OBJECTIVE

To describe preliminary ED experience with thoracic electrical bioimpedance (TEB) for evaluation of patients with complaints suggestive of congestive heart failure (CHF).

METHODS

A 6-month, prospective, observational study was performed using a convenience sample of patients with signs and symptoms consistent with CHF. Patients were excluded if they had received medication prior to arrival in the ED, if they were obese, and if they had unstable vital signs. They also were excluded if they were combative, refused to sign consent, or had invasive lines that did not allow for TEB lead placement. Patients also were excluded if the study could not be completed because the patient was taken from the department for a diagnostic test, or if there were no good follow-up records available 6-12 months after the patient's visit. The patient's physician was blinded to the output of the TEB monitor. Cardiac output (CO), stroke volume (SV), end-diastolic volume (EDV), thoracic fluid index (TFI), and acceleration index (ACI) were recorded at 5-minute intervals. Results were evaluated for the time intervals 0-5 minutes, 30-35 minutes, and 60-65 minutes.

RESULTS

Seven patients were included in the study. The echocardiographic diagnoses were hypertrophic cardiomyopathy (2 cases), dilated cardiomyopathy (2 cases), ischemic cardiomyopathy (1 case), right ventricular hypertrophy (1 case), and pericardial effusion (1 case). Significant changes were seen in all cardiac parameters, with variance from individual to individual.

CONCLUSIONS

Significant differences in TEB variables exist between patients who appear similar on initial examination in the ED. Changes noted on TEB may help to further elucidate physiologic differences. The clinical use of TEB-based hemodynamic measurements to guide presumed CHF patient management remains speculative.

We tested the hypothesis that the prolonged elevated plateau of esophageal temperature (Tes) following moderate exercise is a function of some exercise-related factors and not the increase in heat content and Tes during exercise, by comparing the response to increase Tes during exercise (endogenous heating) and warm-water immersion (exogenous heating). Nine healthy, young [24.0 (1.9) years] subjects performed two separate experiments: (1) 15 min of treadmill exercise at 70% (VO2max) and 15 min rest in a climatic chamber at 29 degrees C, followed by 15 min of immersion in a 42 degrees C water bath and a further 60 min of recovery in the climatic chamber [exercise-water (EW)]; and (2) 15 min of immersion in a 42 degrees C water bath followed by 60 min of recovery in the climatic chamber [water-only (WO)]. Esophageal (Tes) and skin (Tsk) temperatures were recorded at 5-s intervals throughout. The Tes at which the forearm to finger temperature gradient (Tfa-Tfi) abruptly decreases was used to identify the threshold for forearm cutaneous vessel dilation (Thdil) during exercise. Pre-exercise Tes values were 36.64 degrees C and 36.74 degrees C for EW and WO respectively. The EW post-exercise Tes value fell to a stable level of 37.12 degrees C and this value differed by 0.48 degree C (P < 0.05) from baseline, but was similar to Thdil (37.09 degrees C). Despite a 1.2 degrees C increase in Tes during the subsequent warm-water immersion, Tes returned to the post-exercise value (37.11 degrees C). The WO post-immersion Tes fell to a stable plateau of 36.9 degrees C, which was not statistically different from the pre-immersion Tes. The data for both warm-water treatments support the hypothesis that increases in Tes and heat content alone are not the primary mechanisms for the post-exercise elevation in Tes and Thdil. These data also support our previous observation that the exercise-induced elevation in Thdil persists into recovery.

Reducing the risks and impacts of pesticide use on human health and on the environment is one of the objectives of the European Commission Directive 2009/128/EC in the quest for a sustainable use of pesticides. This Directive, developed through European national plans such as Ecophyto plan in France, promotes the introduction of innovative cropping systems relying, for example, on integrated pest management. Risk assessment for human health of the overall pesticide use in these innovative systems is required before the introduction of those systems to avoid that an innovation becomes a new problem.

The objectives of this work were to assess and to compare (1) the human exposure to pesticides used in conventional and innovative cropping systems designed to reduce pesticide needs, and (2) the corresponding risks for human health.

Humans (operator and residents) exposure to pesticides and risks for human health were assessed for each pesticide with the BROWSE model. Then, a method was proposed to represent the overall risk due to all pesticides used in one system. This study considers 3 conventional and 9 associated innovative cropping systems, and 116 plant protection products containing 89 different active substances (i.e. pesticides).

