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1.
Res Social Adm Pharm ; 20(6): 102-112, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38768989

ABSTRACT

BACKGROUND: Prescribing cascades can lead to unnecessary medication use, healthcare costs, and patient harm. Pharmacists oversee prescriptions from multiple prescribers and are well positioned to identify such cascades, making pharmacists key stakeholders to address them. OBJECTIVES: To evaluate community pharmacists' awareness, identification, and management of prescribing cascades and to assess behavioural determinants that may be targeted in future strategies to minimise inappropriate prescribing cascades. METHODS: An online survey was developed using the Theoretical Domains Framework (TDF) and emailed to all registered community pharmacists in Ireland (n = 3775) in November 2021. Quantitative data were analysed using descriptive and inferential statistics. Free-text sections were given to capture reasons for non-resolution of identified prescribing cascades and suggestions to aid prescribing cascade identification and management; this text underwent content analysis. RESULTS: Of the 220 respondents, 51% were aware of the term 'prescribing cascade' before the survey, whilst 69% had identified a potentially inappropriate prescribing cascade in practice. Over one third were either slightly confident (26.4%) or not confident at all (10%) in their ability to identify potentially inappropriate prescribing cascades in patients' prescriptions before the survey, whilst 55.2% were concerned that patients were receiving prescribing cascades they had not identified. Most respondents wanted further information/training to help prescribing cascade identification (88.3%) and management (86.1%). Four predominant TDF domains identified were common to both i) influencing non-resolution of identified prescribing cascades and ii) in the suggestions to help identify and manage prescribing cascades: 'Environmental Context and Resources', 'Social/Professional Role and Identity', 'Social Influences' and 'Memory, Attention and Decision Processes'. CONCLUSIONS: There is a clear need to provide additional resources to help community pharmacists identify and manage prescribing cascades. These findings will support the development of theory-informed behaviour change strategies to aid the minimisation of inappropriate prescribing cascades and decrease the risk of medication-related harm for patients.


Subject(s)
Community Pharmacy Services , Inappropriate Prescribing , Pharmacists , Humans , Community Pharmacy Services/organization & administration , Male , Inappropriate Prescribing/prevention & control , Female , Adult , Cross-Sectional Studies , Middle Aged , Surveys and Questionnaires , Ireland , Health Knowledge, Attitudes, Practice , Professional Role , Practice Patterns, Pharmacists' , Attitude of Health Personnel
2.
Cells ; 13(7)2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38607016

ABSTRACT

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of mono-genetic inherited neurological disorders, whose primary manifestation is the disruption of the pyramidal system, observed as a progressive impaired gait and leg spasticity in patients. Despite the large list of genes linked to this group, which exceeds 80 loci, the number of cellular functions which the gene products engage is relatively limited, among which endoplasmic reticulum (ER) morphogenesis appears central. Mutations in genes encoding ER-shaping proteins are the most common cause of HSP, highlighting the importance of correct ER organisation for long motor neuron survival. However, a major bottleneck in the study of ER morphology is the current lack of quantitative methods, with most studies to date reporting, instead, on qualitative changes. Here, we describe and apply a quantitative image-based screen to identify genetic modifiers of ER organisation using a mammalian cell culture system. An analysis reveals significant quantitative changes in tubular ER and dense sheet ER organisation caused by the siRNA-mediated knockdown of HSP-causing genes ATL1 and RTN2. This screen constitutes the first attempt to examine ER distribution in cells in an automated and high-content manner and to detect genes which impact ER organisation.


Subject(s)
Nervous System Diseases , Spastic Paraplegia, Hereditary , Animals , Humans , Membrane Proteins/metabolism , Membrane Transport Proteins/genetics , GTP-Binding Proteins/metabolism , Spastic Paraplegia, Hereditary/genetics , Mammals/metabolism
3.
Mult Scler J Exp Transl Clin ; 9(3): 20552173231197132, 2023.
Article in English | MEDLINE | ID: mdl-37674981

ABSTRACT

Fingolimod is a multiple sclerosis disease-modifying therapy which sequestrates lymphocytes in the lymph nodes, thereby reducing peripheral blood lymphocytes. Cryptococcal infection is an important adverse effect which should be recognised. We report a case of cutaneous and central nervous system infection who presented with isolated cutaneous symptoms in the absence of neurological or systemic manifestations.

