Low Sensitivity Group Research Articles

Central Visual Field Sensitivity With and Without Background Light Given to the Nontested Fellow Eye in Glaucoma Patients.

This study showed the difference of monocular visual sensitivity between with and without background light given to the nontested fellow eyes in glaucoma patients. Monocular sensitivity measurements of the worse eyes with fellow eye's background light conditions should carefully be considered when assessing the impact of functional impairment in glaucoma patients. The purpose of this study was to investigate the difference between monocular sensitivities measured with and without background light given to the nontested fellow eye in glaucoma patients using a new perimeter named "imo." In this cross-sectional study, we examined 102 eyes of 51 patients (mean age, 65.1±14.9 y) with open-angle glaucoma who were affected with at least 1 significant point in the central 10 degrees. We conducted a routine ophthalmic examination and visual field testing using the Humphrey Field Analyzer 24-2 and 10-2 programs. The eyes were assigned to "better" and "worse" categories based on the visual acuity and central visual thresholding. Subsequently, we compared the central visual sensitivities with and without background light given to the nontested fellow eye. The mean sensitivity (MS) in the central 5 points of the visual field of the worse eyes was better when measured with background light than without background light (P=0.037) given to the nontested fellow eye. No significant difference was seen among the MS in the visual field of the better eyes. After dividing the patients into low (n=25) and high sensitivity (n=26) groups, only the low sensitivity group in worse eyes had higher MS with background light than without background light (P<0.05) given to the nontested fellow eye. Monocular sensitivities measured with background light given to the nontested fellow eye were higher than those without background light in the worse eye group of glaucoma patients. Monocular MS measurements of the worse eyes with fellow eye's background light conditions and their related indices should thus carefully be considered when assessing the impact of functional impairment in glaucoma patients.

Testing the theory of Differential Susceptibility to nightmares: The interaction of Sensory Processing Sensitivity with the relationship of low mental wellbeing to nightmare frequency and nightmare distress.

Propensity to have nightmares has been theorised in terms of diathesis-stress models, with this propensity being seen as negative or even pathological. In contrast, a recent model proposes that nightmare propensity is due to Differential Susceptibility to stimuli, where high susceptibility can be beneficial in positive environments but detrimental in negative environments. This susceptibility to stimuli is assessed as the biobehavioural trait Sensory Processing Sensitivity, which refers to a greater responsivity to internal and external stimuli, and an increased depth of cognitive and emotional processing. To test the Differential Susceptibility Framework for nightmares, 137 participants (females=104, males=33; mean age=33.66 years), recruited from a student population and social media sites, were divided into high (n=39), medium (n=59) and low (n=39) Sensory Processing Sensitivity categories based on their score on the Highly Sensitive Person Scale. Low mental wellbeing and the presence of minor psychiatric problems, measured by the General Health Questionnaire, was found to be significantly correlated with nightmare frequency for the high and medium SPS groups (rs=.29 and .28, respectively), but not for the low Sensory Processing Sensitivity group (r=.19). General Health Questionnaire score was also significantly correlated with trait nightmare distress, for the high Sensory Processing Sensitivity group only (r=.32). These findings in favour of the Differential Susceptibility Framework have aetiology and treatment implications for nightmares that differ from diathesis-stress models.

The Splicing Modulator GEX1A Exhibits Potent Anti-Leukemic Activity Both in Vitro and In Vivo through Inducing an MCL1 Splice-Switch in Pre-Clinical Models of Acute Myeloid Leukemia

