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Childhood is the most crucial stage in human life, as well as for the cognitive and technological development of our species. However, earlier traditional archaeological studies have often neglected the role of children in prehistoric societies and focused on the primary socio-economic elements of daily life in prehistory (e.g. agriculture, animal husbandry, hunting-gathering, and various crafts). The picture of a Neolithic village portrayed by archaeologists mostly comprised adults who were engaged in production and subsistence. Children, were seen as passive until they reached a certain age when they became active in production. Increasing ethnographic and archaeological studies however, portray a contrasting picture as they yield insights into the learning and transmission processes of know-how and skills regarding socio-economic activities, technologies, and craft production which suggest that social roles and identities are all formed during childhood. Thus, although the state of research shows that we still have further steps to go, it is clear that a deeper understanding of childhood and children in prehistory is as essential as understanding the world of adults. In such an attempt, this article focuses on the children of Aşıklı Höyük, an Early Neolithic community in Central Anatolia. We briefly discuss the skeletal evidence emerging from the anthropological analyses, and attempt to approach the roles and identities of children through the lens of grave goods and lithic production technologies.

Heart transplantation is associated with major hurdles, including the limited number of available organs for transplantation, the risk of rejection due to genetic discrepancies, and the burden of immunosuppression. In this study, we demonstrated the feasibility of permanent genetic engineering of the heart during ex vivo perfusion. Lentiviral vectors encoding for short hairpin RNAs targeting beta2-microglobulin (shβ2m) and class II transactivator (shCIITA) were delivered to the graft during two hours of normothermic EVHP. Highly efficient genetic engineering was indicated by stable reporter gene expression in endothelial cells and cardiomyocytes. Remarkably, swine leucocyte antigen (SLA) class I and SLA class II expression levels were decreased by 66% and 76%, respectively, in the vascular endothelium. Evaluation of lactate, troponin T, and LDH levels in the perfusate and histological analysis showed no additional cell injury or tissue damage caused by lentiviral vectors. Moreover, cytokine secretion profiles (IL-6, IL-8, and TNF-α) of non-transduced and lentiviral vector-transduced hearts were comparable. This study demonstrated the ex vivo generation of genetically engineered hearts without compromising tissue integrity. Downregulation of SLA expression may contribute to reduce the immunogenicity of the heart and support graft survival after allogeneic or xenogeneic transplantation.

In the title molecular salt, C26H24N3S+·Br−, the dihedral angles between the thiazole ring and its attached phenyl and benzoyl rings are 54.81 (7) and 85.51 (7)°, respectively. In the crystal, ion pairs are linked by C—H...Br and N—H...Br hydrogen bonds and are connected into helical chains extending along the c-axis direction by weak, electrostatic S...Br− interactions. A Hirshfeld surface analysis was performed, which showed the dominant role of H...H contacts (51.3%).

