Surface electromyography of the vastus lateralis and gluteus medius muscles in post-operative T3-L3 hemilaminectomy dogs: a prospective controlled observational study.

Objective: The objective of this study was to determine if surface electromyography (sEMG) demonstrates differences in muscle activation between normal and dogs recovering from spinal cord injury due to intervertebral disk extrusion. Animals: Two groups of client-owned small-breed chondrodysplastic-type dogs were tested. Group 1 consisted of seven ambulatory paraparetic dogs that had undergone a hemilaminectomy procedure in the T3-L3 region for intervertebral disk extrusion 1 month prior. Group 2 was made up of seven normal dogs that had no history of intervertebral disk disease or spinal surgery. Procedures: Each subject walked 10 feet on a nonslip surface for at least five gait cycles for the sEMG to capture muscle activation of the vastus lateralis and gluteus medius, bilaterally. Muscle activation was quantified as the total myoelectric output area under the curve, averaged across all gait cycles. Results: Muscle activation was significantly greater in the post-operative hemilaminectomy group (p = 0.012). There was a significant difference in muscle activation between each hindlimb in the post-operative hemilaminectomy group, but not in the normal group. The muscle activation was significantly lower on the side that underwent surgery compared to the opposite limb (p = 0.0034). Conclusion and clinical importance: Post-operative hemilaminectomy dogs have greater hindlimb muscle activation compared to normal dogs, which likely represents a lack of descending inhibition secondary to upper motor neuron syndrome. The side of surgery is correlated with decreased muscle activation. Surface EMG can be used to evaluate muscle activity in dogs recovering from spinal decompression surgery.

Malignant Tumors Identified in Adult Polycystic Kidney Disease Can Be Derived from Both Proximal Tubular and Distal Tubular Origins.

Adult polycystic kidney disease (APKD) is a genetic disorder leading to premature renal dysfunction and failure. The prevalence of malignant renal tumors occurring in the APKD setting has been rarely reported. OBJECTIVE: To better characterize malignant renal tumors in nephrectomy specimens of APKD and apply modern pathologic evaluation. METHODS: We reviewed our database of APKD specimens over the past 11 years (from 2012 to 2023) for primary malignant tumors within the kidneys of APKD. RESULTS: Of 48 nephrectomy specimens with APKD evaluated, 10 malignant renal tumors were identified, indicating a prevalence of 20.8 % (10/48). These included three clear cell (cc) renal cell carcinomas (RCC) (ranging from 1 mm to 6.7 cm), three papillary RCCs (2.5, 3.5, and 14 cm with lymph node metastasis), two cases of clear cell papillary (CCP) RCC, one acquired cystic disease (ACD) with associated RCC (4 mm), and one urothelial adenocarcinoma. The urothelial adenocarcinoma was found near a tubulovillous adenoma in a collecting duct and stained positively for GATA3 and Uroplakin-2 but was negative for PAX8 & CDX2. The tumor showed extensive invasion into perirenal fatty tissue and the rectum. Next generating sequencing (NGS) analysis of the tumor showed mutations in TERT, RB1, TP53, ERBB2, and TET1 genes, further supporting its urothelial origin. CONCLUSIONS: We found a prevalence of 20.8%, which was higher than in previous reports of malignant renal tumors in patients who underwent resections for APKD. Renal tumors were mostly from damaged proximal tubular origins (clear cell or papillary RCC), but less commonly were from distal tubular or urothelial cells as well (clear cell papillary RCC and urothelial adenocarcinoma).

Distinct effector functions mediated by Fc regions of bovine IgG subclasses and their interaction with Fc gamma receptors.

