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No description available.

Amyotrophic Lateral Sclerosis is a neurodegenerative disease affecting adults with disease onset averaging between 50-60 years of age. As neurons die, patients experience rapid physical and cognitive decline with death typically following 3-5 years after diagnosis. As there is currently no cure for disease and no treatment to prolong life expectancy, medical management is focused on quality of life. In addition to traditional medical treatments, medical professionals must also consider maximizing autonomy as a way to increase quality of life with a focus on relational and psychological factors. For patients in low-income urban neighborhoods, inequalities affecting agency should be evaluated as part of medical care to increase both autonomy and overall quality of life. / Urban Bioethics

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No description available.

No description available.

TAR DNA Binding Protein-43 (TDP-43) proteinopathy is a disease pathology that underlies a broad field of neurodegenerative disorders. Most prominently, TDP-43 aggregates are the hallmark of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD). The implication of TDP-43 in ALS, in particular, has helped initiate a cascade of research to determine the properties of the previously obscure protein. From these studies, it is now known that TDP-43 is a DNA and RNA binding protein, important for the splicing and regulation of many transcripts. In the disease state, TDP-43 is modified in a way that fuels its accumulation into cytoplasmic aggregates called inclusions. This paper will delineate the current understanding of the mechanisms behind TDP-43 proteinopathy and the resultant clinical conditions. The body of evidence firmly supports a clinical spectrum of TDP-43 proteinopathy that ranges between pure motor neuron disease (MND) and pure frontotemporal dementia (FTD). It also appears that the root cause of neurodegeneration in these disorders comes about through a combination of a gain of toxic function and a loss of normal TDP-43. Continued research into the molecular processes leading to the capitulation of TDP-43 holds great promise for the development of new drug targets to help treat the spectrum of TDP-43 proteinopathy.

Syftet med denna litteraturstudie var att beskriva existentiella och psykosociala upplevelser hos patienter med ALS. Nio kvalitativa artiklar valdes ut och inkluderades till litteraturstudiens resultat. Artiklarna beskrev upplevelser från patienter i olika kontexter där existentiella och psykosociala aspekter berördes. Det framkom i resultatet att patienter upplevde meningsfullhet och att familjen var betydande för deras välmående, men också hopplöshet och känslan av att vara en börda för andra vilket utgjorde svårigheter att finna mening i livet. Patienter upplevde lidande i flera dimensioner och hanterade sin situation med hjälp av olika strategier, attityder och förhållningssätt. Slutsatser som författarna för denna litteraturstudie kunde dra från resultatet var att patienterna går igenom flera dimensioner av lidande vilket ställer krav på sjuksköterskan att lindra dessa. Sjuksköterskan ska också hjälpa patienten att framhäva sina styrkor och skapa en större förståelse för att patienten skall nå acceptans. En annan slutsats som drogs var att familjens involvering i omvårdnaden kunde vara positiv då de står närmast patienten och det visade sig vara en positiv faktor för att acceptera situationen. ALS är en neurodegenerativ sjukdom som förstör motorneuron i hjärnan. Det leder till att den viljestyrda muskulaturen förlorar sin funktion. Till sist drabbas även muskulaturen kring lungorna som leder till minskad lungkapacitet. Från symtomdebut är överlevnadssikten cirka två till fem år där vanligaste dödsorsaken är koldioxidnarkos. Tidigare forskning har framfört positiva och negativa känslor hos patienter med ALS. Upplevelser att kroppen misslyckas i förtid samt behov av att prata om döden framkom. Kommunikation med vården var viktig för att patienter skulle uppleva att sjukdomen var hanterbar. Litteraturstudien använde bärande begrepp såsom lidande och försoning. En kvalitativ ansats användes då upplevelser skulle undersökas och analysen utgick från Fribergs femstegsmodell. Diskussionen utgick från resultatets huvudteman Främjande aspekter för meningsfullhet samt Utmanande aspekter för livsvillkor. Denna litteraturstudie är viktig då den bidrar till en ökad kunskap och förståelse för hur patienter med ALS upplever existentiella och psykosociala aspekter. Genom kunskap kan vården utvecklasoch främja vårdkvaliteteten för patienterna och samtidigt stärka sjuksköterskan i sin yrkesroll.Främjande och utmanande aspekter som påverkade välbefinnandet hos patienter identifierades och diskussionen ledde således till sjuksköterskans funktion samt litteraturstudiens bärande begrepp, lidande och försoning.