Background: Overexpression of anti-apoptotic proteins such as Bcl-2, Bcl-xL and Mcl1 is commonly detected in acute myeloid leukemia (AML) and is correlated with poor patient prognosis. Fortunately, in most AML samples, the expression of pro-apoptotic proteins, including Bax, Bak and Bim, is also increased. This is likely due to a feedback mechanism, which results in AML cells that are particularly vulnerable to treatment with targeted inhibition of anti-apoptotic proteins. However, challenges arise when the important pro-survival proteins named above are either poorly targeted by specific inhibitors (such as BH3-mimetics), as in the case of Mcl1, or when the use of these inhibitors results in severe thrombocytopenia, as in the case of Bcl-xL. Therefore, the development of novel medications to target such molecules with high specificity and low toxicity is of crucial importance. GEX1A, a splicing modulator, induces a large shift in the pattern of exon skipping and intron retention events by inhibiting the SF3B1-PHF5A complex of the U2 snRNP. While GEX1A has shown pre-clinical efficacy in some carcinoma cell lines containing various spiceosomal mutations, the in vitro and in vivo effects of GEX1A in leukemic cells which lack spiceosomal mutations are largely unknown. Experimental procedures: The IC50 of 18 established AML cell lines was determined by treating the cells with GEX1A in vitro using a series of 10-fold dilutions; cell viability was then examined using quantitative colorimetric assays. The in vivo anti-leukemic efficacy of GEX1A was evaluated using xenograft models generated in NSG mice injected with the GEX1A-sensitive human AML cell lines KOPN8, Molm-13, and MV4:11. The molecular mechanism by which GEX1A kills AML cells was then studied. Results: Based on their IC50, 18 established leukemic cell lines can be divided into high (LD50 &lt; 100 nM), moderate (LD50 = 100-500 nM), and low sensitivity (LD50 &gt; 500 nM) groups. We next determined the tolerable dose of GEX1A for in vivo mouse treatment. Intraperitoneal injection of GEX1A significantly improved the survival of leukemic mice compared to the vehicle control group (see Figure). Mechanistically, we found that GEX1A kills leukemic cells by inducing the production of pro-apoptotic Mcl1-S protein at the expense of the pro-survival Mcl1-L protein due to the alternative splicing of the Mcl1 gene. In addition, we found that high levels of Bcl-xL protein predict resistance of leukemic cells to GEX1A treatment. Furthermore, synergistic activity was observed in 2/6 cell lines treated with GEX1A and ABT-263, an inhibitor of Bcl-2/Bcl-xL/Bcl-w, and 6/6 cell lines treated with GEX1A and A-1155463, a highly potent Bcl-xL inhibitor. Conclusion: GEX1A is a novel splicing modulator that shows potent anti-leukemic activity. GEX1A kills leukemic cells by inducing a splicing isoform switch of the Mcl1 gene to produce a pro-apoptotic Mcl1-S protein at the expense of the pro-survival Mcl1-L protein in such cells. GEX1A and a Bcl-xL-specific inhibitor were also combined to show synergistic effects on leukemic cells. Our results indicate that GEX1A may be an effective treatment for leukemic patients when combined with a specific Bcl-xL inhibitor. We are actively evaluating our combination treatment using primary patient samples in in vivo xenograft models. Disclosures No relevant conflicts of interest to declare.

How sensory sensitivity to graininess could be measured?

Considering the lack of the literature and the need for developing a valid method to measure the texture sensitivity, in this study, we investigated the individual sensitivity to discriminate among different levels of graininess. With this purpose, five samples of cocoa-based creams were prepared, by changing the refining time. Samples were first characterized in terms of particles size distribution, by means of laser diffraction. Then, 59 subjects evaluated the cream sample graininess intensity, by using gLM scales, and their liking, by using LAM scales. The graininess scores of each subject were fitted with a power model, already observed with the instrumental results, estimating both the power law exponent and the R2 coefficient, and using them as clustering parameters. Subjects were then clustered into three groups: high sensitivity; moderate sensitivity; low sensitivity. First, as it was hypothesized, results showed a significant difference between the three groups in terms of perceived graininess. Second, even though results showed a significant difference between the three groups in terms of perceived graininess, only little differences were found in terms of liking scores. Indeed, all the samples were equally liked for both the moderate and low sensitivity groups, whereas a significant trend was observed for the highly sensitive subjects who liked more the most refined samples. No significant relationships were found with age, and only a little trend was observed with gender: females seemed to be more sensitive than males. Texture attributes discrimination ability, as for example sensitivity to graininess, could affect food rejection or preferences and choice, but it is poorly investigated. This exploratory study, proposes a method to cluster consumers, based on their sensitivity. A statistical methodology has been developed to discriminate among consumer sensitivity levels. The results provide useful information about graininess sensitivity suggesting that the used methodologies could be applied to other texture properties resulting in a valid tool for the industry in the development and optimization of tailored new products.

