Effects of orofacial myofunctional therapy on masticatory function in individuals submitted to orthognathic surgery: a randomized trial

Abstract Objectives: The esthetic and functional results of orthognathic surgery of severe dentofacial deformities are predictable, however there are differences regarding the effects on stomatognathic system. The aim was to investigate the effects of orofacial myofunctional therapy (OMT) on the masticatory function in individuals with dentofacial deformity submitted to orthognathic surgery (OGS). Material and Methods: Forty-eight individuals (18-40 years) were evaluated, 14 undergoing OMT (treated group-TG), 10 without this treatment (untreated group-UTG) and 24 in a control group with normal occlusion; for clinical aspects the data of an individual was missed (n=46). Chewing was performed using the Expanded protocol of orofacial myofunctional evaluation with scores (OMES-E). Muscle tone and mobility were also analyzed before (P0), three (P1) and six months (P2) after OGS. Surface electromyography of the masseter and temporalis muscles was performed, considering the parameters amplitude and duration of act and cycle, and the number of masticatory cycles. The OMT consisted of ten therapeutic sessions along the postoperative period. The results were compared using parametric and non-parametric tests. Results: TG showed higher scores in P1 and P2 than P0; for the masticatory type the scores in P2 were significantly higher than P0. In addition, the proportion of individuals with adequate tone of lower lip and adequate tongue mobility for TG increased significantly from P1 and P2 in relation to P0. The EMG results showed a decrease in act and cycle duration in P2 in relation to P0 and P1 for the TG; furthermore the values were close to controls. An increase in the number of cycles from P0 to P2 was also observed, indicating faster chewing, which may be attributed to an improvement of balanced occlusion associated with OMT. Conclusion: There were positive effects of OMT on the clinical and electromyography aspects of chewing in individual submitted to orthognathic surgery

Changes in Proteasome Structure and Function Caused by HAMLET in Tumor Cells

BACKGROUND: Proteasomes control the level of endogenous unfolded proteins by degrading them in the proteolytic core. Insufficient degradation due to altered protein structure or proteasome inhibition may trigger cell death. This study examined the proteasome response to HAMLET, a partially unfolded protein-lipid complex, which is internalized by tumor cells and triggers cell death. METHODOLOGY/PRINCIPAL FINDINGS: HAMLET bound directly to isolated 20S proteasomes in vitro and in tumor cells significant co-localization of HAMLET and 20S proteasomes was detected by confocal microscopy. This interaction was confirmed by co-immunoprecipitation from extracts of HAMLET-treated tumor cells. HAMLET resisted in vitro degradation by proteasomal enzymes and degradation by intact 20S proteasomes was slow compared to fatty acid-free, partially unfolded alpha-lactalbumin. After a brief activation, HAMLET inhibited proteasome activity in vitro and in parallel a change in proteasome structure occurred, with modifications of catalytic (beta1 and beta5) and structural subunits (alpha2, alpha3, alpha6 and beta3). Proteasome inhibition was confirmed in extracts from HAMLET-treated cells and there were indications of proteasome fragmentation in HAMLET-treated cells. CONCLUSIONS/SIGNIFICANCE: The results suggest that internalized HAMLET is targeted to 20S proteasomes, that the complex resists degradation, inhibits proteasome activity and perturbs proteasome structure. We speculate that perturbations of proteasome structure might contribute to the cytotoxic effects of unfolded protein complexes that invade host cells

HAMLET Binding to α-Actinin Facilitates Tumor Cell Detachment

Cell adhesion is tightly regulated by specific molecular interactions and detachment from the extracellular matrix modifies proliferation and survival. HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a protein-lipid complex with tumoricidal activity that also triggers tumor cell detachment in vitro and in vivo, suggesting that molecular interactions defining detachment are perturbed in cancer cells. To identify such interactions, cell membrane extracts were used in Far-western blots and HAMLET was shown to bind α-actinins; major F-actin cross-linking proteins and focal adhesion constituents. Synthetic peptide mapping revealed that HAMLET binds to the N-terminal actin-binding domain as well as the integrin-binding domain of α-actinin-4. By co-immunoprecipitation of extracts from HAMLET-treated cancer cells, an interaction with α-actinin-1 and -4 was observed. Inhibition of α-actinin-1 and α-actinin-4 expression by siRNA transfection increased detachment, while α-actinin-4-GFP over-expression significantly delayed rounding up and detachment of tumor cells in response to HAMLET. In response to HAMLET, adherent tumor cells rounded up and detached, suggesting a loss of the actin cytoskeletal organization. These changes were accompanied by a reduction in β1 integrin staining and a decrease in FAK and ERK1/2 phosphorylation, consistent with a disruption of integrin-dependent cell adhesion signaling. Detachment per se did not increase cell death during the 22 hour experimental period, regardless of α-actinin-4 and α-actinin-1 expression levels but adherent cells with low α-actinin levels showed increased death in response to HAMLET. The results suggest that the interaction between HAMLET and α-actinins promotes tumor cell detachment. As α-actinins also associate with signaling molecules, cytoplasmic domains of transmembrane receptors and ion channels, additional α-actinin-dependent mechanisms are discussed

