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Selective attention is a cognitive function that helps filter out unwanted information. Theories such as the biased competition model (Desimone & Duncan, 1995) explain how attentional templates bias processing towards targets in contexts where multiple stimuli compete for resources. However, it is unclear how the anticipation of different levels of competition influences the nature of attentional templates, in a proactive fashion. In this study, we used electroencephalography (EEG) to investigate how the anticipated demands of attentional selection (either high or low stimuli competition contexts) modulate target-specific preparatory brain activity and its relationship with task performance. To do so, participants performed a sex/gender judgment task in a cue-target paradigm where, depending on the block, target and distractor stimuli appeared simultaneously (high competition) or sequentially (low competition). Multivariate Pattern Analysis (MVPA) showed that, in both competition contexts, there was a preactivation of the target category to select, with a ramping-up profile at the end of the preparatory interval. However, cross-classification showed no generalization across competition conditions, suggesting different preparatory formats. Notably, time-frequency analyses showed differences between anticipated competition demands, with higher theta band power for high than low competition, which mediated the impact of subsequent stimuli competition on behavioral performance. Overall, our results show that, whereas preactivation of the internal templates associated with the category to select are engaged in advance in high and low competition contexts, their underlying neural patterns differ. In addition, these codes could not be associated with theta power, suggesting that they reflect different preparatory processes. The implications of these findings are crucial to increase our understanding of the nature of top-down processes across different contexts., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: PD-L1 immunohistochemistry (IHC) is being used as a predictive marker of the benefit derived from immunotherapy in several cancer types, including breast cancer. However, the insight gleaned of the prognostic and predictive value of PD-L1 status and its correlation with molecular characteristics during breast cancer progression remains limited., Methods: We performed an PD-L1 (22C3) assay in pre-treatment primary and metastatic tumor sections from 33 patients with breast carcinoma, matched for post neoadjuvant chemotherapy (p-NACT). PD-L1 expression was evaluated using 3 scoring methods: immune cell (IC) and tumor cell (TC) with a 1% as the cutoff value, and combined positive scores (CPS) with a 1 as the cutoff value. Twenty-two samples from 11 patients had successful fluorescence in situ hybridization (FISH)-based molecular data available for analysis., Results: In the 33 pre-treatment primary tumors, PD-L1 IC, TC, and CPS showed positive correlation with stromal tumor infiltrate lymphocytes (sTIL), histological grade 3, and triple negative breast carcinoma (TNBC). In the matched metastatic tumors, only PD-L1 IC showed a positive correlation with sTIL. The primary tumors showed a higher PD-L1 expression than the matched metastatic tumors by IC and CPS. Negative to positive conversion by CPS was identified in the metastatic tumors from lung, pleura and liver. p-NACT tumors also showed a trend of lower PD-L1 expression compared to the pre-treatment tumors. Six patients had matched samples for molecular and PD-L1 comparison, and none of them showed consistent gene alterations or PD-L1 expression among the primary, p-NACT and metastatic tumors., Conclusion: Our study showed a decrease in PD-L1 expression and disconnected molecular features during breast cancer progression. Repeating PD-L1 IHC testing could be considered in some specific metastatic sites if primary tumors were negative. Further studies are needed to identify other predictive factors for immune checkpoint inhibitor (ICI) therapy in patients with breast carcinoma., Competing Interests: Disclosure No authors have any conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is an ultraorphan neurogenetic disease from the group of neurodegeneration with brain iron accumulation (NBIA) disorders. Here we report cross-sectional and longitudinal data to define the phenotype, to assess disease progression and to estimate sample sizes for clinical trials. We enrolled patients with genetically confirmed MPAN from the Treat Iron-Related Childhood-Onset Neurodegeneration (TIRCON) registry and cohort study, and from additional sites. Linear mixed-effect modelling (LMEM) was used to calculate annual progression rates for the Unified Parkinson's Disease Rating Scale (UPDRS), Barry-Albright Dystonia (BAD) scale, Schwab and England Activities of Daily Living (SE-ADL) scale and the Pediatric Quality of Life Inventory (PedsQL). We investigated 85 MPAN patients cross-sectionally, with functional outcome data collected in 45. Median age at onset was 9 years and the median diagnostic delay was 5 years. The most common findings were gait disturbance (99%), pyramidal involvement (95%), dysarthria (90%), vision disturbances (82%), with all but dysarthria presenting early in the disease course. After 16 years with the disease, 50% of patients were wheelchair dependent. LMEM showed an annual progression rate of 4.5 points in total UPDRS. The total BAD scale score showed no significant progression over time. The SE-ADL scale and the patient- and parent-reported PedsQL showed a decline of 3.9%, 2.14 and 2.05 points, respectively. No patient subpopulations were identified based on longitudinal trajectories. Our cross-sectional results define the order of onset and frequency of symptoms in MPAN, which will inform the diagnostic process, help to shorten diagnostic delay and aid in counselling patients, parents and caregivers. Our longitudinal findings define the natural history of MPAN, reveal the most responsive outcomes and highlight the need for an MPAN-specific rating approach. Our sample size estimations inform the design of upcoming clinical trials., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: One of the most common complaints among menopausal women concerns changes in sexual function. This is attributed to various factors, including anatomical defects in the genital tract, with pelvic organ prolapse (POP) being one of the most prevalent problems affecting women during this stage of their lives. Additionally, symptoms resulting from gonadal hypofunction can also contribute to the development of sexual dysfunction during menopause. This research aimed to explore the way in which postmenopausal patients with POP experienced their sexuality in our setting., Methods: To achieve the proposed objective, we conducted a descriptive, cross-sectional study involving a total of 133 postmenopausal women with POP., Results: The results of our series are consistent with the scarce literature available in our setting and suggest a high rate of sexual dysfunction in postmenopausal patients with POP., Conclusions: We can conclude that POP is associated with the presence of female sexual dysfunction.

