Background: The molecular biological mechanism of tubal factor infertility (TFI) is still unclear. Long noncoding RNAs (lncRNAs) are considered a major part of the competitive endogenous RNA (ceRNA) network and have attracted growing attention. Our study aimed to explore the regulatory mechanisms of lncRNAs associated with TFI and screen potential key genes related to TFI. Materials and Methods: Differentially expressed lncRNAs (DELs) and differentially expressed genes (DEGs) were identified by comparing normal and TFI expression patterns of lncRNAs and mRNAs in eutopic endometrial tissues obtained from 3 normal and 3 TFI patients during implantation. These data were used to develop a protein-protein interaction (PPI) network of DEGs using the STRING online software. The identified DELs and DEGs were then used to construct a ceRNA network, and the Network Analyzer Tool Kit in Cytoscape was used to analyze the ceRNA network topology and stability. Finally, the overlapping genes present in both the ceRNA and PPI networks were selected as the potential key genes related to TFI. Results: Ninety-six DEGs (59 up and 37 down) and 45 DELs (28 up and 17 down) were identified. Thirty-four DEGs were mapped in a PPI network. A ceRNA network, including two lncRNAs (LINC00305 and DLX6-AS1), four microRNAs (hsa-miR-20b-5p, hsa-miR-17-5p, hsa-miR-107, and hsa-miR-24-3p), and four mRNAs (MAP3K3, HMGB3, FAM103A1, and TMEM209), was successfully constructed. Importantly, a potential key gene (TMEM209) related to TFI was identified. Conclusion: The construction of a ceRNA network related to TFI may help elucidate the regulatory mechanism by which genes and lncRNAs function as ceRNA networks. Importantly, TMEM209 may be further evaluated as potential therapeutic targets for TFI.

Keywords: DEGs; DELs; TFI; ceRNA network.

In this review, we summarize the challenges faced by existing oncology treatment sequence decision models and introduce a general framework to conceptualize such models. In the proposed framework, patients with cancer receive at least two lines of therapy (LOTs) followed by palliative care throughout their lifetime. Patients cycle through progression-free and progressive disease health states in each LOT before death. Under this framework, four broad aspects of modeling effectiveness of treatment sequences need exploration. First, disease progression, treatment discontinuation, and the relationship between the two events should be considered. Second, the effectiveness of each LOT depends on its placement in a treatment sequence as the effectiveness of later LOTs may be influenced by the earlier LOTs. Third, the treatment-free interval (TFI; time between discontinuation of earlier LOT and initiation of later LOT) may impact a therapy's effectiveness. Fourth, in the absence of head-to-head trials directly comparing LOTs, indirect treatment comparison (ITC) of outcomes for a specific LOT or even for the entire treatment sequence is important to consider. A search of decision models that estimated effectiveness of at least two lines of oncology therapy was conducted in PubMed (N = 20) and technology appraisals by the National Institute for Health and Care Excellence (N = 26) to assess four methodological aspects related to the model framework: (1) selection of outcomes for effectiveness in a treatment sequence, (2) approaches to adjust the efficacy of a treatment in consideration of its place in the sequence, (3) approaches to address TFIs between LOTs, and (4) incorporation of ITCs to estimate comparators' effectiveness in the absence of direct head-to-head evidence. Most models defined health states based on disease progression on different LOTs while estimating treatment duration outside of the main model framework (30/46) and used data from multiple data sources in different LOTs to model efficacy of a treatment sequence (41/46). No models adjusted efficacy for the characteristics of patients who switched from an earlier LOT to a later LOT or adjusted for the impact of prior therapies, and just six models considered TFIs. While 11 models applied ITC results to estimate efficacy in comparator treatment sequences, the majority limited the ITC to one LOT in the sequence. Thus, there is substantial room to improve the estimation of effectiveness for treatment sequences using existing data when comparing effectiveness of alternative treatment sequences.

Multiple lines of evidence support differences in the megakaryopoiesis during development. Murine in vitro models to study megakaryopoiesis employ cultured megakaryocytes MKs derived from adult bone marrow (BM) or fetal livers (FL) of mouse embryos. Mouse models allow to study the molecular basis for cellular changes utilizing conditional or knock-out models and permit further in vitro genetic or pharmacological manipulations. Despite being extensively used, MKs cultured from these two sources have not been systematically compared. In the present study, we compared BM- and FL-derived MKs, assessing their size, proplatelet production capacity, expression of common MK markers (αIIb, β3, GPIb α, β) and cytoskeletal proteins (filamin A, β1-tubulin, actin), the subcellular appearance of α-granules (VWF), membranes (GPIbβ) and cytoskeleton (F-actin) throughout in vitro development. We demonstrate that FL MKs although smaller in size, spontaneously produce more proplatelets than BM MKs and at earlier stages express more β1-tubulin. In addition, early FL MKs show increased internal GPIbβ staining and present higher GPIbβ (early and late) and VWF (late stages) total fluorescence intensity (TFI)/cell size than BM MKs. BM MKs have up-regulated TPO signaling corresponding to their bigger size and ploidy, without changes in c-Mpl. Expressing endogenous β1-tubulin or the presence of heparin improves BM MKs ability to produce proplatelets. These data suggest that FL MKs undergo cytoplasmic maturation earlier than BM MKs and that this, in addition to higher β1-tubulin levels and GPIb, supported with an extensive F-actin network, could contribute to more efficient proplatelet formation in vitro.