Cattle possess three IgG subclasses. However, the key immune functions, including complement and NK cell activation, and enhancement of phagocytosis, are not fully described for bovine IgG1, 2 and 3. We produced chimeric monoclonal antibodies (mAbs) consisting of a defined variable region linked to the constant regions of bovine IgG1, 2 and 3, and expressed His-tagged soluble recombinant bovine Fc gamma receptors (FcγRs) IA (CD64), IIA (CD32A), III (CD16) and Fcγ2R. Functional assays using bovinized mAbs were developed. IgG1 and IgG3, but not IgG2, activated complement-dependent cytotoxicity. Only IgG1 could activate cattle NK cells to mobilize CD107a after antigen crosslinking, a surrogate assay for antibody-dependent cell cytotoxicity. Both IgG1 and IgG2 could trigger monocyte-derived macrophages to phagocytose fluorescently labelled antigen-expressing target cells. IgG3 induced only weak antibody-dependent cellular phagocytosis (ADCP). By contrast, monocytes only exhibited strong ADCP when triggered by IgG2. IgG1 bound most strongly to recombinant FcγRs IA, IIA and III, with weaker binding by IgG3 and none by IgG2, which bound exclusively to Fcγ2R. Immune complexes containing IgG1, 2 and 3 bound differentially to leukocyte subsets, with IgG2 binding strongly to neutrophils and monocytes and all subclasses binding platelets. Differential expression of the FcγRs on leukocyte subsets was demonstrated by surface staining and/or RT-qPCR of sorted cells, e.g., Fcγ2R mRNA was expressed in monocytes/macrophages, neutrophils, and platelets, potentially explaining their strong interactions with IgG2, and FcγRIII was expressed on NK cells, presumably mediating IgG1-dependent NK cell activation. These data reveal differences in bovine IgG subclass functionality, which do not correspond to those described in humans, mice or pigs, which is relevant to the study of these IgG subclasses in vaccine and therapeutic antibody development.

The global significance of abiotic factors affecting nitrate removal in woodchip bioreactors.

Woodchip bioreactor (WBR) is one of the green infrastructures in the agriculture system to reduce nitrate from agricultural drainage and stormwater. A lot of abiotic factors have been reported that affect nitrate removal lacking a comprehensive understanding. In this study, we studied eight important abiotic factors, including media age, hydraulic retention time (HRT), influent nitrate concentration (Cin), temperature, dissolved organic carbon (DOC), dissolved oxygen (DO), pH, and effective porosity (ρe) of WBR-filling materials. Based on a database that included 10,179 sets of data from 63 peer-reviewed articles, the nitrate removal rate (NRR) and nitrate removal efficiency (NRE) corresponding to the eight abiotic factors by different categories were comprehensively reported. According to this database, this study found the optimal range of abiotic factors for NRR and NRE in WBR were different. Regarding NRR, the optimal range of media age, HRT, Cin, temperature, effluent DOC, DO, pH, and ρe were in the first year, 0-5 h, 10-20 mg L-1, 20-25 °C, 0-5 mg L-1, 0-0.5 mg L-1, 7-8, and 0.6-0.7, respectively. For NRE, the optimal range of media age, HRT, Cin, temperature, effluent DOC, DO, pH, and ρe were in the first year, 500-3000 h, 0-10 mg L-1, 10-15 °C, >50 mg L-1, 0-0.5 mg L-1, 4-5, and 0.4-0.5, respectively. Moreover, the principal component analysis (PCA) indicated the field studies' principal components were different from laboratory studies. Furthermore, the structural equation modeling (SEM) also revealed the causal relationship of the eight abiotic factors on NRR and NRE is totally different. Lessons from this study can be incorporated into DNBR designs, especially improving nitrate removal rates by optimizing different abiotic factors. It also provides insights regarding the contributions of different abiotic factors for NRR and NRE independently and comprehensively.

Identification of Anterior Cervical Spinal Instrumentation Using a Smartphone Application Powered by Machine Learning.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: The purpose of this study is to develop and validate a machine learning algorithm for the automated identification of anterior cervical discectomy and fusion (ACDF) plates from smartphone images of anterior-posterior (AP) cervical spine radiographs. SUMMARY OF BACKGROUND DATA: Identification of existing instrumentation is a critical step in planning revision surgery for ACDF. Machine learning algorithms that are known to be adept at image classification may be applied to the problem of ACDF plate identification. METHODS: A total of 402 smartphone images containing 15 different types of ACDF plates were gathered. Two hundred seventy-five images (∼70%) were used to train and validate a convolution neural network (CNN) for classification of images from radiographs. One hundred twenty-seven (∼30%) images were held out to test algorithm performance. RESULTS: The algorithm performed with an overall accuracy of 94.4% and 85.8% for top-3 and top-1 accuracy, respectively. Overall positive predictive value, sensitivity, and f1-scores were 0.873, 0.858, and 0.855, respectively. CONCLUSION: This algorithm demonstrates strong performance in the classification of ACDF plates from smartphone images and will be deployed as an accessible smartphone application for further evaluation, improvement, and eventual widespread use.Level of Evidence: 3.

