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1.
Heliyon ; 9(11): e21720, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38027844

ABSTRACT

Real-time gait event detection (GED) system can be utilized for gait analysis and tracking fitness activities. GED for various types of terrains (e.g., stair-walk, uneven surfaces, etc.) is still an open research problem. This study presents an inertial sensor-based approach for real-time GED system that works for diverse terrains in an uncontrolled environment. The GED system classifies three types of terrains, i.e., flat-walk, stair-ascend and stair-descend, with an average classification accuracy of 99%. It also accurately detects various gait events, including, toe-strike, heel-rise, toe-off, and heel-strike. It is computationally efficient, implemented on a low-cost microcontroller, works in real-time and can be used in portable rehabilitation devices for use in dynamic environments.

2.
Biol Sex Differ ; 14(1): 35, 2023 05 23.
Article in English | MEDLINE | ID: mdl-37221606

ABSTRACT

INTRODUCTION: Alzheimer's disease (AD) can be characterised in vivo by biomarkers reflecting amyloid-ß (Aß) and tau pathology. However, there is a need for biomarkers reflecting additional pathological pathways. Matrix metalloproteinases (MMPs) have recently been highlighted as candidate biomarkers for sex-specific mechanisms and progression in AD. METHODS: In this cross-sectional study, we investigated nine MMPs and four tissue inhibitors of metalloproteinases (TIMPs) in the cerebrospinal fluid of 256 memory clinic patients with mild cognitive impairment or dementia due to AD and 100 cognitively unimpaired age-matched controls. We studied group differences in MMP/TIMP levels and examined the associations with established markers of Aß and tau pathology as well as disease progression. Further, we studied sex-specific interactions. RESULTS: MMP-10 and TIMP-2 levels differed significantly between the memory clinic patients and the cognitively unimpaired controls. Furthermore, MMP- and TIMP-levels were generally strongly associated with tau biomarkers, whereas only MMP-3 and TIMP-4 were associated with Aß biomarkers; these associations were sex-specific. In terms of progression, we found a trend towards higher MMP-10 at baseline predicting more cognitive and functional decline over time exclusively in women. CONCLUSION: Our results support the use of MMPs/TIMPs as markers of sex differences and progression in AD. Our findings show sex-specific effects of MMP-3 and TIMP-4 on amyloid pathology. Further, this study highlights that the sex-specific effects of MMP-10 on cognitive and functional decline should be studied further if MMP-10 is to be used as a prognostic biomarker for AD.


Subject(s)
Alzheimer Disease , Humans , Female , Male , Matrix Metalloproteinase 10 , Matrix Metalloproteinase 3 , Cross-Sectional Studies
3.
Ulster Med J ; 92(1): 38-42, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36762141

ABSTRACT

Aims: There is evidence of disparate levels of care for members of ethnic minority communities with inflammatory bowel disease in various NHS Trusts and Health Boards in England and Scotland. The purpose of this study was to investigate whether there was any association between the existence of disparate levels of care and the ethnic composition of the management boards of NHS Trusts and Health Boards. It also examined the ethnic composition of Health and Wellbeing Boards associated with these Trusts in England. Method: NHS Trusts in England and Health Boards in Scotland, which had been involved in previous studies of disparate levels of care, were identified through a review of the relevant published papers. Health and Wellbeing Boards associated with these Trusts were then identified. Executive and non-executive membership of the NHS Trust, Health Boards and Health and Wellbeing Boards was determined through scrutiny of their web pages. Results: The proportion of Asians, who were executive officers, was significantly lower than the proportion who were non-executive board members both for trusts who offered disparate care (z = 2.22; p < 0.03) and those which did not (z = 2.24; p < 0.03). There was no significant difference in the proportion of Asians who were non-executive board members between the two types of trust. The proportion of ethnic minority members of English Health and Well-Being Boards, where there was evidence of disparate levels of care received by South Asian patients was significantly greater than on Boards where this was not the case. (z = 2.8. p < 0.005). Conclusions: The relation of these findings to disparate levels of care is unclear. However, it may point to a culture of tokenism, where either the members are not truly representative of underserved communities or they are unable to have any influence on local policy decisions. In either case there is an urgent need to develop better links with minority communities who are underserved so that issues can be effectively identified and remedied.


