Independent Occurrence Research Articles

Independent Occurrence of Two Cases of Lennox — Gastaut Syndrome and Neurofibromatosis in the Family: A Clinical Observation

Developmental and epileptic encephalopathies (DEE) are the most difficult problem in epileptology. Lennox — Gastaut syndrome (LGS) is a developmental and epileptic encephalopathy with onset in childhood, manifested by: frequent polymorphic seizures, including tonic axial ones; severe cognitive impairment; slow activity (with a frequency of <2.5–3.0 Hz) sharp-slow wave in the interictal period on the electroencephalogram, as well as runs of fast activity with a frequency of 10–20 Hz, often associated with tonic seizures; and resistance to therapy. Presumably genetic or forms with an unknown cause account for 20–30 % of cases of LGS, but a family history of epilepsy among patients with LGS is observed in only 2.5 %.The purpose of this work was to describe a familial case of LGS in two siblings.Materials and methods. A retrospective description of the medical history of 3 siblings born in a consanguineous marriage was performed.Results and discussion. There was a similarity in the course of the disease in the two brothers, absolute resistance to drug antiepileptic therapy and temporary effectiveness of hormonal therapy for LGS with a decrease in the duration of the effect from course to course. In addition, the rare parallel existence in this family of another autosomal dominant disease — neurofibromatosis type 1 — is shown.Conclusion. A detailed description of LGS within one family will not only expand doctors’ knowledge of this disease and the difficulties of its treatment, but also improve understanding of the genetic mechanisms of the development of DEE.

Thermodynamics and kinetics of evaporation and thermal decomposition of 1-ethyl- and 1-butyl-3-methylimidazolium methanesulfonate ionic liquids: Experimental and computational study

Knudsen cell mass spectrometry was used to study the evaporation of two ionic liquids, 1-ethyl-3-methylimidazolium methanesulfonate ([EtMIm][MS], MS = CH3SO3) and 1-butyl-3-methylimidazolium methanesulfonate ([BuMIm][MS]), accompanied by thermal decomposition (thermolysis). The independent occurrence of evaporation and thermolysis reactions made it possible to determine their thermodynamic and kinetic characteristics under identical experimental conditions. The saturated vapor pressures were measured and the standard enthalpies of vaporization of [EtMIm][MS](l) and [BuMIm][MS](l) were obtained. The standard thermodynamic functions of formation in the liquid and gaseous states at 298.15 K were estimated from the available experimental data and the results of quantum chemical calculations. The gaseous decomposition products of ionic liquids were identified and the pressures of the thermolysis products of [EtMIm][MS](l) were determined. According to the experimental data and quantum chemical calculations, the thermolysis of [EtMIm][MS](l) occurs through heterogeneous reactions far from the equilibrium state. The kinetics of the reactions is described in two ways. When the degree of sample conversion is used as a variable, the constant reaction rates at the initial stage of thermolysis correspond to a pseudo-zero order reaction with a monotonic increase in the degree of conversion. In the proposed alternative approach, the reaction rates are estimated from the fluxes of thermolysis products and are expressed in terms of ionic liquid concentration.

Comparing clinical outcomes in patients with type 2 diabetes mellitus after ischaemic stroke: Sodium-glucose cotransporter 2 inhibitors users versus non-users. A propensity score matching National Cohort Study.

