Hypothyroidism causing rhabdomyolysis is a known but an uncommon entity. Hashimoto's thyroiditis causing rhabdomyolysis in the absence of precipitating factors is even rarer. Here we report a 42- year-old previously healthy male with hypothyroidism due to Hashimotos thyroiditis complicated by severe rhabdomyolysis and acute kidney injury.

Mustafa Çalışkan, MDa; Ömer Faruk Baycan, MDa; Fatma Betül Çelik, MDa; Tolga Sinan Güvenç, MDb; Adem Atıcı, MDa; Yasemin Çağ, MDa; Oğuz Konal, MDa; Tuğçe İrgi, MDa; Ümmühan Zeynep Bilgili, MDa; Mehmet Ali Ağırbaşlı, MDaa Medeniyet University Faculty of Medicine, Department of Internal Medical Sciences, Division of Cardiology, Istanbul, Turkeyb Istinye University School of Medicine, Department of Internal Medical Sciences, Division of Cardiology, Istanbul, TurkeyCorresponding Author: Tolga Sinan GüvençAddress for correspondence: Maltepe, İstinye Üniversitesi Topkapı Kampüsü, Teyyareci Sami Str. No.3, 34010 Zeytinburnu/İstanbulTel: 0850 283 6000Declarations of interest: none

To our knowledge,this is the first report of 31 Y F has no family history and usually,patients do not manifest symptoms if they are heterozygous.Individuals heterozygous for C282Y who have a coexisting insult to the liver,associated with the use of medications,may present with overt manifestations of iron overload.

Introduction: Today, whereas hypoxemia and respiratory failure is the major challenging problem in the course of severe COVID-19 pneumonia, to control the disease at a mild-moderate stage or to stop the inflammation by recognizing the cytokine storm early should be the most prominent goal. We aimed to reveal the clinical efficacy and safety of short-term high-dose corticosteroids in severe COVID-19. Material and Methods: This retrospective observational study consisted of 54 patients who were given high-dose steroid (HDS (>250 mg/day methylprednisolone, 3 days.). Low-dose steroid (LDS) therapy (dexamethasone 8 mg ) was applied to all patients. HDS group was reviewed in terms of decreasing hospital mortality and preventing fibrosis development in follow-up. Results: During the observation period, out of 317 severe COVID-19 pneumonia hospitalized, HDS and LDS were administered to 54 and 216 patients, respectively. Higher body mass index, younger age, more oxygen need of patients at admission, and more need for advanced oxygen therapy during hospitalization were found in the HDS group (p<0.001). Furthermore, 18.5% of patients in the HDS group had need transfer to the intensive care unit whereas it was 3.8% in LDS (p<0.001). Additionally, the mortality rate was determined higher in the HDS group (25. 9% vs 9.9%, p<0.001). The HDS group had lower saturated O2 [IQR, 85% (76-89), p <0.001], and higher ferritin at admission. It was found that HDS was given simultaneously with the increased ferritin with deepening lymphopenia on the third and fifth days. There was no difference in fibrosis development between HDS patients receive and not (15.4% vs 26.2%, p=0.11) Conclusion: The use of HDS in hospitalized COVID-19 patients remains unclear. Along with this, our study demonstrated the use of high-dose corticosteroids might not be associated with a lower mortality rate among hospitalized severe COVID-19 patients.

Background: During the current ongoing COVID-19 pandemic, studies had reported that patients with asthma would experience increased asthma-associated morbidity because of the respiratory virus SARS-CoV-2 infection, based on experience with other respiratory viral infections. However, some studies suggested that there was no apparent increase in asthma related morbidity in children with asthma, it is even possible that due to reduced exposures due to confinement, such children may have improved outcomes. In order to understand the impact of Covid-19 on asthma control in children, we performed this systematic review and meta-analysis. Methods: We searched PubMed, Embase, and Cochrane Library to find literature from December 2019 to June 2021 related to Covid-19 and children’s asthma control, among which results such as abstracts, comments, letters, reviews and case reports were excluded. The level of asthma control during the COVID-19 pandemic was synthesized and discussed. Results: A total of 20456 subjects were included in 7 studies. Random effect model is used to account for the data. Compared to the same period before the COVID-19 pandemic, asthma exacerbation, asthma admission, emergency room visit reduced a lot. The outcome of use of inhaled corticosteroids and Beta-2 agonists shows no significant difference. Conclusion: Compared to the same period before the COVID-19 pandemic and the measures in response to it, the level of asthma control has been significantly improved. We need to understand the exact factors leading to these improvements and find methods to sustain it.