Top-down and bottom-up mechanisms as reflected by beta and gamma oscillations in speech perception: An individual-difference approach

Recent neurophysiological studies have proposed distinct roles of β and γ oscillations in implementing top-down and bottom-up processes. The present study aims to test this hypothesis in the domain of speech perception. We examined β and γ oscillations elicited to a tone contrast in a passive oddball paradigm, and their relationships with discrimination sensitivity d′ and RT from two groups of healthy adults who showed high and low discrimination sensitivity to the contrast. The low-sensitivity group showed a significant reduction in β, which was further related to d′. Individual differences in RT were related to different frequency bands in the two groups, with a RT-β correlation in the low-sensitivity group, and a RT-γ relation in the high-sensitivity group. Based on these findings, we suggest that β, implicated in top-down processing, reflects individual differences in phonological representations, and that γ, involved in bottom-up processing, reflects individual differences in acoustic encoding.

The effect of oral tactile sensitivity on texture perception and mastication behavior.

Mastication is a notable source of interindividual variation in texture perception and could be linked to oral tactile sensitivity. To better understand the influence of oral tactile sensitivity on mastication behavior, this study measured masticatory behavior and texture discrimination in participants of high (n = 20) and low (n = 21) oral tactile sensitivity. Overall, there was no significant difference between high and low sensitivity participants in their ability to distinguish texture changes (p = .486). However, there were significant differences found between the groups based on their masticatory behaviors including chewing pattern and overall number of chewing cycles. Additionally, those in the high sensitivity group used more stochastic chewing movements, while those in the low sensitivity group were found to use crescent-shaped chewing cycles. It was also noted that in the high sensitivity group, the jaw moved further distances in all phases and moved at a higher velocity when opening but not when closing, when compared to the low sensitivity group. These results show what particular aspects of mastication are most influenced by oral tactile feedback. Chewing patterns have been shown to influence texture and flavor perception, as well as energy intake. However, much of the person-to-person variability in chewing patters comes from unknown sources. This study shows which chewing behaviors are different between a group of individuals with high oral tactile sensitivity and another with low oral tactile sensitivity. These findings highlight the manner in which tactile feedback from the mouth influences chewing.

Oral somatosensatory acuity is related to particle size perception in chocolate

Texture affects liking or rejection of many foods for clinically relevant populations and the general public. Phenotypic differences in chemosensation are well documented and influence food choices, but oral touch perception is less understood. Here, we used chocolate as a model food to explore texture perception, specifically grittiness perception. In Experiment 1, the Just Noticeable Difference (JND) for particle size in melted chocolate was ~5 μm in a particle size range commonly found in commercial chocolates; as expected, the JND increased with particle size, with a Weber Fraction of ~0.17. In Experiment 2, individual differences in touch perception were explored: detection and discrimination thresholds for oral point pressure were determined with Von Frey Hairs. Discrimination thresholds varied across individuals, allowing us to separate participants into high and low sensitivity groups. Across all participants, two solid commercial chocolates (with particle sizes of 19 and 26 μm; i.e., just above the JND) were successfully discriminated in a forced-choice task. However, this was driven entirely by individuals with better oral acuity: 17 of 20 of more acute individuals correctly identified the grittier chocolate versus 12 of 24 less acute individuals. This suggests phenotypic differences in oral somatosensation can influence texture perception of foods.

Abstract P4-13-09: Sequential second line endocrine therapy is still an effective strategy for postmenopausal ER+ and HER2- advanced breast cancer with low sensitivity to initial endocrine therapy

