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1.
Subst Use Addctn J ; : 29767342241228126, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38294429

ABSTRACT

Chronic pain and opioid use disorder (OUD) are public health crises and their co-occurrence has led to further complications and public health impacts. Provision of treatments for comorbid chronic pain and OUD is paramount to address these public health crises. Medications for OUD (MOUD) are gold standard treatments for OUD that have also demonstrated benefit in pain management. However, clinics that provide MOUD for chronic pain or OUD often lack behavioral treatments to address the challenges experienced by individuals with both conditions. Developing and implementing a behavioral treatment that complements MOUD may better equip clinics to provide comprehensive care to the growing proportion of clients who present with comorbid chronic pain and OUD. In the Healing Opioid misuse and Pain through Engagement (HOPE) Trial, we are using an effectiveness-implementation hybrid design to examine the benefits of an integrated behavioral treatment and to determine the feasibility of implementing the integrated treatment into clinics that provide MOUD. The treatment integrated 2 evidence-based treatments-Acceptance and Commitment Therapy and Mindfulness-Based Relapse Prevention-to target the emotional, behavioral, and physiological sequelae of OUD and chronic pain. Implementation feasibility will include assessing changes in implementation readiness and identifying facilitators and barriers to implementing the integrated treatment among all personnel employed in clinics that provide MOUD. This commentary offers an overview of the study and design and details adaptations we made to our study protocol, based largely on clinic personnel time constraints and variable clinic procedures during the COVID-19 pandemic.

2.
Radiographics ; 44(2): e230133, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38236751

ABSTRACT

Parkinsonian syndromes are a heterogeneous group of progressive neurodegenerative disorders involving the nigrostriatal dopaminergic pathway and are characterized by a wide spectrum of motor and nonmotor symptoms. These syndromes are quite common and can profoundly impact the lives of patients and their families. In addition to classic Parkinson disease, parkinsonian syndromes include multiple additional disorders known collectively as Parkinson-plus syndromes or atypical parkinsonism. These are characterized by the classic parkinsonian motor symptoms with additional distinguishing clinical features. Dopamine transporter SPECT has been developed as a diagnostic tool to assess the levels of dopamine transporters in the striatum. This imaging assessment, which uses iodine 123 (123I) ioflupane, can be useful to differentiate parkinsonian syndromes caused by nigrostriatal degeneration from other clinical mimics such as essential tremor or psychogenic tremor. Dopamine transporter imaging plays a crucial role in diagnosing parkinsonian syndromes, particularly in patients who do not clearly fulfill the clinical criteria for diagnosis. Diagnostic clarification can allow early treatment in appropriate patients and avoid misdiagnosis. At present, only the qualitative interpretation of dopamine transporter SPECT is approved by the U.S. Food and Drug Administration, but quantitative interpretation is often used to supplement qualitative interpretation. The authors provide an overview of patient preparation, common imaging findings, and potential pitfalls that radiologists and nuclear medicine physicians should know when performing and interpreting dopamine transporter examinations. Alternatives to 123I-ioflupane imaging for the evaluation of nigrostriatal degeneration are also briefly discussed. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material. See the invited commentary by Intenzo and Colarossi in this issue.


Subject(s)
Iodine Radioisotopes , Nortropanes , Parkinsonian Disorders , Humans , Dopamine Plasma Membrane Transport Proteins/metabolism , Parkinsonian Disorders/diagnostic imaging , Parkinsonian Disorders/metabolism , Tomography, Emission-Computed, Single-Photon/methods
3.
Blood Adv ; 7(16): 4576-4585, 2023 08 22.
Article in English | MEDLINE | ID: mdl-37307169

ABSTRACT

Time to progression of disease (POD) after first-line (1L) therapy is prognostic in mantle cell lymphoma (MCL), although studies have included a broad range of 1L, second-line (2L), and subsequent lines of therapy. The purpose of this study was to evaluate the factors predicting outcomes in patients with relapsed/refractory (R/R) MCL exclusively initiating 2L Bruton's tyrosine kinase inhibitors (BTKis) after 1L rituximab-containing therapy. Patients were accrued from 8 international centers (7 main, 1 validation cohort). Multivariable models evaluating the association between time to POD and clinical/pathologic factors were constructed and converted into nomograms and prognostic indexes predicting outcomes in this population. A total of 360 patients were included, including 160 in the main cohort and 200 in the validation cohort. Time to POD, Ki67 ≥ 30%, and MCL International Prognostic Index (MIPI) were associated with progression-free survival (PFS2) and overall survival (OS2) from the start of 2L BTKis. C-indexes were consistently ≥0.68 in both cohorts. Web/application-based calculators based on nomograms and prognostic indexes to estimate PFS2 and OS2 were constructed. The 2L BTKi MIPI identifies 3 groups with distinct 2-year PFS2, including high risk (14%), intermediate risk (50%), and low risk (64%). Time to POD, Ki67, and MIPI are associated with survival outcomes in patients with R/R MCL receiving 2L BTKis. Simple clinical models incorporating these variables may assist in planning for alternative therapies such as chimeric antigen receptor T-cell therapy, allogeneic stem cell transplantation, or novel agents with alternative mechanisms of action.