INTRODUCTION: The aim of this study was to investigate the important factors affecting the COPD prognosis. MATERIAL AND METHODS: We included 160 hospitalized patients with COPD exacerbation in the study. Hemoglobin-HB, hematocrit-HCT, leukocyte, red cell distribution width- RDW, mean platelet volume, platelet distribution width, plateletcrit, platelet, neutrophil / lymphocyte ratio, platelet / lymphocyte ratio, eosinophil, uric acid, albumin, CRP, procalcitonin, arterial blood gases (PO2, PCO2) pulmonary function test (FEV1, FVC), echocardiography (ejection fraction-EF) GOLD stage, MMRC and BORG scales, Charlson comorbidity index, body mass index-BMI, length of hospital stay were examined on the first day of hospitalization. Admission to the hospital with a new attack, hospitalization in the intensive care unit-ICU, and mortality during the 6 months after discharge were evaluated. RESULTS: High CRP and procalcitonin values were observed in the group with long hospital stay. In mortality group, HB, HCT, BMI and PO2 values were significantly lower than the group without mortality while age and GOLD stage were higher. The age, BORG and MMRC scores, number of exacerbations experienced in the previous 1 year, RDW, eosinophil count, PCO2 were significantly higher in the ICU group than without ICU. HCT, EF values were lower in the ICU group than without ICU. FEV1, FVC values were significantly lower in follow-up attack group than without attack; the duration of COPD and the number of experienced in the previous 1 year were high. CONCLUSION: It has been concluded that the scoring combining selected biomarkers and other factors will be stronger in determining the prognosis.

Background: Various variants of the covid-19 have started to attract attention recently. The clinical course of these variants and possible predictive parameters are being investigated. This study aimed to examine the relationship between thiol levels, which are indicators of oxidative stress, and variant covid-19 types. Methods: In this cross-sectional study, patients with a diagnosis of classic covid-19 and patients with a diagnosis of variant covid-19 with mild and moderate symptoms followed in the clinical observatory of Ankara city hospital were included in the study group. The patients were divided into two groups according to the covid-19 type as variant and classic covid-19, and a healthy control group is added for comparison. A complete blood count and thiol analysis are performed from the venous blood samples. Obtained results were compared between groups, and the ROC analysis is performed. Results: Thiol levels were significantly lower in patients with a diagnosis of Covid-19 compared to the control group. In terms of WBC, lymphocyte, neutrophil, NLR, ferritin and thiol parameters, patients with variant covid-19 differed significantly from patients with a classic covid-19 diagnosis. Thiol levels’ cut-off values to distinguish between variant covid-19 patients and control group from classical covid-19 patients were almost identical (423 and 422 µmol/L, respectively). Conclusions: It seems possible to use thiol as a sensitive, specific and cost-effective marker to suspect variant covid-19 cases. Since this study is probably the first example in this subject, it would form a basis for further studies. Keywords: Covid-19, SARS-CoV-2, variant covid-19, thiol, oxidative stress.

The transcription machinery of archaea can be roughly classified as a simplified version of eukaryotic organisms. The basal transcription factor machinery binds to the TATA-box found around 28 nucleotides upstream of the transcription start site; however, some transcription units lack a clear TATA-box and still have TBP/TFB binding over them. This apparent absence of conserved sequences could be a consequence of sequence divergence associated with the upstream region, operonic and gene organization. Furthermore, earlier studies have found that a structural analysis gains more information compared to a simple sequence inspection. In this work, we evaluated and coded 3630 archaeal promoter sequences of three organisms, Haloferax volcanii, Thermococcus kodakarensis, and Sulfolobus solfataricus into DNA duplex stability, enthalpy, curvature, and bendability parameters. We also split our dataset into conserved TATA and degenerated TATA promoters in order to identify differences among these two classes of promoters. The structural analysis reveals variations in archaeal promoters’ architecture, i.e., a distinctive signal is observed in the TFB, TBP, and TFE binding sites independently of these being TATA-conserved or TATA-degenerated. In addition, the promoter encountering method was validated with upstream regions of 13 other archaea, suggesting that there might be promoter sequences among them. Therefore, we suggest a novel method for locating promoters within the genome of archaea based on energetic/structural features.

