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The aim of this study was to assess the reproducibility of non-verbal facial expressions in unilateral facial paralysis using dynamic four-dimensional (4D) imaging. The Di4D system was used to record five facial expressions of 20 adult patients. The system captured 60 three-dimensional (3D) images per second; each facial expression took 3–4 seconds which was recorded in real time. Thus a set of 180 3D facial images was generated for each expression. The procedure was repeated after 30 min to assess the reproducibility of the expressions. A mathematical facial mesh consisting of thousands of quasi-point ‘vertices’ was conformed to the face in order to determine the morphological characteristics in a comprehensive manner. The vertices were tracked throughout the sequence of the 180 images. Five key 3D facial frames from each sequence of images were analyzed. Comparisons were made between the first and second capture of each facial expression to assess the reproducibility of facial movements. Corresponding images were aligned using partial Procrustes analysis, and the root mean square distance between them was calculated and analyzed statistically (paired Student t -test, P < 0.05). Facial expressions of lip purse, cheek puff, and raising of eyebrows were reproducible. Facial expressions of maximum smile and forceful eye closure were not reproducible. The limited coordination of various groups of facial muscles contributed to the lack of reproducibility of these facial expressions. 4D imaging is a useful clinical tool for the assessment of facial expressions. [ABSTRACT FROM AUTHOR]

Palatal tumours are relatively rare and of variable aetiology, rendering radiological evaluation a daunting process for many. A systematic approach to the imaging of a palatal lump is therefore essential. The hard and soft palates are oral cavity and oropharyngeal structures, respectively. They have different tissue compositions, and therefore, lesions occur with different frequencies at each site. The hard palate has the highest concentration of minor salivary glands in the upper aerodigestive tract and most tumours here are salivary in origin, whereas most tumours at the soft palate are epithelial in origin, i.e., squamous cell carcinomas, in line with other oropharyngeal subsites. The most common malignant tumours of the palate, after squamous cell carcinoma, are minor salivary gland tumours, predominantly adenoid cystic and mucoepidermoid carcinomas. These tumours have a propensity to spread perineurally; understanding the anatomy and imaging features of perineural spread is vital, as it can have significant implications for patient management and tumour resectability. When confronted with a palatal lump, it is important to consider the following: its location on the hard or soft palate; whether it is mucosal or submucosal; the frequently occurring lesions at that site; the most suitable imaging techniques (ultrasound, computed tomography, magnetic resonance imaging); whether there are typical imaging features for any of the common lesions; and whether there are aggressive features, such as bone erosion or perineural spread. This approach allows the radiologist to narrow the differential diagnosis and assist the clinicians with planning treatment. [ABSTRACT FROM AUTHOR]

This article briefly reviews psychological aspects of pain, paying special attention to chronic pain. The review considers the interruptive and interference effects of pain and its impact on a person's identity. The importance of processes related to interruption, interference, and identity will vary across people and the duration of pain. Although brief phasic pain such as that presented in the laboratory will have marked interruptive effects, it is unlikely to produce interference or impact on a person's identity. Acute clinical pain will have both interruptive and interference effects, albeit of a temporary nature, but it is unlikely to have any impact on a person's identity. Chronic persistent pain or frequent recurrent episodic pain, such as headache, may have profound effects on a Person's life. Each of these themes is illustrated with examples drawn from the experimental and clinical literature. [ABSTRACT FROM AUTHOR]

Psychological interventions are a mainstay of modern pain management practice and a recommended feature of a modern pain treatment service. Systematic reviews for the evidence of psychological interventions are reviewed in this article. The evidence for effectiveness is strongest for cognitive behavioural therapy with a focus on cognitive coping strategies and behavioural rehearsal. Most evidence is available for treatments of adult pain, although adolescent chronic pain treatments are also reviewed. It is clear that treatment benefit can be achieved with cognitive behavioural methods. It is possible to effect change in pain, mood, and disability, changes not achieved by chance or by exposure to any other treatment. However, the overall effect sizes of treatments for adults, across all trials, are modest. Reasons for the relatively modest treatment effects are discussed within the context of all treatments for chronic pain being disappointing when measured by the average. Suggestions for improving both trials and evidence summaries are made. Finally, consideration is given to what can be achieved by the pain specialist without access to specialist psychology resource. [ABSTRACT FROM PUBLISHER]

