Interaction Between a High-Fat Diet and Tau Pathology in Mice: Implications for Alzheimer's Disease.

BACKGROUND: Obesity is a modifiable risk factor for Alzheimer's disease (AD). However, its relation with tau pathology (i.e., aberrant tau protein behavior in tauopathies such as AD) has been inconclusive. OBJECTIVE: This study investigated the interaction between a high-fat diet (HFD) and tau pathology in adult male mice. METHODS: Transgenic mice overexpressing human P301S Tau (those with the pathology) and wild-type (WT) littermates were subjected to behavioral tests, functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and western blotting analysis to investigate the effects of prolonged HFD versus regular diet during adulthood. RESULTS: HFD increased body weight in both WT and P301S mice but had minimal effect on blood glucose levels. The brain response to HFD was tau genotype-specific. WT mice exhibited decreased recognition memory and enhanced network connectivity in fMRI, while P301S mice exhibited white matter tract disorganization in DTI as the sole significant finding. The reduction of insulin receptor ß, insulin downstream signaling, neuronal nuclear protein, CD68-positive phagocytic activity, and myelin basic protein level were confined to the cortex of WT mice. In contrast to P301S mice, WT mice showed significant changes in the tau protein and its phosphorylation levels along with increased soluble neurofilament light levels in the hippocampus. CONCLUSIONS: HFD-induced brain dysfunction and pathological changes were blunted in mice with the pathology and more profound in healthy mice. Our findings highlight the need to consider this interaction between obesity and tau pathology when tailoring treatment strategies for AD and other tauopathies.

Particulate matter 2.5 induces the skin barrier dysfunction and cutaneous inflammation via AhR- and T helper 17 cell-related genes in human skin tissue as identified via transcriptome analysis.

Particulate matter (PM2.5) is an environmental pollutant causing skin inflammatory diseases via epidermal barrier damage. However, the mechanism and related gene expression induced by PM2.5 remains unclear. Our aim was to determine the effect of PM2.5 on human skin tissue ex vivo, and elucidate the mechanism of T helper 17 cell-related inflammatory cytokine and skin barrier function. We verified the expression levels of gene in PM2.5-treated human skin tissue using Quantseq (3' mRNA-Seq), and Gene Ontology (GO) terms and protein-protein interaction (PPI) networks were performed. The PM2.5 treatment significantly enhanced the expression of Th 1, 2, 17 and 22 cell-related genes (cut-off value: │1.2 │ > fold change and p < 0.05). Most of all, Th17 cell-related genes are upregulated and those genes are associated with skin epidermal barrier function and Aryl hydrocarbon receptor (AhR), a xenobiotic receptor, pathway. In human keratinocyte cell lines, AhR-regulated genes (e.g. AhRR, CYP1A1, IL6 and IL36G), Th17 cell-related genes (e.g. IL17C) and epidermal barrier-related genes (e.g. SPRR2A and KRT71) are significantly increased after PM2.5. In the protein level, the secretion of IL-6 and IL-36G was increased in human skin tissue following PM2.5 treatment, and the expression of SPRR2A and KRT71 was significantly increased. PM2.5 exposure could ruin the skin epidermal barrier function via AhR- and Th17 cell-related inflammatory pathway.

Usefulness of Allogenic Acellular Dermal Matrix for Prevention of Scalp Depression after Burr Hole Trephination.

OBJECTIVE: Burr hole trephination is a common treatment for chronic subdural hematoma, intracranial hematoma, and intraventricular hematoma due to its effective drainage of hematoma, minimal invasiveness and short operation time. However, cosmetic complications such as scalp depression can occur. The aim of this study was to evaluate the usefulness of an allogenic acellular dermal matrix (ADM) to prevent scalp depression at the burr hole site. METHODS: A retrospective analysis was performed with 75 cases in 66 patients who were treated with burr hole trephination from January 2018 to December 2019. These cases divided into 2 groups; based on the method used to cover the burr hole site: Gelfoam packing only (GPO) and ADM. The degree of the scalp depression was measured from the more recent follow-up brain computed tomography scan. RESULTS: There was a significant difference in the degree of scalp depression between GPO and ADM groups (p=0.003). No significant correlation between patient's age and the degree of scalp depression (GPO: p=0.419, ADM: p=0.790). There were no wound infection complication in either group. CONCLUSION: ADM is a suitable material to prevent scalp depression after burr hole trephination.

