Tremor in motor neuron disease may be central rather than peripheral in origin

BACKGROUND AND PURPOSE: Motor neuron disease (MND) refers to a spectrum of degenerative diseases affecting motor neurons. Recent clinical and post-mortem observations have revealed considerable variability in the phenotype. Rhythmic involuntary oscillations of the hands during action, resembling tremor, can occur in MND, but their pathophysiology has not yet been investigated. METHODS: A total of 120 consecutive patients with MND were screened for tremor. Twelve patients with action tremor and no other movement disorders were found. Ten took part in the study. Tremor was recorded bilaterally using surface electromyography (EMG) and triaxial accelerometer, with and without a variable weight load. Power spectra of rectified EMG and accelerometric signal were calculated. To investigate a possible cerebellar involvement, eyeblink classic conditioning was performed in five patients. RESULTS: Action tremor was present in about 10% of our population. All patients showed distal postural tremor of low amplitude and constant frequency, bilateral with a small degree of asymmetry. Two also showed simple kinetic tremor. A peak at the EMG and accelerometric recordings ranging from 4 to 12 Hz was found in all patients. Loading did not change peak frequency in either the electromyographic or accelerometric power spectra. Compared with healthy volunteers, patients had a smaller number of conditioned responses during eyeblink classic conditioning. CONCLUSIONS: Our data suggest that patients with MND can present with action tremor of a central origin, possibly due to a cerebellar dysfunction. This evidence supports the novel idea of MND as a multisystem neurodegenerative disease and that action tremor can be part of this condition

Linking hydrological connectivity to gully erosion in savanna rangelands tributary to the Great Barrier Reef using structure‐from‐motion photogrammetry

Gully erosion is a major land management challenge globally and a particularly important issue in dry tropical savanna rangelands tributary to the Great Barrier Reef, Australia. This study investigated linkages between hillslope hydrological connectivity pathways and gully geomorphic change in the Burdekin River Basin. High‐resolution (0.1 m) topographic and land cover data derived from low‐cost aerial (via unmanned aircraft system) structure‐from‐motion with multiview stereo photogrammetry (SfM) were used to map fine‐scale connectivity patterns and quantify headcut retreat at the hillslope scale (~150,000 m2). Very high resolution (0.01 m) topographic models derived from ground‐based (via handheld digital camera) SfM were used to quantify the morphology and geomorphic change of several gully arms (300–700 m2) between 2016 and 2018. Median linear, areal, and volumetric headcut (n = 21) retreat rates were 0.2 m, 0.8 m2, and 0.3 m3 yr−1, respectively. At all study sites, the points where modelled hydrological flow lines intersected gullies corresponded to observed geomorphic change, enabling spatially explicit identification of gully extension pathways as a result of overland flow. Application of an index of connectivity demarcated parts of the hillslope most connected to the gully network. Bare areas, roads, and cattle trails were identified as important runoff source areas and hydrological conduits driving gully extension. Ground‐based SfM accurately reconstructed complex morphologic features including undercuts, overhangs, rills, and flutes, providing insights into within‐channel erosion processes. This study contributes to an improved understanding and modelling of hydrogeomorphic drivers of gully erosion in degraded savanna rangelands, ultimately benefiting gully management

Determinants In HIV Counselling And Testing In Couples In North Rift Kenya

Background: Voluntary HIV counselling and testing (VCT) has been shown to be an acceptable and effective tool in the fight against HIV/AIDS. Couple HIV Counselling and Testing (CHCT) however, is a relatively new concept whose acceptance and efficacy is yet to be determined.Objective: To describe factors that motivate couples to attend VCT as a couple. Design: A cross sectional qualitative study.Setting: Moi Teaching and Referral Hospital and Moi University, School of Medicine, Eldoret, KenyaSubjects: Seventy one individuals were interviewed during KII (9) and dyad interviews (31 couples). Ten FGDs involving a total of 109 individuals were held. Results: Cultural practices, lack of CHCT awareness, stigma and fear of results deter CHCT utilisation. Location of centre where it is unlikely to be associated with HIV testing, qualified professional staff and minimal waiting times would enhance CHCT utilisation.Conclusions: CHCT as a tool in the fight against HIV/AIDS in this region of Kenya is feasible as the factors that would deter couples are not insurmountable