Summary: Background: The face can be reanimated after long-term paralysis by free microneurovascular tissue transfer. Flaps from gracilis and pectoralis minor usually require a two-stage procedure with a cross-face nerve graft. Latissimus dorsi has a much longer muscular nerve, the thoracodorsal nerve, which could avoid the need for a second cross-face nerve graft. Our hypothesis is that the neurovascular pedicles of small segments of latissimus dorsi would be long enough to reach the opposite side of the face and to provide a reliable blood and nerve supply to the flaps. Method: To test this hypothesis the thoracodorsal pedicle and its primary branches were dissected in eleven embalmed cadavers. The segmental vessels and nerves were then traced in a series of simulated flaps approximately 8–10 cm × 2–3 cm by micro-dissection, tissue clearing and histology. Results: The thoracodorsal pedicle is 10–14 cm long to where it enters the muscle, and with intra-muscular dissection small chimeric muscle segments 8–10 cm × 2–3 cm can be raised with a clearly defined neurovascular supply. Using micro-dissection the neurovascular pedicle can be lengthened to reach across the face. Segmental arteries and nerves extended to the distal end of all the flaps examined. Artery, vein and nerve run together and are of substantial diameter. Conclusion: Small muscle segments of latissimus dorsi can be raised on long neurovascular pedicles. The vessels and nerves are substantial and the likelihood of surgical complications such as flap necrosis and functional disuse on transplantation appear low. Although in our opinion the use of cross-face nerve grafts and transfer of smaller muscle flaps remains the gold standard in facial reanimation in straightforward cases, the micro-dissected latissimus dorsi flap is a useful option in complex cases of facial reanimation. Clinical Application: Facial reanimation using micro-dissected segments of latissimus dorsi has been performed in four complex cases of facial paralysis. [Copyright &y& Elsevier]

Summary: Background: The present study was conducted to investigate the anatomy of the motor nerve to the gracilis muscle (MNG) to provide the anatomical basis for harvesting a one-stage gracilis transfer with a long nerve for re-animation of the paralysed face. Methods: An anatomical study was performed on 24 lower-limb specimens (from the pelvis down to the knee) from 12 embalmed cadavers. The MNG was dissected from the surface of the muscle to the obturator foramen. Two anatomical regions were defined in the course of the nerve. The first region includes the part of the nerve that can easily be reached through a standard incision in the medial aspect of the thigh, that is, from the surface of the muscle to the posterior border of the adductor brevis muscle and the second region from there to the obturator foramen. Measurements of both anatomical regions and the maximum length of the nerve were taken with a calliper. The anatomical relations of the nerve were also noted and photo-documented. Results: The median maximum length of the MNG from the surface of gracilis to the posterior border of adductor brevis (‘first anatomical region’) was 7.7cm (Range 6.3–10.5cm); from there to the obturator foramen (‘second anatomical region’) the length was 3.7cm (Range 2–6cm), giving a median length of dissection of the nerve as 11.5cm (Range 9.9–13.6cm). Intraneural dissection of the MNG has to be performed proximally in the course of the nerve (the part corresponding to the second anatomical region), just where it runs inside the fascia over the obturator externus muscle. Conclusions: Over 10-cm length of the MNG can be obtained when dissected along the course of the nerve up to the obturator foramen. To achieve the maximum length, intraneural dissection must normally be performed after the nerve passes the posterior border of the adductor brevis. An endoscopic approach or extended proximal incision is recommended to easily reach the proximal part of the nerve as far as the obturator foramen. [Copyright &y& Elsevier]

Abstract: Upon T cell receptor engagement, both the actin cytoskeleton and substrates of tyrosine phosphorylation are remodeled to create a signaling complex at the interface of the antigen-presenting cell and responding T cell. While T cell signaling has been shown to regulate actin reorganization, the mechanisms by which changes in actin dynamics affect early T cell signaling have not been fully explored. Using gelsolin, an actin-binding protein with capping and severing activities, and latrunculin, an actin-depolymerizing agent, we have further investigated the interplay between actin dynamics and the regulation of T cell signaling. Overexpression of gelsolin altered actin dynamics in Jurkat T cells, and alteration of actin dynamics correlated with dysregulation of tyrosine phosphorylation of raft-associated substrates. This perturbation of tyrosine phosphorylation was correlated with inhibition of activation-dependent signaling pathways regulating Erk-1/2 phosphorylation, NF-AT transcriptional activation and IL-2 production. Modification of actin by the depolymerizing agent latrunculin also altered the tyrosine phosphorylation patterns of proteins associated with lipid rafts, and pre-treatment with latrunculin inhibited anti-CD3 mAb-mediated NF-AT activation. Thus, our data indicate that actin cytoskeletal dynamics modulate the tyrosine phosphorylation of raft-associated proteins and subsequent downstream signal transduction. [Copyright &y& Elsevier]

Abstract: The dbl oncogene product is the founding member of a large family of oncogenic proteins that function by activating the small GTP-binding proteins Cdc42, Rac and Rho. Through its substrate GTPases, Dbl transduces proliferative signals from cell-surface receptors to diverse cellular effectors and signaling pathways. The mechanisms by which these multiple signals are integrated, as well as their relative contribution to Dbl-induced cell transformation, are presently poorly understood. We investigated the role of the survival regulators PI3-kinase and Akt in Dbl-induced cell transformation. We found that Dbl induced the phosphorylation of Akt on threonine 308, through the GTPases Rac and Cdc42 and in a PI3-kinase dependent manner. Pharmacological or biochemical interference with this pathway lead to a marked, dose-dependent inhibition of the focus formation activity exhibited by Dbl-expressing cells. Dbl expression stimulated the phosphorylation of the anti-apoptotic Akt substrate Bad, and caused a marked decrease in basal levels of apoptosis. Finally, we found that activated Cdc42 existed in cells in complex with phosphoionositide-dependent kinase-1 (PDK1), the downstream mediator of PI3-kinase action. The data indicate that Dbl signaling stimulate the formation of a novel survival complex, through which anti-apoptotic signals are generated and propagated. [Copyright &y& Elsevier]

An abstract of the article "The α-Tocopherol Transfer Protein," by D. Manor and S. Morley is presented.