Developmental perspectives on interpersonal affective touch

In the last decade, philosophy, neuroscience and psychology alike have paid increasing attention to the study of interpersonal affective touch, which refers to the emotional and motivational facets of tactile sensation. Some aspects of affective touch have been linked to a neurophysiologically specialised system, namely the C tactile (CT) system. While the role of this sys-tem for affiliation, social bonding and communication of emotions have been widely investigated, only recently researchers have started to focus on the potential role of interpersonal affective touch in acquiring awareness of the body as our own, i.e. as belonging to our psychological ‘self’. We review and discuss recent developmental and adult findings, pointing to the central role of interpersonal affective touch in body awareness and social cognition in health and disorders. We propose that interpersonal affective touch, as an interoceptive modality invested of a social nature, can uniquely contribute to the ongoing debate in philosophy about the primacy of the relational nature of the minimal self

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Cellular interactions of HAMLET and their role in cell death

HAMLET is a protein-lipid complex that selectively kills tumor cells. In this thesis, we identified new mechanisms, whereby HAMLET initiates and executes tumor cell death. HAMLET targets several cellular compartments ranging from the plasma membrane to the nucleus. HAMLET rapidly binds to the plasma membrane of tumor cells and the resulting changes in membrane shape and lipid composition activate ion channels and rapid ion fluxes (paper I). Through macropinocytosis, large amounts of HAMLET enter tumor cells, thus reaching intracellular targets (paper II). By interacting with alpha-actinins, HAMLET facilitates tumor cell detachment and perturbs FAK signaling (paper III). Furthermore, HAMLET interacts with HK1, a member of the glycolytic machinery, and thereby disrupts tumor cell metabolism (paper IV). HAMLET also triggers ER stress (paper I). This provides a framework for HAMLET’s ability to rapidly kill a wide range of tumor cells and addresses three major HAMLET questions. 1. How are the tumor cells killed? 2. How is HAMLET internalized by tumor cells? 3. Why do normal differentiated cells survive? We show that HAMLET-induced cell death is initiated at the plasma membrane and requires functional ion channels and p38 MAPK signaling. We identify macropinocytosis as a route for HAMLET internalization and distinguish this process from cell death. Finally, we show that the HAMLET sensitivity reflects tumor cell characteristics, such as c-Myc oncogene expression and altered metabolism, as inhibition of glycolysis increased HAMLET sensitivity. Interestingly, HAMLET does not appear to perturb the membranes of normal differentiated cells, further explaining the tumor selectivity

Målande språk -bildskapande som länk i möten

Vårt syfte med studien är att undersöka och analysera samtalsämnen som kommer upp under bildskapande aktiviteter i förskolan, samt relationen mellan barn-bildmaterial och förskollärare-bildmaterial inspirerade av ett sociomateriellt perspektiv. Då den forskning vi läst mest handlar om den färdiga produkten inom bildskapande aktiviteter vill vi inrikta oss på samtal under bildskapande aktiviteter. Detta gör vi inspirerade av ett sociomateriellt perspektiv då vi inte sett detta tidigare. För att analysera använder vi oss förutom det sociomateriella perspektivet även av begreppen relationell materialism och aktörsskap. Vi använder oss av kvalitativ metod i vår observation då vi har intresse för olika innebörder, tolkningar och meningsskapande som människor i ett specifikt sammanhang är aktörer i. Det vi har sett i våra observationer är att samtalen mest handlar om det konkreta bildskapandet. De vanligaste aktörerna var samspelare vilket stärker synen om att bildaktiviteter är en viktig arena för samspel. Vår slutsats är att vuxnas närvaro och delaktighet i bildskapande verksamhet tillför inspiration och möjlighet till utveckling, men förutsatt att förskollärarna har kunskap och eget intresse

Missbrukande föräldrar, utsatta barn och socialt arbete

The aim of the article is to put together four different studies and research perspectives. The four authors present their own studies about drug addicted mothers; fathers called into question by child welfare authorities; children in foster care; child welfare services. The four studies have a qualitative approach, interviewing parents and children in vulnerable positions and in contact with child welfare authorities. The combined results show the need of coooperation between child welfare and rehabilitation of adults addicted to alcohol and drugs, and the need to have a comprehensive approach to vulnerable families, also during separation. The right of vulnerable children to be heard in research as well as in practice is exemplified and emphasized