Abstract Background:It is unclear how to define responsiveness to endocrine therapy (ET) during the clinical course of advanced breast cancer (ABC), especially in evaluation of the effect of sequential ET. Objective:The goal of the study was to evaluate the efficacy of second line treatment of physician's choice (2nd-line TPC) for estrogen receptor-positive (ER+) and HER2-negative postmenopausal ABC with very low or low sensitivity to initial ET. Methods:A multicenter prospective observational cohort study was performed for 2nd-line TPCs. ABC with low sensitivity to initial ET was defined as recurrence within 5 years (yrs) during adjuvant ET or progression within 9 months (mo.) of initial ET. Similarly, ABC with very low sensitivity to initial ET was defined as recurrence within 2 yrs during adjuvant ET or progression within 3 mo. of initial ET. The expected clinical benefit rate (CBR: defined as patients who achieved CR, PR or SD for 24 weeks) was 50%. The null hypothesis of a CBR of 30% was tested with a one-sided α of 5%. 90% confidence intervals (CIs) were calculated for hypothesis tests. Results: A total of 56 patients (pts) were enrolled, but 7 were ineligible and one discontinued before starting the protocol treatment. The median age was 66 yrs (range: 41-88) and the median BMI was 23.4 kg/m2 (16.4-31.9). All pts were ER+ and 80% were PgR+. Most of pts had a baseline PS of 0 or 1, 90% had invasive ductal carcinoma, and 10% had invasive lobular carcinoma. Postoperative recurrence was detected in 84% and these pts had a median duration of adjuvant ET of 30.5 mo. (5.3-58.9). De novo stage IV ABC was present in 16%, with a median duration of first-line ET of 5 mo. (2.3-10.8). Adjuvant chemotherapy including anthracycline- and/or a taxane-containing regimen was administered in 58% (29/49). As adjuvant ET before initial recurrence, 34 pts received non-steroidal aromatase inhibitors (AIs) (88.0%), 1 received a steroidal AI (2.3%), and 3 received a selective estrogen receptor modulator (SERM). As first line ET in de novo stage IV, 7 pts (14%) were treated with AIs or a SERM (1 case). 2nd-line TPCs were also used, with 40 pts receiving fulvestrant (82%), 5 receiving SERMs (10%), 3 receiving a mTOR inhibitor plus a steroidal AI (6%), and one patient receiving an AI alone. The overall CBR was 44.9% (90% CI: 34.6-57.6, p=0.009), and CBR was similar across following subgroups (PgR+: n=39, 51.3%, 90% CI: 39.6-65.2, p=0.0016; very low sensitivity group: n=17, 58.8%, 90% CI: 42.0-78.8, p=0.003; non-visceral metastases: n=25, 40%, 90% CI; 34.1-65.9, p=0.0175). However, there were not statistically significant CBR in PgR- (n=10, 20.0%, 90% CI; 8.73-50.7, p=0.617), fulvestrant subgroup (n=40, 40.0 %, 90% CI; 29.2-54.2, p=0.063), low sensitive group (n=32, 37.5%, 90% CI; 26.0-53.6, p=0.1326), and visceral metastases (n=24, 48%, 90%CI; 28.2-60.3 p=0.072). The median PFS was 7.1 mo. (95% CI: 5.6-10.6). Conclusion:This study shows that 2nd line ETs was effective and might be a valid option in the sequence of treatments for postmenopausal women with ABC with low sensitivity to initial ET. It was suggested that PgR and visceral metastasis were significant predictive factors for CBR. Citation Format: Araki K, Fujisawa T, Sakamaki K, Kikawa Y, Iwamoto T, Sangai T, Shien T, Takao S, Nishimura R, Takahashi M, Aihara T, Mukai H, Taira N. Sequential second line endocrine therapy is still an effective strategy for postmenopausal ER+ and HER2- advanced breast cancer with low sensitivity to initial endocrine therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-13-09.

Clinical Predictive Factors for the Efficacy of Everolimus in Patients With Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer: A Multicenter Retrospective Cohort Study in Japan.

Purpose:To investigate the clinical predictive factors for the efficacy of everolimus (EVE) for advanced/metastatic breast cancer (AMBC).Methods:Routine practice data of consecutive patients with AMBC who received EVE at 5 institutions in western Japan were retrospectively analyzed in this cohort study (study registration no.: UMIN 000032569). The correlation among time to treatment failure (TTF), overall survival (OS), and clinical background was investigated via univariate and multivariate analyses using Cox hazards model for the clinically important variables.Results:A total of 134 patients were included in the analysis. The median TTF and OS were 5.2 months (95% confidence interval [CI]: 4.1-6.4) and 27.3 months (95% CI: 23.7-30.9), respectively. Multivariate analysis showed that dose reduction of EVE from any initial dose was associated with a longer TTF (hazard ratio [HR]: 0.52; 95% CI: 0.32-0.84, P = .007). Meanwhile, very low hormone sensitivity (ie, relapse within the first 2 years during adjuvant endocrine therapy or progression within 3 months of endocrine therapy immediately before EVE) was associated with a shorter TTF (HR: 2.48; 95% CI: 1.49-4.10, P < .001). In the analysis of stratified treatment outcomes, TTF was longer in the group with <3 liver metastases and in groups other than the very low hormone sensitivity group, regardless of the treatment line of EVE.Conclusions:Low hormone sensitivity and ⩾3 liver metastases were important prognostic factors for the efficacy of EVE. EVE may be less effective in patients with AMBC with these factors, and as such, chemotherapy should be administered instead.