Emerging Technologies in the Treatment of Adult Spinal Deformity.

Outcomes for adult spinal deformity continue to improve as new technologies become integrated into clinical practice. Machine learning, robot-guided spinal surgery, and patientspecific rods are tools that are being used to improve preoperative planning and patient satisfaction. Machine learning can be used to predict complications, readmissions, and generate postoperative radiographs which can be shown to patients to guide discussions about surgery. Robot-guided spinal surgery is a rapidly growing field showing signs of greater accuracy in screw placement during surgery. Patient-specific rods offer improved outcomes through higher correction rates and decreased rates of rod breakage while decreasing operative time. The objective of this review is to evaluate trends in the literature about machine learning, robot-guided spinal surgery, and patient-specific rods in the treatment of adult spinal deformity.

Risk Factors for 30- and 90-Day Readmissions Due To Surgical Site Infection Following Posterior Lumbar Fusion.

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: Identify the independent risk factors for 30- and 90-day readmission because of surgical site infection (SSI) in patients undergoing elective posterior lumbar fusion (PLF). SUMMARY OF BACKGROUND DATA: SSI is a significant cause of morbidity in the 30- and 90-day windows after hospital discharge. There remains a gap in the literature on independent risk factors for readmission because of SSI after PLF procedures. In addition, readmission for SSI after spine surgery beyond the 30-day postoperative period has not been well studied. METHODS: A retrospective analysis was performed on data from the 2012 to 2014 Healthcare Cost and Utilization Project Nationwide Readmissions Database. The authors identified 65,121 patients who underwent PLF. There were 191 patients (0.30%) readmitted with a diagnosis of SSI in the 30-day readmission window, and 283 (0.43%) patients readmitted with a diagnosis of SSI in the 90-day window. Baseline patient demographics and medical comorbidities were assessed. Bivariate and multivariate analyses were performed to examine the independent risk factors for readmission because of SSI. RESULTS: In the 30-day window after discharge, this study identified patients with liver disease, uncomplicated diabetes, deficiency anemia, depression, psychosis, renal failure, obesity, and Medicaid or Medicare insurance as higher risk patients for unplanned readmission with a diagnosis of SSI. The study identified the same risk factors in the 90-day window with the addition of diabetes with chronic complications, chronic pulmonary disease, and pulmonary circulation disease. CONCLUSIONS: Independent risk factors for readmission because of SSI included liver disease, uncomplicated diabetes, obesity, and Medicaid insurance status. These findings suggest that additional intervention in the perioperative workup for patients with these risk factors may be necessary to lower unplanned readmission because of SSI after PLF surgery.

Oral Administration of a Chemically Modified Curcumin, TRB-N0224, Reduced Inflammatory Cytokines and Cartilage Erosion in a Rabbit ACL Transection Injury Model.

OBJECTIVE: To evaluate the effects of TRB-N0224, a chemically modified curcumin (CMC) with zinc binding properties and improved pharmacokinetics, in a rabbit anterior cruciate ligament (ACL) transection injury-induced model of osteoarthritis (OA). DESIGN: Thirty-eight skeletally mature New Zealand white rabbits were studied in 4 groups: a sham with arthrotomy (n = 6), control with ACL transection (n = 6), and 2 treatment groups with ACL transection and administration of TRB-N0224 at low (25 mg/kg/day) (n = 13) and high (50 mg/kg/day) (n = 13) doses. After euthanization at 12 weeks, outcomes were measured by post-necropsy gross morphology, biomechanics, and cartilage and synovium histology. Rabbit blood ELISA quantified cytokine and matrix metalloproteinase (MMP) concentrations at 0, 4, 8, and 12 weeks. RESULTS: Both treatment doses had fewer distal femoral condyle erosive defects than the control; the low dose demonstrated a mean 78% decrease (P < 0.01). Histologically, the low- and high-dose treatment groups had fewer cartilage pathologic changes and less severe synovitis than the control. CMC alone did not have a major effect on the biomechanics of healthy cartilage or cartilage in the ACL transection model, as demonstrated in 5 of the 6 measured properties/regions (P < 0.05). ELISA results suggested that the key mediators of OA, (interleukin) IL-1ß, IL-6, TNFα (tumor necrosis factor-α), MMP-9, and MMP-13, had decreased concentrations with TRB-N0224 treatment at different time points between weeks 4 to 12 (P < 0.05). CONCLUSIONS: In the pathogenesis of OA, an imbalance exists between catabolic and anabolic mediators. These results suggest the potential of TRB-N0224 to modulate MMP and cytokine levels, slowing the macroscopic and histopathological progression of OA.

