OBJECTIVE

Tinnitus is a common and sometimes severely debilitating condition. It has been estimated that approximately 7% of Americans experience tinnitus daily. Hearing difficulties, sleep problems, concentration difficulties, and anxiety are commonly reported associated concerns. Cognitive behavior therapy (CBT) is often recommended to address the psychosocial impact of burdensome tinnitus, as CBT interventions have been shown to be efficacious in reducing tinnitus burden. The presented case demonstrates that a brief (4-session) adapted CBT treatment in an integrated primary care (IPC) setting can result in notable improvements in functioning.

METHODS

Tinnitus severity was monitored with the Tinnitus Handicap Inventory (THI) and the Tinnitus Functional Index (TFI).

RESULTS

The patient reported increased self-efficacy in coping with his tinnitus symptoms. The subjective volume of his tinnitus remained similar over time, but the emotional impact of his symptoms decreased dramatically. Overall THI score decreased from a 48 (moderate impairment) at baseline to a 20 (mild impairment) at discharge. Overall TFI score decreased from a 40 (moderate problem) during first administration to a 9.6 (not a problem) at discharge.

CONCLUSIONS

Brief CBT treatment for tinnitus can be delivered in an IPC setting, consistent with a population-health approach. Such treatment may result in improved quality of life for patients, and the brief approach has the potential to reduce overall cost of care. This case encourages increased identification and treatment of tinnitus within IPC settings, in order to increase access of care for patients with this burdensome condition. (PsycINFO Database Record

BACKGROUND

Different standardized questionnaires are used to assess tinnitus severity, making comparisons across studies difficult. These questionnaires are also used to measure treatment-related changes in tinnitus although they were not designed for this purpose. To solve these problems, a new questionnaire - the Tinnitus Functional Index (TFI) - has been established. The TFI is highly responsive to treatment-related change and promises to be the new gold standard in tinnitus evaluation. The aim of the current study was to validate a German version of the TFI for a German-speaking population in Switzerland.

METHODS

At the ENT department of the University Hospital Zurich, 264 subjects completed an online survey including the German version for Switzerland of TFI, Tinnitus Handicap Inventory (THI), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and sociodemographic variables. Internal consistency of the TFI was calculated with Cronbach's alpha coefficient. Pearson correlation coefficients were used for the test-retest reliability of the TFI and to investigate convergent and discriminant validity between the THI and the BDI and BAI, respectively. Factor analysis was assessed using a principal component analysis with oblique rotation. The different factors extracted were then compared with the original questionnaire.

RESULTS

The German version of the TFI for Switzerland showed an excellent internal consistency (Cronbach's alpha of 0.97) and an excellent test-retest reliability of 0.91. The convergent validity with THI was high (r = 0.86). The discriminant validity with BAI and BDI showed moderate results (BAI: r = 0.60 and BDI: r = 0.65). In the factor analysis only five factors with one main factor could be extracted instead of eight factors as described in the original version. Nevertheless, relations to the original eight subscales could be demonstrated.

CONCLUSIONS

The German version of the TFI for Switzerland is a suitable instrument for measuring the impact of tinnitus. The reliability and validity of this version are comparable with the original version of the TFI. Although this study showed only five factors in the factor analysis, relations to the original eight subscales were identified. Therefore, the German version of the TFI for Switzerland can deliver relevant information regarding the different tinnitus domains.

BACKGROUND

Clinical trial registration number on clinicaltrial.gov: NCT01837368 .

Introduction: To date, guidelines recommend the use of a stepped care approach to treat tinnitus. The current clinical management of tinnitus frequently consists of audiologic interventions and tinnitus retraining therapy (TRT) or cognitive behavioral therapy (CBT). Due to the high heterogeneity of the tinnitus population and comorbidity of tinnitus with insomnia, anxiety, and depression, these interventions may not be sufficient for every patient. The current study aims to determine whether a bimodal therapy for chronic, subjective tinnitus consisting of the combination of TRT and eye movement desensitization reprocessing (EMDR) results in a clinically significant different efficacy in comparison with the prevailing bimodal TRT and CBT therapy.

