During pregnancy and lactation, the adequate intake (AI) for total water intake is increased. This cross-sectional survey aimed to assess Total Fluid Intake (TFI; sum of drinking water and all other fluids) of 300 pregnant and 300 breastfeeding women in Indonesia. A seven-day fluid specific record was used to assess TFI. Mean TFI of pregnant and breastfeeding women were 2332 ± 746 mL/day and 2525 ± 843 mL/day, respectively. No significant difference in TFI between pregnancy trimesters was observed, while TFI of women breastfeeding for 12-24 months postpartum (2427 ± 955 mL/day) was lower than that of the two other groups (0-5 months: 2607 ± 754 mL/day; 6-11 months: 2538 ± 807 mL/day, respectively). Forty-two and 54% of the pregnant and breastfeeding subjects, respectively, did not reach the AI of water from fluids. These AI were actually known by only 14% and 23% of the pregnant and breastfeeding subjects. However, having the knowledge about the AI did not increase the odds of reaching the AI. Concluding that a high proportion of the pregnant and breastfeeding subjects did not reach the AI of water from fluid, it seems pertinent to further assess the fluid intake, as well as their hydration status, in other countries.

OBJECTIVE

A combined chemotherapy of taxane and platinum, with or without anthracycline, has been used as a standard first-line regimen. The purpose of this study was to investigate the effectiveness of second-line chemotherapy for treatment of advanced or recurrent endometrial carcinoma previously treated with a combined chemotherapy of taxane and platinum, with or without anthracycline.

METHODS

During the 2000-2008 study period, 723 patients were diagnosed with endometrial cancer at the Departments of Obstetrics and Gynecology of the Osaka University and the Osaka Rosai Hospitals, Osaka, Japan. The subset of these cases that eventually required treatment by second-line chemotherapy was retrospectively analyzed.

RESULTS

Response rate to second-line chemotherapy was 25%. Treatment-free interval (TFI) of ≥ or <6 months was demonstrated to be significantly associated with the response to second-line chemotherapy (P = 0.0026), progression-free survival (P = 0.0003) and overall survival (P = 0.025). The second-line chemotherapy similar to the first-line regimen was ineffective in all the 7 cases (100%) whose TFI was shorter than 6 months. Multivariate analysis showed that TFI was the most significantly important factor predicting the effectiveness of second-line chemotherapy (the adjusted hazard ratio of TFI on PFS and OS: 3.482, 95% CI, 1.641-7.388, P = 0.0012, and 2.341, 95% CI, 1.034-5.301, P = 0.042, respectively).

CONCLUSIONS

Our present study provides, for the first time, evidence that the majority of refractory or recurrent diseases, if they occur within 6 months of a first-line chemotherapy using taxane and platinum with or without anthracycline, are non-responsive to the current regimens of second-line chemotherapy.

The bimodal requisite for a genetic program and external stimuli is a key feature of sensory circuit formation. However, the contribution of cell-intrinsic codes to directing sensory-specific circuits remains unknown. Here, we identify the earliest molecular program that preselects projection neuron types in the sensory neocortex. Mechanistically, Foxg1 binds to an H3K4me1-enriched enhancer site to repress COUP-TFI, where ectopic acquisition of Foxg1 in layer 4 cells transforms local projection neurons to callosal projection neurons with pyramidal morphologies. Removal of Foxg1 in long-range projection neurons, in turn, derepresses COUP-TFI and activates a layer 4 neuron-specific program. The earliest segregation of projection subtypes is achieved through repression of Foxg1 in layer 4 precursors by early growth response genes, the major targets of the transforming growth factor-β signaling pathway. These findings describe the earliest cortex-intrinsic program that restricts neuronal connectivity in sensory circuits, a fundamental step towards the acquisition of mammalian perceptual behavior.