Effects of Systemic Profiles on Choroidal Thickness in Treatment-Naïve Eyes With Diabetic Retinopathy.

Purpose: The purpose of this study was to analyze the effects of systemic and ocular profiles on subfoveal choroidal thickness (SFChT) in treatment-naïve eyes with diabetic retinopathy (DR). Methods: This study included patients with treatment-naïve DR. They underwent routine laboratory evaluations, including complete blood cell count, liver function tests, kidney function tests, and urinalysis for macroalbuminuria. The systemic and ocular factors associated with the change in SFChT in DR were analyzed. Results: A total of 136 eyes from 136 patients with diabetes and 30 eyes from 30 age-matched healthy controls were recruited. Generalized linear model analyses showed that the SFChT in treatment-naïve eyes with DR was positively associated with the DR grade and estimated glomerular filtration rate (eGFR; P = 0.001) and negatively associated with age (P < 0.001) and serum phosphorus levels (P = 0.001). Treatment-naïve eyes with proliferative DR (PDR; 313.4 ± 9.0 µm) or severe nonproliferative DR (NPDR; 299.7 ± 9.7 µm) had thicker choroid than eyes with mild to moderate NPDR (251.7 ± 11.1 µm) or no DR (231.2 ± 14.5 µm) after adjusting for age, eGFR, and phosphorus levels. Conclusions: Choroid is affected by renal function and the grade of DR in patients with diabetes. Advanced retinopathy is associated with choroidal thickening, and the severity of concomitant renal disease is associated with choroidal thinning.

Strong Correlation of Renal Function with Choroidal Thickness in Patients with Type 2 Diabetes: Retrospective Cross-Sectional Study.

The purpose of this study was to analyze the correlation between renal function and subfoveal choroidal thickness (SFChT) in treatment-naïve proliferative diabetic retinopathy (PDR) patients. This study included 85 eyes of 52 treatment-naïve PDR patients who underwent kidney function testing and urinalysis and 42 eyes of 33 age-matched controls. Treatment-naïve eyes with PDR were categorized into pachychoroid and leptochoroid groups based on the SFChT of the control group. Kidney function profiles were compared between pachychoroid and leptochoroid groups; the relationship between kidney function profile and SFChT was evaluated using regression analysis. Compared with the pachychoroid group, the leptochoroid group had significantly higher serum creatinine (p = 0.026), cystatin C (p = 0.004), and phosphorus (p < 0.001) levels and a lower estimated glomerular filtration rate (eGFR) (p < 0.001). Multivariate linear regression analyses showed that SFChT was positively correlated with eGFR (Cystatin C) (p = 0.007) and negatively correlated with serum phosphorus (p = 0.001). SFChT of patients with eGFR < 30 mL/min/1.73 m2 and serum phosphorus level ≥4.0 mg/dL was less than that of patients with higher eGFR and lower serum phosphorus level. The choroidal thickness of treatment-naïve PDR patients is closely affected by renal function. Kidney function test should be considered if SFChT of patients with treatment-naïve PDR is reduced.

Primary Gliosarcoma with Extracranial Metastasis.

A 69-year-old male presented with a week of worsening headache, mild dizziness and left side weakness, and the radiological work-up of his brain displayed an enhancing mass on the right frontal lobe. The tumor was totally resected. The patient was initially diagnosed with glioblastoma multiforme. His neurologic symptoms recovered after surgery. He underwent adjuvant radiotherapy with concurrent temozolomide. Approximately 7 months after surgery, the patient complained of epigastric pains. Abdominal CT scan showed multiple hepatic metastasis and multiple lymphadenopathy. Chest CT and Torso positron emission tomography-CT scans for additional metastasis study revealed multiple metastatic lesions in the right lung, left pleura, liver, lymph nodes, bones, and muscles. Percutaneous liver biopsy was performed, and associated pathology was consistent with sarcomatous component. After liver biopsy, brain tumor pathology was reviewed, which revealed typical gliomatous and sarcomatous components. The patient was therefore diagnosed with metastatic gliosarcoma. The patient was in a septic condition with aggravated pleural effusion. The patient died 9 months after the diagnosis of primary gliosarcoma.

Changes in Lower Eyelid Position and Shape After Inferior Orbital Wall Reconstruction.

