Search

Human promoter polymorphisms in the chemokine co-receptor 5 gene (CCR5) have been noted for association with mother-to-child transmission of HIV (HIV MTCT) as well as reduced receptor expression in vitro, but have not been clearly associated with CCR5 expression in vivo. Placental expression of CCR5 may be influenced by such polymorphisms as well as other in vivo regulatory factors.We evaluated the associations between infant CCR5 polymorphisms, measures of maternal infection, and placental expression of CCR5 among mother-infant pairs in Blantyre, Malawi. RNA was extracted from placental tissue and used in multiplex real-time PCR to quantify gene expression. Through linear regression, we observed that CCR5-2554T (beta = -0.67, 95% CI = -1.23, -0.11) and -2132T (beta = -0.75, 95% CI = -0.131, -0.18) were significantly associated with reduced placental expression of CCR5. An incremental increase in CCR5 expression was observed for incremental increases in expression of two heparan sulfate genes involved in viral infection, HS3ST3A1 (beta = 0.27, 95% CI = 0.18, 0.35) and HS3ST3B1 (beta = 0.11, 95% CI = 0.06, 0.18). Among HIV infected mothers, an incremental increase in maternal HIV viral load was also associated with higher CCR5 expression (beta = 0.76, 95% CI = 0.12, 1.39). Maternal HIV status had no overall effect (beta = 0.072, 95% CI = -0.57, -0.72). Higher CCR5 expression was observed for mothers with malaria but was not statistically significant (beta = 0.37, 95% CI = -0.43, 1.18).These results provide in vivo evidence for genetic and environmental factors involved in the regulation of CCR5 expression in the placenta. Our findings also suggest that the measurement of placental expression of CCR5 alone is not an adequate indicator of the risk of mother-to-child transmission of HIV.

BACKGROUND:Since the pioneering study by Rosch and colleagues in the 70s, it is commonly agreed that basic level perceptual categories (dog, chair...) are accessed faster than superordinate ones (animal, furniture...). Nevertheless, the speed at which objects presented in natural images can be processed in a rapid go/no-go visual superordinate categorization task has challenged this "basic level advantage". PRINCIPAL FINDINGS:Using the same task, we compared human processing speed when categorizing natural scenes as containing either an animal (superordinate level), or a specific animal (bird or dog, basic level). Human subjects require an additional 40-65 ms to decide whether an animal is a bird or a dog and most errors are induced by non-target animals. Indeed, processing time is tightly linked with the type of non-targets objects. Without any exemplar of the same superordinate category to ignore, the basic level category is accessed as fast as the superordinate category, whereas the presence of animal non-targets induces both an increase in reaction time and a decrease in accuracy. CONCLUSIONS AND SIGNIFICANCE:These results support the parallel distributed processing theory (PDP) and might reconciliate controversial studies recently published. The visual system can quickly access a coarse/abstract visual representation that allows fast decision for superordinate categorization of objects but additional time-consuming visual analysis would be necessary for a decision at the basic level based on more detailed representations.

The Semantic Differential as a telephone survey technique. The public image of an organisation plays an important role in the success thereof since it continually determines whether the environment reacts favourably or unfavourably towards it. It is therefore important to be aware of the public image of an organisation, and which methods can be used to determine it. This study compared two attitude scales (a Likert type mail questionnaire and a Semantic Differential type telephone questionnaire) which can be used in the determination of an organisation's image. A comparison of the two scales produced significant results. These results indicate that a Semantic Differential type scale can be used successfully in telephone surveys. Opsomming Die openbare beeld van 'n organisasie speel 'n belangrike rol in die sukses daarvan aangesien dit deurentyd bepaal of die omgewing gunstig of ongunstig daarteenoor reageer. Dit is gevolglik belangrik dat bestuur kennis neem van die openbare beeld van sy organisasie en hoe daardie beeld bepaal kan word. Met hierdie studie is twee houdingskale ('n Likert-tipe posvraelys en 'n Semantiese Differensiaal-tipe telefoonvraelys) wat in die bepaling van 'n openbare beeld gebruik word, vergelyk. Die bevindinge dui daarop dat 'n aangepaste Semantiese Differensiaal met sukses gebruik kan word in telefoononderhoude.