Proactive cognition brain models are mainstream nowadays. Within these, preparation is understood as an endogenous, top-down function that takes place prior to the actual perception of a stimulus and improves subsequent behavior. Neuroimaging has shown the existence of such preparatory activity separately in different cognitive domains, however no research to date has sought to uncover their potential similarities and differences. Two of these, often confounded in the literature, are Selective Attention (information relevance) and Perceptual Expectation (information probability). We used EEG to characterize the mechanisms that pre-activate specific contents in Attention and Expectation. In different blocks, participants were cued to the relevance or to the probability of target categories, faces vs. names, in a gender discrimination task. Multivariate Pattern (MVPA) and Representational Similarity Analyses (RSA) during the preparation window showed that both manipulations led to a significant, ramping-up prediction of the relevant or expected target category. However, classifiers trained with data from one condition did not generalize to the other, indicating the existence of unique anticipatory neural patterns. In addition, a Canonical Template Tracking procedure showed that there was stronger anticipatory perceptual reinstatement for relevance than for expectation blocks. Overall, the results indicate that preparation during attention and expectation acts through distinguishable neural mechanisms. These findings have important implications for current models of brain functioning, as they are a first step towards characterizing and dissociating the neural mechanisms involved in top-down anticipatory processing., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

In testicular germ cell tumor type II (TGCT), a seminoma subtype expresses an induced pluripotent stem cell (iPSC) panel with four upregulated genes, OCT4/ POU5F1, SOX17, KLF4, and MYC, and embryonal carcinoma (EC) has four upregulated genes, OCT4/ POU5F1, SOX2, LIN28, and NANOG. The EC panel can reprogram cells into iPSC, and both iPSC and EC can differentiate into teratoma. This review summarizes the literature on epigenetic regulation of the genes. Epigenetic mechanisms, such as methylations of cytosines on the DNA string and methylations and acetylations of histone 3 lysines, regulate expression of these driver genes between the TGCT subtypes. In TGCT, the driver genes contribute to well-known clinical characteristics and the driver genes are also important for aggressive subtypes of many other malignancies. In conclusion, epigenetic regulation of the driver genes are important for TGCT and for oncology in general.

