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1.
Nutrients ; 16(16)2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39203858

ABSTRACT

INTRODUCTION: Protein nutrition disorder in alkaptonuria (AKU), resulting in increased homogentisic acid (HGA) before nitisinone therapy and increased tyrosine (TYR) during nitisinone therapy, may benefit from dietetic intervention. The aim of this study was to characterise the diet and their effects prospectively in those who received formal dietetic intervention in the nitisinone-receiving National Alkaptonuria Centre (NAC) patients with those who did not in no-nitisinone Suitability of Nitisinone in Alkaptonuria 2 (SN2 N-) and nitisinone-treated SN2 (SN2 N+) randomised study groups. PATIENTS AND METHODS: A total of 63, 69, and 69 AKU patients from the NAC, SN2 N-, and SN2 N+ were studied for anthropometric (weight, BMI), body composition (including muscle mass, %body fat, hand grip strength), chemical characteristics (serum TYR, serum phenylalanine, urine urea or uUREA, and urine creatinine or uCREAT), and corneal keratopathy. Nitisinone 2 mg and 10 mg were employed in the NAC and SN2 N+ groups, respectively. Dieticians managed protein intake in the NAC, while the SN2 N- and SN2 N+ groups only received advice on self-directed protein restriction during four years of study duration. RESULTS: uUREA decreased in the NAC, SN2 N-, and SN2 N+ groups, showing that protein restriction was achieved in these groups. Body weight and BMI increased in the NAC and SN2 N+ groups. uCREAT decreased significantly in SN2 N- and SN2 N+ compared with the NAC over four years of study. Corneal keratopathy was less frequent in the NAC than in the SN2 N+ group. Active dietetic intervention in NAC stabilised lean body mass (muscle mass, hand grip strength) despite a decrease in uUREA and uCREAT, as well as sTYR. CONCLUSION: Ongoing dietetic intervention prevented loss of lean body mass despite protein restriction and moderated serum tyrosine increase, leading to less prevalent corneal keratopathy. Protein restriction risks fat mass gain.


Subject(s)
Alkaptonuria , Body Composition , Cyclohexanones , Nitrobenzoates , Humans , Male , Female , Middle Aged , Body Composition/drug effects , Aged , Tyrosine/blood , Tyrosine/analogs & derivatives , Adult , Prospective Studies , Body Mass Index , Nutritional Status , Phenylalanine/blood , Anthropometry , Homogentisic Acid/urine , Hand Strength
2.
Water Res ; 215: 118269, 2022 May 15.
Article in English | MEDLINE | ID: mdl-35298992

ABSTRACT

The continued technological developments and decreased purchase costs of ceramic membranes have seen increased recent interest in the technology as an alternative to the more widely used polymeric membranes. This paper assesses the relative technical, practical and economic merits of the two membrane materials in the context of potable water production from surface water sources. The work focuses on phenomena of direct technoeconomic significance, namely cleaning efficacy (manifested as permeability recovery), membrane integrity and incurred labour effort. Topics reviewed thus comprise: (a) practical comparison of the two technologies challenged with the same feedwater, (b) comparative technoeconomic analyses, (c) membrane integrity studies of polymeric membranes - incorporating aged samples extracted from operating installations, (d) sludging incidents, and (e) pilot and full-scale data. Available relevant data reveal: (a) bench-scale comparative tests do not indicate a consistent significant difference in the net permeability between the two membranes; (b) polymeric membranes are subject to a decline in both mechanical strength and permeability from the loss of the hydrophilic agent over a period of years from the action of hypochlorite used for cleaning; (c) the decreased mechanical strength with age of polymeric membranes increases the manual repair requirement and shortens membrane life, respectively impacting on labour and membrane replacement costs where the latter is also determined by the permeability; (d) the chemical and mechanical robustness of ceramic membranes permits more aggressive chemical cleaning, which then affects the chemicals consumption cost; and (e) anecdotal evidence suggests that polymeric membranes challenged with pre-coagulated surface waters may be subject to sludging, the agglomeration of solids in the membrane channels, which may also be age-related. Notwithstanding the above, data from published comparative technoeconomic studies indicate a linear relationship between the overall cost benefit and the membrane module cost ratio mitigated by the relative membrane life and operating flux.