Keywords: Bone marrow; fetal liver; megakaryocytes; proplatelets.

The purposes of this review are to describe the existing research on frailty measurement of older people and to understand their characteristics, with a focus on conceptual definitions, psychometric properties, and diagnostic accuracies. We reviewed the published literature to explore if cross-cultural studies of different types of frailty measurements have been conducted and to determine their applicability in the community setting. Narrative review with limited electronic database search and cross reference searching of included studies was performed. Studies published after year 2001 were searched for using MEDLINE and CINAHL Plus databases with keywords. A total of 5144 search results were obtained, but only 42 frailty measurements were identified in 68 studies. For the type, three different measurements were indicated, namely, self-report instrument (n = 17), clinical observation assessment (n = 19), and mixed frailty assessment instrument (n = 6). Only 12 (29%) measurements examined reliability and validity. Nevertheless, over 35% did not perform any psychometric testing before applying. For diagnosis accuracies, 35 (83%) frailty measurements reported the cut-off value(s) for determining level of the frailty. However, the sensitivity (56%-89.5%) and specificity (52%-91.3%) varied. The applicability was also diverse and some frailty instruments should be only used in some specific population and mode of administration. This review provides an overview of three major types of frailty measurements used in different settings with different purposes. For estimating the prevalence of frailty of older people in a community, the self-report type may be appropriate. The psychometric properties of many reviewed instruments are reported insufficiently. The cut-off value(s) are usually suggested with diverse sensitivity and specificity. Self-report instruments, such as Groningen Frailty Indicator (GFI) and Tilburg Frailty Indicator (TFI), are the most extensively examined in terms of satisfactory psychometric properties. Thus, GFI and TFI, with the current evidence, are recommended to be used in the community setting for frailty screening tools.

Keywords: conceptual definitions; diagnostic accuracies; frailty measurements; instruments; older people; psychometric properties.

The meniscus is one of the most important structures of the knee that needs to be saved if possible. Previous studies showed that increasing time from an anterior cruciate ligament (ACL) injury (TFI) could lead to a meniscal tear, especially medial meniscus (MM). We developed the present study to see if the TFI alone is a predictor of meniscal injury in ACL-deficient knees. We included 111 patients who had a reconstructed ACL injury at our institution from March 2015 to March 2016 in this retrospective cohort study. All demographic data, including age, gender, and body mass index (BMI), were collected. We also recorded the mechanism of injury and the TFI. We extracted the meniscal condition at the time of surgery from the surgical report. All patients were followed up for a mean of 23 months, and the Lysholm score and pain visual analog scale (VAS) score were obtained. The mean TFI of patients with MM tear was 17.4 ± 16.8 months, which was significant than the patients with lateral meniscal (LM) tear (9.3 ± 8.3 months) and intact meniscus (7.4 ± 8.1 months) (p = 0.001). Patients with TFI less than 6 months had a significantly lower rate of MM tear, and increasing TFI more than 6 months could increase the rate of MM tear (p = 0.001). We could not find any association between age, BMI, and gender and meniscal injury. At the latest follow-up, Lysholm and VAS scores in patients with and without meniscal tear were the same. Our study confirms that increasing time from the ACL injury would increase the risk of MM damage. The cutoff point for this risk factor is 6 months from initial injury; therefore, to save the meniscus, it might be better to perform ACL reconstruction within 6 months in ACL-deficient knees.

Purpose: To examine the development of multidimensional frailty, including physical, psychological and social components, over a period of seven years. To determine the effects of sociodemographic factors (gender, age, marital status, education, income) on the development of frailty.

Methods: This longitudinal study was conducted in sample of 479 community-dwelling people aged ≥ 75 years living in the municipality of Roosendaal, the Netherlands. The Tilburg Frailty Indicator (TFI), a self-report questionnaire, was used to collect data about frailty. Frailty was assessed annually.

Results: Frailty increased significantly over seven years among the people who completed the entire TFI all years (n = 121), the average score was 3.75 (SD 2.80) at baseline and 5.05 (SD 3.18) after seven years. Regarding frailty transitions, most participants remained unchanged from their baseline status. The transition from non-frail to frail was present in 8.3% to 12.6% of the participants and 5.1% to 10.7% made a transition from frail to non-frail. Gender (woman), age (≥80 years), marital status (not married/cohabiting), high level of education, and incomes from €601-€1800 were significantly associated with a higher frailty score.

Conclusion: This study showed that multidimensional frailty, assessed with the TFI, increased among Dutch community-dwelling people aged ≥75 years using a follow-up of seven years. Gender, age, marital status, education, and income were associated with frailty transitions. These findings provide healthcare professionals clues to identify people at increased risk of frailty, and target interventions which aim to prevent or delay frailty and its adverse outcomes, such as disability and mortality.

