Clinical features of generalized lipodystrophy in Turkey: A cohort analysis.

AIM: To describe the Turkish generalized lipodystrophy (GL) cohort with the frequency of each complication and the death rate during the period of the follow-up. METHODS: This study reports on 72 patients with GL (47 families) registered at different centres in Turkey that cover all regions of the country. The mean ± SD follow-up was 86 ± 78 months. RESULTS: The Kaplan-Meier estimate of the median time to diagnosis of diabetes and/or prediabetes was 16 years. Hyperglycaemia was not controlled in 37 of 45 patients (82.2%) with diabetes. Hypertriglyceridaemia developed in 65 patients (90.3%). The Kaplan-Meier estimate of the median time to diagnosis of hypertriglyceridaemia was 14 years. Hypertriglyceridaemia was severe (≥ 500 mg/dl) in 38 patients (52.8%). Seven (9.7%) patients suffered from pancreatitis. The Kaplan-Meier estimate of the median time to diagnosis of hepatic steatosis was 15 years. Liver disease progressed to cirrhosis in nine patients (12.5%). Liver disease was more severe in congenital lipodystrophy type 2 (CGL2). Proteinuric chronic kidney disease (CKD) developed in 32 patients (44.4%) and cardiac disease in 23 patients (31.9%). Kaplan-Meier estimates of the median time to diagnosis of CKD and cardiac disease were 25 and 45 years, respectively. Females appeared to have a more severe metabolic disease, with an earlier onset of metabolic abnormalities. Ten patients died during the follow-up period. Causes of death were end-stage renal disease, sepsis (because of recurrent intestinal perforations, coronavirus disease, diabetic foot infection and following coronary artery bypass graft surgery), myocardial infarction, heart failure because of dilated cardiomyopathy, stroke, liver complications and angiosarcoma. CONCLUSIONS: Standard treatment approaches have only a limited impact and do not prevent the development of severe metabolic abnormalities and early onset of organ complications in GL.

Detecting the specific parameters that affect the maturation of farmed sea bass (Dicentrarchus labrax) fillets stored in sunflower oil.

In this study, it was aimed to detect the specific parameters that effect the maturation of farmed sea bass fillets stored in sunflower oil. Sea bass fillets were taken into the pickling solution (2.5% acetic acid and 11% sodium chloride) at 4 °C(±1). Fish meat in each group was analysed for the following parameters; pH, moisture%, acetic acid% and NaCl% in the maturation pickling solution and in sunflower oil. At the end of the 90 days storage, there were not any negative situations about the fish in terms of the scientific approach. It was detected that the skinless samples had the less NaCl and acidity values but scaly and scaleless samples had the higher values. Main reasons are: for the scaly and scaleless samples, the skin acted as a barrier in the pickling solution or oil and for scaly samples, scales depart from the skin and defeat the passing of NaCl and acid to the meat. When evaluating this study results, the fillet group samples which contain more salt and acetic acid are thought to be more appropriate for marinating in terms of shelf-life and quality.

READv2: advanced and user-friendly detection of biological relatedness in archaeogenomics.

The advent of genome-wide ancient DNA analysis has revolutionized our understanding of prehistoric societies. However, studying biological relatedness in these groups requires tailored approaches due to the challenges of analyzing ancient DNA. READv2, an optimized Python3 implementation of the most widely used tool for this purpose, addresses these challenges while surpassing its predecessor in speed and accuracy. For sufficient amounts of data, it can classify up to third-degree relatedness and differentiate between the two types of first-degree relatedness, full siblings and parent-offspring. READv2 enables user-friendly, efficient, and nuanced analysis of biological relatedness, facilitating a deeper understanding of past social structures.

Benchmarking kinship estimation tools for ancient genomes using pedigree simulations.