Subject(s)
Drinking Water , Water Purification , Ceramics , Membranes, Artificial , Polymers
3.
Water Res ; 214: 118198, 2022 May 01.
Article in English | MEDLINE | ID: mdl-35259687

ABSTRACT

A review of the current status of direct and indirect potable water reuse (DPR/IPR) implementation has been conducted, focusing on the regulatory and practical aspects and with reference to the most recent published literature. The review encompasses (a) the principal contaminant types, their required removal and the methods by which their concentration is monitored, (b) regulatory approaches and stipulations in assessing/ratifying treatment schemes and maintaining treated water quality, and (c) existing full-scale installations. Analytical methods discussed include established in-line monitoring tools, such as turbidity measurement, to more recent polymerase chain reaction (PCR)-based assay methods for microbial detection. The key risk assessment tools of quantitative microbial risk assessment (QMRA) and water safety plans (WSPs) are considered in relation to their use in selecting/ratifying treatment schemes, and the components of the treatment schemes from 40 existing IPR/DPR installations summarised. Five specific schemes are considered in more detail. The review reveals:Whilst there are a number of ongoing projects where RO is not used because of the challenge imposed by disposal of RO concentrate, the prevalence of the sequential RO-UV combination implies the importance of quantifying the impact of process upsets on these unit operations.

4.
Water Res ; 191: 116826, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33454648

ABSTRACT

The overall cost, expressed as the present value (PV), of the construction and operation of low-pressure membrane filtration of inland water for potable water supply has been determined for membrane installations across the UK. The analysis was based on 15 full-scale installations installed with hollow fibre and capillary tube polymeric membranes, for which cost and related data were available. The analysis encompassed labour, in addition to energy, chemicals and critical component replacement. PV data were presented as functions of flow capacity (i.e. as cost curves), delineated as capital (CAPEX), operating (OPEX) and total PV normalised against flow rate (PV') the CAPEX excluding the site-specific civil engineering costs. Captured CAPEX data revealed these to be lower than those previously reported, and with a reduced economy of scale. The OPEX PV exceeded the CAPEX by a factor of 3-6 based on a 20-year life cycle, the difference increasing with decreasing flow capacities. Costs associated with unplanned (or "reactive") maintenance, partly associated with the repair of breached membranes and/or permeability recovery following membrane clogging, were found to make up around half the labour costs. Labour costs as a proportion of the flow increased with decreasing flow, exceeding the CAPEX at flows below 30,000 m3/d. Outcomes indicate labour costs associated with process upsets to contribute significantly to the overall cost of the installation over its life cycle, particularly at flows below ~30,000 m3/d. A clear trade-off exists between supplementary capital investment to allay process upsets and the operational costs associated with such events.


Subject(s)
Drinking Water , Water Purification , Bioreactors , Filtration , Membranes, Artificial , Technology
5.
J Shoulder Elbow Surg ; 29(11): 2364-2374, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32666923

ABSTRACT

BACKGROUND: The purpose of this study was to evaluate ultrahigh-molecular-weight polyethylene (UHMWPE) wear and damage from retrieved total elbow arthroplasty components and compare in vivo wear with wear produced in vitro. METHODS: Explanted total elbow components were collected at revision surgery. UHMWPE damage was characterized visually, whereas penetration and wear were quantified using micro-computed tomography and gas pycnometry. Volumetric wear rates were compared with historical hip data, and wear data were compared with reported in vitro wear test data. RESULTS: Humeral bushing damage primarily occurred in the form of burnishing, scratching, and pitting at the articular face in the region of contact with the ulnar component. Wear of the ulnar bushings was concentrated on the edge of the component at the point of contact with the axis pin. Pitting and embedded debris were dominant damage modes, in addition to burnishing and delamination. Backside wear was negligible. The median linear penetration rates of the lateral, medial, and ulnar bushings were 0.14 mm/yr (range, 0.01-0.78 mm/yr), 0.12 mm/yr (range, 0.03-0.55 mm/yr), and 0.11 mm/yr (range, 0.01-0.69 mm/yr), respectively. The volumetric wear rates of the lateral, medial, and ulnar bushings were 5.5 mm3/yr (range, 0.7-37.2 mm3/yr), 5.9 mm3/yr (range, 0.6-25.5 mm3/yr), and 5.5 mm3/yr (range, 1.2-51.2 mm3/yr), respectively. CONCLUSIONS: The observed wear rates were similar to those reported in well-functioning total hip replacement patients with conventional UHMWPE bearings. We found limitations in reported in vitro testing resulting in wear that was not consistent with our retrieval data. We recommend further investigation to clinically validate in vitro simulation to provide appropriate loading protocols for elbow wear simulation.


Subject(s)
Arthroplasty, Replacement, Elbow/instrumentation , Elbow Prosthesis/adverse effects , Polyethylenes , Prosthesis Failure , Adult , Aged , Aged, 80 and over , Elbow Joint , Equipment Failure Analysis , Female , Humans , In Vitro Techniques , Male , Middle Aged , Reoperation , X-Ray Microtomography , Young Adult
6.
Water Res ; 174: 115613, 2020 May 01.
Article in English | MEDLINE | ID: mdl-32092546

