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Purpose: Improvements in breast cancer management continue to increase survival and life expectancy after treatment. Yet the adverse effects of treatment may persist long term, threatening physical, psychological, and social wellbeing, leading to impaired quality of life (QOL). Upper-body morbidity (UBM) such as pain, lymphoedema, restricted shoulder range of motion (ROM), and impaired function are widely reported after breast cancer treatment, but evidence demonstrating its impact on QOL is inconsistent. Therefore, the aim of the study was to conduct a systematic review and meta-analysis evaluating the effect of UBM on QOL following primary breast cancer treatment., Methods: The study was prospectively registered on PROSPERO (CRD42020203445). CINAHL, Embase, Emcare, PsycInfo, PubMed/Medline, and SPORTDiscus databases were searched for studies reporting QOL in individuals with and without UBM following primary breast cancer treatment. Primary analysis determined the standardised mean difference (SMD) in physical, psychological, and social wellbeing scores between UBM + /UBM - groups. Secondary analyses identified differences in QOL scores between groups, according to questionnaire., Results: Fifty-eight studies were included, with 39 conducive to meta-analysis. Types of UBM included pain, lymphoedema, restricted shoulder ROM, impaired upper-body function, and upper-body symptoms. UBM + groups reported poorer physical (SMD =  - 0.99; 95%CI =  - 1.26, - 0.71; p < 0.00001), psychological (SMD =  - 0.43; 95%CI =  - 0.60, - 0.27; p < 0.00001), and social wellbeing (SMD =  - 0.62; 95%CI =  - 0.83, - 0.40; p < 0.00001) than UBM - groups. Secondary analyses according to questionnaire showed that UBM + groups rated their QOL poorer or at equal to, UBM - groups across all domains., Conclusions: Findings demonstrate the significant, negative impact of UBM on QOL, pervading physical, psychological, and social domains., Implications for Cancer Survivors: Efforts to assess and minimise the multidimensional impact of UBM are warranted to mitigate impaired QOL after breast cancer., (© 2023. The Author(s).)

Background: Biliary tract cancers (BTCs) are usually diagnosed at an advanced stage, when the disease is incurable. Currently used tumor biomarkers have limited diagnostic value for BTCs, so there is an urgent need for sensitive and specific biomarkers for their earlier diagnosis. Deregulation of the homeostasis of trace elements is involved in the carcinogenesis of different cancers, including BTCs. The objective of the study is to determine/compare the total concentrations of copper (Cu), zinc (Zn) and iron (Fe) and the proportions of free Cu and Cu bound to ceruloplasmin (Cp) and the isotopic ratio of 65 Cu/ 63 Cu in serum samples from healthy volunteers and cancer patients using inductively coupled plasma-mass spectrometry-based methods (ICP-MS)., Patients and Methods: In this prospective, noninterventional, nonrandomized study 20 patients and 20 healthy volunteers will be enrolled to identify serum Cu, Zn and Fe levels, Cu isotopic fractionation as a predictive biomarker of response to systemic therapy of BTCs, which will be evaluated by computed tomography. Newly developed analytical methods based on ICP-MS will be applied to metal-based biomarker research in oncology., Conclusions: In the study the comparison of the total concentration of selected trace elements, the proportion of free Cu and Cu bound to Cp and the isotopic ratio of 65 Cu/ 63 Cu in serum samples from healthy volunteers and cancer patients will be conducted to provide the foundation for the development of a BTC cancer screening methodology and the data on their usability as a potential predictive biomarker for BTCs of response to systemic therapy., (© 2024 Martina Rebersek et al., published by Sciendo.)