Methods: Patients were randomized in two treatment groups. The experimental group received the bimodal therapy TRT/EMDR and the active control group received the bimodal therapy TRT/CBT. Evaluations took place at baseline (T₀), at the end of the treatment (T₁), and 3 months after therapy (T₂). The tinnitus functional index (TFI) was used as primary outcome measurement. Secondary outcome measurements were the visual analog scale of tinnitus loudness (VAS_Loudness), tinnitus questionnaire (TQ), hospital anxiety and depression scale (HADS), hyperacusis questionnaire (HQ), global perceived effect (GPE), and psychoacoustic measurements.

Findings: The TFI showed clinically significant improvement in both bimodal therapies (mean decrease 15.1 in TRT/CBT; p < 0.001 vs. 16.2 in TRT/EMDR; p < 0.001). The total score on the TQ, HADS, HQ, and VAS_Loudness all demonstrated significant decrease after treatment and follow-up (p < 0.001) in the experimental and the active control group. GPE-measurements revealed that more than 80% (i.e., 84% in TRT/CBT vs. 80% in TRT/EMDR) of the patients experienced substantial improvement of tinnitus at follow up. Treatment outcome remained stable after 3 month follow-up and no adverse events were observed.

Conclusion: Both psychotherapeutic protocols result in a clinically significant improvement for patients with chronic subjective tinnitus. No significant different efficacy was found for the TRT/EMDR treatment compared to the combination of TRT and CBT.

Clinical trial registration: ClinicalTrials.gov, ID: NCT03114878. April 14, 2017.

Keywords: bimodal therapy; chronic subjective tinnitus; cognitive behavioral therapy; eye movement desensitization and reprocessing; psychotherapy; tinnitus retraining therapy.

Patients with relapsed or relapsed/refractory multiple myeloma (RRMM) face poor treatment options by the time third-line therapy is required, despite advances in overall survival in recent years. Treatment free interval (TFI) and opportunities to maintain quality of life (QoL) have been cited as additional measures of efficacy that can be utilized in personalized treatment decisions.

The clinical health outcomes data from PANORAMA-1, the pivotal phase-3 trial comparing panobinostat-bortezomib-dexamethasone (PAN-BTZ-DEX) with placebo (PBO)-BTZ-DEX in RRMM patients treated with 1 to 3 prior regimens, retrospectively assessed TFI as a health outcome measure and metric of patient treatment experience relevant to the RRMM population.

PAN-BTZ-DEX shows promise for prolonged TFI (mean TFI, 7.49 months; 95% CI, 6.02 to 8.71) compared to PBO-BTZ-DEX (mean TFI, 3.86 months; 95% CI, 3.08 to 4.60) for heavily pre-treated advanced RRMM patients), due to the short duration of therapy and extended progression free-survival. Further, QoL during the TFI was similar to baseline.

PAN-BTZ-DEX provides a treatment regimen with prolonged TFI benefits previously not available for RRMM patients. TFI has not been traditionally measured in clinical trials, but should be assessed in prospective data collection given its value to payers, providers, and patients.

Forward osmosis (FO) represents a new promising membrane technology for liquid separation driven by the osmotic pressure of aqueous solution. Organic polymeric FO membranes are subject to severe internal concentration polarization due to asymmetric membrane structure, and low stability due to inherent chemical composition. To address these limitations, this study focuses on the development of a new kind of thin-film inorganic (TFI) membrane made of microporous silica xerogels immobilized onto a stainless steel mesh (SSM) substrate. The FO performances of the TFI membrane were evaluated upon a lab-scale cell-type FO reactor using deionized water as feed solution and sodium chloride (NaCl) as draw solution. The results demonstrated that the TFI membrane could achieve transmembrane water flux of 60.3 L m(-2) h(-1) driven by 2.0 mol L(-1) NaCl draw solution at ambient temperature. Meanwhile, its specific solute flux, i.e. the solute flux normalized by the water flux (0.19 g L(-1)), was 58.7% lower than that obained for a commercial cellulose triacetate (CTA) membrane (0.46 g L(-1)). The quasi-symmetry thin-film microporous structure of the silica membrane is responsible for low-level internal concentration polarization, and thus enhanced water flux during FO process. Moreover, the TFI membrne demonstrated a substantially improved stability in terms of mechanical strength, and resistance to thermal and chemical stimulation. This study not only provides a new method for fabricating quasi-symmetry thin-film inorganic silica membrane, but also suggests an effective strategy using this alternative membrane to achieve improved FO performances for scale-up applications.

OBJECTIVE

To understand the relation between 2D:4D ratio, frailty, and cognitive decline in community-dwelling elderly people.