This nationwide cohort study evaluated the impact of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on patients with type 2 diabetes mellitus (T2DM) after ischaemic stroke (IS), aiming to compare clinical outcomes between SGLT2i-treated patients and those not receiving SGLT2i. Utilizing Taiwan's National Health Insurance Research Database, we identified 707 patients with T2DM treated with SGLT2i and 27 514 patients not treated with SGLT2i after an IS, respectively, from 1 May 2016 to 31 December 2019. Propensity score matching was applied to balance baseline characteristics. The follow-up period extended from the index date (3 months after the index acute IS) until the independent occurrence of the study outcomes, 6 months after discontinuation of the index drug, or the end of the study period (31 December 2020), whichever came first. After propensity score matching, compared with the non-SGLT2i group (n = 2813), the SGLT2i group (n = 707) exhibited significantly lower recurrent IS rates (3.605% per year vs. 5.897% per year; hazard ratio: 0.55; 95% confidence interval: 0.34-0.88; p = 0.0131) and a significant reduction in all-cause mortality (5.396% per year vs. 7.489% per year; hazard ratio: 0.58; 95% confidence interval: 0.39-0.85; p = 0.0058). No significant differences were observed in the rates of acute myocardial infarction, cardiovascular death, heart failure hospitalization, or lower limb amputation. Our findings indicate significantly lower risks of recurrent IS and all-cause mortality among patients with T2DM receiving SGLT2i treatment. Further studies are required to validate these results and investigate the underlying mechanisms behind the observed effects.

Cortical and Trabecular Bone Modeling and Implications for Bone Functional Adaptation in the Mammalian Tibia.

Bone modeling involves the addition of bone material through osteoblast-mediated deposition or the removal of bone material via osteoclast-mediated resorption in response to perceived changes in loads by osteocytes. This process is characterized by the independent occurrence of deposition and resorption, which can take place simultaneously at different locations within the bone due to variations in stress levels across its different regions. The principle of bone functional adaptation states that cortical and trabecular bone tissues will respond to mechanical stimuli by adjusting (i.e., bone modeling) their morphology and architecture to mechanically improve their mechanical function in line with the habitual in vivo loading direction. This principle is relevant to various research areas, such as the development of improved orthopedic implants, preventative medicine for osteopenic elderly patients, and the investigation of locomotion behavior in extinct species. In the present review, the mammalian tibia is used as an example to explore cortical and trabecular bone modeling and to examine its implications for the functional adaptation of bones. Following a short introduction and an exposition on characteristics of mechanical stimuli that influence bone modeling, a detailed critical appraisal of the literature on cortical and trabecular bone modeling and bone functional adaptation is given. By synthesizing key findings from studies involving small mammals (rodents), large mammals, and humans, it is shown that examining both cortical and trabecular bone structures is essential for understanding bone functional adaptation. A combined approach can provide a more comprehensive understanding of this significant physiological phenomenon, as each structure contributes uniquely to the phenomenon.

Clinical Outcomes in Type 2 Diabetes Patients After Acute Myocardial Infarction: AComparison of Sodium-Glucose Cotransporter 2 Inhibitors vs. Non-Users.

To compare clinical outcomes in patients with type 2 diabetes (T2D) after acute myocardial infarction (AMI) using sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs. non-use of SGLT2i. A national cohort study based on the Taiwan National Health Insurance Research Database enrolled 944 patients with T2D who had experienced AMI and were treated with SGLT2i and 8,941 patients who did not receive SGLT2i, respectively, from May 1, 2016, to December 31, 2019. We used propensity score matching to balance covariates across study groups. The follow-up period was from the index date to the independent occurrence of the study outcomes, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. The SGLT2i group exhibited a significantly lower incidence of cardiovascular death (0.865% per year vs. 2.048% per year; hazard ratio (HR): 0.42; 95% confidence interval (CI): 0.24-0.76; P = 0.0042), heart failure hospitalization (1.987% per year vs. 3.395% per year; HR: 0.59; 95% CI: 0.39-0.89; P = 0.0126), and all-cause mortality (3.406% per year vs. 4.981% per year, HR: 0.69; 95% CI: 0.50-0.95; P = 0.0225) compared with the non-SGLT2i group. There were no significant differences between the two groups in the incidence of AMI, ischemic stroke, coronary revascularization, major adverse cardiovascular events, composite renal outcomes, or lower limb amputation. These findings suggest that the use of SGLT2i may have favorable effects on clinical outcomes in patients with T2D after AMI.

The Klebsiella pneumoniae carbapenemase (KPC) β-Lactamase Has Evolved in Response to Ceftazidime Avibactam.