Subject(s)
Hematopoietic Stem Cell Transplantation , Lymphoma, Mantle-Cell , Adult , Humans , Lymphoma, Mantle-Cell/pathology , Ki-67 Antigen , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prognosis
4.
Sci Rep ; 13(1): 3770, 2023 03 07.
Article in English | MEDLINE | ID: mdl-36882452

ABSTRACT

Upside-down jellyfish, genus Cassiopea (Péron and Lesueur, 1809), are found in shallow coastal habitats in tropical and subtropical regions circumglobally. These animals have previously been demonstrated to produce flow both in the water column as a feeding current, and in the interstitial porewater, where they liberate porewater at rates averaging 2.46 mL h-1. Since porewater in Cassiopea habitat can be nutrient-rich, this is a potential source of nutrient enrichment in these ecosystems. This study experimentally determines that porewater release by Cassiopea sp. jellyfish is due to suction pumping, and not the Bernoulli effect. This suggests porewater release is directly coupled to bell pulsation rate, and unlike vertical jet flux, should be unaffected by population density. In addition, we show that bell pulsation rate is positively correlated with temperature, and negatively correlated with animal size. As such, we would predict an increase in the release of nutrient-rich porewater during the warm summer months. Furthermore, we show that, at our field site in Lido Key, Florida, at the northernmost limit of Cassiopea range, population densities decline during the winter, increasing seasonal differences in porewater release.


Subject(s)
Cnidaria , Scyphozoa , Animals , Suction , Ecosystem , Florida
5.
Contemp Clin Trials ; 126: 107096, 2023 03.
Article in English | MEDLINE | ID: mdl-36693589

ABSTRACT

BACKGROUND: Chronic pain and opioid use disorder (OUD) individually represent a risk to health and well-being. Concerningly, there is evidence that they are frequently co-morbid. While few treatments exist that simultaneously target both conditions, preliminary work has supported the feasibility of an integrated behavioral treatment targeting pain interference and opioid misuse. This treatment combined Acceptance and Commitment Therapy (ACT) and Mindfulness-Based Relapse Prevention (ACT+MBRP). This paper describes the protocol for the adequately powered efficacy study of this integrated treatment. METHODS: A multisite randomized controlled trial will examine the efficacy of ACT+MBRP in comparison to a parallel education control condition, focusing on opioid safety and pain education. Participants include veterans (n = 160; 21-75 years old) recruited from three Veterans Administration (VA) Healthcare Systems with chronic pain who are on a stable dose of buprenorphine. Both conditions include twelve weekly 90 min group sessions delivered via telehealth. Primary outcomes include pain interference (Patient Reported Outcome Measurement Information System - Pain Interference) and hazardous opioid use (Current Opioid Misuse Measure), which will be examined at the end of the active treatment phase and through 12 months post-intervention. Secondary analyses will evaluate outcomes including pain intensity, depression, pain-related fear, and substance use, as well as treatment mechanisms. CONCLUSION: This study will determine the efficacy of an integrated behavioral treatment program for pain interference and hazardous opioid use among veterans with chronic pain and OUD who are prescribed buprenorphine, addressing a critical need for more integrated treatments for chronic pain and OUD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04648228.


Subject(s)
Acceptance and Commitment Therapy , Buprenorphine , Chronic Pain , Opioid-Related Disorders , Veterans , Humans , Young Adult , Adult , Middle Aged , Aged , Analgesics, Opioid/therapeutic use , Chronic Pain/drug therapy , Opioid-Related Disorders/drug therapy , Buprenorphine/therapeutic use
6.
Chemosphere ; 286(Pt 1): 131596, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34346326