METHODS

A total of 175 community-dwelling elderly people were included. To determine frailty, participants completed the Tilburg Frailty Indicator (TFI) and the Survey of Health, Ageing and Retirement in Europe (SHARE-FI). Cognitive functioning was determined using the Mini-Mental State Examination (MMSE). 2D and 4D finger lengths of each hand were measured using a scanner. Barthel Index, Lawton, and Brody scale were also completed for each participant to determine the level of daily living functioning.

RESULTS

We did not find any correlations between 2D:4D ratio and frailty measures. We found a significant correlation between 2D:4D ratio and MMSE scores in the women sampled.

CONCLUSIONS

We cannot ascertain any contribution of prenatal exposure to androgens to the frailty status of community-dwelling elderly people. We found that reduced prenatal exposure to testosterone in women may contribute to the prevention of cognitive decline in elderly women.

OBJECTIVE

This study aimed to determine the effect of surface treatments such as tooth reduction and extending the etching time on microtensile bond strength (μTBS) of composite resin to normal and fluorotic enamel after microabrasion.

METHODS

Fifty non-carious anterior teeth were classified into two groups of normal and fluorotic (n=25) using Thylstrup and Fejerskov index (TFI=4-6). Teeth in each group were treated with five modalities as follows and restored with OptiBond FL and Z350 composite resin: 1-Etching (30 seconds), bonding, filling (B); 2-Tooth reduction (0.3mm), etching, bonding, filling (R-B); 3-Microabrasion (120 seconds), etching, bonding, filling (MB); 4- Microabrasion, tooth reduction, etching, bonding, filling (M-R-B); and 5- Microabrasion, etching (60 seconds), bonding, filling (M-2E-B). Ten experimental groups (n=5) were designed; 150 rectangular samples (10 in each group) with a cross-sectional area of 1×1mm2 were prepared for μTBS test. Failure mode was determined under a stereomicroscope and one specimen was selected from each group for scanning electron microscopy (SEM) analysis. Data were analyzed using two-way ANOVA and Tukey's test.

RESULTS

The μTBS to normal enamel was higher than to fluorotic enamel in all groups except for group (R-B). The Maximum and minimum μTBS were noted in the group (normal, reduction, bonding) and (fluorosed, microabrasion, bonding), respectively. Tooth reduction increased μTBS more effectively than extended etching time after microabrasion.

CONCLUSIONS

Fluorosis may reduce μTBS of composite resin to enamel. Microabrasion reduced the bond strength. Tooth reduction and extended etching time increased μTBS of composite resin to both normal and fluorotic enamel.

Introduction: The prevalence of lateral bony impingements [i.e., Sinus Tarsi (STI), Talo-Fibular (TFI) and Calcaneo-Fibular (CFI)] and their association with Peritalar Subluxation (PTS) have not been clearly established for progressive collapsing foot deformity (PCFD).This study aims to assess the prevalence of STI, TFI and CFI in PCFD, in addition to their association with PTS. We hypothesized that STI and TFI would be more prevalent than CFI.

Materials and methods: Seventy-two continuous symptomatic PCFD cases were retrospectively reviewed. Weightbearing computed tomography (WBCT) was used to assess lateral impingements and classified as STI, TFI and CFI. PTS was assessed by the percent of uncovered and the incongruence angle of the middle facet, and the overall foot deformity was determined by the foot and ankle offset (FAO). Data were collected by two fellowship-trained independent observers.

Results: Intra-observer and inter-observer reliabilities for impingement assessment ranged from substantial to almost perfect. STI was present in 84.7%, TFI in 65.2% and CFI in 19.4%. PCFD with STI showed increased middle facet uncoverage (p = 0.0001) and FAO (p = 0.0008) compared to PCFD without STI. There were no differences in FAO and middle facet uncoverage in PCFD with TFI and without TFI. PCFD with CFI was associated with STI in 100% of cases. PCFD with CFI showed decreased middle facet incongruence (p = 0.04) and higher FAO (p = 0.006) compared to PCFD without CFI.

Conclusions: STI and TFI were more prevalent than CFI in PCFD. However, only STI was associated with PTS. Conversely, CFI was associated with less PTS, suggesting a different pathological mechanism which could be a compensatory subtalar behavior caused by deep layer failure of the deltoid ligament and talar tilt.