Objective: Before June 2022, the treatment cost of Burkitt lymphoma (BL) in Ghana was mainly borne by the child's family or caregiver. We determined the treatment cost of BL in children and its psychological impact on parents and caregivers., Method: This prospective observational study assessed the direct medical and nonmedical costs (US dollars [USD]) incurred during the treatment of a child with BL for 6 consecutive months using a cost diary. Productivity losses and the psychological impact on parents and caregivers were assessed using a self-administered questionnaire and the Caregiver Quality of Life Index-Cancer (CQOLC)., Results: Of the 25 participants, 7 abandoned the treatment of their children, and 4 withdrew because the children passed away. The median (Q1, Q3) cost for treating BL per child for caregivers/parents (N = 12) was USD 947.42 (USD 763.03, USD 1953.05). Direct medical costs formed 71% (USD 11 458.97) of total treatment costs. Working hours of parents before the child's cancer diagnosis decreased from a median (Q1, Q3) of 44.00 (20.00, 66.00) hours to 1.50 (0, 20.00) hours after the diagnosis. The mean (SD) CQOLC score was 107.92 (15.89), with higher scores in men (111.00 [17.26]), married participants (111.26 [17.29]), Higher National Diploma certificate holders (113.00 [1.41]), and participants earning a monthly income more than USD 84.60., Conclusion: Treatment costs reduced the overall household income of 5 families. Parents and caregivers experienced reduced work hours and loss of employment. CQOLC scores were higher in married participants, those with a higher educational background, and those with higher income., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Accurate epidemiological data are vital in estimating the burden of disease in a country. Little is known about the incidence of childhood cancer in Ghana. This study describes the incidence patterns of cancer in children below 14 years and 11 months from 2015 to 2019 at the only two main pediatric cancer referral centers in Ghana: Korle Bu Teaching Hospital (KBTH) and Komfo Anokye Teaching Hospital (KATH)., Method: Data on the incidence of cancer in children below 14 years and 11 months were collected retrospectively between 1st January 2015 and 31st December 2019 from patients' medical folders at KBTH and the cancer registry at the pediatric units of KATH. Descriptive statistics were used to describe the data. Incident rates expressed as age-specific rates (ASRs) per 100,000 person-years using population estimates for age groups and sex in each year, were determined by age groups (0-4, 5-9, 10-14 years and 11 months), sex, region of residence and cancer types based on the International Childhood Cancer Classification, third edition., Results: The total ASR per 100,000 person-years from 2015 to 2019 was 9.36 based on 1073 cases observed. The ASR increased from 1.6 per 100,000 person-years in 2015-2.41 in 2017, thereafter decreasing to 1.45 in 2019. The ASR was higher in male children (2.10 per 100,000 person-years), children between 0 and 4 years (0.27 per 100,000 person-years), and children living in the Greater Accra region (4.17 per 100,000 person-years). The most prevalent cancers were lymphomas (2.17 per 100,000 person-years) and leukemia (1.88 per 100,000 person-years)., Conclusion: The study provides baseline information on the incidence patterns of childhood cancer from 2015 to 2019, addressing a critical gap in childhood cancer epidemiology in Ghana., Competing Interests: Declaration of Competing Interest The authors have no competing interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Worldwide, the leading cause of invasive candidiasis and the fourth leading cause of hospital-acquired infections are the Candida species (spp.) group. One of the most important tools in fighting such drug-resistant fungi is the appropriate use of antifungal agents., Objectives: The study aimed to determine echinocandins' general prescribing patterns and how they are associated with the treatment period., Method: A quantitative, observational, and descriptive was used, and included patients receiving antifungal treatment in a private hospital in Gauteng, South Africa between 01 January 2015 to 31 December 2015., Results: Of the 146 patient files included, 102 patients (69.9%) received caspofungin and 44 patients (30.1%) were treated with anidulafungin. For the former, 99 (97.1%) patients received a loading dose (LD) of 70 mg, while 200 mg anidulafungin was only prescribed to 30 patients (68.2%). In line with maintenance dose guidelines, the majority (98.1%) of caspofungin-treated patients received 50 mg IV daily, whereas 4 (3.9%) patients were treated at higher doses (70 mg daily). Anidulafungin was administered at various maintenance doses, including 400 mg (2.3% of patients), 200 mg (52.3%), 100 mg (43.2%) and 50 mg (2.3%) IV daily., Conclusion: Our results can be utilised to produce a hospital-specific algorithm in terms of Candida-infected patients., Contribution: These findings contribute to our understanding of prescribing patterns of antifungal agents and the impact thereof on treating Candida spp. Infections., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2023. The Authors.)