Klebsiella pneumoniae carbapenemase KPC is an important resistance gene that has disseminated globally in response to carbapenem use. It is now being implicated as a resistance determinant in Ceftazidime Avibactam (CAZ-AVI) resistance. Given that CAZ-AVI is a last-resort antibiotic, it is critical to understand how resistance to this drug is evolving. In particular, we were interested in determining the evolutionary response of KPC to CAZ-AVI consumption. Through phylogenetic reconstruction, we identified the variable sites under positive selection in the KPC gene that are correlated with Ceftazidime Avibactam (CAZ-AVI) resistance. Our approach was to use a phylogeny to identify multiple independent occurrences of mutations at variable sites and a literature review to correlate CAZ-AVI resistance with the mutations we identified. We found the following sites that are under positive selection: P104, W105, A120, R164, L169, A172, D179, V240, Y241, T243, Y264, and H274. The sites that correlate with CAZ-AVI resistance are R164, L169, A172, D179, V240, Y241, T243, and H274. Overall, we found that there is evidence of positive selection in KPC and that CAZ-AVI is the major selective pressure.

An Eco-evolutionary Model on Surviving Lysogeny Through Grounding and Accumulation of Prophages.

Temperate phages integrate into the bacterial genomes propagating along with the bacterial genomes. Multiple phage elements, representing diverse prophages, are present in most bacterial genomes. The evolutionary events and the ecological dynamics underlying the accumulation of prophage elements in bacterial genomes have yet to be understood. Here, we show that the local wastewater had 7% of lysogens (hosting mitomycin C-inducible prophages), and they showed resistance to superinfection by their corresponding lysates. Genomic analysis of four lysogens and four non-lysogens revealed the presence of multiple prophages (belonging to Myoviridae and Siphoviridae) in both lysogens and non-lysogens. For large-scale comparison, 2180 Escherichia coli genomes isolated from various sources across the globe and 523 genomes specifically isolated from diverse wastewaters were analyzed. A total of 15,279 prophages were predicted among 2180 E. coli genomes and 2802 prophages among 523 global wastewater isolates, with a mean of ~ 5 prophages per genome. These observations indicate that most putative prophages are relics of past bacteria-phage conflicts; they are "grounded" prophages that cannot excise from the bacterial genome. Prophage distribution analysis based on the sequence homology suggested the random distribution of E. coli prophages within and between E. coli clades. The independent occurrence pattern of these prophages indicates extensive horizontal transfers across the genomes. We modeled the eco-evolutionary dynamics to reconstruct the events that could have resulted in the prophage accumulation accounting for infection, superinfection immunity, and grounding. In bacteria-phage conflicts, the bacteria win by grounding the prophage, which could confer superinfection immunity.

“Standby Youth”?

Approaches explaining the dynamics of informal youth participation during crisis typically examine youngsters’ political activity in light of the general understanding of political participation. In this article, I argue that such an approach falls short of understanding the motivations behind youth engagement during a crisis. Therefore, this qualitative study aims to investigate the motivations that triggered youth engagement in COVID-19–related protests and how they developed in response to government actions. It does so through 20 semi-structured interviews conducted across Bosnia and Herzegovina in the first six months of 2021 with 20 youth who had either no previous political participation experience or only voting engagement. The primary focus is on examining the motivations for two informal political activities—expression of opinion and protest. The findings reveal that the action-reaction patterns were not independent occurrences but evolved through three different stages each of which depended on distinctive motivations.

Fitness effects ofmutations to SARS-CoV-2 proteins.

