Multi-year diagnosis of unpredictable fouling occurrences in a full-scale membrane bioreactor.

The membrane bioreactor (MBR) at the Traverse City Regional Wastewater Treatment Plant has experienced sudden and unpredictable periods of substantial permeability decline since 2011. Early observations detected irregularly-shaped Gram-positive bacteria that correlated with plant upsets. Use of biomolecular techniques, such as DNA sequencing of laboratory isolates and the mixed liquor microbial community, and fluorescent in situ hybridization, identified the dispersed organisms as members of the genus Staphylococcus. However, Staphylococcus species were consistently present during normal operation and therefore were more likely to be an indicator of the upset, not the cause. The results suggest that these microorganisms are responding to specific influent wastewater constituents. We chemically analysed seven mixed liquor samples from periods of permeability decline in 2017 and 2018, and four samples from a period of normal operation. During upset conditions, the total carbohydrate content exceeded that of normal operation by 40%. Additionally, mixed liquor calcium concentrations were 65% above normal during the upset in 2017. It is hypothesized and supported through multivariate statistical analysis and estimation of specific resistance to filtration values that a calcium-intermediated polymer bridging mechanism with extracellular polymeric substance constituents is a major contributor to fouling and permeability disruptions in the Traverse City MBR.

Inhibition of early response genes prevents changes in global joint metabolomic profiles in mouse post-traumatic osteoarthritis.

OBJECTIVE: Although joint injury itself damages joint tissues, a substantial amount of secondary damage is mediated by the cellular responses to the injury. Cellular responses include the production and activation of proteases (MMPs, ADAMTSs, Cathepsins), and the production of inflammatory cytokines. The trajectory of cellular responses is driven by the transcriptional activation of early response genes, which requires Cdk9-dependent RNA Polymerase II phosphorylation. Our objective was to determine whether inhibition of cdk9-dependent early response gene activation affects changes in the joint metabolome. DESIGN: To model post-traumatic osteoarthritis, we subjected mice to non-invasive Anterior Cruciate Ligament (ACL)-rupture joint injury. Following injury, mice were treated with flavopiridol - a potent and selective inhibitor of Cdk9 kinase activity - to inhibit Cdk9-dependent transcriptional activation, or vehicle control. Global joint metabolomics were analyzed 1 h after injury. RESULTS: We found that injury induced metabolomic changes, including increases in Vitamin D3 metabolism, anandamide, and others. Inhibition of primary response gene activation immediately after injury largely prevented the global changes in the metabolomics profiles. Cluster analysis of joint metabolomes identified groups of injury-induced and drug-responsive metabolites. CONCLUSIONS: Metabolomic profiling provides an instantaneous snapshot of biochemical activity representing cellular responses. We identified two sets of metabolites that change acutely after joint injury: those that require transcription of primary response genes, and those that do not. These data demonstrate the potential for inhibition of early response genes to alter the trajectory of cell-mediated degenerative changes following joint injury, which may offer novel targets for cell-mediated secondary joint damage.

Characterization of synovial fluid metabolomic phenotypes of cartilage morphological changes associated with osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is a multifactorial disease with etiological heterogeneity. The objective of this study was to classify OA subgroups by generating metabolomic phenotypes from human synovial fluid. DESIGN: Post mortem synovial fluids (n = 75) were analyzed by high performance-liquid chromatography mass spectrometry (LC-MS) to measure changes in the global metabolome. Comparisons of healthy (grade 0), early OA (grades I-II), and late OA (grades III-IV) donor populations were considered to reveal phenotypes throughout disease progression. RESULTS: Global metabolomic profiles in synovial fluid were distinct between healthy, early OA, and late OA donors. Pathways differentially activated among these groups included structural deterioration, glycerophospholipid metabolism, inflammation, central energy metabolism, oxidative stress, and vitamin metabolism. Within disease states (early and late OA), subgroups of donors revealed distinct phenotypes. Synovial fluid metabolomic phenotypes exhibited increased inflammation (early and late OA), oxidative stress (late OA), or structural deterioration (early and late OA) in the synovial fluid. CONCLUSION: These results revealed distinct metabolic phenotypes in human synovial fluid, provide insight into pathogenesis, represent novel biomarkers, and can move toward developing personalized interventions for subgroups of OA patients.