Sexually transmitted infections (STIs) should form part of the comprehensive healthcare agenda for adolescents and young people (A&Y) and testing plays a strategic role in STI prevention. However, little attention has been paid to the social and programmatic obstacles to this practice among A&Y. The aim of this study is to describe the prevalence of testing for syphilis and HIV reported by a group of A&Y, analyzing its relationship with variables potentially indicative of inequities related to vulnerability to STIs. This was a cross-sectional survey applied to students at public high schools in three cities in the state of São Paulo, Brazil. The responses of 369 young people who reported having started sexual life were analyzed. The analysis included description of the frequencies of demographic and socioeconomic variables and their associations with testing for syphilis and HIV through the chi-square test. The concentration index (CI) was also calculated, with construction of the respective concentration curve for the associated variables. Positive associations were found between occurrence of testing and living in homes with up to three inhabitants, living in a marital situation with a regular or committed partnership, previous use of primary care services and previous use of hospitals or emergency services. The concentration curve for testing STIs showed significant contributions from the associated variables. The findings indicated that situations of inequity need to be addressed in order to reduce A&Y's vulnerability to STIs., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Facioscapulohumeral dystrophy (FSHD) is caused by mutations leading to the aberrant expression of the DUX4 transcription factor in muscles. DUX4 was proposed to induce cell death, but the involvement of different death pathways is still discussed. A possible pro-apoptotic role of DUX4 was proposed, but as FSHD muscles are characterized by necrosis and inflammatory infiltrates, non-apoptotic pathways may be also involved., Methods: We explored DUX4-mediated cell death by focusing on the role of one regulated necrosis pathway called necroptosis, which is regulated by RIPK3. We investigated the effect of necroptosis on cell death in vitro and in vivo experiments using RIPK3 inhibitors and a RIPK3-deficient transgenic mouse model., Results: We showed in vitro that DUX4 expression causes a caspase-independent and RIPK3-mediated cell death in both myoblasts and myotubes. In vivo, RIPK3-deficient animals present improved body and muscle weights, a reduction of the aberrant activation of the DUX4 network genes, and an improvement of muscle histology., Conclusions: These results provide evidence for a role of RIPK3 in DUX4-mediated cell death and open new avenues of research., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Introduction: Class III malocclusions are some of the most difficult occlusal anomalies to be treated. Some patients with this condition may require orthognathic surgery, while others may be treated with dental camouflage. Proper patient assessment and selection remains critical in order to achieve favorable results., Objectives: This report outlines the case of an 18-year-old male who sought retreatment for a severe skeletal Class III dentofacial deformity after undergoing orthodontic camouflage treatment involving mandibular arch extractions. A treatment plan comprising dental decompensation and orthognathic surgery was implemented in order to achieve optimal facial and occlusal results., Results: After 28 months of treatment, skeletal and dental correction was achieved and facial features were significantly improved. The orthognathic surgery required a 20-mm sagittal maxillomandibular skeletal correction, combined with a 4-mm correction of the midlines and a 2-mm impaction of the maxilla., Conclusion: Dental compensation may be a risky treatment alternative for severe dentoskeletal discrepancies. In these patients, orthodontics combined with orthognathic surgery is the recommended treatment option.

Purpose: To evaluate the outcome of SPOT scleral lenses in the management of irregular astigmatism in patients with corneal ectasia and penetrating keratoplasty. Second, we analyzed patients' characteristics and tolerance, comfort, and geometries of fitted lenses., Method: Over a 5-year period, we included patients experiencing irregular astigmatism fitted with SPOT scleral contact lenses, from the University Hospital of Clermont-Ferrand, France. Data collected included corneal diseases, refractive error, best-corrected visual acuity (VA) with SPOT lenses, geometry of the lens, number of adjustment consultations, and the duration of follow-up. Comfort, quality of vision, less handling, and satisfaction were evaluated using visual analog scales after a 6-month follow-up period., Results: Sixty-five patients were included, analyzing 107 eyes. Eighty percent of patients still daily wore lenses after a follow-up of 22.3±13.8 months. Visual acuity improved by 0.47±0.51 logarithm of the minimum angle of resolution (average increase of 5 lines) (P<0.001) after wearing scleral lenses. Comfort, quality of vision, less handling, and satisfaction of contact lenses were excellent (>75/100). Contact lenses were daily worn 10.0±4.1 hr/day. Most patients wore size M (17 mm) lenses (53.3% of patients), with an average sagittal height of 5.2±1.2 mm. Internal toricity was used in 30% of cases. Best geometry was found after 2.69±0.87 consultations., Conclusion: SPOT scleral contact lenses are an effective and well tolerated method to improve the VA of patients with irregular astigmatism., Competing Interests: The authors have no funding or conflict of interest to disclose., (Copyright © 2021 Contact Lens Association of Ophthalmologists.)

Facioscapulohumeral dystrophy (FSHD, OMIM: 158900, 158901) is the most common dystrophy in adults and so far, there is no treatment. Different loci of the disease have been characterized and they all lead to the aberrant expression of the DUX4 protein, which impairs the function of the muscle, ultimately leading to cell death. Here, we used gene editing to try to permanently shut down DUX4 expression by targeting its poly(A) sequence. We used transcription activator-like effector nucleases (TALEN) and CRISPR-Cas9 nucleases in vitro on FSHD myoblasts. More than 150 TOPO clones were sequenced and only indels were observed in 4%. Importantly, in 2 of them, the DUX4 poly(A) signal was eliminated at the genomic level but DUX4 mRNA was still produced thanks to the use of a non-canonical upstream poly(A) signal sequence. These experiments show that targeting DUX4 PAS at the genomic level might not be an appropriate gene editing strategy for FSHD therapy.

Facioscapulohumeral dystrophy (FSHD) is characterized by a loss of repressive epigenetic marks leading to the aberrant expression of the DUX4 transcription factor. In muscle, DUX4 acts as a poison protein though the induction of multiple downstream genes. So far, there is no therapeutic solution for FSHD. Because DUX4 is a transcription factor, we developed an original therapeutic approach, based on a DNA decoy trapping the DUX4 protein, preventing its binding to genomic DNA and thereby blocking the aberrant activation of DUX4's transcriptional network. In vitro , transfection of a DUX4 decoy into FSHD myotubes reduced the expression of the DUX4 network genes. In vivo , both double-stand DNA DUX4 decoys and adeno-associated viruses (AAVs) carrying DUX4 binding sites reduced transcriptional activation of genes downstream of DUX4 in a DUX4-expressing mouse model. Our study demonstrates, both in vitro and in vivo , the feasibility of the decoy strategy and opens new avenues of research., Competing Interests: A patent named “Treatment of facioscapulohumeral dystrophy” has been filed and includes J.D., V.M. and T.V. as named inventors. The remaining authors declare no competing interests., (© 2020 The Authors.)