Bu araştırmanın amacı öz düzenlemeli öğrenme yaklaşımının görsel sanatlar öğretmeni adaylarının sanat eleştirisi dersine yönelik akademik başarılarına ve kalıcılığa etkisini incelemektir. Nicel araştırma yöntemlerinden deneysel yöntemin ön test son test kontrol gruplu yarı deneysel modeli ile gerçekleştirilen araştırmanın çalışma grubunu, 2014-2015 Güz Döneminde, Atatürk Üniversitesi Kazım Karabekir Eğitim Fakültesi Resim İş Eğitimi Ana Bilim Dalı’nda öğrenim gören 38 öğretmen adayı oluşturmaktadır. Araştırmada öz düzenlemeli öğrenmenin görsel sanatlar öğretmeni adaylarının akademik başarılarına etkisini kontrol etmek için akademik başarı testi kullanılmıştır. Dersler deney grubunda öz düzenlemeli öğrenme yaklaşımına uygun olarak, kontrol grubuna ise sunuş yoluyla öğrenme yaklaşımına dayalı olarak işlenmiştir. Verilerin analizinde SPSS 19 Paket Programı kullanılmıştır. Non-parametrik verilerin toplanması için "İlişkisiz Ölçümler İçin Mann Whitney U-Testi", öntest-sontest, son test- kalıcılık puanlarını karşılaştırmak için non-parametrik istatistik tekniklerinden "İlişkili Ölçümler İçin Wilcoxon İşaretli Sıralar Testi" kullanılmıştır. Araştırma bulgularına göre; deney ve kontrol gruplarının son test puanlarına bakıldığında her iki öğrenme ortamında da akademik başarıda belli bir artış gözlenmiştir. Deney grubu ile kontrol grubu son test puanları karşılaştırıldığında; deney grubundakilerin akademik başarılarının kontrol grubundakilere göre daha yüksek olduğu görülmektedir. Bu bulgu; öz düzenlemeye dayalı öğretimin daha etkili bir öğrenme ortamı sağladığını ve öğrencilerin akademik başarılarını arttırmada daha etkili olduğunu göstermektedir. Ayrıca; deney ve kontrol gruplarının kalıcılık puanlarına bakıldığında her iki öğrenme ortamında da yapılan öğretimin kalıcılığını sürdürdüğü görülmüştür. Deney grubu ile kontrol grubu kalıcılık puanları karşılaştırıldığında; deney grubunun kalıcılık puanları kontrol grubuna göre daha yüksektir. Araştırma sonuçlarına dayanarak; öz düzenlemeli öğrenme yaklaşımının öğretmen adaylarının akademik başarılarına ve sanat eleştirisi dersi tutumlarına olumlu yönde etki ettiği söylenebilir.

In the title molecule, C28H27N3O3S, the heterocyclic portion of the tetrahydroisoquinoline unit is planar and an intramolecular N—H...N hydrogen bond and a C—H...π(ring) interaction help to determine the overall conformation. In the crystal, a layer structure with the layers parallel to (10\overline{1}) is generated by O—H...O and C—H...O hydrogen bonds.

In an effort to develop a potent antidiabetic drug, new quinoxaline derivative, 2-(4-((3-methyl-2-oxoquinoxalin-1(2H)-yl)methyl)-4,5-dihydro-1H-1,2,3-triazol-1-yl)-N-(p-tolyl)acetamide (MOQTA) was synthesized and characterized by XRD and various spectroscopic tools (IR, 1H &13C NMR, ESI-MS). The geometric optimization of the molecule was calculated with Density Functional Theory (DFT) method by B3LYP with a 6–311++G(d,p) basis set. Frontier Molecular Orbitals (FMOs) and Molecular Electrostatic Potential (MEP) surfaces of the title compound were generated. Furthermore, Hirshfeld surface analysis (HSA) and 2D fingerprint plots were presented. The calculated MEP and HSA surface interactions were compared in terms of hydrogen bonds and π-π stacking interactions obtained by X-ray packing analyses. X-ray crystallographic structure analysis revealed that the N—HN, C—HO and C—HN intermolecular hydrogen bonds were in agreement with those obtained by HSA. Moreover, MOQTA was assessed for its in vitro anti-diabetic activity. Likewise, molecular docking analyses were conducted to examine the binding mode between MOQTA and the enzymes α-glucosidase and α-amylase. Finally, the physicochemical, pharmacokinetic and toxicological properties of MOQTA have been evaluated by using in silico absorption, distribution, metabolism, excretion and toxicity analysis prediction.

