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Three experiments investigated 4-, 6-, and 8-month-old infants' perception of the audible, visible, and combined attributes of bimodally specified syllables. Ninety-six infants in each experiment were habituated to a person mouthing and uttering a syllable and then tested for detection of changes of either the audible, visible, or combined attributes of the syllable. When the attributes of the syllable were produced in an adult-directed manner, all three age groups discriminated the audible and bimodal attribute changes but only the 8-month-olds discriminated the visible one. When the difference between the familiar and novel attributes of the syllable was enhanced by testing with a novel syllable produced in an infant-directed manner, all three age groups detected all three types of changes. Finally, to test the possible role of audiovisual synchrony in responsiveness, infants were tested with an asynchronous syllable spoken either by the same person or by a novel person following habituation to a synchronous syllable. Results suggested that at four months infants attended primarily to the featural information, at six months primarily to the asynchrony, and at eight months to both features independently. These results help identify some of the important dimensions of multimodal speech during early development. [ABSTRACT FROM AUTHOR]

Adenomatosis is a rare lesion of unknown etiology, defined as multiple (usually 5 or more) adenomas in one kidney. A case of renal adenomatosis in a 68-year-old woman treated previously for urolithiasis, who underwent nephrectomy because of the nonfunctional left kidney is reported. Apart from multiple adenomas, numerous hyperplastic lesions involving single tubules were present in the resected kidney. Both adenomas and hyperplastic lesions exhibited the expression of alpha-methylacyl-coenzyme A racemase (AMACR). Renal adenomatosis is worth special attention, since renal papillary adenomas are suggested as precursor lesions of papillary renal cell carcinoma that show similar AMACR expression.

Xanthogranulomatous inflammation of the urethra and the urinary bladder is a very rare pathological condition characterized by a chronic inflammatory infiltration composed mainly of foamy macrophages, with the presence of multinucleated giant cells. In a clinical examination, it can mimic urinary bladder carcinoma. This report presents the extremely rare case of a co-existing xanthogranulomatous urethritis and cystitis in a 64-year-old woman with recurrent dysuria, and with the suspicion of malignancy - as indicated on the basis of a cystoscopic examination. The standard treatment of this disorder is surgical resection, but in the presented case, only a diagnostic biopsy was performed. Because of the persistence of clinical symptoms, a cystoscopic examination and biopsy was repeated three times in a two year period. There was no malignancy seen in the repeated biopsies.

Few studies have evaluated cytokeratin's (CK) staining patterns in atypical endometrial hyperplasia (AEH) coexisting with early-stage endometrial cancer (EC). We aimed to assess the staining patterns of selected CKs (CK7, CK19, CK20, CK AE1/AE3) in 74 patients with coexisting AEH and EC by independently analyzing both morphological variables. Specimens were collected from women with AEH and EC who underwent surgical interventions between 2012 and 2019 at the Department of Obstetrics and Gynecology of Vilnius University Hospital "Santaros Klinikos" in Vilnius, Lithuania. Immunostaining was also qualitatively classified as being heterogeneous or intense. The results revealed heterogeneous CK7 expression in all AEH cases and intense staining in 95.95% cases of AEH. The heterogeneous expression of CK7 was detected in all EC specimens. Intense CK7 expression was observed in 95.09% cases of EC G1 and in all G2 ECs. Heterogenous CK19 expression was present in all AEH specimens with intense staining in 92.42% of cases. Heterogeneous CK19 expression was observed in all EC samples with intense expression in 86.27% cases of EC G1 and 100% cases of EC G2. Interestingly, a significant relationship was found when comparing the heterogeneous expression of CK19 between AEH and well-differentiated EC. A significant difference was reported in the intense expression of CK AE1/AE3 ( p = 0.031; p = 0.029) between AEH and G2 ECs and in the intense expression of CK AE1/AE3 between G1 and G2 ECs. CK20 staining was not a characteristic feature for AEH and early-stage EC. CK staining is present either in AEH or in early-stage endometrioid-subtype EC in different manners. Heterogeneous CK19 expression was significantly more common in AEH than in EC. CK20 expression was not associated with either AEH nor early-stage EC. An intense expression of CK AE1/AE3 was mainly present in moderately differentiated ECs, whereas the intense reactivity of AE1/AE3 showed a significant difference in well to moderately differentiated uterine tumors. The clinical implication of CK staining may aid in the more accurate diagnosis of AEH and early-stage EC as well as detect micrometastases leading to better oncological outcomes.