There is growing interest in uncovering genetic kinship patterns in past societies using low-coverage palaeogenomes. Here, we benchmark four tools for kinship estimation with such data: lcMLkin, NgsRelate, KIN, and READ, which differ in their input, IBD estimation methods, and statistical approaches. We used pedigree and ancient genome sequence simulations to evaluate these tools when only a limited number (1 to 50 K, with minor allele frequency ≥0.01) of shared SNPs are available. The performance of all four tools was comparable using ≥20 K SNPs. We found that first-degree related pairs can be accurately classified even with 1 K SNPs, with 85% F1 scores using READ and 96% using NgsRelate or lcMLkin. Distinguishing third-degree relatives from unrelated pairs or second-degree relatives was also possible with high accuracy (F1 > 90%) with 5 K SNPs using NgsRelate and lcMLkin, while READ and KIN showed lower success (69 and 79% respectively). Meanwhile, noise in population allele frequencies and inbreeding (first-cousin mating) led to deviations in kinship coefficients, with different sensitivities across tools. We conclude that using multiple tools in parallel might be an effective approach to achieve robust estimates on ultra-low-coverage genomes.

Deciphering the Clinical Presentations in LMNA-related Lipodystrophy: Report of 115 Cases and a Systematic Review.

CONTEXT: Lipodystrophy syndromes are a heterogeneous group of rare genetic or acquired disorders characterized by generalized or partial loss of adipose tissue. LMNA-related lipodystrophy syndromes are classified based on the severity and distribution of adipose tissue loss. OBJECTIVE: We aimed to annotate all clinical and metabolic features of patients with lipodystrophy syndromes carrying pathogenic LMNA variants and assess potential genotype-phenotype relationships. METHODS: We retrospectively reviewed and analyzed all our cases (n = 115) and all published cases (n = 379) curated from 94 studies in the literature. RESULTS: The study included 494 patients. The most common variants in our study, R482Q and R482W, were associated with similar metabolic characteristics and complications though those with the R482W variant were younger (aged 33 [24] years vs 44 [25] years; P < .001), had an earlier diabetes diagnosis (aged 27 [18] vs 40 [17] years; P < .001) and had lower body mass index levels (24 [5] vs 25 [4]; P = .037). Dyslipidemia was the earliest biochemical evidence described in 83% of all patients at a median age of 26 (10) years, while diabetes was reported in 61% of cases. Among 39 patients with an episode of acute pancreatitis, the median age at acute pancreatitis diagnosis was 20 (17) years. Patients who were reported to have diabetes had 3.2 times, while those with hypertriglyceridemia had 12.0 times, the odds of having pancreatitis compared to those who did not. CONCLUSION: This study reports the largest number of patients with LMNA-related lipodystrophy syndromes to date. Our report helps to quantify the prevalence of the known and rare complications associated with different phenotypes and serves as a comprehensive catalog of all known cases.

Population Genomic History of the Endangered Anatolian and Cyprian Mouflons in Relation to Worldwide Wild, Feral, and Domestic Sheep Lineages.

Once widespread in their homelands, the Anatolian mouflon (Ovis gmelini anatolica) and the Cyprian mouflon (Ovis gmelini ophion) were driven to near extinction during the 20th century and are currently listed as endangered populations by the International Union for Conservation of Nature. While the exact origins of these lineages remain unclear, they have been suggested to be close relatives of domestic sheep or remnants of proto-domestic sheep. Here, we study whole genome sequences of n = 5 Anatolian mouflons and n = 10 Cyprian mouflons in terms of population history and diversity, comparing them with eight other extant sheep lineages. We find reciprocal genetic affinity between Anatolian and Cyprian mouflons and domestic sheep, higher than all other studied wild sheep genomes, including the Iranian mouflon (O. gmelini). Studying diversity indices, we detect a considerable load of short runs of homozygosity blocks (<2 Mb) in both Anatolian and Cyprian mouflons, reflecting small effective population size (Ne). Meanwhile, Ne and mutation load estimates are lower in Cyprian compared with Anatolian mouflons, suggesting the purging of recessive deleterious variants in Cyprian sheep under a small long-term Ne, possibly attributable to founder effects, island isolation, introgression from domestic lineages, or differences in their bottleneck dynamics. Expanding our analyses to worldwide wild and feral Ovis genomes, we observe varying viability metrics among different lineages and a limited consistency between viability metrics and International Union for Conservation of Nature conservation status. Factors such as recent inbreeding, introgression, and unique population dynamics may have contributed to the observed disparities.

