A model organism pipeline provides insight into the clinical heterogeneity of TARS1 loss-of-function variants.

Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed, essential enzymes that complete the first step of protein translation: ligation of amino acids to cognate tRNAs. Genes encoding ARSs have been implicated in myriad dominant and recessive phenotypes, the latter often affecting multiple tissues but with frequent involvement of the central and peripheral nervous systems, liver, and lungs. Threonyl-tRNA synthetase (TARS1) encodes the enzyme that ligates threonine to tRNATHR in the cytoplasm. To date, TARS1 variants have been implicated in a recessive brittle hair phenotype. To better understand TARS1-related recessive phenotypes, we engineered three TARS1 missense variants at conserved residues and studied these variants in Saccharomyces cerevisiae and Caenorhabditis elegans models. This revealed two loss-of-function variants, including one hypomorphic allele (R433H). We next used R433H to study the effects of partial loss of TARS1 function in a compound heterozygous mouse model (R432H/null). This model presents with phenotypes reminiscent of patients with TARS1 variants and with distinct lung and skin defects. This study expands the potential clinical heterogeneity of TARS1-related recessive disease, which should guide future clinical and genetic evaluations of patient populations.

Cellular Therapy in Experimental Autoimmune Encephalomyelitis as an Adjuvant Treatment to Translate for Multiple Sclerosis.

This study aims to evaluate and compare cellular therapy with human Wharton's jelly (WJ) mesenchymal stem cells (MSCs) and neural precursors (NPs) in experimental autoimmune encephalomyelitis (EAE), a preclinical model of Multiple Sclerosis. MSCs were isolated from WJ by an explant technique, differentiated to NPs, and characterized by cytometry and immunocytochemistry analysis after ethical approval. Forty-eight rats were EAE-induced by myelin basic protein and Freund's complete adjuvant. Forty-eight hours later, the animals received intraperitoneal injections of 250 ng/dose of Bordetella pertussis toxin. Fourteen days later, the animals were divided into the following groups: a. non-induced, induced: b. Sham, c. WJ-MSCs, d. NPs, and e. WJ-MSCs plus NPs. 1 × 105. Moreover, the cells were placed in a 10 µL solution and injected via a stereotaxic intracerebral ventricular injection. After ten days, the histopathological analysis for H&E, Luxol, interleukins, and CD4/CD8 was carried out. Statistical analyses demonstrated a higher frequency of clinical manifestation in the Sham group (15.66%) than in the other groups; less demyelination was seen in the treated groups than the Sham group (WJ-MSCs, p = 0.016; NPs, p = 0.010; WJ-MSCs + NPs, p = 0.000), and a lower cellular death rate was seen in the treated groups compared with the Sham group. A CD4/CD8 ratio of <1 showed no association with microglial activation (p = 0.366), astrocytes (p = 0.247), and cell death (p = 0.577) in WJ-MSCs. WJ-MSCs and NPs were immunomodulatory and neuroprotective in cellular therapy, which would be translated as an adjunct in demyelinating diseases.

Testing the efficacy of a narrative short film in educating the public about providing emotional support to individuals with fertility problems.

BACKGROUND: To educate the public on how best to support people with fertility problems, a narrative short film "Ten Things Not to Say to Someone Struggling with Infertility" was created, depicting the impact that helpful versus unhelpful dialogue has on someone with fertility problems. METHODS: Before and after watching the video, 419 participants from the public were presented with a hypothetical vignette describing a woman experiencing fertility problems and asked about the likelihood that they would endorse a series of helpful and unhelpful statements when communicating with the protagonist. Pre and post endorsement of helpful versus unhelpful statements were compared, as were self-perceived knowledge about the mental health aspects of fertility problems, confidence in providing emotional support to someone with fertility problems, and empathy for the protagonist. RESULTS: Participants endorsed fewer unhelpful statements after the video relative to before (M(SD) = 2.2(2.3) vs. 1.3(2.3), p < .001) and fewer participants endorsed at least one unhelpful statement (72% to 47%, p < .001). Self-perceived knowledge of fertility problems, confidence in providing support, and empathy increased at post-test (ps < .001; Cohen's d = .56-.83) indicating medium-large effects. CONCLUSIONS: A narrative short film appears to be an effective dissemination strategy for sensitizing the public to the emotional struggles of individuals experiencing fertility problems.