Prediction of running-induced Achilles tendinopathy with pain sensitivity - a 1-year prospective study.

Background and aims Achilles tendinopathy is common among runners, but the etiology remains unclear. High mechanical pain sensitivity may be a predictor of increased risk of developing Achilles tendinopathy in this group. The purpose of this study was to investigate whether local pain sensitivity could predict the development of Achilles tendinopathy in recreational male runners. The overall hypothesis was that high pain sensitivity would be related to a higher risk of developing Achilles tendinopathy among recreational male runners. Methods Ninety-nine recreational male runners were recruited and followed prospectively for 1 year. At baseline and after 500 km of running the pressure pain threshold (PPT) was assessed at the infraspinatus and at the Achilles tendon (AT-PPT). Based on the AT-PPT at baseline, a median split was used to divide the runners into two groups. The high pain sensitivity groups was defined as runners displaying a pain pressure threshold below 441 kPa on the Achilles tendon, while the low pain sensitivity group was defined as runners displaying a pain pressure threshold above 441 kPa on the Achilles tendon, respectively. Subsequently, the cumulative risk difference between the two groups was assessed by using the pseudo-observation method. Results High pain sensitivity runners sustained 5%-point (95% CI: -0.18 to 0.08) more Achilles tendinopathy episodes during the first 1,500 km. No significant group differences in risk were found at 100, 250, 500, 1,000 and 1,500 km of running. Conclusions No significant association was found between mechanical pain sensitivity in the Achilles tendon and the risk of developing Achilles tendinopathy. However, the risk difference indicated a association between a high mechanical pain sensitivity and an increased risk of developing Achilles tendinopathy. It is plausible that changes in pain sensitivity were masked by unmeasured covariates, such as the differences in progression/regression of training volume and running speed between the two groups. This study was limited in size, which limited the possibility to account for covariates, such as differences in progression/regression of running speed between runners. With the limitations in mind, future studies should control the training volume, speed and running shoes in the design or account for it in the analysis. Implications Pain sensitivity of the Achilles tendon seems not to be related to an increased risk of developing Achilles pain in relation to running.

Effects of noise sensitivity on psychophysiological responses to building noise

The present study aims to explore the effects of noise sensitivity on psychophysiological responses to floor impact noises and road traffic noise. A standard impact source (i.e. an impact ball) and two real impact sources (i.e. an adult's walking and a child's running) were used to record floor impact noises, while road traffic noise was introduced as an outdoor noise stimulus. A total of 34 subjects were recruited based on their self-rated noise sensitivity and classified into low and high noise sensitivity groups. During the laboratory experiments, all the noise stimuli were presented for 5 min each, and the subjects rated their annoyance with each stimulus at the end of each session. Their physiological responses (heart rate: HR, electrodermal activity: EDA, and respiratory rate: RR) were measured throughout the experiment. The obtained noise annoyance ratings increased with increasing noise levels for all the sources, and the high noise sensitivity group exhibited higher annoyance ratings than the low noise sensitivity group. All physiological measures varied significantly with the duration of noise exposure. In particular, the EDA and RR values decreased sharply after 30 s, demonstrating strong habituation over time. Noise sensitivity was found to significantly affect physiological responses, whereas noise levels showed no significant influence.

High-dose 8% capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy: single-center experience

High-dose capsaicin patch is effective in treatment of neuropathic pain in HIV-associated neuropathy and diabetic neuropathy. There are no studies assessing effectiveness of high-dose capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy. We sought to determine the effectiveness of treatment of pain associated with chemotherapy-induced peripheral neuropathy with high-dose capsaicin patch. Our study group consisted of 18 patients with clinically confirmed oxaliplatin-induced neuropathy. Baseline characteristic including underling disease, received cumulative dose of neurotoxic agent, neuropathic symptoms, prior treatment and initial pain level were recorded. Pain was evaluated with Numeric Rating Scale prior to treatment with high-dose capsaicin and after 1.8 day and after 8 and 12 weeks after introducing treatment. Patients were divided into two groups accordingly to the amount of neurotoxic agent that caused neuropathy (high sensitivity and low sensitivity group). Most frequent symptoms of chemotherapy-induced neuropathy were: pain (88.89%), paresthesis (100%), sock and gloves sensation (100%) and hypoesthesis (100%). Initial pain level was 7.45 ± 1.14. Mean cumulative dose of oxaliplatin after which patients developed symptoms was 648.07 mg/m2. Mean pain level after 12 weeks of treatment was 0.20 ± 0.41. When examined according to high and low sensitivity to neurotoxic agent patients with low sensitivity had higher pain reduction, especially after 8 days after introducing treatment (69.55 ± 12.09 vs. 49.40 ± 20.34%; p = 0.02) and after 12 weeks (96.96 ± 5.56 vs. 83.93 ± 18.59%; p = 0.04). High-dose capsaicin patch is an effective treatment for pain associated with chemotherapy-induced neuropathy in patients treated with oxaliplatin. Patients with lower sensitivity to neurotoxic agents have better response to treatment and pain reduction.