ABSTRACT

One of the primary drivers of Phosphorus (P) limitation in aquatic systems is P adsorption to sediments. Sediments adsorb more P in freshwater compared to other natural solutions, but the mechanism driving this difference is poorly understood. To provide insights into the mechanism, we conducted batch experiments of P adsorption to calcite in freshwater and seawater, and used computer software to develop complexation models. Our simulations revealed three main reasons that, combining together, may explain the greater P adsorption to calcite in freshwater vs. seawater. First, aqueous speciation of P makes a difference. The ion pair CaPO4- is much more abundant in freshwater; although seawater has more Ca2+ ions, MgHPO40 and NaHPO40 are more thermodynamically favored. Second, the adsorbing species of P make a difference. The ion pair CaPO4- (the preferred adsorbate in freshwater) is able to access adsorption sites that are not available to HPO42- (the preferred adsorbate in seawater), thereby raising the maximum concentration of P that can adsorb to the calcite surface in freshwater. Third, water chemistry affects the competition among ions for surface sites. Other ions (including P) compete more effectively against CO32- when immersed in freshwater vs. seawater, even when the concentration of HCO3-/CO32- is higher in freshwater vs. seawater. In addition, we found that under oligotrophic conditions, P adsorption is driven by the higher energy adsorption sites, and by the lower energy sites in eutrophic conditions. This study is the first to model P adsorption mechanisms to calcite in freshwater and seawater.


Subject(s)
Calcium Carbonate , Water Pollutants, Chemical , Adsorption , Fresh Water , Phosphorus , Water Pollutants, Chemical/analysis
7.
Proc Natl Acad Sci U S A ; 118(30)2021 07 27.
Article in English | MEDLINE | ID: mdl-34301888

ABSTRACT

Water mixing is a critical mechanism in marine habitats that governs many important processes, including nutrient transport. Physical mechanisms, such as winds or tides, are primarily responsible for mixing effects in shallow coastal systems, but the sheltered habitats adjacent to mangroves experience very low turbulence and vertical mixing. The significance of biogenic mixing in pelagic habitats has been investigated but remains unclear. In this study, we show that the upside-down jellyfish Cassiopea sp. plays a significant role with respect to biogenic contributions to water column mixing within its shallow natural habitat ([Formula: see text] m deep). The mixing contribution was determined by high-resolution flow velocimetry methods in both the laboratory and the natural environment. We demonstrate that Cassiopea sp. continuously pump water from the benthos upward in a vertical jet with flow velocities on the scale of centimeters per second. The volumetric flow rate was calculated to be 212 L⋅h-1 for average-sized animals (8.6 cm bell diameter), which translates to turnover of the entire water column every 15 min for a median population density (29 animals per m2). In addition, we found Cassiopea sp. are capable of releasing porewater into the water column at an average rate of 2.64 mL⋅h-1 per individual. The release of nutrient-rich benthic porewater combined with strong contributions to water column mixing suggests a role for Cassiopea sp. as an ecosystem engineer in mangrove habitats.


Subject(s)
Ecosystem , Environment , Scyphozoa/physiology , Water/physiology , Animals , Population Density
8.
Lancet Infect Dis ; 21(5): 647-656, 2021 05.
Article in English | MEDLINE | ID: mdl-33676595

ABSTRACT

BACKGROUND: To address the increasing incidence of gonorrhoea and antimicrobial resistance, we compared the efficacy of Listerine and Biotène mouthwashes for preventing gonorrhoea among men who have sex with men (MSM). METHODS: The OMEGA trial was a multicentre, parallel-group, double-blind randomised controlled trial among MSM, done at three urban sexual health clinics and one general practice clinic in Australia. Men were eligible if they were diagnosed with oropharyngeal gonorrhoea by nucleic acid amplification test (NAAT) in the previous 30 days or were aged 16-24 years. They were randomly assigned to receive Listerine (intervention) or Biotène (control) via a computer-generated sequence (1:1 ratio, block size of four). Participants, clinicians, data collectors, data analysts, and outcome adjudicators were masked to the interventions after assignment. Participants were instructed to rinse and gargle with 20 mL of mouthwash for 60 s at least once daily for 12 weeks. Oropharyngeal swabs were collected by research nurses every 6 weeks, and participants provided saliva samples every 3 weeks, to be tested for Neisseria gonorrhoeae with NAAT and quantitative PCR. The primary outcome was proportion of MSM diagnosed with oropharyngeal N gonorrhoeae infection at any point over the 12-week period, defined as a positive result for either oropharyngeal swabs or saliva samples by NAAT, and the cumulative incidence of oropharyngeal gonorrhoea at the week 12 visit. A modified intention-to-treat analysis for the primary outcome was done that included men who provided at least one follow-up specimen over the 12-week study period. The trial was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12616000247471). FINDINGS: Between March 30, 2016, and Oct 26, 2018, 786 MSM were screened and 256 were excluded. 264 MSM were randomly assigned to the Biotène group and 266 to the Listerine group. The analysis population included 227 (86%) men in the Biotène group and 219 (82%) in the Listerine group. Oropharyngeal gonorrhoea was detected in ten (4%) of 227 of MSM in the Biotène group and in 15 (7%) of 219 in the Listerine group (adjusted risk difference 2·5%, 95% CI -1·8 to 6·8). The cumulative incidence of oropharyngeal gonorrhoea at the week 12 visit did not differ between the two mouthwash groups (adjusted risk difference 3·1%, 95% CI -1·4 to 7·7). INTERPRETATION: Listerine did not reduce the incidence of oropharyngeal gonorrhoea compared with Biotène. However, previous research suggests that mouthwash might reduce the infectivity of oropharyngeal gonorrhoea; therefore, further studies of mouthwash examining its inhibitory effect on N gonorrhoeae are warranted to determine if it has a potential role for the prevention of transmission. FUNDING: Australian National Health and Medical Research Council.