A machine of the same: Repetition in the foundational discourse of the Argentinean "being" (1976-1983).

Using the example of the military regime in Argentina (1976-1983) and relevant archival materials, this article demonstrates the prerequisite of exalted language in constructing an enemy and how a discursive 'machine of the same' was put into operation. The author argues that what made this operation unique is its structure of repetition that stimulated "the tendency to merge" what is "foreigner-to-the-ego", and the "enemy outside" into a single concept in the Argentinian national psyche.As a theoretical lens, the author examines the military regime's language through Freud's understanding of groups and civilization and Laplanche's proposition that cultural narratives in the form of mytho-symbolic explanations help us translate the sexual drive and offer a "solution" to the helplessness of the infant-adult.The author further claims that at other times a cultural narration functions as an anti-translation device when set against the emergence of a new net of significations. The nation's founding narrative of an Occidental-Spanish-Catholic "being" that first effaced its indigenous origins and then its Arabic and Jewish inheritance was brought back by the military regime as a mytho-symbolic narration that formed a shield against the repressed remnants of the enigmatic message pressing for a new translation.

Dutch Translation of the Yost Self-Report Lower Extremity Lymphedema Screening Questionnaire in Women.

BACKGROUND: Validated questionnaires of self-reported LEL are important in the assessment and diagnosis of LEL. The aim of this study was to validate and translate a Dutch version of the screening questionnaire, the LELSQ developed and validated by Yost et al. Methods: We tested the questionnaire on a group of healthy women and a group of patients diagnosed with LEL. The translation was carried out using the forward and backward method from English to Dutch. STATISTICAL ANALYSES: SPSS (IBM corp, Armonk, New York, NY, USA) version 28.0.1.0 (001) was used for statistical analysis in the process of validation. The internal consistency was assessed by determining Cronbach's alpha. The reliability was tested by test-retest reliability. The validity was determined by ROC analysis, and content and face validity were evaluated. RESULTS: The internal consistency score in both groups had a strong value (0.83 to 0.90). The test-retest reliability was also strong in both groups. Face and content validity showed the LELSQ is an easy, understandable questionnaire that is not too time-consuming in the early detection of LEL. The ROC analysis showed an AUC value of 0.93, indicating strong validity. CONCLUSIONS: The validated Dutch translation showed high values for internal consistency, test-retest reliability, and validity, which allows us to implement the questionnaire in the early detection of LEL after gynecological cancer treatment.

Wearable ultrasound devices: An emerging era for biomedicine and clinical translation.

In recent years, personalized diagnosis and treatment have gained significant recognition and rapid development in the biomedicine and healthcare. Due to the flexibility, portability and excellent compatibility, wearable ultrasound (WUS) devices have become emerging personalized medical devices with great potential for development. Currently, with the development of the ongoing advancements in materials and structural design of the ultrasound transducers, WUS devices have improved performance and are increasingly applied in the medical field. In this review, we provide an overview of the design and structure of WUS devices, focusing on their application for diagnosis and treatment of various diseases from a clinical application perspective, and then explore the issues that need to be addressed before clinical translation. Finally, we summarize the progress made in the development of WUS devices, and discuss the current challenges and the future direction of their development. In conclusion, WUS devices usher an emerging era for biomedicine with great clinical promise.

Multiscale modeling uncovers 7q11.23 copy number variation-dependent changes in ribosomal biogenesis and neuronal maturation and excitability.

