Lower Extremity Exoskeleton

Develop a lower extremity device that provides assistance, support, and gait correction for children with cerebral palsy who display crouch gait as a symptom. The device will be designed for children ages 7-12. The device will be adjustable to accommodate varying levels of gait irregularity, weakness and human growth. The device would assist walking and stair climbing by providing bilateral support at hips, knees and ankle joints. The device will be designed for ease of donning and doffing. Battery, drive and control electronics will be designed to reside in a minimalistic backpack (outside the scope of this project)

Expressions 2000

https://openspace.dmacc.edu/expressions/1019/thumbnail.jp

Metabolic control via nutrient-sensing mechanisms: role of taste receptors and the gut-brain neuroendocrine axis

Nutrient sensing plays an important role in ensuring that appropriate digestive or hormonal responses are elicited following the ingestion of fuel substrates. Mechanisms of nutrient sensing in the oral cavity have been fairly well characterized and involve lingual taste receptors. These include heterodimers of G protein-coupled receptors (GPCRs) of the taste receptor type 1 (T1R) family for sensing sweet (T1R2-T1R3) and umami (T1R1-T1R3) stimuli, the T2R family for sensing bitter stimuli, and ion channels for conferring sour and salty tastes. In recent years, several studies have revealed the existence of additional nutrient-sensing mechanisms along the gastrointestinal tract. Glucose sensing is achieved by the T1R2-T1R3 heterodimer on enteroendocrine cells, which plays a role in triggering the secretion of incretin hormones for improved glycemic and lipemic control. Protein hydrolysates are detected by Ca2+-sensing receptor, the T1R1-T1R3 heterodimer, and G protein-coupled receptor 92/93 (GPR92/93), which leads to the release of the gut-derived satiety factor cholecystokinin. Furthermore, several GPCRs have been implicated in fatty acid sensing: GPR40 and GPR120 respond to medium- and long-chain fatty acids, GPR41 and GPR43 to short-chain fatty acids, and GPR119 to endogenous lipid derivatives. Aside from the recognition of fuel substrates, both the oral cavity and the gastrointestinal tract also possess T2R-mediated mechanisms of recognizing nonnutrients such as environmental contaminants, bacterial toxins, and secondary plant metabolites that evoke a bitter taste. These gastrointestinal sensing mechanisms result in the transmission of neuronal signals to the brain through the release of gastrointestinal hormones that act on vagal and enteric afferents to modulate the physiological response to nutrients, particularly satiety and energy homeostasis. Modulating these orally accessible nutrient-sensing pathways using particular foods, dietary supplements, or pharmaceutical compounds may have therapeutic potential for treating obesity and metabolic diseases

Use of Poems Written by Physicians to Elicit Critical Reflection by Students in a Medical Biochemistry Course

PurposeCritical reflection helps to animate humanistic values needed for professional behavior in medical students. We wanted to learn whether poems written by physicians could foster such critical reflection. To do so, we determined whether the poems elicited dissonance (i.e., recognition of their own or others behavior as incongruent with their values) and subsequent reflection or critical reflection by teams of students in a medical biochemistry course.Subjects and MethodsThirty learning teams of five to seven members each (total of 196 first-year osteopathic medical students) related four humanistic values or characteristics of professional behavior to an associated poem written by a physician. Their written individual and team reports were assessed for dissonance, reflection and critical reflection. We also determined whether dissonance (if it occurred) was resolved through preservation of students’ values and behavior (and rejection of other’s behavior) or through reconciliation of their own incongruent humanistic values and professional behavior.ResultsAll 30 teams exhibited dissonance and reflection in their written reports, and 18 teams showed critical reflection. Fifteen of the latter 18 teams displayed reconciliation after critical reflection, and five of those 15 teams also showed preservation. The other 15 teams exhibited preservation, but not reconciliation, after either critical reflection (three teams) or reflection (12 teams). At least two teams exhibited related but deeper critical reflection in more open-ended written work outside the formal assignment of this exercise.ConclusionsThe poems we used were virtually certain to evoke dissonance in learning teams. Behavior exhibited by patients or health care personnel in some of the poems contradicts most people’s values for proper behavior. Placing focus on imperfect behavior by others can, however, limit recognition of one’s own hypocritical actions. To obviate such limitations of more structured assignments, we encourage provision of tacit opportunities for critical reflection outside structured formal assignments. The exercise we used led at least two teams of students to exhibit deeper critical reflection, outside the formal assignment, in order to reconcile their incongruent values and professional behavior. Moreover, the exercise itself led most teams to exhibit critical reflection needed to animate humanistic values and professional behavior in medical students

Use of Poems Written by Physicians to Elicit Critical Reflection by Students in a Medical Biochemistry Course

PurposeCritical reflection helps to animate humanistic values needed for professional behavior in medical students. We wanted to learn whether poems written by physicians could foster such critical reflection. To do so, we determined whether the poems elicited dissonance (i.e., recognition of their own or others behavior as incongruent with their values) and subsequent reflection or critical reflection by teams of students in a medical biochemistry course.Subjects and MethodsThirty learning teams of five to seven members each (total of 196 first-year osteopathic medical students) related four humanistic values or characteristics of professional behavior to an associated poem written by a physician. Their written individual and team reports were assessed for dissonance, reflection and critical reflection. We also determined whether dissonance (if it occurred) was resolved through preservation of students’ values and behavior (and rejection of other’s behavior) or through reconciliation of their own incongruent humanistic values and professional behavior.ResultsAll 30 teams exhibited dissonance and reflection in their written reports, and 18 teams showed critical reflection. Fifteen of the latter 18 teams displayed reconciliation after critical reflection, and five of those 15 teams also showed preservation. The other 15 teams exhibited preservation, but not reconciliation, after either critical reflection (three teams) or reflection (12 teams). At least two teams exhibited related but deeper critical reflection in more open-ended written work outside the formal assignment of this exercise.ConclusionsThe poems we used were virtually certain to evoke dissonance in learning teams. Behavior exhibited by patients or health care personnel in some of the poems contradicts most people’s values for proper behavior. Placing focus on imperfect behavior by others can, however, limit recognition of one’s own hypocritical actions. To obviate such limitations of more structured assignments, we encourage provision of tacit opportunities for critical reflection outside structured formal assignments. The exercise we used led at least two teams of students to exhibit deeper critical reflection, outside the formal assignment, in order to reconcile their incongruent values and professional behavior. Moreover, the exercise itself led most teams to exhibit critical reflection needed to animate humanistic values and professional behavior in medical students