Low-grade appendiceal mucinous neoplasm (LAMN) is a tumor that primarily originates from the appendix and belongs to the family of appendiceal mucinous neoplasms (AMNs). In 50% of female patients, AMNs (particularly LAMNs) have a tendency to metastasize to organs in the genital tract, where the neoplasm can mimic the features of primary ovarian mucinous cancer (POMC). The present case report reviewed the difficulties in differentiating between these two types of tumors. In the present case report, a 61-year-old female patient was admitted to the Second Department of Gynecological Surgery and Gynecological Oncology, University Clinical Hospital no. 4 at Lublin Medical University (Lublin, Poland) with the diagnosis of a right ovarian mass. After performing ultrasound and computed tomography (CT) scans and laboratory analysis, the patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, appendectomy and resection of the Douglas peritoneum. Notably, the postoperative pathological assessment revealed LAMN with metastases to the right ovary and omentum. Immunohistochemically, cytokeratin 20 and caudal type homeobox 2 both stained positively, whereas paired box gene 8 stained negatively. After surgery, the patient received the recommended hyperthermic intraperitoneal chemotherapy at the Department of Surgical Oncology at Lublin Medical University. After 1 year, a CT scan was performed, which indicated no evidence of recurrent disease. In conclusion, observations from the present case report suggest that gynecologists should be conscious of the possibility of malignancies of gastrointestinal origin in cases of ovarian tumors instead of making direct assumptions of POMC. If the mucinous mass involves the base of the appendix or if there is a suspicion of positive margins, then cytoreductive surgery and right-sided hemicolectomy must be performed. In addition, identifying the origin of mucinous tumors in the right ovary and/or the appendix requires the histopathological examination of a panel of markers using immunohistochemistry., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Kawecka et al.)

Background: Digital therapeutic care (DTC) programs are unsupervised app-based treatments that provide video exercises and educational material to patients with nonspecific low back pain during episodes of pain and functional disability. German statutory health insurance can reimburse DTC programs since 2019, but evidence on efficacy and reasonable pricing remains scarce. This paper presents a probabilistic sensitivity analysis (PSA) to evaluate the efficacy and cost-utility of a DTC app against treatment as usual (TAU) in Germany., Objective: The aim of this study was to perform a PSA in the form of a Monte Carlo simulation based on the deterministic base case analysis to account for model assumptions and parameter uncertainty. We also intend to explore to what extent the results in this probabilistic analysis differ from the results in the base case analysis and to what extent a shortage of outcome data concerning quality-of-life (QoL) metrics impacts the overall results., Methods: The PSA builds upon a state-transition Markov chain with a 4-week cycle length over a model time horizon of 3 years from a recently published deterministic cost-utility analysis. A Monte Carlo simulation with 10,000 iterations and a cohort size of 10,000 was employed to evaluate the cost-utility from a societal perspective. Quality-adjusted life years (QALYs) were derived from Veterans RAND 6-Dimension (VR-6D) and Short-Form 6-Dimension (SF-6D) single utility scores. Finally, we also simulated reducing the price for a 3-month app prescription to analyze at which price threshold DTC would result in being the dominant strategy over TAU in Germany., Results: The Monte Carlo simulation yielded on average a €135.97 (a currency exchange rate of EUR €1=US $1.069 is applicable) incremental cost and 0.004 incremental QALYs per person and year for the unsupervised DTC app strategy compared to in-person physiotherapy in Germany. The corresponding incremental cost-utility ratio (ICUR) amounts to an additional €34,315.19 per additional QALY. DTC yielded more QALYs in 54.96% of the iterations. DTC dominates TAU in 24.04% of the iterations for QALYs. Reducing the app price in the simulation from currently €239.96 to €164.61 for a 3-month prescription could yield a negative ICUR and thus make DTC the dominant strategy, even though the estimated probability of DTC being more effective than TAU is only 54.96%., Conclusions: Decision-makers should be cautious when considering the reimbursement of DTC apps since no significant treatment effect was found, and the probability of cost-effectiveness remains below 60% even for an infinite willingness-to-pay threshold. More app-based studies involving the utilization of QoL outcome parameters are urgently needed to account for the low and limited precision of the available QoL input parameters, which are crucial to making profound recommendations concerning the cost-utility of novel apps., (©Daniel Lewkowicz, Erwin Bottinger, Martin Siegel. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 29.06.2023.)

Background: Due to familial liability, siblings of children with ASD exhibit elevated risk for language delays. The processes contributing to language delays in this population remain unclear., Methods: Considering well-established links between attention to dynamic audiovisual cues inherent in a speaker's face and speech processing, we investigated if attention to a speaker's face and mouth differs in 12-month-old infants at high familial risk for ASD but without ASD diagnosis (hr-sib; n = 91) and in infants at low familial risk (lr-sib; n = 62) for ASD and whether attention at 12 months predicts language outcomes at 18 months., Results: At 12 months, hr-sib and lr-sib infants did not differ in attention to face (p = .14), mouth preference (p = .30), or in receptive and expressive language scores (p = .36, p = .33). At 18 months, the hr-sib infants had lower receptive (p = .01) but not expressive (p = .84) language scores than the lr-sib infants. In the lr-sib infants, greater attention to the face (p = .022) and a mouth preference (p = .025) contributed to better language outcomes at 18 months. In the hr-sib infants, neither attention to the face nor a mouth preference was associated with language outcomes at 18 months., Conclusions: Unlike low-risk infants, high-risk infants do not appear to benefit from audiovisual prosodic and speech cues in the service of language acquisition despite intact attention to these cues. We propose that impaired processing of audiovisual cues may constitute the link between genetic risk factors and poor language outcomes observed across the autism risk spectrum and may represent a promising endophenotype in autism., (© 2022 Association for Child and Adolescent Mental Health.)