Knowledge of the fitness effects of mutations to SARS-CoV-2 can inform assessment of new variants, design of therapeutics resistant to escape, and understanding of the functions of viral proteins. However, experimentally measuring effects of mutations is challenging: we lack tractable lab assays for many SARS-CoV-2 proteins, and comprehensive deep mutational scanning has been applied to only two SARS-CoV-2 proteins. Here, we develop an approach that leverages millions of publicly available SARS-CoV-2 sequences to estimate effects of mutations. We first calculate how many independent occurrences of each mutation are expected to be observed along the SARS-CoV-2 phylogeny in the absence of selection. We then compare these expected observations to the actual observations to estimate the effect of each mutation. These estimates correlate well with deep mutational scanning measurements. For most genes, synonymous mutations are nearly neutral, stop-codon mutations are deleterious, and amino acid mutations have a range of effects. However, some viral accessory proteins are under little to no selection. We provide interactive visualizations of effects of mutations to all SARS-CoV-2 proteins (https://jbloomlab.github.io/SARS2-mut-fitness/). The framework we describe is applicable to any virus for which the number of available sequences is sufficiently large that many independent occurrences of each neutral mutation are observed.

From Bound to Free: On the Degrammaticalization of the Polish Intensifying Prefix prze-

ABSTRACTBased on empirical material derived from the National Corpus of Polish and supplemental web-based sources, this paper provides an account of a recent change affecting the Polish intensifying prefix prze-, namely the emergence of its autonomous uses. It is argued that the development at issue exemplifies a rare linguistic process known as degrammaticalization, which incorporates phenomena running counter to a prototypical grammaticalization scenario. Firstly, the investigated Polish element seems to have undergone phonetic strengthening, as suggested by its relatively common separate spelling and occasional capitalization in non-edited, spontaneous written data. Secondly, the emancipated form has increased its morphosyntactic flexibility, as reflected by its appearance in reduplicative constructions, co-occurrence with verb phrases, independent occurrence in predicative settings, and the possibility of extraposition. And thirdly, it has been affected by semantic enrichment, i.e., it has additionally acquired an evaluative (positive) sense. The analyzed change is further claimed to be fueled by paradigmatic analogy to the frequent, well-established neoclassical elements super(-) and mega(-), which function as prefixal intensifiers as well as free intensifying and evaluative items, coupled with the general tendency for language change to involve renewal, whereby older expressive forms become superseded by novel, more vigorous expressions with the same meaning contents.

Epidemiological review of multiple primary malignant neoplasms of the prostate, kidney, and bladder

Background. In recent years, an increase in the incidence of multiple primary malignancies has been observed. Multiple primary malignancies are an independent occurrence and development of two or more neoplasms of different histological origin in one patient.Aim. To evaluate epidemiological, clinical and morphological aspects of primary multiple malignant neoplasms of the prostate, kidney, and bladder.Materials and methods. Data analysis of the work report of the Saratov region oncological service in 2019, presented by the Regional Clinical Oncological Dispensary, patient case histories in the archive of the medical information system was performed.We performed a comparative analysis of the literature sources and data we obtained based to the following criteria: topographic anatomical combination of tumor locations, distribution of tumor combinations depending on time of occurrence (synchronous, metachronous), dynamics of urogenital multiple primary malignancies diagnosis in 2012-2019, distribution by gender and age, combination of stages of tumor process in both tumors, distribution by combination of histological types.Results. Between 2012 and 2019, 783 cases of multiple primary tumors with lesions in the urogenital system were identified. We studied 186 cases with a combination of two malignant neoplasms in the prostate, kidney, and bladder. Tumors developed synchronously in 36 % of patients, metachronously in 64 %. Mean patient age was 75 years. Half of the cases were in the group of localized stages - 90 (48.4 %), with the most common combination of TI-TII stages observed in 46 (24.7 %) cases. Combinations of acinar adenocarcinoma of the prostate with urothelial carcinoma of the bladder (34.7 %), clear cell renal carcinoma (27.8 %), papillary urothelial carcinoma of the bladder (12.5 %) were the most common according to histological diagnosis of primary multiple tumors of the urogenital system.Conclusion. Over the recent years we can observe a steady growth of diagnosable urogenital multiple primary malignancies. Morphological verification of the tumor and revelation of the most frequent histological types allows to assume the presence of the common mechanisms of development and the influence of tumor microenvironment on the growth of both tumors in a multiple primary malignancies pair.