No description available.

Amyotrophic lateral sclerosis (ALS) is a devastating disease characterized by the progressive degeneration of motor neurons. Dominantly-inherited mutations to the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) cause 3-6% of all ALS cases. The complete mechanism behind the toxicity of mutant SOD1 remains unclear, although significant evidence points to aberrant or incomplete metal-binding having a role in a toxic gain-of-function. However, the relevance of the metal-binding of SOD1 to mutant-SOD1-linked ALS remains controversial. Direct assessments of protein metal-binding from transgenic, SOD1-overexpressing rodent models of the disease are difficult to acquire due to the non-covalent nature of the interaction. The relatively small amount of disease-afflicted spinal cord tissue in which the motor neurons reside compounds the difficulty of measuring the protein metal binding of SOD1 from transgenic mice. This dissertation addresses the metals bound to SOD1 throughout the disease course in transgenic mice using a novel mass spectrometry assay. The methodology developed here offers the first detailed examination of partially unfolded intermediates of SOD1 present in the spinal cord of pre-symptomatic, symptomatic, and end-stage transgenic mice overexpressing the ALS-associated SOD1 mutation G93A (glycine mutated to alanine at position 93). These results were compared to age-matched transgenic mice expressing wild-type SOD1 that do not develop ALS symptoms. To extract SOD1 from relevant spinal cord tissue, a 300 ��m necropsy punch was used to remove a small piece of tissue from the ventral or dorsal gray matter of a 1 mm-thick slice of spinal cord. Physiological salts that interfere with electrospray mass spectrometry were removed by binding the proteins to a C4 Ziptip��, a pipette tip containing hydrophobic, reversed-phase packing material. Washing the Ziptip-bound proteins with water eliminated interfering salts. Bound proteins could then be eluted into a mass spectrometer with low concentrations of acetonitrile plus formic acid. Electrospray ionization conditions were determined that could keep both copper and zinc bound to SOD1. Using a high-resolution Fourier transform-ion cyclotron resonance mass spectrometer, we used the assay to collect isotopically-resolved protein mass data. Theoretical protein isotope distributions were calculated from the empirical formulas of SOD1 and matched to the experimental data with a least squares fitting algorithm to determine the multiple intermediates of SOD1 present. Spinal cord tissue, wild-type in particular, was notable for containing significantly more one-metal SOD1 than any other tissue, despite having 3-fold less SOD1 than liver. We quantitatively compared the levels of soluble, partially unfolded intermediates of SOD1 from wild-type and G93A SOD1 spinal cords. Wild-type mouse spinal cord contained significantly more of all of the partially unfolded intermediates copper-deficient SOD1, disulfide reduced SOD1, and apo SOD1. The amount of zinc-containing SOD1 was exceptionally high in wild-type mice, comprising 60% of the total SOD1 in wild-type spinal cord. The larger amounts of these SOD1 intermediates in wild-type transgenic mice indicate that they are not directly responsible for toxicity in vivo. However, copper-containing, zinc-deficient SOD1 was the one species found in higher concentrations in G93A SOD1 spinal cord. The concentration was on average 0.6-0.8 ��M in G93A spinal cord, compared to 0.1-0.3 ��M zinc-deficient SOD1 found in the wild-type mouse spinal cord. A concentration above 0.5 ��M zinc-deficient SOD1 was sufficient to induce motor neuron death in vitro. These results suggest that copper-containing, zinc-deficient SOD1 could be the toxic species responsible for motor neuron death in ALS. / Graduation date: 2013