Increased postural stiffness in patients with knee osteoarthritis who are highly sensitized

Abstract Aims To evaluate the effect of widespread pain sensitization on postural stability during quiet standing tasks in patients with knee osteoarthritis. Methods Patients (56) stood quietly on a force platform for 1 min in 4 conditions (each repeated 3 times): (i) firm surface (FS) with open eyes (OE), (ii) FS with closed eyes (CE), (iii) soft foam surface (SS) with OE, and (iv) SS with CE. Postural stability was quantified by Center of Pressure (CoP) variables extracted from the force platform. Pressure pain thresholds (PPTs), were assessed bilaterally with a handheld pressure algometer (1 cm2 probe) at: (i) four sites in the knee region (3 cm medial to the midpoint of the medial edge of the patella; 2 cm proximal to the superior edge of the patella; 3 cm lateral to the mid-point of the lateral edge of the patella; and centre of the patella), (ii) tibialis anterior muscle, and (iii) extensor carpi radialis longus muscle. The PPT values from tibialis anterior and extensor carpi radialis longus muscles were used to divide the patients in high and low sensitization groups (two-steps clustering). Results PPT values at bilateral knees sites were lower in the high sensitivity [median (range) of all sites: 423 (153, 1129) kPa] compared with low sensitivity group [822 (305, 2051) kPa] (P &lt; 0.05). CoP range in the anterior–posterior direction was reduced in high sensitivity group (41±16 mm) compared with the low sensitivity group (51±16 mm) during the SS with CE (P &lt; 0.05) condition. Conclusions The lower CoP Range suggests stiffer postural strategy in patients with higher widespread pain sensitivity compared with low sensitivity patients during sensory restrictions. The lack of mobility found in high sensitivity patients under such restrictions might be related to the impaired integration of sensory information due to the parallel processing of the nociceptive information.

Quantification of Oral Roughness Perception and Comparison with Mechanism of Astringency Perception.

Texture contributes to food acceptance, but oral texture perception is incompletely understood. Presently, we quantified individual sensitivities to lingual tactile roughness and assessed the impact of age, salivary flow (SF), and fungiform papillae density (FPD) on threshold and suprathreshold perception. Additionally, we tested the hypothesis that individuals highly sensitive to tactile roughness exhibit sensitivity to astringent stimuli. Detection thresholds (DTs) were determined using the staircase method for surface roughness from stainless steel coupons (Ra; 0.177-0.465 µm) and astringency elicited by epigallocatechin gallate (EGCG; 0-1.64 mM) and tannic acid (TA; 0-0.71 mM) from 30 individuals. Suprathreshold sensitivity was assessed from intensity ratings of electroforming comparator surfaces with roughnesses ranging from 0.51 to 22.8 µm and astringent stimuli ranging from 0 to 5.2 mM (EGCG) and from 0 to 1.9 mM (TA). SF, FPD, and astringent food pleasantness scores were collected. Variability in threshold roughness sensitivity enabled dividing subjects into high (RHi; n = 16) and low (RLo; n = 14) sensitivity groups; however, no significant differences in age, FPD, or SF were observed across these cohorts. Interestingly, compared with RLo, the RHi group exhibited greater sensitivity to EGCG but not TA astringency and indicated greater pleasantness from astringent foods (e.g., unripe bananas and dark chocolate). When participants were allocated into high (SalivaHi; n = 15) or low SF (SalivaLo; n = 15) groups, TA-evoked astringency thresholds were significantly lower in SalivaHi whom also indicated greater pleasantness from astringent red wines. For suprathreshold assessments of surface roughness or astringency, no significant associations were identified with age, FPD, or SF. Suprathreshold roughness sensitivity was, however, associated with suprathreshold sensitivity to EGCG but not TA astringency.