Copy number variation (CNV) at 7q11.23 causes Williams-Beuren syndrome (WBS) and 7q microduplication syndrome (7Dup), neurodevelopmental disorders (NDDs) featuring intellectual disability accompanied by symmetrically opposite neurocognitive features. Although significant progress has been made in understanding the molecular mechanisms underlying 7q11.23-related pathophysiology, the propagation of CNV dosage across gene expression layers and their interplay remains elusive. Here we uncovered 7q11.23 dosage-dependent symmetrically opposite dynamics in neuronal differentiation and intrinsic excitability. By integrating transcriptomics, translatomics, and proteomics of patient-derived and isogenic induced neurons, we found that genes related to neuronal transmission follow 7q11.23 dosage and are transcriptionally controlled, while translational factors and ribosomal genes are posttranscriptionally buffered. Consistently, we found phosphorylated RPS6 (p-RPS6) downregulated in WBS and upregulated in 7Dup. Surprisingly, p-4EBP was changed in the opposite direction, reflecting dosage-specific changes in total 4EBP levels. This highlights different dosage-sensitive dyregulations of the mTOR pathway as well as distinct roles of p-RPS6 and p-4EBP during neurogenesis. Our work demonstrates the importance of multiscale disease modeling across molecular and functional layers, uncovers the pathophysiological relevance of ribosomal biogenesis in a paradigmatic pair of NDDs, and uncouples the roles of p-RPS6 and p-4EBP as mechanistically actionable relays in NDDs.

A Biallelic Variant of the RNA Exosome Gene, EXOSC4, Associated with Neurodevelopmental Defects Impairs RNA Exosome Function and Translation.

The RNA exosome is an evolutionarily conserved complex required for both precise RNA processing and decay. Pathogenic variants in EXOSC genes, which encode structural subunits of this complex, are linked to several autosomal recessive disorders. Here, we describe a missense allele of the EXOSC4 gene that causes a collection of clinical features in two affected siblings. This missense variant (NM_019037.3: exon3:c.560T>C), changes a leucine residue within a conserved region of EXOSC4 to proline (p.Leu187Pro). The two affected individuals show prenatal growth restriction, failure to thrive, global developmental delay, intracerebral and basal ganglia calcifications, and kidney failure. Homozygosity for the damaging variant was identified by exome sequencing with Sanger sequencing to confirm segregation. To explore the functional consequences of this amino acid change, we modeled EXOSC4-L187P in the corresponding budding yeast protein, Rrp41 (Rrp41-L187P). Cells that express Rrp41-L187P as the sole copy of the essential Rrp41 protein show growth defects. Steady-state levels of both Rrp41-L187P and EXOSC4-L187P are decreased compared to controls and EXOSC4-L187P shows decreased co-purification with other RNA exosome subunits. RNA exosome target transcripts accumulate in rrp41-L187P cells, including the 7S precursor of 5.8S rRNA. Polysome profiles show a decrease in actively translating ribosomes in rrp41-L187P cells as compared to control cells with incorporation of 7S pre-rRNA into polysomes. This work adds EXOSC4 to the structural subunits of the RNA exosome that have been linked to human disease and defines foundational molecular defects that could contribute to the adverse phenotypes caused by EXOSC pathogenic variants.

The m6A reader SlYTH2 negatively regulates tomato fruit aroma by impeding the translation process.

N6-methyladenosine (m6A) is a fundamentally important RNA modification for gene regulation, whose function is achieved through m6A readers. However, whether and how m6A readers play regulatory roles during fruit ripening and quality formation remains unclear. Here, we characterized SlYTH2 as a tomato m6A reader protein and profiled the binding sites of SlYTH2 at the transcriptome-wide level. SlYTH2 undergoes liquid-liquid phase separation and promotes RNA-protein condensate formation. The target mRNAs of SlYTH2, namely m6A-modified SlHPL and SlCCD1B associated with volatile synthesis, are enriched in SlYTH2-induced condensates. Through polysome profiling assays and proteomic analysis, we demonstrate that knockout of SlYTH2 expedites the translation process of SlHPL and SlCCD1B, resulting in augmented production of aroma-associated volatiles. This aroma enrichment significantly increased consumer preferences for CRISPR-edited fruit over wild type. These findings shed light on the underlying mechanisms of m6A in plant RNA metabolism and provided a promising strategy to generate fruits that are more attractive to consumers.

