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Acta Neurologica Belgica Aug 2023
Topics: Humans; MELAS Syndrome; Autoantibodies; Membrane Proteins
PubMed: 36333640
DOI: 10.1007/s13760-022-02135-4 -
Molecular Genetics and Metabolism Nov 2023Mitochondrial DNA m.3243A > G mutation causes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and its associated multi-organ disorders,...
Mitochondrial DNA m.3243A > G mutation causes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and its associated multi-organ disorders, including diabetes. To clarify associations between m.3243A > G organ heteroplasmy and clinical phenotypes, including the age at death, we combined genetic and pathological examinations from seven unreported and 36 literature cases of autopsied subjects. Clinical characteristics of subjects were as follows: male, 13; female, 28; unknown, 2; the age at death, 36.9 ± 20.2 [4-82] years; BMI, 16.0 ± 2.9 [13.0-22.3]; diabetes, N = 21 (49%), diabetes onset age 38.6 ± 14.2 years; deafness, N = 27 (63%); stroke-like episodes (StLEp), N = 25 (58%); congestive heart failure (CHF), N = 15 (35%); CHF onset age, 51.3 ± 14.5 years. Causes of death (N = 32) were as follows: cardiac, N = 13 (41%); infection, N = 8 (25%); StLEp, N = 4 (13%); gastrointestinal, N = 4 (13%); renal, N = 2 (6%); hepatic, N = 1 (2%). High and low heteroplasmies were confirmed in non-regenerative and regenerative organs, respectively. Heteroplasmy of the liver, spleen, leukocytes, and kidney for all subjects was significantly associated with the age at death. Furthermore, the age at death was related to juvenile-onset (any m.3243A > G-related symptoms appeared before 20) and stroke-like episodes. Multiple linear regression analysis with the age at death as an objective variable showed the significant contribution of liver heteroplasty and juvenile-onset to the age at death. m.3243A > G organ heteroplasmy levels, particularly hepatic heteroplasmy, are significantly associated with the age at death in deceased cases.
Topics: Humans; Male; Female; Adult; Middle Aged; Aged; Child, Preschool; Child; Adolescent; Young Adult; Aged, 80 and over; Heteroplasmy; DNA, Mitochondrial; Mutation; Diabetes Mellitus; Stroke; Liver; MELAS Syndrome
PubMed: 37660570
DOI: 10.1016/j.ymgme.2023.107691 -
Cureus Mar 2024This case report presents a description of a hypertrophic left ventricle with reduced ejection fraction in a man in his mid-twenties with clinical, radiologic, and...
This case report presents a description of a hypertrophic left ventricle with reduced ejection fraction in a man in his mid-twenties with clinical, radiologic, and biochemical features of a rare syndrome called mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). A literature review of this uncommon syndrome and MELAS cardiomyopathy has been conducted.
PubMed: 38665734
DOI: 10.7759/cureus.56980 -
Frontiers in Genetics 2024Patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) usually present with multisystemic dysfunction with a wide range of...
BACKGROUND
Patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) usually present with multisystemic dysfunction with a wide range of clinical manifestations. When the tests for common mitochondrial DNA (mtDNA) point mutations are negative and the mtDNA defects hypothesis remains, urine epithelial cells can be used to screen the mitochondrial genome for unknown mutations to confirm the diagnosis.
CASE PRESENTATION
A 66-year-old Chinese woman presented with symptoms of MELAS and was initially misdiagnosed with acute encephalitis at another institution. Although genetic analysis of blood lymphocyte DNA was negative, brain imaging, including magnetic resonance imaging, magnetic resonance spectroscopy, and clinical and laboratory findings, were all suggestive of MELAS. Finally, the patient was eventually diagnosed with MELAS with the mtDNA 5783G>A mutation in the MT-TC gene with a urinary sediment genetic test.
CONCLUSION
This case report expands the genetic repertoire associated with MELAS syndrome and highlights the importance that full mtDNA sequencing should be warranted beside the analysis of classical variants when a mitochondrial disorder is highly suspected. Furthermore, urine sediment genetic testing has played a crucial role in the diagnosis of MELAS.
PubMed: 38881794
DOI: 10.3389/fgene.2024.1367716 -
Acta Parasitologica Mar 2024Skeeter syndrome is a severe local allergic response to mosquito bites that is accompanied by considerable inflammation and, in some cases, a systemic response like...