Interfacially stabilized nonaqueous lipid-based foams, which we name here oleofoams, are rarely encountered as opposed to the large number of aqueous foams stabilized by molecular or particulate emulsifiers. There is no case well described in the literature with a convincing characterization of the interfacial contribution to oleofoam stability. Methods for filling this gap are described here, which reach out to a large part of the lipid phase diagram. We bring here complete evidence that lipidic crystals made of a high fraction of fully soluble monoglyceride (MG) in oil do not only adsorb at the oil-air interface but also can easily form a jammed, closely packed layer of crystals around the bubbles of a foam produced by whipping (Pickering effect). Very fine bubbles, soft textures, or firmer ones such as for shaving foams could be obtained, with a high air fraction (up to 75%), which is unprecedented. A thin, jammed layer of crystals on bubbles can cause bubbles to retain nonspherical shapes in the absence of bulk effects for times much longer than the characteristic capillary relaxation time for bare bubbles, which is actual evidence for Pickering-type interfacial stabilization. By comparing to foams obtained by depressurization, we show that whipping is necessary for bubble wrapping with a layer of crystals. The origin of high stability against Ostwald ripening at long times is also discussed. Furthermore, we show that these Pickering whipped foams have rheological properties dominated by interfacial or film contributions, which is of high interest for food and cosmetics applications because of their high moduli. This system can be considered to be a model of the crystallization behavior of MG in oil, which is similar to that in many fats. Our methods are very general in the context of lipid-based foaming, in particular, from food materials, and were used in patent applications. [ABSTRACT FROM AUTHOR]

This study reports the synthesis, characterization and importance of a novel diethyl 2-(2-(2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)acetyl)hydrazono)malonate (MQOAHM). Two independent molecular structures of the disordered MQOAHM have been established by XRD‑single‑crystal analysis in a ratio of 0.596(3)/0.404(3), MQOAHM (a) and MQOAHM (b), respectively. MQOAHM was characterized by means of various spectroscopic tools ESI-MS, IR, 1H &13C NMR analyses. Density Functional Theory (DFT) method, B3LYP, 6–311++G(d,p) basis set was used to optimize MQOAHM molecule. The obtained theoretical structure and experimental structure were superimposed on each other, and the correlation between them was calculated. The Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) were created, and the energy gap between these orbitals was calculated. For analyzing intermolecular interactions, Molecular Electrostatic Potential (MEP) and Hirshfeld Surface Analysis were studied. For a fair comparative study, the two forms of the title compound were docked together with 18 approved drugs and N3 under precisely the same conditions. The disordered molecule structure's binding scores against 7BQY were −7.0 and −6.9 kcal/mol−1 for MQOAHM (a) and MQOAHM (b), respectively. Both the forms show almost identical superimposed structures and scores indicating that the disorder of the molecule, in this study, has no obvious effect. The high binding score of the molecule was attributed to the multi-hydrogen bond and hydrophobic interactions between the ligand and the receptor's active amino acid residues. Worth pointing out here that the aim of using the free energy in Silico molecular docking approach is to rank the title molecule compared to the wide range of approved drugs and a well-established ligand N3. The binding scores of all the molecules used in this study are ranged from −9.9 to −4.5 kcal/mol−1. These results and the supporting statistical analyses suggest that this malonate-based ligand merits further research in the context of possible therapeutic agents for COVID-19. Cheap computational techniques, PASS, Way2drug and ADMET, online software tools, were used in this study to uncover the title compound's potential biological activities and cytotoxicity.

In this study, two new salicylideneaniline derivative compounds which are an isomer of each other have been synthesized and characterized by X-Ray Diffraction (XRD) technique, IR spectroscopy, and theoretical method. While (E)-4-(dihydroxyamino)-2-(((4-fluorophenyl)imino) methyl)phenol (1), crystalizes triclinic P-1 space group, (E)-4-(dihydroxyamino)-2-(((3-fluorophenyl)imino)methyl)phenol (2) crystalizes monoclinic P21/c space group. Both of the molecules which adopt (E) configuration with respect to the central C=N bond have strong intermolecular O―H∙∙∙N hydrogen bonds. These O―H∙∙∙N hydrogen bonds create S(6) motifs according to graph set notation. The optimized geometries of the molecules have been calculated by using Density Functional Theory (DFT) with the 6-31G(d,p) basis set. Molecular Electrostatic Potential (MEP) map and Frontier Molecular Orbitals have been made for the optimized geometries. In addition to these studies, the theoretical IR spectra of the compounds, the experimental IR spectra of which have been recorded at 4000-400 cm-1 interval, have also been calculated with same level theory. The experimental and theoretical results were compared to each other.