The modelling results obtained with BROWSE showed that innovative cropping systems such as low input or no herbicide systems would reduce the risk for human health in comparison to the corresponding conventional cropping systems. On the contrary, BROWSE showed that conservation tillage system would lead to unacceptable risks in the conditions of our study, because of a high number of pesticide applications, and especially of some herbicides. For residents, the dermal absorption was the main exposure route while ingestion was found to be negligible. For operators, inhalation was also a predominant route of exposure. In general, human exposure to pesticides and human health risks were found to be correlated to the treatment frequency index TFI (number of registered doses of pesticides used per hectare for one copping season), confirming the relationship between the reduction of pesticide use and the reduction of risks.

Assessment with the BROWSE model helped to identify cropping systems with decreased risks from pesticides for human health and to propose some improvements to the cropping systems by identifying the pesticides that led to unacceptable risks.

The aim of this trial was to investigate the efficacy and toxicity of combination chemotherapy with etoposide and ifosfamide (ETI) in the management of heavily pretreated recurrent or persistent epithelial ovarian cancer (EOC). Patients with recurrent or persistent EOC who had measurable disease and at least two prior chemotherapy participating in this phase II trial were to receive etoposide at a dose of 100 mg/m(2)/day intravenously (IV) on days 1 to 3 in combination with ifosfamide 1 g/m(2)/day IV on days 1 to 5, every 21 days. Thirty-seven patients were treated; about 78% had previously received more than two separate regimens. The response rate (RR) was 18.9% and median duration of response was 7 months (range, 1-15). Treatment free interval prior to ETI (TFI) has significant correlation with RR rate (P=0.034). Patients (n=6) with TFI>> or =6 months had 50% of RR, while patients (n=31) with TFI <6 months had 12.9%. Median survival was 9 months at a median follow-up of 9.2 months. Grade 3 or 4 toxicities included neutropenia in 20.1% of the 139 cycles of ETI, anemia in 7.2% and thrombocytopenia in 8.6%. The ETI produces relatively low toxicity and modest activity in heavily pretreated recurrent or persistent EOC. This is significant in patients with TFI>> or =6 months.

In the field of electronic countermeasure, the recognition of radar signals is extremely important. This paper uses GNU Radio and Universal Software Radio Peripherals to generate 10 classes of close-to-real multipulse radar signals, namely, Barker, Chaotic, EQFM, Frank, FSK, LFM, LOFM, OFDM, P1, and P2. In order to obtain the time-frequency image (TFI) of the multipulse radar signal, the signal is Choi-Williams distribution (CWD) transformed. Aiming at the features of the multipulse radar signal TFI, we designed a distinguishing feature fusion extraction module (DFFE) and proposed a new HRF-Net deep learning model based on this module. The model has relatively few parameters and calculations. The experiments were carried out at the signal-to-noise ratio (SNR) of -14 ∼ 4 dB. In the case of -6 dB, the recognition result of HRF-Net reached 99.583% and the recognition result of the network still reached 97.500% under -14 dB. Compared with other methods, HRF-Nets have relatively better generalization and robustness.

Objective: To evaluate the relationship between insomnia and multidimensional frailty.

Background: Frailty has major implications on adverse health outcomes of older adults. In recent years, multidimensional nature of frailty has been increasingly recognised. Many frail older adults also suffer from insomnia.

Methods: This was a cross-sectional observational study including 454 community-dwelling adults aged 60 and older. Insomnia was defined as a subjective experience of inadequate sleep duration or quality that affects social functioning during the day, based on the Athens Insomnia Scale (AIS), and multidimensional frailty was based on Tilburg Frailty Indicator (TFI). The STROBE checklist was used to guide the submission.

Results: Mean age was 69.1 years old, 211 (46.5%) of participants suffered from insomnia, and 185 (40.7%) of participants were frail. There was a significant relationship between insomnia and multidimensional frailty (physical, psychological and social dimensions). Insomnia was associated with frailty, adjusting for sociodemographic characteristics and comorbidity OR of 6.863 (95% CI: 4.237-11.116).

Conclusion: Frailty was independently predicted by insomnia. Future researches should determine whether there is a causal relationship between insomnia and multidimensional frailty, with the ultimate goal of providing interventions to reverse or prevent frailty.

Relevance to clinical practice: This study emphasises the importance of assessment and treatment of insomnia, potentially contributing to the reversion and prevention of frailty in community-dwelling older adults.

Keywords: cross-sectional study; frailty; insomnia; older adults.