Discovery of A G-Quadruplex Unwinder That Unleashes the Translation of G-Quadruplex-Containing mRNA without Inducing DNA Damage.

To explore the mechanisms and therapeutic strategies for G-quadruplex (G4) mediated diseases, it is crucial to manipulate and intervene in intracellular G4 structures using small molecular tools. While hundreds of G4 stabilizers have been developed, there is a significant gap in the availability of G4 unwinding agents. Here, we propose a strategy to disrupt G-quadruplexes by forming G-C hydrogen bonds with chemically modified cytidine trimers. We validated a good G4 unwinder, the 2'-F cytidine trimer (2'-F C3). 2'-F C3 does not inhibit cell growth nor cause severe DNA damage at a concentration below 10 µM. Moreover, 2'-F C3 does not affect gene transcription nor RNA splicing, while it significantly enhances the translation of G4-containing mRNA and upregulates RNA splicing, RNA processing and cell cycle pathways. The discovery of this G4 unwinder provides a functional tool for the chemical modulation of G4s in living cells.

Individualized high-resolution analysis to categorize diverse learning and memory deficits in tau rTg4510 mice exposed to low-intensity blast.

Mild traumatic brain injury (mTBI) resulting from low-intensity blast (LIB) exposure in military and civilian individuals is linked to enduring behavioral and cognitive abnormalities. These injuries can serve as confounding risk factors for the development of neurodegenerative disorders, including Alzheimer's disease-related dementias (ADRD). Recent animal studies have demonstrated LIB-induced brain damage at the molecular and nanoscale levels. Nevertheless, the mechanisms linking these damages to cognitive abnormalities are unresolved. Challenges preventing the translation of preclinical studies into meaningful findings in "real-world clinics" encompass the heterogeneity observed between different species and strains, variable time durations of the tests, quantification of dosing effects and differing approaches to data analysis. Moreover, while behavioral tests in most pre-clinical studies are conducted at the group level, clinical tests are predominantly assessed on an individual basis. In this investigation, we advanced a high-resolution and sensitive method utilizing the CognitionWall test system and applying reversal learning data to the Boltzmann fitting curves. A flow chart was developed that enable categorizing individual mouse to different levels of learning deficits and patterns. In this study, rTg4510 mice, which represent a neuropathology model due to elevated levels of tau P301L, together with the non-carrier genotype were exposed to LIB. Results revealed distinct and intricate patterns of learning deficits and patterns within each group and in relation to blast exposure. With the current findings, it is possible to establish connections between mice with specific cognitive deficits to molecular changes. This approach can enhance the translational value of preclinical findings and also allow for future development of a precision clinical treatment plan for ameliorating neurologic damage of individuals with mTBI.

A randomized phase 2 study of HLX22 plus trastuzumab biosimilar HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric cancer.

