Identification and Characterization of Pain Processing Patterns Among Patients with Chronic Primary Pain: A replication.

OBJECTIVES To develop individual and effective treatment plans for patients with chronic pain, we aimed to replicate Grolimund et al's (2017) empirical categorization of chronic pain patients on a new and larger sample. Moreover, this work aimed to extend previous knowledge by considering various treatment outcomes and exploratorily analyzing which coping skills might be particularly relevant for treatment success in each subtype. METHODS Latent class analysis was used to identify homogenous subtypes with different pain processing patterns using the pain processing questionnaire (FESV). RESULTS By analyzing 602 inpatients with chronic primary pain, we identified three subtypes: (1) severely burdened individuals with low coping skills, (2) mildly burdened individuals with high coping skills, and (3) moderately burdened individuals with moderate coping skills. Pain interference, psychological distress, cognitive and behavioral coping skills improved after treatment in all subtypes. Pain-related mental interference significantly improved only in subtypes (1) and (3). Only individuals of subtype (3) reported significant reductions in pain intensity after treatment. Exploratory regression analysis suggested that of subtype (1), the most promising targets in reducing pain interference and psychological distress post-treatment might be to foster relaxation techniques, counteractive activities, and cognitive restructuring. None of the FESV dimensions significantly predicted treatment outcomes among individuals of subtype (2). Individuals of subtype (3) might benefit the most from experiencing more competence during treatment. DISCUSSION Our findings highlight the importance of identifying and characterizing subtypes of chronic primary pain patients and that these subtypes should be considered for individualized and effective treatment

Improvements in pain coping predict treatment success among patients with chronic primary pain.

OBJECTIVE Given the increasing incidence and prevalence of chronic pain, effective treatments for chronic pain are needed. This study aimed to investigate the role of cognitive and behavioral pain coping regarding the prediction of treatment outcomes among inpatients with chronic primary pain participating in an interdisciplinary multimodal treatment program. METHODS At intake and discharge, 500 patients with chronic primary pain completed questionnaires on pain intensity, pain interference, psychological distress, and pain processing. RESULTS Patients' symptoms, cognitive and behavioral pain coping improved significantly after treatment. Similarly, separate cognitive and behaviroal coping skills improved significantly after treatment. Hierarchical linear models revealed no significant associations of pain coping with reductions in pain intensity. Whereas the overall level and improvements in cognitive pain coping predicted reductions in pain interference and psychological distress, the overall level and improvements in behavioral pain coping were associated with reductions in pain interference alone. DISCUSSION Since pain coping seems to influence both pain interference and psychological distress, improving cognitive and behavioral pain coping during an interdisciplinary multimodal pain treatment seems to be a key component in the successful treatment of inpatients with chronic primary pain, enabling them to function better physically and mentally despite their chronic pain. Clinically, it might be worth fostering and exercising cognitive restructuring as well as action planning in treatment to reduce both pain interference and psychological distress levels post-treatment. In addition, practicing relaxation techniques might help reduce pain interference post-treatment, whereas making experiences of personal competence might help reduce psychological distress post-treatment

How Treatment Motivation Predicts Favorable Outcomes in Interdisciplinary Multimodal Pain Treatment Among Patients with Chronic Primary Pain.

As motivation for psychological treatment at intake has been shown to predict favorable outcomes after an inpatient stay, this study aimed to further characterize the different components of psychological treatment motivation that predict favorable treatment outcomes. 294 inpatients with chronic primary pain participating in an interdisciplinary multimodal pain treatment in a tertiary psychosomatic university clinic completed a battery of psychological questionnaires at intake and discharge. Treatment motivation was assessed at intake using the scales of the FPTM-23 questionnaire, while pain intensity, pain interference, anxiety, and depression were assessed both at intake and discharge. After treatment, pain intensity, pain interference, anxiety, and depression were significantly reduced. While higher levels on the FPTM-23 scale of suffering predicted smaller decreases in anxiety after treatment, higher scores on the scale of hope, i.e., lower levels of hopelessness, predicted lower levels of pain interference, anxiety, and depression after treatment. None of the scales of treatment motivation predicted pain intensity levels after treatment. Above and beyond providing symptom relief, reducing hopelessness and fostering hope regarding the treatment process and outcome might help clinicians treat patients with chronic primary pain more effectively

War experiences and relationship problems predict pain sensitivity cross-sectionally among patients with chronic primary pain.