Keywords: AAFD; Flatfoot; Impingement; PCFD; Peritalar subluxation; Progressive collapsing foot deformity.

Tumor necrosis factor (TNF)‑α and TNF receptor 1 (TNF‑R1) play diverse roles in modulating the neuronal damage induced by cerebral ischemia. The present study compared the time‑dependent changes of TNF‑α and TNF‑R1 protein expression levels in the hippocampal subfield cornu ammonis 1 (CA1) between adult and young gerbils following transient forebrain ischemia (tFI), via western blot and immunohistochemistry analyses. In adult gerbils, delayed neuronal death of pyramidal neurons, the principal neurons in CA1, was recorded 4 days after tFI; however, in young gerbils, delayed neuronal death was recorded 7 days after tFI. TNF‑α protein expression levels gradually increased in both groups following tFI; however, TNF‑α expression was higher in young gerbils compared with adult gerbils. TNF‑R1 protein expression levels markedly increased in both groups 1 day after tFI. Subsequently, TNF‑R1 expression gradually decreased in young gerbils, whereas TNF‑R1 expression levels were irregularly altered in adult gerbils following tFI. Notably, TNF‑α immunoreactivity significantly increased in pyramidal neurons in both groups 1 day after tFI; however, the patterns altered between both groups. In adult gerbils, TNF‑α immunoreactivity was rarely exhibited in pyramidal neurons 4 days after tFI due to neuronal death, suggesting that TNF‑α immunoreactivity was newly expressed in astrocytes. In young gerbils, TNF‑α immunoreactivity increased in pyramidal neurons 4 days after tFI, and TNF‑α immunoreactivity was newly expressed in astrocytes. In addition, TNF‑R1 immunoreactivity was exhibited in pyramidal cells of both sham groups, and significantly increased 1 day after tFI; however, the patterns altered between both groups. In adult gerbils, TNF‑R1 immunoreactivity was rarely exhibited 4 days after tFI, and astrocytes newly expressed TNF‑R1 immunoreactivity. In young gerbils, TNF‑R1 immunoreactivity increased in pyramidal neurons 4 days after tFI; however, TNF‑R1 immunoreactivity was not reported in pyramidal neurons and astrocytes thereafter. Taken together, the results of the present study suggest that different expression levels of TNF‑α and TNF‑R1 in ischemic CA1 between adult and young gerbils may be due to age‑dependent differences of tFI‑induced neuronal death.

Keywords: age; astrocyte; delayed neuronal death; pyramidal neuron; transient forebrain ischemia; tumor necrosis factor‑receptor 1; tumor necrosis factor‑α.

Development of cortical regions with precise, sharp, and regular boundaries is essential for physiological function. However, little is known of the mechanisms ensuring these features. Here, we show that determination of the boundary between neocortex and medial entorhinal cortex (MEC), two abutting cortical regions generated from the same progenitor lineage, relies on COUP-TFI (chicken ovalbumin upstream promoter-transcription factor I), a patterning transcription factor with graded expression in cortical progenitors. In contrast with the classical paradigm, we found that increased COUP-TFI expression expands MEC, creating protrusions and disconnected ectopic tissue. We further developed a mathematical model that predicts that neuronal specification and differential cell affinity contribute to the emergence of an instability region and boundary sharpness. Correspondingly, we demonstrated that high expression of COUP-TFI induces MEC cell fate and protocadherin 19 expression. Thus, we conclude that a sharp boundary requires a subtle interplay between patterning transcription factors and differential cell affinity.

INTRODUCTIONThis protocol describes a method for establishing a green fluorescent protein (GFP) calibration curve using dilutions of recombinant GFP and blue fluorescent beads. The total fluorescence intensity (TFI) per mRNA molecule is first calculated by imaging serial dilutions of purified enhanced GFP (eGFP) to determine the TFI within a specific volume. A calibration curve of fluorescence intensity in a given voxel per molecule of GFP is then used to determine the number of GFP molecules in the sample of formaldehyde fixed cells to be imaged. This is followed by a method for detection of single molecules in formaldehyde-fixed and live cells. These cells have been cotransfected with mRNA reporter and MCP-xFP plasmids, where MCP-xFP refers to a fluorescent protein fused to the MS2 capsid protein. It is important to collect micrographs and establish the calibration curve on the same day that the cells are imaged, using the same equipment configuration, camera settings, and image acquisition parameters.