Subject(s)
Anti-Infective Agents, Local/therapeutic use , Gonorrhea/prevention & control , Mouthwashes/therapeutic use , Adult , Australia , Double-Blind Method , Drug Combinations , Glucose Oxidase , Homosexuality, Male , Humans , Lactoperoxidase , Male , Multicenter Studies as Topic , Muramidase , Neisseria gonorrhoeae/drug effects , New Zealand , Respiratory Tract Infections/prevention & control , Salicylates/therapeutic use , Sexual and Gender Minorities , Surveys and Questionnaires , Terpenes/therapeutic use , Young Adult
9.
Lancet ; 397(10277): 892-901, 2021 03 06.
Article in English | MEDLINE | ID: mdl-33676628

ABSTRACT

BACKGROUND: Covalent Bruton's tyrosine kinase (BTK) inhibitors are efficacious in multiple B-cell malignancies, but patients discontinue these agents due to resistance and intolerance. We evaluated the safety and efficacy of pirtobrutinib (working name; formerly known as LOXO-305), a highly selective, reversible BTK inhibitor, in these patients. METHODS: Patients with previously treated B-cell malignancies were enrolled in a first-in-human, multicentre, open-label, phase 1/2 trial of the BTK inhibitor pirtobrutinib. The primary endpoint was the maximum tolerated dose (phase 1) and overall response rate (ORR; phase 2). This trial is registered with ClinicalTrials.gov, NCT03740529. FINDINGS: 323 patients were treated with pirtobrutinib across seven dose levels (25 mg, 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, and 300 mg once per day) with linear dose-proportional exposures. No dose-limiting toxicities were observed and the maximum tolerated dose was not reached. The recommended phase 2 dose was 200 mg daily. Adverse events in at least 10% of 323 patients were fatigue (65 [20%]), diarrhoea (55 [17%]), and contusion (42 [13%]). The most common adverse event of grade 3 or higher was neutropenia (32 [10%]). There was no correlation between pirtobrutinib exposure and the frequency of grade 3 treatment-related adverse events. Grade 3 atrial fibrillation or flutter was not observed, and grade 3 haemorrhage was observed in one patient in the setting of mechanical trauma. Five (1%) patients discontinued treatment due to a treatment-related adverse event. In 121 efficacy evaluable patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) treated with a previous covalent BTK inhibitor (median previous lines of treatment 4), the ORR with pirtobrutinib was 62% (95% CI 53-71). The ORR was similar in CLL patients with previous covalent BTK inhibitor resistance (53 [67%] of 79), covalent BTK inhibitor intolerance (22 [52%] of 42), BTK C481-mutant (17 [71%] of 24) and BTK wild-type (43 [66%] of 65) disease. In 52 efficacy evaluable patients with mantle cell lymphoma (MCL) previously treated with covalent BTK inhibitors, the ORR was 52% (95% CI 38-66). Of 117 patients with CLL, SLL, or MCL who responded, all but eight remain progression-free to date. INTERPRETATION: Pirtobrutinib was safe and active in multiple B-cell malignancies, including patients previously treated with covalent BTK inhibitors. Pirtobrutinib might address a growing unmet need for alternative therapies for these patients. FUNDING: Loxo Oncology.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Lymphoma, B-Cell/drug therapy , Lymphoma, Mantle-Cell/drug therapy , Protein Kinase Inhibitors/therapeutic use , Adult , Aged , Aged, 80 and over , Female , Humans , Lymphoma, B-Cell/pathology , Lymphoma, Mantle-Cell/pathology , Male , Middle Aged , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Treatment Outcome
10.
Article in English | MEDLINE | ID: mdl-33632090