Antioxidants and NOX1/NOX4 inhibition blocks TGFβ1-induced CCN2 and α-SMA expression in dermal and gingival fibroblasts.

TGFbeta induces fibrogenic responses in fibroblasts. Reactive oxygen species (ROS)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) may contribute to fibrogenic responses. Here, we examine if the antioxidant N-acetylcysteine (NAC), the NOX inhibitor diphenyleneiodonium (DPI) and the selective NOX1/NOX4 inhibitor GKT-137831 impairs the ability of TGFbeta to induce profibrotic gene expression in human gingival (HGF) and dermal (HDF) fibroblasts. We also assess if GKT-137831 can block the persistent fibrotic phenotype of lesional scleroderma (SSc) fibroblasts. We use real-time polymerase chain reaction and Western blot analysis to evaluate whether NAC and DPI impair the ability of TGFbeta1 to induce expression of fibrogenic genes in fibroblasts. The effects of GKT-137831 on TGFbeta-induced protein expression and the persistent fibrotic phenotype of lesional scleroderma (SSc) fibroblasts were tested using Western blot and collagen gel contraction analyses. In HDF and HGF, TGFbeta1 induces CCN2, CCN1, endothelin-1 and alpha-smooth muscle actin (SMA) in a fashion sensitive to NAC. Induction of COL1A1 mRNA was unaffected. Similar results were seen with DPI. NAC and DPI impaired the ability of TGFbeta1 to induce protein expression of CCN2 and alpha-SMA in HDF and HGF. GKT-137831 impaired TGFbeta-induced CCN2 and alpha-SMA protein expression in HGF and HDF. In lesional SSc dermal fibroblasts, GKT-137831 reduced alpha-SMA and CCN2 protein overexpression and collagen gel contraction. These results are consistent with the hypothesis that antioxidants or NOX1/4 inhibition may be useful in blocking profibrotic effects of TGFbeta on dermal and gingival fibroblasts and warrant consideration for further development as potential antifibrotic agents

Concomitant IDH-wildtype glioblastoma and IDH1-mutant anaplastic astrocytoma in a patient with constitutional mismatch repair deficiency syndrome

Constitutional mismatch repair deficiency (CMMRD) is a rare and often under-recognized tumour predisposition syndrome, presenting with both extracranial and malignant brain tumours that occur in children and/or young adults [1]. The genetic defects underlying this disease are biallelic germline mutations in one of the DNA mismatch repair (MMR) genes leading to a constitutional DNA repair defect that causes a cancer predisposition syndrome with early onset [2]. This mechanism is different from Lynch syndrome (LS) where a heterozygous germline loss-of-function mutation is observed and the patients are more prone to develop colon and genitourinary cancers as adults [1]. This article is protected by copyright. All rights reserved

TGFβ1-induced CCN2 and αSMA protein expression in human dermal and gingival fibroblasts is reduced by N-acetylcysteine and diphenyleneiodonium.

<p>Human dermal fibroblasts (A) and human gingival fibroblasts (B) were serum-starved overnight. Cells were incubated with either N-acetylcysteine (10 mM) or diphenyleneiodonium (10 μM) for 45 min followed by treatment with or without TGFβ1 (4ng/ml) for 24 hours. Protein lysates were prepared and subjected to western blot analysis with the indicated antibodies. β-actin was used to normalize for protein loading. Representative western blots are shown (n = 3).</p

Inhibition of NOX4 reduces TGFβ1-induced CCN2 and αSMA protein expression in human dermal and gingival fibroblasts and the overexpression of CCN2 and α-SMA, as well as the contractility of lesional SSc dermal fibroblasts.

<p>Human dermal fibroblasts (A) and human gingival fibroblasts (B) were serum-starved overnight. Cells were incubated with GKT-137831 (30 μM) for 45 min followed by treatment with or without TGFβ1 (4ng/ml) for 24 hours. Protein lysates were prepared and subjected to western blot analysis with the indicated antibodies. β-actin was used to normalize for protein loading. Representative western blots are shown (n = 3). <b>(C)</b> Dermal fibroblasts cultured from healthy individuals (NF, normal fibroblasts) and those with scleroderma (systemic sclerosis, SSc) were serum-starved overnight. Cells were incubated with GKT-137831 (30μM) for 24 hours. Protein lysates were prepared and subjected to western blot analysis with the indicated antibodies. GAPDH was used to normalize for protein loading. Representative western blots containing lysates from three different patients are shown (n = 3). (D) NF and SSc fibroblasts were cultured within 3D-collagen lattices in the presence and absence of GKT-137831 (30 μM). After polymerization, the gels were mechanically detached from the wells, and the contraction of the gel was quantified. Results are expressed as a mean +/- SD (n = 3). One-Way ANOVA with post-hoc Tukey test was conducted. * = p<0.05 relative to SSc (-) GKT.</p