In males, Leydig cells are the main producers of testosterone and insulin-like 3 (INSL3), two hormones essential for sex differentiation and reproductive functions. Chicken ovalbumin upstream promoter-transcription factors I (COUP-TFI/NR2F1) and COUP-TFII (NR2F2) belong to the steroid/thyroid hormone nuclear receptor superfamily of transcription factors. In the testis, COUP-TFII is expressed and plays a role in the differentiation of cells committed to give rise to fully functional steroidogenic adult Leydig cells. Steroid production has also been shown to be diminished in COUP-TFII-depleted Leydig cells, indicating an important functional role in steroidogenesis. Until now, only a handful of target genes have been identified for COUP-TFII in Leydig cells. To provide new information into the mechanism of action of COUP-TFII in Leydig cells, we performed microarray analyses of COUP-TFII-depleted MA-10 Leydig cells. We identified 262 differentially expressed genes in COUP-TFII-depleted MA-10 cells. Many of the differentially expressed genes are known to be involved in lipid biosynthesis, lipid metabolism, male gonad development, and steroidogenesis. We validated the microarray data for a subset of the modulated genes by RT-qPCR. Downregulated genes included Hsd3b1, Cyp11a1, Prlr, Shp/Nr0b2, Fdx1, Scarb1, Inha and Gsta3. Finally, analysis of the Gsta3 and Inha gene promoters showed that at least two of the downregulated genes are potentially new direct targets for COUP-TFII. These data provide new evidence that further strengthens the important nature of COUP-TFII in steroidogenesis, androgen homeostasis, cellular defense, and differentiation in mouse Leydig cells.

Keywords: COUP-TFII; Gsta3; Leydig cells; NR2F2; Nuclear receptor; Steroidogenesis; Transcriptomics.

Purpose: To (a) develop a preconditioned water-fat total field inversion (wfTFI) algorithm that directly estimates the susceptibility map from complex multi-echo gradient echo data for water-fat regions and to (b) evaluate the performance of the proposed wfTFI quantitative susceptibility mapping (QSM) method in comparison with a local field inversion (LFI) method and a linear total field inversion (TFI) method in the spine.

Methods: Numerical simulations and in vivo spine multi-echo gradient echo measurements were performed to compare wfTFI to an algorithm based on disjoint background field removal (BFR) and LFI and to a formerly proposed TFI algorithm. The data from 1 healthy volunteer and 10 patients with metastatic bone disease were included in the analysis. Clinical routine computed tomography (CT) images were used as a reference standard to distinguish osteoblastic from osteolytic changes. The ability of the QSM methods to distinguish osteoblastic from osteolytic changes was evaluated.

Results: The proposed wfTFI method was able to decrease the normalized root mean square error compared to the LFI and TFI methods in the simulation. The in vivo wfTFI susceptibility maps showed reduced BFR artifacts, noise amplification, and streaking artifacts compared to the LFI and TFI maps. wfTFI provided a significantly higher diagnostic confidence in differentiating osteolytic and osteoblastic lesions in the spine compared to the LFI method (p = .012).

Conclusion: The proposed wfTFI method can minimize BFR artifacts, noise amplification, and streaking artifacts in water-fat regions and can thus better differentiate between osteoblastic and osteolytic changes in patients with metastatic disease compared to LFI and the original TFI method.

Keywords: MEDI; QSM; TFI; osteoblastic; osteolytic; spine; vertebral metastases.

Background: Transradial percutaneous coronary intervention (PCI; TRI) reduces adverse outcomes when compared with transfemoral PCI (TFI). However, TRI is also used less in high-risk patients. It remains unknown how baseline patient risk influences access-site choice among PCI operators and whether the absolute benefit of TRI is greater among patients at high risk for bleeding, acute kidney injury (AKI), and death.

Methods: We analyzed 28 005 PCIs performed in a 7-hospital system between July, 01, 2009 and April 30, 2018, to assess the choice of access-site (TRI versus TFI) as a function of baseline risk for bleeding, AKI, and death, and examined whether the association between TRI use (versus TFI) and in-hospital outcomes is influenced by baseline risk.

Results: Among 28 005 PCIs, over a 9-year period, TRI increased over time, however, a risk-treatment paradox for TRI use was observed not only for bleeding risk, but also AKI, and mortality risks, where TRI use was lower in those at highest risk. Operator variability with TRI was large. The incidences of bleeding, AKI, and death were higher with TFI versus TRI. The absolute risk difference between TRI and TFI increased with increasing baseline risk. The number needed to treat to prevent one adverse event with TRI (versus TFI) in low-, moderate- and high-risk groups, respectively, was 259, 82, and 32 for bleeding; 194, 53, and 40 for AKI; and 957, 78, and 18 for death.