Background: Transgenic animals are widely used for research and for most of them, genotyping is unavoidable. Published protocols may be powerful but may also present disadvantages such as their cost or the requirement of additional steps/equipment. Moreover, if more than one strain must be genotyped, several protocols may need to be developed., Methods: we adapted the existing amplification-resistant mutation protocol to develop the 1-h universal genotyping protocol (1-HUG), which allows the robust genotyping of genetically modified mice in 1 h from sample isolation to polymerase chain reaction gel running., Results: This protocol allows the genotyping of different mouse models including mdx mouse, and FLExDUX4 and HSA-MerCreMer alone or in combination. It can be applied to different types of genomic modifications and to sexing., Conclusions: The 1-HUG protocol can be used routinely in any laboratory using mouse models for neuromuscular diseases., (© 2020 Wiley Periodicals, Inc.)

Objectives: To describe antirheumatic medicine prescribing patterns and to estimate the total annual direct medicine cost of rheumatoid arthritis (RA) in the private health sector of South Africa., Methods: A retrospective, cross-sectional drug utilization study was performed on medicine claims data from January 1, 2014, to December 31, 2014, for a total of 4,352 patients with RA. Patients were divided into those with RA only and those with RA and other chronic disease list conditions. Antirheumatic treatment was categorized into bridge therapy (nonsteroidal anti-inflammatory drugs [NSAIDs] and corticosteroids only) and therapy for advanced disease (NSAIDs, corticosteroids, and disease-modifying antirheumatic drugs [DMARDs] or biologics). Cost-driving products, the 90% drug utilization (DU90%) segment, mean, and median medicine item costs were calculated., Results: Annual direct RA medicine cost summed to €4,115,569.70. The mean ± SD (median) cost per medicine item was €45.87 ± €250.35 (€9.01). DMARDs represented 47.6% (n = 42,699) and biologics 2.4% (n = 2,150) of the 89,728 medicine items claimed. The DU90% of bridge therapy products accounted for 92.8% of the total medicine cost, with celecoxib as the main cost driver because of high volume and mean cost. The therapy for advanced disease DU90% segment accounted for 34.7% of the total medicine cost, with adalimumab as the main cost driver because of high mean cost., Conclusions: The direct medicine treatment cost of RA in the South African private health sector is driven by the high volume of DMARDs and the high mean costs of biologics, particularly adalimumab., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Facioscapulohumeral dystrophy (FSHD) is characterized by the contraction of the D4Z4 array located in the sub-telomeric region of the chromosome 4, leading to the aberrant expression of the DUX4 transcription factor and the mis-regulation of hundreds of genes. Several therapeutic strategies have been proposed among which the possibility to target the polyadenylation signal to silence the causative gene of the disease. Indeed, defects in mRNA polyadenylation leads to an alteration of the transcription termination, a disruption of mRNA transport from the nucleus to the cytoplasm decreasing the mRNA stability and translation efficiency. This review discusses the polyadenylation mechanisms, why alternative polyadenylation impacts gene expression, and how targeting polyadenylation signal may be a potential therapeutic approach for FSHD.

Introduction: Little is known about the burden of rheumatoid arthritis (RA) in South Africa. The aim of this study was to establish the prevalence of RA and coexisting chronic disease list (CDL) conditions in the private health sector of South Africa., Methods: A retrospective, cross-sectional analysis was performed on medicine claims data from 1 January 2014 to 31 December 2014 to establish the prevalence of RA. The cohort of RA patients was then divided into those with and those without CDL conditions, to determine the number and type of CDL conditions per patient, stratified by age group and gender., Results: A total 4352 (0.5%) patients had RA, of whom 69.3% (3016) presented with CDL conditions. Patients had a median age of 61.31 years (3.38; 98.51), and 74.8% were female. Patients with CDL conditions were older than those patients without (p < 0.001; Cohen's d = 0.674). Gender had no influence on the presence of CDL conditions (p = 0.456). Men had relatively higher odds for hyperlipidemia (OR 1.83; CI 1.33-2.51; p < 0.001) and lower odds for asthma (OR 0.83; CI 0.48-1.42; p = 0.490) than women. In combination with hyperlipidemia, the odds for asthma were reversed and strongly increased (OR 6.74; CI 2.07-21.93; p = 0.002). The odds for men having concomitant hyperlipidemia, hypertension, type 2 diabetes mellitus and hypothyroidism were insignificant and low (OR 0.40; CI 0.16-1.02; p = 0.055); however, in the absence of hypothyroidism, the odds increased to 3.26 (CI 2.25-4.71; p < 0.001)., Conclusion: Hypothyroidism was an important discriminating factor for comorbidity in men with RA. This study may contribute to the body of evidence about the burden of RA and coexisting chronic conditions in South Africa.