PURPOSE: To use morphological measurements to analyze changes in the position and shape of the lower eyelid after inferior orbital wall reconstruction. METHODS: This study included 47 eyes from 47 patients with blowout fractures. Digital photographs were taken in primary gaze immediately before and after surgery; the degree of enophthalmos was recorded. Several eyelid parameters were measured, including marginal reflex distance 1 (MRD1), MRD2, lower eyelid length (LEL), lower medial palpebral fissure area, lower central palpebral fissure area (LCA), and lower lateral palpebral fissure area. RESULTS: The exophthalmometry values (P < 0.001), MRD2 (P < 0.001), LEL (P < 0.001), LCA (P = 0.022), and lower lateral palpebral fissure area (P = 0.038) on the injured side before surgery were significantly smaller than those on the contralateral, uninjured side. Following surgery, the MRD2 increased from 5.01 ±â€Š0.65 mm to 5.60 ±â€Š0.78 mm (P < 0.001), LEL from 25.62 ±â€Š2.11 mm to 26.64 ±â€Š2.29 mm (P < 0.001), lower medial palpebral fissure area from 7.10 ±â€Š3.97 mm to 10.37 ±â€Š3.40 mm (P < 0.001), and LCA from 20.28 ±â€Š4.79 mm to 21.25 ±â€Š5.14 mm (P = 0.008). Multivariate linear regression analysis revealed that changes in the MRD2 (P = 0.019) and LCA (P = 0.048) were associated with enophthalmos improvement. CONCLUSION: The central and medial portions of the lower eyelid are retracted after inferior orbital reconstruction in patients with blowout fractures. The amount of central retraction on the lower eyelid is associated with the amount of enophthalmos improvement.

Effects of botulinum toxin type A on the treatment of dry eye disease and tear cytokines.

PURPOSE: To determine the effects of botulinum toxin type A (BTX-A) injection on dry eye signs, symptoms, and tear cytokine levels in patients with intractable dry eye disease (DED). METHODS: In this prospective study, patients with intractable DED were randomized to a BTX-A (group A) or control group (group B). Patients were injected with BTX-A or normal saline in the medial part of the upper and lower eyelids. Before and at 2 weeks, 1 month, 2 months, and 4 months after injection, dry eye signs; tear film break-up time (TBUT), Schirmer I test, corneal fluorescein staining (CFS), and symptoms; ocular surface disease index (OSDI); and frequency of lubricants were assessed. The tear levels of matrix metalloproteinase (MMP)-9 and serotonin were measured before and at 1 month after injection. RESULTS: Fifty-two eyes from 26 patients (mean age, 57.7 years) were included. The TBUT was higher at 2 weeks and at 1 month in group A. The Schirmer I test and OSDI scores were also better in group A for up to 2 months. The CFS grades in group A were significantly lower until 4 months. Repeated measures analysis of variance (RMANOVA) demonstrated significant differences between the two groups over time for the Schirmer I test (p = 0.002), CFS (p = 0.025), OSDI (p = 0.020), and frequency of lubricants (p = 0.029). The MMP-9 conversion rate of group A (76.92%) was significantly higher than that of group B (38.46%, p = 0.005). The tear serotonin level in group A was reduced from 2.76 ± 0.34 to 1.73 ± 0.14 ng/mL (p < 0.001). No complications were observed during the study. CONCLUSION: BTX-A injection into the medial part of eyelid improves dry eye signs and symptoms and reduces tear cytokine levels. BTX-A is thus a potential treatment option for patients with intractable DED.

Clinical and Histopathological Features of Post Burn Pruritus.

The aim of the study was to evaluate the clinical and histopathological characteristics of patients with post burn pruritus. The authors took skin samples from 62 burn patients with or without pruritus. The measured skin condition includes thickness and paresthesia. Various clinical features were rated on patient assessment scale (PSAS) and observer scar assessment scale. The samples were stained with hematoxylin & eosin, Masson's trichrome, Verhoeff's elastic, and toluidine blue stain. The stained samples were analyzed in terms of epidermal thickness, mononuclear cell infiltration, collagen bundles, elastic fibers, and mast cell distribution. A total of 62 patients were divided into group A (43 patients with pruritus) and group B (19 patients without). The mean (±SD) intensity of itch in group A patients was 4.58 (±3.24). Group A patients had thickened epidermises and higher scores on the PSAS and observer scar assessment scale, especially on the PSAS score. Sensations, including stinging and electric shock sensations, were more frequent in group A than in group B. Histological analysis revealed that group A patients had thinner collagen bundles and more increased mast cell counts, while others did not. Patients suffering from post burn pruritus had distinctive clinical and histopathological features, such as prominent mast cell deposition and thin collagen bundles, compared with group B patients. These results may help better understand post burn pruritus.