Stakeholders perception of HIV sero-discordant couples in western Kenya

Objective: To describe the perceptions of key stakeholders regarding the counselling needs of HI V sero-discordant couples as part of preparation for a clinical trial involving HIV sero-discordant couples. Design: Qualitative study using key informant and couple interviews. Setting: Moi Teaching and Referral Hospital (MTRH). Subjects: A purposive sample of nine key informants and 31 couple interviews totaling 71 participants. The couple interviews consisted of HI V untested, HI V concordant (positive and negative) and discordant couples. Results: Seventy one individuals participated in nine key informant and 31 couple interviews. The responses identified the following as key issues in counselling HIV discordant couples: The need for education on the meaning of HI V sero-discordancy including potential sources of infection; assistance in disclosing HIV test results to one\'s partner; discussion of the stigma surrounding formula feeding. Overall, the participants supported safer sexual practices in discordant partnerships. Conclusions: Psychosocial support of HI V sero-discordant couples should include messages about the meaning, mechanisms and implications of sero-discordancy. Culturally appropriate HI Vdisclosure and safer sex messages are also needed to support these partnerships. East African Medical Journal Vol. 85 (7) 2008: pp. 326-33

Home-based HIV counselling and testing in Western Kenya

Background Objective: To describe our experience with the feasibility and acceptance of home-based HIV counselling and testing (HBCT) in two large, rural, administrative divisions of western Kenya.Design: Setting: Results: Conclusion : Home-based HIV counselling and testing was feasible among this rural population in western Kenya, with a majority of the population accepting to get tested. These data suggest that scaling-up of HBCT is possible and may enable large numbers of individuals to know their HIV serostatus in sub-Saharan Africa. More research is needed to describe the cost-effectiveness and clinical impact of this approach. There were 47,066 households approached in 294 villages: 97% of households allowed entry. Of the 138,026 individuals captured, 101,167 individuals were eligible for testing: 89% of adults and 58% of children consented to HIV testing. The prevalence of HIV in these communities was 3.0%: 2.7% in adults and 3.7% among children. Prevalence was highest in the 36-45 year age group and was almost always higher among women and girls. All persons testing HIV-positive were referred to Academic Model Providing Access to Healthcare (AMPATH) for further assessment and care; all consenting persons were counselled on HIV risk-lowering behaviours.Kosirai and Turbo Divisions, Rift Valley Province, Kenya.The USAID-AMPATH Partnership conducted  population-based, house-to-house HIV counselling and testing in western Kenya between June 2007 and June 2009. All individuals aged ≥13 years and all eligible children were offered HBCT. Children were eligible if they were above 13 years of age, and their mother was either HIVpositive or had unknown HIV serostatus, or if their mother was deceased or whose vital status was unknown.: The World Health Organisation (WHO) estimates that only 12% of men and 10% of women in sub-Saharan Africa have been tested for HIV and know their test results. Home-based counselling and testing (HBCT) offers a novel approach to complement facility-based provider initiated testing and counselling (PITC) and voluntary counselling and testing (VCT) and could greatly increase HIV prevention opportunities. However, there is almost no evidence that large-scale, door-to-door testing is even feasible in settings with both limited resources and significant stigma around HIV and AIDS

Triangulating’ AMPATH: Demonstration of a multi-perspective strategic programme evaluation method

Clinical programmes are typically evaluated on operational performance metrics of cost, quality and outcomes. Measures of patient satisfaction are used to assess the experience of receiving care, but other perspectives, including those of staff and communities, are not often sought or used to assess and improve programmes. For strategic planning, the Kenyan HIV/AIDS programme AMPATH (Academic Model Providing Access to Healthcare) sought to evaluate its performance in 2006. The method used for this evaluation was termed ‘triangulation,’ because it used information from three different sources – patients, communities, and programme staff. From January to August 2006, Indiana University external evaluators and AMPATH staff gathered information on strengths, weaknesses and suggestions for improvement of AMPATH. Activities included in-depth key-informant semi-structured interviews of 26 AMPATH clinical and support staff, 56 patients at eight clinic sites, and seven village health dialogues (mabaraza) at five sublocations within the AMPATH catchment area. Data sources included field notes and transcripts of translated audio recordings,which were subjected to qualitative content analysis. Eighteen  recommendations for programme improvement emerged, including ten from all three respondent perspectives. Three recommendations were cited by patients and in mabaraza, but not by staff. Triangulation uncovered improvement emphases that an internal assessment would miss. AMPATH and Kenyan Ministry of Health leadership have deliberated these recommendations and accelerated strategic change actions, including rural satellite programmes, collaboration with village-based workers, and door-to-door village-based screening and counselling