In the scientific literature, a selected number of reports have investigated the impact of proliferative activity on the development and progression of uterine carcinosarcomas (UC). The aim of the present retrospective study was to compare the immunohistochemical proliferation markers [Ki67, proliferating cell nuclear antigen (PCNA), minichromosome maintenance complex component 3 (MCM3), and topoisomerase IIα (topoIIα)] assessment in both components of UC. A total of 30 paraffin-embedded slides of UCs, obtained from patients who underwent surgery between January 1, 2006, and December 31, 2020, were analyzed. Medical records and clinicopathological data of patients were reviewed. Formalin-fixed, paraffin-embedded tissue sections were immunostained with monoclonal antibodies against Ki67, PCNA, MCM3 and topoIIα. Ki67-positive nuclear immunoreactivity was reported in 20 (67%) and 16 (53%) UC carcinomatous and sarcomatous components, respectively. In the epithelial component, Ki67 positive staining was related to the International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.025), and histological grade (G1 vs. G2/G3, P=0.031). Nuclear PCNA reactivity was observed in 18 (60%) and 16 (53%) carcinomatous and sarcomatous components, respectively. Notably, all four cases with omental metastases were PCNA-positive, and a relationship between staining pattern and the existence of metastases was of significant value (P=0.018). MCM3-positive nuclear staining was found nearly twice as high in the carcinomatous (n=19; 63%), compared with the sarcomatous (n=11; 37%) component, respectively, and MCM3 expression in the epithelial component was related to clinical stage (P=0.030), and the existence of omental metastasis (P=0.012). In addition, out of the 30 UCs, 17 (57%) and 13 (43%) showed topoIIα positivity in the carcinomatous and sarcomatous UC components, respectively. A significant relationship between protein immunoreactivity and FIGO stage (P=0.049), and omental metastasis (P=0.026) was revealed to exist. However, no significant differences between expression of proliferation markers and clinicopathological features in the sarcomatous UC component were identified. Finally, a significant correlation between each protein immunohistochemical staining was demonstrated, particularly in the sarcomatous UC component. Collectively, a combined analysis of Ki67, PCNA, MCM3, and topoIIα may provide more detailed information of cell-cycle alterations determining the heterogeneity of uterine carcinosarcomas., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Pyra et al.)

Cytokeratins (CKs) are the largest subgroup of intermediate filament proteins, preferentially expressed in epithelial tissues. CKs play a critical role in determining epithelial structural integrity under stressful conditions in addition to their various fundamental functions in cellular proliferation, apoptosis, migration, adherence and molecular signaling. Immunohistochemical CKs staining could be evaluated with a proper comprehension of their task limitations and their association with the normal morphology to avoid misdiagnosis. Herein, we critically review the CKs expression patterns in ECs in relation to clinicopathological features and patients' outcome. We also briefly discussed the recent advantage of CKs immunohistochemical staining in the detection of EC micrometastasis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Digital therapeutic care apps provide a new effective and scalable approach for people with nonspecific low back pain (LBP). Digital therapeutic care apps are also driven by personalized decision-support interventions that support the user in self-managing LBP, and may induce prolonged behavior change to reduce the frequency and intensity of pain episodes. However, these therapeutic apps are associated with high attrition rates, and the initial prescription cost is higher than that of face-to-face physiotherapy. In Germany, digital therapeutic care apps are now being reimbursed by statutory health insurance; however, price targets and cost-driving factors for the formation of the reimbursement rate remain unexplored., Objective: The aim of this study was to evaluate the cost-effectiveness of a digital therapeutic care app compared to treatment as usual (TAU) in Germany. We further aimed to explore under which circumstances the reimbursement rate could be modified to consider value-based pricing., Methods: We developed a state-transition Markov model based on a best-practice analysis of prior LBP-related decision-analytic models, and evaluated the cost utility of a digital therapeutic care app compared to TAU in Germany. Based on a 3-year time horizon, we simulated the incremental cost and quality-adjusted life years (QALYs) for people with nonacute LBP from the societal perspective. In the deterministic sensitivity and scenario analyses, we focused on diverging attrition rates and app cost to assess our model's robustness and conditions for changing the reimbursement rate. All costs are reported in Euro (€1=US $1.12)., Results: Our base case results indicated that the digital therapeutic care strategy led to an incremental cost of €121.59, but also generated 0.0221 additional QALYs compared to the TAU strategy, with an estimated incremental cost-effectiveness ratio (ICER) of €5486 per QALY. The sensitivity analysis revealed that the reimbursement rate and the capability of digital therapeutic care to prevent reoccurring LBP episodes have a significant impact on the ICER. At the same time, the other parameters remained unaffected and thus supported the robustness of our model. In the scenario analysis, the different model time horizons and attrition rates strongly influenced the economic outcome. Reducing the cost of the app to €99 per 3 months or decreasing the app's attrition rate resulted in digital therapeutic care being significantly less costly with more generated QALYs, and is thus considered to be the dominant strategy over TAU., Conclusions: The current reimbursement rate for a digital therapeutic care app in the statutory health insurance can be considered a cost-effective measure compared to TAU. The app's attrition rate and effect on the patient's prolonged behavior change essentially influence the settlement of an appropriate reimbursement rate. Future value-based pricing targets should focus on additional outcome parameters besides pain intensity and functional disability by including attrition rates and the app's long-term effect on quality of life., (©Daniel Lewkowicz, Attila M Wohlbrandt, Erwin Bottinger. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 07.02.2022.)