The case report by Sicim et al. is the placement of extra-anatomical bypasses in bilateral common carotid arteries. The similar previous reports of the extra-anatomical bypass usually indicate unilateral bypass. Whether or not the Willis' circle is incomplete is difficult to judge during emergency surgery, and the authors' judgment seems to have been correct in the sense that it could maintain cerebral perfusion reliably and quickly. The direct perfusion and extraanatomical bypass of carotid artery is a reasonable strategy in patients with cerebral malperfusion.

Mucopolysaccharidoses (MPSs) are rare, heterogeneous inborn errors of metabolism (IEM) diagnosed through a combination of clinical, biochemical, and genetic investigations. The aim of this study was molecular characterization of the largest cohort of Iranian MPS patients (302 patients from 289 unrelated families), along with tracking their ethnicity and geographical origins. 185/289 patients were studied using an IEM-targeted NGS panel followed by complementary Sanger sequencing, which led to the diagnosis of 154 MPS patients and 5 non-MPS IEMs (diagnostic yield: 85.9%). Furthermore, 106/289 patients who were referred with positive findings went through re-analysis and confirmatory tests which confirmed MPS diagnosis in 104. Among the total of 258 MPS patients, 225 were homozygous, and 9 had copy number variations, and 90 had novel variants. MPS IV was the most common type (34.8%) followed by MPS I (22.7%) and MPS VI (22.5%). Geographical origin analysis unveiled a pattern of distribution for frequent variants in ARSB (c.430G>A, c.962C>T, c.281C>A), GALNS (c.319G>A, c.860C>T, c.1042A>G), and IDUA (c.1A>C, c.1598C>G). Our extensive patient cohort reveals the genetic and geographic landscape of MPS in Iran, which provides insight into the genetic epidemiology of MPS and can facilitate a more cost-effective, time-efficient diagnostic approach based on the region-specific variants.

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal syndrome of immune dysregulation that is classified into primary and secondary forms. The standard of care is established with dexamethasone and etoposide, but there are currently no guidelines for refractory HLH or cases triggered by infection or malignancy. [1] We describe here a series of pediatric patients with malignancy-associated HLH (m-HLH) to discuss the complexities in the initial diagnostic considerations, the balance of therapeutic regimens and their toxicities, and the novel use of emapalumab and ruxolitinib in patients with refractory disease.

Essential thrombocythemia is chronic myeloproliferative neoplasia, as defined by WHO in 2016, with the best prognosis. A small percentage of ET cases can be considered Familial ET. In this report we describe 6 cases of Familial ET, evaluating the heterogeneity of the mutational state and the clinical presentation.

Spontaneous pseudoaneurysm of the aortic arch is an exceptionally rare and potentially life-threatening condition.Diagnosis of pseudoaneurysms of the aortic arch mainly depends on imaging examinations.Contrast-enhanced echocardiography, as a non-invasive, bed-side and radiation-free tool, plays an important role in the rapid diagnosis and postoperative follow-up of pseudoaneurysms of the aortic arch.

Protein allergens is a health risk for consumption of soybeans. To understand allerginicity mechanism, T cell epitopes of 7 soybean allergens were predicted and screened by abilities to induce cytokine interleukin 4. The relationships among amino acid composition, properties, allergenicity and pepsin hydrolysis sites were analyzed. Among the 138 T cell epitopes identified, YIKDVFRVIPSEVLS, KDVFRVIPSEVLSNS, DVFRVIPSEVLSNSY of Gly m 6.0501 (P04347), and AKADALFKAIEAYLL, ADALFKAIEAYLLAH of Gly m 4.0101 (P26987) were the most possible epitope candidates. In T cell epitopes pattern, the frequencies of amino acids Q, D, E, P and G decreased, while F, I, N, V, K and H increased. Hydrophobic residues at positions p1 and p2 and positively charged residues in positions p13 might contribute to allergenicity. Most of epitopes could be hydrolyzed by pepsin into small polypeptides within 12 residues length, and the anti-digestive epitope regions contained I, V, S, N, and Q residues. T cell epitopes EEQRQQEGVIVELSK from Gly m 5.03 (P25974) showed resistantence to pepsin hydrolysis and would cause a higher Th2 cell response. This research provides basis for the development of hypoallergenic soybean products in the soybean industry as well as for the immunotherapy design for protein allergy.