Keywords: Community-dwelling older people; Multidimensional frailty; Tilburg Frailty Indicator (TFI); Transitions.

Background: More than 50 million women suffer from infertility worldwide, among whom 30% have associated fallopian tube pathology. Fortunately, the diagnostic accuracy of tubal patency has been enhanced with the consistent development of ultrasound imaging technology, especially the invention of transvaginal 4-dimensional hysterosalpingo-contrast sonography (TV 4D HyCoSy). However, detailed imaging data for evaluating the tubal condition for spontaneous conception and assessing the necessity of assisted reproductive technology (ART) have yet to be amassed.

Methods: Patients with tubal factor infertility (TFI) who received TV 4D HyCoSy were recruited for this study. They were divided into two groups according to the method of conception: the natural pregnancy group (patients who naturally conceived within 3 months after TV 4D HyCoSy) and the assisted reproduction group (patients who failed to conceive naturally within the 3 months but successfully conceived through ART). Logistic regression analysis was performed to examine the data obtained from participants' medical history and TV 4D HyCoSy investigation.

Results: Of the initial 1,433 women, 348 were excluded due to exclusion criteria or lack of follow-up. A total of 1,085 TFI patients were finally included, with individuals in the natural pregnancy group accounting for 27.74% (n=301), and those in the ART group accounting for 37.33% (n=405). The age was younger and the duration of infertility was shorter in the group of women who conceive spontaneously after TV 4D HyCoSy (P<0.05). In terms of imaging data, their endometrial thickness was thinner, right fallopian tube wall was more intact, morphology of the right fallopian tube was smoother, and their ovarian motility (bilateral), fallopian tube visualization (bilateral) and overflow condition of the contrast agent from the fimbriae of fallopian tube (bilateral) were better. In addition, the resistance of the contrast agent injection was less likely to be persistent, reflux was less likely to happen and 0/1 dispersion of the contrast agent around the ovary (bilateral) were more likely to be annular (P<0.05).

Conclusions: The imaging data gathered from TV 4D HyCoSy in TFI patients were comprehensive, which suggested that TV 4D HyCoSy could have potential to be used to assess the necessity of post-HyCoSy ART intervention in patients with TFI. This could be of benefit in reducing the incidence of overtreatment and potential complications of ART.

Keywords: Transvaginal 4-dimensional hysterosalpingo-contrast sonography (TV 4D HyCoSy); assisted reproductive technology (ART); pregnancy; tubal factor infertility (TFI).

Background: Dental fluorosis (DF) has been one of the most prevalent pediatric dental conditions associated with aesthetic concern and treatment needs. This study aimed to identify the longitudinal clinical change in the severity of DF in 8-12-year-old children and its association with gender, age, severity, and tooth type.

Methods: This observational study assessed the dental aspects of the 92 Colombian children in 2015 (mean age at beginning 9.71 years ± 1.23) and 2018 (mean age 13.69 years ± 1.41), from an area with high DF prevalence. DF was recorded in all permanent teeth by two calibrated examiners using the Thylstrup and Fejerskov Index (TFI). DF severity change (maximum-TFI-score) was analyzed with descriptive analysis at the tooth level. Associated factors were evaluated with the generalized linear model, binomial family, and logarithmic link function.

Results: TFI scores ranged between 1 (very mild) to 6 (severe), being score 2 (41.7%) the most prevalent. After three years, 29.6% of the teeth presented score reduction, 24.1%, increased and 46.3% did not change; the significant association was related to increasing of the basal TFI = 1 score (44.2%) (RR = 9.7; 95% CI 1.7-56.5; p = 0.01) and with canines, premolars and second-permanent-molars teeth group (RR = 3.3; 95% CI 1.9-5.6; p = 0.005).

Conclusion: The present study based on clinical features about DF confirms the dynamic post-eruptive nature of this condition. After three years of follow-up, a considerable proportion of the teeth changed to a higher score. Furthermore, the canines, premolars, and second-permanent-molars showed a higher incidence of an increase in severity of TFI score.

Keywords: Dental fluorosis; Longitudinal; Permanent dentition; Severity.

Background: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC). Biomarkers for mRCC patients treated with ICI are limited, and body composition is underutilized in mRCC. We investigated the association between body composition and clinical outcomes in ICI-treated mRCC patients.

Methods: We performed a retrospective analysis of 79 ICI-treated mRCC patients at Winship Cancer Institute from 2015-2020. Baseline CT images were collected at mid-L3 and segmented using SliceOMatic v5.0 (TomoVision). Density of skeletal muscle (SM), subcutaneous fat, inter-muscular fat, and visceral fat were measured and converted to indices by dividing by height(m)² (SMI, SFI, IFI, and VFI, respectively). Total fat index (TFI) was defined as the sum of SFI, IFI, and VFI. Patients were characterized as high versus low for each variable at gender-specific optimal cuts using overall survival (OS) as the primary outcome. A prognostic risk score was created based on the beta coefficient from the multivariable Cox model after best subset variable selection. Body composition risk score was calculated as IFI + 2*SM mean + SFI and patients were classified as poor (0-1), intermediate (2), or favorable risk (3-4). Kaplan-Meier method and Log-rank test were used to estimate OS and PFS and compare the risk groups. Concordance statistics (C-statistics) were used to measure the discriminatory magnitude of the model.