BACKGROUND: Gastric cancer is the fifth most common cancer and the fourth most common cause of cancer death worldwide, yet the prognosis of advanced disease remains poor. METHODS: This was a randomized, double-blinded, phase 2 trial (ClinicalTrials.gov: NCT04908813). Patients with locally advanced/metastatic HER2-positive gastric/gastroesophageal junction cancer and no prior systemic antitumor therapy were randomized 1:1:1 to 25 mg/kg HLX22 (a novel anti-HER2 antibody) + HLX02 (trastuzumab biosimilar) + oxaliplatin and capecitabine (XELOX) (group A), 15 mg/kg HLX22 + HLX02 + XELOX (group B), or placebo + HLX02 + XELOX (group C) in 3-week cycles. Primary endpoints were progression-free survival (PFS) and objective response rate (ORR) assessed by independent radiological review committee (IRRC). FINDINGS: Between November 29, 2021, and June 6, 2022, 82 patients were screened; 53 were randomized to group A (n = 18), B (n = 17), and C (n = 18). With 14.3 months of median follow-up, IRRC-assessed median PFS was prolonged with the addition of HLX22 (A vs. C, 15.1 vs. 8.2 months, hazard ratio [HR] 0.5 [95% confidence interval (CI) 0.17-1.27]; B vs. C, not reached vs. 8.2 months, HR 0.1 [95% CI 0.04-0.52]). Confirmed ORR was comparable among groups (A vs. B vs. C, 77.8% vs. 82.4% vs. 88.9%). Treatment-related adverse events (TRAEs) were observed in 18 (100%), 16 (94.1%), and 17 (94.4%) patients, respectively. One (5.6%) patient in group C reported a grade 5 TRAE. CONCLUSIONS: Adding HLX22 to HLX02 and XELOX prolonged PFS and enhanced antitumor response in the first-line treatment of HER2-positive gastric cancer, with manageable safety. FUNDING: Shanghai Henlius Biotech, Inc.

eIF6 Promotes Gastric Cancer Proliferation and Invasion by Regulating Cell Cycle.

OBJECTIVE: To investigate the role and function of eIF6 in gastric cancer (GC). METHODS: The expression level of eIF6 in GC tissues and normal tissues was detected in different high-throughput sequencing cohorts. Survival analysis, gene differential analysis, and enrichment analysis were performed in the TCGA cohort. Biological networks centered on eIF6 were constructed through two different databases. Immunohistochemistry (IHC) and Western blot were used to detect protein expression of eIF6, and qRT-PCR was used to detect eIF6 mRNA expression. The correlation between the expression of eIF6 in GC tissues and clinicopathological parameters of GC was analyzed. siRNA knockout of eIF6 was used to study the proliferation, migration, and invasion. The effects of eIF6 on cell cycle and Cyclin B1 were detected by flow cytometry and Western blot. RESULTS: eIF6 was significantly overexpressed in GC tissues and predicted poor prognosis. In addition, 113 differentially expressed genes were detected in cancer-related biological pathways and functions by differential analysis. Biological networks revealed interactions of genes and proteins with eIF6. The expression intensity of eIF6 in cancer tissues was higher than that in adjacent tissues (P = 0.0001), confirming the up-regulation of eIF6 expression in GC tissues. The expression level of eIF6 was statistically significant with pTNM stage (P = 0.006). siRNA knockout of eIF6 significantly reduced the proliferation, colony formation, migration, and invasion ability of GC cells. Silencing of eIF6 also inhibited the cell cycle of GC cells in G2/M phase and decreased the expression level of CyclinB1. CONCLUSION: Our study suggests that eIF6 is up-regulated in GC and may promote the proliferation, migration, and invasion of GC by regulating cell cycle.

Psychometric testing of the Chinese version of the Perinatal Infant Care Social Support tool: a methodological study.

PURPOSE: This study aimed to translate the Perinatal Infant Care Social Support (PICSS) instrument into Chinese and to verify the reliability and validity of the translated version. METHODS: This study used a cross-sectional design to examine the reliability and validity of the Chinese version of the PICSS (C-PICSS). A cohort of 150 first-time mothers in China participated, attending hospital follow-up care at 6 weeks postpartum. Data were collected after obtaining informed consent from the mothers. RESULTS: The majority of mothers were aged between 20 and 29 years, with a mean age of 26.25 (±3.90) years. An item analysis of the 19 items in the C-PICSS showed that all items had an item-total score correlation above 0.2. This resulted in a Kaiser-Meyer-Olkin value of 0.92 and a significant Bartlett's test of sphericity (χ2=1,778.65, p<.001), confirming the suitability of the data for factor analysis. Correlation analyses revealed a strong positive relationship between infant care social support and general social support (r=.62, p<.001), and a negative relationship between infant care social support and postpartum depression (r=-.38, p<.001). Higher scores for infant care social support were associated with reporting positive relationships with their husbands (t=3.72, p<.001) and high levels of spousal involvement (t=4.09, p<.001). In terms of structural support, spouses were identified as the primary source. CONCLUSION: The research results indicate that C-PICSS is reliable and valid as an indicator of social support for infant care among Chinese mothers.