Safe and long-term electrical stimulation of neurons requires charge injection without damaging the electrode and tissue. A common strategy to diminish adverse effects includes the modification of electrodes with materials that increases the charge injection capacity. Due to its high capacitance, the conducting polymer PEDOT:PSS is a promising coating material; however, the neural stimulation performance in terms of stability and safety remains largely unexplored. Here, PEDOT:PSS-coated platinum (Pt-PEDOT:PSS) microelectrodes are examined for neural stimulation and compared to bare platinum (Pt) electrodes. Microelectrodes in a bipolar configuration are used to deliver current-controlled, biphasic pulses with charge densities ranging from 64 to 255  μ C cm -2 . Stimulation for 2 h deteriorates bare Pt electrodes through corrosion, whereas the PEDOT:PSS coating prevents dissolution of Pt and shows no degradation. Acute stimulation of primary cortical cells cultured as neurospheres shows similar dependency on charge density for Pt and Pt-PEDOT:PSS electrodes with a threshold of 127  μ C cm -2 and increased calcium response for higher charge densities. Continuous stimulation for 2 h results in higher levels of cell survival for Pt-PEDOT:PSS electrodes. Reduced cell survival on Pt electrodes is most profound for neurospheres in proximity of the electrodes. Extending the stimulation duration to 6 h increases cell death for both types of electrodes; however, neurospheres on Pt-PEDOT:PSS devices still show significant viability whereas stimulation is fatal for nearly all cells close to the Pt electrodes. This work demonstrates the protective properties of PEDOT:PSS that can be used as a promising approach to extend electrode lifetime and reduce cell damage for safe and long-term neural stimulation., Competing Interests: The authors have no conflicts to disclose., (© 2023 Author(s).)

Background and Objectives : The aim of this study was to assess the differences in Doppler indices of the uterine (Ut), umbilical (UA), and middle cerebral artery (MCA) in diabetic versus non-diabetic pregnancies by conducting a comprehensive systematic review of the literature with a meta-analysis. Materials and Methods : PubMed, Web of Science, and SCOPUS were searched for studies that measured the pulsatility index (PI), resistance index (RI), and systolic/diastolic ratio index (S/D ratio) of the umbilical artery, middle cerebral artery, and uterine artery in diabetic versus non-diabetic pregnancies. Two reviewers independently evaluated the eligibility of studies, abstracted data, and performed quality assessments according to standardized protocols. The standardized mean difference (SMD) was used as a measure of effect size. Heterogeneity was assessed using the I2 statistic. Publication bias was evaluated by means of funnel plots. Results : A total of 62 publications were included in the qualitative and 43 in quantitative analysis. The UA-RI, UtA-PI, and UtA-S/D ratios were increased in diabetic compared with non-diabetic pregnancies. Subgroup analysis showed that levels of UtA-PI were significantly higher during the third, but not during the first trimester of pregnancy in diabetic versus non-diabetic pregnancies. No differences were found for the UA-PI, UA-S/D ratio, MCA-PI, MCA-RI, MCA-S/D ratio, or UtA-RI between diabetic and non-diabetic pregnancies. Conclusions : This meta-analysis revealed the presence of hemodynamic changes in uterine and umbilical arteries, but not in the middle cerebral artery in pregnancies complicated by diabetes.

A high level of genetic purity in crop varieties must be achieved and maintained for agronomic performance, encouraging investment and innovation in plant breeding and ensuring that the improvements in productivity and quality imparted by breeders are delivered to the consumer. Since the success of hybrid seed production is dependent upon the genetic purity of the parental lines, in this study, the experimental F1 exp maize hybrid and its parental inbreeds were used as a model system to examine the discriminative power of morphological, biochemical and SSR markers for seed purity assay. The highest number of off-type plants was estimated by morphological markers. According to the comparison of prolamins and albumins banding patterns of parental and derived F1 exp seeds, genetic impurities could not be detected. Molecular analysis detected two types of genetic profile irregularity. Beside its use for verifying varieties of maize, report on umc 1545 primer pair ability to detect non-specific bands (i.e., off-types), in both the maternal component and F1 exp , which is the first report on this issue yet, strongly supports the recommendation of this SSR marker use for more accurate and time-efficient maize hybrids and parental lines genetic pyrity testing.