Genetic variants that result in truncation in desmoplakin ( DSP ) are a known cause of arrhythmogenic cardiomyopathy (AC). In homozygous carriers, the combined involvement of skin and heart muscle is well defined, however, this is not the case in heterozygous carriers. The aim of this work is to describe cutaneous findings and analyze the molecular and ultrastructural cutaneous changes in this group of patients. Four women and eight men with a mean age of 48 ± 14 years were included. Eight met definitive criteria for AC, one was borderline and three were silent carriers. No relevant macroscopic changes in skin and hair were detected. However, significantly lower skin temperature (29.56 vs. 30.97 °C, p = 0.036) and higher transepidermal water loss (TEWL) (37.62 vs. 23.95 g m 2 h 1, p = 0.028) were observed compared to sex- and age-matched controls. Histopathology of the skin biopsy showed widening of intercellular spaces and acantholysis of keratinocytes in the spinous layer. Immunohistochemistry showed a strongly reduced expression of DSP in all samples. Trichogram showed regular nodules (thickening) compatible with pseudomonilethrix. Therefore, regardless of cardiac involvement, heterozygous patients with truncation-type variants in DSP have lower skin temperature and higher TEWL, constant microscopic skin involvement with specific patterns and pseudomonilethrix in the trichogram.

Objective: To evaluate the clinical features, pathologic features, and prevalence of human papilloma virus (HPV) in squamous cell carcinoma (SCC) of the bladder. SCC of the bladder is known to be associated with conditions that cause chronic inflammation/irritation. The literature is inconsistent regarding the association of HPV with pure SCC of the bladder., Methods: A multi-institutional study identified cases of SCC of the bladder. Pure squamous histology and the absence of urothelial carcinoma in situ were required for inclusion. Clinical and pathologic features were collected, and tissues were evaluated for high-risk HPV using p16 immunohistochemistry and in situ hybridization., Results: We identified 207 cases of SCC of the bladder. Risk factors for bladder cancer included smoking (133/207, 64%) and chronic bladder irritation (83/207, 40%). The majority (155/207, 75%) of patients had > pT2 disease. Mean tumor size was 5.6 ± 3.0 cm and 36/207 (17%) patients had lymph node positive disease. p16 immunohistochemistry was positive in 52/204 (25%) cases but high-risk HPV was identified with in situ hybridization in only 1 (0.5%) case. Tumor size, stage, number of lymph nodes removed, number of positive lymph nodes, lymphovascular invasion, perineural invasion, and positive margins each were associated with cancer-specific mortality when adjusted for demographic factors. A multivariate analysis of variable importance further revealed sex and race as important factors in predicting cancer-specific mortality., Conclusion: SCC of the bladder is an aggressive histologic subtype. Although bladder SCC can express p16, it is not typically associated with high-risk HPV, although rare cases can occur., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Autism spectrum disorder (ASD) often has a significant impact on all family members, including parents and siblings of the person who suffers the disorder. This case-control study explores potential factors that help explain the impact of having an older sibling with ASD on several developmental domains, and to test whether these factors could explain their satisfaction on family quality of life (FQoL)., Methods: A total of 78 unaffected siblings of children with ASD (Sibs-ASD) and siblings of children with typical development (Sibs-TD) from 6 to 12 years old were evaluated., Results: Our analyses show significant differences between groups in motor skills, severity of autistic traits, satisfaction on FQoL, and social support (ps < .05). Moreover, social support acts as positive factor protecting from the negative effect of having a sibling with ASD on satisfaction of FQoL (R 2  = .32)., Conclusions: Our findings highlight the variability in the developmental abilities of the unaffected school-age children with familiar risk factors and emphasize the need for supervising development of all Sibs-ASD over different time points. Social support may be a critical aspect to consider in interventions for improving the satisfaction on FQoL.