Interim results from the 2-cohort, phase 2 KEYNOTE-100 study (NCT02674061) of 376 patients with previously treated advanced recurrent ovarian cancer (ROC) showed that pembrolizumab monotherapy was associated with an objective response rate (ORR) of 8.0% (95% CI, 5.4-11.2). We present outcomes for the Japanese patients (n=21) enrolled in KEYNOTE-100. Patients with epithelial ROC had received either 1-3 prior chemotherapy lines and had platinum- or treatment-free interval (PFI; TFI) of 3-12 months (cohort A) or 4-6 prior chemotherapy lines and had PFI/TFI of ≥3 months (cohort B). All patients received pembrolizumab 200 mg every 3 weeks as monotherapy for 2 years or until progression, death, unacceptable toxicity, or consent withdrawal. Primary objectives were ORR per RECIST v1.1 for each cohort and PD-L1 tumor expression. The relationship between PD-L1 expression (measured as combined positive score [CPS]) and ORR was assessed. Twenty-one Japanese patients (cohort A, n=19; cohort B, n=2) were treated. Median (range) age was 57 (37-78) years; 19 (90.5%) patients had ECOG status of 0, and 16 (76.2%) patients had stage III-IV disease. ORR was 19.0% (95% CI, 5.4-41.9) and seemed to increase with increasing PD-L1 expression. Thirteen (61.9%) patients had treatment-related adverse events (TRAEs), and 5 (23.8%) had grade 3-4 TRAEs. There were no treatment-related deaths in this subpopulation. Pembrolizumab monotherapy was associated with antitumor activity in Japanese patients with ROC, with no new safety signals identified in this subpopulation. The data suggested a trend toward higher PD-L1 expression among some patients with higher ORR.

Introduction: Tinnitus is a complex symptom requiring a thorough multidisciplinary assessment to construct an individual's tinnitus profile. The Antwerp University Hospital hosts a tertiary tinnitus clinic providing intensive, multidisciplinary tinnitus care in the form of combinational psychological treatment with either Tinnitus Retraining Therapy (TRT)/Cognitive Behavioral Therapy (CBT) or TRT/eye movement desensitization and reprocessing therapy (EMDR), high-definition transcranial direct current stimulation (HD-tDCS), and physical therapy treatment (in cases of somatic influence of the neck or the temporomandibular area). Several factors may contribute to therapy effect of which the role of gender has recently gained more interest. As such, the current manuscript explores gender differences in the outcome of different tinnitus treatments.

Methods: Data on treatment outcome of four distinct tinnitus treatments (1. HD-tDCS; 2. orofacial physical therapy; 3. combination TRT + CBT; and 4. combination TRT + EMDR) were pooled and compared. Treatment outcome was assessed via the Tinnitus Functional Index (TFI). Participants completed the TFI at baseline, immediately after treatment and after 9 weeks (±3 weeks) follow-up. To explore the effect of gender on different treatment outcomes, a linear mixed model was designed including Time point, Gender, and Therapy Group as fixed factors as well as all interactions between these factors.

Results: TFI scores improved significantly over time regardless of therapy group (p < 0.0001). A mean TFI decrease of at least 13 points was obtained by all participants except by those in the HD-tDCS. Significant interactions between Gender and Time point were identified in all groups except for the TRT +EMDR group. Female subjects improved more extensively than males in the HD-tDCS (p = 0.0009) and orofacial therapy group (p = 0.0299). Contrarily, in the TRT +CBT group, male participants showed a significant improvement whereas the mean TFI scores of female subjects remained on baseline levels (p = 0.0138).

Conclusion: Our data suggest that male and female tinnitus patients seem to react differently to different therapy options. We strongly encourage further prospective studies to discern the relevance of gender in therapy outcome.

Keywords: CBT; HDtDCS; TRT; gender; gender-related outcome; neuromodulation; tDCS; tinnitus.

OBJECTIVE

The aim of this investigation was to assess the effect of loading on ultrasonic scaler tip displacement amplitude, using a scanning laser vibrometer.

METHODS

Four generators were selected for this investigation including: Cavitron Select (Dentsply), Cavitron SPS (Dentsply), Piezon Master 400 (EMS) and Mini Piezon (EMS). The insert designs used with these generators included the TFI-10 and TFI-3 (with the Dentsply generators) and P-tip (with the EMS generators). The insert tips were contacted against tooth surfaces with loads of 0.25, 0.5 and 1.0 N. The scanning laser vibrometer was then used to scan the vibrating scalers at various generator power settings.