Background: The objective of this study was to assess the complex relationship between the multiple determinants of the caregiving process, the caregiver burden, and depression during the COVID-19 pandemic in Serbia., Methods: A cross-sectional study was conducted on a nationally representative sample (n = 798) during the COVID-19 pandemic in Serbia from March to September 2020. A nine-section questionnaire designed for this study included the characteristics of caregivers, characteristics of care and care recipients, COVID-19 related questions, and the following standardized instruments: 12-Item Short-Form Health Survey, Fatigue Severity Scale, Activities of Daily Living Scale and Instrumental Activities of Daily Living Scale, Zarit Caregiver Burden Scale, and Beck Depression Inventory. Path analysis was used for the simultaneous assessment of the direct and indirect relationships of all determinants., Results: More than two thirds (71.9%) of informal caregivers experienced a burden, and more than one quarter (27.1%) had depression symptomatology. Self-rated physical health, need for psychosocial support, and caregiver burden were the main direct predictors of depression. Multiple determinants of the caregiving process had indirect effects on depressive symptomatology via the caregiver burden as a mediating factor., Conclusions: The subjective burden presented a significant risk factor for depressive symptoms in caregivers during the COVID-19 pandemic. The provision of psychosocial support was identified as an important opportunity to reduce depressive risk in informal caregivers.

Background: The age of onset of cluster headache (CH) attacks most commonly is between 20 and 40 years old, although CH has been reported in all age groups. There is increasing evidence of CH with early or late onset and a different course of the disorder. The aim of the study was to analyze the influence of the age of onset on clinical features, disorder course, and therapy effectiveness in CH patients., Methods: A retrospective and cross-sectional analysis was performed on 182 CH patients divided into three groups according to the age of onset. The first group consisted of patients with the first CH attack before 20 years of age, the second group was patients with age of onset between 20 and 40 years of age, and the third group was patients with age of onset after 40 years of age. Demographic data, features of CH periods and attacks, and the response to standardized treatment were compared among the groups., Results: Patients with CH onset after 40 years of age reported a lower number of autonomic features and less frequently had conjunctival injection and nasal congestion/rhinorrhea phenomena during their attacks. Diagnostic delay was the longest in the patients with CH onset before 20 years of age., Conclusion: The influence of the age of onset of CH is intriguing for further studies and could possibly extend the knowledge about CH pathophysiology. From a clinical point of view, the differences in CH presentation are insufficient to preclude a correct diagnosis and treatment because the same criteria could be applied regardless of patient age., (© International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Euclid is a European Space Agency medium-class mission selected for launch in 2019 within the Cosmic Vision 2015-2025 program. The main goal of Euclid is to understand the origin of the accelerated expansion of the universe. Euclid will explore the expansion history of the universe and the evolution of cosmic structures by measuring shapes and red-shifts of galaxies as well as the distribution of clusters of galaxies over a large fraction of the sky. Although the main driver for Euclid is the nature of dark energy, Euclid science covers a vast range of topics, from cosmology to galaxy evolution to planetary research. In this review we focus on cosmology and fundamental physics, with a strong emphasis on science beyond the current standard models. We discuss five broad topics: dark energy and modified gravity, dark matter, initial conditions, basic assumptions and questions of methodology in the data analysis. This review has been planned and carried out within Euclid's Theory Working Group and is meant to provide a guide to the scientific themes that will underlie the activity of the group during the preparation of the Euclid mission.

Cholecystokinin (CCK) and gastrin stimulate growth of pancreatic cancer. Although down-regulation of gastrin inhibits growth of pancreatic cancer, the contribution of endogenous CCK to tumor growth is unknown. The purpose of this study was to evaluate the role of endogenous CCK on autocrine growth of pancreatic cancer. Pancreatic cancer cell lines were analyzed for CCK mRNA and peptide expression by real-time RT-PCR and radioimmunoassay, respectively. The effect of endogenous CCK on growth was evaluated by treating cancer cells with CCK neutralizing antibodies and by down-regulating CCK mRNA by RNAi. Wild-type pancreatic cancer cells expressed significantly lower CCK mRNA and peptide levels than gastrin. Neither treatment of pancreatic cancer cells with CCK antibodies nor the down-regulation of CCK mRNA and peptide by shRNAs altered growth in vitro or in vivo. Conversely, when gastrin mRNA expression was down-regulated, the same cells failed to produce tumors in spite of having sustained levels of endogenous CCK. Pancreatic cancer cells produce CCK and gastrin; however, the autocrine production of gastrin is more important for stimulating tumor growth.

