ACL Recovery Aid

This project changed its scope throughout the two quarters. Originally, it was a student proposed project to create a low-cost brace to help patients after anterior cruciate ligament (ACL) reconstruction surgery. The brace was to be worn during the day and help stretch the ACL to speed up the recovery time. After meeting with Dr. McSorley, a physical therapist local to San Luis Obispo, we decided to change the scope of the project. Dr. McSorley mentioned that the recovery process for ACL patients stops at night when they go to sleep. Creating a brace that could be worn at night would improve the recovery process. The brace had to be adjustable for different extends of stretching and comfortable to be worn overnight. Most of the design was done before the project change was made. However, most of the elements could be kept as mainly the application was changed. The brace fits around the knee and attaches at the upper and lower leg. There is a gear mechanism on the side that allows the user to adjust the stretch of the knee. One important aspect that Dr. McSorley brought up was that the brace had to apply the correct forces on the leg to prevent reinjury of the ACL. The brace must apply a force on the top front of the knee and the bottom back of the leg. The device functions by attaching around the knee. The user can adjust the brace, so it stretches the knee to a comfortable degree. Although most testing was not possible because of the COVID-19 situation, the brace should work as intended. The brace is made of aluminum and attaches to the leg with Velcro straps to provide support and durability. The padding provides comfort to the user

Sandwich-type zeolite intergrowths with MFI and the novel extralarge pore IDM-1 as ordered end-members

Stacking faults are two-dimensional planar defects frequently arising in zeolites, modifying their properties and potentially affecting their performance in catalysis and separation applications. In classical zeolite intergrowths, a topologically unique zeolite layer may often pile up after some spatial transformation (lateral translation, rotation, and/or reflection) that may occur in different amounts or directions with about similar probabilities, leading to a difficult to control disorder. Here, we present a new kind of zeolite intergrowth that requires an additional topologically distinct layer rather than a spatial transformation of a unique one. Stacking of the so-called pentasil layers produces the well-known medium pore zeolite MFI. Intercalation in strict alternation of a topologically distinct second layer sandwiched between pentasil layers expands the structure to produce the new extra-large pore IDM-1. Stacking disorder modulates the structural expansion along the stacking direction. The disordered materials have been studied by simulation of the X-ray diffraction patterns using the program DIFFaX and by Cs-corrected high-resolution electron microscopy. We show that disorder does not occur at random but in extended domains and can be controlled all the way from MFI to IDM-1 by just varying the concentration of the synthesis mixture

Synaptic Deficits Are Rescued in the p25/Cdk5 Model of Neurodegeneration by the Reduction of β-Secretase (BACE1)

Alzheimer's disease (AD) is the most common cause of dementia, and is characterized by memory loss and cognitive decline, as well as amyloid β (Aβ) accumulation, and progressive neurodegeneration. Cdk5 is a proline-directed serine/threonine kinase whose activation by the p25 protein has been implicated in a number of neurodegenerative disorders. The CK-p25 inducible mouse model exhibits progressive neuronal death, elevated Aβ, reduced synaptic plasticity, and impaired learning following p25 overexpression in forebrain neurons. Levels of Aβ, as well as the APP processing enzyme, β-secretase (BACE1), are also increased in CK-p25 mice. It is unknown what role increased Aβ plays in the cognitive and neurodegenerative phenotype of the CK-p25 mouse. In the current work, we restored Aβ levels in the CK-p25 mouse to those of wild-type mice via the partial genetic deletion of BACE1, allowing us to examine the Aβ-independent phenotype of this mouse model. We show that, in the CK-p25 mouse, normalization of Aβ levels led to a rescue of synaptic and cognitive deficits. Conversely, neuronal loss was not ameliorated. Our findings indicate that increases in p25/Cdk5 activity may mediate cognitive and synaptic impairment via an Aβ-dependent pathway in the CK-p25 mouse. These findings explore the impact of targeting Aβ production in a mouse model of neurodegeneration and cognitive impairment, and how this may translate into therapeutic approaches for sporadic AD.National Institutes of Health (U.S.) (Grant NIH R01NS051874)Ruth L. Kirschstein National Research Service Award (Predoctoral Fellowship F31GM80055-03

Tissue Determinants of Human NK Cell Development, Function, and Residence.

Immune responses in diverse tissue sites are critical for protective immunity and homeostasis. Here, we investigate how tissue localization regulates the development and function of human natural killer (NK) cells, innate lymphocytes important for anti-viral and tumor immunity. Integrating high-dimensional analysis of NK cells from blood, lymphoid organs, and mucosal tissue sites from 60 individuals, we identify tissue-specific patterns of NK cell subset distribution, maturation, and function maintained across age and between individuals. Mature and terminally differentiated NK cells with enhanced effector function predominate in blood, bone marrow, spleen, and lungs and exhibit shared transcriptional programs across sites. By contrast, precursor and immature NK cells with reduced effector capacity populate lymph nodes and intestines and exhibit tissue-resident signatures and site-specific adaptations. Together, our results reveal anatomic control of NK cell development and maintenance as tissue-resident populations, whereas mature, terminally differentiated subsets mediate immunosurveillance through diverse peripheral sites. VIDEO ABSTRACT

A Dietary Regimen of Caloric Restriction or Pharmacological Activation of SIRT1 to Delay the Onset of Neurodegeneration