Heterogeneity of glycan biomarker clusters as an indicator of recurrence in pancreatic cancer.

Outcomes following tumor resection vary dramatically among patients with pancreatic ductal adenocarcinoma (PDAC). A challenge in defining predictive biomarkers is to discern within the complex tumor tissue the specific subpopulations and relationships that drive recurrence. Multiplexed immunofluorescence is valuable for such studies when supplied with markers of relevant subpopulations and analysis methods to sort out the intra-tumor relationships that are informative of tumor behavior. We hypothesized that the glycan biomarkers CA19-9 and STRA, which detect separate subpopulations of cancer cells, define intra-tumoral features associated with recurrence. We probed this question using automated signal thresholding and spatial cluster analysis applied to the immunofluorescence images of the STRA and CA19-9 glycan biomarkers in whole-block sections of PDAC tumors collected from curative resections. The tumors (N = 22) displayed extreme diversity between them in the amounts of the glycans and in the levels of spatial clustering, but neither the amounts nor the clusters of the individual and combined glycans associated with recurrence. The combined glycans, however, marked divergent types of spatial clusters, alternatively only STRA, only CA19-9, or both. The co-occurrence of more than one cluster type within a tumor associated significantly with disease recurrence, in contrast to the independent occurrence of each type of cluster. In addition, intra-tumoral regions with heterogeneity in biomarker clusters spatially aligned with pathology-confirmed cancer cells, whereas regions with homogeneous biomarker clusters aligned with various non-cancer cells. Thus, the STRA and CA19-9 glycans are markers of distinct and co-occurring subpopulations of cancer cells that in combination are associated with recurrence. Furthermore, automated signal thresholding and spatial clustering provides a tool for quantifying intra-tumoral subpopulations that are informative of outcome.

Mapping Past Distributions of Marine Mollusks Using Shell Death Assemblages

Marine species assessments rely heavily on baseline surveys conducted after the 1960s, long after many anthropogenic pressures began, which could lead to misinformed management decisions and poor conservation outcomes. In this study, we collaborated with Florida Fish and Wildlife to conduct stock assessments for mollusks of the west Florida shelf that incorporate shell death assemblages. One of our first assessments was of the Florida Fighting Conch, Strombus alatus, an abundant gastropod that is also under consideration as a replacement fishery for the threatened Queen Conch. Live and dead shells were collected from >300 dredge tows between 2008-2018 covering the entire west Florida shelf. Shells were age-partitioned by 14C- and AAR-calibrated taphonomic criteria. Counts were converted to densities per m2. Inverse distance weighting interpolation of S. alatus death assemblages reveals multiple population centers along the coast and a rapid decrease in density with depth from 25-120 m. In contrast, live conchs were absent in our dredge samples from shelf depths deeper than 40 m. These differences are confirmed by single-visit occupancy methods that account for variation in detectability across the samples. Live-dead differences in spatial distribution are probably influenced by time averaging in death assemblages, which increases detectability of conchs in deeper habitats, where they may be too rare to be sampled alive. However, extirpation of offshore populations was also indicated by independent natural history collection occurrence records, which show numerous live-collected conchs from 1940-1980 but none afterwards, despite an increase in sampling effort. These results suggest that live-dead comparisons can reveal biodiversity loss at the scale of large marine ecosystems.

Self-consistent nanoflare heating in model active regions: MHD avalanches

ABSTRACT Straightened cylindrical models of coronal loops have been standard for decades, and shown to support nanoflare-like heating, but the influence of geometric curvature in models upon the heating produced has not been discussed in depth. Heating, its spatiotemporal distributions, and the associated mechanisms responsible are discussed, and compared with those from straightened models of a coronal loop. Previously, magnetohydrodynamic avalanches have been generalized to curved loops, and shown to be viable. From that study, the associated heating is analysed and discussed in depth. Heating is seen to arise from processes originally instigated, yet not dominated, by magnetic reconnection, producing bursty, aperiodic nanoflares, dispersed evenly throughout the corona, but with a modest bias away from footpoints. One novelty arising is the simultaneous yet independent occurrence of nanoflare-like events at disjoint sites along individual strands, anticipating some features recently seen in ‘campfires’ by Solar Orbiter. With a view to future refinements in the model and to the inclusion of additional physical effects, the implications of this analysis are discussed.

