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Identification Of The Functional Binding Pocket For Compounds Targeting Small-Conductance Ca²⁺-Activated Potassium Channels., Miao Zhang, John M Pascal, Marcel Schumann, Roger S Armen, Ji-Fang Zhang

Department of Molecular Physiology and Biophysics Faculty Papers

Small- and intermediate-conductance Ca(2+)-activated potassium channels, activated by Ca(2+)-bound calmodulin, have an important role in regulating membrane excitability. These channels are also linked to clinical abnormalities. A tremendous amount of effort has been devoted to developing small molecule compounds targeting these channels. However, these compounds often suffer from low potency and lack of selectivity, hindering their potential for clinical use. A key contributing factor is the lack of knowledge of the binding site(s) for these compounds. Here we demonstrate by X-ray crystallography that the binding pocket for the compounds of the 1-ethyl-2-benzimidazolinone (1-EBIO) class is located at the calmodulin-channel interface. …

Curcumin-Loaded Magnetic Nanoparticles For Breast Cancer Therapeutics And Imaging Applications., Murali M. Yallapu, Shadi F. Othman, Evan Curtis, Nichole A. Bauer, Neeraj Chauhan, Deepak Kumar, Meena Jaggi, Subhash C. Chauhan

All Faculty Articles - School of Engineering and Computer Science

BACKGROUND: The next generation magnetic nanoparticles (MNPs) with theranostic applications have attracted significant attention and will greatly improve nanomedicine in cancer therapeutics. Such novel MNP formulations must have ultra-low particle size, high inherent magnetic properties, effective imaging, drug targeting, and drug delivery properties. To achieve these characteristic properties, a curcumin-loaded MNP (MNP-CUR) formulation was developed.

METHODS: MNPs were prepared by chemical precipitation method and loaded with curcumin (CUR) using diffusion method. The physicochemical properties of MNP-CUR were characterized using dynamic light scattering, transmission electron microscopy, and spectroscopy. The internalization of MNP-CUR was achieved after 6 hours incubation with MDA-MB-231 breast …

Quantitative And Qualitative Comparison Of A New Prosthetic Suspension System With Two Existing Suspension Systems For Lower Limb Amputees, A. Eshraghi, Noor Azuan Abu Osman, M.T. Karimi, H. Gholizadeh, S. Ali, Wan Abu Bakar Wan Abas

Research Publications (2011 to 2015)

OBJECTIVE: The objectives of this study were to compare the effects of a newly designed magnetic suspension system with that of two existing suspension methods on pistoning inside the prosthetic socket and to compare satisfaction and perceived problems among transtibial amputees. DESIGN: In this prospective study, three lower limb prostheses with three different suspension systems were fabricated for ten transtibial amputees. The participants used each of the three prostheses for 1 mo in random order. Pistoning inside the prosthetic socket was measured by motion analysis system. The Prosthesis Evaluation Questionnaire was used to evaluate satisfaction and perceived problems with each …

Clinical Evaluation Of Two Prosthetic Suspension Systems In A Bilateral Transtibial Amputee, Hossein Gholizadeh, Noor Azuan Abu Osman, Mojtaba Kamyab, Arezoo Eshraghi, Asa Gulaug Luviksdottir, Wan Abu Bakar Wan Abas

Research Publications (2011 to 2015)

The effects of Seal-In X5 and Dermo liner (Össur) on suspension and patient's comfort in lower limb amputees are unclear. In this report, we consider the case of a 51-yr-old woman with bilateral transtibial amputation whose lower limbs were amputated because of peripheral vascular disease. The subject had bony and painful residual limbs, especially at the distal ends. Two prostheses that used Seal-In X5 liners and a pair of prostheses with Dermo liners were fabricated, and the subject wore each for a period of 2 wks. Once the 2 wks had passed, the pistoning within the socket was assessed and …

Eeg Spectral Analysis On Muslim Prayers, H. Doufesh, T. Faisal, K.S. Lim, F. Ibrahim

Research Publications (2011 to 2015)