Conclusions: This analysis of a large multicenter cohort of patients with PCI demonstrates a risk-treatment paradox for TRI use, not only for bleeding, but also for AKI and death. Despite this, a greater absolute risk difference favoring TRI was observed among patients with the highest baseline risk. Addressing the risk-treatment paradox by preferentially selecting TRI across the spectrum of risk, but especially high-risk cases, may be an important potential strategy for improving outcomes with PCI.

Keywords: acute kidney injury; hemorrhage; hospitals; incidence; percutaneous coronary intervention.

Purpose Tinnitus, or the perception of sounds that occur without an external sound source, is a prevalent condition worldwide. For a subset of adults, tinnitus causes significant distress and impairment. Several patient-reported outcome measures have been developed to assess severity of tinnitus distress. However, at present, the field lacks a brief measure that is sensitive to treatment change. The purpose of the current study was to develop and preliminarily validate a brief questionnaire for tinnitus severity from two existing measures of tinnitus-related distress, the Tinnitus Handicap Inventory (THI) and Tinnitus Functional Index (TFI). Method Using data from nine study samples in the United States and United Kingdom, we conducted exploratory and confirmatory factor analyses to identify a short measure with good psychometric properties. We also assessed sensitivity to treatment-related change by examining associations with change in the TFI and THI. Finally, we conducted a confirmatory factor analysis of the final short questionnaire in a new sample of adults seeking treatment for tinnitus-related distress. Results We identified 10 items from the THI and TFI that exhibited limited loadings on secondary factors. The resulting Tinnitus Severity Short Form achieved good to excellent fit, including in a unique sample of individuals seeking online treatment for tinnitus, and appeared sensitive to treatment-related change. Conclusions The Tinnitus Severity Short Form developed in the current study may be a useful tool for the assessment of subjective severity and distress associated with tinnitus, especially when patient burden is a concern. Further research is necessary to fully validate the questionnaire for the assessment of treatment-related change.

Objective: The Tilburg Frailty Instrument (TFI) is an instrument for assessing frailty in community-dwelling older people. Since its development, many studies have been carried out examining the psychometric properties. The aim of this study was to provide a review of the main findings with regard to the reliability and validity of the TFI.

Methods: We conducted a literature search in the PubMed and CINAHL databases on May 30, 2020. An inclusion criterion was the use of the entire TFI, part B, referring to the 15 components. No restrictions were placed on language or year of publication.

Results: In total, 27 studies reported about the psychometric properties of the TFI. By far, most of the studies (n = 25) were focused on community-dwelling older people. Many studies showed that the internal consistency and test-retest reliability are good, which also applies for the criterion and construct validity. In many studies, adverse outcomes of interest were disability, increased health-care utilization, lower quality of life, and mortality. Regarding disability, studies predominantly show results that are excellent, with an area under the curve (AUC) >0.80. In addition, the TFI showed good associations with lower quality of life and the findings concerning mortality were at least acceptable. However, the association of the TFI with some indicators of health-care utilization can be indicated as poor (eg, visits to a general practitioner, hospitalization).

Conclusion: Since population aging is occurring all over the world, it is important that the TFI is available and well known that it is a user-friendly instrument for assessing frailty and its psychometric properties being qualified as good. The findings of this assessment can support health-care professionals in selecting interventions to reduce frailty and delay its adverse outcomes, such as disability and lower quality of life.

Keywords: Tilburg Frailty Indicator; frailty; older people; reliability; validity.

Background: Transcranial Direct Current Stimulation (tDCS) aims to induce cortical plasticity by modulating the activity of brain structures. The broad stimulation pattern, which is one of the main limitations of tDCS, can be overcome with the recently developed technique called High-Definition tDCS (HD-tDCS).

Objective: Investigation of the effect of HD-tDCS on tinnitus in a large patient cohort.

Methods: This prospective study included 117 patients with chronic, subjective, non-pulsatile tinnitus who received six sessions of anodal HD-tDCS of the right Dorsolateral Prefrontal Cortex (DLPFC). Therapy effects were assessed by use of a set of standardized tinnitus questionnaires filled out at the pre-therapy (T_pre), post-therapy (T_3w) and follow-up visit (T_10w). Besides collecting the questionnaire data, the perceived effect (i.e., self-report) was also documented at T_10w.