BACKGROUND
Skeeter syndrome is a severe local allergic response to mosquito bites that is accompanied by considerable inflammation and, in some cases, a systemic response like fever. People with the syndrome develop serious allergies, ranging from rashes to anaphylaxis or shock. The few available studies on mosquito venom immunotherapy have utilized whole-body preparations and small sample sizes. Still, owing to their little success, vaccination remains a promising alternative as well as a permanent solution for infections like Skeeter's.
METHODS
This study, therefore, illustrated the construction of an epitope-based vaccine candidate against Skeeter Syndrome using established immunoinformatic techniques. We selected three species of mosquitoes, Anopheles melas, Anopheles funestus, and Aedes aegypti, to derive salivary antigens usually found in mosquito bites. Our construct was also supplemented with bacterial epitopes known to elicit a strong TH1 response and suppress TH2 stimulation that is predicted to reduce hypersensitivity against the bites.
RESULTS
A quality factor of 98.9496, instability index of 38.55, aliphatic index of 79.42, solubility of 0.934747, and GRAVY score of -0.02 indicated the structural (tertiary and secondary) stability, thermostability, solubility, and hydrophilicity of the construct, respectively. The designed Aedes-Anopheles vaccine (AAV) candidate was predicted to be flexible and less prone to deformability with an eigenvalue of 1.5911e-9 and perfected the human immune response against Skeeter (hypersensitivity) and many mosquito-associated diseases as we noted the production of 30,000 Th1 cells per mm with little (insignificant production of Th2 cells. The designed vaccine also revealed stable interactions with the pattern recognition receptors of the host. The TLR2/vaccine complex interacted with a free energy of - 1069.2 kcal/mol with 26 interactions, whereas the NLRP3/vaccine complex interacted with a free energy of - 1081.2 kcal/mol with 16 molecular interactions.
CONCLUSION
Although being a pure in-silico study, the in-depth analysis performed herein speaks volumes of the potency of the designed vaccine candidate predicting that the proposition can withstand rigorous in-vitro and in-vivo clinical trials and may proceed to become the first preventative immunotherapy against mosquito bite allergy.
Topics: Animals; Insect Bites and Stings; Anopheles; Aedes; Epitopes; Hypersensitivity; Vaccines; Humans
PubMed: 38194049
DOI: 10.1007/s11686-023-00771-1 -
Cureus Nov 2023A patient with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, a rare mitochondrial disease characterized by myopathy,...
A patient with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, a rare mitochondrial disease characterized by myopathy, epilepsy, encephalopathy, acidosis, and recurrent cerebral ischemic episodes, underwent systemic hematogenous ozone therapy for 17 years. Despite advancements in the study of mitochondrial diseases, there are currently no available treatments for MELAS. The patient in this case has received over 280 sessions of systemic hematic ozone therapy since 2003 (from the age of 10 years) till the time of publication, without reporting any adverse effects, achieving a normal level of development considering the comorbidities. Possible mechanisms of action of systemic hematogenous ozone therapy include improved efficiency of the mitochondrial oxidative chain through the induction of antioxidant enzymes (catalase, superoxide dismutases {SOD}, peroxidase). More studies are needed to evaluate the actual safety of long-term systemic hematogenous ozone therapy in patients with mitochondrial diseases.
PubMed: 38054163
DOI: 10.7759/cureus.48261 -
Acta Neurologica Belgica Aug 2023
Topics: Humans; MELAS Syndrome; Lactic Acid; Stroke; Magnetic Resonance Spectroscopy
PubMed: 35674909
DOI: 10.1007/s13760-022-01999-w -
European Journal of Case Reports in... 2024
PubMed: 38584895
DOI: 10.12890/2024_004388 -
Acta Neurologica Belgica Aug 2023
Topics: Humans; Diagnosis, Differential; Stroke; MELAS Syndrome; DNA, Mitochondrial; Mutation
PubMed: 35882776
DOI: 10.1007/s13760-022-02047-3 -
Acta Neurologica Belgica Oct 2023
Topics: Humans; MELAS Syndrome; Stroke; Neurodegenerative Diseases; Calcinosis; Brain; Magnetic Resonance Imaging
PubMed: 35752746
DOI: 10.1007/s13760-022-02000-4