Do genetically informed distribution models improve range predictions in past climates? A case study with balsam poplar

Species distribution models (SDMs) are one of the most widely used approaches to predict changes in habitat suitability in response to climate change. However, as typically implemented, SDMs treat species as genetically uniform throughout their ranges and thereby ignore potentially important genetic differences between populations. While numerous studies have used SDMs to model genetically based subgroupings within species, the ability of such models to be transferred to new times has rarely been evaluated. Here, we used standard and genetically informed distribution models (gSDMs) to predict the future and past range of balsam poplar (Populus balsamifera L.). We then assessed model transferability of standard SDMs and gSDMs using balsam poplar fossil pollen and macrofossil occurrences. In general, standard and gSDMs performed similarly through time, with both predicting a northward expanding range from refugia as glaciers receded over the past 22 ky BP and declining suitable area in future climates. Both standard and gSDMs showed moderate abilities to distinguish balsam poplar fossils from pseudo-absences but tended to predict lower suitability at fossil sites during the Pleistocene-Holocene transition. Although gSDMs applied to balsam poplar did not prove more transferable than standard SDMs, they provided numerous unique insights, such as the change in suitable area of genetic clusters through time and potential refugial locations. We argue more research is needed to determine which species may benefit most from the gSDM approach and to test gSDMs with temporally or spatially independent occurrences, as is often recommended for standard SDMs.

Formal Theories of Occurrences and Substitutions

Formal Theories of Occurrences and Substitutions

Palate evolution in early-branching crocodylomorphs: Implications for homology, systematics, and ecomorphology.

Living crocodylomorphs have an ossified secondary palate with a posteriorly positioned choana that enables their semi‐aquatic, predatory ecology. In contrast, the earliest branching members of Crocodylomorpha have an open palate with anteriorly positioned choanae. The evolution of an ossified secondary palate and a posteriorly positioned choana features strongly in hypotheses of broad‐scale phylogenetic relationships within Crocodylomorpha. Renewed investigations into palatal morphology among extinct members of the clade show surprising variability in the anatomy of the palate, with at least one and potentially a second independent occurrence of “eusuchian‐type” palate outside of Eusuchia. Understanding the trajectory of crocodylomorph palatal evolution is, therefore, a key to inferring crocodylomorph interrelationships and ecomorphology. To document early‐branching crocodylomorph palatal anatomy, we developed an anatomical comparative dataset using computed tomography scan data and literature, comprising 12 early‐branching crocodylomorph taxa. To understand discrete phenotypic changes in palatal structure, we compiled a phylogenetically broadly sampled character‐taxon matrix from the existing literature, and revised its palatal characters, adding 10 new palatal characters. Our comparative anatomical investigations allow us to propose an adapted hypothesis for the closure of the palate and the posterior migration of the choana. Our phylogenetic findings corroborate previous research showing that non‐crocodyliform crocodylomorphs (“sphenosuchians”) are paraphyletic, with the exclusion of the clade Hallopodidae. Non‐mesoeucrocodylian crocodyliforms (“protosuchians”) are paraphyletic, but form three monophyletic clades: Notochampsoidea, Shartegosuchoidea, and Gobiosuchidae. We find a potential association between secondary palate development and dietary shifts, particularly with regard to hypothesized origins of herbivory.