Our objective was to evaluate the pathologic features and clinical outcomes in cases of invasive penile squamous cell carcinoma (SCC) and the association with p16 immunohistochemistry (IHC) and human papilloma virus (HPV) in situ hybridization (ISH). A retrospective multi-institutional database search was conducted for invasive SCC of the penis diagnosed between 2007 and 2018 that had undergone surgical resection. Pathologic features, p16 IHC, and HPV ISH were investigated with clinical outcomes. A total of 102 patients were included in the study. The average age was 63 ± 13.3 years. Based on histology, 46% of tumors displayed an HPV-related subtype, whereas p16 was positive in 52% of all cases. Tumor histology correlated well with p16 positivity (P < .001), and p16 IHC accurately predicted the presence of HPV in 25/26 (96%) cases. On multivariate analysis, perineural invasion was associated with local disease recurrence (P = .02), whereas lymphovascular invasion was associated with progression to metastatic disease (P = .002) and increased overall mortality (P = .02). Urethral involvement was also associated with increased overall mortality (P = .02). In addition, HPV-related tumors based on histologic features correlated with lower rates of metastatic disease (P = .007). HPV is a common cause of penile SCC and can be diagnosed by tumor histology and confirmed by overexpression of p16 on IHC. The presence of lymphovascular invasion, perineural invasion, and urethral involvement are poor prognostic indicators, whereas HPV-related tumors based on histology may have lower risk for metastatic disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

An ecotoxicological survey of soils that were polluted with wastes from lindane (γ-HCH) production assessed the effects of organochlorine compounds on the metabolism of microbial communities and the toxicity of these compounds to a native earthworm (Allolobophora chlorotica). Furthermore, the bioremediation role of earthworms as facilitators of soil washing and the microbial degradation of these organic pollutants were also studied. Soil samples that presented the highest concentrations of ε-HCH, 2,4,6-trichlorophenol, pentachlorobenzene and γ-HCH were extremely toxic to earthworms in the short term, causing the death of almost half of the population. In addition, these soils inhibited the heterotrophic metabolic activity of the microbial community. These highly polluted samples also presented substances that were able to activate cellular detoxification mechanisms (measured as EROD and BFCOD activities), as well as compounds that were able to cause endocrine disruption. A few days of earthworm activity increased the extractability of HCH isomers (e.g., γ-HCH), facilitating the biodegradation of organochlorine compounds and reducing the intensity of endocrine disruption in soils that had low or medium contamination levels., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim is to achieve a transgenerational view of single motherhood in Spain, to look at which contexts it arises in, how it changes with the introduction of assisted reproduction, and how the role of religion in Spanish society permeates medical practice and affects the lives of women patients. I examine single motherhood and investigate two interconnected themes: (a) being a mother and being mothered are both permeated with sociocultural, political, religious, economic and psychological significance; (b) Spain led Europe in multiple births due to assisted reproduction, thus ethical conflicts and patient rights are analyzed.

Background: The severity and progression of rotator cuff tears have forced research on new treatment pathways such as metalloprotease inhibition, which has shown a reduction in healing time and improvement in the structure of collagen fibers., Objective: To evaluate the use of doxycycline as a healing enhancer in rotator cuff tears after surgical treatment., Material and Methods: 20 patients were included; they were divided into two groups, 10 with the use of doxycycline and 10 without it after arthroscopic repair with one-year follow-up. Doxycycline was given orally, 100 mg once a day for one month. Every subject in the test was diagnosed with rotator cuff tear confirmed by MRI with Patte and Goutallier scores below 2. We used the arthroscopic double row technique. Post-op follow-up was 12 months with clinical scales (UCLA, Constant and forward flexion strength)., Results: Both groups reported almost complete healing of rotator cuff tears after surgical treatment during the twelve months of follow-up; forward flexion strength was the only score that reported improvement in the doxycycline group during every check-up., Discussion: Doxycycline use after arthroscopic cuff tear repair could improve the clinical outcome, but we do not know how yet; however larger sample and randomized trials should be developed.