Validation of the Test for Substitution Patterns - in individuals with symptomatic knee osteoarthritis

Background: Few tools evaluates quality of movements in individuals with knee osteoarthritis (OA). The Test for Substitution Patterns (TSP) is developed to measure the ability to perform five functional movements regarding postural control and altered movement patterns (1). TSP is validated and reliable in individuals with anterior cruciate ligament injury, but has not yet been evaluated in individuals with knee OA. Objectives: To study the relationships between the OA modified TSP (OA-TSP) and self-reported knee function as measured with the Knee Injury and osteoarthritis Outcome Score (KOOS) and the 30-s chair stand test (30-s CST) in individuals with symptomatic knee OA. A second aim was to study the discriminative ability of the OA-TSP for unilateral knee pain. Methods: Sixty-two individuals with symptomatic knee osteoarthritis were included using consecutive sampling. Health status was assessed with the EuroQol five dimension scale (EQ5D, 0-1 worst-best), and knee function in five subscales for KOOS (pain, symptoms, ADL, quality of life and sport/recreation, 0-100 worst-best). The 30-s CST-test measured the number of rises in 30 seconds. In the OA-TSP, substitution patterns are observed and scored from 0-3 (no substitution pattern-poorly performed) during five standardized functional movements. The maximum score is 54 points/side with score of 108 points. Median and min-max were used for all descriptive data. Spearman´s correlation and Wilcoxon signed rank test were used for analyzes. A correlation coefficient rs ≥±0.50 is considered large, ±0.30 to < 0.50 moderate and ±0.10 < 0.30 small. Results: The median age was 54 years (30-61), 76% were women. The median Body Mass Index was 25 (18-48) and EQ5D 0.8 (0.29-1.00). There were no significant differences between the gender regarding BMI and EQ5D. Median OA-TSP total score was 29 (10-70). Median KOOS pain was 75 (36-100), symptoms 71 (21-96), ADL 87 (30-100), and sport/rec 50 (0-100). In the 30-s CST the median was 16 raises (5-32). Moderate, significant correlations were observed between TSP total score and KOOS pain and KOOS ADL (rs=-0.30; p=0.03, rs=-0.35; p=0.01 respectively) and small correlations between TSP and KOOS sport/recreation and KOOS symptoms (rs=-0.13; p=0.36, rs=-0.22; p=0.11 respectively). There was a moderate, significant correlation between TSP total score and 30-s CST (rs=-0.34; p<0.01). Discriminative ability for the TSP for unilateral knee pain was found to be significant worse in the painful side, with median 18 (2-36) vs. 14 (7-37) in the not painful side, p=0.001. Conclusion: The OA-TSP could be used as a functional test to detect altered knee alignment interpreted as an early sign of knee OA and assist the physiotherapist in functional testing during the rehabilitation of individuals with symptomatic knee OA. References 1. Trulsson A et al. Relationships between postural orientation and self reported function, hop performance and muscle power in subjects with anterior cruciate ligament injury. BMC Musculoskelet Disord. 2010;11:143

HAMLET: functional properties and therapeutic potential.

Human α-lactalbumin made lethal to tumor cells (HAMLET) is the first member in a new family of protein-lipid complexes that kills tumor cells with high selectivity. The protein component of HAMLET is α-lactalbumin, which in its native state acts as a substrate specifier in the lactose synthase complex, thereby defining a function essential for the survival of lactating mammals. In addition, α-lactalbumin acquires tumoricidal activity after partial unfolding and binding to oleic acid. The lipid cofactor serves the dual role as a stabilizer of the altered fold of the protein and a coactivator of specific steps in tumor cell death. HAMLET is broadly tumoricidal, suggesting that the complex identifies conserved death pathways suitable for targeting by novel therapies. Sensitivity to HAMLET is defined by oncogene expression including Ras and c-Myc and by glycolytic enzymes. Cellular targets are located in the cytoplasmic membrane, cytoskeleton, mitochondria, proteasomes, lysosomes and nuclei, and specific signaling pathways are rapidly activated, first by interactions of HAMLET with the cell membrane and subsequently after HAMLET internalization. Therapeutic effects of HAMLET have been demonstrated in human skin papillomas and bladder cancers, and HAMLET limits the progression of human glioblastomas, with no evidence of toxicity for normal brain or bladder tissue. These findings open up new avenues for cancer therapy and the understanding of conserved death responses in tumor cells