Complex regional pain syndrome (CRPS), formerly known as Sudeck's dystrophy and causalgia, is a disabling and distressing pain syndrome. We here provide a review based on the current literature concerning the epidemiology, etiology, pathophysiology, diagnosis, and therapy of CRPS. CRPS may develop following fractures, limb trauma or lesions of the peripheral or CNS. The clinical picture comprises a characteristic clinical triad of symptoms including autonomic (disturbances of skin temperature, color, presence of sweating abnormalities), sensory (pain and hyperalgesia), and motor (paresis, tremor, dystonia) disturbances. Diagnosis is mainly based on clinical signs. Several pathophysiological concepts have been proposed to explain the complex symptoms of CRPS: (i) facilitated neurogenic inflammation; (ii) pathological sympatho-afferent coupling; and (iii) neuroplastic changes within the CNS. Furthermore, there is accumulating evidence that genetic factors may predispose for CRPS. Therapy is based on a multidisciplinary approach. Non-pharmacological approaches include physiotherapy and occupational therapy. Pharmacotherapy is based on individual symptoms and includes steroids, free radical scavengers, treatment of neuropathic pain, and finally agents interfering with bone metabolism (calcitonin, biphosphonates). Invasive therapeutic concepts include implantation of spinal cord stimulators. This review covers new aspects of pathophysiology and therapy of CRPS.

Numerous studies report gender differences in emotional reactivity in health and disease and the perception of odors is closely linked to the limbic system. In order to investigate gender differences in the emotional perception of odors we extended the Sniffin' Stick Test with analogue rating scales for hedonic (pleasantness/unpleasantness) and intensity estimates. We matched 172 healthy subjects (86 females and 86 males) on age in order to balance the study population for three age strata (A: 19-39 years, B: 40-59, C: 60 years and above). Overall odors in our statistical analysis demonstrated significant gender differences for the absolute hedonic estimates but not for the relative hedonic and not for the intensity estimates. These findings demonstrate that women evaluate the pleasantness of perceived odors in a more extreme manner than men without significant differences in hedonic polarity (pleasantness/unpleasantness). Thus, we report a singular significant effect of gender on the dimension valence (hedonic estimation) independent from the dimension intensity. Our findings are in accordance with gender differences in facial reactivity to auditory stimuli and differences in the evaluation of emotional pictures. Investigating olfactory sensitivity females detected n-butanol and discriminated the 16 odors of the test significantly better than males. These results indicate that females possess higher olfactory sensitivity.

An earlier study in humans comparing the olfactory sensitivity of both nostrils revealed a small but significant advantage of the right nostril for detection and for olfactory quality discrimination. However lateralization was not evaluated for the perception of odor intensity and hedonic evaluation (pleasantness/unpleasantness). Thus we investigated lateralization of olfactory intensity and hedonic evaluation in right-handed healthy volunteers (n=186) from the HeDoS-F database (Hedonic Database of Smell-Franconia). For olfactory evaluation the Sniffin' Stick Test was employed with the parameters detection, discrimination, identification and extended by analogue hedonic and intensity rating scales. Over all odors subjects rated the perceived intensity significantly higher following stimulation of the right compared to the left nostril. The analysis of the single odors of the Sniffin' Stick Test consistently confirmed higher intensity ratings for the right compared to the left nostril reaching a statistically significant difference for 10 out of 16 odors. In contrast we found no significant differences between the nostrils for the hedonic estimates over all odors. Differences in odor detection, discrimination and identification did not reach a statistically significant level, but for all these parameters the scores of the right nostril were slightly higher compared to the left nostril. For odor identification, however, a statistical tendency was observed. Based on our results we concluded that olfactory intensity estimates represent the most sensitive parameter of olfactory lateralization.