Two new one-dimensional coordination polymers of barium (II) and strontium (II)-acesulfamato complexes such as [Ba(C4H4NO4S)2(H2O)]n (1) and [Sr(C4H4NO4S)2(H2O)]n (2) have been synthesized and their molecular structures were identified by X-ray diffraction technique. Both barium (II) and strontium (II) complexes crystallize in the centrosymmetric monoclinic space group P121/c1 and barium (II) and strontium (II) ions, which are surrounded by O- and N-atoms, have the coordination number of nine. Each complex forms a structure like a polymer extending parallel to the a-axis. The molecular structures of those complexes were stabilized by O―H···O and C―H···O hydrogen bonds. Besides identifying their crystallographic structures, the geometric parameters were also calculated using density functional theory (B3LYP) with 6-31G base sets for the asymmetric units of the complexes. The calculated geometrical parameters were also compared to the geometric parameters of X-ray diffraction technique. Furthermore, molecular electrostatic potential maps were constructed and frontier molecular orbital calculations were done for the synthesized complexes. The results of the experimental and theoretical IR studies were also compared.

This paper presents an analysis of the possible performance of a proposed airborne rotor type electricity generator wind turbine design. The innovative design proposal by inventor is based on the rotation of the airborne structure with blades attached to the airborne zeppelin and thus it is called an airborne rotor generator. In this paper computational fluid dynamics analysis of a model close to the proposed design is carried out and the results are presented. The proposed design examples are set to produce 10-100KW. The electrical energy generated through two symmetrically placed alternators at both ends of the zeppelin is transferred to the ground-based system through the tethered cords used to also stabilize the system. Thus, an airborne rotor generator is formed.

In the title molecule, C18H16N2O3, the five-membered ring has an envelope conformation, with the substituted C atom deviating by 0.342 (4) Å from the mean plane P calculated for the remainder of the non-H atoms of the 2,3-dihydro-1H-indene fragment. The mean planes of quinazoline-2,4(1H,3H)-dione fragment and P form a dihedral angle of 59.08 (4)°. In the crystal, pairs of N—H...O hydrogen bonds link molecules into inversion dimers, and weak C—H...O hydrogen bonds and π–π interactions between the benzene rings of the quinazoline ring systems [centroid–centroid distance = 3.538 (3) Å] further consolidate the packing.

In the title compound, C12H17N3O2S, the 4-methyl-2-methylsulfanyl-6-oxo-1,6-dihydropyrimidine-5-carbonitrile part of the molecule is almost planar (r.m.s deviation = 0.062 Å). In the crystal, molecules form centrosymmetric dimers via pairs of N—H...O hydrogen bonds.

In the title molecule, C17H21FN2S, the mean planes of the benzene ring and the thiourea fragment form a dihedral angle of 61.93 (9)°. In the crystal, pairs of weak N—H...S interactions link the molecules, forming inversion dimers.

In the crystal structure of the title compound, [Cu(C4H4NO4S)2(C2H8N2)2], the Cu2+ ion resides on a centre of symmetry. The environment of Cu2+ ion is a distorted octahedron. The axial bond lengths between the CuII ion and the N atoms are considerably longer than the equatorial bond distances between the CuII ion and the N atoms of the ethylenediamine ligand as a consequence of the Jahn–Teller effect. The molecular conformation is stabilized by intramolecular N—H...O hydrogen bonds. In the crystal, molecules are connected by intermolecular N—H...O hydrogen bonds into chains running along the a axis.

Subunit vaccines containing universal tumor associated antigens (TAAs) present an attractive treatment modality for cancer primarily due to their safety and potential to generate long-term immunological responses that can safeguard against recurrences. However, TAA-based subunit vaccines require potent adjuvants for therapeutic efficacy. Using a novel form of the 4-1BBL costimulatory molecule, SA-4-1BBL, as the adjuvant of choice, we previously demonstrated that a single vaccination with survivin (SVN) as a bona fide self TAA was effective in eradicating weakly immunogenic 3LL tumors in >70% of C57BL/6 mice. The present study was designed to i) assess the therapeutic efficacy of a prime-boost vaccination and ii) investigate the mechanistic basis of vaccine efficacy. Our data shows that a prime-boost vaccination strategy was effective in eradicating 3LL lung carcinoma in 100% of mice. The vaccine efficacy was correlated with increased percentages of CD8(+) T cells expressing IFN-γ as well as potent killing responses of both CD8(+) T and NK cells in the absence of detectable antibodies to ssDNA as a sign of autoimmunity. Antibody depletion of CD8(+) T cells one day before vaccination completely abrogated therapeutic efficacy, whereas depletion of CD4(+) T cells had no effect. Importantly, NK cell depletion had a moderate (∼50% reduction), but significant (p