Sex-specific ecology has management implications, but rapid sex-chromosome turnover in fishes hinders development of markers to sex monomorphic species. Here, we use annotated genomes and reduced-representation sequencing data for two Australian percichthyids, the Macquarie perch Macquaria australasica and the golden perch M. ambigua, and whole genome resequencing data for 50 Macquarie perch of each sex, to detect sex-linked loci, identify a candidate sex-determining gene and develop an affordable sexing assay. In-silico pool-seq tests of 1,492,004 Macquarie perch SNP loci revealed that a 275-Kb scaffold, containing the transcription factor SOX1b gene, was enriched for gametologous loci. Within this scaffold, 22 loci were sex-linked in a predominantly XY system, with females being homozygous at all 22, and males being heterozygous at two or more. Seven XY-gametologous loci were within a 146-bp region. Being ~38 Kb upstream of SOX1b, it might act as an enhancer controlling SOX1b transcription in the bipotential gonad that drives gonad differentiation. A PCR-RFLP sexing assay, targeting one of the Y-linked SNPs, tested in 66 known-sex Macquarie perch and two individuals of each sex of three confamilial species, and amplicon sequencing of 400 bp encompassing the 146-bp region, revealed that the few sex-linked positions differ between species and between Macquarie perch populations. This indicates sex-chromosome lability in Percichthyidae, also supported by non-homologous scaffolds containing sex-linked loci for Macquarie- and golden perches. The resources developed here will facilitate genomic research in Percichthyidae. Sex-linked markers will be useful for determining genetic sex in some populations and studying sex chromosome turnover.

Predicting the quaternary structure of protein complex is an important problem. Inter-chain residue-residue contact prediction can provide useful information to guide the ab initio reconstruction of quaternary structures. However, few methods have been developed to build quaternary structures from predicted inter-chain contacts. Here, we introduce a gradient descent optimization algorithm (GD) to build quaternary structures of protein dimers utilizing inter-chain contacts as distance restraints. We evaluate GD on several datasets of homodimers and heterodimers using true or predicted contacts. GD consistently performs better than a simulated annealing method and a Markov Chain Monte Carlo simulation method. Using true inter-chain contacts as input, GD can reconstruct high-quality structural models for homodimers and heterodimers with average TM-score ranging from 0.92 to 0.99 and average interface root mean square distance (I-RMSD) from 0.72 Å to 1.64 Å. On a dataset of 115 homodimers, using predicted inter-chain contacts as input, the average TM-score of the structural models built by GD is 0.76. For 46% of the homodimers, high-quality structural models with TM-score >= 0.9 are reconstructed from predicted contacts. There is a strong correlation between the quality of the reconstructed models and the precision and recall of predicted contacts. If the precision or recall of predicted contacts is >20%, GD can reconstruct good models for most homodimers, indicating only a moderate precision or recall of inter-chain contact prediction is needed to build good structural models for most homodimers. Moreover, the accuracy of reconstructed models positively correlates with the contact density in dimers.