Predicting the Potential Geographical Distribution of Medicinal Plant (<i>Taxus baccata</i>, L. subsp. Wallichiana) in Shimla District, Himachal Pradesh

The population of medicinal plant, Taxus baccata (Himalayan yew) is declining due to over harvesting of its bark and leaves, most wild populations are threatened and are endangered in the Himalaya. As a consequence, the species has already become endangered, facing risk of extinction soon. The present study has been conducted to predict the potential habitats for Taxus baccata in Shimla using the MaxEnt modeling. Through Multi-co linearity test only 19 variables along with 52 Spatio-temporally independent species occurrence locations were used for modeling. IDW method was used to interpolate the soil data. The result shows that the best AUC of 0.971 ± 0.015 was obtained when the model was set at 100 replication and 1000 iterations. The interpretation of variables revealed that, apart from climatic and topographic parameters, edaphic factor also has influential impact on the distribution of plant. The jackknife test shows that edaphic factor (phosphorus, carbon, nitrogen, pH), topographic and Environmental factor BIO14 (Precipitation of Driest Month) and BIO11 (Mean Temperature of Coldest Quarter) were the key predictor variables associated with its distribution. The success of this model could be promising in determining potential distribution of Himalayan yew and its reintroduction can be useful in the study of species ecology, biogeography, and conservation planning in the Himalaya.

Adjustment for Multimorbidity in Estimations of the Burden of Diseases Using Korean NHIS Data.

The current multimorbidity correction method in the Global Burden of Disease studies assumes the independent occurrence of diseases. Those studies use Monte-Carlo simulations to adjust for the presence of multiple disease conditions for all diseases. The present study investigated whether the above-mentioned assumption is reasonable based on the prevalence confirmed from actual data. This study compared multimorbidity-adjusted years of lived with disability (YLD) obtained by Monte-Carlo simulations and multimorbidity-adjusted YLD using multimorbidity prevalence derived from National Health Insurance Service data. The 5 most common diseases by sex and age groups were selected as diseases of interest. No significant differences were found between YLD estimations made using actual data and Monte-Carlo simulations, even though assumptions about the independent occurrence of diseases should be carefully applied. The prevalence was not well reflected according to disease characteristics in those under the age of 30, among whom there was a difference in YLD between the 2 methods. Therefore, when calculating the burden of diseases for Koreans over the age of 30, it is possible to calculate the YLD with correction for multimorbidity through Monte-Carlo simulation, but care should be taken with under-30s. It is useful to apply the efficiency and suitability of calibration for multiplicative methods using Monte-Carlo simulations in research on the domestic disease burden, especially in adults in their 30s and older. Further research should be carried out on multimorbidity correction methodology according to the characteristics of multiple diseases by sex and age.

Thyroid-Related Hormone Levels in Clinical Patients With Moderately Severe-to-Profound Sudden Sensorineural Hearing Loss: A Prospective Study.

Objectives: Sudden sensorineural hearing loss (SSNHL) is a common otological emergency, causing a measure of hearing loss and affecting the quality of life. This study aims to investigate the association of thyroid-related hormone levels with moderately severe-to-profound SSNHL.Methods: The study included 70 patients with moderately severe-to-profound SSNHL and 100 age- and sex-matched healthy controls. Peripheral venous blood samples were taken from the participants, and their thyroid-related hormone levels were measured at admission and 1 week after treatment.Results: In moderately severe-to-profound SSNaHL patients, the concentrations of total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) (all P < 0.05) were significantly lower than in the control group. The TT3, TT4, FT3, and TSH levels were significantly higher in the effective group than in the ineffective group (all P < 0.05). Linear correlation analysis revealed that TSH level (R = 0.707, P < 0.05) elevation after treatment successfully predicted a favorable outcome of hearing recovery. Logistic regression analyses suggested low FT3 and TSH levels to be independent occurrence predictors, while the increase of TSH level may be an independent favorable outcome predictor.Conclusions: The results suggest that low FT3 and TSH levels are risk factors for moderately severe-to-profound SSNHL. By discovering the positive association between TSH elevation and hearing recovery, along with the potential novel predictors of FT3 and TSH, our study may contribute valuable insights to the research and treatment of moderately severe-to-profound SSNHL.