Safety and efficacy of thrombopoeitin mimetics for refractory immune thrombocytopenia purpura in patients with systemic lupus erythematosus or antiphospholipid syndrome: a case series.

Background While thrombopoeitin (TPO) agonists that act to simulate platelet production have been approved for use in steroid-refractory chronic immune thrombocytopenia purpura (ITP), there are few data on the safety and efficacy of these medications in patients with concurrent systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS). Given that these agents can increase all hematopoietic cell lineages, it is unclear if there is an increased risk for exacerbation of the underlying lymphocyte-driven autoimmune disease in this population. Case summaries This case series includes four patients with SLE, one with concurrent APS, who were treated for steroid-refractory ITP with TPO mimetics at the University of Virginia between 2005 and 2015. In three of the four cases the medication was successful in improving platelet counts and preventing bleeding events. In addition, none of the patients experienced thrombosis or worsening of their underlying autoimmune disease. Conclusions This case series suggests that TPO mimetics are safe and moderately effective in patients with ITP in the setting of SLE or APS and do not contribute to increased disease activity.

Dermatomyositis panniculitis: a clinicopathological and immunohistochemical study of 18 cases.

BACKGROUND: Panniculitis occurring in dermatomyositis is uncommon, with only a few cases described in the literature, most of them as case reports. OBJECTIVE: This report describes the clinicopathological and immunohistochemical findings in a series of 18 patients with panniculitis associated with dermatomyositis. METHODS: In each patient, we collected the clinical data of the cutaneous lesions as well as the characteristic clinical and laboratory findings. A series of histopathologic findings was recorded in the biopsy of each patient. A panel of antibodies was used in some cases to investigate the immunophenotype of the infiltrate. Data of treatment and follow-up were also collected. RESULTS: Of the 18 patients, 13 were female and 5 were male, ranging in age from 13 to 74 years (median, 46.4 years). In addition to panniculitis, all patients presented pathognomonic cutaneous findings of DM and reported proximal muscle weakness prior to the diagnosis of panniculitis. Muscle biopsy was performed in 17 patients and MRI in one, all with the diagnosis of inflammatory myopathy. None of the patients presented any associated neoplasia. Panniculitis lesions were located in the upper or lower limbs. Histopathology showed a mostly lobular panniculitis with lymphocytes as the main component of the infiltrate. Most cases showed also numerous plasma cells and lymphocytes surrounding necrotic adipocytes (rimming) were frequently seen. Lymphocytic vasculitis and abundant mucin interstitially deposited between collagen bundles of the dermis were also frequent findings. Late-stage lesions showed hyaline necrosis of the fat lobule and calcification. Immunohistochemistry demonstrated that most lymphocytes of the infiltrate were T-helper lymphocytes, with some B lymphocytes in the lymphoid aggregates and small clusters of CD-123-positive plasmacytoid dendritic cells in the involved fat lobule. CONCLUSION: Panniculitis in dermatomyositis is rare. Histopathologic findings of panniculitis dermatomyositis are identical to those of lupus panniculitis. Therefore, the final diagnosis requires clinic-pathologic correlation.

Chemistry to conservation: using otoliths to advance recreational and commercial fisheries management.