Objectives: Fungi belonging to the Metarhizium anisopliae complex comprise ubiquitous arthropod pathogenic moulds used as mycopesticides. Rare cases of human infections due to M. anisopliae have been reported. We hypothesize misidentifications of fungal strains implicated in these cases or used in mycopesticides., Methods: A review of the literature was conducted to identify previously published cases. We collected some of these previous described strains and reported new cases, and a French mycopesticide containing M. anisopliae. All identifications were performed based on elongation factor-1α gene sequencing., Results: We report eight new cases of Metarhizium infection in humans (three from France and five from Australia). The strains isolated from these cases, and three others from already published cases and reported as M. anisopliae, were molecularly identified based on elongation factor-1α (Ef1-α) gene sequencing as follows: Metarhizium robertsii (six), Metarhizium guizhouense (three), Metarhizium brunneum (one) and Metarhizium pingshaense (one)., Conclusions: In this study, we report new human cases of Metarhizium infections, and, based on Ef-1α gene sequencing, we demonstrate the misidentification of species in case reports. We also correct the species identification of a strain reported as M. anisopliae used in a commercially available mycopesticide. According to our results, none of the strains from the human infection reports reviewed belongs to the species M. anisopliae., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Muscular dystrophies are characterized by weakness and wasting of skeletal muscle tissues. Several drugs targeting the myostatin pathway have been used in clinical trials to increase muscle mass and function but most showed limited efficacy. Here we show that the expression of components of the myostatin signaling pathway is downregulated in muscle wasting or atrophying diseases, with a decrease of myostatin and activin receptor, and an increase of the myostatin antagonist, follistatin. We also provide in vivo evidence in the congenital myotubular myopathy mouse model (knock-out for the myotubularin coding gene Mtm1) that a down-regulated myostatin pathway can be reactivated by correcting the underlying gene defect. Our data may explain the poor clinical efficacy of anti-myostatin approaches in several of the clinical studies and the apparent contradictory results in mice regarding the efficacy of anti-myostatin approaches and may inform patient selection and stratification for future trials.

Purpose: Alkali burns are the most common, severe chemical ocular injuries, their functional prognosis depending on corneal wound healing efficiency. The purpose of our study was to compare the benefits of amniotic membrane (AM) grafts and homogenates for wound healing in the presence or absence of previous all-trans retinoic acid (atRA) treatment., Methods: Fifty male CD1 mice with reproducible corneal chemical burn were divided into five groups, as follows: group 1 was treated with saline solution; groups 2 and 3 received untreated AM grafts or grafts treated with atRA, respectively; and groups 4 and 5 received untreated AM homogenates or homogenates treated with atRA, respectively. After 7 days of treatment, ulcer area and depth were measured, and vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) were quantified., Results: AM induction by atRA was confirmed via quantification of retinoic acid receptor β (RARβ), a well-established retinoic acid-induced gene. Significant improvements of corneal wound healing in terms of ulcer area and depth were obtained with both strategies. No major differences were found between the efficiency of AM homogenates and grafts. This positive action was increased when AM was pretreated with atRA. Furthermore, AM induced a decrease in VEGF and MMP-9 levels during the wound healing process. The atRA treatment led to an even greater decrease in the expression of both proteins., Conclusions: Amnion homogenate is as effective as AM grafts in promoting corneal wound healing in a mouse model. A higher positive effect was obtained with atRA treatment.

Background: Primary healthcare (PHC) is central to increased access and transformation in South African healthcare. There is limited literature about services required by occupational therapists in PHC. Despite policy being in place, the implementation of services at grassroots level does not always occur adequately., Objectives: This study aimed at gaining an understanding of the challenges of being disabled and the services required by occupational therapists (OTs) in rural communities in order to better inform the occupational therapy (OT) training curriculum., Method: An exploratory, descriptive qualitative design was implemented using purposive sampling to recruit 23 community healthcare workers from the uGu district. Snowball sampling was used to recruit 37 members of the uGu community, which included people with disability (PWD) and caregivers of PWDs. Audio-recorded focus groups and semi-structured interviews were used to collect data, which were thematically analysed. Ethical approval was obtained from the Biomedical and Research Ethics Committee of the University of KwaZulu-Natal (BE248/14)., Results: Two main themes emerged namely: firstly, the challenges faced by the disabled community and secondly appropriate opportunities for intervention in PHC. A snapshot of the social and physical inaccessibility challenges experienced by the community was created. Challenges included physical and sexual abuse, discrimination and marginalisation. Community-based rehabilitation and ideas for health promotion and prevention were identified as possible strategies for OT intervention., Conclusion: The understanding of the intervention required by OT in PHC was enhanced through obtaining the views of various stakeholders' on the role. This study highlighted the gaps in community-based services that OTs should offer in this context., Competing Interests: The authors declare that they have no financial or personal relationships which may have inappropriately influenced them in writing this article.