Increased activity of TRPV3 in keratinocytes in hypertrophic burn scars with postburn pruritus.

Postburn pruritus is a common distressing sequela of burn wounds. Empirical antipruritic treatment often fails to have a satisfactory outcome, as the mechanism of it has not been fully elucidated. The aim of this study was to evaluate the manifestation of transient receptor potential vanilloid 3 (TRPV3), transient receptor potential ankyrin 1 (TRPA1), and other related receptors in postburn pruritus. Sixty-five burn patients with (n = 40) or without (n = 25) pruritus were investigated, including skin biopsies. Keratinocytes and fibroblasts from skin biopsy samples were separated. Real time-PCR showed that mRNA of TRPV3 was significantly increased in keratinocytes from pruritic burn scars than in keratinocytes from nonpruritic burn scars. With TRPV3 activation, intracellular Ca2+ concentrations were more significantly increased in keratinocytes from pruritic burn scars than in those from nonpruritic ones. Additionally, mRNA and protein levels of protease-activated receptor 2 (PAR2) and neurokinin-1 receptor (NK1R) were also significantly increased in pruritic burn scars. In conclusion, it was confirmed that TRPV3, PAR2, and NK1R were highly expressed in pruritic burn scars. These results may help determine a novel mechanism for postburn pruritus.

Clinical and Histopathological Features of Post Burn Pruritus.

The aim of the study was to evaluate the clinical and histopathological characteristics of patients with post burn pruritus. The authors took skin samples from 62 burn patients with or without pruritus. The measured skin condition includes thickness and paresthesia. Various clinical features were rated on patient assessment scale (PSAS) and observer scar assessment scale. The samples were stained with hematoxylin & eosin, Masson's trichrome, Verhoeff's elastic, and toluidine blue stain. The stained samples were analyzed in terms of epidermal thickness, mononuclear cell infiltration, collagen bundles, elastic fibers, and mast cell distribution. A total of 62 patients were divided into group A (43 patients with pruritus) and group B (19 patients without). The mean (±SD) intensity of itch in group A patients was 4.58 (±3.24). Group A patients had thickened epidermises and higher scores on the PSAS and observer scar assessment scale, especially on the PSAS score. Sensations, including stinging and electric shock sensations, were more frequent in group A than in group B. Histological analysis revealed that group A patients had thinner collagen bundles and more increased mast cell counts, while others did not. Patients suffering from post burn pruritus had distinctive clinical and histopathological features, such as prominent mast cell deposition and thin collagen bundles, compared with group B patients. These results may help better understand post burn pruritus.

Reference values of lead in blood and related factors among Korean adolescents: the Korean National Health and Nutrition Examination Survey 2010-2013.

PURPOSE: This study aimed to assess the reference values and factors influencing blood lead levels among Korean adolescents. METHODS: The study population consisted of 1,585 adolescents (801 males, 784 females; aged 10-19 years) who participated in the Korea National Health and Nutrition Examination Survey 2010-2013. We analyzed blood lead concentrations in relation to demographic/lifestyle characteristics for all participants. "Reference values" of blood lead levels were calculated as the upper limit of the 95% confidence interval of the 95th percentile. RESULTS: The average "reference value" for blood lead concentrations among Korean adolescents was 2.25 µg/dL (2.49 µg/dL for males, 2.07 µg/dL for females), and the geometric mean of the blood lead concentrations was 1.34 µg/dL. Males had higher blood lead concentrations than females (male, 1.48 µg/dL; female, 1.19 µg/dL; P<0.001). Elementary school students had higher blood lead concentrations than junior and senior high school students (1.44 µg/dL vs. 1.31 µg/dL, P<0.001). Participants living in detached houses had higher blood lead concentrations than those living in apartments (P<0.001) and current smokers had higher concentrations than nonsmokers or participants with secondhand smoke exposure (P<0.05). Additionally, participants with excessive alcohol consumption had higher levels than non-drinkers (P<0.001). CONCLUSION: This study provides national reference data on blood lead concentrations stratified by demographic and lifestyle factors among Korean adolescents. Further studies are needed to elucidate the relationship between increased lead exposure and demographic factors including type of housing.