Results: Most patients were male (73%) and most received ICI as first (35%) or second-line (51%) therapy. The body composition poor-risk patients had significantly shorter OS (HR: 6.37, p<0.001), PFS (HR: 4.19, p<0.001), and lower chance of CB (OR: 0.23, p=0.044) compared to favorable risk patients in multivariable analysis. Patients with low TFI had significantly shorter OS (HR: 2.72, p=0.002), PFS (HR: 1.91, p=0.025), and lower chance of CB (OR: 0.25, p=0.008) compared to high TFI patients in multivariable analysis. The C-statistics were higher for body composition risk groups and TFI (all C-statistics ≥ 0.598) compared to IMDC and BMI.

Conclusions: Risk stratification using the body composition variables IFI, SM mean, SFI, and TFI may be prognostic and predictive of clinical outcomes in mRCC patients treated with ICI. Larger, prospective studies are warranted to validate this hypothesis-generating data.

Keywords: adiposity; biomarkers; body composition; immune checkpoint inhibitors; mRCC; prognostic model; sarcopenia.

Background: Little is known about rates of access site (transradial (TRI) or transfemoral (TFI)) preference for percutaneous coronary intervention (PCI) and in-hospital costs of patients undergoing these procedures in lower-and middle-countries. Here, we report on access site use, in-hospital costs and outcomes of patients undergoing PCI in Vietnam.

Methods: Information from 868 patients were included in the cohort of 1022 patients recruited into the first PCI registry in Vietnam. The total hospital costs and in-hospital outcomes of patients undergoing TRI and TFI were compared. Hospital costs were obtained from the hospital admission system, and major adverse cardiac events, major bleeding events and length of stay were identified through review of medical records.

Findings: TRI was the dominant access site for interventionists (694/868 patients). The TFI group reported more lesions of the left main artery, more previous coronary artery bypass grafts and previous PCI in comparison with the TRI group (all p < 0.05). The TRI group was associated with a lower overall cost of admission (the adjusted difference was -1526.3 USD, 95% confident interval CI (-1996.2; -1056.3), shorter length of hospital stay (-2 days, CI (-2.8; -1.2)) and lower rates of major bleeding post-procedure. Procedural factors such as radial access site, left main disease, PCI ≥2 stents, and PCI ≥ 2 lesions having the most impact on the in-hospital cost of patients undergoing PCI.

Interpretations: Among patients undergoing PCI, TRI was associated with lower costs and favourable clinical outcomes relative to TFI.

Funding: This research received partial financial support from Curtin University, Australia.

Keywords: BARC, Bleeding Academic Research Consortium; CABG, Coronary artery bypass grafts; CHD, Coronary heart disease; Hospital cost; LOS, Length of stay; MACE, Major adverse cardiac event; Outcomes; PCI, Percutaneous coronary intervention; Percutaneous coronary intervention; TFI, Transfemoral intervention; TRI, Transradial intervention; VNHI, Vietnam National Heart Institute; Vietnam.

Purpose: To evaluate the effects of different treatment time of 5.25% Sodium hypochlorite (NaOCl) on the microshear bond strength (μSBS), attenuated total reflection Fourier transform infrared (ATR-FTIR) and etching pattern in mild and moderate fluorotic enamel.

Study design: Forty-eight fluorotic molars were divided into two groups: mild and moderate fluorotic enamel which were classified by a Thylstrup and Fejerskov index (TFI). Based on the application time (0s, 60s, 120s, 180s) of 5.25% NaOCl, each group was sectioned into four parts. Then the etched enamel was bonded with resin and tested to acquire μSBS. The statistical method was two-way ANOVA and Least Significant Difference (LSD) test at α = 0.05. Besides, fracture modes were observed under a stereo microscope. SEM was used to evaluated the enamel-etching pattern and organic content on the fluorotic enamel surface were investigated by ATR-FTIR.

Results: Duration of 5.25% NaOCl at 60s or 120s significantly increased the μSBS of fluorotic enamel compared to 0s (p<0.05). Fracture modes indicated that dominating failures were set in the bonding interface but whose proportion decreased when 5.25% NaOCl was applied. The enamel-etching pattern in 180s was deepest under SEM. Spectra of enamel samples manifested an obvious and gradual removal of its organic phase after duration of NaOCl increased.

Conclusion: The maximal μSBS is acquired by using 5.25% NaOCl at 60s for mild fluorotic enamel but 120s for the moderate. The prolonged application time of 5.25% NaOCl prior to phosphoric acid etching improves enamel-etching pattern. Treatment of 5.25% NaOCl decreases proteins on the fluorotic enamel surface.