Introduction: The assessment of intestinal membrane permeability properties of new chemical entities is a crucial step in the drug discovery and development process and a variety of in vitro models, methods and techniques are available to estimate the extent of oral drug absorption in humans. However, variations in certain physiological and physico-chemical factors are often not reflected in the results and the complex dynamic interplay between these factors is sometimes oversimplified with in vitro models. Areas covered: In vitro models to evaluate drug pharmacokinetics are briefly outlined, while both physiological and physico-chemical factors that may have an influence on these techniques are critically reviewed. The shortcomings identified for some of the in vitro techniques are discussed in conjunction with novel ways to improve and thereby overcome some challenges. Expert opinion: Although conventional in vitro methods and theories are used as basic guidelines to predict drug absorption, critical evaluations have identified some shortcomings. Advancements in technology have made it possible to investigate and understand the role of physiological and physico-chemical factors in drug delivery more clearly, which can be used to improve and refine the techniques to more closely mimic the in vivo environment.

We report the case of a twenty-year-old man with a unilateral maculopathy responsible for an acute visual acuity loss and a sudden absolute central scotoma. His schizoid personality made the medical history fruitless. The patient's best corrected visual acuity was 20/60. Clinical examination revealed a strictly unilateral maculopathy with pigment remodeling and hyper-autofluorescent areas. Through this case report, we describe the characteristics of the lesion and the pathway to the diagnosis: a laser pointer-induced photic injury., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: In persons suffering from rheumatoid arthritis (RA), the metacarpophalangeal (MCP) joints are commonly affected, resulting in inflammation, pain, joint instability, diminished grip strength and difficulties with function. However, the effectiveness of Kinesio Taping ® of the MCP joints in alleviating the symptoms has not been established., Aim: To determine the effectiveness of bilateral Kinesio Taping ® of the MCP joints on pain, range of motion, grip strength and hand function in elderly individuals previously diagnosed with RA., Methods: A repeated measure, experimental design was used over a 7-week period with the Kinesio Taping group ( n = 30) receiving bilateral space correction Kinesio Taping ® of the MCP joints with a joint protection (JP) group ( n = 31) participating in JP workshops. The Kinesio Tape ® was worn for 3 days a week with four applications during the data collection process. For the control group, 2-hour JP educational-behavioural workshops were run weekly for 4 weeks. Weekly assessments were completed for grip strength, ulnar deviation and pain (VAS), and two pre-intervention assessments and one post-intervention assessment was completed for the Michigan Hands Outcomes Questionnaire (MHQ)., Results: Kinesio Taping ® of the MCP joints showed a significant decrease in pain ( p = 0.001) and improved range of motion ( p = 0.001 bilaterally). JP was found to have a significant improvement in grip strength ( p = 0.001 bilaterally) and in the work ( p = 0.01) and activities of daily living (ADL) ( p = 0.01) sections of the MHQ. No significant difference was found between groups after intervention in the majority of outcomes ( p = 0.24) except for grip strength where a significant difference was found., Conclusion: Kinesio Taping ® of the MCP joints is an effective conservative intervention to improve pain and MCP ulnar deviation in individuals with RA.Significance of the work: Kinesio Taping ® of the MCP joints of individuals with RA showed a significant decrease in pain ( p = 0.00) and improved range of motion ( p = 0.001 bilaterally). JP was found to significantly improve grip strength ( p = 0.001 bilaterally) and in the work ( p = 0.01) and ADL ( p = 0.01) sections of the MHQ. No significant difference was found between groups after intervention in the majority of outcomes ( p = 0.24) except for grip strength where a significant difference was found ( p = 0.001)., Competing Interests: The authors declare that they have no financial or personal relationship(s) which may have inappropriately influenced them in writing this article.’

Pharmacists have a long history of helping Canadians with minor ailments. This often has involved management with over-the-counter medications. If pharmacists felt that the best care required something more robust, they would refer the patient to a physician. In hopes of improving the care of such ailments, Canadian provinces have granted pharmacists the option of selecting medications traditionally under physician control. This review examines the Canadian perspective on pharmacists prescribing for minor ailments and the evidence of value for these programs. It might provide guidance for other jurisdictions contemplating such a move.

This article presents the results of a survey conducted on Speech-Language Therapists (SLTs) regarding current practices in the assessment of English Additional Language (EAL) speakers in South Africa. It forms part of the rationale for a broader (PhD) study that critiques the use of assessment instruments on EAL speakers from an indigenous linguistic and cultural background. This article discusses an aspect of the broader research and presents the background, method, findings, discussion and implications of the survey. The results of this survey highlight the challenges of human and material resources to, and the dominance of English in, the profession in South Africa. The findings contribute to understanding critical factors for acquiring reliable and valid assessment results with diverse populations, particularly the implications from a cultural and linguistic perspective.