BACKGROUND Most patients suffering from chronic pain are more susceptible to pain and pressure due to higher pain sensitivity. Since psychosocial factors play a central role in developing and maintaining chronic pain, investigating associations between pain sensitivity and psychosocial stressors promises to advance the biopsychosocial understanding of chronic pain. OBJECTIVES We aimed to replicate Studer et al.'s (2016) findings about associations of psychosocial stressors with pain sensitivity in a new sample of patients with chronic primary pain (ICD-11, MG30.0). METHODS A pain provocation test was used on both middle fingers and earlobes to assess pain sensitivity among 460 inpatients with chronic primary pain. Potentially life-threatening accidents, war experiences, relationship problems, certified inability to work, and adverse childhood experiences were assessed as potential psychosocial stressors. Structural equation modeling was used to investigate associations between psychosocial stressors and pain sensitivity. RESULTS We partially replicated Studer et al.'s findings. Similar to the original study, patients with chronic primary pain showed enhanced pain sensitivity values. Within the investigated group, war experiences (β = 0.160, p < .001) and relationship problems (β = 0.096, p = .014) were associated with higher pain sensitivity. In addition, the control variables of age, sex, and pain intensity also showed a predictive value for higher pain sensitivity. Unlike Studer et al., we could not identify a certified inability to work as a predictor of higher pain sensitivity. CONCLUSIONS This study showed that beyond age, sex, and pain intensity, the psychosocial stressors of war experiences and relationship problems were associated with higher pain sensitivity

Functional characterization of the first missense variant in <i>CEP78</i>, a founder allele associated with cone-rod dystrophy, hearing loss and reduced male fertility

Inactivating variants in the centrosomal CEP78 gene have been found in cone-rod dystrophy with hearing loss (CRDHL), a particular phenotype distinct from Usher syndrome. Here, we identified and functionally characterized the first CEP78 missense variant c.449T>C, p.(Leu150Ser) in three CRDHL families. The variant was found in a biallelic state in two Belgian families and in a compound heterozygous state-in trans with c.1462-1G>T-in a third German family. Haplotype reconstruction showed a founder effect. Homology modeling revealed a detrimental effect of p.(Leu150Ser) on protein stability, which was corroborated in patients' fibroblasts. Elongated primary cilia without clear ultrastructural abnormalities in sperm or nasal brushes suggest impaired cilia assembly. Two affected males from different families displayed sperm abnormalities causing infertility. One of these is a heterozygous carrier of a complex allele in SPAG17, a ciliary gene previously associated with autosomal recessive male infertility. Taken together, our data indicate that a missense founder allele in CEP78 underlies the same sensorineural CRDHL phenotype previously associated with inactivating variants. Interestingly, the CEP78 phenotype has been possibly expanded with male infertility. Finally, CEP78 loss-of-function variants may have an underestimated role in misdiagnosed Usher syndrome, with or without sperm abnormalities

Functional characterization of the first missense variant in CEP78, a founder allele associated with cone-rod dystrophy, hearing loss, and reduced male fertility

Inactivating variants in the centrosomal CEP78 gene have been found in cone-rod dystrophy with hearing loss (CRDHL), a particular phenotype distinct from Usher syndrome. Here, we identified and functionally characterized the first CEP78 missense variant c.449T>C, p.(Leu150Ser) in three CRDHL families. The variant was found in a biallelic state in two Belgian families and in a compound heterozygous state-in trans with c.1462-1G>T-in a third German family. Haplotype reconstruction showed a founder effect. Homology modeling revealed a detrimental effect of p.(Leu150Ser) on protein stability, which was corroborated in patients' fibroblasts. Elongated primary cilia without clear ultrastructural abnormalities in sperm or nasal brushes suggest impaired cilia assembly. Two affected males from different families displayed sperm abnormalities causing infertility. One of these is a heterozygous carrier of a complex allele in SPAG17, a ciliary gene previously associated with autosomal recessive male infertility. Taken together, our data indicate that a missense founder allele in CEP78 underlies the same sensorineural CRDHL phenotype previously associated with inactivating variants. Interestingly, the CEP78 phenotype has been possibly expanded with male infertility. Finally, CEP78 loss-of-function variants may have an underestimated role in misdiagnosed Usher syndrome, with or without sperm abnormalities

Bioconjugation of supramolecular metallacages to integrin ligands for targeted delivery of cisplatin