ABSTRACT

ABSTRACT: The key issues with Neisseria gonorrhoeae infections, in Australia and elsewhere, are coincident increases in disease rates and in antimicrobial resistance (AMR), although these factors have not been shown to be correlated. Despite advances in diagnosis, control of this disease remains elusive, and incidence in Australia continues to increase. Of the Australian jurisdictions, New South Wales (NSW) has the highest N. gonorrhoeae notifications, and over the five-year period 2015-2019, notifications in NSW have increased above the national average (by 116% versus 85%, respectively). Gonococcal disease control is reliant on effective antibiotic regimens. However, escalating AMR in N. gonorrhoeae is a global health priority, as the collateral injury of untreated infections has substantive impacts on sexual and newborn health. Currently, our first-line therapy for gonorrhoea is also our last line, with no ideal alternative identified. Despite some limitations, gentamicin is licensed and readily available in Australia, and is proposed for treatment of resistant N. gonorrhoeae in national guidelines; however, supportive published microbiological data are lacking. Analysis of gonococcal resistance patterns within Australia for the period 1991-2019, including 35,000 clinical isolates from NSW, illustrates the establishment and spread of population-level resistance to all contemporaneous therapies. An analysis of gentamicin susceptibility on 2,768 N. gonorrhoeae clinical isolates from NSW, for the period 2015-2020, demonstrates that the median minimum inhibitory concentration (MIC) for gentamicin in NSW has remained low, at 4.0 mg/L, and resistance was not detected in any isolate. There has been no demonstration of MIC drift over time (p = 0.91, Kruskal-Wallis test), nor differences in MIC distributions according to patients' sex or site of specimen collection. This is the first large-scale evaluation of gentamicin susceptibility in N. gonorrhoeae in Australia. No gentamicin resistance was detected in clinical isolates, 2015-2020, hence this is likely to be an available treatment option for resistant gonococcal infections in NSW.


Subject(s)
Gentamicins/therapeutic use , Gonorrhea/drug therapy , Neisseria gonorrhoeae/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial , Female , Gentamicins/pharmacology , Gonorrhea/microbiology , Humans , Male , Microbial Sensitivity Tests , New South Wales , Sex Factors
11.
J Ment Health ; 29(2): 207-216, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31989852

ABSTRACT

Background: There is a significant lack of outcomes research examining the effectiveness of digital interventions for reducing suicidal ideation and self-harm.Aims: To systematically review the effectiveness of digital interventions for reducing suicidal ideation and self-harm in adult populations. The possible mediating effects of depression are also discussed.Methods: The databases Pubmed, Medline, PsycInfo, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, IEEEXplore, ACM and CRESP were searched. Only randomised controlled trials (RCTs) were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Studies were assessed for methodological quality and risk of bias using standard assessment criteria.Results: Fourteen RCTs were reviewed, reporting data on 3455 participants. Although findings were more consistent for the effectiveness of online Cognitive Behavioural Therapy (CBT), Mindfulness-Based CBT and Dialectical Behavioural Therapy, there was insufficient research to consider any as evidence-based treatments for suicidal ideation and self-harm.Conclusions: Digital interventions for suicidal ideation and self-harm can be a safe and acceptable option for individuals unwilling or unable to access face-to-face interventions. However, further research is needed to understand the types of interventions that could support people and the risk-benefit ratio of digital interventions for these individuals.


Subject(s)
Cognitive Behavioral Therapy/methods , Self-Injurious Behavior/prevention & control , Suicidal Ideation , Telemedicine , Humans , Mindfulness , Mobile Applications , Randomized Controlled Trials as Topic , Treatment Outcome
12.
Asia Pac J Ophthalmol (Phila) ; 7(5): 331-338, 2018.
Article in English | MEDLINE | ID: mdl-29984563

ABSTRACT

PURPOSE: To assess the impact of inclusive eye health programs for people with disabilities. DESIGN: A synthesis evaluation study. METHODS: A cross-disciplinary team of ophthalmologists, evaluation, and disability-inclusive development advisors purposively selected evaluation reports of CBM-supported inclusive eye health programs in low- and middle-income countries. Employing a change-promoting paradigm, salient achievements and challenges were narratively analyzed and recommendations suggested based on a previously developed framework for strengthening disability inclusion in eye health programs. RESULTS: Evaluations from 10 programs implemented in 6 countries (Cambodia, Egypt, Ethiopia, Indonesia, Pakistan, Vietnam) from 2011 to 2016 were identified. Training of medical staff and government officials resulted in increased awareness about disability rights and improved physical accessibility of eye health facilities. Relevant information about inclusion in eye health was incorporated in national eye health training curricula in some countries. Information, education, and communication material about eye health neglected patients with hearing and learning impairments. An overly narrow focus on disability inclusion confounded intersectoral barriers to eye health services. Collaboration of eye health staff with disability peoples organizations improved significantly but evidence of its impact was elusive. Collection of disability-disaggregated data posed significant challenges and made it difficult to demonstrate increased access to eye health programs by people with disabilities. CONCLUSIONS: Introduction of disability inclusion in eye health systems of countries with limited resources poses significant challenges. Future programs striving to improve access to eye health services for marginalized populations including people with disabilities might consider more flexible and contextualized approaches.