Obesity Alters the Microbial Community Profile in Korean Adolescents.

Obesity is an increasing public health concern worldwide. According to the latest Organization for Economic Co-operation and Development (OECD) report (2014), the incidence of child obesity in Korea has exceeded the OECD average. To better understand and control this condition, the present study examined the composition of the gut microbial community in normal and obese adolescents. Fecal samples were collected from 67 obese (body mass index [BMI] ≥ 30 kg/m2, or ≥ 99th BMI percentile) and 67 normal (BMI < 25 kg/m2 or < 85th BMI percentile) Korean adolescents aged 13-16 years and subjected to 16S rRNA gene sequencing. Analysis of bacterial composition according to taxonomic rank (genus, family, and phylum) revealed marked differences in the Bacteroides and Prevotella populations in normal and obese samples (p < 0.005) at the genus and family levels; however, there was no difference in the Firmicutes-to-Bacteroidetes (F/B) ratio between normal and obese adolescents samples at the phylum level (F/B normal = 0.50 ± 0.53; F/B obese = 0.56 ± 0.86; p = 0.384). Statistical analysis revealed a significant association between the compositions of several bacterial taxa and child obesity. Among these, Bacteroides and Prevotella showed the most significant association with BMI (p < 0.0001 and 0.0001, respectively). We also found that the composition of Bacteroides was negatively associated with triglycerides (TG), total cholesterol, and high-sensitive C-reactive protein (hs-crp) (p = 0.0049, 0.0023, and 0.0038, respectively) levels, whereas that of Prevotella was positively associated with TG and hs-crp levels (p = 0.0394 and 0.0150, respectively). We then applied the association rule mining algorithm to generate "rules" to identify the association between the populations of multiple bacterial taxa and obesity; these rules were able to discriminate obese from normal states. Therefore, the present study describes a systemic approach to identify the association between bacterial populations in the gut and childhood obesity.

The relationship between primary headache and constipation in children and adolescents.

PURPOSE: Many patients presenting with headache also complain of constipation; the relationship between these two symptoms has not been explored in detail. The aim of this study was to investigate the association between primary headache and constipation. METHODS: This retrospective study included all children who attended the Inje University Sanggye Paik Hospital complaining of headache, and who had been followed up for at least 100 days. Patients were divided into 2 groups: group A, in whom the headache improved after treatment for constipation, and group B, in whom headache was not associated with constipation. RESULTS: Of the 96 patients with primary headache, 24 (25.0%) also had constipation (group A). All 24 received treatment for constipation. Follow-up revealed an improvement in both headache and constipation in all patients. Group B contained the remaining 72 children. Comparison of groups A and B indicated a significant difference in sex ratio (P=0.009, chi-square test). Patients with probable tension-type headache were more likely to be in Group A (P=0.006, chi-square test). CONCLUSION: Resolution of constipation improves headache in many patients diagnosed with primary headache, especially those with probable tension-type headache. We suggest that either constipation plays a key role in triggering headache, or that both constipation and headache share a common pathophysiology.

Increased expression of three types of transient receptor potential channels (TRPA1, TRPV4 and TRPV3) in burn scars with post-burn pruritus.

Post-burn pruritus is a common distressing consequence of burn wounds. Empirical treatment often fails to have a satisfactory outcome on post-burn pruritus, as the mechanism of post-burn pruritus has not been fully elucidated. The aim of this study was to evaluate the manifestation of transient receptor potential (TRP) channels in post-burn pruritus. Fifty-one burn patients with (n=33) or without (n=18) pruritus were investigated, including skin biopsies. Not unexpectedly, the scarred body area was larger in the former group. In immunohistochemistry, TPRV3 was significantly elevated in the epidermis of burn scars with pruritus. Furthermore, real time- PCR showed that mRNA of TRPA1 and TRPV4 was increased in itching burn scars. Staining for substance P and CGRP did not differ between the 2 grouped, but the former neuropeptide was increased in burn scars. These results may help determine a specific therapeutic approach for post-burn pruritus.