This study investigated the proposition of relaxation offered by performing the Muslim prayers by measuring the alpha brain activity in the frontal (F3-F4), central (C3-C4), parietal (P3-P4), and occipital (O1-O 2) electrode placements using the International 10-20 System. Nine Muslim subjects were asked to perform the four required cycles of movements of Dhuha prayer, and the EEG were subsequently recorded with open eyes under three conditions, namely, resting, performing four cycles of prayer while reciting the specific verses and supplications, and performing four cycles of acted salat condition (prayer movements without any recitations). Analysis of variance (ANOVA) tests revealed that …

Neuroangiogenesis: A Vascular Basis For Alzheimer's Disease And Cognitive Decline During Aging, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Angiogenesis directs development of the brain's microcirculation during antenatal and postnatal development, but its role later in life is less well recognized. I contend that during senescence a reduced cerebral capillary density accounts in part for the vascular cognitive impairment observed in many older persons and possibly for some forms of Alzheimer's disease. I propose that neuroangiogenesis is essential throughout adult life for maintaining the microcirculation of the cerebral cortex and elsewhere in the brain and that it commonly declines with old age. To support this hypothesis I have examined the neurological literature for relevant studies on cerebral capillary density …

Chronic Kidney Disease Is Associated With Increased Coronary Artery Atherosclerosis As Revealed By Multidetector Computed Tomographic Angiography, Sion K Roy, Albert Cespedes, Dong Li, Tae-Young Choi, Matthew J Budoff

The Texas Heart Institute Journal

Chronic kidney disease (CKD) is an independent risk factor for cardiovascular events. We evaluated whether multidetector computed tomographic angiography (MDCTA) revealed a link between pre-dialysis CKD and coronary artery atherosclerosis.

We retrospectively analyzed 549 patients who underwent MDCTA. Patients were divided into 3 groups: normal glomerular filtration rate (GFR) (GFR >90 mL/min/1.73 m2 body surface area), mild CKD (>60GFR≤90 mL/min/1.73 m2), and moderate CKD (>30GFR≤60 mL/min/1.73 m2). Normality testing was performed to determine if continuous variables were modeled in Gaussian distribution before analysis of variance was applied. The χ2 test was used to compare GFR subgroups. Multiple linear …

Adjusting For Under-Identification Of Aboriginal And/Or Torres Strait Islander Births In Time Series Produced From Birth Records: Using Record Linkage Of Survey Data And Administrative Data Sources, D Lawrence, D Christensen, F Mitrou, Glenn Draper, G Davis, S Mckeown, Daniel Mcaullay, G Pearson, S R Zubrick

Research outputs 2012

Background: Statistical time series derived from administrative data sets form key indicators in measuring progress in addressing disadvantage in Aboriginal and Torres Strait Islander populations in Australia. However, inconsistencies in the reporting of Indigenous status can cause difficulties in producing reliable indicators. External data sources, such as survey data, provide a means of assessing the consistency of administrative data and may be used to adjust statistics based on administrative data sources. Methods. We used record linkage between a large-scale survey (the Western Australian Aboriginal Child Health Survey), and two administrative data sources (the Western Australia (WA) Register of Births and …

Can Exercise Ameliorate Treatment Toxicity During The Initial Phase Of Testosterone Deprivation In Prostate Cancer Patients? Is This More Effective Than Delayed Rehabilitation?, Robert Newton, Dennis Taaffe, Nigel Spry, Prue Cormie, Suzanne Chambers, Robert Gardiner, David Shum, David Joseph, Daniel Galvao

Research outputs 2012

Background: There has been substantial increase in use of androgen deprivation therapy as adjuvant management of prostate cancer. However, this leads to a range of musculoskeletal toxicities including reduced bone mass and increased skeletal fractures compounded with rapid metabolic alterations, including increased body fat, reduced lean mass, insulin resistance and negative lipoprotein profile, increased incidence of cardiovascular and metabolic morbidity, greater distress and reduced quality of life. Numerous research studies have demonstrated certain exercise prescriptions to be effective at preventing or even reversing these treatment toxicities. However, all interventions to date have been of rehabilitative intent being implemented after a …