Subject(s)
Delivery of Health Care, Integrated/organization & administration , Disabled Persons/rehabilitation , Eye Diseases/therapy , Health Services Accessibility/organization & administration , Health Services for Persons with Disabilities/organization & administration , Ophthalmology/organization & administration , Cooperative Behavior , Developing Countries , Education, Medical/organization & administration , Health Facilities , Health Knowledge, Attitudes, Practice , Humans , Ophthalmology/education , Patient Rights , Program Development
13.
Int J Pharm ; 544(1): 141-152, 2018 Jun 10.
Article in English | MEDLINE | ID: mdl-29649519

ABSTRACT

PURPOSE: This study was performed to investigate how increasing the active pharmaceutical ingredient (API) content within a formulation affects the dispersion of particles and the aerosol performance efficiency of a carrier based dry powder inhalable (DPI) formulation, using a custom dry powder inhaler (DPI) development rig. METHODS: Five formulations with varying concentrations of API beclomethasone dipropionate (BDP) between 1% and 30% (w/w) were formulated as a multi-component carrier system containing coarse lactose and fine lactose with magnesium stearate. The morphology of the formulation and each component were investigated using scanning electron micrographs while the particle size was measured by laser diffraction. The aerosol performance, in terms of aerodynamic diameter, was assessed using the British pharmacopeia Apparatus E cascade impactor (Next generation impactor). Chemical analysis of the API was observed by high performance liquid chromatography (HPLC). RESULTS: Increasing the concentration of BDP in the blend resulted in increasing numbers and size of individual agglomerates and densely packed BDP multi-layers on the surface of the lactose carrier. BDP present within the multi-layer did not disperse as individual primary particles but as dense agglomerates, which led to a decrease in aerosol performance and increased percentage of BDP deposition within the Apparatus E induction port and pre-separator. CONCLUSION: As the BDP concentration in the blends increases, aerosol performance of the formulation decreases, in an inversely proportional manner. Concurrently, the percentage of API deposition in the induction port and pre-separator could also be linked to the amount of micronized particles (BDP and Micronized composite carrier) present in the formulation. The effect of such dose increase on the behaviour of aerosol dispersion was investigated to gain greater insight in the development and optimisation of higher dosed carrier-based formulations.


Subject(s)
Drug Carriers/chemistry , Dry Powder Inhalers , Aerosols , Anti-Asthmatic Agents/chemistry , Anti-Inflammatory Agents/chemistry , Beclomethasone/chemistry , Drug Compounding , Excipients/chemistry , Glucocorticoids/chemistry , Lactose/chemistry , Microscopy, Electron, Scanning , Particle Size , Stearic Acids/chemistry
15.
J Water Health ; 15(6): 863-872, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29215351

ABSTRACT

Moringa oleifera seeds are well known for their ability to cause flocculation in turbid water and facilitate bacterial inhibition. These effects are due to the cationic polypeptide MO2.1, which affects the surface charge of suspended particles and causes lysis of bacterial cells. However, the attachment of bacteria to MO2.1 prevents further bacterial attachment, reducing the effectiveness of the seeds. This research investigated the effect of surfactants on functionality and reuse of Moringa seeds to develop a sustainable water treatment technique. The seed extracts (MO2.1) were used with a functionalised sand system, and the sands were exposed to commercially available (ionic and non-ionic) surfactants, dodecyl glucoside and sodium dodecyl sulfate. Artificially polluted water contaminated with Escherichia coli was used to evaluate the efficiency of the system. The non-ionic surfactant was found to be effective at separating E. coli from the functionalised sand without the detachment of the MO2.1 and subsequent loss of the system efficiency. This was successfully repeated four times. The results demonstrated a sustainable, reusable technique to inhibit bacterial contamination in water.