4.
Qual Life Res ; 32(12): 3531-3545, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37522941

ABSTRACT

PURPOSE: This study aimed to investigate the supportive care needs of Australian melanoma patients and their caregivers to form the basis for improving services. METHODS: General and melanoma-related supportive care needs in melanoma patients were measured using the SCNS-SF34 and SCNS-M12 respectively, whereas caregivers completed the SCNS-P&C. Patients also completed the MCQ-28 and FCRI-9, with all participants completing the QLQ-C30, DASS-21, and questions measuring utilisation and preference for supportive health services. Multivariable stepwise logistic regression was used to identify variables associated with unmet needs in melanoma patients. RESULTS: A total of 56 early-stage patients, 100 advanced-stage patients, and 37 caregivers participated. At least three-quarters ([Formula: see text] 75%) of each participant group reported at least one unmet need. Of the ten most reported unmet needs in each participant group, at least six ([Formula: see text] 60%) were related to psychological and emotional well-being, with access to a psychologist the most desired service (> 25%). Fear of cancer recurrence was equally prevalent in both patient groups at a level indicative of need for intervention. Advanced-stage patients reported significantly (p < 0.05) more unmet psychological, physical and daily living, and sexuality needs, and significantly (p < 0.05) worse functioning than early-stage patients. CONCLUSION: Australian melanoma patients and caregivers report substantial unmet supportive care needs, particularly regarding their psychological and emotional well-being. Psychological and emotional well-being services, such as access to a clinical psychologist or implementation of patient-reported outcome measures, should be incorporated into routine melanoma care to address unmet patient and caregiver needs and improve well-being.


Subject(s)
Caregivers , Melanoma , Humans , Cross-Sectional Studies , Caregivers/psychology , Neoplasm Recurrence, Local , Surveys and Questionnaires , Australia , Quality of Life/psychology , Social Support , Health Services Needs and Demand
5.
Front Chem ; 10: 1000765, 2022.
Article in English | MEDLINE | ID: mdl-36465859

ABSTRACT

The plight of antimicrobial resistance continues to limit the availability of antibiotic treatment effective in combating resistant bacterial infections. Despite efforts made to rectify this issue and minimise its effects on both patients and the wider community, progress in this area remains minimal. Here, we de-novo designed a peptide named KDEON WK-11, building on previous work establishing effective residues and structures active in distinguished antimicrobial peptides such as lactoferrin. We assessed its antimicrobial activity against an array of bacterial strains and identified its most potent effect, against Pseudomonas aeruginosa with an MIC value of 3.12 µM, lower than its counterparts developed with similar residues and chain lengths. We then determined its anti-biofilm properties, potential mechanism of action and in vitro cytotoxicity. We identified that KDEON WK-11 had a broad range of antimicrobial activity and specific capabilities to fight Pseudomonas aeruginosa with low in vitro cytotoxicity and promising potential to express anti-lipopolysaccharide qualities, which could be exploited to expand its properties into an anti-sepsis agent.

6.
Nutrients ; 14(20)2022 Oct 18.
Article in English | MEDLINE | ID: mdl-36297048

ABSTRACT

Objective: To determine the impact of a family-based assessment-and-intervention healthy lifestyle programme on health knowledge and beliefs of children and families affected by obesity. Second, to compare the health knowledge of the programme cohort to those of a national cohort in Aotearoa/New Zealand (NZ). Design: This mixed-methods study collected health knowledge and health belief data in a questionnaire at baseline and 12-, 24-, and 60-month follow-up assessments. Health knowledge over time was compared with baseline knowledge and with data from a nationally representative survey. A data-driven subsumption approach was used to analyse open-text responses to health belief questions across the study period. Setting: Taranaki region, a mixed urban−rural setting in NZ. Participants: Participants (caregiver/child dyads) from the Whanau Pakari randomised trial. Results: A greater proportion of the cohort correctly categorised foods and drinks as healthy or unhealthy at 12 months compared to baseline for most questionnaire items. Retention of this health knowledge was evident at 24- and 60-month follow-ups. More than twice as many participants correctly reported physical activity recommendations at follow-up compared to baseline (p < 0.001). Health knowledge of participants was similar to the national survey cohort at baseline, but surpassed it at 12 and 24 months. Participant beliefs around healthy lifestyles related to physical functioning, mental and emotional wellbeing, and enhancement of appearance, and gained greater depth and detail over time. Conclusions: This study demonstrates the important role that community-level healthy lifestyle programmes can have in knowledge-sharing and health promotion.