Effects Of Short-Term Training With Uncoupled Cranks In Trained Cyclists, Jack Burns, Jeremiah Peiffer, Chris Abbiss, Greig Watson, Angus Burnett, Paul Laursen

Research outputs 2012

Purpose: Manufacturers of uncoupled cycling cranks claim that their use will increase economy of motion and gross efficiency. Purportedly, this occurs by altering the muscle-recruitment patterns contributing to the resistive forces occurring during the recovery phase of the pedal stroke. Uncoupled cranks use an independentclutch design by which each leg cycles independently of the other (ie, the cranks are not fixed together). However, research examining the efficacy of training with uncoupled cranks is equivocal. The purpose of this study was to determine the effect of short-term training with uncoupled cranks on the performance-related variables economy of motion, gross efficiency, maximal …

Maternal Work Hours In Early To Middle Childhood Link To Later Adolescent Diet Quality, Jianghong Li, Therese O'Sullivan, Sarah Johnson, Fiona Stanley, Wendy H. Oddy

Research outputs 2012

Objective: Previous studies on maternal work hours and child diet quality have reported conflicting findings possibly due to differences in study design, lack of a comprehensive measure of diet quality and differing ages of the children under investigation. The present study aimed to prospectively examine the impact of parental work hours from age 1 year to age 14 years on adolescent diet quality.

Design: Multivariate linear regression models were used to examine independent associations between parents' work hours at each follow-up and across 14 years and adolescent diet quality at age 14 years. A diet quality index was based on …

Effects Of Two Contrast Training Programs On Jump Performance In Rugby Union Players During A Competition Phase, C K Argus, N D Gill, J W Keogh, Michael Mcguigan, W G Hopkins

Research outputs 2012

Purpose: There is little literature comparing contrast training programs typically performed by team-sport athletes within a competitive phase. We compared the effects of two contrast training programs on a range of measures in high-level rugby union players during the competition season. Methods: The programs consisted of a higher volume-load (strength-power) or lower volume-load (speed-power) resistance training; each included a tapering of loading (higher force early in the week, higher velocity later in the week) and was performed twice a week for 4 wk. Eighteen players were assessed for peak power during a bodyweight countermovement jump (BWCMJ), bodyweight squat jump (BWSJ), …

Prolonged Sedentary Time And Physical Activity In Workplace And Non-Work Contexts: A Cross-Sectional Study Of Office, Customer Service And Call Centre Employees, A A Thorp, G N Healy, E Winkler, B K Clark, P A Gardiner, N Owen, David Dunstan

Research outputs 2012

Background: To examine sedentary time, prolonged sedentary bouts and physical activity in Australian employees from different workplace settings, within work and non-work contexts.Methods: A convenience sample of 193 employees working in offices (131), call centres (36) and customer service (26) was recruited. Actigraph GT1M accelerometers were used to derive percentages of time spent sedentary (<100 counts per>minute; cpm), in prolonged sedentary bouts (≥20 minutes or ≥30 minutes), light-intensity activity (100-1951 cpm) and moderate-to-vigorous physical activity (MVPA; ≥1952 cpm). Using mixed models adjusted for confounders, these were compared for: work days versus non-work days; work hours versus non-work hours (work days only); …

Anxiety, Depression, And Comorbid Anxiety And Depression: Risk Factors And Outcome Over Two Years, O P Almeida, B Draper, J Pirkis, J Snowdon, N T Lautenschlager, G Byrne, Moira Sim, N Stocks, N Kerse, L Flicker, J J Pfaff

Research outputs 2012

Background: This study aimed to determine: (1) the prevalence of depression, anxiety, and depression associated with anxiety (DA); (2) the risk factor profile of depression, anxiety, and DA; (3) the course of depression, anxiety, and DA over 24 months. Methods: Two-year longitudinal study of 20,036 adults aged 60+ years. We used the Patient Health Questionnaire and the Hospital Anxiety and Depression Scale anxiety subscale to establish the presence of depression and anxiety, and standard procedures to collect demographic, lifestyle, psychosocial, and clinical data. Results: The prevalence of anxiety, depression, and DA was 4.7%, 1.4%, and 1.8%. About 57% of depression …