ABSTRACT

Operational and financial constraints challenge effective removal of natural organic matter (NOM), and specifically disinfection by-product (DBP) precursors, at remote and/or small sites. Granular activated carbon (GAC) is a widely used treatment option for such locations, due to its relatively low maintenance and process operational simplicity. However, its efficacy is highly dependent on the media capacity for the organic matter, which in turn depends on the media characteristics. The influence of GAC media properties on NOM/DBP precursor removal has been studied using a range of established and emerging media using both batch adsorption tests and rapid small-scale column tests. DBP formation propensity (DBPFP) was measured with reference to trihalomethanes (THMs) and haloacetic acids (HAAs). All GAC media showed no selectivity for specific removal of precursors of regulated DBPs; DBP formation was a simple function of residual dissolved organic carbon (DOC) levels. UV254 was found to be a good surrogate measurement of DBPFP for an untreated water source having a high DOC. Due to the much-reduced concentration of DBP precursors, the correlation was significantly poorer for the coagulation/flocculation-pretreateed water source. Breakthrough curves generated from the microcolumn trials revealed DOC removal and consequent DBP reduction to correlate reasonably well with the prevalence pores in the 5-10 nm range. A 3-6 fold increase in capacity was recorded for a 0.005-0.045 cm3/g change in 5-10 nm-sized pore volume density. No corresponding correlation was evident with other media pore size ranges.


Subject(s)
Drinking Water , Water Pollutants, Chemical , Water Purification , Charcoal , Disinfection , Trihalomethanes
7.
Mol Psychiatry ; 25(5): 918-938, 2020 05.
Article in English | MEDLINE | ID: mdl-30862937

ABSTRACT

The biological fingerprint of environmental adversity may be key to understanding health and disease, as it encompasses the damage induced as well as the compensatory reactions of the organism. Metabolic and hormonal changes may be an informative but incomplete window into the underlying biology. We endeavored to identify objective blood gene expression biomarkers for psychological stress, a subjective sensation with biological roots. To quantify the stress perception at a particular moment in time, we used a simple visual analog scale for life stress in psychiatric patients, a high-risk group. Then, using a stepwise discovery, prioritization, validation, and testing in independent cohort design, we were successful in identifying gene expression biomarkers that were predictive of high-stress states and of future psychiatric hospitalizations related to stress, more so when personalized by gender and diagnosis. One of the top biomarkers that survived discovery, prioritization, validation, and testing was FKBP5, a well-known gene involved in stress response, which serves as a de facto reassuring positive control. We also compared our biomarker findings with telomere length (TL), another well-established biological marker of psychological stress and show that newly identified predictive biomarkers such as NUB1, APOL3, MAD1L1, or NKTR are comparable or better state or trait predictors of stress than TL or FKBP5. Over half of the top predictive biomarkers for stress also had prior evidence of involvement in suicide, and the majority of them had evidence in other psychiatric disorders, providing a molecular underpinning for the effects of stress in those disorders. Some of the biomarkers are targets of existing drugs, of potential utility in patient stratification, and pharmacogenomics approaches. Based on our studies and analyses, the biomarkers with the best overall convergent functional evidence (CFE) for involvement in stress were FKBP5, DDX6, B2M, LAIR1, RTN4, and NUB1. Moreover, the biomarker gene expression signatures yielded leads for possible new drug candidates and natural compounds upon bioinformatics drug repurposing analyses, such as calcium folinate and betulin. Our work may lead to improved diagnosis and treatment for stress disorders such as PTSD, that result in decreased quality of life and adverse outcomes, including addictions, violence, and suicide.


Subject(s)
Adaptor Proteins, Signal Transducing/blood , DEAD-box RNA Helicases/blood , Nogo Proteins/blood , Proto-Oncogene Proteins/blood , Receptors, Immunologic/blood , Stress, Psychological/blood , Tacrolimus Binding Proteins/blood , beta 2-Microglobulin/blood , Adult , Biomarkers/blood , Female , Gene Expression , Humans , Male , Mental Disorders/blood , Mental Disorders/genetics , Middle Aged , Molecular Targeted Therapy , Precision Medicine , Predictive Value of Tests , Telomere Homeostasis
8.
Mol Psychiatry ; 24(4): 501-522, 2019 04.
Article in English | MEDLINE | ID: mdl-30755720

ABSTRACT

We endeavored to identify objective blood biomarkers for pain, a subjective sensation with a biological basis, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We studied psychiatric patients, a high risk group for co-morbid pain disorders and increased perception of pain. For discovery, we used a powerful within-subject longitudinal design. We were successful in identifying blood gene expression biomarkers that were predictive of pain state, and of future emergency department (ED) visits for pain, more so when personalized by gender and diagnosis. MFAP3, which had no prior evidence in the literature for involvement in pain, had the most robust empirical evidence from our discovery and validation steps, and was a strong predictor for pain in the independent cohorts, particularly in females and males with PTSD. Other biomarkers with best overall convergent functional evidence for involvement in pain were GNG7, CNTN1, LY9, CCDC144B, and GBP1. Some of the individual biomarkers identified are targets of existing drugs. Moreover, the biomarker gene expression signatures were used for bioinformatic drug repurposing analyses, yielding leads for possible new drug candidates such as SC-560 (an NSAID), and amoxapine (an antidepressant), as well as natural compounds such as pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), and apigenin (a plant flavonoid). Our work may help mitigate the diagnostic and treatment dilemmas that have contributed to the current opioid epidemic.