Results: The Tinnitus Functional Index (TFI) and Tinnitus Questionnaire (TQ) total scores improved significantly over time (p_TFI<0.01; p_TQ<0.01), with the following significant post hoc comparisons: T_pre vs. T_10w (p_TFI<0.05; p_TQ<0.05) and T_3w vs. T_10w (p_TFI<0.01; p_TQ<0.01). The percentage of patients reporting an improvement of their tinnitus at T_10w was 47%. Further analysis revealed a significant effect of gender with female patients showing a larger improvement on the TFI and TQ (p_TFI<0.01; p_TQ<0.05).

Conclusions: The current study reported the effects of HD-tDCS in a large tinnitus population. HD-tDCS of the right DLPFC resulted in a significant improvement of the tinnitus perception, with a larger improvement for the female tinnitus patients.

Keywords: Gender; High-definition transcranial direct current stimulation (HD-tDCS); Large cohort; Neuromodulation; Non-invasive brain stimulation; Tinnitus; Transcranial direct current stimulation (tDCS); Treatment.

Background: Two validated German-language versions of the Tinnitus Functional Index (TFI) exist, one for Switzerland and one for Germany. The TFI is considered to be a possible new standard questionnaire for evaluation of tinnitus severity and tinnitus treatment.

Objective: Considering the standardization taking place in tinnitus evaluation, our aim was to compare the two German-language TFI versions and to recommend only one TFI version in the German-speaking area.

Materials and methods: The two German-language TFI versions were compared in a multicenter and randomized online questionnaire study with a crossover design.

Results: The total score of the two TFI versions did not differ in the total population. However, when further divided in terms of population and order of presentation of the TFI versions, there were significant differences in some cases, albeit with only moderate effect sizes. This suggests that the two versions are slightly different but still comparable. In factor analysis for the TFI version for Germany, in the entire population as well as in the Swiss population, six factors could be extracted. In contrast, for the German and Swiss TFI versions, only five factors could be extracted in the German population, and for the Swiss TFI version, only five factors in the Swiss population.

Conclusion: The two German-language versions of the TFI are well comparable with each other. However, the factor analysis rather argues for use of the TFI version for Germany in the entire German-speaking region.

Zusammenfassung: HINTERGRUND: Es existieren zwei deutschsprachige, validierte Versionen des Tinnitus Functional Index (TFI), eine für die Schweiz und eine für Deutschland. Der TFI gilt als möglicher neuer Standard-Fragebogen für die Evaluation eines Tinnitus-Schweregrads und einer Tinnitus-Therapie.

Ziel der arbeit: In Anbetracht der stattfindenden Standardisierung bei der Tinnitus-Evaluation war es unser Ziel, die beiden TFI-Versionen miteinander zu vergleichen und im deutschsprachigem Raum nur eine TFI-Version zu empfehlen.

Material und methoden: Die beiden deutschsprachigen TFI-Versionen wurden in einer multizentrischen randomisierten Online-Fragebogenstudie im Cross-over-Design miteinander verglichen.

Ergebnisse: Die Gesamtscores der beiden TFI-Versionen unterschieden sich in der gesamten Population nicht. Bei weiterer Aufschlüsselung in Bezug auf die Population und Reihenfolge der abgegeben TFI-Versionen zeigten sich allerdings teilweise signifikante Unterschiede mit jedoch nur moderaten Effektstärken. Dies deutet darauf hin, dass sich die beiden Versionen leicht unterscheiden, aber trotzdem miteinander vergleichbar sind. Bei der Faktoranalyse konnten bei der TFI-Version für Deutschland in der gesamten Population wie auch für die schweizerische Population 6 Faktoren extrahiert werden. Hingegen konnten bei der deutschen Population in beiden TFI-Versionen und bei der schweizerischen Population in der schweizerischen TFI-Version nur 5 Faktoren extrahiert werden.

Schlussfolgerung: Die beiden deutschsprachigen Versionen des TFI sind gut miteinander vergleichbar. Jedoch spricht die Faktoranalyse eher für die Verwendung der TFI-Version für Deutschland im gesamten deutschsprachigen Raum.

Keywords: Cross-cultural survey; Factor analysis; Questionnaire; TFI; Validation.

Purpose: To evaluate the influence of time from injury and meniscus tears on the side-to-side difference in anterior tibial translation (SSD-ATT) as measured on lateral monopodal weightbearing radiographs in both primary and secondary ACL deficiencies.

