between DOM composition and photooxidation, which has important implications for carbon cycling in diverse surface waters.

Formation of Targeted and Novel Disinfection Byproducts during Chlorine Photolysis in the Presence of Bromide.

Chlorine photolysis is an advanced oxidation process that relies on the combination of direct chlorination by free available chlorine, direct photolysis, and reactive oxidants to transform contaminants. In waters that contain bromide, free available bromine and reactive bromine species can also form. However, little is known about the underlying mechanisms or formation potential of disinfection byproducts (DBPs) under these conditions. We investigated reactive oxidant generation and DBP formation under dark conditions, chlorine photolysis, and radical-quenched chorine photolysis with variable chlorine (0-10 mg-Cl2/L) and bromide (0-2,000 µg/L) concentrations, as well as with free available bromine. Probe loss rates and ozone concentrations increase with chlorine concentration and are minimally impacted by bromide. Radical-mediated processes partially contribute to the formation targeted DBPs (i.e., trihalomethanes, haloacetic acids, haloacetonitriles, chlorate, and bromate), which increase with increasing chlorine concentration. Chlorinated novel DBPs detected by high-resolution mass spectrometry are attributable to a combination of dark chlorination, direct halogenation by reactive chlorine species, and transformation of precursors, whereas novel brominated DBPs are primarily attributable to dark bromination of electron-rich formulas. The formation of targeted and novel DBPs during chlorine photolysis in waters with elevated bromide may limit treatment applications.

The epigenetic immunomodulator, HBI-8000, enhances the response and reverses resistance to checkpoint inhibitors.

BACKGROUND: Treatment with immune checkpoint inhibitors (ICIs) targeting CTLA-4 and the PD-1/PD-L1 axis is effective against many cancer types. However, due in part to unresponsiveness or acquired resistance, not all patients experience a durable response to ICIs. HBI-8000 is a novel, orally bioavailable class I selective histone deacetylase inhibitor that directly modifies antitumor activity by inducing apoptosis, cell cycle arrest, and resensitization to apoptotic stimuli in adult T cell lymphoma patients. We hypothesized that HBI-8000 functions as an epigenetic immunomodulator to reprogram the tumor microenvironment from immunologically cold (nonresponsive) to hot (responsive). METHOD: Mice bearing syngeneic tumors (MC38 and CT26 murine colon carcinoma and A20 B-cell lymphoma were treated daily with HBI-8000 (orally), alone or in combination with PD-1, PD-1 L, or CTLA-4 antibodies. MC38 tumors were also analyzed in nanoString gene expression analysis. RESULTS: HBI-8000 augmented the activity of ICI antibodies targeting either PD-1, PD-L1 or CTLA-4, and significantly increased tumor regression (p < 0.05) in the above models. Gene expression analysis of the treated MC38 tumors revealed significant changes in mRNA expression of immune checkpoints, with enhanced dendritic cell and antigen-presenting cell functions, and modulation of MHC class I and II molecules. CONCLUSIONS: These findings suggest that HBI-8000 mediates epigenetic modifications in the tumor microenvironment, leading to improved efficacy of ICIs, and provide strong rationale for combination therapies with ICIs and HBI-8000 in the clinical setting. PRECIS: As an HDACi, HBI-8000 plays an important role in priming the immune system in the tumor microenvironment. The current preclinical data further justifies testing combination of HBI-8000 and ICIs in the clinic.

Indigenous data and health: critical approaches to 'race'/ethnicity and Indigenous data governance.

'Race'/ethnicity data have become increasingly institutionalised within research on Indigenous health. While these data are important to monitoring the differential distribution of health risks and benefits in racialised societies, their uncritical and undertheorised use can perpetuate harmful biologically deterministic and essentialist approaches to Indigenous health. In addition, narratives of Indigenous health are often still shaped by colonial logics, with Indigenous data rights, priorities and governance overlooked or ignored. Researchers need to critique the use of 'race'/ethnicity concepts and data in Indigenous health research. This requires an explicit shift away from describing 'race'/ethnicity as 'risk factors' to examining processes by which 'race'/ethnicity become meaningful in relation to health outcomes for Indigenous communities. In addition, researchers need to consider how Indigenous rights to health data are recognised, including the application of frameworks or principles of Indigenous data sovereignty.