Subject(s)
Pain/drug therapy , Pain/genetics , Precision Medicine/methods , Adult , Aged , Biomarkers/blood , Biomarkers, Pharmacological/blood , Computational Biology/methods , Contractile Proteins/genetics , Contractile Proteins/metabolism , Drug Repositioning/methods , Female , Gene Expression/genetics , Gene Expression Profiling/methods , Genomics/methods , Humans , Male , Middle Aged , Transcriptome/genetics
9.
Data Brief ; 20: 1620-1628, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30263914

ABSTRACT

Alkaptonuria is a rare genetic disorder characterized by a high level of circulating (and urine) homogentisic acid (HGA), which contributes to ochronosis when it is deposited in connective tissue as a pigmented polymer. In an observational study carried out by National AKU Centre (NAC) in Liverpool, a total of thirty-nine AKU patients attended yearly visits in varying numbers. At each visit a mixture of clinical, joint and spinal assessments were carried out and the results calculated to yield an AKUSSI (Alkaptonuria Severity Score Index), see "Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre" (Ranganath at el., 2018). The aim of this data article is to produce visual representation of the change in the components of AKUSSI over 3 years, through radar charts. The metabolic effect of nitisinone is shown through box plots.

10.
Water Res ; 144: 46-54, 2018 11 01.
Article in English | MEDLINE | ID: mdl-30014978

ABSTRACT

Whilst the fouling of MBR membrane surfaces has been very extensively explored by the academic community, there is an increasingly widespread recognition by practitioners of the issue of clogging of membrane channels with sludge solids, sometimes termed "sludging". The study undertaken has quantified this phenomenon using a bespoke test cell allowing a flat sheet membrane channel to be viewed directly during operation and the accumulated solids determined by digital image processing. Sludging behaviour has then been correlated both with the sludge properties, from sludge samples taken from both an industrial and municipal MBR, and the permeability decline rate data. The work has revealed the expected trends in fouling propensity, as quantified by the exponent n of the Δp/Δt = m.exp(nJ) correlation from classical flux-step tests. With zero membrane aeration the industrial samples exhibited sludging, the filling of the complete thickness of the membrane channel with sludge solids, whereas for municipal sludge the solids formed a cake layer which did not fill the channel. In the absence of sludging the permeability decline followed the expected pattern of increasing at the elevated soluble COD and capillary suction time values of the industrial sludge, compared with municipal sludge at the same solids concentration range (8-12 g.L-1). However, there was no evident correlation between fouling (permeability decline without sludging) and sludging: incipient sludging did not appear to influence permeability, though can be assumed to negatively impact on long-term operation, or relate to the sCOD concentration. Sludging instead appeared to depend on the sludge physical properties, and primarily the viscosity: sludge samples at high viscosities were found to exhibit a different air-scour pattern to that at normal MLSS concentrations. Outcomes suggest that sludging is caused by rheological conditions promoting bubble coalescence and bubble stream constriction, reducing the exposure of the membrane surface to scouring air.


Subject(s)
Bioreactors , Sewage/chemistry , Waste Disposal, Fluid/instrumentation , Biofouling , Biological Oxygen Demand Analysis , Equipment Design , Image Processing, Computer-Assisted , Industrial Waste , Membranes, Artificial , Permeability , Rheology , Viscosity , Waste Disposal, Fluid/methods
11.
Mol Genet Metab ; 125(1-2): 127-134, 2018 09.
Article in English | MEDLINE | ID: mdl-30055994

ABSTRACT

QUESTION: Does Nitisinone prevent the clinical progression of the Alkaptonuria? FINDINGS: In this observational study on 39 patients, 2 mg of daily nitisinone inhibited ochronosis and significantly slowed the progression of AKU over a three-year period. MEANING: Nitisinone is a beneficial therapy in Alkaptonuria. BACKGROUND: Nitisinone decreases homogentisic acid (HGA), but has not been shown to modify progression of Alkaptonuria (AKU). METHODS: Thirty-nine AKU patients attended the National AKU Centre (NAC) in Liverpool for assessments and treatment. Nitisinone was commenced at V1 or baseline. Thirty nine, 34 and 22 AKU patients completed 1, 2 and 3 years of monitoring respectively (V2, V3 and V4) in the VAR group. Seventeen patients also attended a pre-baseline visit (V0) in the VAR group. Within the 39 patients, a subgroup of the same ten patients attended V0, V1, V2, V3 and V4 visits constituting the SAME Group. Severity of AKU was assessed by calculation of the AKU Severity Score Index (AKUSSI) allowing comparison between the pre-nitisinone and the nitisinone treatment phases. RESULTS: The ALL (sum of clinical, joint and spine AKUSSI features) AKUSSI rate of change of scores/patient/month, in the SAME group, was significantly lower at two (0.32 ±â€¯0.19) and three (0.15 ±â€¯0.13) years post-nitisinone when compared to pre-nitisinone (0.65 ±â€¯0.15) (p < .01 for both comparisons). Similarly, the ALL AKUSSI rate of change of scores/patient/month, in the VAR group, was significantly lower at one (0.16 ±â€¯0.08) and three (0.19 ±â€¯0.06) years post-nitisinone when compared to pre-nitisinone (0.59 ±â€¯0.13) (p < .01 for both comparisons). Combined ear and ocular ochronosis rate of change of scores/patient/month was significantly lower at one, two and three year's post-nitisinone in both VAR and SAME groups compared with pre-nitisinone (p < .05). CONCLUSION: This is the first indication that a 2 mg dose of nitisinone slows down the clinical progression of AKU. Combined ocular and ear ochronosis progression was arrested by nitisinone.