Aims Volcanic eruptions play an important role in vegetation dynamics and its historical range of variability. However, large events are infrequent and eruptions with significant imprint in today vegetation occurred far in the past, limiting our understanding of ecological process. Volcanoes in southern Andes have been active during the last 10 ka, and support unique ecosystems such as the Araucaria-Nothofagus forest as part of the Valdivian Temperate Rainforest Hotspot. Araucaria is an endangered species, strongly fragmented and well adapted to disturbances. Yet it was suggested that volcanism might have increased the fragmentation of its populations. To provide an insight into the vegetation responses to past volcanic disturbances, a paleoecological study was conducted to assess the role of volcanic disturbance on the vegetation dynamics and if the current fragmentation has been caused by volcanism. Location Araucaria forest-steppe ecotone in northern Patagonia. Methods Pollen and tephra analysis from a sedimentary record. Results During the last 9 kyr, 39 tephrafall buried the vegetation around Lake Relem, more frequently between 4-2 ka. The vegetation was sensitive to small tephrafall but seldom caused significant changes. However, the large eruption of Sollipulli-Alpehue (~3 ka) might change the environmental conditions affecting severely the forest and grassland, as suggested by the pollen record. Ephedra dominated early successional stage, perhaps facilitating Nothofagus regeneration recovering original condition after ~500 years. Slight increase of pollen percentage from Araucaria and Nothofagus obliqua-type could be indicative of sparse biological legacies distributed in the landscape. The analysis showed that vegetation resisted without permanent changes, recovering relatively fast after the large eruption. Conclusion The relative stability of Araucaria pollen in the study area after several tephrafall suggests no change in its past geographical distribution at the current forest-steppe ecotone, thus I found no evidence that volcanic eruptions would have affected its current conservation status.

Rheumatic heart disease is the most common cause of mitral valve stenosis. Left atrial appendage thrombus is associated with mitral stenosis, but in rare cases the thrombus can extend to the left atrial cavity. We present a case of a severe rheumatic mitral stenosis and associated large left atrial thrombus, with embolic sequelae.

Chinese hamster ovary (CHO) cells are widely used for producing recombinant proteins. To enhance their growth, productivity, and product quality, practically media reformulation has been one of key focuses with several technical challenges which are due to the myriad of intricate molecular and regulatory mechanisms underlying the media effects on culture behaviours; it is highly required to systematically characterize metabolic bottlenecks of cell cultures in various media conditions. To do so, we combined multivariate statistical analysis with flux balance analysis of a genome-scale metabolic model of CHO cells based on the culture profiles of CHO-DG44 under one commercial medium and two in-house media. At the outset, we used partial least square regression to identify metabolite exchanges that are correlated to specific growth and productivity. By using a commercial medium as reference, we found sub-optimal level of four nutrients and two metabolic wastes that plausibly hinder cell growth and productivity with in-house media. Subsequently, we elucidated that the recycling of lactate and ammonia wastes to be affected by both glutamine and asparagine metabolisms mechanistically, and further modulated by hitherto unsuspected folate and choline supplements. In summary, the current work successfully demonstrated how multivariate statistical analysis can be synergistically combined with in silico analysis of metabolic models to uncover the mechanistic elements underlying the differing performance of various media. Our approach for the systematic identification of promising nutrient targets thus paves the way for cell culture medium reformulation to enhance cellular growth and recombinant protein production.

Proteins are involved in numerous cellular activities such as transport and catalysis. Misfolding during biosynthesis and malfunctioning as a molecular machine may lead to physiological disorders and metabolic problems. Protein folding and mechanical work may be viewed as thermodynamic energetically favorable processes in which stochastic nonequilibrium intermediate states may be present with conditions such as thermal fluctuations. In my opinion, measuring those thermal fluctuations may be a way to access the energy exchange between the protein and the physiological environment and to better understand how those nonequilibrium states may influence the misfolding/folding process and the efficiency of the molecular engine cycle. Here, I discuss luminescence thermometry as a possible way to measure those temperature fluctuations from a single molecule experimental perspective with its current technical limitations and challenges.

CASP (Critical Assessment of Structure prediction) conducts community experiments to determine the state of the art in computing protein structure from amino acid sequence. The process relies on the experimental community providing information about not yet public or about to be solved structures, for use as targets. For some targets, the experimental structure is not solved in time for use in CASP. Calculated structure accuracy improved dramatically in this round, implying that models should now be much more useful for resolving many sorts of experimental difficulty. To test this, selected models for seven unsolved targets were provided to the experimental groups. These models were from the AlphaFold2 group, who overall submitted the most accurate predictions in CASP14. Four targets were solved with the aid of the models, and, additionally, the structure of an already solved target was improved. An a-posteriori analysis showed that in some cases models from other groups would also be effective. This paper provides accounts of the successful application of models to structure determination, including molecular replacement for X-ray crystallography, backbone tracing and sequence positioning in a Cryo-EM structure, and correction of local features. The results suggest that in future there will be greatly increased synergy between computational and experimental approaches to structure determination.