Background: A sore throat is the reason behind 4 million visits to health care services per year in Spain. The management of these ailments is usually associated with an inappropriate use of medicines. Community pharmacists are often the first point of contact for patients under the healthcare system and play a major role in the management of minor ailments., Objective: To characterize the pharmacists' professional practice in oropharyngeal condition in terms of patients' requests and pharmacists' interventions performed., Setting: Community pharmacies throughout Spanish territory., Method: Cross-sectional multicenter observational study, undertaken between November 2012 and March 2013. Patients were recruited consecutively in the participant pharmacies. Eligible patients were those making a consultation related to an oropharyngeal condition or requesting treatment for an oropharyngeal condition. A univariate descriptive analysis showing the frequency of occurrence of the different variables was performed. This was completed with a multivariate statistical analysis through a multiple correspondence method, in order to analyze the potential association between the pharmacist profile and the intervention provided., Main Outcome Measure: Professional Pharmacy Service requested (dispensing/counselling/medication review with follow-up), reason for consultation, source of the recommendation, Pharmacist's intervention and reason for referral., Results: 710 pharmacies and 3,547 patients participated in the study. The most frequently requested service was dispensing (44.7 %), followed by counselling (31.8 %). Regarding dispensing, the majority of patients requested a throat preparation, mostly antiseptics. Symptoms associated with the pharmacy consultation were mainly throat symptoms (70.8 %), voice symptoms (24.9 %), and mouth/tongue/lip symptoms (10.1 %). The most common pharmacist intervention was "selection of pharmacological treatment", followed by "dispensing the requested medicine"; 6.51 % of the patients were referred to a general practitioner, mainly due to fever and other symptoms associated with infection. No relationship between the pharmacist profile and the intervention performed was found., Conclusion: The most frequently requested professional service was the dispensing service, mainly for treating throat symptoms. Community pharmacists play a major role in managing patients with an oropharyngeal condition. They can keep them out of general practice or act as referral agents when a more severe disease is identified.

Unlabelled: Rhinophyma, a progressive, disfiguring disease of the nose, is considered the final stage of acne rosacea. In its early stages, rhinophyma can be managed with medical treatment using isotretinoin or oral antibiotics (metronidazole). However, severe cases usually are refractory to medical approaches. Surgical therapies to treat these severe refractory cases have been described. This report describes a simple, safe, efficient, and cost-effective approach to the treatment of severe rhinophyma using a scalpel and the electroscalpel, instruments readily available in every operating room., Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Chicks of altricial birds may perceive predation risk by acoustic cues produced by predators. This capacity involves changes to a less conspicuous behavior to avoid being detected and predated. However, little is known about the physiological mechanisms underlying this capacity. Potential mechanisms may involve corticosterone and testosterone, two hormones related to begging, an acoustic signal, which could be used by predators to locate and predate the nest. However, given the species-specificity of this relationship, it is difficult to make particular predictions. We manipulated perceived risk of nest predation in the common blackbird (Turdus merula) and analyzed nestlings' plasma levels of these hormones to look for nest predation risk effects. Our experimental manipulation showed hormonal changes in response to nest predation risk. Chicks under a high risk of nest predation reduced their corticosterone plasma levels but increased their testosterone levels in comparison with nestlings exposed to a low nest predation risk. We explain our results as mechanisms to reduce begging activity and discuss them within the framework of hormonal modifications in developing animals. These findings highlight the importance of studying nest predation from the unusually considered chick perspective and underlined the benefits from including physiological variables in the study of predator-prey interactions., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective. To analyze 25 years of mortality of extremely low-birth-weight (ELBW) neonates (≤1000 g) in a private hospital in Mexico City and to establish the current viability limit for ELBW neonates. Methods. We designed a prospective observational study of all ELBW neonates born between 1985 and 2009. Neonatal mortality, early neonatal mortality, and the 120-day mortality rate were analyzed in 5-year intervals by two categories of birth weight (501-750 g and 751-1000 g). Results. Among the 50,823 total births, 158 were ELBW (3.1 per 10(3)). Neonatal mortality (death ≤28 days) decreased for the 501-750 g neonates from 88.9% (1985-1989) to 55.6% (2005-1999) (P = .008) and for 751-1000 g neonates also decreased from 50% to 5.3% (P = .002). The 120-day mortality for neonates over 500 g diminished: 501-750 g neonates, 88.9% to 61.1% (P = .02) and for 751-1000 g neonates, 62.5% to 15.8% (P = .002). The highest viability limit was established in neonates who weighed ≥650 g and were ≥26 weeks in gestational age. Conclusions. The survival of ELBW neonates has improved in Mexico particularly in private hospitals, and it was more evident over the years 2004-2009. These data suggest that it is possible to increase the ELBW neonates survive in developing counties.