Background: Low back pain (LBP) is the leading cause of worldwide years lost because of disability, with a tremendous economic burden for health care systems. Digital therapeutic care (DTC) programs provide a scalable, universally accessible, and low-cost approach to the multidisciplinary treatment of LBP. Moreover, novel decision support interventions such as personalized feedback messages, push notifications, and data-driven activity recommendations amplify DTC by guiding the user through the program while aiming to increase overall engagement and sustainable behavior change., Objective: This systematic review aims to synthesize recent scientific literature on the impact of DTC apps for people with LBP and outline the implementation of add-on decision support interventions, including their effect on user retention and attrition rates., Methods: We searched bibliographic databases, including MEDLINE, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database, from March 1, 2016, to October 15, 2020, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and conducted this review based on related previously published systematic reviews. Besides randomized controlled trials (RCTs), we also included study designs with the evidence level of at least a retrospective comparative study. This enables the consideration of real-world user-generated data and provides information regarding the adoption and effectiveness of DTC apps in a real-life setting. For the appraisal of the risk of bias, we used the Risk of Bias 2 Tool and the Risk of Bias in Non-Randomized Studies of Interventions Tool for the RCTs and nonrandomized trials, respectively. The included studies were narratively synthesized regarding primary and secondary outcome measures, DTC components, applied decision support interventions, user retention, and attrition rates., Results: We retrieved 1388 citations, of which 12 studies are included in this review. Of the 12 studies, 6 (50%) were RCTs and 6 (50%) were nonrandomized trials. In all included studies, lower pain levels and increased functionality compared with baseline values were observed in the DTC intervention group. A between-group comparison revealed significant improvements in pain and functionality levels in 67% (4/6) of the RCTs. The study population was mostly homogeneous, with predominantly female, young to middle-aged participants of normal to moderate weight. The methodological quality assessment revealed moderate to high risks of biases, especially in the nonrandomized trials., Conclusions: This systematic review demonstrates the benefits of DTC for people with LBP. There is also evidence that decision support interventions benefit overall engagement with the app and increase participants' ability to self-manage their recovery process. Finally, including retrospective evaluation studies of real-world user-generated data in future systematic reviews of digital health intervention trials can reveal new insights into the benefits, challenges, and real-life adoption of DTC programs., (©Daniel Lewkowicz, Tamara Slosarek, Sarah Wernicke, Antonia Winne, Attila M Wohlbrandt, Erwin Bottinger. Originally published in JMIR Rehabilitation and Assistive Technology (https://rehab.jmir.org), 19.11.2021.)

Background: Unnecessary healthcare utilization, non-adherence to current clinical guidelines, or insufficient personalized care are perpetual challenges and remain potential major cost-drivers for healthcare systems around the world. Implementing decision support systems into clinical care is promised to improve quality of care and thereby yield substantial effects on reducing healthcare expenditure. In this article, we evaluate the economic impact of clinical decision support (CDS) interventions based on electronic health records (EHR)., Methods: We searched for studies published after 2014 using MEDLINE, CENTRAL, WEB OF SCIENCE, EBSCO, and TUFTS CEA registry databases that encompass an economic evaluation or consider cost outcome measures of EHR based CDS interventions. Thereupon, we identified best practice application areas and categorized the investigated interventions according to an existing taxonomy of front-end CDS tools., Results and Discussion: Twenty-seven studies are investigated in this review. Of those, twenty-two studies indicate a reduction of healthcare expenditure after implementing an EHR based CDS system, especially towards prevalent application areas, such as unnecessary laboratory testing, duplicate order entry, efficient transfusion practice, or reduction of antibiotic prescriptions. On the contrary, order facilitators and undiscovered malfunctions revealed to be threats and could lead to new cost drivers in healthcare. While high upfront and maintenance costs of CDS systems are a worldwide implementation barrier, most studies do not consider implementation cost. Finally, four included economic evaluation studies report mixed monetary outcome results and thus highlight the importance of further high-quality economic evaluations for these CDS systems., Conclusion: Current research studies lack consideration of comparative cost-outcome metrics as well as detailed cost components in their analyses. Nonetheless, the positive economic impact of EHR based CDS interventions is highly promising, especially with regard to reducing waste in healthcare.