Otolith chemistry is an effective technique for evaluating fish environmental history, but its utility in fisheries management has not been comprehensively examined. Thus, a review of otolith chemistry with emphasis on management applicability is presented. More than 1500 otolith chemistry manuscripts published from 1967 to 2015 are reviewed and descriptive case studies are used to illustrate the utility of otolith chemistry as a fisheries management tool. Otolith chemistry publications span a wide variety of topics (e.g. natal origins, habitat use, movement, stock discrimination and statistical theory) and species in freshwater and marine systems. Despite the broad distribution of manuscripts in a variety of fisheries, environmental and ecological journals, the majority of publications (83%, n = 1264) do not describe implications or applications of otolith chemistry for fisheries management. This information gap is addressed through case studies that illustrate management applications of otolith chemistry. Case studies cover numerous topics (e.g. natal origins, population connectivity, stock enhancement, transgenerational marking, pollution exposure history and invasive species management) in freshwater and marine systems using sport fishes, invasive fishes, endangered fishes and species of commercial and aquaculture importance. Otolith chemistry has diverse implications and applications for fisheries management worldwide. Collaboration among fisheries professionals from academia, government agencies and non-governmental organizations will help bridge the research-management divide and establish otolith chemistry as a fisheries management tool.

Symptomatic and asymptomatic secondary transmission of Cryptosporidium parvum following two related outbreaks in schoolchildren.

Two related outbreaks (in 2009 and 2012) of cryptosporidiosis in Norwegian schoolchildren during a stay at a remote holiday farm provided us with a natural experiment to investigate possible secondary transmission of Cryptosporidium parvum IIa A19G1R1. After the children had returned home, clinical data and stool samples were obtained from their household contacts. Samples were investigated for the presence of Cryptosporidium oocysts by immunofluorescence antibody test. We found both asymptomatic and symptomatic infections, which are likely to have been secondary transmission. Laboratory-confirmed transmission rate was 17% [4/23, 95% confidence interval (CI) 7·0-37·1] in the 2009 outbreak, and 0% (95% CI 0-16·8) in the 2012 outbreak. Using a clinical definition, the probable secondary transmission rate in the 2012 outbreak was 8% (7/83, 95% CI 4·1-16·4). These findings highlight the importance of hygienic and public health measures during outbreaks or individual cases of cryptosporidiosis. We discuss our findings in light of previous studies reporting varying secondary transmission rates of Cryptosporidium spp.

Strict anoxic conditions significantly impact the metabolism of particulate and colloidal organic matter and bio-P compared to aerobic conditions.

Fully anoxic suspended growth treatment of domestic wastewater is rarely performed in practice at large scale. However, recent advances in membrane aerated biofilm reactor (MABR) technology can enable the "hybrid" concept that couples nitrification in the MABR with anoxic suspended growth for biological nitrogen removal. Small scale sequencing batch reactors were constructed to compare high-rate anoxic metabolization of influent carbon and biological phosphorus removal side-by-side with a conventional aerated system in a low-strength domestic wastewater (COD/TN ratio of approximately 6). Little differences existed in the oxidation of soluble readily biodegradable organic material between the two systems, but hydrolysis of particulate and colloidal organic matter in the anoxic reactor over a range of solid retention times was 60 % of the aerobic reactor. Reduced hydrolysis limited the amount of carbon available to ferment to volatile fatty acid (VFA), adversely impacting anoxic biological phosphorus removal (bio-P) process rates, and ortho-P removal performance was diminished by more than half at equivalent SRTs. At optimal growth conditions, i.e., an SRT of approximately 8 days and with supplementary VFA, ortho-P removal from the influent averaged roughly 75 %. Experimentation with supplemented acetic acid showed reduced anoxic metabolic efficiency, quantified via a P/O ratio of 0.90 versus 1.7 for the aerobic system, although overall anoxic bio-P removal demonstrably increased with external carbon.

Surgical or Endovascular Treatment of MCA Aneurysms: An Agreement Study.