Methods: Data from 69 patients (43 males/26 females, median age 27-percentile 25-75: 20-37), were retrospectively extracted from their medical records. All had a primary or secondary ACL deficiency as confirmed by MRI and clinical examination, with a bilateral weightbearing radiograph of the knees at 15°-20° flexion available. Meniscal status was assessed on MRI images by a radiologist and an independent orthopaedic surgeon. ATT and posterior tibial slope (PTS) were measured on the lateral monopodal weightbearing radiographs for both the affected and the contralateral healthy side. A paired t-test was used to compare affected/healthy knees. Independent t-tests were used to compare primary/secondary ACL deficiencies, time from injury (TFI) (≤ 4 years/ > 4 years) and meniscal versus no meniscal tear.

Results: ATT of the affected side was significantly greater than the contralateral side (6.2 ± 4.4 mm vs 3.5 ± 2.8 mm; p < 0.01). There was moderate correlation between ATT and PTS in both the affected and healthy knees (r = 0.43, p < 0.01 and r = 0.41, p < 0.01). SSD-ATT was greater in secondary ACL deficiencies (4.7 ± 3.8 vs 1.9 ± 3.2 mm; p < 0.01), patients with a TFI greater than 4 years (4.2 ± 3.8 vs 2.0 ± 3.0 mm; p < 0.01) and with at least one meniscal tear (3.9 ± 3.8 vs 0.7 ± 2.2 mm; p < 0.01). Linear regression showed that, in primary ACL deficiencies, SSD-ATT was expected to increase (+ 2.7 mm) only if both a meniscal tear and a TFI > 4 years were present. In secondary ACL deficiencies, SSD-ATT was mainly influenced by the presence of meniscal tears regardless of the TFI.

Conclusion: SSD-ATT was significantly greater in secondary ACL deficiencies, patients with a TFI greater than 4 years and with at least one meniscal tear. These results confirm that SSD-ATT is a time- and meniscal-dependent parameter, supporting the concept of gradual sagittal decompensation in ACL-deficient knees, and point out the importance of the menisci as secondary restraints of the anterior knee laxity. Monopodal weightbearing radiographs may offer an easy and objective method for the follow-up of ACL-injured patients to identify early signs of soft tissue decompensation under loading conditions.

Level of evidence: Level III.

Keywords: ACL deficiency; Anterior tibial translation; Knee sagittal decompensation; Weightbearing radiographs.

Literature suggests that the occurrence of psychological trauma (PT) from various negative life experiences beyond events mentioned in the DSM-criterion A, receives little to no attention when comorbid with psychosis. In fact, despite research indicating the intricate interplay between PT and psychosis, and the need for trauma-focused interventions (TFI), there continue to be mixed views on whether treating PT would worsen psychosis, with many practitioners hesitating to initiate treatment for this reason. This study, therefore, aimed to understand patient perspectives on the role of PT in psychosis and related treatment options. A qualitative exploratory approach was adopted using in-depth interviews with individuals experiencing psychosis. The Global Assessment of Functioning (GAF) scale was administered on a predetermined maximum variation sample resulting in two groups of participants- those with moderate-mild disability (GAF 54-80; n = 10) and those experiencing moderate-severe disability (GAF 41-57; n = 10). With the former group, a semi-structured interview schedule was used, while with the latter, owing to multiple symptoms and difficulty in cognitive processing, a structured interview schedule was used. Results from interpretative phenomenological analysis (IPA) indicated that traumatic loss was central to experienced PT, but received no attention; this often contributed to the psychotic experience and/or depression, through maintenance factors such as cognitive distortions and attenuated affective responses. Further, the experience of loss seems to be more consequential to trauma-related symptoms than the event itself. Participants opined strongly the need for TFI and the role of it in promoting recovery from psychosis.