Keywords: Etching pattern; Fluorotic enamel; Microshear bond strength; Sodium hypochlorite.

Background: Food avoidance secondary to disease or stress can lead to weight loss and rapid deterioration of clinical condition in the common marmoset (Callithrix jacchus). Currently, there are no data supporting the use of any pharmaceuticals as an appetite stimulant in this species; however, benzodiazepines are frequently used for this purpose in other species.

Methods: Six marmosets were used in a crossover study design to evaluate the benzodiazepine midazolam as an appetite stimulant and anxiolytic. Total food intake (TFI) and latency to eat (LTE) were measured following administration of oral and injectable midazolam in non-anxious and anxious states.

Results: Injectable midazolam increased TFI and decreased LTE in anxious marmosets, but had no effect in non-anxious animals. Oral midazolam had no effect on appetite in either state.

Conclusions: Injectable midazolam may be an effective treatment for anxiety-induced inappetence in marmosets. Individual response to both oral and injectable midazolam may vary.

Keywords: benzodiazepine; hyperphagia; inappetence; non-human primate.

This study aims to test whether the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) differs between patients who developed tinnitus following a traumatic brain injury (TBI), and those without a history of TBI. This was a parallel pilot, open-label, non-randomized, clinical trial to compare the efficacy of low frequency rTMS on tinnitus symptoms in patients with and without a TBI history. Patients with moderate to severe tinnitus symptoms based on the Tinnitus Handicap Inventory (THI) and the Tinnitus Functional Index (TFI) were enrolled in the study. Validated questionnaires (THI and TFI) were used to quantify the severity of tinnitus symptoms and hearing impairment (Hearing Handicap Index - HHI) before and after ten sessions of rTMS of the left primary auditory cortex. Hearing threshold levels as well as speech reception and speech discrimination thresholds were also compared. The number of patients who experienced a reduction in their subjective tinnitus symptoms was greater and sustained longer in patients without a history of TBI. The same was seen with subjective symptoms of hearing impairment. In conclusion, our preliminary results suggest tinnitus patients without a history of TBI respond better to low frequency rTMS than those with a history of TBI, suggesting that treatments could be more effective if tailored to tinnitus etiology.

Keywords: TBI; Tinnitus; rTMS.

Chlamydia trachomatis (CT) causes pelvic inflammatory disease, which may result in tubal factor infertility (TFI) in women. Serologic assays may be used to determine the proportion of women with and without TFI who have had previous CT infection and to generate estimates of infertility attributable to chlamydia. Unfortunately, most existing CT serologic assays are challenged by low sensitivity and, sometimes, specificity for prior CT infection; however, they are currently the only available tests available to detect prior CT infection. Modeling methods such as finite mixture modeling may be a useful adjunct to quantitative serologic data to obtain better estimates of CT-related infertility. In this article, we review CT serological assays, including the use of antigens preferentially expressed during upper genital tract infection, and suggest future research directions. These methodologic improvements, coupled with creation of new biomarkers for previous CT infection, should improve our understanding of chlamydia's contribution to female infertility.

Keywords: antibody; chlamydia; diagnosis; infertility; serology.

Introduction: Tinnitus is a condition with a subjective nature that requires self-report questionnaires for its assessment. Aspects such as quality of life, sleep or intrusiveness have been addressed by multiple tinnitus questionnaires, but the high responsiveness to treatment effects of the Tinnitus Functional Index (TFI) makes this questionnaire part of the standard practice in tinnitus screening. To date, the TFI has been translated to more than 20 languages and used in more than 22 countries. In this study, the TFI was translated to Dutch and validated through a clinical population in the Netherlands.

Methods: After a back-translation procedure, the Dutch TFI was filled-out by 377 patients in the tinnitus outpatient clinic at the Ear, Nose and Throat (ENT) department of the University Medical Center Groningen, in the Netherlands. Reliability and construct validity of the questionnaire were assessed by correlations with one other tinnitus questionnaire (Tinnitus Handicap Inventory, THI) and with three psychological functioning questionnaires (Rand-36, Cantril's ladder and the Hospital Anxiety and Depression Scale (HADS)). The eight-factor structure of the Dutch TFI was tested by means of exploratory factor analysis using three different models (ICM-CFA, ESEM and ESEM-CFA).

Results: The Dutch TFI showed a high internal consistency (α = 0.95), and construct validity was proven by moderate-to high-convergent correlations with the THI (r = 0.47-0.79) and by moderate convergent (r = 0.55-0.67) and good-to moderate-divergent (r = 0.12-0.47) correlations with the psychological functioning questionnaires. The eight-factor structure of the TFI was confirmed for the Dutch version by the three models.

Conclusion: The Dutch version of the TFI is a reliable instrument for screening tinnitus impact in a clinical population, and its psychometric properties are comparable to the original TFI and other validated tinnitus questionnaires.

Keywords: Confirmatory factor analysis; Psychometric; Questionnaire; Responsiveness; Tinnitus; Translation; Treatment; Validation.