BACKGROUND AND PURPOSE: MCA aneurysms are still commonly clipped surgically despite the recent development of a number of endovascular tools and techniques. We measured clinical uncertainty by studying the reliability of decisions made for patients with middle cerebral artery (MCA) aneurysms. MATERIALS AND METHODS: A portfolio of 60 MCA aneurysms was presented to surgical and endovascular specialists who were asked whether they considered surgery or endovascular treatment to be an option, whether they would consider recruitment of the patient in a randomized trial, and whether they would provide their final management recommendation. Agreement was studied using κ statistics. Intrarater reliability was assessed with the same, permuted portfolio of cases of MCA aneurysm sent to the same specialists 1 month later. RESULTS: Surgical management was the preferred option for neurosurgeons (n = 844/1320; [64%] responses/22 raters), while endovascular treatment was more commonly chosen by interventional neuroradiologists (1149/1500 [76.6%] responses/25 raters). Interrater agreement was only "slight" for all cases and all judges (κ = 0.094; 95% CI, 0.068-0.130). Agreement was no better within specialties or with more experience. On delayed requestioning, 11 of 35 raters (31%) disagreed with themselves on at least 20% of cases. Surgical management and endovascular treatment were always judged to be a treatment option, for all patients. Trial participation was offered to patients 65% of the time. CONCLUSIONS: Individual clinicians did not agree regarding the best management of patients with MCA aneurysms. A randomized trial comparing endovascular with surgical management of patients with MCA aneurysms is in order.

Reliability of the Diagnosis of Cerebral Vasospasm Using Catheter Cerebral Angiography: A Systematic Review and Inter- and Intraobserver Study.

BACKGROUND AND PURPOSE: Conventional angiography is the benchmark examination to diagnose cerebral vasospasm, but there is limited evidence regarding its reliability. Our goals were the following: 1) to systematically review the literature on the reliability of the diagnosis of cerebral vasospasm using conventional angiography, and 2) to perform an agreement study among clinicians who perform endovascular treatment. MATERIALS AND METHODS: Articles reporting a classification system on the degree of cerebral vasospasm on conventional angiography were systematically searched, and agreement studies were identified. We assembled a portfolio of 221 cases of patients with subarachnoid hemorrhage and asked 17 raters with different backgrounds (radiology, neurosurgery, or neurology) and experience (junior ≤10 and senior >10 years) to independently evaluate cerebral vasospasm in 7 vessel segments using a 3-point scale and to evaluate, for each case, whether findings would justify endovascular treatment. Nine raters took part in the intraobserver reliability study. RESULTS: The systematic review showed a very heterogeneous literature, with 140 studies using 60 different nomenclatures and 21 different thresholds to define cerebral vasospasm, and 5 interobserver studies reporting a wide range of reliability (κ = 0.14-0.87). In our study, only senior raters reached substantial agreement (κ ≥ 0.6) on vasospasm of the supraclinoid ICA, M1, and basilar segments and only when assessments were dichotomized (presence or absence of ≥50% narrowing). Agreement on whether to proceed with endovascular management of vasospasm was only fair (κ ≤ 0.4). CONCLUSIONS: Research on cerebral vasospasm would benefit from standardization of definitions and thresholds. Dichotomized decisions by experienced readers are required for the reliable angiographic diagnosis of cerebral vasospasm.

Anaplastic astroblastoma-sarcoma in neurofibromatosis Type 1.

Astroblastoma is a distinctive brain tumor when its histologic features occur in pure form. More often, the tumor pattern is seen to emerge in infiltrative astrocytic tumors. The former are rare. Astroblastoma as a de novo component of gliosarcoma has not previously been described. Furthermore, astroblastoma has only once been reported to occur in the setting of neurofibromatosis Type I (NF1), a condition more often associated with pilocytic and diffuse or infiltrative astrocytic tumors. Herein, we describe a unique case of anaplastic de novo astroblastoma-sarcoma, in essence a variant of gliosarcoma, occurring in a 50-year-old female with documented NF1. Genetic study (fluorescence in situ hybridization) demonstrated no chromosomal losses or gains. Testing for abnormalities of chromosomes 7, 9, 10, 12, 17, 19 and 20, including the EGFR, p16, PTEN, MDM2 and NF1 gene regions, we found the tumor to exhibit a deletion of PTEN, monosomy 17 and gains of chromosomes 19 and 20q. The latter alterations, having been reported in astroblastoma, were noted in both tumor components, thus confirming the common origin of the glial and sarcomatous elements.