Subject(s)
Inflammatory Bowel Diseases , State Medicine , Humans , Ethnicity , Minority Groups , England , Inflammatory Bowel Diseases/therapy
4.
Med Leg J ; 91(1): 23-25, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35624539

ABSTRACT

Khan v Meadows, which was decided recently by the Supreme Court, will have a profound effect on day-to-day clinical practice and future clinical negligence cases. It has clarified the scope of duty of care and to a significant extent links it to the questions being asked by patients of their doctors and by doctors of their colleagues. Will courts now consider that when a patient consults a doctor, he or she is seeking an answer to a specific question or a more general question hidden within that specific question? Clearly the onus will be on clinicians to define exactly what is wanted by the patient or by a colleague.


Subject(s)
Malpractice , Physicians , Humans , Grassland
5.
Plast Reconstr Surg ; 150(3): 630e-638e, 2022 09 01.
Article in English | MEDLINE | ID: mdl-35791281

ABSTRACT

BACKGROUND: Electrical injuries of the scalp are a frequent occurrence in developing countries. Burns can be contact or conductive and result in extensive tissue damage. The authors present their experience with treatment of scalp and calvarial electrical injuries and propose a management algorithm. METHODS: This was a retrospective cohort study comprising all patients with electrical injuries of the scalp treated at the authors' center between January of 2010 and December of 2016. Noncontrast computed tomography scans were obtained to assess viability of the calvarium in patients who presented more than 2 weeks after injury. Single-stage débridement and reconstruction were performed. All nonviable soft tissue and bone was removed. Soft-tissue reconstruction was performed with skin grafts, local scalp flaps, pedicled trapezius flaps, and free flaps (anterolateral thigh, latissimus dorsi, and scapular). Cranioplasty was performed in a delayed manner with autologous bone grafts. RESULTS: Over a 7-year period, a total of 52 patients underwent scalp reconstruction for high-voltage (44 patients) and low-voltage (eight patients) electrical injury. All patients underwent successful soft-tissue reconstruction. Osteomyelitis with draining sinuses developed in three patients; these patients underwent flap re-elevation and bone débridement, which resulted in a healed wound and stable reconstruction. Cranioplasty was performed with split calvarial grafts in two patients and split rib grafts in four patients. One patient underwent scalp tissue expansion for hair restoration. CONCLUSION: The authors propose an algorithm for reconstruction of electrical injuries of the scalp. Thorough débridement of the calvarium is the most important determinant of a successful outcome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Subject(s)
Free Tissue Flaps , Plastic Surgery Procedures , Soft Tissue Injuries , Algorithms , Free Tissue Flaps/surgery , Humans , Plastic Surgery Procedures/methods , Retrospective Studies , Scalp/injuries , Scalp/surgery , Skin Transplantation , Soft Tissue Injuries/surgery , Treatment Outcome
6.
Comput Methods Biomech Biomed Engin ; 24(9): 945-955, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33356542

ABSTRACT

Electromyography (EMG) is the study of electrical activity in the muscles. We classify EMG signals from surface electrodes (channels) using Artificial Neural Network (ANN). We evaluate classification performance of 10 different hand motions using several feature-channel combinations with wrapper method. Highest classification accuracy of 98.7% is achieved with each feature-channel combination. Compared to previous studies, we achieve the highest accuracy for 10 classes with lower number of feature-channel combination. We reduce ANN complexity without compromising the classification accuracy for deployment in low-end hardware with limited computational power along with improving the design of a low-cost hardware for EMG signal acquisition.


Subject(s)
Electromyography , Forearm , Pattern Recognition, Automated , Algorithms , Humans , Motion , Movement , Signal Processing, Computer-Assisted
7.
Trop Biomed ; 36(3): 630-639, 2019 Sep 01.
Article in English | MEDLINE | ID: mdl-33597485

ABSTRACT

The type and amount of resources available significantly influences the structure and dynamics of food webs. In this study, we analyzed differences in species richness of scavengers based on carcass type in Riyadh, Saudi Arabia. We collected insects from experimental carcasses of three different types, domestic dogs (Canidae, Canis lupus familiaris), Hijazi goats (Bovidae, Capra aegagrus hircus), and camels (Camelidae, Camelus dromedarius). Data collection was conducted during the decay stage in June, 2016. We used mitochondrial cytochrome c oxidase subunit I (mtCOI) barcodes as a marker for the molecular identification of the scavenger insects. The results showed that there were more insects on the camels and goats than the dogs. In total, seven species were found on all carrions. Six species were found on the camels and goats, but only five were found on the dog. Musca domestica was the most collected species of flies whereas, Necrobia rufipes was the most collected species of beetles. Overall, this study showed that carrion type had an effect on the type and number of insects attracted to the carrions. Thus, one of the significant factors that influence the associated scavenger assemblage is a carcass type.