Colonial histories, racism and health-The experience of Maori and Indigenous peoples.

The health of Maori, the Indigenous peoples of Aotearoa, New Zealand, like that of almost all Indigenous peoples worldwide, is characterised by systematic inequities in health outcomes, differential exposure to the determinants of health, inequitable access to and through health and social systems, disproportionate marginalisation and inadequate representation in the health workforce. As health providers, we are often taught that 'taking a history' is a critical component of a patient consultation to ensure that the underlying conditions are treated rather than the often superficial presenting symptoms. In the same way, attempts to make sense of the health and well-being of Indigenous peoples is inadequate unless health providers engage critically with the history of their respective nations and any subsequent patterns of privilege or disadvantage. Understanding this history, within the framework of western imperialism and other similar colonial projects, allows us to make sense of international patterns of Indigenous health status. While health commentators acknowledge the unequal health outcomes of Indigenous people, and an increasing number also link these inequities to Indigenous marginalisation resulting from historic events, very few go further and expose the deep relationship between racism and coloniality and how these continue to be the basic determinants of Indigenous health today. This work includes honest examination of the role that science and the health disciplines have played historically in colonisation through the subjugation of Indigenous ways of knowing and knowledge production, as well as being complicit in the creation and maintenance of a fabricated hierarchy of humankind. Despite the 'science' of this racial hierarchy being discredited, it retains a false validity in our societies. As long as oppressive systems that continue to re-inscribe racism and white privilege remain in communities, including our academic communities, coloniality continues its discrimination. Indigenous voices on migration, ethnicity, racisma and health will always demand the elimination of inequities in health but to do so will require a parallel commitment to critically interrogating all of our histories and our disciplines, as well as examining how our practice, including research, disrupts or maintains global systems of racism and coloniality.

Induction of apoptosis by HBI-8000 in adult T-cell leukemia/lymphoma is associated with activation of Bim and NLRP3.

Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell malignancy caused by human T-cell lymphotropic virus 1. Treatment options for acute ATL patients include chemotherapy, stem cell transplantation, and recently the anti-chemokine (C-C motif) receptor 4 antibody, although most patients still have a poor prognosis and there is a clear need for additional options. HBI-8000 is a novel oral histone deacetylase inhibitor with proven efficacy for treatment of T-cell lymphomas that recently received approval in China. In the present study, we evaluated the effects of HBI-8000 on ATL-derived cell lines and primary cells obtained from Japanese ATL patients. In most cases HBI-8000 induced apoptosis in both primary ATL cells and cell lines. In addition, findings obtained with DNA microarray suggested Bim activation and, interestingly, the contribution of the NLR family, pyrin domain containing 3 (NLRP3) inflammasome pathway in HBI-8000-induced ATL cell death. Further investigations using siRNAs confirmed that Bim contributes to HBI-8000-induced apoptosis. Our results provide a rationale for a clinical investigation of the efficacy of HBI-8000 in patients with ATL. Although the role of NLRP3 inflammasome activation in ATL cell death remains to be verified, HBI-8000 may be part of a novel therapeutic strategy for cancer based on the NLRP3 pathway.

Six cases of silicosis: implications for health surveillance of stonemasons.