Subject(s)
Pediatric Obesity , Child , Humans , Pediatric Obesity/prevention & control , Pediatric Obesity/psychology , Healthy Lifestyle , Health Promotion/methods , Behavior Therapy , Life Style
7.
Australas J Dermatol ; 63(4): e331-e335, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36125195

ABSTRACT

Optical Coherence Tomography (OCT) is a useful non-invasive diagnostic tool for diagnosing and monitoring treatment of basal cell carcinomas. We describe the use of OCT in a patient with Basal Cell Naevus Syndrome. Through measuring tumour depth on OCT, management of individual tumours was triaged accordingly using 0.4 mm tumour depth as a cut-off for surgical and non-surgical management. OCT has potential to reduce unnecessary excisions and associated morbidity in this population of patients.


Subject(s)
Basal Cell Nevus Syndrome , Carcinoma, Basal Cell , Skin Neoplasms , Humans , Skin Neoplasms/pathology , Basal Cell Nevus Syndrome/diagnostic imaging , Tomography, Optical Coherence/methods , Carcinoma, Basal Cell/pathology
8.
Acta Neuropathol Commun ; 10(1): 40, 2022 03 28.
Article in English | MEDLINE | ID: mdl-35346366

ABSTRACT

Hereditary spastic paraplegias (HSPs) are a group of inherited, progressive neurodegenerative conditions characterised by prominent lower-limb spasticity and weakness, caused by a length-dependent degeneration of the longest corticospinal upper motor neurons. While more than 80 spastic paraplegia genes (SPGs) have been identified, many cases arise from mutations in genes encoding proteins which generate and maintain tubular endoplasmic reticulum (ER) membrane organisation. The ER-shaping proteins are essential for the health and survival of long motor neurons, however the mechanisms by which mutations in these genes cause the axonopathy observed in HSP have not been elucidated. To further develop our understanding of the ER-shaping proteins, this study outlines the generation of novel in vivo and in vitro models, using CRISPR/Cas9-mediated gene editing to knockout the ER-shaping protein ADP-ribosylation factor-like 6 interacting protein 1 (ARL6IP1), mutations in which give rise to the HSP subtype SPG61. Loss of Arl6IP1 in Drosophila results in progressive locomotor deficits, emulating a key aspect of HSP in patients. ARL6IP1 interacts with ER-shaping proteins and is required for regulating the organisation of ER tubules, particularly within long motor neuron axons. Unexpectedly, we identified physical and functional interactions between ARL6IP1 and the phospholipid transporter oxysterol-binding protein-related protein 8 in both human and Drosophila model systems, pointing to a conserved role for ARL6IP1 in lipid homeostasis. Furthermore, loss of Arl6IP1 from Drosophila neurons results in a cell non-autonomous accumulation of lipid droplets in axonal glia. Importantly, treatment with lipid regulating liver X receptor-agonists blocked lipid droplet accumulation, restored axonal ER organisation, and improved locomotor function in Arl6IP1 knockout Drosophila. Our findings indicate that disrupted lipid homeostasis contributes to neurodegeneration in HSP, identifying a potential novel therapeutic avenue for the treatment of this disorder.


Subject(s)
Liver X Receptors , Spastic Paraplegia, Hereditary , Animals , Disease Models, Animal , Drosophila/metabolism , Endoplasmic Reticulum/metabolism , Humans , Liver X Receptors/agonists , Membrane Transport Proteins/genetics , Spastic Paraplegia, Hereditary/drug therapy , Spastic Paraplegia, Hereditary/genetics
9.
Front Neurosci ; 15: 784987, 2021.
Article in English | MEDLINE | ID: mdl-34867178

ABSTRACT

Optic atrophy (OA) with autosomal inheritance is a form of optic neuropathy characterized by the progressive and irreversible loss of vision. In some cases, this is accompanied by additional, typically neurological, extra-ocular symptoms. Underlying the loss of vision is the specific degeneration of the retinal ganglion cells (RGCs) which form the optic nerve. Whilst autosomal OA is genetically heterogenous, all currently identified causative genes appear to be associated with mitochondrial organization and function. However, it is unclear why RGCs are particularly vulnerable to mitochondrial aberration. Despite the relatively high prevalence of this disorder, there are currently no approved treatments. Combined with the lack of knowledge concerning the mechanisms through which aberrant mitochondrial function leads to RGC death, there remains a clear need for further research to identify the underlying mechanisms and develop treatments for this condition. This review summarizes the genes known to be causative of autosomal OA and the mitochondrial dysfunction caused by pathogenic mutations. Furthermore, we discuss the suitability of available in vivo models for autosomal OA with regards to both treatment development and furthering the understanding of autosomal OA pathology.