The title compound, C7H6O5·H2O, is a new polymorph of the structures reported by Jiang et al. (2000) [Acta Cryst. C56, 594–595] and Okabe et al. (2001) [Acta Cryst. E57, o764–o766]. The gallic acid molecule is essentially planar (r.m.s. deviation = 0.550 Å). An intramolecular O—H...O hydrogen bond occurs in the gallic acid molecule, which is linked to the water molecule by a further O—H...O hydrogen bond. In the crystal, the components are linked by O—H...O hydrogen bonds. The hydrogen-bonding pattern differs from those reported for the previous polymorphs.

In the title compound, [Zn(C7H3NO4)(C10H9N3)(H2O)]·H2O, the ZnII atom has a distorted octahedral coordination geometry. One of the water molecules is coordinated with the ZnII ion and this molecule forms an O—H...O interaction with the lattice water molecule. The pyridine-2,6-dicarboxylate ligand is almost planar (r.m.s. deviation = 0.0242 Å). In the crystal, C—H...O, C—H...N, O—H...O and N—H...O hydrogen bonds are present.

In the title compound, C14H8INO2, the dihedral angle between the isoindole ring and the phenyl ring of the 1-iodobenzene group is 84.77 (15)°. There is a short intermolecular I...O contact of 3.068 (3) Å in the crystal.

The asymmetric unit of the title compound, [Ni(C2H8N2)3](C5H2N2O4)·1.67H2O, consists of three [Ni(en)3]2+ dications (en is ethylenediamine), three [(pzdc)3]2− dianions (pzdc is pyrazole-3,5-dicarboxylate) and five water molecules. In each complex dication, the NiII atom is coordinated by six N atoms from three en ligands forming a distorted octahedral coordination geometry. In the crystal, the ions and water molecules are linked into a three-dimensional framework by a large number of N—H...O and O—H...O hydrogen bonds.

In the title compound, C13H9N3S2, the thiophene and phenyl rings are oriented at dihedral angles of 8.00 (7) and 6.31 (7)°, respectively, with respect to the central thiadiazole ring. No significant C—H...S and π–π interactions exist in the crystal structure.

Background/objectives: Phenylketonuria is a hereditary metabolic disorder characterized by a deficiency of phenylalanine hydroxylase. The main treatment for PKU is a phenylalanine-restricted diet. The exclusion of protein rich natural foods and inclusion of low-Phe substitutes may give rise to an imbalanced diet, and the increased risk of overweight and obesity in PKU is a cause for concern. We aimed to evaluate the body composition and nutritional biochemical biomarkers in adult PKU patients who are on Phe-restricted and essential amino acid-supplemented nutrition therapy and to investigate the relationships between these parameters and patient gender, adherence to dietary therapy, and disease type, defined as mild or classic PKU., Methods: The study group comprised 37 PKU patients and 26 healthy siblings as controls. The participants were assessed based on an analysis of anthropometric parameters, body composition, and biochemical test results., Results: PKU patients do not have a higher incidence of overweight and obesity than healthy controls, the proportion of energy derived from carbohydrates in their diets was below the recommended level, and their total energy intake was below the recommended daily allowance. It was remarkable that patients with a treatment adherence ratio of <50% displayed a higher prevalence of overweight and abdominal obesity in comparison to those with a more favorable treatment adherence ratio., Conclusions: In view of the growing prevalence of overweight in the general population, PKU patients should be kept under close long-term follow-up. Particularly in the group with low treatment compliance, more caution should be taken in terms of adverse outcomes.