BACKGROUND: Silicosis is one of the oldest occupational lung diseases, but it continues to cause significant morbidity and mortality worldwide. AIMS: To report cases of silicosis presenting to two specialist respiratory clinics. METHODS: A retrospective analysis of prospectively collected data of cases of silicosis in workers referred to specialist respiratory clinics. RESULTS: Over the course of 6 years, six cases were identified. The patients were all male with an age range between 24 and 39 years. The duration of silica exposure ranged between 7 and 20 years (mean 13 years). Four cases were entirely asymptomatic at presentation, and two cases described minimal shortness of breath on exertion. Pulmonary function tests were normal in three cases, and a mild restrictive ventilatory defect was documented in the other cases. All had a low apparent predicted probability of pneumoconiosis based on health questionnaires, spirometry and duration of silica exposure. The initial chest X-ray was abnormal in all six cases with radiological evidence of silicosis (International Labour Office profusion category ≥1/1) on imaging, and all had evidence of silicosis on high-resolution computed tomography (HRCT). Three patients had already progressed to progressive massive fibrosis on HRCT scanning at the time of referral to specialist respiratory services. CONCLUSIONS: The appearances of these six cases of silicosis in young, asymptomatic construction workers emphasizes the importance of enforcing effective exposure control and comprehensive surveillance programmes. Our observations highlight the importance of having a low threshold for early radiological screening to promote early and effective detection of this disease.

Systemic lupus erythematosus complicating simple silicosis.

Inhalation of crystalline silica is known to result in silicosis: an irreversible, disabling and potentially fatal occupational lung disease, which is associated with a variety of pulmonary and non-pulmonary complications including autoimmunity. A potential link between silicosis and systemic lupus erythematosus (SLE) is currently recognized only in cases of acute or accelerated silicosis. We report a case of SLE, a disease which usually affects young females, arising in a male former stonemason with simple silicosis. Epidemiological and clinical literature on the association of silica exposure and development of SLE are briefly reviewed. This case report and literature review highlight the link between occupational silica exposure and autoimmune disease including SLE, establishes that even simple silicosis appears linked to development of autoimmunity and emphasizes the importance of an occupational history, especially in male patients who develop SLE.

Mediators of antiretroviral adherence: a multisite international study.

The purpose of this study was to investigate the effects of stressful life events (SLE) on medication adherence (3 days, 30 days) as mediated by sense of coherence (SOC), self-compassion (SCS), and engagement with the healthcare provider (eHCP) and whether this differed by international site. Data were obtained from a cross-sectional sample of 2082 HIV positive adults between September 2009 and January 2011 from sites in Canada, China, Namibia, Puerto Rico, Thailand, and US. Statistical tests to explore the effects of stressful life events on antiretroviral medication adherence included descriptive statistics, multivariate analysis of variance, analysis of variance with Bonferroni post-hoc analysis, and path analysis. An examination by international site of the relationships between SLE, SCS, SOC, and eHCP with adherence (3 days and 30 days) indicated these combined variables were related to adherence whether 3 days or 30 days to different degrees at the various sites. SLE, SCS, SOC, and eHCP were significant predictors of adherence past 3 days for the United States (p = < 0.001), Canada (p = 0.006), and Namibia (p = 0.019). The combined independent variables were significant predictors of adherence past 30 days only in the United States and Canada. Engagement with the provider was a significant correlate for antiretroviral adherence in most, but not all, of these countries. Thus, the importance of eHCP cannot be overstated. Nonetheless, our findings need to be accompanied by the caveat that research on variables of interest, while enriched by a sample obtained from international sites, may not have the same relationships in each country.

A multinational study of self-compassion and human immunodeficiency virus-related anxiety.