10.
BMC Bioinformatics ; 22(1): 427, 2021 Sep 08.
Article in English | MEDLINE | ID: mdl-34496765

ABSTRACT

BACKGROUND: In mammalian cells the endoplasmic reticulum (ER) comprises a highly complex reticular morphology that is spread throughout the cytoplasm. This organelle is of particular interest to biologists, as its dysfunction is associated with numerous diseases, which often manifest themselves as changes to the structure and organisation of the reticular network. Due to its complex morphology, image analysis methods to quantitatively describe this organelle, and importantly any changes to it, are lacking. RESULTS: In this work we detail a methodological approach that utilises automated high-content screening microscopy to capture images of cells fluorescently-labelled for various ER markers, followed by their quantitative analysis. We propose that two key metrics, namely the area of dense ER and the area of polygonal regions in between the reticular elements, together provide a basis for measuring the quantities of rough and smooth ER, respectively. We demonstrate that a number of different pharmacological perturbations to the ER can be quantitatively measured and compared in our automated image analysis pipeline. Furthermore, we show that this method can be implemented in both commercial and open-access image analysis software with comparable results. CONCLUSIONS: We propose that this method has the potential to be applied in the context of large-scale genetic and chemical perturbations to assess the organisation of the ER in adherent cell cultures.


Subject(s)
Endoplasmic Reticulum , Image Processing, Computer-Assisted , Animals , Cell Line , Humans , Software
11.
J Paediatr Child Health ; 57(12): 1942-1948, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34196427

ABSTRACT

AIM: Expert recommendations for child/adolescent obesity include extensive investigation for weight-related comorbidities, based on body mass index (BMI) percentile cut-offs. This study aimed to estimate the cost of initial investigations for weight-related comorbidities in children/adolescents with obesity, according to international expert guidelines. METHODS: The annual mean cost of investigations for weight-related comorbidities in children/adolescents was calculated from a health-funder perspective using 2019 cost data obtained from three New Zealand District Health Boards. Prevalence data for child/adolescent obesity (aged 2-14 years) were obtained from the New Zealand Health Survey (2017/2018), and prevalence of weight-related comorbidities requiring further investigation were obtained from a previous New Zealand study of a cohort of children with obesity. RESULTS: The cost of initial laboratory screening for weight-related comorbidities per child was NZD 28.36. Based on national prevalence data from 2018/2019 for children with BMI greater than the 98th percentile (obesity cut-off), the total annual cost for initial laboratory screening for weight-related comorbidities in children/adolescents aged 2-14 years with obesity was estimated at NZD 2,665,840. The cost of further investigation in the presence of risk factors was estimated at NZD 2,972,934. CONCLUSIONS: Investigating weight-related comorbidities in New Zealand according to international expert guidelines is resource-intensive. Ways to further determine who warrants investigation with an individualised approach are required.


Subject(s)
Pediatric Obesity , Adolescent , Body Mass Index , Child , Comorbidity , Humans , New Zealand/epidemiology , Pediatric Obesity/epidemiology , Prevalence
12.
Pediatr Obes ; 16(1): e12693, 2021 01.
Article in English | MEDLINE | ID: mdl-32959996

ABSTRACT

OBJECTIVE: To determine whether 12-month BMI SDS reductions persisted at 24 months in a multi-disciplinary assessment and intervention program for children and adolescents with obesity, and whether secondary outcomes improved. METHODS: This was a community-based 12-month RCT in Aotearoa/New Zealand. Eligible participants were aged 5 to 16 years with BMI ≥98th centile or BMI >91st centile with weight-related comorbidities. The low-intensity control received comprehensive home-based baseline assessments and advice, and 6-monthly follow-up. The high-intensity intervention received the same assessments and advice, but also weekly multidisciplinary sessions. Primary outcome was BMI SDS at 12 months. Secondary outcomes included cardiovascular and metabolic markers. RESULTS: 121 participants (60% of participants at baseline) were assessed at 24 months. BMI SDS reduction at 12 months was lost at 24 months in the modified intention-to-treat analysis [Control -0.03 (95%CI -0.14, 0.09) and Intervention -0.02 (-0.12, 0.08); P = .93]. However, sweet drink intake was reduced, water intake increased, and there were improvements in cardiovascular fitness in the high-intensity intervention. ≥70% attendance in the high-intensity intervention resulted in a persistent BMI SDS reduction of -0.22 after 24 months (95%CI -0.38, -0.06). CONCLUSIONS: This trial was negative in terms of primary outcome at 24 months. However, high engagement led to sustained treatment effect, and there were multiple improvements in health measures.