Retrospective Evaluation of the Results of Low-Dose Intravenous Thrombolytic Therapy in Acute Ischemic Stroke.

Objectives: This study aimed to investigate the clinical data of patients with acute ischemic stroke who received low-dose intravenous (IV) thrombolytic therapy (0.9 mg/kg; maximum 50 mg) for various reasons, compare the obtained results with those of patients who received standard-dose thrombolytic therapy, and discuss them in light of the literature. Methods: Patients who received IV thrombolytic therapy within 4.5 h of symptom onset between January 2015 and June 2018 were retrospectively reviewed. Patients were divided into the low-dose group (0.9 mg/kg; max. 50 mg) and the standard-dose group (0.9 mg/kg; max 90 mg) according to the thrombolytic therapy dose, after which demographic data and clinical results were analyzed. Results: A total of 109 patients receiving thrombolytic therapy (19 patients in the low-dose group and 90 patients in the standard-dose group) were included in the study. There was no significant difference between the two groups in terms of good outcome rates (47.4% vs. 52.2%). There was no statistically significant difference in terms of symptomatic and asymptomatic intracerebral hemorrhage rates. Conclusion: Our study showed similar efficacy and safety for low-dose IV thrombolytic therapy compared with standard-dose IV thrombolytic therapy administered within 4.5 h of symptom onset in patients with acute ischemic stroke.

Mitochondrial Protein Synthesis and mtDNA Levels Coordinated through an Aminoacyl-tRNA Synthetase Subunit.

The aminoacylation of tRNAs by aminoacyl-tRNA synthetases (ARSs) is a central reaction in biology. Multiple regulatory pathways use the aminoacylation status of cytosolic tRNAs to monitor and regulate metabolism. The existence of equivalent regulatory networks within the mitochondria is unknown. Here, we describe a functional network that couples protein synthesis to DNA replication in animal mitochondria. We show that a duplication of the gene coding for mitochondrial seryl-tRNA synthetase (SerRS2) generated in arthropods a paralog protein (SLIMP) that forms a heterodimeric complex with a SerRS2 monomer. This seryl-tRNA synthetase variant is essential for protein synthesis and mitochondrial respiration. In addition, SLIMP interacts with the substrate binding domain of the mitochondrial protease LON, thus stimulating proteolysis of the DNA-binding protein TFAM and preventing mitochondrial DNA (mtDNA) accumulation. Thus, mitochondrial translation is directly coupled to mtDNA levels by a network based upon a profound structural modification of an animal ARS.

Predictive Factors for Functional Outcomes After Intravenous Thrombolytic Therapy in Acute Ischemic Stroke.

The objective of our study is to detect the patient group that will most benefit from intravenous (IV) thrombolytic therapy by showing predictive factors of good functional outcomes. The present study covers 88 patients who were admitted to our clinic within the first 4.5 hours from the onset of stroke symptoms, diagnosed with acute ischemic stroke and who received IV thrombolytic therapy between May 2014 and June 2017 as a result of a retrospective analysis of a database prospectively collected. The patients with a score of ≤2 on modified Rankin scale within 3 months were accepted as good functional outcome and those with a score of >2 were accepted as poor functional outcome. As a result, within the period of 3 months posttreatment, good functional outcomes were obtained in 45 (51.1%) patients and poor functional outcomes were obtained in 43 (48.9%) patients. In comparisons, cardioembolic stroke group was statistically significantly higher in the good functional outcome group (P = .03). Pretreatment National Institute of Health Stroke Scale (NIHSS) scores (P < .001), presence of proximal hyperintense middle cerebral artery sign in noncontrast computed brain tomography (P = .03), and being aged ≥80 and older (P = .04) were markedly higher in the group with poor functional outcomes. In conclusion, our study demonstrated that cardioembolic strokes may have an impact on good functional outcomes and being aged 80 and older, presence of proximal HMCAS in computed brain tomography, and pretreatment NIHSS scores may have an impact on poor functional outcomes.