Subject(s)
Cadaver , Coleoptera/classification , Diptera/classification , Food Chain , Animals , Camelus , Dogs , Goats , Saudi Arabia
8.
Tropical Biomedicine ; : 630-639, 2019.
Article in English | WPRIM (Western Pacific) | ID: wpr-780553

ABSTRACT

@#The type and amount of resources available significantly influences the structure and dynamics of food webs. In this study, we analyzed differences in species richness of scavengers based on carcass type in Riyadh, Saudi Arabia. We collected insects from experimental carcasses of three different types, domestic dogs (Canidae, Canis lupus familiaris), Hijazi goats (Bovidae, Capra aegagrus hircus), and camels (Camelidae, Camelus dromedarius). Data collection was conducted during the decay stage in June, 2016. We used mitochondrial cytochrome c oxidase subunit I (mtCOI) barcodes as a marker for the molecular identification of the scavenger insects. The results showed that there were more insects on the camels and goats than the dogs. In total, seven species were found on all carrions. Six species were found on the camels and goats, but only five were found on the dog. Musca domestica was the most collected species of flies whereas, Necrobia rufipes was the most collected species of beetles. Overall, this study showed that carrion type had an effect on the type and number of insects attracted to the carrions. Thus, one of the significant factors that influence the associated scavenger assemblage is a carcass type.

9.
Neurotoxicology ; 69: 11-16, 2018 12.
Article in English | MEDLINE | ID: mdl-30149051

ABSTRACT

Delirium is an acute state of confusion and a fluctuating level of consciousness. It is precipitated by physical illness or trauma, such as pneumonia, heart infarction, or hip fracture. Delirium is common among elderly hospitalized patients, and as many as 50% of hip fracture patients may develop delirium. Delirium may precipitate dementia, but recent studies indicate that delirium is caused by unknown neurotoxic mechanisms that are different from those that are associated with dementia. Experimental studies have shown that high extracellular levels of sodium are neurotoxic. We sampled lumbar cerebrospinal fluid (CSF) from hip fracture patients during hip surgery and analyzed metal ions that influence neuronal function. Eight patients who developed delirium after surgery had 21% higher CSF sodium than 17 patients who did not develop delirium (median value 175 mmol/L; range 154-188, vs. 145 mmol/L (112-204; p < 0.008) or 39 patients who underwent elective surgery under spinal anesthesia without developing delirium (145 mmol/L; 140-149; p = 0.0004). Seven patients who had developed delirium before CSF sampling had a median CSF sodium of 150 mmol/L (144-185; p = 0.3). CSF potassium was also 21% higher in patients who developed delirium (p = 0.024), but remained within the physiological range. Serum sodium and potassium were normal in all patient groups. This study, on a small sample of patients, confirms the neurotoxic potential and clinical importance of high extracellular levels of sodium in the brain. High CSF sodium would likely affect cerebral function and could precipitate delirium; further, it could interact with dementia-specific mechanisms to precipitate dementia development.


Subject(s)
Delirium/cerebrospinal fluid , Hip Fractures/cerebrospinal fluid , Hip Fractures/surgery , Postoperative Complications/cerebrospinal fluid , Sodium/cerebrospinal fluid , Sodium/toxicity , Aged , Aged, 80 and over , Cohort Studies , Delirium/etiology , Delirium/psychology , Female , Hip Fractures/psychology , Humans , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Complications/psychology , Prospective Studies
10.
Dement Geriatr Cogn Dis Extra ; 7(3): 374-385, 2017.
Article in English | MEDLINE | ID: mdl-29282410