Olfactory Discrimination Predicts Cognitive Decline Among Community-Dwelling Older Adults, Hamid Sohrabi, Kristyn Bates, Mg Weinborn, A N Johnston, A Bahramian, Kevin Taddei, Simon Laws, Mark Rodrigues, Michael Morici, Matthew Howard, Georgia Martins, A Mackay-Sim, Se Gandy, Ralph Martins

Research outputs 2012

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46-86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions …

Viability Of Healthcare Service Delivery Alternatives For The Australian Mining Sector, Patricia Williams, Margaret Giles

Research outputs 2012

The changing and demanding nature of the mining workforce in rural and remote Australia brings unique challenges to the delivery of healthcare services. In an attempt to control costs whilst delivering cost effective and quality healthcare, new models of delivery must be considered. For a workforce that is fly-in/fly-out, the provision of healthcare is problematic given the lack of consistency in location. A cost-benefit framework is analysed comparing three models of service provision using travel to a major location, locum services and remote health monitoring. Ultimately, new models of care must be considered to address the issues of increasing workforce …

Changes In Dairy Food And Nutrient Intakes In Australian Adolescents, Carole Parker, Wendy Vivian, Wendy H. Oddy, Lawrie J Beilin, Trevor A. Mori, Therese O'Sullivan

Research outputs 2012

Dairy nutrients, such as calcium, are particularly important in adolescence, a critical time for growth and development. There are limited Australian data following individuals through adolescence, evaluating changes in dairy nutrient and dairy product consumption. We used a validated food frequency questionnaire to investigate consumption in adolescents participating in both the 14 and 17 year follow-ups of the Western Australian Pregnancy Cohort (Raine) Study. Most adolescents did not reach age and gender specific recommended daily intakes for calcium or magnesium at 14 years, and this decreased as they aged to 17 years (from 33.0% to 29.2% meeting for calcium, P < 0.05, and from 33.6% to 20.5% meeting for magnesium, P < 0.01). Mean intakes of calcium, potassium, riboflavin and vitamin A also decreased with age (P < 0.01). Mean dairy intake decreased from 536 ± 343 g/day to 464 ± 339 g/day (P < 0.01), due mostly to a decrease in regular milk, although flavoured milk consumption increased in boys. Cheese and butter were the only products to show a significantly increased consumption over the period. Girls decreased from 2.2 to 1.9 serves/day of dairy, while boys remained relatively steady at 2.9 to 2.8 serves/day. Our findings suggest that dairy product consumption decreases over adolescence. This may have implications for bone mass, development and later health.

Clinical And Biomarker Changes In Dominantly Inherited Alzheimer's Disease, R J Bateman, C Xiong, T L Benzinger, A M Fagan, A Goate, N C Fox, D S Marcus, N J Cairns, X Xie, T M Blazey, D M Holtzman, A Santacruz, V Buckles, A Oliver, K Moulder, P M Aisen, B Ghetti, W M Klunk, E Mcdade, Ralph Martins, C M Masters, R Mayeux, J M Ringman, M M Rossor, P M Schofield, R M Sperling, S Salloway, J M Morris

Research outputs 2012

Background: The order and magnitude of pathologic processes in Alzheimer's disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer's disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease.

Methods: In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant's age at baseline assessment and the parent's age at the onset of symptoms of Alzheimer's disease to …

Lifestyle And Late Life Cognitive Health: Sufficient Evidence To Act Now?, Bruce Barber, D Ames, Kathryn Ellis, Ralph Martins, C Masters, C Szoeke

Research outputs 2012

No abstract provided.