Subject(s)
Bacterial Adhesion/drug effects , Glucosides/pharmacology , Moringa oleifera/chemistry , Peptides/pharmacology , Surface-Active Agents/pharmacology , Water Purification/methods , Adsorption , Bacteria/drug effects , Drinking Water/microbiology , Escherichia coli/drug effects , Escherichia coli/isolation & purification , Flocculation , Plant Extracts/chemistry , Recycling , Seeds/chemistry
16.
Chemistry ; 23(64): 16219-16230, 2017 Nov 16.
Article in English | MEDLINE | ID: mdl-28763123

ABSTRACT

Mercury pollution threatens the environment and human health across the globe. This neurotoxic substance is encountered in artisanal gold mining, coal combustion, oil and gas refining, waste incineration, chloralkali plant operation, metallurgy, and areas of agriculture in which mercury-rich fungicides are used. Thousands of tonnes of mercury are emitted annually through these activities. With the Minamata Convention on Mercury entering force this year, increasing regulation of mercury pollution is imminent. It is therefore critical to provide inexpensive and scalable mercury sorbents. The research herein addresses this need by introducing low-cost mercury sorbents made solely from sulfur and unsaturated cooking oils. A porous version of the polymer was prepared by simply synthesising the polymer in the presence of a sodium chloride porogen. The resulting material is a rubber that captures liquid mercury metal, mercury vapour, inorganic mercury bound to organic matter, and highly toxic alkylmercury compounds. Mercury removal from air, water and soil was demonstrated. Because sulfur is a by-product of petroleum refining and spent cooking oils from the food industry are suitable starting materials, these mercury-capturing polymers can be synthesised entirely from waste and supplied on multi-kilogram scales. This study is therefore an advance in waste valorisation and environmental chemistry.


Subject(s)
Mercury/chemistry , Plant Oils/chemistry , Sulfur/chemistry , Adsorption , Air Pollutants/chemistry , Calorimetry, Differential Scanning , Polymers/chemical synthesis , Polymers/chemistry , Recycling , Soil Pollutants/chemistry , Surface Properties , Thermogravimetry , Water Pollutants, Chemical/chemistry
17.
Schizophr Res ; 180: 28-35, 2017 02.
Article in English | MEDLINE | ID: mdl-27567291

ABSTRACT

In this review, we seek to answer the following question: Do findings in the current literature support the idea that thalamo-cortical dysfunction in schizophrenia is due to structural abnormalities in the thalamus? We base our review on the existing literature of design-unbiased stereological studies of the postmortem thalamus from subjects with schizophrenia. Thus, all reported results are based upon the use of unbiased principles of sampling to determine volume and/or total cell numbers of thalamus or its constituent nuclei. We found 28 such papers covering 26 studies. In a series of tables we list all positive and negative findings from the total thalamus, the mediodorsal, pulvinar and anterior nuclei, as well as less frequently studied thalamic regions. Only four studies examined the entire thalamus and the results were inconsistent. We found largely consistent evidence for structural changes (reduced volume and cell numbers) in the pulvinar located in the posterior thalamus. In contrast, findings in the mediodorsal thalamic nucleus are inconsistent, with the largest and most recent studies generally failing to support earlier reports of a lower number of neurons in schizophrenia. Thus, the current findings of stereological studies of the thalamus in schizophrenia support the idea that thalamo-cortical dysfunction in schizophrenia might be attributable, at least in part, to structural alterations in the pulvinar that could impair thalamic inputs to higher order cortical association areas in the frontal and parietal lobes. However, more studies are needed before robust conclusions can be drawn.


Subject(s)
Schizophrenia/pathology , Thalamus/pathology , Humans
18.
ACS Appl Mater Interfaces ; 8(35): 22860-8, 2016 Sep 07.
Article in English | MEDLINE | ID: mdl-27508925

ABSTRACT

We report the electrochemical detection of the redox active cardiac biomarker myoglobin (Mb) using aptamer-functionalized black phosphorus nanostructured electrodes by measuring direct electron transfer. The as-synthesized few-layer black phosphorus nanosheets have been functionalized with poly-l-lysine (PLL) to facilitate binding with generated anti-Mb DNA aptamers on nanostructured electrodes. This aptasensor platform has a record-low detection limit (∼0.524 pg mL(-1)) and sensitivity (36 µA pg(-1) mL cm(-2)) toward Mb with a dynamic response range from 1 pg mL(-1) to 16 µg mL(-1) for Mb in serum samples. This strategy opens up avenues to bedside technologies for multiplexed diagnosis of cardiovascular diseases in complex human samples.


Subject(s)
Nanostructures , Aptamers, Nucleotide , Biomarkers , Biosensing Techniques , Cardiovascular Diseases , Electrochemical Techniques , Electrodes , Humans , Myoglobin , Phosphorus
19.
Bioresour Technol ; 203: 228-35, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26735877

ABSTRACT

Biocrude was produced from Tetraselmis sp. - a marine alga and Arthrospira platensis - a fresh water alga using hydrothermal liquefaction (HTL) process. Considering the constraints in cultivating algae for replacing 100% petrocrude, this study evaluated the option of blending and co-processing algal biocrude with petrocrude. Biocrudes obtained from algal strains cultivated in fresh water and sea water were blended with petrocrude at 10% concentration and the characteristics were studied using FT-IR and CNS SIMDIST. True Boiling Point (TBP) distillation was carried out to assess yields and properties of distillates of blended biocrudes. Biocrudes obtained from both algae were light crudes and the blended crudes recorded distillate yields of 76-77 wt%. The yield of light naphtha fraction of biocrude blends was 29-30%; whereas the yield of diesel fraction was about 18%. This study proposes blending and co-processing of algal biocrude with petrocrude to produce drop-in biofuels.