Phenothiazines (PTZ) are antipsychotics known to modulate a variety of neurotransmitter activities that include dopaminergic and cholinergic signaling and have been identified as potential anticancer agents in vitro. However, it is important to also test whether a highly cytotoxic, repurposed, or novel PTZ has low toxicity and neuromodulatory activity in vivo using vertebrate model organisms, such as zebrafish. In this study, we synthesized novel phenothiazines and screened them in vitro in liver cancer and in vivo in zebrafish embryos/larvae. The syntheses of several intermediate PTZ 10-yl acyl chlorides were followed by elemental analysis and determination of 1 H NMR and 13 C NMR mass (ESI + ) spectra of a large number of novel PTZ 10-carboxamides. Cytotoxicities of 28 PTZ derivatives (1-28) screened against Hep3B and SkHep1 liver cancer cell lines revealed five intermediate and five novel leads along with trifluoperazine (TFP), prochlorperazine (PCP), and perphenazine, which are relatively more cytotoxic than the basic PTZ core. Overall, the derivatives were more cytotoxic to Hep3B than SkHep1 cells. Moreover, in silico target screening identified cholinesterases as some of the commonest targets of the screened phenothiazines. Interestingly, molecular docking studies with acetylcholinesterase (AChE) and butyrylcholinesterase proteins showed that the most cytotoxic compounds 1 , 3 , PCP, and TFP behaved similar to Huprin W in their amino acid interactions with the AChE protein. The highly cytotoxic intermediate PTZ derivative 1 exhibited a relatively lower toxicity profile than those of 2 and 3 during the zebrafish development. It also modulated in vivo the cholinesterase activity in a dose-dependent manner while significantly increasing the total cholinesterase activity and/or ACHE mRNA levels, independent of the liver cancer cell type. Our screen also identified novel phenothiazines, i.e., 8 and 10 , with significant cytotoxic and cholinesterase modulatory effects in liver cancer cells; yet both compounds had low levels of toxicity in zebrafish. Moreover, they modulated the cholinesterase activity or expression of ACHE in a cancer cell line-specific manner, and compound 10 significantly inhibited the cholinesterase activity in zebrafish. Accordingly, using a successful combination of in silico, in vitro, and in vivo approaches, we identified several lead anticancer and cholinesterase modulatory PTZ derivatives for future research., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Gold standard method for the treatment of critical-sized bone defects is the autogenous bone grafting procedure. A number of new and potentially useful adjuncts currently are being investigated to enhance the success of bone grafting. We propose to evaluate the effect of the most known and easily obtained 2 biological materials, fat graft and platelet-rich plasma (PRP), on bone graft healing. Twenty-seven New Zealand male rabbits were included in this randomized, controlled study. Two-sided 15-mm diameter bone defects were created in the parietal bones and the bones taken were replaced right-to-left and vice versa with 1 control group, 1 fat graft applied group, and the last one PRP applied group. Histologic evaluation and 3-dimensional maxillofacial computerized tomography were performed and bone density was calculated. In radiologic analysis, bone density was significantly different in the PRP group compared with the control and fat graft group in the 12th week ( P <0.05). In histologic scoring analysis, the PRP group had a better score than the control and fat graft group, while the fat graft group was worse than the control group in the 6th week ( P <0.05). The addition of PRP had a positive effect whereas fat graft had a negative effect on bone graft healing compared with the control group., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Introduction: Delays in the diagnosis and referral of aortic stenosis (AS) during the coronavirus disease 2019 (COVID-19) pandemic may have affected the haemodynamic status of AS patients. We aimed to compare clinical and haemodynamic characteristics of severe AS patients referred for transcatheter aortic valve implantation (TAVI) or balloon aortic valvuloplasty (BAV) before the pandemic versus two subsequent periods., Methods: This study compared three 1‑year historical cohorts: a pre-COVID-19 group (PCOV), a 1st-year COVID-19 group (COV-Y1) and a 2nd-year COVID-19 group (COV-Y2). The main parameters were baseline New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic pressure (LVEDP). Demographics, procedural characteristics and 30-day clinical outcomes were assessed. The transition time between heart team decision and TAVI was examined. Pairwise group comparisons were performed (PCOV vs COV-1Y and COV-1Y vs COV-2Y)., Results: A total of 720 patients were included with 266, 249 and 205 patients in the PCOV, COV-Y1 and COV-Y2 groups, respectively. BAV was performed in 28 patients (4%). NYHA class did not differ across the cohorts. Compared to PCOV, LVEF was slightly lower in COV-Y1 (58% (49-60%) vs 57% (45-60%), p = 0.03); no difference was observed when comparing COV-Y1 and COV-Y2. LVEDP was higher in COV-Y1 than in PCOV (20 mm Hg (16-26 mm Hg) vs 17 mm Hg (13-24 mm Hg), p = 0.01). No difference was found when comparing LVEDP between COV-Y1 and COV-Y2. Thirty-day mortality did not differ between groups. Transition time was reduced in the COVID era. Duration of hospital stay declined over the study period., Conclusions: Patients undergoing TAVI during the COVID-19 pandemic had more advanced AS illustrated by lower LVEF and higher LVEDP, but there were no differences in clinical outcome. The TAVI pathway became more efficient., (© 2023. The Author(s).)