A NWB-based dataset and processing pipeline of human single-neuron activity during a declarative memory task.

A challenge for data sharing in systems neuroscience is the multitude of different data formats used. Neurodata Without Borders: Neurophysiology 2.0 (NWB:N) has emerged as a standardized data format for the storage of cellular-level data together with meta-data, stimulus information, and behavior. A key next step to facilitate NWB:N adoption is to provide easy to use processing pipelines to import/export data from/to NWB:N. Here, we present a NWB-formatted dataset of 1863 single neurons recorded from the medial temporal lobes of 59 human subjects undergoing intracranial monitoring while they performed a recognition memory task. We provide code to analyze and export/import stimuli, behavior, and electrophysiological recordings to/from NWB in both MATLAB and Python. The data files are NWB:N compliant, which affords interoperability between programming languages and operating systems. This combined data and code release is a case study for how to utilize NWB:N for human single-neuron recordings and enables easy re-use of this hard-to-obtain data for both teaching and research on the mechanisms of human memory.

Anticancer effects of resveratrol in canine hemangiosarcoma cell lines.

Hemangiosarcoma (HSA) is a highly malignant tumour with aggressive biological behaviour. HSAs are more common in dogs than other domestic animals. The median survival time of dogs with HSA remains short, even with chemotherapy and surgery. Therefore, there is a critical need to improve the adjuvant chemotherapeutic regimens to improve clinical outcomes in dogs with HSA. Resveratrol has been shown to possess strong anti-proliferative and/or pro-apoptotic properties in human cancer cell lines. Nevertheless, the potential anticancer effects of resveratrol have not been reported in canine HSAs. The objective of this study is to determine the growth inhibitory effects of resveratrol in HSA cells when used alone or in combination with doxorubicin, a commonly used chemotherapeutic agent. Frog and DD-1 canine HSA cell lines were treated with varying concentrations of resveratrol with and without doxorubicin. Cell viability was measured by the MTT assay. The expression of apoptotic proteins, activation of p38 mitogen-activated protein kinase (MAPK), AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinase 1/2 (ERK1/2) were assessed by western blotting. Similar to human cancer cell lines, resveratrol markedly inhibited the growth and induced apoptosis in both HSA cell lines. Mechanistically, resveratrol activated p38 MAPK, but did not affect the AMPK or the ERK1/2 pathways. Additional experiments showed that resveratrol augmented the growth-inhibitory and apoptotic effects of doxorubicin in both HSA cell lines. These findings suggest that resveratrol has pro-apoptotic effects in canine HSA cells; therefore, its use as a potential adjunct therapy in canine HSA patients warrants further investigation.

Endoscopy-related infections and toxic reactions: an international comparison.

This article is an analysis of the characteristics of exogenous endoscopy-related infections, pseudoinfections, and toxic reactions that have occurred worldwide during the period 1974 - 2004. A systematic review of the scientific literature published between 1966 and 2004 was conducted in Medline and the Food and Drug Administration Reports database, using a prospective protocol developed by the authors. The literature review identified 140 outbreaks, reported in 134 scientific articles. More than 94 % of the outbreaks identified could have been prevented by improved decontamination processes. Proper decontamination practices and the improvement of surveillance systems could reduce the clinical burden associated with exogenous endoscopy-related events.

Effect of Preservative Pretreatment on the Biological Durability of Corn Straw Fiber/HDPE Composites.