Purpose: The problem of time distribution of suicide has aroused the interest of various investigators in the past. A population-based study on the association of the birthday in relation to the time of suicide taking into account sex and the chosen suicide method was conducted., Methods: The study included all residents of Bavaria who died between 1998 and 2003 and whose death was classified as suicide by the death certificate. In sum, 11378 deaths from suicide were included. The suicide ratios in various time frames around the individuals' birthdays were compared with expected suicide ratios., Results: The occurrence of suicide did not vary around the birthday. Different time frames (3, 7, 14, 30, and 90 days) before as well as after the individuals' birthdays were taken into account. Even after dichotomization regarding the chosen method as well as sex differences, no significant association between birthdays and dates of suicide could be found., Conclusion: There is no evidence for a "birthday blues" effect on suicide.

Background: Numerous studies have been conducted collecting normative values dependent on age for the three major components of the Sniffin' Stick Test (threshold of n-butanol, and identification and discrimination of odors). Less is known about the influence of age on the hedonic and intensity evaluation of odors. Thus, the objective of this study was to analyze the influence of age on the hedonic and intensity estimates in a large human population., Methods: Two hundred one single data sets established the Hedonic Database of Smell-Franconia (HeDoS-F) with the parameters age, gender, odor threshold, odor discrimination, oder identification, intensity estimates, and hedonic estimates (median age: 39 years, interquartile range: 28, minimum age: 19, maximum age: 83, men: 103, women: 98). For olfactory testing the Sniffin' Stick Test was used, and hedonic and intensity estimates were registered using visual analogue rating scales. For statistical analysis, we separated the study population into three age groups (19-39 years, 40-59 years, and > or = 60 years), and parametric and nonparametric tests were calculated., Results: We found a significant influence of age on threshold, discrimination, and identification with a decrease in the higher age class. Over all odors the summed intensity estimates did not depend on age, whereas the summed relative hedonic estimates increased with the beginning of the fifth decade., Conclusion: Our study suggests that, for perceived odors, olfactory pleasure increases at later stages of the life span, whereas the perceived intensity of odors remains stable.

Nicotine presented to the nasal cavity at low concentrations evokes 'odorous' sensations, and at higher concentrations 'burning' and 'stinging' sensations. A study in smokers and nonsmokers provided evidence of a relationship between the experience with the pharmacological action of S-(-)-nicotine and the perceived pleasantness/unpleasantness following nasal stimulation with S-(-)-nicotine. Mecamylamine, a nicotinic acetylcholine-receptor-(nAch-R) antagonist, was able to block painful responses following chemical stimulation of the human tongue and to block responses from the rat's ethmoidal nerve. The aim of our study in humans was to investigate the effects of mecamylamine on the olfactory and the trigeminal chemoreception of nicotine enantiomers. In order to achieve this aim, we determined-before and after mecamylamine-(1) detection thresholds, trigeminal thresholds, and intensity estimates (stimulus intensity) and (2) recorded the negative mucosal potential (NMP) following nasal stimulation with nicotine in a placebo-controlled double blind study (n = 15). CO(2) was used as a trigeminal and H(2)S as an olfactory control stimulus. Mecamylamine significantly increased trigeminal thresholds of S-(-)-nicotine and reduced intensity estimates and NMPs following stimulation with nicotine enantiomers, whereas mecamylamine did not influence NMPs and trigeminal intensity estimates following stimulation with CO(2). In contrast, mecamylamine did neither influence detection thresholds nor olfactory intensity estimates following stimulation with olfactory nicotine concentrations. These results demonstrate that the trigeminal nasal chemoreception of nicotine enantiomers, in contrast to CO(2), is mediated by nAch-Receptors and give evidence that the olfactory chemoreception of nicotine is independent from peripheral nAch-Receptors.