Protein aggregation in plant mitochondria lacking Lon1 inhibits translation and induces unfolded protein responses.

Loss of Lon1 led to stunted plant growth and accumulation of nuclear-encoded mitochondrial proteins including Lon1 substrates. However, an in-depth label-free proteomics quantification of mitochondrial proteins in lon1 revealed that the majority of mitochondrial-encoded proteins decreased in abundance. Additionally, we found that lon1 mutants contained protein aggregates in the mitochondrial that were enriched in metabolic enzymes, ribosomal subunits and PPR-containing proteins of the translation apparatus. These mutants exhibited reduced general mitochondrial translation as well as deficiencies in RNA splicing and editing. These findings support the role of Lon1 in maintaining a functional translational apparatus for mitochondrial-encoded gene translation. Transcriptome analysis of lon1 revealed a mitochondrial unfolded protein response reminiscent of the mitochondrial retrograde signalling dependent on the transcription factor ANAC017. Notably, lon1 mutants exhibited transiently elevated ethylene production, and the shortened hypocotyl observed in lon1 mutants during skotomorphogenesis was partially alleviated by ethylene inhibitors. Furthermore, the short root phenotype was partially ameliorated by introducing a mutation in the ethylene receptor ETR1. Interestingly, the upregulation of only a select few target genes was linked to ETR1-mediated ethylene signalling. Together this provides multiple steps in the link between loss of Lon1 and signalling responses to restore mitochondrial protein homoeostasis in plants.

Dynamic decoding and dual synthetic data for automatic correction of grammar in low-resource scenario.

Grammar error correction systems are pivotal in the field of natural language processing (NLP), with a primary focus on identifying and correcting the grammatical integrity of written text. This is crucial for both language learning and formal communication. Recently, neural machine translation (NMT) has emerged as a promising approach in high demand. However, this approach faces significant challenges, particularly the scarcity of training data and the complexity of grammar error correction (GEC), especially for low-resource languages such as Indonesian. To address these challenges, we propose InSpelPoS, a confusion method that combines two synthetic data generation methods: the Inverted Spellchecker and Patterns+POS. Furthermore, we introduce an adapted seq2seq framework equipped with a dynamic decoding method and state-of-the-art Transformer-based neural language models to enhance the accuracy and efficiency of GEC. The dynamic decoding method is capable of navigating the complexities of GEC and correcting a wide range of errors, including contextual and grammatical errors. The proposed model leverages the contextual information of words and sentences to generate a corrected output. To assess the effectiveness of our proposed framework, we conducted experiments using synthetic data and compared its performance with existing GEC systems. The results demonstrate a significant improvement in the accuracy of Indonesian GEC compared to existing methods.

Tuning tRNAs for improved translation.

Transfer RNAs have been extensively explored as the molecules that translate the genetic code into proteins. At this interface of genetics and biochemistry, tRNAs direct the efficiency of every major step of translation by interacting with a multitude of binding partners. However, due to the variability of tRNA sequences and the abundance of diverse post-transcriptional modifications, a guidebook linking tRNA sequences to specific translational outcomes has yet to be elucidated. Here, we review substantial efforts that have collectively uncovered tRNA engineering principles that can be used as a guide for the tuning of translation fidelity. These principles have allowed for the development of basic research, expansion of the genetic code with non-canonical amino acids, and tRNA therapeutics.

Transcultural adaptation of the Adaptive Behavior Assessment System (ABAS-3).