AIM: This study represents an initial effort at examining the association between the construct of self-compassion and human immunodeficiency virus (HIV)-related anxiety in a multinational population with HIV disease. BACKGROUND: Previous studies have found that self-compassion is a powerful predictor of mental health, demonstrating positive and consistent linkages with various measures of affect, psychopathology and well-being, including anxiety. METHODS: Cross-sectional data from a multinational study conducted by the members of the International Nursing Network for HIV Research (n = 1986) were used. The diverse sample included participants from Canada, China, Namibia, the United States of America and the territory of Puerto Rico. Study measures included the anxiety subscale of the Symptom Checklist-90 instrument, the Brief Version Self-Compassion Inventory and a single item on anxiety from the Revised Sign and Symptom Checklist. FINDINGS: Study findings show that anxiety was significantly and inversely related to self-compassion across participants in all countries. We examined gender differences in self-compassion and anxiety, controlling for country. Levels of anxiety remained significantly and inversely related to self-compassion for both males (P = 0.000) and females (P = 0.000). Levels of self-compassion and anxiety varied across countries. CONCLUSIONS: Self-compassion is a robust construct with cross-cultural relevance. A culturally based brief treatment approach aimed at increasing self-compassion may lend itself to the development of a cost effective adjunct treatment in HIV disease, including the management of anxiety symptoms.

Limitations of conventional approaches to identify photochemically produced reactive intermediates involved in contaminant indirect photodegradation.

Dissolved organic matter (DOM) mediated indirect photodegradation can play an important role in the degradation of aquatic contaminants. Predicting the rate of this process requires knowledge of the photochemically produced reactive intermediates (PPRI) that react with the compound of interest, as well as the ability of individual DOM samples to produce PPRI. Key PPRI are typically identified using quencher studies, yet this approach often leads to results that are difficult to interpret. In this work, we analyze the indirect photodegradation of atorvastatin, carbamazepine, sulfadiazine, and benzotriazole using a diverse set of 48 waters from natural and engineered aquatic systems. We use this large data set to evaluate relationships between PPRI formation and indirect photodegradation rate constants, which are directly compared to results using standard quenching experiments. These data demonstrate that triplet state DOM (3DOM) and singlet oxygen (1O2) are critical PPRI for atorvastatin, carbamazepine, and sulfadiazine, while hydroxyl radical (˙OH) contributes to the indirect photodegradation of benzotriazole. We caution against relying on quenching studies because quenching of 3DOM limits the formation of 1O2 and all studied quenchers react with ˙OH. Furthermore, we show that DOM composition directly influences indirect photodegradation and that low molecular weight, microbial-like DOM is positively correlated with the indirect photodegradation rates of carbamazepine, sulfadiazine, and benzotriazole.

Cancer-preventive rexinoid modulates neutral lipid contents of mammary epithelial cells through a peroxisome proliferator-activated receptor γ-dependent mechanism.

Synthetic rexinoids effectively suppress both estrogen receptor-positive and estrogen receptor-negative mammary tumors in animal models, which makes them prime candidates for a novel class of cancer-preventive agents. When used in combination with chemotherapy for non-small-cell lung cancer, the rexinoid bexarotene was most effective for patients who developed hypertriglyceridemia as a side effect. Although serum triglycerides originate from the liver, the effect of bexarotene on lipogenesis in breast epithelial cells is not known. Gene expression studies with normal mammary epithelial cells indicated that rexinoids modulate lipid metabolism, particularly enzymes involved in triglyceride synthesis. High-content analysis revealed dose-dependent accumulation of neutral lipids within adipocyte differentiation-related protein-associated cytoplasmic lipid droplets after long-term bexarotene treatment. Bexarotene also induced mRNA and protein levels for peroxisome proliferator-activated receptor (PPAR) γ, whereas selective knockdown of PPARγ attenuated the induction of both lipid droplets and adipocyte differentiation-related protein. Pharmacological activation of PPARγ, but not PPARα or retinoic acid receptors, effectively induced lipid accumulation. Furthermore, the combination of the PPARγ agonist rosiglitazone with bexarotene synergistically suppressed the growth of human mammary epithelial cells and revealed a strong, nonlinear, inverse correlation of cell growth with lipid droplet accumulation in the cell population. These findings indicate that rexinoids activate a lipogenic program in mammary epithelial cells through a retinoid X receptor/PPARγ-mediated mechanism. It is noteworthy that combining low doses of bexarotene with the PPARγ agonist rosiglitazone provides effective growth suppression of mammary epithelial cells, potentially dissociating systemic adverse effects associated with standard bexarotene treatment from the antiproliferative effects on mammary epithelium.