Children with autism spectrum disorder (ASD) display differences in multisensory function as quantified by several different measures. This study estimated the stability of variables derived from commonly used measures of multisensory function in school-aged children with ASD. Participants completed: a simultaneity judgment task for audiovisual speech, tasks designed to elicit the McGurk effect, listening-in-noise tasks, electroencephalographic recordings, and eye-tracking tasks. Results indicate the stability of indices derived from tasks tapping multisensory processing is variable. These findings have important implications for measurement in future research. Averaging scores across repeated observations will often be required to obtain acceptably stable estimates and, thus, to increase the likelihood of detecting effects of interest, as it relates to multisensory processing in children with ASD., (©AAIDD.)

Planning a sequence of two motor elements is much more than concatenating two independent movements. However, very little is known about the cognitive strategies that are used to perform fluent sequences for intentional object manipulation. In this series of studies, the participants' task was to reach for and pick to place a wooden cylinder to set it on a place pad of three different diameters, which served to modify terminal accuracy constraints. Participants were required to perform the sequences (1) at their preferred speed or (2) as fast as possible. Action kinematics were recorded with the Qualisys motion-capture system in order to implement a real-time protocol to get participants to engage in a true interactive relation. Results revealed that with low internal constraints (at preferred speed), low coupling between the two elements of the motor sequence was observed, suggesting a step-by-step planning strategy. Under high constraints (at fastest speed), an important terminal accuracy effect back propagated to modify early kinematic parameters of the first element, suggesting strong coupling of the parameters in an encapsulated planning strategy. In Studies 2 and 3, we further manipulated instructions and timing constraints to confirm the importance of time and predictability of external information for coupled planning. These findings overall sustain the hypothesis that coupled planning can take place in a pick and place task when anticipatory strategies are possible. This mode of action planning may be the key reason why motor intention can be read through the observation of micro variations in body kinematics.

Young girls before menarche or menstruating adolescent women may experience long-term drug-resistant chronic pelvic pain, as well as other symptoms associated with pelvic mass. In such cases, it is of great importance to consider ovarian endometrioma in the differential diagnosis. In general, endometrioma is recognized as an ovarian cyst. However, in most cases, the pathology represents pseudocyst with a partial or complete endometrial-like lining with extraovarian adhesions and endometriotic implants which are likely to occur at the sites of ovarian adhesions and at the ceiling of the ovarian fossa. Ovarian endometriomas occur in 17-44% patients with endometriosis and account for 35% of all benign ovarian cysts. The time span from the onset of menarche to the time of endometrioma formation, which requires surgical intervention, has been evaluated to be a minimum of 4 years. The pathogenesis of early-life endometrioma may be different from other types of endometriosis. Diagnosis is often delayed, especially in adolescents, who tend to wait too long before seeking professional help. The three specific aims of treatment in adolescents with endometriosis and endometriomas are control of symptoms, prevention of further progression of the disease as well as preservation of fertility. Increasing evidence demonstrates association between ovarian endometriosis and ovarian cancer. In the present mini-review, we draw the particular attention of clinicians to such a possibility, even if relatively infrequently reported.

Background: The expression of p53 has been studied not only in primary human ovarian carcinomas, but also in borderline ovarian tumors, however, the results were discordant. Expression patterns of proteins involved in cell proliferation and apoptosis have been investigated in various human neoplasms, including female genital tract neoplasms., Objective: The aim of this investigation was to assess the staining pattern and immunolocalization of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors (BOTs)., Design: The study group consisted of 42 women who underwent pelvic surgery between 2006-2015. The median patients' age was 46 years. The immunoperoxidase technique was employed using antibodies against p53, Ki-67, MCM3, PCNA, and topoisomerase IIα., Results: For p53, nuclear expression was observed in BOTs, however, cytoplasmatic immunoreactivity was also detected. Altogether, 25 (60%) tumors demonstrated positive p53 immunostaining, including overexpression found in 6 (14%). There were no significant differences in p53 expression between subgroups of clinicopathological variables. Immunoexpression of Ki-67, MCM3, PCNA, and topoisomerase IIα was nuclear. Ki-67 expression was positive in 12 (29%) cases and there was a trend towards a relationship between patients' age and Ki-67 staining (P=0.08). Interestingly, a significantly higher Ki-67 expression was found in tumors of ≥10 cm in diameter compared to smaller tumors (P=0.008). MCM3 expression was detected in 38 (90%) tumors, and PCNA expression in 28 (67%), yet none of clinicopathological factors was related to them. Topoisomerase IIα expression was present in 14 (33%) cases and, interestingly, its significantly higher expression was observed in BOTs of ≥10 cm in diameter compared to smaller tumors (P=0.008). Moreover, Spearman's correlation revealed highly significant positive associations between Ki-67 and topoisomerase IIα (R=0.403, P=0.008) and Ki-67 and MCM3 (R=0.469, P=0.001)., Conclusions: We report a high positive immunostaining rate for p53, suggesting a role of TP53 alterations in the development of BOTs in humans. The new finding of higher topoisomerase IIα immunostaining positivity in BOTs of ≥10 cm may be clinically relevant and requires further studies on larger patient groups.