This study describes the cross-cultural adaptation to Brazilian Portuguese of the Adaptive Behavior Assessment System (ABAS-3), which assesses 11 skills areas within three major adaptive domains: the conceptual, social, and practical. The translation was performed by two independent translators, which was followed by the synthesis of the translations by two experts and then an analysis of the synthesis by 33 specialists from the areas of health and education (three per subscale) who were experts in the domains evaluated by ABAS-3. Of the 1121 items of the five ABAS-3 forms, 82 (7.31%) needed revision. There was good agreement between the specialists in respect of most items, with only minor adjustments being required. There was good evidence of content validity and the adequacy of the adaptation in respect of the conceptual, idiomatic, and semantic aspects of the items of the instrument. This initial process of cross-cultural adaptation was necessary because adaptive behavior is strongly influenced by environmental factors such as socioeconomic status and culture.

Translation and validation of the Tinnitus Functional Index (TFI) into Kannada: a tool for clinical and research use in the Indian population.

PURPOSE: The Tinnitus Functional Index (TFI) is a widely recognized measure for evaluating tinnitus and is frequently used in both therapeutic and research contexts. Unfortunately, TFI is currently not available in any Indian languages. In a multilingual country like India, cross-cultural adaptation, translation, and validation of such scales in regional languages are critical to improving their use for clinical and research purposes. Therefore, this study focused on translating and validating the TFI in Kannada for use among the Indian population. MATERIALS AND METHODS: The original version of TFI was translated with the help of audiologists and linguistic experts who were proficient in Kannada. The translated version was content validation by five audiologists and a cognitive debriefing by native speakers to check the familiarity of words. The final version (TFI-K) was then administered to 181 participants with tinnitus. Along with the TFI, other scales like Tinnitus Handicap Inventory (THI) were also obtained to check the convergent validity. The obtained data was then subjected to various statistical analyses like internal consistency, convergent and discriminant validity, and factor analysis. RESULTS: The TFI-K was found to have an excellent internal consistency (Cronbach's α = 0.974) and good convergent validity (p < 0.001; r = 0.778) with THI-K. A principal component analysis with varimax rotation showed communalities ranging from 0.64 to 0.91. Scree plots with the TFI-K component showed a sharp decline after the first factor and approximately four factors above the eigenvalue of 1. The factor analysis results suggest that the TFI-K has a structurally intact 8-factor loading, with a few exceptions that are discussed in detail. CONCLUSION: The TFI-K has demonstrated remarkable dependability and satisfactory integrity, making it a valuable tool for assessment and treatment planning in clinical and research settings.

Tinnitus is known to impinge multiple domains.Assessing multiple domains provides a comprehensive understanding of the impact of tinnitus.Tinnitus Functional Index (TFI) has been cross-culturally translated into Kannada.Tinnitus Functional Index in Kannada (TFI-K) is reliable and valid and can be used clinically and in research.

Outcomes of co-designed communities of practice that support members to address public health issues.

Communities of practice are commonly used to support members in responding to public health issues. This study evaluated the outcomes of five co-designed communities of practice to determine if members' expectations were met, if knowledge sharing between members extended to knowledge translation, and if that supported members in addressing public health issues. Data were collected through an initial needs assessment, observations were made during community of practice sessions over 1 year, and qualitative interviews were conducted at the end of that year. The findings provided evidence that members' expectations were met, knowledge sharing took place within the communities of practice, and personal benefits gained supported members in advancing knowledge sharing with other members to knowledge translation outside their community of practice. Results demonstrate three outcomes of knowledge translation for members: disseminating knowledge to others, applying knowledge to make small-scale changes in practice and leveraging the knowledge to expand its reach beyond members' organizations. While the scale and speed of expanding outcomes were below initial expectations as indicated in the initial needs assessments, members remained optimistic about achieving larger-scale impacts in the future. This study showed that communities of practice achieve gradual progress rather than quick wins. Co-design supports the facilitators in meeting members' needs, which can positively contribute to members sharing knowledge and translating that knowledge to support their practice to address public health issues.