Subject(s)
Alkaptonuria/drug therapy , Cyclohexanones/administration & dosage , Nitrobenzoates/administration & dosage , Ochronosis/drug therapy , 4-Hydroxyphenylpyruvate Dioxygenase/metabolism , Alkaptonuria/epidemiology , Alkaptonuria/metabolism , Alkaptonuria/pathology , Disease Progression , Female , Homogentisic Acid/metabolism , Humans , Male , Middle Aged , Ochronosis/epidemiology , Ochronosis/metabolism , Ochronosis/pathology , United Kingdom
12.
J Thromb Haemost ; 16(9): 1743-1752, 2018 09.
Article in English | MEDLINE | ID: mdl-29984467

ABSTRACT

Essentials Chronic kidney disease (CKD) is associated with procoagulant and inflammatory biomarkers. We studied the association of CKD and venous thromboembolism (VTE) in a case-cohort study. Factor VIII, D-dimer and C-reactive protein appeared to explain the association of CKD and VTE. Statin use was protective against VTE in those with and without CKD. SUMMARY: Background Chronic kidney disease (CKD) is associated with venous thromboembolism (VTE) risk via unknown mechanisms. Whether factors associated with reduced VTE risk in the general population might also be associated with reduced VTE risk in CKD patients is unknown. Objectives To determine whether thrombosis biomarkers attenuate VTE risk, and whether factors associated with reduced VTE risk are similarly effective in CKD patients. Methods Baseline biomarkers were measured in a cohort (294 VTE cases; 939 non-cases) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a nationwide prospective cohort study of 30 239 persons aged ≥45 years with 4.3 years of follow-up. The hazard ratio (HR) of VTE per 10 mL min-1 1.73 m-2 decrease in estimated glomerular filtration rate (eGFR), and the percentage attenuation of this HR by each biomarker, were calculated. Associations of protective factors (physical activity, lower body mass index [BMI], and aspirin, warfarin and statin use) with VTE were estimated in those with and without CKD. Results The HR for VTE with lower eGFR was 1.13 (95% confidence interval [CI] 1.02-1.25), and VTE risk was attenuated by 23% (95% CI 5-100) by D-dimer, by 100% (95% CI 50-100) by factor VIII, and by 15% (95% CI 2-84) by C-reactive protein. Normal BMI was associated with lower VTE risk in those without CKD (HR 0.47, 95% CI 0.32-0.70), but not in those with CKD (HR 1.07, 95% CI 0.51-2.22). Statin use, physical activity and warfarin use were associated with lower VTE risk in both groups. Conclusions Procoagulant and inflammatory biomarkers mediated the association of eGFR with VTE. Higher physical activity, statin use and warfarin use mitigated VTE risk in those with CKD and those without CKD, but normal BMI did not mitigate VTE risk in CKD patients.


Subject(s)
Pulmonary Embolism/etiology , Renal Insufficiency, Chronic/complications , Venous Thromboembolism/etiology , Venous Thrombosis/etiology , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Biomarkers , C-Reactive Protein/analysis , Creatinine/blood , Exercise , Factor VIII/analysis , Female , Fibrin Fibrinogen Degradation Products/analysis , Glomerular Filtration Rate , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Inflammation , Male , Middle Aged , Prospective Studies , Pulmonary Embolism/epidemiology , Pulmonary Embolism/prevention & control , Renal Insufficiency, Chronic/blood , Risk , Thinness , Thrombophilia/blood , Thrombophilia/drug therapy , Thrombophilia/etiology , Venous Thromboembolism/epidemiology , Venous Thromboembolism/prevention & control , Venous Thrombosis/epidemiology , Venous Thrombosis/prevention & control
13.
J Psychiatr Pract ; 24(2): 117-120, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29509182