RESULTS

The tips generally showed an increase in displacement amplitude with increasing power setting, although this increase was often nonlinear. Displacement amplitudes of like tips were generally found to be significantly different from each other at all loads. For individual inserts, loading caused a significant difference in tip response from the unloaded situation and also between loads.

CONCLUSIONS

This investigation has demonstrated that there is a high variability associated with dental ultrasonic scaler inserts. Clinicians and researchers should be aware of this variability as it may affect both clinical procedures and future research.

The frequent, widespread use of pesticides in agriculture adversely affects biodiversity, human health, and water quality. In 2008, the French government adopted an environmental policy plan, "Ecophyto 2018", to halve pesticide use within 10years. Trends in synthetic pesticide sales and use in France were described, through three different indicators: the number of unit doses (NUD), the quantity of active ingredient (QAI), and the treatment frequency index (TFI). Changes in pesticide use on seven of the principal arable crops in France since the implementation of this policy plan were analyzed, together with the impact of changes in pesticide use on water quality. No evidence was found for a decrease in pesticide sales at national level between 2008 and 2013. In terms of the TFI values for individual crops, the only decrease in pesticide use observed since 2001 was for soft wheat. This decrease was very slight, and pesticide use did not decline more rapidly after 2006 than before. Changes in pesticide use differed between French regions and crops. Water pollution did not decrease during the period studied. Possible explanations for the lack of effectiveness of the French environmental plan are considered in the context of European legislation.

There is a need for more accurate Chlamydia trachomatis (CT) IgG antibody tests for tubal factor infertility (TFI) diagnostics. We evaluated the predictive value for TFI of Medac ELISA plus (MOMP) and multitarget Mikrogen ELISA (MOMP-CPAF-TARP). Based on Medac ELISA plus results, 183 subfertile women underwent either hysterosalpingography or laparoscopy to diagnose TFI. TFI was defined as extensive adhesions and/or distal occlusion of at least one tube. Women not fulfilling the definition of TFI served as controls. Serum was subsequently tested with Mikrogen ELISA and results were compared. 48 patients had TFI, 135 were controls. Mikrogen ELISA tested 125 patients positive/borderline of which 32% had TFI. Medac ELISA plus tested 77 patients positive/borderline of which 29.9% had TFI. Mikrogen tested 40 out of 48 TFI patients positive/borderline, Medac 23 out of 48. Kappa value was 0.34. PPV of Mikrogen ELISA and Medac ELISA plus were respectively 32% (95% CI 26%-39%) and 30% (95% CI 24%-37%), and NPV 86% (95% CI 81%-91%) and 76% (95% CI 70%-82%). Both tests were comparable in the prediction of TFI. However, Mikrogen ELISA had a higher NPV and might be more reliable in identifying patients without TFI. Kappa-value showed limited concordance between both tests.

The change of serum soluble Klotho (sKlotho) content is related to a variety of osteoarthropathy. However, its association with the severity of skeletal fluorosis (SF) is not clear. Here, the association of tea fluoride exposure with serum sKlotho levels and the severity of SF were investigated and further verified in a rat model of fluorosis. A cross sectional case control study was conducted in residents over 50 years old from brick-tea drinking areas in Qinghai and Xinjiang Provinces, China. Concentrations of fluoride in brick tea water and urine were determined by ion selective electrode method, and the levels of serum sKlotho were determined by ELISA method. Linear regression and ordered logistic regression models were constructed to examine the relationship among fluoride exposure, serum sKlotho levels and the severity of SF. The kidney and small intestine of Wistar rats were isolated for detection of Klotho by immunohistochemistry (IHC), and femoral artery blood was sampled to measure the serum levels of sKlotho. An increase of 1 mg/day in tea fluoride intake (TFI) was associated with a 12.070 pg/mL (95% CI: 0.452-23.689) increase in serum sKlotho levels and a 1.163-fold (95% CI: 1.007-1.342) increase in the severity of SF after adjusting for age, gender, and ethnicity. Serum sKlotho levels were also positively associated with the severity of SF (P < 0.05). The mediation analysis showed that serum sKlotho levels mediated 17.76% of the increase in the severity of SF caused by an increase of 1 mg/day of TFI. Moreover, a significant increase of serum sKlotho levels in fluoride-exposed groups was also seen in the rat model. The present study suggests that serum sKlotho may be a potential mediator of SF in brick tea-type fluorosis endemic areas.