Background: Mitochondrial diseases are the most common group of inherited metabolic disorders, causing difficulties in definite diagnosis due to clinical and genetic heterogeneity. Clinical components are predominantly associated with pathogenic variants shown in nuclear or mitochondrial genomes that affect vital respiratory chain function. The development of high-throughput sequencing technologies has accelerated the elucidation of the genetic etiology of many genetic diseases that previously remained undiagnosed. Methods: Thirty affected patients from 24 unrelated families with clinical, radiological, biochemical, and histopathological evaluations considered for mitochondrial diseases were investigated. DNA isolated from the peripheral blood samples of probands was sequenced for nuclear exome and mitochondrial DNA (mtDNA) analyses. MtDNA sequencing was also performed from the muscle biopsy material in one patient. For segregation, Sanger sequencing is performed for pathogenic alterations in five other affected family members and healthy parents. Results: Exome sequencing revealed 14 different pathogenic variants in nine genes encoding mitochondrial function peptides ( AARS2, EARS2, ECHS1, FBXL4, MICOS13, NDUFAF6, OXCT1, POLG , and TK2 ) in 12 patients from nine families and four variants in genes encoding important for muscle structure ( CAPN3, DYSF, and TCAP ) in six patients from four families. Three probands carried pathogenic mtDNA variations in two genes ( MT-ATP6 and MT-TL1 ). Nine variants in five genes are reported for the first time with disease association: ( AARS2 : c.277C>T/p.(R93*), c.845C>G/p.(S282C); EARS2 : c.319C>T/p.(R107C), c.1283delC/p.(P428Lfs*); ECHS1 : c.161G>A/p.(R54His); c.202G>A/p.(E68Lys); NDUFAF6 : c.479delA/p.(N162Ifs*27); and OXCT1 : c.1370C>T/p.(T457I), c.1173-139G>T/p.(?). Conclusion: Bi-genomic DNA sequencing clarified genetic etiology in 67% (16/24) of the families. Diagnostic utility by mtDNA sequencing in 13% (3/24) and exome sequencing in 54% (13/24) of the families prioritized searching for nuclear genome pathologies for the first-tier test. Weakness and muscle wasting observed in 17% (4/24) of the families underlined that limb-girdle muscular dystrophy, similar to mitochondrial myopathy, is an essential point for differential diagnosis. The correct diagnosis is crucial for comprehensive genetic counseling of families. Also, it contributes to making treatment-helpful referrals, such as ensuring early access to medication for patients with mutations in the TK2 gene., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gedikbasi, Toksoy, Karaca, Gulec, Balci, Gunes, Gunes, Aslanger, Unverengil, Karaman, Basaran, Demirkol, Gokcay and Uyguner.)