ABSTRACT

Venlafaxine is a selective serotonin and norepinephrine reuptake inhibitor commonly used for the treatment of depression. Although listed as an adverse reaction, seizure activity associated with a therapeutic dose of venlafaxine has rarely been documented. A review of the literature reveals only 2 cases of venlafaxine-induced seizures, both of which were generalized tonic-clonic seizures in patients on doses at the higher end of the therapeutic range. We report the case of a 44-year-old woman undergoing antituberculosis therapy who suffered complex partial seizures after ingestion of a low therapeutic dose of venlafaxine extended release (ER). Her first seizure was observed soon after venlafaxine ER was titrated from 37.5 to 75 mg daily, with a total of 9 witnessed complex partial seizures. After titrating the dose of the venlafaxine ER back down to 37.5 mg daily and beginning lamotrigine anticonvulsant therapy, the patient exhibited no further seizures. The development of seizure activity under therapeutic dosing of venlafaxine should be brought to the attention of the health care prescriber. The potential for drug-drug interactions involving venlafazine, particularly in combination with multiple drugs, such as isoniazid and levofloxacin, needs to be recognized.


Subject(s)
Depressive Disorder, Major/drug therapy , Seizures/chemically induced , Serotonin and Noradrenaline Reuptake Inhibitors/adverse effects , Venlafaxine Hydrochloride/adverse effects , Adult , Delayed-Action Preparations/adverse effects , Female , Humans , Serotonin and Noradrenaline Reuptake Inhibitors/administration & dosage , Venlafaxine Hydrochloride/administration & dosage
14.
Osteoporos Int ; 29(5): 1135-1145, 2018 05.
Article in English | MEDLINE | ID: mdl-29450584

ABSTRACT

Studying dietary patterns is often more informative than individual nutrients or foods. We found that a Prudent dietary pattern (rich in vegetables and fish) was associated with reduced loss of total hip BMD in older men. A Prudent dietary pattern may be a potential lifestyle strategy for minimizing bone loss. INTRODUCTION: This study aimed to identify baseline dietary patterns using factor analysis in a cohort of older men and to evaluate whether the dietary patterns were associated with bone mineral density change (%ΔBMD) at the total hip and femoral neck over time. METHODS: Participants (n = 4379; mean age 72.9 ± 5.5 years) were from the Osteoporotic Fractures in Men (MrOS) prospective cohort study and had dietary data collected at baseline (March 2000-April 2002) and BMD measured at baseline and Visit 2 (March 2005-May 2006). Dietary intake was assessed with a brief Block food frequency questionnaire (FFQ); factor analysis was used to derive dietary patterns. BMD was measured by dual-energy x-ray absorptiometry (DXA); %ΔBMD was calculated from baseline to Visit 2. We used generalized linear regression to estimate least square (LS) means of %ΔBMD in quartiles of the dietary pattern scores adjusted for potential confounding factors. RESULTS: Two major dietary patterns were derived: Prudent (abundant in vegetables, salad, and non-fried fish) and Western (rich in hamburger, fries, processed meats, cheese, and sweets/desserts). There was an inverse association between adherence to the Prudent pattern and total hip %ΔBMD (p-trend = 0.028 after adjusting for age and clinical site; p-trend = 0.033 after further adjustment for smoking, calcium supplement use, diabetes, hypertension, and total energy intake). No other consistent associations between dietary patterns and %ΔBMD were observed. CONCLUSIONS: Greater adherence to a Prudent dietary pattern may attenuate total hip BMD loss (%ΔBMD) in older men.


Subject(s)
Bone Density/physiology , Diet/statistics & numerical data , Feeding Behavior/physiology , Absorptiometry, Photon/methods , Aged , Aging/physiology , Diet/adverse effects , Diet Surveys , Factor Analysis, Statistical , Femur Neck/physiology , Hip Joint/physiology , Humans , Life Style , Longitudinal Studies , Male , Osteoporosis/etiology , Osteoporosis/physiopathology , Osteoporosis/prevention & control , Prospective Studies
15.
Water Res ; 128: 267-277, 2018 01 01.
Article in English | MEDLINE | ID: mdl-29107911

ABSTRACT

Dairy cattle treated wastewaters are potential resources for production of microalgae biofuels. A study was conducted to evaluate the capability of Arthrospira platensis cultivated in dairy farm wastewater for biodiesel production. The biomass of Arthrospira platensis was found to be 4.98 g L-1 and produced 30.23 wt% lipids to dry biomass cultivated in wastewater which was found nitrogen stressed in photo bioreactor. The extracted lipid displayed a suitable fatty acid profile for biodiesel, although the content of linolenic acid was found a little higher than the standard EN14214. It was found that nitrogen stressed medium increase the total lipid content but temperature and intensities of light were the most important factors to control the quantity of linolenic acid and hence the quality of biodiesel, while the optimum CO2 helped to achieve maximum biomass and triacylglycerols. The Arthrospira platensis offer a good option for the treatment of wastewater before final discharge.