Altered expression levels of N‑methyl‑D‑aspartate receptor (NMDAR), a ligand‑gated ion channel, have a harmful effect on cellular survival. Hyperthermia is a proven risk factor of transient forebrain ischemia (tFI) and can cause extensive and severe brain damage associated with mortality. The objective of the present study was to investigate whether hyperthermic preconditioning affected NMDAR1 immunoreactivity associated with deterioration of neuronal function in the gerbil hippocampal CA1 region following tFI via histological and western blot analyses. Hyperthermic preconditioning was performed for 1 h before tFI, which was developed by ligating common carotid arteries for 5 min. tFI‑induced cognitive impairment under hyperthermia was worse compared with that under normothermia. Loss (death) of pyramidal neurons in the CA1 region occurred fast and was more severe under hyperthermia compared with that under normothermia. NMDAR1 immunoreactivity was not observed in the somata of pyramidal neurons of sham gerbils with normothermia. However, its immunoreactivity was strong in the somata and processes at 12 h post‑tFI. Thereafter, NMDAR1 immunoreactivity decreased with time after tFI. On the other hand, NMDAR1 immunoreactivity under hyperthermia was significantly increased in the somata and processes at 6 h post‑tFI. The change pattern of NMDAR1 immunoreactivity under hyperthermia was different from that under normothermia. Overall, accelerated tFI‑induced neuronal death under hyperthermia may be closely associated with altered NMDAR1 expression compared with that under normothermia.

Immunohistochemistry for calcitonin gene-related peptide (CGRP), tyrosine hydroxylase and calbindin D-28k was performed on the glossopharyngeal and vagal ganglia in mCOUP-TFI knockout mice to know the effect of its deficiency on different types of primary sensory neurons. In wild type and heterozygous mice, the glossopharyngeal and vagal ganglia contained abundant CGRP-, tyrosine hydroxylase- and calbindin D-28k-immunoreactive (IR) neurons. In the ganglia of mCOUP-TFI knockout mice, a 38% decrease of CGRP-IR neurons was detected. However, the number of tyrosine hydroxylase- or calbindin D-28k-neurons was not altered by the mCOUP-TFI deficiency. In the tongue of knockout mice, the number of CGRP-IR nerve fibers decreased compared to wild-type and heterozygous mice. The development of CGRP-IR petrosal neurons, which supply innervation of the tongue, may depend on mCOUP-TFI.

Objective: The aim of this paper was to develop an appropriate scale measuring healthcare students' anxiety during the transition from school to work.

Methods: After an extensive literature review and panel discussion to prove the face validity and content validity, the initial item pool was reduced to 52 items. In a pilot study, a sample of four hundred and twenty-four healthcare students participated, and exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used. Psychometric properties-construct validity, convergent validity, discriminant validity, goodness of fit, and reliabilities-were also analyzed.

Results: After the use of EFA, the 52 items were reduced to 31 items in four factors, with 66.70% of the total variance explained. The Cronbach's alpha values ranged between 0.91 and 0.93. The study also used CFA to validate the EFA model, and the results demonstrated that with the same thirty-one items in a 7-point Likert scale, the model was a better fit in four factors: "inexperience in professional knowledge and skills" (nine items; factor loadings: 0.642-0.867; 43.72% of the variance explained), "fear of death" (eight items; factor loadings: 0.745-0.831; 9.94% of the variance explained), "fear of being infected" (eight items; factor loadings: 0.678-0.866; 7.86% of the variance explained), and "interpersonal interactions" (six items; factor loadings: 0.704-0.913; 5.18% of the variance explained). The CFA model demonstrated a good model fit in the χ²/df ratio (1.17; p = 0.016), CFI (0.99), TFI (0.99), and RMSEA (0.02). The composite reliabilities ranged from 0.89 to 0.92, confirming the StWTA-HS scale's stability and internal consistency. The convergent validity and discriminant validity were also confirmed. The StWTA-HS scale has been proven to be a stable scale to measure healthcare students' school-to-work transition anxiety.

Keywords: confirmatory factor analysis; exploratory factor analysis; healthcare students; scale development; school-to-work transition anxiety.

Background: The aims of this study were to assess the potential of 16 anthropometric, body composition and endocrine indexes as predictors of high liver fat and determine the most appropriate cut-off points in US adolescents.