Cisplatin occupies a crucial role in the treatment of various malignant tumours. However, its efficacy and applicability are heavily restricted by severe systemic toxicities and drug resistance. Our study exploits the active targeting of supramolecular metallacages to enhance the activity of cisplatin in cancer cells while reducing its toxicity. Thus, Pd2L4 cages (L = ligand) have been conjugated to four integrin ligands with different binding affinity and selectivity. Cage formation and encapsulation of cisplatin was proven by NMR spectroscopy. Upon encapsulation, cisplatin showed increased cytotoxicity in vitro, in melanoma A375 cells overexpressing αvβ3 integrins. Moreover, ex vivo studies in tissue slices indicated reduced toxicity towards healthy liver and kidney tissues for cage-encapsulated cisplatin. Analysis of metal content by ICP-MS demonstrated that encapsulated drug is less accumulated in these organs compared to the ‘free’ one

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Gentileschis Judith i Oslo

Summary The painting Judith and the maidservant with the head of Holofernes (oil on canvas, 136 x 159,5) inven.no 02073, came to the National Gallery (NG ) in Oslo as a Caravaggio in 1945, was reattributed to Orazio or Artemisia Gentileschi in 1951, and is today attributed to Orazio (1563-1639) by NG and most scholars, while a small minority has pointed at Artemisia (1593-1653). The Judith is unsigned and undated (probable dating varies from 1608-1616). There were no earlier documents known to the NG than from a sale in Paris in 1895, when the painting was bought by Wang Kunsthandel and sold to a private collection in Norway, whose estate subsequently sold it to NG. This thesis is quoting an Italian researcher bringing the provenance now back to 1817, and discussing an earlier text presenting the work. Because of the lack of written material, the painting itself is the most important witness to its own history and main source of knowledge. The thesis concentrates on finding as much as possible based on the object, combined with earlier research and new comparative analysis. The methods used are the most classic tools in art history. In kind cooperation with the NG it has also been possible to follow the new technical investigations, including pigment-tests and Xrays, which has enabled a thorough analysis of the work. This confirms for the first time that all pigments correspond to the 1600s, while the stylistic analyses confirm the affiliation with the Gentileschi studio. The X-rays reveal a possibility of another background. The thesis has focused on the motive depicted in Oslo by a rather deep dip into Judith s iconography from the Book of Judith, and by identifying Judith s red brocade dress, searching for possible patrons. The path leads (among others) to the Medici-family in Florence, although it is not possible to conclude in lack of written documents. While discussing the problematic methods of attribution in general, shortcomings of stylistic comparisons and especially problems with the authorship of father and daughter in other works, the aim has been to look closely at the material mainly by widening the comparative analyses with the 12 other known Judith-works by the Gentileschis. Describing and building on earlier research, the comparisons have focused on new questions and arguments into mainly three areas: 1) Composition, 2) Use of dramatic and psychological instruments and 3) Use of jewelry and symbols. The formal analysis points to both father and daughter. A special cameo with a symbol in the hair of Oslo-Judith bears a strong resemblance to other Judiths by Artemisia, as noted in international research since 1991, but barely mentioned in Norway. By comparing the symbol in this piece of jewelry to those in all of Artemisia s Judiths, and quoting earlier research, it is possible to find a connecting thread through all of them. Artemisias active use of symbols strengthens both the virtue and the virtù of her Judiths through the depiction of Greek goddesses, and the thesis concludes that the work in Oslo is in fact a Judith-Athena. The thesis also compares Judith in Oslo with Susanna and the elders in Pommersfelden. Although it may never be possible to conclude with certainty about the authorship, (and considering that the father probably often helped his daughter in the beginning), the thesis pinpoints several arguments for the daughter s hand in the painting

[The sociolinguistic meaning of hand and nerves and their emotional expression].

The sociolinguistic meaning of hand and nerves and their emotional expression Abstract. This article on the sociolinguistic occurrence of the hand and nerves in our everyday language reveals that the German language has a rich repertoire of metaphors and proverbs referring to fingers, hands, arms and nerves, expressing our feelings including pain. There are - on the one hand - not only plenty of expressions and phrases describing the physical purpose of the upper extremity, but - on the other hand - also countless metaphorical terms related to psychological, emotional or social contents. In contrast to medical terminology, everyday language does not hesitate to name the psychosocial dimension of things - High five