One of the most essential ecosystem services provided by high-Andean páramos is streamflow buffering. A combination of soil, vegetation and climate characteristics provides páramos with an exceptional ability to store, regulate and supply water, particularly in their natural state. However, páramo catchments are seldom pristine. Agriculture is one of the most widespread human activities in páramos and considerably affects their soil hydrophysical properties. This research assesses how soil properties are affected by the conversion from natural páramo vegetation to fallow, onion, or potato crops. We measured Soil Organic Matter (SOM), Bulk density (Bd), pH and electric conductivity (EC) at three depths (0–5, 10–15 and 20–25 cm), in a stratified random survey of different land uses in the Eastern Cordillera of Colombia. Samples were collected in wet and dry seasons. Agricultural use affects all the studied properties, increasing Bd (+0.11 g cm-3), decreasing SOM (-5.5%), and increasing pH (+1.3) and EC (+187 µS cm-1). Seasonality did not have a significant effect on the studied properties under natural vegetation; however, there were significant differences between wet season and dry season in agricultural soils in SOM (-7.2% and +5.7% in fallow and potato crop, respectively) and Bd (-0.22 gr cm-3 in crops). These changes show that agriculture in páramo grasslands leads to a significant decrease in soil porosity and water-holding capacity, which affects adversely the ecosystem hydrological regulation capacity. This paper contributes to a better understanding of the complexity of Andean páramos and provide crucial information to improve soil management, a key aspect for ensuring the sustainable provision of hydrological ecosystem services offered by Andean and other mountain ecosystems.

The host pathogen interactome can be visualized as a vast continuous network in which molecular mimicry of host proteins by pathogens constitutes a strategy to hijack the host pathways. Despite extensive work in this field, there is no dedicated resource for mimicked domains and motifs in host pathogen interactome. In this work, we collated all the data regarding the experimental host pathogen (HP) and host-host (HH) protein-protein interactions (PPIs). The domains and sequence linear motifs of the proteins were annotated using CD Search and ScanProsite. Host and pathogen proteins with a shared host interactor and similar domain/motif constitute a linear pair. A linear pair that exhibits global structural domain similarity (Domain linear pair; DLP) or local sequence motif similarity (Motif Linear Pair; MLP) has a high probability of being co-expressed and co-localized. 2,06,449 DLPs and 38,45,643 MLPs were identified in 50,812 experimental HP-PPIs and organized in a web- based resource, ImitateDB, accessible at http://imitatedb.sblab-nsit.net. ImitateDB provides user-friendly access to the mimicry data. It can be queried by protein UniProt ID, pathogen, domain, motif, or interaction detection method. The results are externally integrated using hyperlinked domain PSSM ID, motif ID and protein ID. Kinase, UL36, Smc and DEXDc were frequent DLP domains whereas Protein Kinase C, Casein Kinase 2, glycosylation and myristoylation sites were frequent MLP motifs. Novel DLP domains SANT, Tudor, PhoX and MLP motifs Microbodies C-terminal targeting signal, Ubiquitin-interacting motif and Lipocalin signature were proposed. ImitateDB constitutes a resource for researchers in the field of infectious diseases and microbiology.

The filamentous fungus Magnaporthe oryzae has the potential to be developed as an alternative platform organism for the heterologous production of industrially important enzymes. M. oryzae is easy to handle, fast-growing and unlike yeast, posttranslational modifications like N-glycosylations are similar to the human organism. Here, we established M. oryzae as a host for the expression of the unspecific peroxygenase from the basidiomycete Agrocybe aegerita (AaeUPO). UPOs are attractive biocatalysts for selective oxyfunctionalization of non-activated carbon-hydrogen bonds. To improve and simplify the isolation of AaeUPO in M. oryzae, we fused a Magnaporthe signal peptide for protein secretion and set it under control of the strong EF1-promotor. The success of the heterologous production of full-length AaeUPO in M. oryzae and the secretion of the functional enzyme was confirmed by a peroxygenase-specific enzyme assay. These results offer the possibility to establish the filamentous ascomycete M. oryzae as a broad applicable alternative expression system. This is in particular valid for proteins that cannot or not in sufficient yields produced in established systems.