Aims: The aim of the study was to compare emotional information processing in patients with severe alcohol use disorder in short-term abstinence (<1 month) and long-term abstinence (at least 6 months to 9 years) with control participants., Methods: We studied the variation in pupil diameter during the presentation of pictures of human interactions associated with positive, negative or neutral valences., Results: Overall, the results of the short-term abstinent group revealed greater pupil dilation regardless of the valence of the pictures while the pupillary response of long-term abstainers did not differ from the control group. More specifically, according to each valence, the pupil response to neutral pictures was greater for both patient groups than for controls. For the long-term abstainers, a negative correlation was found between the length of abstinence and the pupillary response to emotional stimuli., Conclusion: In long-term abstainers group, the high activation by neutral stimuli suggests however some difficulties in the processing of nonemotional stimuli, considered emotional ones and may constitute a potential relapse factor or the maintenance of addiction., (© The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

We present here a toolbox for the real-time motion capture of biological movements that runs in the cross-platform MATLAB environment (The MathWorks, Inc., Natick, MA). It provides instantaneous processing of the 3-D movement coordinates of up to 20 markers at a single instant. Available functions include (1) the setting of reference positions, areas, and trajectories of interest; (2) recording of the 3-D coordinates for each marker over the trial duration; and (3) the detection of events to use as triggers for external reinforcers (e.g., lights, sounds, or odors). Through fast online communication between the hardware controller and RTMocap, automatic trial selection is possible by means of either a preset or an adaptive criterion. Rapid preprocessing of signals is also provided, which includes artifact rejection, filtering, spline interpolation, and averaging. A key example is detailed, and three typical variations are developed (1) to provide a clear understanding of the importance of real-time control for 3-D motion in cognitive sciences and (2) to present users with simple lines of code that can be used as starting points for customizing experiments using the simple MATLAB syntax. RTMocap is freely available (http://sites.google.com/site/RTMocap/) under the GNU public license for noncommercial use and open-source development, together with sample data and extensive documentation.

As social animals, it is crucial to understand others' intention. But is it possible to detect social intention in two actions that have the exact same motor goal? In the present study, we presented participants with video clips of an individual reaching for and grasping an object to either use it (personal trial) or to give his partner the opportunity to use it (social trial). In Experiment 1, the ability of naïve participants to classify correctly social trials through simple observation of short video clips was tested. In addition, detection levels were analyzed as a function of individual scores in psychological questionnaires of motor imagery, visual imagery, and social cognition. Results revealed that the between-participant heterogeneity in the ability to distinguish social from personal actions was predicted by the social skill abilities. A second experiment was then conducted to assess what predictive mechanism could contribute to the detection of social intention. Video clips were sliced and normalized to control for either the reaction times (RTs) or/and the movement times (MTs) of the grasping action. Tested in a second group of participants, results showed that the detection of social intention relies on the variation of both RT and MT that are implicitly perceived in the grasping action. The ability to use implicitly these motor deviants for action-outcome understanding would be the key to intuitive social interaction.

Adenoma malignum (AM), also referred to as "minimal deviation adenocarcinoma", is an extremely uncommon variant of highly-differentiated adenocarcinoma of the uterine cervix. The study presented herein describes a case of uterine AM found out after hysteroscopy. An early-stage, well-differentiated mucinous uterine adenocarcinoma was diagnosed post-operatively. A subsequent immunohistochemical assessment of a panel of antibodies was applied, in order to distinguish between female genital tract malignancies.