Retinoic acid (RA), an active metabolite of Vitamin A, and Bone Morphogenetic Protein 4 (BMP-4) pathways control the transcription of Proopiomelanocortin (POMC), the precursor of ACTH. We describe a novel mechanism by which RA and BMP-4 act together in the context of pituitary corticotroph tumoral cells to regulate POMC transcription. BMP-4 and RA exert a potentiated inhibition on POMC gene expression. This potentiation of the inhibitory action on POMC transcription was blocked by the inhibitory Smads of the BMP-4 pathway (Smad6 and Smad7), a negative regulator of BMP-4 signaling (Tob1) and a blocker of RA pathway (COUP-TFI). AtT-20 corticotrophinoma cells express RA receptors (RARβ, RXRα and RXRγ) which associate with factors of BMP-4 (Smad4 and Smad1) signaling cascade in transcriptional complexes that block POMC transcription. COUP-TFI and Tob1 disrupt these complexes. Deletions and mutations of the POMC promoter and a specific DNA binding assay show that the complexes bind to the RARE site in the POMC promoter. The enhanced inhibitory interaction between RA and BMP-4 pathways occurs also in another relevant corticotroph gene promoter, the Corticotropin-releasing hormone receptor 1 (CRH-R1). The understanding of the molecules that participate in the control of corticotroph gene expression contribute to define more precise targets for the treatment of corticotrophinomas.

The interaction of a single-chain variable fragment (scFv) directed against human tissue factor (TF) was predicted using an in silico approach with the aim to establish a most likely mechanism of inhibition. The structure of the TF inhibiting scFv (TFI-scFv) was predicted using homology modeling, and complementarity-determining regions (CDRs) were identified. The CDR was utilized to direct molecular docking between the homology model of TFI-scFv and the crystal structure of the extracellular domains of human tissue factor. The rigid-body docking model was refined by means of molecular dynamic (MD) simulations, and the most prevalent cluster was identified. MD simulations predicted improved interaction between TFI-scFv and TF and propose the formation of stable complex for duration of the 600-ns simulation. Analysis of the refined docking model suggests that the interactions between TFI-scFv would interfere with the allosterical activation of coagulation factor VII (FVII) by TF. This interaction would prevent the formation of the active TF:VIIa complex and in so doing inhibit the initiation phase of blood coagulation as observers during in vitro testing.

Combinations of two high-energy forage finishing diets and two initial body condition scores (BCSs) in a 2 × 2 factorial experimental design were evaluated on cull Holstein-Friesian (HF) cows to improve animal performance and carcass characteristics, aimed at achieving proper fatness and conformation scores (a minimum of '4' and 'O', respectively) required for the marketing of high-value loin steaks. The two finishing diets were (i) conventional maize silage complemented with concentrate diet and (ii) wet maize ear silage (pastone) complemented with dry-herbage diet. The two initial body condition levels were (i) low BCS < 5 (LBCS) and (ii) high BCS>> 5 (HBCS). The HBCS animals had the greatest potential to respond to the finishing diets. They needed a smaller total feed intake (TFI) and a shorter finishing period (FP) to meet the marketing requirements. The average feed budgets necessary to finish cull dairy cows and to achieve the minimum scores '4' and 'O' of carcass classification were 2.31 and 3.61 t of dry matter (DM)/cow for HBCS and LBCS animals, respectively, while the FP lasted an average of 143 and 224 days for HBCS and LBCS animals, respectively. With regard to the two feeding diets, we found no differences for TFI, carcass characteristics and loin muscle features, such as weight, diameter and intramuscular fat.

Background: Immunoassays based on label-free technologies (label-free immunoassay [LFIA]) offer an innovative approach to clinical diagnostics and demonstrate great promise for therapeutic drug monitoring (TDM) of monoclonal antibody (mAb) drugs. An LFIA measures immunocomplex formation in real time and allows for quantification on initial binding rate, which facilitates fast measurement within a few minutes.

Methods: Based on thin-film interferometry (TFI) technology, open-access LFIAs were developed for the quantification of the mAb drugs adalimumab (ADL) and infliximab (IFX) and for the detection of the antidrug antibodies (ADAs) to the mAb drugs (ADL-ADAs and IFX-ADAs).

Results: The LFIAs for active mAb drugs (ADL and IFX) and for ADAs (ADL-ADAs and IFX-ADAs) were validated. The analytical measurement range (AMR) for both ADL and IFX was from 2 to 100 μg/mL. The AMR for ADL-ADAs was from 5 to 100 μg/mL and for IFX-ADAs was 10 to 100 μg/mL. In the comparison of LFIAs and reporter gene assays, the correlation coefficient was 0.972 for the quantification of ADL and 0.940 for the quantification of IFX. The concordance rate was 90% for the detection of ADL-ADAs and 76% for the detection of IFX-ADAs.

Conclusions: The LFIAs for active mAb drugs and ADAs were appropriate for the TDM of ADL and IFX. The TFI technology has unique advantages compared with other technologies used for the measurement of mAb drugs. Label-free technologies, especially those allowing for open-access LFIAs, have great potential for clinical diagnostics.