Two Maximal Isometric Contractions Attenuate The Magnitude Of Eccentric Exercise-Induced Muscle Damage, Hsin-Lian Chen, Kazunori Nosaka, Alan Pearce, Trevor C Chen

Research outputs 2012

This study investigated whether maximal voluntary isometric contractions (MVC-ISO) would attenuate the magnitude of eccentric exercise-induced muscle damage. Young untrained men were placed into one of the two experimental groups or one control group (n = 13 per group). Subjects in the experimental groups performed either two or 10 MVC-ISO of the elbow flexors at a long muscle length (20° flexion) 2 days prior to 30 maximal isokinetic eccentric contractions of the elbow flexors. Subjects in the control group performed the eccentric contractions without MVC-ISO. No significant changes in maximal voluntary concentric contraction peak torque, peak torque angle, range of …

A Randomised Trial Of Robotic And Open Prostatectomy In Men With Localised Prostate Cancer, Robert Gardiner, J Yaxley, G Coughlin, N Dunglison, S Occhipinti, S Younie, R Carter, S Williams, R J Medcraft, Bennett Nigel, M F Lavin, Suzanne Chambers

Research outputs 2012

Background: Prostate cancer is the most common male cancer in the Western world however there is ongoing debate about the optimal treatment strategy for localised disease. While surgery remains the most commonly received treatment for localised disease in Australia more recently a robotic approach has emerged as an alternative to open and laparoscopic surgery. However, high level data is not yet available to support this as a superior approach or to guide treatment decision making between the alternatives. This paper presents the design of a randomised trial of Robotic and Open Prostatectomy for men newly diagnosed with localised prostate cancer …

Chronic Low Back Pain Is Associated With Reduced Vertebral Bone Mineral Measures In Community-Dwelling Adults, Andrew Briggs, Leon Straker, Angus Burnett, John Wark

Research outputs 2012

Background: Chronic low back pain (CLBP) experienced in middle-age may have important implications for vertebral bone health, although this issue has not been investigated as a primary aim previously. This study investigated the associations between CLBP and dual energy X-ray absorptiometry (DXA)-derived vertebral bone mineral measures acquired from postero-anterior and lateral-projections, among community-dwelling, middle-aged adults. Methods. Twenty-nine adults with CLBP (11 male, 18 female) and 42 adults with no history of LBP in the preceding year (17 male, 25 female) were evaluated. Self-reported demographic and clinical data were collected via questionnaires. Areal bone mineral density (aBMD) was measured in the …

Intense Physical Activity Is Associated With Cognitive Performance In The Elderly, Belinda Brown, Jeremiah Peiffer, Hamid Sohrabi, Alinda Mondal, Veer Bala Gupta, Stephanie Rainey-Smith, Kevin Taddei, S Burnham, K Ellis, C Szoeke, C L Masters, D Ames, C Rowe, Ralph Martins

Research outputs 2012

Numerous studies have reported positive impacts of physical activity on cognitive function. However, the majority of these studies have utilised physical activity questionnaires or surveys, thus results may have been influenced by reporting biases. Through the objective measurement of routine levels of physical activity via actigraphy, we report a significant association between intensity, but not volume, of physical activity and cognitive functioning. A cohort of 217 participants (aged 60-89 years) wore an actigraphy unit for 7 consecutive days and underwent comprehensive neuropsychological assessment. The cohort was stratified into tertiles based on physical activity intensity. Compared with individuals in the lowest …

Tp53 Codon 72 Polymorphism Affects Accumulation Of Mtdna Damage In Human Cells, Serena Altilia, Aurelia Santoro, Davide Malagoli, Catia Lanzarini, Josué Adolfo Ballesteros Álvarez, Gianluca Galazzo, Donald Carl Porter, Paolina Crocco, Giuseppina Rose, Giuseppe Passarino, Igor Roninson, Claudio Franceschi, Stefano Salvioli

Faculty Publications

Human TP53 gene is characterised by a polymorphism at codon 72 leading to an Arginine-to-Proline (R/P) substitution. The two resulting p53 isoforms have a different subcellular localisation after stress (more nuclear or more mitochondrial for the P or R isoform, respectively). p53P72 variant is more efficient than p53R72 in inducing the expression of genes involved in nuclear DNA repair. Since p53 is involved also in mitochondrial DNA (mtDNA) maintenance, we wondered whether these p53 isoforms are associated with different accumulation of mtDNA damage. We observed that cells bearing p53R72 accumulate lower amount of mtDNA damage upon rotenone stress with respect …