Methods: A cross-sectional study was conducted on a population of 816 adolescents aged 12-17 years. The FibroScan^® 502V2 device was used to estimate the controlled attenuation parameter (CAP). Body fat percentage, fat mass, trunk fat percentage and trunk fat mass were measured by dual-energy X-ray absorptiometry. Anthropometric data and metabolic parameters were determined. Receiver operating characteristic curves were analysed to estimate the optimal cut-off points that best identify adolescents with high liver fat (CAP ≥90th percentile).

Results: In boys, triponderal mass index (TMI) had the highest area under curve (AUC) value (0.865) and the optimal cut-off score for TMI was 17.47 kg/m³ , which had 81.32 sensitivity and 82.99 specificity. In girls, trunk fat index (TFI) had the highest AUC value (0.826) and its optimal cut-off score in screening for high liver fat was 3.76 kg/m² , which had 74.04 sensitivity and 88.03 specificity. Fat mass index (FMI) index had the second highest AUC values (0.863 in boys 0.812 in girls) in both sex; the cut-off point for the detection of high liver fat was <8.66 kg/m² for girls and <7.45 kg/m² for boys.

Conclusion: Assessment of TMI in boys, TFI in girls, and FMI in both sexes are low-cost and easy-to-use parameters that may be useful as early screening tools for possible high liver fat in adolescents.

Keywords: adolescents; anthropometric indexes; controlled attenuation parameter; fatty liver disease; liver steatosis; transient elastography.

Introduction: Dental fluorosis is a major endemic oral disease characterized by hypo mineralization of enamel caused due to consumption of water containing high concentration of fluoride during developmental stages of teeth.

Aim: To assess the prevalence of dental fluorosis among 11-14 years old school children in endemic fluoride areas of Haryana and to find their treatment needs.

Materials and methods: A cross-sectional study was conducted among 2200 school children in endemic fluoride areas of Haryana (India) for a period of six months. Dental fluorosis was recorded by the Thylstrup-Fejerskov index (TF index) given by Thylstrup A, Fejerskov O.

Statistical analysis: Data entry and analysis were performed using Statistical Package of Social Sciences (SPSS) software version 18.0. Chi square test was used to find association between TFI scores and gender, age categories. The level of significance was set at 0.05.

Results: Prevalence of dental fluorosis (TFI) reached 96.6% with most children falling in TFI score 2, 3, 4 and 5 categories. Mean TFI score of study population was found to be 3.19 ± 1.551. There was significant difference found between gender and prevalence of dental fluorosis (P = 0.00).

Conclusion: Our findings showed the increased prevalence of dental fluorosis in endemic fluoride areas with mild to moderate level of dental fluorosis.

Keywords: Dental fluorosis; Haryana; Thylstrup-Fejerskov index; endemic areas.

Does C-reactive protein (CRP), as a marker of persisting low-grade inflammation, identify Chlamydia trachomatis IgG antibody test (CAT)-positive women who are at the highest risk for tubal factor infertility (TFI)?

No association was found between slightly elevated CRP (seCRP) levels and TFI in our CAT-positive patient population.In the fertility work-up, CAT is used to estimate the risk for TFI and to select high-risk patients for additional invasive diagnostic procedures (e.g. hysterosalpingography and laparoscopy). However, a high number of false positives exist among CAT-positive patients. In a previous study, it has been suggested that women with TFI may be identified more accurately when combining CAT with CRP, a marker for persistent low-grade inflammation.Our original retrospective cohort consisted of 887 consecutive female patients who visited the fertility clinic of a tertiary care centre between 2007 and 2015. All CAT-positive women who underwent laparoscopy (as the reference test for evaluation of tubal function) and who had not undergone previous pelvic surgery were included in the study. CRP was determined in spare serum samples, and medical data was obtained by chart review.A total of 101 women (11.4%) were CAT-positive, and 64 of these 101 women (7.2%) met all inclusion criteria. CAT was performed with an ELISA. TFI was assessed by laparoscopy and strictly defined as extensive peri-adnexal adhesions and/or distal occlusion of at least one tube. In spare sera, CRP was performed with a high-sensitivity CRP ELISA, and CRP levels between 3 and 10 mg/L were defined as positive. Analyses were corrected for BMI, endometriosis and smoking.