Keywords: Adalimumab; Antidrug Antibodies; Inflximab; Label-Free Immunoassays; Monoclonal Antibody Drugs; Thin-Film Interferometry.

Objective: To predict mortality with the Tilburg Frailty Indicator (TFI) in a sample of community-dwelling older people, using a follow-up of 7 years.

Design: Longitudinal.

Setting and participants: 479 Dutch community-dwelling people aged 75 years or older.

Measurements: The TFI, a self-report questionnaire, was used to collect data about total, physical, psychological, and social frailty. The municipality of Roosendaal (a town in the Netherlands) provided the mortality dates.

Results: Total, physical, and psychological frailty predicted mortality, with unadjusted hazard ratios of 1.295, 1.168, and 1.194, and areas under the receiver operating characteristic curves of 0.664, 0.671, and 0.567, respectively. After adjustment for age and gender, the areas under the curves for total, physical, and psychological frailty were 0.704, 0.702, and 0.652, respectively. Analyses using individual components of the TFI show that difficulty in walking and unexplained weight loss predict mortality.

Conclusions and implications: This study has shown the predictive validity of the TFI for mortality in community-dwelling older people. Our study demonstrated that physical and psychological frailty predicted mortality. Of the individual TFI components, difficulty in walking consistently predicted mortality. For identifying frailty, using the integral instrument is recommended because total, physical, psychological, and social frailty and its components have proven their value in predicting adverse outcomes of frailty, for example, increase in health care use and a lower quality of life.

Keywords: Frailty; Tilburg Frailty Indicator (TFI); community-dwelling older people; mortality.

OBJECTIVE

Patients with cervical cancer recurrence after concurrent chemoradiotherapy (CCRT) who are not candidates for surgical resection or salvage radiotherapy have a dismal prognosis. The predictive factors for the effects of chemotherapy and prognostic factors in these patients were analyzed.

METHODS

We collected data for patients with recurrent cervical cancer who were primarily treated with CCRT between 2000 and 2013. Among them, 57 patients treated with only systemic chemotherapy were analyzed for the overall survival (OS), the overall response rate (ORR), and prognostic factors.

RESULTS

The median age was 47 years. Inside the irradiated field recurrence occurred in 24, outside in 20 and both in 13 patients. Time to recurrence after the CCRT (i.e., therapy-free interval; TFI) were <6 months in 11, 6-12 months in 15, ≥12 months in 23 patients, and persistent disease in 8 patients. The median OS was 18 months and ORR was 15.7%. Those with a longer TFI showed a tendency for better ORR (p = 0.051) and those receiving a taxane-containing regimen showed significantly higher ORR (p = 0.0232). Multivariate analysis revealed a significant correlation between the median OS and TFI (HR = 4.688, 95% CI = 2.178-11.10, p < 0.0001) and chemotherapy response (HR = 20.08, 95% CI = 3.936-368.4, p < 0.0001). Furthermore, even in patients with stable disease, the median OS increased corresponding to the length of the TFI (p < 0.0001).

CONCLUSIONS

TFI has predictive value for response to chemotherapy and prognosis of patients with recurrent cervical cancer after definitive CCRT.

OBJECTIVE

An important question is whether frailty syndrome affects the assessment of quality of life or whether frailty syndrome may reduce the benefits of a cardiac pacemaker implantation.

BACKGROUND

Frailty syndrome is known risk factor for quality of life evaluation after selected cardiology invasive procedures.

METHODS

The study was designed as single-centre prospective study.

METHODS

The study included 171 patients aged ≥60 years who were qualified for pacemaker implantation. Quality of life was evaluated twice-before and 6 months after implantation using MLHF questionnaire. A frailty syndrome evaluation using the Tilburg Frailty Indicator (TFI) was performed prior to pacemaker implantation. A DDDR pacemaker was implanted in each patient.

RESULTS

Frailty syndrome was identified in half of the patients with indications for cardiac pacemaker implantation. There was an improvement in quality of life in the six months after pacemaker implantation in all of the robust and frailty syndrome-affected patients that were included into the study-in general, physical and emotional domains.

CONCLUSIONS

Implantation of cardiac pacemaker influences the compensation quality of life evaluation in patients with sinus node dysfunction. Presence of frailty influences worse quality of life of patients when evaluated before cardiac pacemaker implantation.

CONCLUSIONS

Frailty should be evaluated in all older patients qualified for pacemaker implantation to evaluate high-risk group, optimise therapeutic approach and to intense education activities for patients and family.