Animal Cognition, The Importance Of Touch, And The Cit, Deirdre Yeater

Presidential Seminar on the Catholic Intellectual Tradition

A presentation of Professor Yeater's incorporation in her class PSCC103 of 5 in- class discussions comparing human and non-human species, particularly dolphins, with an emphasis on the Catholic Intellectual Tradition and the importance of touch. PSCC-103, The Human Community: The Individual and Society, is a 3 credit course which engages students in a study of the relationship between psychology – the science of human behavior and mental processes, and the Catholic intellectual tradition – which is characterized by rigorous intellectual inquiry and an openness to scientific ideas. This course aims to help us understand ourselves as human persons, as well …

Depression, Anxiety, And Symptom Profiles Among Female And Male Victims Of Sexual Violence, Ekta Choudhary, Merideth Smith, Robert M. Bossarte

Faculty & Staff Scholarship

No abstract provided.

Osteochondral Tissue Engineering: Scaffolds, Stem Cells And Applications., Patcharakamon Nooeaid, Vehid Salih, Justus P. Beier, Aldo R. Boccaccini

Peninsula Dental School

Osteochondral tissue engineering has shown an increasing development to provide suitable strategies for the regeneration of damaged cartilage and underlying subchondral bone tissue. For reasons of the limitation in the capacity of articular cartilage to self-repair, it is essential to develop approaches based on suitable scaffolds made of appropriate engineered biomaterials. The combination of biodegradable polymers and bioactive ceramics in a variety of composite structures is promising in this area, whereby the fabrication methods, associated cells and signalling factors determine the success of the strategies. The objective of this review is to present and discuss approaches being proposed in osteochondral …

Potential Role Of Plasma Myeloperoxidase Level In Predicting Long-Term Outcome Of Acute Myocardial Infarction, Mehmet Gungor Kaya, Ridvan Yalcin, Kaan Okyay, Fatih Poyraz, Nilufer Bayraktar, Hatice Pasaoglu, Bulent Boyaci, Atiye Cengel

The Texas Heart Institute Journal

We investigated the prognostic importance of plasma myeloperoxidase levels in patients with ST-elevation myocardial infarction (STEMI) at long-term follow-up, and we analyzed the correlations between plasma myeloperoxidase levels and other biochemical values.

We evaluated 73 consecutive patients (56 men; mean age, 56 ±11 yr) diagnosed with acute STEMI and 46 age- and sex-matched healthy control participants. Patients were divided into 2 groups according to the median myeloperoxidase level (Group 1: plasma myeloperoxidase ≤68 ng/mL; and Group 2: plasma myeloperoxidase >68 ng/mL). Patients were monitored for the occurrence of major adverse cardiovascular events (MACE), which were defined as cardiac death; reinfarction; …

Mid-Aortic Syndrome In A 3-Year-Old Girl Successfully Treated By Aorto-Aortic Grafting And Renal Artery Implantation Into The Graft, Tanja Kersnik Levart, Tomislav Klokocovnik

The Texas Heart Institute Journal

Mid-aortic syndrome, an uncommon acquired or congenital condition characterized by segmental narrowing of the abdominal or distal descending thoracic aorta, is frequently accompanied by ostial stenosis of the aorta's branches. If left untreated, it can result in life-threatening complications secondary to severe hypertension.

We report the case of a 3-year-old girl with congenital mid-aortic syndrome, who was diagnosed by chance in the course of a viral illness, and whose high blood pressure values were first dismissed as inaccurate. Attempts to achieve medical or endovascular control of her hypertension were unsuccessful. She was thereafter successfully treated by aorto–aortic bypass grafting, resection …

A Systematic Review Of Physical Activity Interventions In Hispanic Adults, Melinda J. Ickes, Manoj Sharma

Kinesiology and Health Promotion Faculty Publications

Healthy People 2020 aims to achieve health equity, eliminate disparities, and improve the health of all groups. Regular physical activity (PA) improves overall health and fitness and has the capability to reduce risk for chronic diseases. Identifying barriers which relate to the Hispanic population is important when designing PA interventions. Therefore, the purpose was to review existing PA interventions targeting Hispanic adults published between 1988 and 2011. This paper was limited to interventions which included more than 35% Hispanic adults (n = 20). Most of the interventions were community based (n = 16), although clinical, family-based, and faith-based …