Subject(s)
Aquatic Organisms/chemistry , Biofuels , Biomass , Chemical Fractionation/methods , Chlorophyta/chemistry , Petroleum , Biofuels/analysis , Distillation , Fresh Water , Hydrolysis , Petroleum/analysis , Seawater , Spectroscopy, Fourier Transform Infrared
20.
Rev. peru. med. integr ; 1(3): 5-11, 2016. tab, graf
Article in English | MTYCI, LILACS | ID: biblio-876540

ABSTRACT

Objectives: To describe acute toxicity, antibacterial activity and phytochemical assessment of Chlorella vulgaris and Spirulina platensis powders. Material and Methods: FeCl3 test, Wagner test, Keller Killiani test, frothing test, alkaline solution and dilute acid; concentrated sulphuric acid were used for phytochemical analysis. Antibacterial screening of the extracts was conducted using the disc gel diffusion method in E. coli, S. aureus and B. cereus clinical strains. In order to evaluate acute toxicity and its effects on haematological and biochemical parameters; 15 albino rats were grouped into five groups: I (powder of aqueous extract of Chlorella vulgaris), II (powder of methanol extract of Chlorella vulgaris), III (powder of aqueous extract of Spirulina platensis), IV (powder of methanol extract of Spirulina platensis) and V (control). The dosage was 25g/day/rat. After six days, haematological and biochemical parameters and gross pathologic changes were evaluated. Results: Alkaloids and flavonoids were detected from the methanol extracts of both Chlorella vulgaris and Spirulina platensis (Arthrospira). Only cardiac glycosides and steroids were detected from Spirulina's extracts. Chlorella vulgaris extracts significantly inhibited B. cereus. Rats fed with Chlorella vulgaris and Spirulina platensis powder showed an increase in white blood cell counts and haemoglobin level compared to negative control rats (p<0.001). Serum glumatic oxalate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) had normal values but significative differences between groups (p<0.001). Conclusion: This powder is rich in bioactive phytochemicals but only Chlorella's extracts have shown antibacterial effect. Signs of toxicity weren't found in any parameter.


Objetivos: Describir la toxicidad aguda, efecto antibacteriano y análisis fitoquímico de los polvos de Chlorella vulgaris y Spirulina platensis. Materiales y métodos: Se realizaron las pruebas de FeCl3, Keller Killiani, de saponinas, solución alcalina y de concentración de ácido sulfúrico para el análisis fitoquímico. El efecto antibacteriano de los extractos fue evaluado mediante el método de difusión con discos en cepas de E. coli, S. aureus y B. cereus. Para evaluar la toxicidad aguda y los efectos del polvo en parámetros hematológicos y bioquímicos, se agruparon 15 ratas albinas en cinco grupos: I (polvo de extracto acuoso de Chlorella vulgaris); II (polvo de extracto metanólico de Chlorella vulgaris); III (polvo de extracto acuoso de Spirulina platensis); IV (polvo de extracto metanólico de Spirulina platensis), y V (grupo control). La dosis usada fue de 25 g/día/rata. Después de seis días, se evaluaron todos los parámetros y cambios macroscópicos en los órganos. Resultados: Se encontraron alcaloides y flavonoides en los extractos metanólicos de Chlorella vulgaris y Spirulina platensis (Arthrospira). Se detectaron glucósidos cardiacos y esteroides en los extractos de Spirulina platensis. Los extractos de Chlorella vulgaris inhibieron el crecimiento de Bacillus cereus. Las ratas alimentadas con los polvos de Chlorella vulgaris y Spirulina platensis incrementaron el conteo de leucocitos y los valores de hemoglobina comparados con el grupo control (p<0,001). Las transaminasas (SGOT y SGPT) se encontraron en valores normales, pero con diferencias significativas entre los grupos (p<0,001). Conclusiones: Estos polvos son ricos en componentes fitoquímicos activos, pero solo los extractos de Chorella vulgaris mostraron efecto antibacteriano. No se encontraron signos de toxicidad aguda en ningún parámetro.


Subject(s)
Animals , Rats , Chlorella vulgaris/chemistry , Disk Diffusion Antimicrobial Tests , Phytochemicals , Plant Extracts/toxicity , Models, Animal
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