Relative Effects of Sensory Modalities and Importance of Fatty Acid Sensitivity on Fat Perception in a Real Food Model

IntroductionFat can be perceived through mouthfeel, odour and taste, but the influence of these modalities on fat perception remains undefined. Fatty acids are stimuli and individual sensitivity to fatty acids varies. Studies show association between fatty acid sensitivity, dietary intake and BMI, but results are conflicting. Therefore, this study examined this association, and the effect of modalities on fat perception.MethodsTwo sub-studies were conducted. In study 1 (n = 46), fat intensity was assessed by milk/cream mixtures varying by five fat levels. Fat intensity was rated under four conditions: mouthfeel odour-masked, mouthfeel-masked, odour masked and with no masking. Mouthfeel masking was achieved using thickener and paraffin, odour masking using nose-clips. Fatty acid sensitivity was measured by 3-AFC staircase method using milk containing oleic acid (0.31–31.4 mM). In study 2 (n = 51), more fat levels were added into the intensity rating. A 2-AFC discrimination test was used to confirm whether fat levels could be distinguished. In the sensitivity test, a wider range of oleic acid was included. ResultsFat intensity was rated higher without nose clips (p < 0.0001), implying that odour increased fat perception. Mouthfeel-masked samples were rated higher, showing that increased viscosity and lubricity enhanced fat perception (p < 0.0001). Participants could distinguish fat levels based on “taste” in rating tests and 2-AFC tests. Participants were divided into high-/medium-/low-sensitivity groups. No significant difference was found in fat intensity between groups; however, the high-sensitivity group discriminated more fat levels. No association between sensitivity groups, nutrient intake or BMI was found.ConclusionMouthfeel and odour can enhance fat perception. Fat level can be discriminated based on taste.Electronic supplementary materialThe online version of this article (doi:10.1007/s12078-016-9211-5) contains supplementary material, which is available to authorized users.

Children exposed to intimate partner violence: Identifying differential effects of family environment on children's trauma and psychopathology symptoms through regression mixture models

The majority of analytic approaches aimed at understanding the influence of environmental context on children's socioemotional adjustment assume comparable effects of contextual risk and protective factors for all children. Using self-reported data from 289 maternal caregiver-child dyads, we examined the degree to which there are differential effects of severity of intimate partner violence (IPV) exposure, yearly household income, and number of children in the family on posttraumatic stress symptoms (PTS) and psychopathology symptoms (i.e., internalizing and externalizing problems) among school-age children between the ages of 7–12 years. A regression mixture model identified three latent classes that were primarily distinguished by differential effects of IPV exposure severity on PTS and psychopathology symptoms: (1) asymptomatic with low sensitivity to environmental factors (66% of children), (2) maladjusted with moderate sensitivity (24%), and (3) highly maladjusted with high sensitivity (10%). Children with mothers who had higher levels of education were more likely to be in the maladjusted with moderate sensitivity group than the asymptomatic with low sensitivity group. Latino children were less likely to be in both maladjusted groups compared to the asymptomatic group. Overall, the findings suggest differential effects of family environmental factors on PTS and psychopathology symptoms among children exposed to IPV. Implications for research and practice are discussed.

Determinants of altered intracellular endocrine-immune interplay in Bosnian war refugees suffering from PTSD

Posttraumatic Stress Disorder (PTSD) has been repeatedly linked to changes in glucocorticoid (GC) sensitivity. To increase our understanding of this phenomenon and its potential relevance for PTSD development and treatment, the current study investigates the interplay between two key moderators, glucocorticoid receptor (GRα) and GR co-chaperone FKBP5, and their relation to GC sensitivity.A GC sensitivity assay was performed in 52 Bosnian war refugees (19m; 40.8±8.7 years) clinically diagnosed with PTSD to divide the patient group into a high (HS) and a low (LS) GC sensitivity group. Expression of GRα and FKBP5 mRNA was quantified by real-time RT-PCR.Links between gene expression and GC sensitivity were driven by the HS group of PTSD patients, which also showed increased expression of GRα but not FKBP5 compared to the LS group. Further, expressions of FKBP5 and GRα were strongly correlated in the HS patient group, while this association was missing in the LS PTSD group.Our findings suggest that PTSD phenotypes may be characterized by differences in intracellular signaling transduction processes. The associations of expression of GRα and FKBP5 in the high-sensitive PTSD subgroup may thereby reflect physiological adaptation to preserve immune-relevant GC signaling. Further research is needed to understand the role and consequences of GRα-FKBP5 dissociation in low GC sensitivity PTSD patients.