Purpose. To review the clinical outcome of patients with hypertensive uveitis. Methods. Retrospective review of uveitis patients with elevated intraocular pressure (IOP) > 25 mmHg and >1-year follow-up. Data are uveitis type, etiology, viral (VU) and nonviral uveitis (NVU), IOP, and medical and/or surgical treatment. Results. In 61 patients, IOP values are first 32.9 mmHg (SD: 9.0), highest 36.6 mmHg (SD: 9.9), 3 months after the first episode 19.54 mmHg (SD: 9.16), and end of follow-up 15.5 mmHg (SD: 6.24). Patients with VU (n = 25) were older (50.6 y/35.7 y, p = 0.014) and had more unilateral disease (100%/72.22%  p = 0.004) than those with NVU (n = 36). Thirty patients (49.2%) had an elevated IOP before topical corticosteroid treatment. Patients with viral uveitis might have higher first elevated IOP (36.0/27.5 mmHg, p = 0,008) and maximal IOP (40.28/34.06 mmHg, p = 0.0148) but this was not significant when limited to the measurements before the use of topical corticosteroids (p = 0.260 and 0.160). Glaucoma occurred in 15 patients (24.59%) and was suspected in 11 (18.03%) without difference in viral and nonviral groups (p = 0.774). Conclusion. Patients with VU were older and had more unilateral hypertensive uveitis. Glaucoma frequently complicates hypertensive uveitis. Half of the patients had an elevated IOP before topical corticosteroid treatment.

Optimal control models of biological movements are used to account for those internal variables that constrain voluntary goal-directed actions. They, however, do not take into account external environmental constraints as those associated to social intention. We investigated here the effects of the social context on kinematic characteristics of sequential actions consisting in placing an object on an initial pad (preparatory action) before reaching and grasping as fast as possible the object to move it to another location (main action). Reach-to-grasp actions were performed either in an isolated condition or in the presence of a partner (audience effect), located in the near or far space (effect of shared reachable space), and who could intervene on the object in a systematic fashion (effect of social intention effect) or not (effect of social uncertainty). Results showed an absence of audience effect but nevertheless an influence of the social context both on the main and the preparatory actions. In particular, a "localized" effect of shared reachable space was observed on the main action, which was smoother when performed within the reachable space of the partner. Furthermore, a "global" effect of social uncertainty was observed on both actions with faster and jerkier movements. Finally, social intention affected the preparatory action with higher wrist displacements and slower movements when the object was placed for the partner rather than placed for self-use. Overall, these results demonstrate specific effects of action space, social uncertainty and social intention on the planning of reach-to-grasp actions, in particular on the preparatory action, which was performed with no specific execution constraint. These findings underline the importance of considering the social context in optimal models of action control for human-robot interactions, in particular when focusing on the implementation of motor parameters required to afford intuitive interactions.

Unlabelled: Glomus tumors, especially multiple ones, are uncommon skin and soft tissue neoplasms occasionally seen in various internal organs. Involvement of the external genital organs including penis is extremely rare, and until now, scarce cases have been reported in the available literature., Materials and Methods: A routine histologic and immunohistochemical staining for pan-muscle actin, α-smooth muscle actin, desmin, CD31, and CD34 was applied for diagnosis of the lesions., Results: Three soft, bluish, and tender tumors localized on the ventral aspect of the glans penis in a 9-year-old boy were found. Furthermore, 3 other lesions situated on the fingers and the plantar surface of the foot were later sequentially noted. Local excisions of all tumors were performed, and glomangiomas were diagnosed based on typical microscopic features as well as immunohistochemical findings, that is, positive immunoexpression for actin but negative for desmin, CD31, and CD34. No recurrence was noted during the 5-year follow-up., Conclusions: On the basis of our experience, conservative surgical procedure is sufficient for penile glomus tumors. However, each patient should be carefully examined for possible extragenital lesions.

Cyclooxygenase inhibitors (COX) are a complex group of pharmacological compounds characterized by significant efficacy in chemoprevention of epithelial origin tumors, especially colorectal ones. It was found that inducible isoform of COX - COX-2 plays an important role in cancer growth and dissemination, e.g., by increase of cellular proliferation, reduction of apoptosis, promotion of local invasiveness and angiogenesis. COX inhibitors decrease prostaglandins' synthesis, but COX-independent mechanisms of their preventive and therapeutical activity were also proven. The influence of COX inhibitors on growth of esophageal squamous cell carcinoma and its precursor lesions was not completely clear. Most studies based on human cancer cell lines revealed antiproliferative and proapoptotic ability of both nonselective (previously called non-steroidal antiinflammatory drugs--NSAIDs) and selective COX-2 inhibitors (coxibs). In in vivo studies performed on animals exposed to chemical carcinogens, the chemopreventive effect was achieved exclusively after administration of experimental selective COX-2 inhibitors, but in the only human trial, supplementation of selective COX-2 inhibitor--celecoxib turned out ineffective. However, many epidemiological data proved effect of prolonged administration of nonselective COX inhibitors, especially acetylsalicylic acid on decreased risk of esophageal squamous cell carcinoma. Few reports concerning application of selective COX-2 inhibitors in patients with invasive squamous cell carcinoma are insufficient for ultimate evaluation of this method of therapy.