Subject(s)
Biofuels , Lipids/biosynthesis , Spirulina/metabolism , Waste Management/methods , Biomass , Bioreactors , Carbon Dioxide/metabolism , Culture Techniques , Dairying , Farms , Fatty Acids , Lipids/analysis , Microalgae , Nitrogen , Spirulina/growth & development , Spirulina/radiation effects , Temperature , Wastewater/chemistry
16.
JIMD Rep ; 40: 31-37, 2018.
Article in English | MEDLINE | ID: mdl-28942493

ABSTRACT

Nitisinone, although unapproved for use in alkaptonuria (AKU), is currently the only homogentisic acid lowering therapy with a potential to modify disease progression in AKU. Therefore, safe use of nitisinone off-label requires identifying and managing tyrosine keratopathy. A 22-year-old male with AKU commenced 2 mg daily nitisinone after full assessment. He was issued an alert card explaining potential ocular symptoms such as red eye, tearing, ocular pain and visual impairment and how to manage them. On his first and second annual follow-up visits to the National Alkaptonuria Centre (NAC), there was no corneal keratopathy on slit lamp examination. On his third follow-up annual visit to the NAC, he was found to have typical dendritiform corneal keratopathy in both eyes which was asymptomatic. Nitisinone was suspended until a repeat slit lamp examination, 2 weeks later, confirmed that the keratopathy had resolved. He recommenced nitisinone 2 mg daily with a stricter low protein diet. On his fourth annual follow-up visit to the NAC, a routine slit lamp examination showed mild corneal keratopathy in the left eye. This is despite him reporting no ocular symptoms. This case highlights the fact that corneal keratopathy can occur without symptoms and any monitoring plan with off-label use of nitisinone in AKU will need to take this possibility into account. This is also the first time that typical corneal keratopathy has been described with the use of low dose nitisinone in AKU without symptoms.

17.
Water Res ; 126: 208-215, 2017 12 01.
Article in English | MEDLINE | ID: mdl-28957697

ABSTRACT

The power demanded for the application of mechanically-imposed shear on an immersed flat sheet (iFS) membrane bioreactor (MBR) has been compared to that of conventional membrane air scouring. Literature correlations based on the Ostwald model were used to define the rheological characteristics of an MBR sludge. The correlation of specific power demand (P'¯, in Watts per m2 membrane area) with shear rate γ in s-1 was developed from first principles through a consideration of the force balance on the system in the case of mechanically-imposed shear. The corresponding aeration imposed shear correlation was interpreted from literature information. The analysis revealed the energy required to impose a shear mechanically through oscillation (or reciprocation) of the membrane to be between 20 and 70% less than that demanded for providing the same shear by conventional aeration of the immersed membrane. The energy saving increases with decreasing shear in accordance with a power demand ratio (aeration:mechanical) of 1400γ-1.4 for a specific sludge rheology. Whilst the absolute P'¯ value is dependent on the sludge rheology, the aeration:mechanical power demand ratio is determined by the difference in the two exponents in the respective correlations between P'¯ and γ. Consequently, aeration-imparted shear becomes energetically favoured beyond some threshold shear rate value (∼180 s-1, based on the boundary conditions applied in the current study). The outcomes qualitatively corroborate findings from the limited practical measurement of energy demand in MBRs fitted with reciprocating immersed membranes.


Subject(s)
Bioreactors , Conservation of Energy Resources , Membranes, Artificial , Sewage , Waste Disposal, Fluid/methods , Air , Models, Theoretical , Pressure , Rheology , Waste Disposal, Fluid/instrumentation
18.
Eur J Neurol ; 24(12): 1464-1470, 2017 12.
Article in English | MEDLINE | ID: mdl-28872212

ABSTRACT

BACKGROUND AND PURPOSE: Galectin-3 is a biomarker of atherosclerotic and cardiovascular disease, and may be a useful marker for ischaemic stroke risk. METHODS: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort enrolled and examined 30 239 US participants between 2003 and 2007 (41% black, 59% white and 55% in the southeastern stroke belt). Baseline galectin-3 was measured in 526 subjects with incident ischaemic stroke over 5.4 years and in a cohort random sample (CRS) of 947 participants. Cox proportional hazards models were used to calculate hazard ratios (HRs) of ischaemic stroke by quartiles of galectin-3. RESULTS: In the CRS, galectin-3 was significantly higher with older age, black race, female sex, body mass index, hypertension, diabetes mellitus and kidney disease, and also in those who developed incident stroke. Participants with galectin-3 levels in the fourth versus first quartile had a 2.3-fold increased stroke risk [95% confidence interval (CI) 1.6, 3.4] in an unadjusted model. An interaction with age was found (P = 0.06), and therefore age-stratified analyses were performed. Amongst those younger than age 64, baseline galectin-3 in the second-fourth quartiles was associated with increased stroke risk (HR 3.0, 95% CI 1.6, 5.5) compared to the first quartile in an age-, race- and sex-adjusted model. The HR was 2.0 (95% CI 1.0, 4.0) with multivariable adjustment. There was no association amongst older participants. CONCLUSIONS: Galectin-3 was associated with incident ischaemic stroke in younger but not older individuals. Confirmation of this finding, and elucidation of its implications for stroke pathophysiology and prevention, is needed.