The tumour-associated antigen, Ep-CAM, is over-expressed in colorectal carcinoma (CRC). In the present study, a recombinant Ep-CAM protein or a human anti-idiotypic antibody (anti-Id) mimicking Ep-CAM, either alone or in combination, was used for vaccination of CRC patients (n=9). GM-CSF was given as an adjuvant cytokine. A cellular immune response was assessed by measuring anti-Ep-CAM lymphoproliferation, IFN-gamma production (ELISPOT) and by analysing the TCR BV gene usage within the CD4+ and CD8+ T-cell subsets followed by CDR3 fragment analysis. A proliferative and/or IFN-gamma T-cell response was induced against the Ep-CAM protein in eight out of nine patients, and against Ep-CAM-derived peptides in nine out of nine patients. Analysis of the TCR BV gene usage showed a significantly higher usage of BV12 family in CD4+ T cells of patients both before and after immunisation than in those of healthy control donors (p<0.05). In the CD8+ T-cell subset, a significant (p<0.05) increase in the BV19 usage was noted in patients after immunisation. In individual patients, a number of TCR BV gene families in both CD4+ and CD8+ T cells were over-expressed mainly in post-immunisation samples. Analysis of the CDR3 length polymorphism revealed a higher degree of clonality in post-immunisation samples than in pre-immunisation samples. In vitro stimulation with Ep-CAM protein confirmed the expansion of anti-Ep-CAM T-cell clones. The results indicate that immunisation with the Ep-CAM protein and/or anti-Id entails the induction of an anti-Ep-CAM T-cell response in CRC patients, and suggest that BV19+ CD8+ T cells might be involved in a vaccine-induced immune response.

Purpose: The tumor-associated antigen Ep-CAM (epithelial cell adhesion molecule) is overexpressed in colorectal carcinoma (CRC). The aim of the present study was to evaluate and compare the safety and immunogenicity of a recombinant Ep-CAM protein and a human anti-idiotypic antibody (anti-Id) mimicking Ep-CAM., Experimental Design: Patients with resected American Joint Committee on Cancer stages II-IV CRC without remaining macroscopic disease received intradermal/subcutaneous injections of Ep-CAM (400 microg/dose; n = 7) or anti-Id (500 microg/dose; n = 6) at weeks 0, 2, and 6 in combination with granulocyte macrophage colony-stimulating factor (75 microg/day, for 4 consecutive days)., Results: Adverse reactions were mild (grade I-II). All patients immunized with the Ep-CAM protein produced Ep-CAM-specific IgG antibodies, predominantly IgG1 and IgG3 subclasses, whereas no humoral response was induced by the anti-Id vaccine. All patients, with one exception in each group, mounted an Ep-CAM-specific proliferative T-cell response. The immune response was more rapid, potent, and protracted after Ep-CAM in comparison with anti-Id vaccination. Interferon-gamma-secreting cells (ELISPOT) were detected in both immunization groups against the Ep-CAM protein as well as various Ep-CAM-derived MHC class I- and II-restricted peptides. Flow cytometry analysis showed that Ep-CAM-specific interferon-gamma- and perforin-producing cells predominantly resided within CD8(+)CD56- and CD8(dim)CD56+ T cells., Conclusions: Ep-CAM protein in combination with granulocyte macrophage colony-stimulating factor induced a long-lasting, Th1-biased humoral and cellular immune response compared with anti-Id. Ep-CAM-specific T cells and natural killer-like T cells responding in a MHC class I- and II-restricted manner were also induced. Vaccination with Ep-CAM protein may warrant further investigation as a novel therapeutic approach to CRC.

GA733/EpCAM is an oncofetal antigen abundantly expressed in colorectal carcinoma. This antigen can spontaneously induce a humoral and cellular antitumor immunity and may therefore be a suitable target structure for immunotherapy. Patients with advanced colorectal carcinoma have been treated with monoclonal antibodies (MAb17-1A) against this structure. The data indicate that the chimeric variant was not superior to the original mouse MAb. Addition of cytokines and chemotherapeutics may improve the therapeutic effect of the MAb. A particularly interesting regimen is a combination of MAb17-1A/GM-CSF/alpha-IFN/5-Fu. The GA733 protein antigen can also be used as a vaccine. Patients with colorectal carcinoma stages B and C were vaccinated with this protein antigen in combination with GM-CSF as an adjuvant cytokine. A strong type I T cell response was induced that seemed to be MHC class I as well as class II restricted. No systemic side effects were noted.