Routine examinations during chemotherapy containing anthracyclines evaluate heart function before treatment and monitor cardiotoxic effects during and after therapy. A number of methods are useful in cardiac assessment, including electrocardiography, radiology techniques (RTG, CT, MRI,PET-CT, PET-MRI), echocardiography, radioisotope imaging techniques (scintigraphy, MUGA,PET), and ultra-structure evaluation in biopsy samples. Nevertheless, there is a continuous need for new methods to predict future damage at the initial stages of cardiac changes. In recent years the therapeutic usefulness of biochemical blood parameters in anthracycline-treated patients has been assessed. The levels of cardiac troponins (cTnI, cTnT), natriuretic peptides (ANP, BNP), and endothelin 1 have been included in the studies. Heart-type fatty acid binding protein (H-FABP) is another promising factor showing cardiomyocytic impairment. However, the clinical use of biochemical parameters in diagnosing anthracycline-related cardiotoxicity is still a controversial issue.

Psoriasis and psoriatic arthritis (PsA) are not uncommon among the pediatric population. Recognizing and treating these chronic disorders in children present unique challenges for the dermatologist. Paucity of clinical trials and a dearth of available treatment modalities, many of which carry significant risk or adverse effects, can make treating pediatric psoriasis and PsA a daunting task. This review attempts to define and consolidate the current state of knowledge with regards to this disease spectrum. The need for further clinical trials to investigate treatment options in the pediatric population is also discussed., (Copyright 2004 Blackwell Publishing, Inc.)

Objectives: Given the increasingly common use of complementary medicine in cancer patients, we tested the in vitro cytotoxicity of aqueous extracts of 15 traditional Chinese herbs with purported anticancer properties on ovarian and breast cancer cell lines., Methods: Cell viability after treatment with herbal extract was measured by metabolism of a tetrazolium substrate. Apoptosis was measured by nuclear and DNA fragmentation and Annexin V binding., Results: One herb, Herba Scutellaria barbatae, was cytotoxic to 100% (11 of 11) of actively proliferating ovarian lines tested and 50% (2 of 4) of actively proliferating breast cell lines tested. Confluent cultures were resistant to killing by herb, whereas subconfluent cultures were sensitive. Resistant proliferating cell lines expressed higher levels of bcl2. Transfection of the most sensitive ovarian cancer cell line (A2780) with bcl2 resulted in a noticeable protection against apoptosis, but there was no protection in other transfected lines., Conclusions: These results will be useful in guiding future studies of herbal aqueous extracts, as well as providing information for clinicians when patients are concurrently using these herbs along with conventional cancer therapies.

Several theories have stressed the importance of intersensory integration for development but have not identified specific underlying integration mechanisms. The author reviews and synthesizes current knowledge about the development of intersensory temporal perception and offers a theoretical model based on epigenetic systems theory, proposing that responsiveness to 4 basic features of multimodal temporal experience--temporal synchrony, duration, temporal rate, and rhythm--emerges in a sequential, hierarchical fashion. The model postulates that initial developmental limitations make intersensory synchrony the basis for the integration of intersensory temporal relations and that the emergence of responsiveness to the other, increasingly more complex, temporal relations occurs in a hierarchical, sequential fashion by building on the previously acquired intersensory temporal processing skills.

Human infants' responsiveness to the audible and visible features of human faces was studied by habituating them to a person speaking a prepared script in an adult-directed manner and then administering a series of separate test trials where a person could be seen, heard, or seen and heard singing. When habituated to a female person speaking in an adult-directed manner and tested with a singing female 4, 6, and 8-month-old infants responded to the audible, visible, and bimodal changes, whereas 3-month-old infants only responded to the visual and bimodal changes. In contrast, when habituated to a male person speaking in an adult-directed manner and tested with a singing female, all age groups discriminated all three types of changes. These findings demonstrate that infants are responsive to differences between low- and high-prosody content inherent in both the facial and vocal characteristics of the human face and that, whereas responsiveness to the visible and bimodal features associated with differences between adult-directed speech and singing is present as early as 3 months of age, responsiveness to the audible features emerges between 3 and 4 months of age depending on whether gender differences are present as well.

Using a habituation/test procedure, the author investigated adults' and infants' perception of auditory-visual temporal synchrony. Participants were familiarized with a bouncing green disk and a sound that occurred each time the disk bounced. Then, they were given a series of asynchrony test trials where the sound occurred either before or after the disk bounced. The magnitude of the auditory-visual temporal asynchrony threshold differed markedly in adults and infants. The threshold for the detection of asynchrony created by a sound preceding a visible event was 65 ms in adults and 350 ms in infants and for the detection of asynchrony created by a sound following a visible event was 112 ms in adults and 450 ms in infants. Also, infants did not respond to asynchronies that exceeded intervals that yielded reliable discrimination. Infants' perception of auditory-visual temporal unity is guided by a synchrony and an asynchrony window, both of which become narrower in development.