Subject(s)
Pediatric Obesity/diagnosis , Pediatric Obesity/therapy , Weight Reduction Programs/methods , Adolescent , Body Mass Index , Child , Child, Preschool , Female , Follow-Up Studies , Health Behavior , Humans , Intention to Treat Analysis , Linear Models , Male , New Zealand , Pediatric Obesity/psychology , Treatment Outcome , Weight Reduction Programs/organization & administration
13.
J Healthc Qual ; 43(2): 67-75, 2021.
Article in English | MEDLINE | ID: mdl-32568811

ABSTRACT

OBJECTIVE: Caesarean section surgical site infection (SSI) is a surgical wound site infection occurring within 30 days of surgery with a reported incidence of 3-15%. This quality improvement (QI) project aimed to reduce caesarean section SSI by 50% in a tertiary maternity center. METHODS: Using multidisciplinary team approach, the project was designed with evidence-based interventions. The Royal College of Physicians of Ireland/Royal College of Surgeons in Ireland "Preventing Surgical Site Infections Key Recommendations for Practice" guideline was used as standard perioperative care. A care bundle was designed targeting preoperative personal patient preparation, preoperative prophylactic antibiotics, and strict skin preparation technique, all measured using a patient survey. The rate of SSI was followed for 14 months. The Model for Improvement methodology was used to implement change. RESULTS: Surgical site infection rate decreased from 6.7% (n = 684 caesarean sections, n = 46 SSI) to 3.45% (n = 3,206 caesarean sections, n = 110 SSI), p = .0006. Reduction occurred in both elective (4.4%-2.7%) and emergency (9.1%-4.1%) caesarean section groups. There was excellent adherence to all three elements of the care bundle. The 50% reduction in caesarean section SSI was sustained over the 14-month period, significantly reducing maternal morbidity. CONCLUSIONS: The success of this QI project is attributable to frontline ownership and empowerment of patients and staff.


Subject(s)
Cesarean Section , Surgical Wound Infection , Female , Humans , Perioperative Care , Pregnancy , Quality Improvement , Surgical Wound Infection/prevention & control
14.
Brain Sci ; 10(9)2020 Sep 17.
Article in English | MEDLINE | ID: mdl-32957716

ABSTRACT

Mitochondrial morphology, distribution and function are maintained by the opposing forces of mitochondrial fission and fusion, the perturbation of which gives rise to several neurodegenerative disorders. The large guanosine triphosphate (GTP)ase dynamin-related protein 1 (Drp1) is a critical regulator of mitochondrial fission by mediating membrane scission, often at points of mitochondrial constriction at endoplasmic reticulum (ER)-mitochondrial contacts. Hereditary spastic paraplegia (HSP) subtype SPG61 is a rare neurodegenerative disorder caused by mutations in the ER-shaping protein Arl6IP1. We have previously reported defects in both the ER and mitochondrial networks in a Drosophila model of SPG61. In this study, we report that knockdown of Arl6IP1 lowers Drp1 protein levels, resulting in reduced ER-mitochondrial contacts and impaired mitochondrial load at the distal ends of long motor neurons. Increasing mitochondrial fission, by overexpression of wild-type Drp1 but not a dominant negative Drp1, increases ER-mitochondrial contacts, restores mitochondrial load within axons and partially rescues locomotor deficits. Arl6IP1 knockdown Drosophila also demonstrate impaired autophagic flux and an accumulation of ubiquitinated proteins, which occur independent of Drp1-mediated mitochondrial fission defects. Together, these findings provide evidence that impaired mitochondrial fission contributes to neurodegeneration in this in vivo model of HSP.