The effects of alkaline copper quaternary (ACQ) and zinc borate (ZB) on the resistance of corn stalk fiber (CSF)-reinforced high-density polyethylene (HDPE) composites to biodegradation were examined. Both biocides could inhibit termites, mold fungi, and wood-decay fungi, even at high CSF formulations (i.e., 60%). Additionally, ACQ enhanced the resistance of the composite materials to certain biotic stresses better than ZB. The CSF/HDPE composites treated with ACQ at the 3.0% level exhibited a superior performance against termites, white rot fungi, and brown rot fungi. ACQ treatment at the 1% level was optimal for inhibiting soft rot fungi. Furthermore, mold growth was not observed on ACQ-treated CSF/HDPE samples. The untreated CSF/HDPE composites were more susceptible to mold infections and decay than the untreated poplar/HDPE composites, likely because of an incomplete removal of the pith. The chemical features of the corn stalk may also have influenced these differences, but this possibility will need to be explored in future investigations. Furthermore, the CSF component of CSF/HDPE composites is highly susceptible to fungal attacks, with the soft rot fungus inducing the largest mass losses, followed by the white rot fungus, and then the brown rot fungus.

Natural killer cell activity: age, estrous- and circadian-stage dependence and inverse correlation with metastatic potential.

The timing within the estrous cycle of surgical removal of a transplanted murine mammary tumor profoundly influences the frequency of pulmonary metastases. We investigated the potential role of the immune response in this phenomenon by measuring splenic natural killer (NK) cell activity and interleukin-2 (IL-2) production in syngeneic tumor-free mice of two age groups at each of two circadian times and in each of four estrous stages. Estrous stage was determined by assessment of vaginal smear cellularity immediately prior to killing and spleen harvest. In a single-cell splenocyte preparation, NK cytotoxicity against a standard tumor cell target was assessed using a radiolabeled chromium release assay while IL-2 activity was determined in a bioassay utilizing the IL-2-dependent CTLL-2 cell line. Mice from the younger group were found to have eight-fold higher NK activity and 35% greater IL-2 production. After normalization of NK and IL-2 values for age, a highly statistically significant difference in NK activity was found among the four estrous and between the two circadian stages of sacrifice. NK activity was greater during the daily resting span across every estrous stage. IL-2 values were highest in diestrus and proestrus when sampled in the light span and in estrus-metestrus when sampled in the dark. The stages within the fertility cycle associated with lowest metastatic potential (proestrus/estrus) correspond precisely with those of highest splenocyte NK activity. These results indicate that an important component of the cellular immune response varies rhythmically both during the fertility and circadian cycles of the host. The rhythmic changes in NK activity may be in part responsible for the similarly rhythmic frequency of postsurgical metastatic dissemination.

Evaluation of comprehensive program for diabetes care at primary health-care level.

The Swedish National Board of Health and Welfare published its first diabetes health-care program in 1977. The impact of the program was evaluated in the Stockholm County after 4 yr. The results showed that the educational program had reached greater than or equal to 1 staff member in 86% of the 104 primary health-care centers (PHCCs). Several organizational changes had taken place as a result of the program. The 10 "best" PHCCs were compared with a random sample of the centers with regard to patient outcomes. Patients from the 10 best centers had gotten a more comprehensive education, were more knowledgeable about foot care, tested glucose more often, and used less medication. The metabolic control was the same for both groups of patients. The PHCC staffs reported the following roadblocks to change: lack of knowledge of diabetes care, insufficient cooperation between staff members, poor contact with specialists, and absence of guidelines for diabetes care. The staffs in the best centers spent twice as much time in staff meetings and continuing education as those from the random sample of centers. The findings led us to formulate a new strategy for the program. The main objective of the new approach is to create organizational changes within the centers. Thus, local knowledge and creativity can be utilized. Preliminary data demonstrate that 84% of the locally developed plans for reorganization of diabetes care had been accomplished within 1 yr.