Increased expression of the aryl hydrocarbon receptor in patients with chronic inflammatory skin diseases.

Polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are major environmental pollutants, and their effects on the human body critically depend on the aryl hydrocarbon receptor (AhR). The aim of this study was to evaluate the significance of the AhR and its ligands in chronic inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. Expression of AhR-related mRNA was increased in lesional skin from patients with AD and psoriasis compared to those of normal skin from healthy controls. The AhR and aryl hydrocarbon receptor nuclear translocator were colocalized in the nuclei of keratinocytes at the lower epidermis of psoriatic lesions, which suggested activation of the AhR pathway. After treatment of normal human epidermal keratinocytes with TCDD or PCBs, IL-6 and IL-8 production were increased. The results of this study suggest that AhR is highly expressed in the acute lesional skin of patients with AD and psoriasis, and the AhR pathway is activated especially in psoriasis.

Genome-wide association study of liver enzymes in korean children.

Liver enzyme elevations, as an indicator of liver function, are widely associated with metabolic diseases. Genome-wide population-based association studies have identified a genetic susceptibility to liver enzyme elevations and their related traits; however, the genetic architecture in childhood remains largely unknown. We performed a genome-wide association study to identify new genetic loci for liver enzyme levels in a Korean childhood cohort (n = 484). We observed three novel loci (rs4949718, rs80311637, and rs596406) that were multiply associated with elevated levels of alanine transaminase and aspartate transaminase. Although there are some limitations, including genetic power, additional replication and functional characterization will support the clarity on the genetic contribution that the ST6GALNAC3, ADAMTS9, and CELF2 genes have in childhood liver function.

Efficient data extraction method for near-infrared spectroscopy (NIRS) systems with high spatial and temporal resolution.

An hardware-efficient method for the extraction of hemodynamic responses in near-infrared spectroscopy systems is proposed to increase the spatial and temporal resolution. The performance improvement is attributed to high signal-to-noise ratio receivers, a modulation scheme, and a multi-input-multi-output based data extraction algorithm. The proposed system shows more than twofold improvement in the figure of merit compared to conventional designs. Experimental results support the validity of the proposed system.

Evaluation of the clinical efficacy of fractional radiofrequency microneedle treatment in acne scars and large facial pores.

BACKGROUND: Fractional technology overcomes the problems of ablative lasers, such as inaccurate depth control and damage to the epidermis. Minimally invasive fractional radiofrequency microneedle devices allow for more-selective heating of the dermis. OBJECTIVE: To evaluate the clinical efficacy of fractional radiofrequency microneedle (ERM) treatment in acne scars and large facial pores. MATERIALS AND METHODS: Thirty patients with acne scars and large facial pores were enrolled. Bipolar radiofrequency energy was delivered to the skin through the electrodes of the FRM device. Skin lesions were evaluated according to grade of acne scars, Investigator Global Assessment of large pores, skin surface roughness, transepidermal water loss (TEWL), dermal density, microscopic and composite image, sebum measurement, and questionnaires regarding patient satisfaction. RESULTS: The grade of acne scars and Investigator Global Assessment of large pores improved in more than 70% of all patients. Skin surface roughness, dermal density, and microscopic and composite images also improved, whereas TEWL and sebum measurement did not change. CONCLUSION: Clinical improvement from FRM treatment appeared to be related to dermal matrix regeneration. FRM treatment may be effective in improving acne scars and facial pores.

Modal warping: real-time simulation of large rotational deformation and manipulation.

This paper proposes a real-time simulation technique for large deformations. Green's nonlinear strain tensor accurately models large deformations; however, time stepping of the resulting nonlinear system can be computationally expensive. Modal analysis based on a linear strain tensor has been shown to be suitable for real-time simulation, but is accurate only for moderately small deformations. In the present work, we identify the rotational component of an infinitesimal deformation and extend traditional linear modal analysis to track that component. We then develop a procedure to integrate the small rotations occurring at the nodal points. An interesting feature of our formulation is that it can implement both position and orientation constraints in a straightforward manner. These constraints can be used to interactively manipulate the shape of a deformable solid by dragging/twisting a set of nodes. Experiments show that the proposed technique runs in real-time, even for a complex model, and that it can simulate large bending and/or twisting deformations with acceptable realism.