15.
J Clin Microbiol ; 58(7)2020 06 24.
Article in English | MEDLINE | ID: mdl-32295892

ABSTRACT

Members of the Mycobacterium abscessus complex (MABC) are multidrug-resistant nontuberculous mycobacteria and cause opportunistic pulmonary infections in individuals with cystic fibrosis (CF). In this study, genomic analysis of MABC isolates was performed to gain greater insights into the epidemiology of circulating strains in Ireland. Whole-genome sequencing (WGS) was performed on 70 MABC isolates that had been referred to the Irish Mycobacteria Reference Laboratory between 2006 and 2017 across nine Irish health care centers. The MABC isolates studied comprised 52 isolates from 27 CF patients and 18 isolates from 10 non-CF patients. WGS identified 57 (81.4%) as M. abscessus subsp. abscessus, 10 (14.3%) as M. abscessus subsp. massiliense, and 3 (4.3%) as M. abscessus subsp. bolletii Forty-nine (94%) isolates from 25 CF patients were identified as M. abscessus subsp. abscessus, whereas 3 (6%) isolates from 2 CF patients were identified as M. abscessus subsp. massiliense Among the isolates from non-CF patients, 44% (8/18) were identified as M. abscessus subsp. abscessus, 39% (7/18) were identified as M. abscessus subsp. massiliense, and 17% (3/18) were identified as M. abscessus subsp. bolletii WGS detected two clusters of closely related M. abscessus subsp. abscessus isolates that included isolates from different CF centers. There was a greater genomic diversity of MABC isolates among the isolates from non-CF patients than among the isolates from CF patients. Although WGS failed to show direct evidence of patient-to-patient transmission among CF patients, there was a predominance of two different strains of M. abscessus subsp. abscessus Furthermore, some MABC isolates were closely related to global strains, suggesting their international spread. Future prospective real-time epidemiological and clinical data along with contemporary MABC sequence analysis may elucidate the sources and routes of transmission among patients infected with MABC.


Subject(s)
Mycobacterium Infections, Nontuberculous , Mycobacterium abscessus , Genomics , Humans , Ireland/epidemiology , Mycobacterium Infections, Nontuberculous/epidemiology , Mycobacterium abscessus/genetics , Nontuberculous Mycobacteria/genetics
17.
J Nutr Educ Behav ; 52(5): 528-534, 2020 05.
Article in English | MEDLINE | ID: mdl-31780274

ABSTRACT

OBJECTIVE: To understand facilitators and barriers to engagement in a multidisciplinary assessment and intervention program for children and adolescents with obesity, particularly for Maori, the Indigenous people of New Zealand. METHODS: Whanau Pakari participants and caregivers (n = 71, 21% response rate) referred to the family-based healthy lifestyles program in Taranaki, New Zealand, were asked to participate in a confidential survey, which collected self-reported attendance levels and agreement with statements around service accessibility and appropriateness and open-text comments identifying barriers and facilitators to attendance. RESULTS: Self-reported attendance levels were higher when respondents reported sessions to be conveniently located (P = .03) and lower when respondents considered other priorities as more important for their family (P = .02). Maori more frequently reported that past experiences of health care influenced their decision to attend (P = .03). Facilitators included perceived convenience of the program, parental motivation to improve child health, and ongoing support from the program. CONCLUSIONS AND IMPLICATIONS: Program convenience and parental and/or self-motivation to improve health were facilitators of attendance. Further research is required to understand the relationship between past experiences with health care and subsequent engagement with services.


Subject(s)
Health Knowledge, Attitudes, Practice , Health Promotion , Health Services Accessibility/statistics & numerical data , Healthy Lifestyle , Adolescent , Child , Female , Humans , Male , Motivation , New Zealand , Parents , Pediatric Obesity , Surveys and Questionnaires
18.
Front Neurosci ; 13: 1051, 2019.
Article in English | MEDLINE | ID: mdl-31680803

ABSTRACT

The hereditary spastic paraplegias (HSPs) are a group of inherited neurodegenerative conditions whose characteristic feature is degeneration of the longest axons within the corticospinal tract which leads to progressive spasticity and weakness of the lower limbs. Though highly genetically heterogeneous, the majority of HSP cases are caused by mutations in genes encoding proteins that are responsible for generating and organizing the tubular endoplasmic reticulum (ER). Despite this, the role of the ER within neurons, particularly the long axons affected in HSP, is not well understood. Throughout axons, ER tubules make extensive contacts with other organelles, the cytoskeleton and the plasma membrane. At these ER contacts, protein complexes work in concert to perform specialized functions including organelle shaping, calcium homeostasis and lipid biogenesis, all of which are vital for neuronal survival and may be disrupted by HSP-causing mutations. In this article we summarize the proteins which mediate ER contacts, review the functions these contacts are known to carry out within neurons, and discuss the potential contribution of disruption of ER contacts to axonopathy in HSP.