Introduction: Primary intraocular lymphoma (PIOL), associated with primary central nervous system lymphoma (PCNSL), is a rare malignancy disease. By way of a seven-year experience of a tertiary center, we discuss the presentation and we review the diagnostic and therapeutic modalities., Observations: We report six cases of PIOL associated with PCNSL. For all patients, the clinical presentation was a vitreoretinal syndrome. The diagnosis was histologically confirmed by vitreal sample or brain biopsy. Five patients developed a diffuse large B-cell lymphoma. Only one patient developed a T-cell lymphoma. The treatment consisted of conformational radiation therapy, systemic chemotherapy and intravitreal injections of methotrexate. The median survival after the diagnosis was 24 months., Discussion: PIOL, associated with PCNSL, is the most common type of ocular lymphoma. In most cases, ocular manifestations inaugurate the disease. PIOL is often fatal because of ultimate central nervous system presentation. The role of the ophthalmologist consists in early diagnosis. Typical clinical findings include vitroretinal tumor syndrome but can mascarade other eye pathologies. Diagnosis requires histology. The majority of PIOL is diffused large B-cell lymphoma. Decisions are made through multidisciplinary consultation. PIOL exhibits high responsiveness to methotrexate., Conclusion: Through a literature review and many illustrations, we discuss epidemiological, clinical, histological, radiological and treatment characteristics of PIOL associated with PCNSL., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Loss-of-function mutations in the myotubularin gene (MTM1) cause X-linked myotubular myopathy (XLMTM), a fatal, congenital pediatric disease that affects the entire skeletal musculature. Systemic administration of a single dose of a recombinant serotype 8 adeno-associated virus (AAV8) vector expressing murine myotubularin to Mtm1-deficient knockout mice at the onset or at late stages of the disease resulted in robust improvement in motor activity and contractile force, corrected muscle pathology, and prolonged survival throughout a 6-month study. Similarly, single-dose intravascular delivery of a canine AAV8-MTM1 vector in XLMTM dogs markedly improved severe muscle weakness and respiratory impairment, and prolonged life span to more than 1 year in the absence of toxicity or a humoral or cell-mediated immune response. These results demonstrate the therapeutic efficacy of AAV-mediated gene therapy for myotubular myopathy in small- and large-animal models, and provide proof of concept for future clinical trials in XLMTM patients.

We report the case of a 19-year-old woman with a combined hamartoma of the retinal pigment epithelium and retina incidentally discovered during her first eye exam. By way of this case, we describe and illustrate the epidemiological and clinical characteristics of the condition and its potential complications., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Manipulation of the mouse genome by site-specific mutagenesis has been extensively used to study gene function and model human disorders. Mouse models of myotubular myopathy (XLMTM), a severe congenital muscular disorder due to loss-of-function mutations in the MTM1 gene, have been generated by homologous recombination and shown that myotubularin is essential for skeletal muscle. However, since the Mtm1 deletion occurred constitutively or shortly after birth in these mice, it is not known whether myotubularin is required during adulthood, an important issue in the context of not only muscle biology but also therapies. To delete the Mtm1 gene in adult muscle fibers, we constructed a recombinant adeno-associated vector (AAV) that expresses the Cre recombinase under the muscle-specific desmin promoter. We report that a single injection of this vector into muscles of 3-month-old Mtm1 conditional mice leads to a myotubular myopathy phenotype with myofiber atrophy, disorganization of organelle positioning, such as mitochondria and nuclei, T-tubule defects and severe muscle weakness. In addition, our results show that MTM1-related atrophy and dysfunction correlate with abnormalities in satellite cell number and markers of autophagy, protein synthesis and neuromuscular junction transmission. The expression level of atrogenes was also analyzed. Therefore, we provide a valuable tissue model that recapitulates the main features of the disease, and it is useful to study pathogenesis and evaluate therapeutic strategies. We establish the proof-of-concept that myotubularin is required for the proper function of skeletal muscle during adulthood, suggesting that therapies will be required for the entire life of XLMTM patients.

Myotubular myopathy (MTM) is a severe congenital muscle disease characterized by profound weakness, early respiratory failure and premature lethality. MTM is defined by muscle biopsy findings that include centralized nuclei and disorganization of perinuclear organelles. No treatments currently exist for MTM. We hypothesized that aberrant neuromuscular junction (NMJ) transmission is an important and potentially treatable aspect of the disease pathogenesis. We tested this hypothesis in two murine models of MTM. In both models we uncovered evidence of a disorder of NMJ transmission: fatigable weakness, improved strength with neostigmine, and electrodecrement with repetitive nerve stimulation. Histopathological analysis revealed abnormalities in the organization, appearance and size of individual NMJs, abnormalities that correlated with changes in acetylcholine receptor gene expression and subcellular localization. We additionally determined the ability of pyridostigmine, an acetylcholinesterase inhibitor, to ameliorate aspects of the behavioral phenotype related to NMJ dysfunction. Pyridostigmine treatment resulted in significant improvement in fatigable weakness and treadmill endurance. In all, these results describe a newly identified pathological abnormality in MTM, and uncover a potential disease-modifying therapy for this devastating disorder.