Beyond power laws: a new approach for analyzing single molecule photoluminescence intermittency.

The photoluminescence intermittency (PI) exhibited by single emitters has been studied for over a decade. To date, the vast majority of PI analyses involve parsing the data into emissive and non-emissive events, constructing histograms of event durations, and fitting these histograms to either exponential or power law probability distributions functions (PDFs). Here, a new method for analyzing PI data is presented where the data are used directly to construct a cumulative distribution function (CDF), and maximum-likelihood estimation techniques are used to determine the best fit of a model PDF to the CDF. Statistical tests are then employed to quantitatively evaluate the hypothesis that the CDF (data) is represented by the model PDF. The analysis method is outlined and applied to PI exhibited by single CdSe∕CdS core-shell nanocrystals and the organic chromophore violamine R isolated in single crystals of potassium-acid phthalate. Contrary to previous studies, the analysis presented here demonstrates that the PI exhibited by these systems is not described by a power law. The analysis developed here is also used to quantify heterogeneity within PI data obtained from a collection of CdSe/CdS nanocrytals, and for the determination of statistically significant changes in PI accompanying perturbation of the emitter. In summary, the analysis methodology presented here provides a more statistically robust approach for analyzing PI data.

Change and variability in Antarctic coastal exposure, 1979-2020.

Increased exposure of Antarctica's coastal environment to open ocean and waves due to loss of a protective sea-ice "buffer" has important ramifications for ice-shelf stability, coastal erosion, important ice-ocean-atmosphere interactions and shallow benthic ecosystems. Here, we introduce a climate and environmental metric based on the ongoing long-term satellite sea-ice concentration record, namely Coastal Exposure Length. This is a daily measure of change and variability in the length and incidence of Antarctic coastline lacking any protective sea-ice buffer offshore. For 1979-2020, ~50% of Antarctica's ~17,850-km coastline had no sea ice offshore each summer, with minimal exposure in winter. Regional summer/maximum contributions vary from 45% (Amundsen-Bellingshausen seas) to 58% (Indian Ocean and Ross Sea), with circumpolar annual exposure ranging from 38% (2019) to 63% (1993). The annual maximum length of Antarctic coastal exposure decreased by ~30 km (~0.32%) per year for 1979-2020, composed of distinct regional and seasonal contributions.

Impact of ozone-biologically active filtration on the breakthrough of Perfluoroalkyl acids during granular activated carbon treatment of municipal wastewater effluent.

The presence of perfluoroalkyl acids (PFAAs) in municipal wastewater has highlighted the need to develop PFAA treatment approaches for wastewater effluent and potable reuse applications. Ozone (O3) and biologically active filtration (BAF) were investigated as standalone and combined pretreatment processes to improve the performance of granular activated carbon (GAC) for PFAA removal from wastewater effluent. As individual processes, ozonation at all three investigated doses (0.35, 0.75, 1.0 mg O3/mg DOC) and BAF at both tested empty bed contact times (EBCT; 15 and 20 min) led to significant improvement in PFAA removal by subsequent GAC treatment. With respect to standalone ozonation, the specific O3 dose of 0.75 mg O3/mg DOC was proven to be the optimum operating condition as further increase of the specific ozone dose to 1.0 mg O3/mg DOC did not provide considerable additional improvement. Extending the EBCT during standalone BAF from 15 to 20 minutes significantly improved the efficacy of GAC for the removal of tested PFAAs. Pretreatment with O3-BAF (0.75 mg O3/mg DOC; 20 min EBCT) in tandem outperformed both standalone ozonation and BAF for the removal of PFAA by GAC. Characterization of effluent organic matter (EfOM) by size exclusion chromatography (SEC) and Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR-MS) before and after pretreatments suggest that among multiple co-occurring phenomena, the shift towards smaller and more polar EfOM may have predominantly alleviated pore constriction/blockage without having adverse impact on direct site competition. This observation is supported by SEC and FT-ICR-MS results indicating reduced EfOM molecular size through O3 and BAF pretreatment as well as transition to more hydrophilic byproducts.