19.
Article in English | MEDLINE | ID: mdl-31262760

ABSTRACT

Mycobacterium chimaera is a slow-growing nontuberculous Mycobacterium species belonging to the Mycobacterium avium complex (MAC). It has been identified globally as the cause of a large outbreak of cardiovascular infections following open heart surgery, but it can also cause respiratory infections in individuals with underlying structural pulmonary disease. Invasive M. chimaera infections are associated with poor clinical responses, and the optimal antibiotic treatment regimen for these infections is not known. In this study, the drug susceptibility profiles of clinical and environmental M. chimaera isolates for antimicrobial agents that are commonly considered for treatment of MAC infections were determined. All M. chimaera isolates were susceptible to clarithromycin, with a median MIC of 2 µg/ml, while 98% (85/87 isolates) were susceptible to amikacin. Twenty-five percent of isolates (22/87 isolates) had intermediate susceptibility and 52% (46/87 isolates) were resistant to moxifloxacin. Similarly, 39% of isolates (34/87 isolates) had intermediate susceptibility and 39% (34/87 isolates) were resistant to linezolid. MIC breakpoints derived from the literature were used to determine resistance to rifampin (16/87 isolates [18%]), ethambutol (10/87 isolates [11%]), rifabutin (2/87 isolates [2%]), and streptomycin (1/87 isolates [1%]). In conclusion, our results showed that clarithromycin, amikacin, rifabutin, and streptomycin had the best activity against M. chimaera isolates, while susceptibility rates were lower for rifampin and ethambutol. In contrast, there was a high prevalence of isolates that were not susceptible to moxifloxacin or linezolid. While factors in addition to antibiotic susceptibility may determine the outcomes of treatment of M. chimaera infections, our results should inform the selection of antimicrobials as part of the overall therapeutic strategy.


Subject(s)
Mycobacterium avium Complex/drug effects , Mycobacterium/drug effects , Amikacin/pharmacology , Ethambutol , Linezolid/pharmacology , Microbial Sensitivity Tests , Moxifloxacin/pharmacology , Rifampin/pharmacology , Streptomycin/pharmacology
20.
Australas J Dermatol ; 59(2): 118-123, 2018 May.
Article in English | MEDLINE | ID: mdl-28425573

ABSTRACT

BACKGROUND/OBJECTIVES: Patient information leaflets (PILs) are frequently provided to patients following dermatological surgery to provide advice and reassurance in the community. This evaluation reviewed the guidance specified in postoperative PILs across the 40 Australian dermatology teaching departments and clinics. METHODS: All 40 departments and clinics were identified and asked to provide their postoperative information leaflets on sutured wound care (preferable) or excision biopsy (September-October 2015). For each PIL, 10 preselected parameters were evaluated. RESULTS: In total, 28/40 (70%) of units responded. From these units, 11/28 (39.3%) stated they do not use a postoperative PIL. Of the 17 units that provided PILs, the mode minimum dressing duration was 24 (6/17; 35.3%) and 48 h (6/17; 35.3%). For haemostatic advice, 12 PILs specified the time to press on a bleeding wound, with the most common advice being 10 (3/12; 25%) and 20 min (3/12; 25%). Of the 14 PILs that provided analgesic advice, the mode information suggested using paracetamol only and avoiding aspirin (4/14, 28.6%). Two or more signs of infection were stated in 11/17 (64.7%) PILs; 7/17 (41.2%) advised applying petroleum jelly to the wound, almost all PILs highlighted the contact for postoperative problems 16/17 (94.1%), and 5/17 (29.4%) leaflets mentioned scarring. Altogether 8/17 (47.1%) of PILs advised on the timeframe until active exercise could resume postoperatively. CONCLUSION: Guidance provided in Australian postoperative dermatological PILs is heterogeneous. A consensus checklist or template would be beneficial and ensure that advice provided to patients is more consistent; this could be adapted for local factors.


Subject(s)
Dermatologic Surgical Procedures , Pamphlets , Patient Education as Topic/standards , Postoperative Care , Surgical Wound/therapy , Analgesics/therapeutic use , Australia , Bandages , Dermatologic Surgical Procedures/adverse effects , Hemorrhage/therapy , Humans , Infections/diagnosis , Pain, Postoperative/drug therapy , Surgical Wound/complications
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