ABSTRACT

OBJECTIVES: This study aimed to investigate the relationship between cerebrospinal fluid (CSF) S100B astrocyte-derived protein and delirium and to perform stratified analyses according to clinical and CSF markers of dementia. METHODS: We performed a prospective cohort study in a university hospital setting. The participants were patients admitted for hip fracture (n = 98) or for elective surgery (n = 50). Delirium was assessed daily perioperatively in hip fracture patients using the Confusion Assessment Method. A consensus-based diagnosis of prefracture dementia was made using all available information. CSF was drawn at the onset of spinal anesthesia. S100B and phosphorylated tau (P-tau) concentrations were measured using electrochemiluminescence immunoassay and enzyme-linked immunosorbent assays, respectively. RESULTS: In the hip fracture population (n = 98) there was no significant difference in CSF S100B concentrations between patients with ongoing preoperative (i.e., prevalent) delirium (n = 36, median [interquartile range] 1.11 µg/L [0.91-1.29]) and patients who never developed delirium (n = 46, 1.08 µg/L [0.92-1.28], p = 0.92). In patients without preoperative delirium, those who developed delirium postoperatively (i.e., incident delirium) (n = 16, 1.38 µg/L [1.08-1.62]) had higher concentrations of S100B than the 46 who never did (p = 0.013). This difference was confined to patients with pathological concentrations of P-tau (≥60 ng/L, n = 38). We also found that P-tau and S100B were correlated in CSF in the elective surgery patients. CONCLUSIONS: CSF S100B was elevated in patients with incident delirium who also had pathological levels of the Alzheimer disease biomarker P-tau, suggesting vulnerability caused by a preexisting process of astrocytic activation and tau pathology.

11.
Development ; 144(22): 4125-4136, 2017 11 15.
Article in English | MEDLINE | ID: mdl-29061636

ABSTRACT

During CNS development, interneuron precursors have to migrate extensively before they integrate in specific microcircuits. Known regulators of neuronal motility include classical neurotransmitters, yet the mechanisms that assure interneuron dispersal and interneuron/projection neuron matching during histogenesis remain largely elusive. We combined time-lapse video microscopy and electrophysiological analysis of the nascent cerebellum of transgenic Pax2-EGFP mice to address this issue. We found that cerebellar interneuronal precursors regularly show spontaneous postsynaptic currents, indicative of synaptic innervation, well before settling in the molecular layer. In keeping with the sensitivity of these cells to neurotransmitters, ablation of synaptic communication by blocking vesicular release in acute slices of developing cerebella slows migration. Significantly, abrogation of exocytosis primarily impedes the directional persistence of migratory interneuronal precursors. These results establish an unprecedented function of the early synaptic innervation of migrating neuronal precursors and demonstrate a role for synapses in the regulation of migration and pathfinding.


Subject(s)
Cell Movement , Interneurons/cytology , Neural Stem Cells/cytology , Synapses/metabolism , Animals , Cell Shape , Cerebellum/cytology , Cerebellum/ultrastructure , Electrophysiological Phenomena , Female , Glutamates/metabolism , Interneurons/metabolism , Male , Mice, Inbred C57BL , Models, Biological , Neural Stem Cells/metabolism , PAX2 Transcription Factor/metabolism , gamma-Aminobutyric Acid/metabolism
12.
J Vis (Tokyo) ; 20(2): 251-261, 2017.
Article in English | MEDLINE | ID: mdl-28515659

ABSTRACT

ABSTRACT: A series of experiments involving the particle image velocimetry technique are carried out to analyse the quantitative effectiveness of the synthesized vortical structures towards actual flow separation control. The streamwise vortices are synthesized from the synthetic jet actuator and introduced into the attached and separating boundary layer developed on the flat plate surface. Two types of actuators with different geometrical set-ups are used to analyse the evolution of vortical structures in the near wall region and their impact towards achieving separation delay in the boundary layer. First, a single circular jet is synthesized by varying actuator operating parameters and issued into the boundary layer to evaluate the dynamics of the interaction between the vortical structures and the near wall low momentum fluid in the separated region. Second, an array of jets has been issued into the artificially separated region to assess the effectiveness of various vortical structures towards achieving the reattachment of the separated flow in the streamwise direction.