Episodic Plate Tectonics on Europa: Evidence for Widespread Patches of Mobile-Lid Behavior in the Antijovian Hemisphere.

A nearly pole-to-pole survey near 140°E longitude on Europa revealed many areas that exhibit past lateral surface motions, and these areas were examined to determine whether the motions can be described by systems of rigid plates moving across Europa's surface. Three areas showing plate-like behavior were examined in detail to determine the sequence of events that deformed the surface. All three areas were reconstructed to reveal the original pre-plate motion surfaces by performing multi-stage rotations of plates in spherical coordinates. Several motions observed along single plate boundaries were also noted in previous works, but this work links together isolated observations of lateral offsets into integrated systems of moving plates. Not all of the surveyed surface could be described by systems of rigid plates. There is evidence that the plate motions did not all happen at the same time, and that they are not happening today. We conclude that plate tectonic-like behavior on Europa occurs episodically, in limited regions, with less than 100 km of lateral motion accommodated along any particular boundary before plate motions cease. Europa may represent a world perched on the theoretical boundary between stagnant and mobile lid convective behavior, or it may represent an additional example of the wide variations in possible planetary convective regimes. Differences in observed strike-slip sense and plate rotation directions between the northern and southern hemispheres raise the question of whether tidal forces may influence plate motions.

The rexinoid bexarotene represses cyclin D1 transcription by inducing the DEC2 transcriptional repressor.

Bexarotene is an RXR-selective vitamin A analog that has been shown to prevent ER-negative mammary tumorigenesis in animal models. While investigating the mechanism by which bexarotene prevents ER-negative breast cancer development, we found that the expression of cyclin D1, a critical cell cycle promoter, was repressed by bexarotene in vitro and in vivo. Time course and cycloheximide experiments show that repression of cyclin D1 is a late effect and requires new protein synthesis. Previously we discovered that DEC2 (differentially expressed in chondrocytes-2), a helix-loop-helix transcription repressor, was induced by bexarotene in human mammary epithelial cells. Therefore, we hypothesized that bexarotene represses the transcription of cyclin D1 through induction of DEC2. Luciferase reporter studies demonstrated that either bexarotene treatment or forced expression of DEC2 can repress the transcription of a cyclin D1 promoter reporter by affecting the basal transcriptional activity. Results from chromatin immunoprecipitation experiments showed that bexarotene treatment causes the recruitment of DEC2 and HDAC1 (histone deacetylase 1) to the cyclin D1 promoter. Co-immunoprecipitation confirms the interaction between DEC2 and HDAC1, suggesting that the recruitment of HDAC1 to the cyclin D1 promoter is through DEC2. Trichostatin A, a HDAC inhibitor, reverses the cyclin D1 repression by bexarotene, suggesting that repression of cyclin D1 involves histone deacetylation. Knock-down of DEC2 by siRNA abolishes the cyclin D1 repression, further supporting our hypothesis. Finally, we demonstrated that overexpression of DEC2 dramatically inhibited cell proliferation and repressed the expression of cyclin D1 in human mammary epithelial cells. These results suggest that bexarotene down-regulates cyclin D1 through induction of DEC2, followed by recruitment of HDAC1 to the cyclin D1 promoter causing transcriptional repression. By elucidating the mechanism by which rexinoids inhibit cell proliferation, it will be possible to develop more effective and less toxic drugs to prevent ER-negative breast cancers.

Determining levels of fecal incontinence in the community: a New Zealand cross-sectional study.