MAIN RESULTS AND THE ROLE OF CHANCE

There was no statistically significant association between seCRP level and TFI after adjusting for BMI, endometriosis and smoking (odds ratio 1.0; 95% CI 0.3-3.3; n = 64).

Our retrospective study had a small sample size due to a low CAT-positivity rate and a conservative clinical policy with regard to invasive diagnostic testing. Additionally, CRP levels were only measured once, while they may change throughout the menstrual cycle and in time.Contrary to previous findings, our results show CRP is not suitable as a marker of persistent low-grade inflammation in CAT-positive women. Other inflammatory markers and immunogenetic host factors should be studied on their clinical validity and utility to improve non-invasive risk assessment for TFI in the fertility work-up.This work was partially supported by the European EuroTrans-Bio Grant [Reference number 110012 ETB] and the Eurostars grant (E!9372). S.A.M., a full-time employee of Amsterdam University Medical Centres location VUMC (0.56 fte) and the Maastricht University Medical Center (0.44 fte), is the founder (2011) and CEO of TubaScan Ltd, a spin-off company, Dept. of Medical Microbiology and Infection Prevention, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands. S.O. and E.F.v.E. at the time of conducting this research had a partial appointment at TubaScan Ltd.

Four hundred and eighty 1-day-old Japanese quail chicks from white and brown strains, 240 birds from each strain, were divided into 4 treatment groups with 6 replicates each (10 birds/replicate). Both strains of quail were fed diets containing 0%, 3%, 6%, and 9% pomegranate peel (PP) powder for a period of 42 days. Results revealed that the final body weight (BW), total feed intake (TFI), body weight gain (BWG), gizzard percentage, and eviscerated carcass weight of white growing quails were significantly (P < 0.05) higher than the brown strain. Quail group fed with 6% PP powder had the highest (P < 0.001) average final BW and BWG (P < 0.001). The dietary PP powder at different levels significantly (P = 0.032) decreased TFI, but had no significant effect on carcass traits except for the liver percentage. Quails fed diet 3% and 9% PP powder had significant (P < 0.001) increased count of immune cells, and improved antioxidant potency. White quails fed diet 3% and 6% PP powder had greater expression of hepatic GHR gene. The expression of hepatic IGF-1 gene was significantly (P < 0.05) higher for brown quails fed diet 6% and 9% PP powder. White quails recorded the highest value of total return (TR). Quails fed diet 6% and 9% PP powder significantly (P < 0.001) recorded higher net return (NR) values. In conclusion, dietary inclusion of PP powder at levels up to 9% for Japanese quail strains improved the growth performance, increased antioxidant properties, enhanced hepatic gene expression, and did not show any adverse influence on carcass quality and blood indices of Japanese quail. Moreover, it increased the NR.

Keywords: Carcass traits; Economics of production; Gene expression; Growth performance; Pomegranate peel; Quail.

Background: Frailty is a multidimensional and dynamic state that has adverse physical, psychological, and social outcomes. The Tilburg Frailty Indicator (TFI) has the most robust evidence of reliability and validity for assessing frailty. However, the characteristics of TFI have not been investigated in detail. This study aimed to set a cut-off score for frailty and evaluate frailty-associated factors in community-dwelling older adults.

Methods: This cross-sectional study assessed frailty according to both the TFI and Fried criteria. The Geriatric Depression Scale, basic and instrumental activities of daily living, and Hospital Anxiety and Depression Scale-Anxiety subscale were also implemented.

Results: This study included 166 older adults. The area under the receiver operating characteristic curve was 0.735 (95% confidence interval [CI]: 0.648-0.823). A TFI cut-off point of 8, showed a sensitivity of 60% and specificity of 72.5% for the prediction of frailty (p<0.05). Frailty according to the TFI was more associated with the physical and psychological parameters, while frailty according to the Fried score was more closely related to the physical parameters (p<0.05).

Conclusion: The results of this study suggested an optimal TFI cut-off score of 8 as a frailty instrument in community-dwelling older adults. Additionally, the TFI included physical, psychological, and social aspects, thereby providing a multidimensional evaluation of frailty.

Keywords: Frailty; Older adults; Tilburg Frailty Indicator.

Purpose: To identify patients who would benefit from third and subsequent lines of chemotherapy in recurrent epithelial ovarian cancer (EOC).