Caloric restriction (CR) is a dietary regimen known to promote lifespan by slowing down the occurrence of age-dependent diseases. The greatest risk factor for neurodegeneration in the brain is age, from which follows that CR might also attenuate the progressive loss of neurons that is often associated with impaired cognitive capacities. In this study, we used a transgenic mouse model that allows for a temporally and spatially controlled onset of neurodegeneration to test the potentially beneficial effects of CR. We found that in this model, CR significantly delayed the onset of neurodegeneration and synaptic loss and dysfunction, and thereby preserved cognitive capacities. Mechanistically, CR induced the expression of the known lifespan-regulating protein SIRT1, prompting us to test whether a pharmacological activation of SIRT1 might recapitulate CR. We found that oral administration of a SIRT1-activating compound essentially replicated the beneficial effects of CR. Thus, SIRT1-activating compounds might provide a pharmacological alternative to the regimen of CR against neurodegeneration and its associated ailments.National Institutes of Health (U.S.) (Grant PO1 AG027916

Partial Nephrectomy in the Treatment of Localized Renal Cell Carcinoma — Experience of Taichung Veterans General Hospital

BackgroundPartial nephrectomy has been considered an effective and efficient method in the treatment of localized renal cell carcinoma. Herein, we retrospectively review our experience with partial nephrectomy in the treatment of localized renal cell carcinoma and compared it with patients who received radical nephrectomy.MethodsFrom 1982 to 2005, 35 patients who received partial nephrectomy for localized renal cell carcinoma were enrolled in this study. Ten patients were female (28.6%). The median age was 70 years (range, 42–82 years). Sixteen (45.7%) patients had pathologic T1a tumors; 17 (48.6%) patients had pathologic T1b tumors and 2 (5.7%) patients had pathologic T2 tumor (7 cm). In the meantime, 128 patients who had T1N0M0 renal cell carcinoma and who received radical nephrectomy were assigned to a control group. Thirty-nine patients (30.5%) were female in this group. The median age was 62 years (range, 30–83 years). The tumor characteristics, location, surgical techniques and patient survival were subsequently compared.ResultsThe median tumor size in the partial nephrectomy group was 3.9 cm (range, 1.5–7.0 cm), and it was 4.5 cm (range, 1–6.5 cm) in radical nephrectomy group. The tumor size was smaller in the partial nephrectomy group (p = 0.003). The median follow-up period was 4.38 years (range, 0.05–17.99 years) in the partial nephrectomy group and 5.66 years (range, 0.01–22.25 years) in the radical nephrectomy group. There was no local recurrence or distant metastasis in the partial nephrectomy group. The 5-year overall survival was 85.0% compared with 91.4% in the radical nephrectomy group (p = 0.126). The 5-year disease-specific survival in the partial nephrectomy group was 100%. The postoperative serum creatinine level increased to > 2.0 mg/dL in 5 (14.3%) patients in the partial nephrectomy group, but no patient needed hemodialysis during follow-up.ConclusionFrom our review, partial nephrectomy is safe and provides excellent disease control in the treatment of localized renal cell carcinoma in selected patients. Renal function preservation was observed in the partial nephrectomy group, while the operated kidney showed functioning in the follow-up nuclear medicine survey

Lipopolysaccharide-stimulated Leukocytes Contribute to Platelet Aggregative Dysfunction, Which is Attenuated by Catalase in Rats

Endotoxemia causes several hematological dysfunctions, including platelet degranulation or disseminated intravascular coagulation, which lead to thrombotic and hemorrhagic events. Here, we tested the hypothesis that bacterial lipopolysaccharide (LPS)-stimulated leukocytes contribute to platelet aggregative dysfunction, and this function is attenuated by antioxidants. Plateletrich plasma (PRP) was prepared from whole blood of normal and endotoxemic rats. The ability of platelet aggregation was measured by an aggregometer. LPS (50–100 μg/mL) was incubated with PRP, whole blood and PRP with polymorphonuclear leukocytes (PMNs) for 30 minutes, 60 minutes and 90 minutes, and platelet aggregation was detected. LPS-induced platelet aggregative dysfunction was undetectable in intact PRP which was isolated from normal whole blood, whereas it was detected in PRP isolated from endotoxemic rats and LPS-treated whole blood. Moreover, the effect of LPS-induced platelet aggregative dysfunction on intact PRP was observed when the PMNs were added. LPS-induced platelet aggregative dysfunction was significantly attenuated by catalase alone and in combination with NG-nitro-L-arginine methyl ester, but not by NG-nitro-L-arginine methyl ester alone. These results indicate that LPS-stimulated PMNs modulate platelet aggregation during LPS treatment and the effects are reversed by antioxidants. PMNs serve as an approach to understand LPS-induced platelet aggregative dysfunction during endotoxemia. During this process, the generation of reactive oxygen species, hydrogen peroxide especially, from LPS-stimulated PMNs could be an important potential factor in LPS-induced platelet aggregative dysfunction. Catalase contributes to the prevention of platelet dysfunction during LPS-induced sepsis

Convenient Adhesive Strength Evaluation Method in Terms of the Intensity of Singular Stress Field

A convenient evaluation method is proposed for the debonding adhesive strength in terms of the intensity of singular stress field (ISSF) appearing at the end of interface. The same FEM mesh pattern is applied to unknown problems and reference problems. It is found that the ISSF is obtained accurately by focussing on the FEM stress at the adhesive corner. Then, the debonding condition can be expressed as a constant value of critical ISSF. The usefulness of the present solution is verified by comparing with the results of the conventional method