Subject(s)
Body Mass Index , Brain Ischemia/etiology , Galectin 3/blood , Hypertension/complications , Stroke/etiology , Age Factors , Aged , Biomarkers , Blood Proteins , Brain Ischemia/blood , Brain Ischemia/epidemiology , Female , Galectins , Humans , Hypertension/blood , Incidence , Male , Middle Aged , Risk Factors , Sex Factors , Stroke/blood , Stroke/epidemiology , White People
19.
Water Res ; 122: 1-9, 2017 10 01.
Article in English | MEDLINE | ID: mdl-28570957

ABSTRACT

A reflection of the place cost analysis holds in membrane process technology research and development is provided. The review encompassed two membrane processes and applications: (a) reverse osmosis (RO) for seawater desalination, and (b) membrane bioreactor (MBR) technology for wastewater treatment. The cost analysis undertaken extended to (i) the determination of operating expenditure (OPEX) trends using simple analytical expressions, (ii) the subsequent estimation of the sensitivity of OPEX to individual system parameters, and (iii) published data on CAPEX for individual full-scale installations or from cost analyses. An appraisal of the peer-reviewed literature through a survey of a leading scientific database was also carried out. This bibliometric analysis was based on authors' keywords; it aimed to establish the profile of process cost for each of the two applications when compared with other popular research topics. The OPEX analysis, ostensibly through a consideration of specific energy demand in kWh per m3 permeate, revealed it to relate primarily to hydrodynamics in the case of RO, and to both membrane fouling and air scouring for MBRs. The bibliometric analysis of research trends revealed a marked difference in emphasis on cost aspects between the two research areas, with the focus on cost specifically being 16 times greater for RO desalination of seawater than MBR treatment of wastewater. MBR research appears to be dominated by fouling and foulant characterisation, making up almost a quarter of all studies, notwithstanding evidence from practitioners that other process parameters are as important in determining MBR process OPEX and operability.


Subject(s)
Membranes, Artificial , Water Purification/economics , Bioreactors , Filtration , Osmosis , Wastewater
20.
J Thromb Haemost ; 15(6): 1086-1094, 2017 06.
Article in English | MEDLINE | ID: mdl-28393470

ABSTRACT

Essentials Coagulation factors (F) IX and XI have been implicated in cardiovascular disease (CVD) risk. We studied associations of FIX and FXI with incident coronary heart disease (CHD) and stroke. Higher FIX antigen was associated with incident CHD risk in blacks but not whites. Higher levels of FIX antigen may be a CHD risk factor among blacks. SUMMARY: Background Recent studies have suggested the importance of coagulation factor IX and FXI in cardiovascular disease (CVD) risk. Objectives To determine whether basal levels of FIX or FXI antigen were associated with the risk of incident coronary heart disease (CHD) or ischemic stroke. Patients/Methods The REasons for Geographic And Racial Differences in Stroke (REGARDS) study recruited 30 239 participants across the contiguous USA between 2003 and 2007. In a case-cohort study within REGARDS, FIX and FXI antigen were measured in participants with incident CHD (n = 609), in participants with incident ischemic stroke (n = 538), and in a cohort random sample (n = 1038). Hazard ratios (HRs) for CHD and ischemic stroke risk were estimated with Cox models per standard deviation higher FIX or FXI level, adjusted for CVD risk factors. Results In models adjusting for CHD risk factors, higher FIX levels were associated with incident CHD risk (HR 1.19; 95% confidence interval [CI] 1.01-1.40) and the relationship of higher FXI levels was slightly weaker (HR 1.15; 95% CI 0.97-1.36). When stratified by race, the HR of FIX was higher in blacks (HR 1.39; 95% CI 1.10-1.75) than in whites (HR 1.06; 95% CI 0.86-1.31). After adjustment for stroke risk factors, there was no longer an association of FIX levels with ischemic stroke, whereas the association of FXI levels with ischemic stroke was slightly attenuated. Conclusions Higher FIX antigen levels were associated with incident CHD in blacks but not in whites. FIX levels may increase CHD risk among blacks.


Subject(s)
Coronary Disease/blood , Coronary Disease/ethnology , Factor IX/metabolism , Factor XI/metabolism , Myocardial Ischemia/blood , Myocardial Ischemia/ethnology , Stroke/metabolism , Black or African American , Aged , Black People , C-Reactive Protein/metabolism , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Risk Factors , Stroke/genetics , Treatment Outcome , United States , White People
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