13.
BMJ Case Rep ; 20172017 Apr 23.
Article in English | MEDLINE | ID: mdl-28438753

ABSTRACT

Small bowel diverticulosis of the jejunum and ileum is an uncommon finding with a prevalence rate of 0.2% to 1.3% at autopsy and 0.3% to 1.9% on small bowel studies. Diagnosis can be difficult because there are no pathognomonic features or clinical symptoms that are specific for small bowel diverticulosis. Though rare, it is critical to keep the possibility of small bowel diverticulosis in mind when evaluating cases of malabsorption, chronic abdominal pain, haemorrhage, perforation and intestinal obstruction, especially in patients with connective tissue disorders, a family history of diverticula and a personal history of colonic diverticulosis. Guidelines for the treatment of complicated small bowel diverticulosis are not clearly defined. However, the consensus in treatment is to do a small bowel resection with primary anastomosis. We report three interesting cases of jejunoileal diverticula that presented in an occult manner and later progressed to more emergent manifestations.


Subject(s)
Diverticular Diseases/diagnosis , Ileal Diseases/diagnosis , Intestine, Small , Jejunal Diseases/diagnosis , Aged , Aged, 80 and over , Diagnosis, Differential , Diagnostic Imaging , Disease Progression , Diverticular Diseases/pathology , Diverticular Diseases/therapy , Female , Humans , Ileal Diseases/pathology , Ileal Diseases/therapy , Jejunal Diseases/pathology , Jejunal Diseases/therapy , Male
14.
BMJ Case Rep ; 20172017 Jan 31.
Article in English | MEDLINE | ID: mdl-28143859

ABSTRACT

In ∼60% of cases, hepatic artery anatomy is of the normal variant. However, in 40% of cases, anomalies can exist. Preserving the hepatic blood supply is paramount in hepatobiliary procedures. We report an aberrant right hepatic artery coursing retroportally, with an aberrant left hepatic artery originating directly from the coeliac artery in a patient who underwent an elective pancreaticoduodenectomy (Whipple procedure).


Subject(s)
Anatomic Variation , Bile Duct Neoplasms/surgery , Celiac Artery/abnormalities , Cholangiocarcinoma/surgery , Hepatic Artery/abnormalities , Pancreaticoduodenectomy , Splenic Artery/abnormalities , Celiac Artery/diagnostic imaging , Computed Tomography Angiography , Female , Hepatic Artery/diagnostic imaging , Humans , Middle Aged , Splenic Artery/diagnostic imaging
15.
J Med Entomol ; 53(6): 1276-1282, 2016 11.
Article in English | MEDLINE | ID: mdl-27452291

ABSTRACT

Necrophagous species of insects provide useful complementary data to estimate the postmortem interval in forensic cases. Here, for the first time, we report on insect specimens collected from human corpses in Riyadh, Kingdom of Saudi Arabia. During the study, 14 beetle larvae were collected from the outdoor corpse (case report one) and five flies and seven beetles were collected from the indoor corpse (case report two). Sequencing was performed to study the mitochondrial DNA (mtDNA) as the prospective basis of an identification technique. The sequencing focused on a section of the cytochrome oxidase I encoding region of mtDNA. Two beetle species, Dermestes frischii (Kugelann) and Dermestes maculatus (De Geer) (Coleoptera: Dermestidae), and one fly species, Chrysomya albiceps (Wiedemann) (Diptera: Calliphoridae), were identified. These results will be instrumental in the implementation of a Saudi database of forensically relevant insects.


Subject(s)
Coleoptera/physiology , Diptera/physiology , Animals , Base Sequence , Cadaver , Coleoptera/classification , Coleoptera/genetics , Coleoptera/growth & development , Diptera/classification , Diptera/genetics , Diptera/growth & development , Electron Transport Complex IV/genetics , Entomology , Forensic Sciences , Humans , Insect Proteins/genetics , Larva/classification , Larva/genetics , Larva/growth & development , Larva/physiology , Mitochondrial Proteins/genetics , Saudi Arabia , Sequence Alignment
16.
Am J Physiol Renal Physiol ; 310(11): F1229-42, 2016 06 01.
Article in English | MEDLINE | ID: mdl-27009341

ABSTRACT

Glutamine synthetase (GS) catalyzes the recycling of NH4 (+) with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of the present study was to determine the role of PT GS in ammonia metabolism under basal conditions and during metabolic acidosis. We generated mice with PT-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Under basal conditions, PT-GS-KO increased urinary ammonia excretion significantly. Increased ammonia excretion occurred despite decreased expression of key proteins involved in renal ammonia generation. After the induction of metabolic acidosis, the ability to increase ammonia excretion was impaired significantly by PT-GS-KO. The blunted increase in ammonia excretion occurred despite greater expression of multiple components of ammonia generation, including SN1 (Slc38a3), phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and Na(+)-coupled electrogenic bicarbonate cotransporter. We conclude that 1) GS-mediated ammonia recycling in the PT contributes to both basal and acidosis-stimulated ammonia metabolism and 2) adaptive changes in other proteins involved in ammonia metabolism occur in response to PT-GS-KO and cause an underestimation of the role of PT GS expression.