Knowledge on characteristics of people that seek help for tinnitus is scarce. The primary objective of this study was to describe differences in characteristics between people with tinnitus that seek help compared to those who do not seek help. Next, we described differences in characteristics between those with and without tinnitus. In this cross-sectional study, we sent a questionnaire on characteristics in different domains; demographic, tinnitus-specific, general- and psychological health, auditory and noise- and substance behaviour. We assessed if participants had sought help or planned to seek help for tinnitus. Tinnitus distress was defined with the Tinnitus Functional Index. Differences between groups (help seeking: yes/no, tinnitus: yes/no) were described. 932 people took part in our survey. Two hundred and sixteen participants were defined as having tinnitus (23.2%). Seventy-three of those sought or planned to seek help. A constant tinnitus pattern, a varying tinnitus loudness, and hearing loss, were described more frequently in help seekers. Help seekers reported higher TFI scores. Differences between help seekers and people not seeking help were mainly identified in tinnitus- and audiological characteristics. These outcomes might function as a foundation to explore the heterogeneity in tinnitus patients.

Objective: This study aimed to develop an appropriate scale accessing healthcare students' and providers' humanistic professional awareness (HPAS-HSP).

Methods: Following a literature review, stakeholder interviews, and panel discussions for item generation, 65 items for the HPAS-HSP scale were created based on a nine-point Likert scale, with 9 indicating "strongly agree" and 1 indicating "strongly disagree." A pilot study using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), with seven hundred twenty-five medical care students and providers in Taiwan as the total sample number of the study, was administered to examine the practicability of the HPAS-HSP scale. The statistics software SPSS and AMOS 24.0 were used to examine the psychometric properties of the scale, including internal consistency, convergent validities, discriminant validities, and exploratory and confirmatory factor analysis.

Results: The EFA resulted in 21 items in three factors, with 66.221% of the total variance explained: "personal integrity and accountability" (9 items; 51.763% of the variance explained), "sensitivity to others" (6 items; 8.667% of the variance explained), and "medical professional competence" (6 items; 5.791% of the variance explained). The Cronbach's alphas for the three subscales and the entire questionnaire ranged from 0.892 to 0.949. The CFA results yielded 20 items, with the same three factors, and demonstrated good model fit in the χ ²/df ratio (1.130; p = 0.140), CFI (0.998), TFI (0.998), and RMSEA (0.013). The composite alphas ranged between 0.900 and 0.969. Convergent and discriminant validity also confirmed the stability and consistency of the scale.

Conclusion: The statistical results demonstrated that the HPAS-HSP scale can be a measure to assess healthcare students' and providers' humanistic professional awareness.

Keywords: healthcare students and providers; humanistic professional awareness; psychometric properties; scale development.

Background: Frailty is prevalent in kidney transplant recipients and associated with multiple health care challenges. The association between frailty and outcomes has been extensively studied in kidney transplant recipients, but the status of frailty and its associated factors are not well studied, hindering efforts to develop strategies to improve care and reduce frailty.

Objectives: To identify the factors that are associated with frailty in kidney transplant recipients comprehensively.

Design and participants: The associated factors of frailty were explored by a cross-sectional study of 185 kidney transplant recipients.

Measurements: Data were collected using the general information questionnaire, the Charlson comorbidity index, the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, the Connor-Davidson Resilience Scale, the Perceived Social Support Scale and the Tilburg Frailty Indicator. Data were analyzed using the multiple linear regression analysis.

Results: A total of 75 (40.5%) kidney transplant recipients were assessed as frail by Chinese TFI. Age (β = 0.228), time post-transplant (β = 0.055), sleep quality (β = 0.224) and psychological resilience (β = -0.038) entered the final multiple regression equation and accounted for 41.8% of the total frailty variation (R² = 0.418, F = 21.31, p < 0.05).

Conclusions: Frailty was common among kidney transplant recipients. Old age, long time after transplantation, poor sleep quality and low psychological resilience were main associated factors for frailty. Integrated care interventions are therefore needed for this vulnerable population to prevent or delay frailty.

Keywords: cross-sectional study; frailty; kidney transplant.