Association Between Meibomian Gland Testing and Ocular Surface Sensitivity.

To assess whether corneal sensitivity is associated with clinical tests assessing the tear film and meibomian glands. Subjects were recruited based on the history of contact lens wear and the extent of meibomian gland dropout. Clinical examination included assessment of symptoms, redness of the lower eyelid margin, lipid layer thickness, esthesiometry of the inferior cornea and palpebral conjunctiva, noninvasive tear breakup time, Schirmer test assessment, and meibomian gland assessment through orifice count and expressed meibum quality grade. Subjects were grouped into a high corneal sensitivity (HS) group or low corneal sensitivity (LS) group, based on the median sensitivity measure. Groups for palpebral conjunctival sensitivity were created in the same manner. Mann-Whitney U tests were used for comparisons of sensitivity groups, and a Spearman rho correlation coefficient was used to study the associations between each tear film characteristic and the sensitivities. Fifty-seven subjects with an average age of 34.7 years (SD = 15.1) were included in the analysis, of which 63.2% were female. The median corneal and conjunctival thresholds for sensation were 0.5 and 1.4 g/mm, respectively. The average noninvasive tear breakup time [HS: 7.8 seconds [interquartile range (IQR) = 5.7]; LS: 11.6 seconds (IQR = 8.4); P = 0.05] and Schirmer test assessments [HS: 16.0 mm (IQR = 15.0); LS: 25.0 mm (IQR = 19.0); P = 0.04] were significantly different between the palpebral conjunctival HS and LS groups. All other group comparisons and correlations were not statistically significant. The palpebral conjunctival sensitivity may be more critical than the corneal sensitivity when assessing dry eye.

Factors affecting platinum sensitivity in cervical cancer.

The present study aimed to investigate the association between nedaplatin (NDP) sensitivity and the expression of biological factors in cervical cancer. A total of 45 cervical cancer specimens, including 18 pretreatment biopsies and 27 surgical specimens, were used in histoculture drug response assays to determine the chemosensitivity of cervical cancer specimens to NDP. Each specimen was assessed for immunohistochemical expression of Ki-67, p53, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3, cyclooxygenase-2 (COX-2), and excision repair cross-complementation group 1 (ERCC1). The results revealed that low or negative expression of p53, Bcl-2 and COX-2, and high or positive expression of cleaved caspase-3 were significantly correlated with high sensitivity to NDP. However, there were no significant differences in Ki-67, Bax or ERCC1 expression between the low and high sensitivity groups. These findings indicate that sensitivity to platinum may be easily predicted by immunostaining for the detection of these specific factors in pretreatment biopsies or surgical specimens. The expression profiles of these targets may therefore provide additional information for planning individualized chemotherapy in the treatment of cervical cancer.

Cortical hyperexcitability and sensitivity to discomfort glare

It is well established that there are two main aspects to glare, the visual impairment and the discomfort, known as disability and discomfort glare, respectively. In contrast to the case of disability glare we understand very little about the underlying mechanisms or physiology of discomfort glare. This study attempts to elucidate the neural mechanisms involved using fMRI and glare sources with controlled levels of retinal illuminance. Prior to carrying out the fMRI experiment, we determined each participant's discomfort glare threshold. The participants were then divided into two groups of equal size based on their ranked sensitivity to discomfort glare, a low and high sensitivity group. In the fMRI experiment each participant was presented with three levels of glare intensity whilst simultaneously required to carry out a simple behavioral task. We compared BOLD responses between the two groups and found that the group more sensitive to glare had an increased response that was localized at three discrete, bilateral cortical locations: one in the cunei, one in the lingual gyri and one in the superior parietal lobules. This increased response was present for all light levels tested, whether or not they were intense enough to cause discomfort glare. Based on the results, we present the case that discomfort glare may be a response to hyperexcitability or saturation of visual neurons.