Keywords: Brick tea-type fluorosis; Mediation analysis; Serum sKlotho; Skeletal fluorosis; Tea fluoride intake.

The genome of Pseudomonas fluorescens F113, a model rhizobacterium and a plant growth-promoting agent, encodes three putative type VI secretion systems (T6SSs); F1-, F2- and F3-T6SS. Bioinformatic analysis of the F113 T6SSs has revealed that they belong to group 3, group 1.1, and group 4a, respectively, similar to those previously described in Pseudomonas aeruginosa. In addition, in silico analyses allowed us to identify genes encoding a total of five orphan VgrG proteins and eight putative effectors (Tfe), some with their cognate immunity protein (Tfi) pairs. Genes encoding Tfe and Tfi are found in the proximity of P. fluorescens F113 vgrG, hcp, eagR and tap genes. RNA-Seq analyses in liquid culture and rhizosphere have revealed that F1- and F3-T6SS are expressed under all conditions, indicating that they are active systems, while F2-T6SS did not show any relevant expression under the tested conditions. The analysis of structural mutants in the three T6SSs has shown that the active F1- and F3-T6SSs are involved in interbacterial killing while F2 is not active in these conditions and its role is still unknown.. A rhizosphere colonization analysis of the double mutant affected in the F1- and F3-T6SS clusters showed that the double mutant was severely impaired in persistence in the rhizosphere microbiome, revealing the importance of these two systems for rhizosphere adaption.

UNASSIGNED

The aim of this study was to determine if a customized stimulus from the Otoharmonics Levo System reduces tinnitus perceptions and reactions for people with bothersome tinnitus.

UNASSIGNED

Sixty participants were randomized to 1 of 3 groups that used sound therapy devices during sleep that differed in their acoustic stimulus: (a) tinnitus-matched (TM), (b) noise stimulus (NS), and (c) bedside sound generator (BSG). Outcome measures were the Tinnitus Functional Index (TFI), numeric rating scale of tinnitus loudness, and tinnitus loudness match. A Bayesian hierarchical model was fit to estimate the differences in treatment efficacy among groups.

UNASSIGNED

Average tinnitus reactions and perceptions improved across treatment groups. We are at least 87% certain that treatment with TM or NS reduces mean TFI compared to treatment with BSG, with an estimated relative efficacy of 4.5-5 points greater reduction. We are at least 95% certain that treatment with TM results in greater reduction in mean numeric rating scale (NRS) of tinnitus loudness compared to the other groups, with an estimated relative efficacy of about 0.75 points greater reduction.

UNASSIGNED

This study offers some support for greater average improvement in reactions to tinnitus with TM or NS devices compared to the BSG device. The TM group, compared to the BSG and NS groups, showed a greater reduction in ratings of tinnitus loudness on the NRS on average.

UNASSIGNED

https://doi.org/10.23641/asha.5545759.

OBJECTIVE

To identify prognostic factors of recurrent endometrial cancer, and clarify whether the treatment-free interval (TFI) predicts outcome in a wide spectrum of patients.

METHODS

The clinical data of 60 patients treated for recurrent stage I-IV endometrial cancer between 1997 and 2012 were reviewed retrospectively. The Kaplan-Meier method and Cox regression analysis were used to estimate overall survival (OS) following recurrence and determine the factors influencing outcomes.