Distinct responses of neurons and astrocytes to TDP-43 proteinopathy in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease caused by motor neuron loss, resulting in muscle wasting, paralysis and eventual death. A key pathological feature of ALS is cytoplasmically mislocalized and aggregated TDP-43 protein in >95% of cases, which is considered to have prion-like properties. Historical studies have predominantly focused on genetic forms of ALS, which represent ∼10% of cases, leaving the remaining 90% of sporadic ALS relatively understudied. Additionally, the role of astrocytes in ALS and their relationship with TDP-43 pathology is also not currently well understood. We have therefore used highly enriched human induced pluripotent stem cell (iPSC)-derived motor neurons and astrocytes to model early cell type-specific features of sporadic ALS. We first demonstrate seeded aggregation of TDP-43 by exposing human iPSC-derived motor neurons to serially passaged sporadic ALS post-mortem tissue (spALS) extracts. Next, we show that human iPSC-derived motor neurons are more vulnerable to TDP-43 aggregation and toxicity compared with their astrocyte counterparts. We demonstrate that these TDP-43 aggregates can more readily propagate from motor neurons into astrocytes in co-culture paradigms. We next found that astrocytes are neuroprotective to seeded aggregation within motor neurons by reducing (mislocalized) cytoplasmic TDP-43, TDP-43 aggregation and cell toxicity. Furthermore, we detected TDP-43 oligomers in these spALS spinal cord extracts, and as such demonstrated that highly purified recombinant TDP-43 oligomers can reproduce this observed cell-type specific toxicity, providing further support to a protein oligomer-mediated toxicity hypothesis in ALS. In summary, we have developed a human, clinically relevant, and cell-type specific modelling platform that recapitulates key aspects of sporadic ALS and uncovers both an initial neuroprotective role for astrocytes and the cell type-specific toxic effect of TDP-43 oligomers

Impact of disease, cognitive and behavioural factors on caregiver outcome in amyotrophic lateral sclerosis

Up to 50% of patients with amyotrophic lateral sclerosis (ALS) show mild to moderate cognitive-behavioural change alongside their progressive functional impairment. This study examines the relative impact of patients' disease symptoms, behavioural change and current executive function and social cognition abilities on psychosocial outcomes in spouse caregivers of people with ALS. Thirty-five spouse caregivers rated their own levels of depression and anxiety, subjective burden and marital satisfaction. Caregivers also rated their partner's everyday behaviour. The patients were assessed for disease severity and cognitive function, with composite scores derived for executive function and social cognition. Regression analyses revealed that caregiver burden was predicted by the severity of patients' limb involvement and behavioural problems. Depression was predicted by patients' limb involvement, while behavioural problems and patient age predicted caregiver anxiety. Current marital satisfaction was predicted by patient behavioural problems beyond the level of pre-illness marital satisfaction. In conclusion, the study highlights the potential impact of ALS patients' functional impairment and behavioural change on ALS caregivers' psychosocial functioning. Clinical communication with ALS families should emphasise both physical and psychological challenges presented by the disease

3D Printed PLA Scaffolds to Promote Healing of Large Bone Defects

One challenge modern medicine faces is the ability to repair large bone defects and stimulate healing. Small defects typically heal naturally, but large bone defects do not and current solutions are to replace the missing tissue with biologically inert materials such as titanium. This limits the amount of bone healing as the defect is not repaired but rather replaced. The focus of our research is to develop a method of using 3D printing to create biodegradable scaffolds which promote bone in-growth and replacement. To accomplish this we used poly lactic acid (PLA) filament and a desktop 3D printer. To promote bone healing and provide mechanical support our team investigated different design methodologies to provide a scaffold of customizable stiffness while allowing cell attachment and in-growth. Our team used CAD modeling to create unique architecture design systems which we analyzed for stiffness using Finite Element Analysis (FEA). We developed a unit cell method of scaffold construction that allowed for customized stiffness of irregular shapes. We 3D printed our designs using a desktop 3D printer and verified our stiffness through mechanical tension and compression testing. We investigated cell viability of the scaffolds by immersing test specimens in culturing media and fibroblast cells. Fibroblast cells are from the same lineage as osteoblast cells but are much faster growing, allowing for more efficient testing. Specimens were left in the media for one week then a total cell count was performed. Scaffold designs were then evaluated based on stiffness and cell viability. We have produced several different viable models with appropriate stiffness for human trabecular bone and good cellular adhesion