Introduction: Tinnitus prevalence numbers in the literature range between 5 and 43%, depending on the studied population and definition. It is unclear when tinnitus becomes pathologic. Objectives: To assess the tinnitus prevalence in the Dutch general population with different cutoffs for definition. Methods: In this cross-sectional study, a questionnaire was sent to a sample (n = 2,251) of the Nivel (Netherlands Institute for Health Services Research) Dutch Health Care Consumer Panel. Three questions were asked to assess the presence of tinnitus, duration, and frequency of the complaint. We classified people as having pathologic tinnitus when participants experienced it for 5-60 min (daily or almost daily or weekly), or tinnitus for >60 min or continuously (daily or almost daily or weekly or monthly), so tinnitus impact on daily life was measured with the Tinnitus Functional Index (TFI) and a single-item question. Answers were stratified to mid-decade years of age. Prevalence numbers were weighted by gender and age to match the Dutch population. Results: Nine hundred thirty-two of 2,251 participants (41%) filled out the questionnaire. The median age was 67.0 (IQR 17) years. Three hundred thirty-eight of 932 (36%) experienced tinnitus for an undefined amount of time during the last year. Two hundred sixteen of 932 (23%) met our definition of having pathologic tinnitus (21% when weighted for age and gender). The median TFI score for all pathologic tinnitus participants was 16.6 (IQR 21.8). A percentage of 50.4% of the pathologic tinnitus participants had a TFI in the range 0-17, which can be interpreted as not a problem. Conclusion: Twenty-three percent (unweighted) or 21% (weighted) of our sample met our definition of pathologic tinnitus, which was based on a combination of duration and frequency over the last year. The TFI score of 47.7% of the pathologic tinnitus participants is ≥18. This indicates that they consider the tinnitus to be at least "a small problem" [11.1% (unweighted) or 8.9% (weighted) of the total study group]. This study illustrates the difficulties with defining pathologic tinnitus. In addition, it demonstrates that tinnitus prevalence numbers vary with different definitions and, consequently, stresses the importance of using a uniform definition of tinnitus.

Keywords: definition; general population; prevalence; tinnitus; tinnitus heterogeneity.

Objective: This study aims to investigate the clinical efficacy of laparoscopy and hysteroscopy in the treatment of tubal-factor infertility (TFI) to provide a basis for predicting postoperative pregnancy rates. Methods: The clinical data of 336 patients who underwent laparoscopy and hysteroscopy for TFI between February 2018 and December 2018 in the Department of Reproductive Gynecology at the First People's Hospital of Yunnan were retrospectively analyzed. After implementing the inclusion and exclusion criteria, 278 patients were included in the study. The patients were grouped according to pelvic adhesions, hydrosalpinx, twisted fallopian tubes, and fimbriae structure. The impact of the extent of fallopian tube diseases on postoperative pregnancy outcomes was analyzed. Results: Of the 278 patients, 129 got pregnant (pregnancy rate = 46.4%). Pelvic adhesions, hydrosalpinx, twisted/folded fallopian tubes, and damage to the fimbriae of the fallopian tubes were found to affect the natural pregnancy rate after surgery, and it decreased significantly with the aggravation of the disease (P < 0.001). Of the 129 patients who had natural pregnancies, 29 had ectopic pregnancies (ectopic pregnancy rate = 22.48%). Twisted/folded fallopian tubes and damage to the fimbriae structure significantly increased the incidence of postoperative ectopic pregnancy (P < 0.001). Conclusion: Laparoscopy and hysteroscopy are effective treatments for TFI. Pelvic adhesions, twisted/folded fallopian tubes, hydrosalpinx, and damage to the fimbriae of the fallopian tubes can affect postoperative pregnancy outcomes and lead to failure of a natural pregnancy after the operation. The incidence of ectopic pregnancy increases with the degree of fallopian tube twisting/folding and the degree of damage to the fimbriae of the fallopian tubes.

Keywords: clinical efficacy; hysteroscopy; laparoscopy; pregnancy rate; tubal infertility.

Objectives: To examine the diagnostic performance of the Tilburg Frailty Indicator (TFI), 11-factor modified frailty index (mFI-11), and 5-factor modified frailty index (mFI-5) for frailty defined by Frailty Phenotype (FP), as well as to compare the predictive ability of TFI, mFI-11, and mFI-5 for adverse outcomes in hospital among elderly patients undergoing gastric cancer surgery.

Design: A prospective cohort study.

Setting: Hospitalization setting, Nanjing, China.

Participants: We recruited 259 elderly patients undergoing gastric cancer surgery from a tertiary hospital.

Measurements: Frailty was assessed by the FP, TFI, mFI-11, and mFI-5 before surgery, respectively. The receiver operating characteristic (ROC) curves were plotted to compared the diagnostic performance of TFI, mFI-11, and mFI-5 using FP as the reference. ROC curves were used to examine the performance of TFI, mFI-11, and mFI-5 in predicting adverse outcomes. The area under the curve (AUC)>0.70 was regarded as an indicator of good performance.

Results: The prevalence of frailty ranged from 8.5% (mFI-11) to 45.9% (TFI). The AUCs of TFI (AUC: 0.764, p<0.001) was significantly greater than that of mFI-11 (AUC: 0.600, p=0.033) and mFI-5 (AUC: 0.600, p=0.0311) in the detection of frailty defined by FP, with quite different sensitivity and specificity at their original cutoffs. TFI and mFI-11 both had statistically significant but similarly inadequate predictive accuracy for adverse outcomes in hospital, including total complications (AUCs: 0.618; 0.621), PLOS (AUCs: 0.593; 0.639), increased hospital costs (AUCs: 0.594; 0.624), and hypoproteinemia (AUCs: 0.573; 0.600). For the mFI-5, only the predictive ability for hypoproteinemia was statistically significant, with poor accuracy (AUC: 0.592, p<0.0055).