RESULTS

The median age at initial treatment was 59 (range 38-80) years and the median post-recurrence overall survival time was 40.0 (range 1.8-156.7) months. Multivariate analysis showed lymph node metastasis (hazard ratio (HR) 2.80; 95% confidence interval (95%CI) 1.29-6.09; p=0.009), TFI (HR 0.33; 95% CI 0.15-0.76; p=0.008), and symptomatic recurrence (HR 2.31, 95% CI 1.11-4.83, p=0.0025) were independent prognostic factors. Patients whose tumors recurred after a TFI≥12 months had better response rates than did those with a TFI<12 months (p<0.001).

CONCLUSIONS

TFI is a significant prognostic factor in recurrent endometrial cancer. Furthermore, the effect of chemotherapy on recurrent endometrial cancer is probably influenced by the duration of TFI.

Dry eye (DE) disease is a multifactorial disease of the outer ocular surface characterized by several ocular symptoms and mainly by tear film instability. We have developed an optical imaging system, the tear film imager (TFI), which is the first instrument that can directly image the muco-aqueous tear layer physical dimension in vivo and evaluate its parameters in a noninvasive mode with nanometer axial resolution. This instrument provides quantified information about many attributes of the tear film, including muco-aqueous layer thickness, lipid layer thickness, thickness change rate, and the break-up time. The TFI performances are based on simultaneous acquisition of large field of view (FOV) imagery and fast spectrometric measurement of the interference from the thin tear film sublayers. Herein, after describing the instrument and the methodology of the measurements, we use a tear film mock-up to quantify device accuracy (2.2 nm) and repeatability (0.25 nm standard deviation). In conclusion, we present a new technology for the assessment of the tear film with an unprecedented axial resolution and excellent accuracy and reproducibility.

BACKGROUND

Early identification of problems is essential in minimising the unintended consequences of opioid therapy. This study aimed to develop a brief scale that identifies and quantifies recent aberrant behaviour among diverse patient populations receiving long-term opioid treatment.

METHODS

40 scale items were generated via literature review and expert panel (N=19) and tested in surveys of: (i) N=41 key experts, and (ii) N=426 patients prescribed opioids >3 months (222 pain patients and 204 opioid substitution therapy (OST) patients). We employed item and scale psychometrics (exploratory factor analyses, confirmatory factor analyses and item-response theory statistics) to refine items to a brief scale.

RESULTS

Following removal of problematic items (poor retest-reliability or wording, semantic redundancy, differential item functioning, collinearity or rarity) iterative factor analytic procedures identified a 10-item unifactorial scale with good model fit in the total sample (N=426; CFI=0.981, TLI=0.975, RMSEA=0.057), and among pain (CFI=0.969, TLI=0.960, RMSEA=0.062) and OST subgroups (CFI=0.989, TFI=0.986, RMSEA=0.051). The 10 items provided good discrimination between groups, demonstrated acceptable test-retest reliability (ICC 0.80, 95% CI 0.60-0.89; Cronbach's alpha=0.89), were moderately correlated with related constructs, including opioid dependence (SDS), depression and stress (DASS subscales) and Social Relationships and Environment domains of the WHO-QoL, and had strong face validity among advising clinicians.

CONCLUSIONS

The Opioid-Related Behaviours In Treatment (ORBIT) scale is brief, reliable and validated for use in diverse patient groups receiving opioids. The ORBIT has potential applications as a checklist to prompt clinical discussions and as a tool to quantify aberrant behaviour and assess change over time.

New Zealand is a supplier of refrigerated raw meat to world markets. To maintain this supply, from regulatory and commercial perspectives, production standards need to deliver products that are both hygienically adequate and commercially viable. A dynamic Temperature Function Integration (TFI) model, as a form of predictive microbiology, was used jointly by regulators and processors to develop justifiable criteria for the management of refrigeration during the production of hot and warm-boned meat, the post-slaughter handling of ovine carcasses and the handling of offals. Current processes operating according to accepted standards for Good Manufacturing Practice (GMP) were quantified in terms of TFI. The hygienic adequacy of new processes were similarly determined using the TFI model and compared to relevant GMP standards. From a regulatory perspective, the dynamic TFI model has provided a rapid and cost effective method of quantifying a temperature dependent process in terms of the potential for microbial proliferation. It has also produced a method for determining parameters for new or intended processes by comparing the potential for microbial proliferation with previously validated outputs, and has complemented traditional quantitative microbiology to provide a rapid, cost effective method of verifying that a process is performing according to design parameters. However, it could not be used to validate standards for processing in the absence of existing standards for GMP, or in the absence of microbial standards previously established using the principles of risk assessment.