X-linked myotubular myopathy is a severe congenital myopathy caused by deficiency of the lipid phosphatase, myotubularin. Recent studies of human tissue and animal models have discovered structural and physiological abnormalities in myotubularin-deficient muscle, but the impact of myotubularin deficiency on myogenic stem cells within muscles is unclear. In the present study, we evaluated the viability, proliferative capacity, and in vivo engraftment of myogenic cells obtained from severely symptomatic (Mtm1δ4) myotubularin-deficient mice. Mtm1δ4 muscle contains fewer myogenic cells than wild-type (WT) littermates, and the number of myogenic cells decreases with age. The behavior of Mtm1δ4 myoblasts is also abnormal, because they engraft poorly into C57BL/6/Rag1null/mdx5cv mice and display decreased proliferation and increased apoptosis compared with WT myoblasts. Evaluation of Mtm1δ4 animals at 21 and 42 days of life detected fewer satellite cells in Mtm1δ4 muscle compared with WT littermates, and the decrease in satellite cells correlated with progression of disease. In addition, analysis of WT and Mtm1δ4 regeneration after injury detected similar abnormalities of satellite cell function, with fewer satellite cells, fewer dividing cells, and increased apoptotic cells in Mtm1δ4 muscle. These studies demonstrate specific abnormalities in myogenic cell number and behavior that may relate to the progression of disease in myotubularin deficiency, and may also be used to develop in vitro assays by which novel treatment strategies can be assessed., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

This paper focuses on the reciprocal capacity building that occurred through collaborative research between occupational therapy departments from six higher education institutions in South Africa, community-based organizations and a disabled people's organization on disabled youth and their livelihoods. The authors aimed to identify principles for collaboration and capacity building from the pilot phase and first phase of the main study. Occupational therapy departments place students in communities for service learning experience, but little collaboration with disabled people's organizations and communities in research processes occurs that could enrich such partnerships and inform relevant curriculum development. Secondary data from different sources including a transcript of a focus-group interview with the researchers in the pilot phase, workshop reports, and transcripts of free-writing exercises done by researchers were analysed thematically, both inductively and deductively. Two themes are explored: first, reciprocal building of organizational capacity and, second, generating collaborative relationships. The principles that were identified are integral to the strengths and challenges faced when multiple organizations work together over a wide geographical area on a complex research topic that also builds capacity reciprocally.

Sprouting angiogenesis is associated with extensive extracellular matrix (ECM) remodeling. The molecular mechanisms involved in building the vascular microenvironment and its impact on capillary formation remain elusive. We therefore performed a proteomic analysis of ECM from endothelial cells maintained in hypoxia, a major stimulator of angiogenesis. Here, we report the characterization of lysyl oxidase-like protein-2 (LOXL2) as a hypoxia-target expressed in neovessels and accumulated in the endothelial ECM. LOXL2 belongs to the lysyl oxidase family of secreted enzymes involved in ECM crosslinking. Knockdown experiments in Tg(fli1:egfp)y1 zebrafish embryos resulted in lack of intersegmental vessel circulation and demonstrated LOXL2 involvement in proper capillary formation. Further investigation in vitro by loss and gain of function experiments confirmed that LOXL2 was required for tubulogenesis in 3D fibrin gels and demonstrated that this enzyme was required for collagen IV assembly in the ECM. In addition, LOXL2 depletion down-regulated cell migration and proliferation. These data suggest a major role for LOXL2 in the organization of endothelial basal lamina and in the downstream mechanotransductive signaling. Altogether, our study provides the first evidence for the role of LOXL2 in regulating angiogenesis through collagen IV scaffolding.

The avian uncoupling protein 3 (UCP3), mainly expressed in muscle tissue, could be involved in fatty acid (FA) metabolism, limitation of reactive oxygen species production, and/or nonshivering thermogenesis. We recently demonstrated that UCP3 mRNA expression was increased by isoproterenol (Iso), a β-agonist, in chicken Pectoralis major. This upregulation was associated with changes in FA metabolism and variations in the activation of AMP-activated protein kinase (AMPK) and in the expression of the transcription factors peroxisome proliferator-activated receptor (PPAR)α, PPARβ/δ, and PPARγ coactivator-1α (PGC-1α). The aim of the present study was to elucidate the mechanisms involving AMPK and PPARα in UCP3 regulation in primary cultures of chick myoblasts. Avian UCP3 mRNA expression, associated with p38 mitogen-activated protein kinase (p38 MAPK) activation, was increased by Iso and/or FAs. The PKA pathway mediated the effects of Iso on UCP3 expression. FA stimulation also led to AMPK activation. Furthermore, the direct involvement of AMPK on UCP3 regulation was shown by using 5-aminoimidazole-4-carboxyamide ribonucleoside and Compound C. The use of the p38 MAPK inhibitor SB202190, which was associated with AMPK activation, also dramatically enhanced UCP3 mRNA expression. Finally the PPARα agonist WY-14643 strongly increased UCP3 mRNA expression. This study highlights the control of UCP3 expression by the β-adrenergic system and FA in chick myoblasts and demonstrates that its expression is directly regulated by AMPK and by PPARα. Overexpression of avian UCP3 might modulate energy utilization or limit oxidative stress when mitochondrial metabolism of FA is triggered by catecholamines.