Conclusion: The TFI performed slightly better than mFI-11 and mFI-5 in our study. Moreover, future studies are needed to further determine an optimal frailty instrument with great diagnostic and predictive accuracy.

Keywords: Elderly; diagnostic performance; frailty; gastric cancer; predictive ability.

The aim of this in vitro study was to estimate the effect of the species concentration of 45S5 bioactive glass (BAG) used as pretreatment on the microshear bond strength (MSBS) of dental fluorosis (DF). Based on the Thylstrup and Fejerskov index, 80 teeth were randomly divided equally into four groups: TFI 0, sound dentin; TFI 1-3, mild fluorosis; TFI 4-5, moderate fluorosis; and TFI 6-9, severe fluorosis. Each group was randomized into five subgroups. After preparing the dentin hypersensitivity model of DF, the dentin was pretreated as follows, Subgroup 1: deionized water (Control group); Subgroup 2: 1% BAG; Subgroup 3: 5% BAG; Subgroup 4: 10% BAG, and Subgroup 5: 20% BAG. Stochastically one specimen was selected from each subgroup for scanning electron microscope and energy dispersive spectrometer analysis. After being made of resin-tooth bonding samples, the remains were in water bath at 37 °C for 24 hr. Subsequently, samples from each subgroup were randomly selected to test MSBS without aging, or after a thermocycle of 5,000 and 10,000 times, respectively. The fracture modes were analyzed. Compared with the group of 1% BAG and Control, the exposure area of tubules in 5%, 10%, and 20% BAG group had significant difference (p < .05). MSBS results indicated that there were significant differences between 10% BAG with other groups. The 20% BAG group showed the lowest MSBS among all groups. Pretreatment of 10% BAG solution may be conductive to enhance the bond strength of DF, while 20% BAG solution adversely.

Keywords: bioactive glass; dentin hypersensitivity; desensitizing; fluorosis; microshear bond strength.

Background: Multidimensional frailty, including physical, psychological, and social components, is associated to disability, lower quality of life, increased healthcare utilization, and mortality. In order to prevent or delay frailty, more knowledge of its determinants is necessary; one of these determinants is lifestyle. The aim of this study is to determine the association between lifestyle factors smoking, alcohol use, nutrition, physical activity, and multidimensional frailty.

Methods: This cross-sectional study was conducted in two samples comprising in total 45,336 Dutch community-dwelling individuals aged 65 years or older. These samples completed a questionnaire including questions about smoking, alcohol use, physical activity, sociodemographic factors (both samples), and nutrition (one sample). Multidimensional frailty was assessed with the Tilburg Frailty Indicator (TFI).

Results: Higher alcohol consumption, physical activity, healthy nutrition, and less smoking were associated with less total, physical, psychological and social frailty after controlling for effects of other lifestyle factors and sociodemographic characteristics of the participants (age, gender, marital status, education, income). Effects of physical activity on total and physical frailty were up to considerable, whereas the effects of other lifestyle factors on frailty were small.

Conclusions: The four lifestyle factors were not only associated with physical frailty but also with psychological and social frailty. The different associations of frailty domains with lifestyle factors emphasize the importance of assessing frailty broadly and thus to pay attention to the multidimensional nature of this concept. The findings offer healthcare professionals starting points for interventions with the purpose to prevent or delay the onset of frailty, so community-dwelling older people have the possibility to aging in place accompanied by a good quality of life.

Keywords: Tilburg Frailty Indicator; frailty; lifestyle; older people.

Aim: To investigate the impact of tinnitus on professional musicians in the UK.

Background: Tinnitus is the experience of sound when an external source is absent, primarily associated with the ageing process, hearing loss, and noise exposure. Amongst populations exposed to industrial noise, noise exposure and noise-induced hearing loss (NIHL) have been found to be the factors most associated with tinnitus. The risk of NIHL amongst professional musicians is greater than that amongst the general population, meaning they may be at increased risk of tinnitus.

Methods: Seventy-four professional musicians completed an online survey involving closed and open-ended questions, and completed the Tinnitus fuctional Index (TFI) questionnaire. Descriptive statistics and thematic analysis of open-ended qualitative responses were used to analyse the data.

Results: Three themes were generated from the analysis of the responses to the open-ended questions. These themes were: (1) the impact of tinnitus on the lives of professional musicians, (2) professional musician experience of tinnitus services, support, and hearing health and safety, and (3) the support professional musicians want. The mean global TFI score for professional musicians was 39.05, interpreted as tinnitus being a moderate problem. Comparisons with general population data revealed lower TFI scores for the TFI subscales of 'sense of control' and 'intrusiveness' for professional musicians and higher for auditory difficulties associated with tinnitus amongst professional musicians.

Conclusion: Tinnitus can negatively impact on professional musicians' lives. There is a need for bespoke self-help groups, awareness raising, and education to prevent tinnitus and promote hearing health among musicians.

Keywords: hearing health; lived experience; musicians; occupational noise exposure; public health; tinnitus.