Normal sexual development and reproductive function depend on precise temporal and quantitative expression of the pituitary gonadotropins, LH and FSH. LHβ-subunit gene expression is achieved by transcription factors acting at highly conserved and closely spaced cis-elements in the proximal 200 base pairs of the promoter. We now demonstrate that LHβ promoter activity is further regulated by the orphan nuclear receptors, chicken ovalbumin upstream promoter-transcription factors (COUP-TFI and COUP-TFII). These data establish that COUP-TFs are expressed in primary pituitary gonadotropes and two gonadotrope-derived cell lines. COUP-TFs bind to two promoter regions in the LHβ gene which overlap but are distinct from two previously defined cis-elements for another orphan nuclear receptor, steroidogenic factor-1 (SF-1). Transient transfection studies demonstrated that COUP-TFs stimulate LHβ gene promoter activity in the absence of SF-1, but blunt SF-1-mediated stimulation of gene expression in a reporter construct containing both SF-1 cis-elements (GSEs). Evaluation of constructs containing mutations or truncations in the GSEs revealed a complex pattern of activation and inhibition by COUP-TF on this promoter, suggesting multiple mechanisms by which this factor modulates LHβ gene expression. To our knowledge, these data are the first to demonstrate COUP-TF expression and function in pituitary gonadotropes.

Ikari is a new guide catheter for transradial intervention (TRI) that produces stronger back-up force by utilizing an unfavorable angle between the subclavian and brachiocephalic arteries. We report the initial results of the Ikari guide catheter based on the experience of a single center. Six operators performed a total of 102 coronary interventions for 91 patients using the Ikari guide catheter, while 101 interventions were performed with the transfemoral approach (TFI) during the same period. A left Ikari catheter was used in 63 procedures, and a right Ikari catheter was used in 39. The success rate for the procedure was 97% with a 6 French Ikari catheter. All failures were due to tortuous brachiocephalic arteries. For the Ikari procedure, the average fluorescence time was 14.5 9.5 minutes and the dye volume used was 153 53 ml; these results were equal to or better than those of TFI during the same period (20.1 12.2 minutes and 184 61 ml, respectively). These preliminary data suggest that an acceptable success rate can be achieved in TRI using appropriate guides, such as an Ikari catheter.

BACKGROUND

Anthropometric variation can be fruitfully utilized to investigate microevolutionary processes. Anthropometric variations in the Indian subcontinent based on stature and three indices (Cephalic Index, Nasal Index, and Total Facial Index) are highly variable and discriminative among populations across geographical regions.

OBJECTIVE

Anthropometric variation in stature, Cephalic Index (CI), Nasal Index (NI) and Total Facial Index (TFI) were investigated with respect to ethnic, linguistic, geographical and climatic affiliation, across the Indian subcontinent.

METHODS

Published data on anthropometric variations of 531 populations from the Indian subcontinent were analysed using discriminant analysis and spatial autocorrelation analysis.

RESULTS

Discriminant analysis of the four anthropometric variables shows that stature and NI are good discriminators for populations of different languages. Stature, NI and CI discriminate well among populations of diverse ethnic origin and climatic conditions in different regions. TFI is not a good discriminator for populations of diverse ethnic, linguistic and climatic attributes. Spatial autocorrelation analysis showed significant departure from randomness, suggesting geographic structuring. The Moran's I estimate is positive and statistically significant for the four variables at low distances but exhibits significant negative association at higher values.

CONCLUSIONS

The results suggest geographical clines for the four anthropometric variables and indicate the influence of population structure on the studied variables.