Subject(s)
Acidosis/metabolism , Ammonia/metabolism , Glutamate-Ammonia Ligase/genetics , Kidney Tubules, Proximal/metabolism , Animals , Bicarbonates/metabolism , Cation Transport Proteins/metabolism , Glutamate-Ammonia Ligase/metabolism , Mice , Mice, Knockout
18.
J Infect Public Health ; 9(4): 443-51, 2016.
Article in English | MEDLINE | ID: mdl-26688375

ABSTRACT

Our objective was to evaluate the impact of using an imipenem de-escalation protocol for empiric febrile neutropenia on the development of carbapenem resistance. A pre-post intervention design was used. The intervention was adopting the imipenem de-escalation approach, which began on January 1, 2012. A retrospective chart review of cases of febrile neutropenia bacteremia was performed one year before and one year after the intervention. We compared the development of carbapenem resistance between the two study periods. Seventy-five episodes of febrile neutropenia bacteremia were included in the study. They had similar demographics, clinical features and outcomes. There were 78 and 12 pathogens in the primary and follow-up blood cultures, respectively. Approximately 61% and 66% of the primary and follow-up blood cultures, respectively, were gram-negative bacteria with similar carbapenem resistance profiles in the two study periods. In our study population, 57% of the gram-negative bacteria were ESBL pathogens. The resistance of the gram-negative bacteria to piperacillin/tazobactam (72% versus 53%, p=0.161), imipenem (16% versus 11%, p=0.684), and meropenem (8% versus 16%, p=0.638) did not significantly change after our policy change. In conclusion, the use of the carbapenem de-escalation approach for febrile neutropenia in our institution was not associated with an increase in carbepenem resistance. Future prospective multi-center studies are recommended to further confirm the current findings.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Drug Utilization , Febrile Neutropenia/drug therapy , Gram-Negative Bacteria/drug effects , Imipenem/therapeutic use , beta-Lactam Resistance , Adult , Aged , Female , Humans , Male , Middle Aged , Non-Randomized Controlled Trials as Topic , Prevalence
20.
J Inherit Metab Dis ; 38(6): 1075-83, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25896882

ABSTRACT

Glutamine synthetase (GS) deficiency is an ultra-rare inborn error of amino acid metabolism that has been described in only three patients so far. The disease is characterized by neonatal onset of severe encephalopathy, low levels of glutamine in blood and cerebrospinal fluid, chronic moderate hyperammonemia, and an overall poor prognosis in the absence of an effective treatment. Recently, enteral glutamine supplementation was shown to be a safe and effective therapy for this disease but there are no data available on the long-term effects of this intervention. The amino acid glutamine, severely lacking in this disorder, is central to many metabolic pathways in the human organism and is involved in the synthesis of nicotinamide adenine dinucleotide (NAD(+)) starting from tryptophan or niacin as nicotinate, but not nicotinamide. Using fibroblasts, leukocytes, and immortalized peripheral blood stem cells (PBSC) from a patient carrying a GLUL gene point mutation associated with impaired GS activity, we tested whether glutamine deficiency in this patient results in NAD(+) depletion and whether it can be rescued by supplementation with glutamine, nicotinamide or nicotinate. The present study shows that congenital GS deficiency is associated with NAD(+) depletion in fibroblasts, leukocytes and PBSC, which may contribute to the severe clinical phenotype of the disease. Furthermore, it shows that NAD(+) depletion can be rescued by nicotinamide supplementation in fibroblasts and leukocytes, which may open up potential therapeutic options for the treatment of this disorder.


Subject(s)
Amino Acid Metabolism, Inborn Errors/genetics , Glutamate-Ammonia Ligase/deficiency , Glutamine/blood , Hyperammonemia/genetics , NAD/blood , NAD/deficiency , B-Lymphocytes/cytology , Cell Culture Techniques , Dietary Supplements , Fibroblasts/cytology , Glutamate-Ammonia Ligase/genetics , Humans , Point Mutation
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