Materials and methods: Recurrent EOC patients who received third, fourth, or fifth-line palliative chemotherapy were retrospectively analyzed. Patients' survival outcomes were assessed according to chemotherapy lines. Based on the best objective response, patients were divided into good-response (stable disease [SD] or better) and poor-response (progressive disease [PD] or those who died before response assessment) groups. Survival outcomes were compared between the two groups, and factors associated with chemotherapy responses were investigated.

Results: A total of 189 patients were evaluated. Ninety-four and ninety-five patients were identified as good and poor response group respectively, during the study period of 2008 to 2021. The poor response group showed significantly worse progression-free survival (PFS; median 2.1 vs. 9.7 months; p < 0.001) and overall survival (OS; median, 5.0 vs. 22.9 months; p < 0.001) compared with the good response group. In multivariate analysis adjusting for clinicopathologic factors, short treatment free interval (hazard ratio [HR]: 5.557; 95% confidence interval [CI]: 2.403-12.850), platinum-resistant EOC (HR; 2.367; 95% CI: 1.017-5.510), and non-serous/endometrioid histologic type (HR: 5.045; 95% CI: 1.152-22.088) were identified as independent risk factors for poor response. There was no difference in serious adverse events between good and poor-response groups (p=0.167).

Conclusion: Third and subsequent lines of chemotherapy could be carefully considered for palliative purposes in recurrent EOC patients with serous or endometrioid histology, initial platinum sensitivity, and long TFIs from the previous chemotherapy regimen.

Keywords: Drug therapy; Epithelial ovarian cancer; Prognosis; Recurrence; Survival; Treatment response.

The axon initial segment (AIS) is a specialized structure that controls neuronal excitability via action potential (AP) generation. Currently, AIS plasticity with regard to changes in length and location in response to neural activity has been extensively investigated, but how AIS diameter is regulated remains elusive. Here we report that COUP-TFI (chicken ovalbumin upstream promotor-transcription factor 1) is an essential regulator of AIS diameter in both developing and adult mouse neocortex. Either embryonic or adult ablation of COUP-TFI results in reduced AIS diameter and impaired AP generation. Although COUP-TFI ablations in sparse single neurons and in populations of neurons have similar impacts on AIS diameter and AP generation, they strengthen and weaken, respectively, the receiving spontaneous network in mutant neurons. In contrast, overexpression of COUP-TFI in sparse single neurons increases the AIS diameter and facilitates AP generation, but decreases the receiving spontaneous network. Our findings demonstrate that COUP-TFI is indispensable for both the expansion and maintenance of AIS diameter and that AIS diameter fine-tunes action potential generation and synaptic inputs in mammalian cortical neurons.

Keywords: Action potential; Axon initial segment; COUP-TFI; Diameter.

OBJECTIVE

We report a phase II clinical study of the combination of irinotecan (CPT-11) and pegylated liposomal doxorubicin (PLD) in platinum- and taxane-resistant recurrent ovarian cancer, based on the recommended doses determined in a phase I trial.

METHODS

PLD was administered intravenously at a dose of 30 mg/m2 on day 3. CPT-11 was administered intravenously at a dose of 80 mg/m2 on days 1 and 15, according to the recommendations of the phase I study. A single course of chemotherapy lasted 28 days, and patients underwent at least 2 courses until disease progression. The primary endpoint was antitumor efficacy, and the secondary endpoints were adverse events, progression-free survival (PFS), and overall survival (OS).

RESULTS

The response rate was 32.3% and the disease control rate was 64.5%. Grade 3 and 4 neutropenia, anemia, and a decrease in platelet count were observed in 17 (54.9%), 3 (9.7%), and 1 patient (3.2%), respectively. In terms of grade 3 or higher non-hematologic toxicities, grade 3 nausea occurred in 1 patient (3.2%), vomiting in 3 patients (9.7%), and grade 3 diarrhea and fatigue in 1 patient (3.2%). The median PFS and OS rates were 2 months and not reached, respectively. Of the 11 patients with a treatment-free interval (TFI) of ≥3 months, the response rate was 63.3%, and the median PFS was 7 months.

CONCLUSIONS

The treatment outcomes for the 31 patients enrolled in this study were unsatisfactory. However, sub-analysis suggested that patients with a TFI of ≥3 months had a good response rate and PFS. This suggests that CPT-11/PLD combination therapy may be a chemotherapy option for platinum-resistant recurrent ovarian cancer.