BACKGROUND: Fecal incontinence is a socially stigmatized condition, and its prevalence in the community has been problematic to quantify because of difficulty with its definition. OBJECTIVE: This study estimates the community prevalence of fecal incontinence in New Zealand by 3 scales of measurement: patient perceptions of a "problem with bowel control," their symptoms, and their quality of life. DESIGN/MAIN OUTCOME MEASURES: A postal survey of 2000 people, aged >18, randomly selected from the national electoral roll, was performed. This used a validated, reliability-tested, anonymous questionnaire, the Comprehensive Fecal Incontinence Questionnaire, incorporating the identification of a "problem with bowel control," the Fecal Incontinence Severity Index, and the Fecal Incontinence Quality of Life Scale. RESULTS: The response rate was 68.7%. A total of 14.7% (95% CI: 12.6-16.7) of participants "felt they had a problem with bowel control" and 12.4% (95% CI: 10.5-14.5) had fecal incontinence when defined using the Fecal Incontinence Severity Index table as "leakage of liquid or solid stool ≥ 1/month." In terms of quality of life, 26.8% of the population (95% CI: 24.2-29.4) noted some impairment on the Fecal Incontinence Quality of Life Scale. In total, 155 (13.2%) participants reported at least 2 of the 3 possible diagnostic measures, and this may provide a way to incorporate the 3 measures into a new definition of fecal incontinence. LIMITATIONS: This study incorporated a new "generic" question enquiring about an individual's perception of a bowel control problem and also introduced a "cutoff" value for Fecal Incontinence Quality of Life Scale to attempt to identify those with any impairment "due to accidental bowel leakage." CONCLUSIONS: This study helps to highlight some of the challenges involved with suitably identifying those who have fecal incontinence within the community. The prevalence rate of 13.2% represents a realistic measure of the burden of fecal incontinence in the general population, and further research in this area is recommended.

Regulatory role for macrophage migration inhibitory factor in acute respiratory distress syndrome.

Migration inhibitory factor (MIF) is known to exert significant pro-inflammatory effects and has the potential to override the anti-inflammatory action of glucocorticoids. In this study we have identified significant quantities of MIF in the alveolar airspaces of patients with acute respiratory distress syndrome (ARDS). We show in alveolar cells from patients with ARDS that MIF augments pro-inflammatory cytokine secretion (TNF alpha and IL-8), anti-MIF significantly attenuates TNF alpha and IL-8 secretion and MIF overrides, in a concentration-related fashion, the anti-inflammatory effects of glucocorticoids. These findings suggest that MIF may act as a mediator sustaining the pulmonary inflammatory response in ARDS and that an anti-MIF strategy may represent a novel therapeutic approach in inflammatory diseases such as ARDS.

Atlantoaxial rotatory fixation after ventriculoperitoneal shunting.

Ventriculoperitoneal (VP) shunting is a common neurosurgical procedure in the pediatric population. Atlantoaxial rotatory fixation (AARF) is not uncommon in this same group. We present the first reported case of AARF following a VP shunt procedure. A 10-year-old boy, with hydrocephalus and a left temporal arachnoid cyst since birth, underwent a revision of his VP and cystoperitoneal shunts. A second operation was performed 2 days later to optimize catheter placement. Postoperative neck pain was attributed to tunneling of the subcutaneous catheter. 2 months after surgery, the child had minimal neck discomfort but maintained his head in a "cock-robin" position. Plain radiographs and computed tomographic (CT) images confirmed AARF. The child was admitted and placed in halo traction. After 3 days of traction, analgesics, sedation, and muscle relaxants, anatomic re-alignment of the C1-C2 vertebral complex was confirmed on CT scan. Following 3 months of immobilization in a halo-vest apparatus, the halo was removed. At 8-year follow-up, the clinical examination is normal and repeat imaging studies remain normal. Due to surgical positioning, and postoperative signs attributed to normal postoperative pain, an AARF was not initially recognized. This case represents the first time that AARF has been reported following a VP shunt procedure.