The article focuses on the association between chronic pain and depression and their management in context of patient care. Topics include morbidity associated with the conditions, hypotheses for mechanism of the relation between the two conditions such as one involving psychological mediators, and their links with serotonin and norepinephrine. Methods of their management include cognitive behavior therapy and hypnosis, antidepressants and mood stabilizers, and interventional treatments.

• US-guided transoral core needle biopsy (CNB) is safe, feasible and accurate. • There are advantages over other modalities for some medial head and neck pathology. • Technique enhances diagnosis, informs decision making, potentially avoids surgery. • US-guided transoral CNB is simple to perform requiring a short general anaesthetic. [ABSTRACT FROM AUTHOR]

Background: Estrogen receptor-positive (ER-positive) metastatic breast cancer is often intractable due to endocrine therapy resistance. Although ESR1 promoter switching events have been associated with endocrine-therapy resistance, recurrent ESR1 fusion proteins have yet to be identified in advanced breast cancer. Patients and methods: To identify genomic structural rearrangements (REs) including gene fusions in acquired resistance, we undertook a multimodal sequencing effort in three breast cancer patient cohorts: (i) mate-pair and/or RNAseq in 6 patientmatched primary-metastatic tumors and 51 metastases, (ii) high coverage (>500×) comprehensive genomic profiling of 287- 395 cancer-related genes across 9542 solid tumors (5216 from metastatic disease), and (iii) ultra-high coverage (>5000×) genomic profiling of 62 cancer-related genes in 254 ctDNA samples. In addition to traditional gene fusion detection methods (i.e. discordant reads, split reads), ESR1 REs were detected from targeted sequencing data by applying a novel algorithm (copyshift) that identifies major copy number shifts at rearrangement hotspots. Results: We identify 88 ESR1 REs across 83 unique patients with direct confirmation of 9 ESR1 fusion proteins (including 2 via immunoblot). ESR1 REs are highly enriched in ER-positive, metastatic disease and co-occur with known ESR1 missense alterations, suggestive of polyclonal resistance. Importantly, all fusions result from a breakpoint in or near ESR1 intron 6 and therefore lack an intact ligand binding domain (LBD). In vitro characterization of three fusions reveals ligand-independence and hyperactivity dependent upon the 30 partner gene. Our lower-bound estimate of ESR1 fusions is at least 1% of metastatic solid breast cancers, the prevalence in ctDNA is at least 10× enriched. We postulate this enrichment may represent secondary resistance to more aggressive endocrine therapies applied to patients with ESR1 LBD missense alterations. Conclusions: Collectively, these data indicate that N-terminal ESR1 fusions involving exons 6-7 are a recurrent driver of endocrine therapy resistance and are impervious to ER-targeted therapies. [ABSTRACT FROM AUTHOR]

Elucidating the molecular regulation of macrophage migration is essential for understanding the pathophysiology of multiple human diseases, including host responses to infection and autoimmune disorders. Macrophage migration is supported by dynamic rearrangements of the actin cytoskeleton, with formation of actin-based structures such as podosomes and lamellipodia. Here we provide novel insights into the function of the actin-bundling protein l -plastin (LPL) in primary macrophages. We found that podosome stability is disrupted in primary resident peritoneal macrophages from LPL −/− mice. Live-cell imaging of F-actin using resident peritoneal macrophages from LifeACT-RFP + mice demonstrated that loss of LPL led to decreased longevity of podosomes, without reducing the number of podosomes initiated. Additionally, macrophages from LPL −/− mice failed to elongate in response to chemotactic stimulation. These deficiencies in podosome stabilization and in macrophage elongation correlated with impaired macrophage transmigration in culture and decreased monocyte migration into murine peritoneum. Thus, we have identified a role for LPL in stabilizing long-lived podosomes and in enabling macrophage motility. [ABSTRACT FROM AUTHOR]

Summary Nasopharyngeal (NP) pneumococcal carriage predisposes children to pneumococcal infections. Defining the proportion of pneumococcal isolates that are antibiotic-resistant enables the appropriate choice of empiric therapies. The antibiogram of NP carriage isolates derived from a pediatric population following the introduction of the 13-valent pneumococcal conjugate vaccine was defined in this study. [ABSTRACT FROM AUTHOR]