The most influential papers in direct anterior approach to total hip arthroplasty.

BACKGROUND: Citation analysis is a commonly used method for appraising the impact of academic publications within a particular field of study. A gap exists in the citation analysis literature with regard to the topic of direct anterior approach (DAA) hip arthroplasty. The purpose of this study is to identify the 50 most frequently cited publications related to this topic. METHODS: The Clarivate Analytics Web of Knowledge database was utilized to search for publications relating to DAA hip arthroplasty. The top 50 most cited articles that met inclusion criteria were recorded and reviewed for various metrics. RESULTS: The top 50 publications were cited a total of 3521 times, with an average of 86.3 total citations per year between 1980 and 2019. 47 of the 50 articles identified had been published since the year 2000. Cohort designs were the most common study type. CONCLUSIONS: This analysis provides insight into factors that characterize highly cited articles on the specific topic of DAA hip arthroplasty. These factors include higher levels of evidence, recent publication, and origin in the United States. Citations of DAA hip arthroplasty papers appear to be on the rise. The curation and analysis of this set of 50 articles will provide orthopaedic surgery clinicians, researchers, and residency program directors a guide for quickly isolating influential articles on the topic of DAA hip arthroplasty. This may serve as a quick reference for clinical decision-making, foundation for further research, and curriculum on DAA hip arthroplasty.

Culture Conditions that Support Expansion and Chondrogenesis of Middle-Aged Rat Mesenchymal Stem Cells.

OBJECTIVE: Rats are an early preclinical model for cartilage tissue engineering, and a practical species for investigating the effects of aging. However, rats may be a poor aging model for mesenchymal stem cells (MSCs) based on laboratory reports of a severe decline in chondrogenesis beyond young adulthood. Such testing has not been conducted with MSCs seeded in a scaffold, which can improve the propensity of MSCs to undergo chondrogenesis. Therefore, the objective of this study was to evaluate chondrogenesis of middle-aged rat MSCs encapsulated in agarose. DESIGN: MSCs from 14- to 15-month-old rats were expanded, seeded into agarose, and cultured in chondrogenic medium with or without 5% serum for 15 days. Samples were evaluated for cell viability and cartilaginous extracellular matrix (ECM) accumulation. Experiments were repeated using MSCs from 6-week-old rats. RESULTS: During expansion, middle-aged rat MSCs demonstrated a diminishing proliferation rate that was improved ~2-fold in part by transient exposure to chondrogenic medium. In agarose culture in defined medium, middle-aged rat MSCs accumulated ECM to a much greater extent than negative controls. Serum supplementation improved cell survival ~2-fold, and increased ECM accumulation ~3-fold. Histological analysis indicated that defined medium supported chondrogenesis in a subset of cells, while serum-supplementation increased the frequency of chondrogenic cells. In contrast, young rat MSCs experienced robust chondrogenesis in defined medium that was not improved with serum-supplementation. CONCLUSIONS: These data demonstrate a previously-unreported propensity of middle-aged rat MSCs to undergo chondrogenesis, and the potential of serum to enhance chondrogenesis of aging MSCs.

Postoperative Complications Associated With Metabolic Syndrome Following Adult Spinal Deformity Surgery.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: The objective of this study was to examine the effect of metabolic syndrome on 30-day postoperative complications following corrective surgery for the adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA: Metabolic syndrome has been shown to increase the risk of cardiovascular morbidity and mortality. Few studies have examined the effect of metabolic syndrome on patients with ASD undergoing surgery. MATERIALS AND METHODS: We performed a retrospective cohort study of patients who underwent spinal fusion for ASD. Patients were divided into 2 groups based on the presence or absence of metabolic syndrome, which was defined as a combination of hypertension, diabetes mellitus, and obesity. Baseline patient characteristics and operative variables were compared between the 2 groups. We also compared the incidence of 30-day postoperative complications between the 2 groups. A multivariable regression analysis was then performed to identify 30-day postoperative complications that were independently associated with metabolic syndrome. RESULTS: A total of 6696 patients were included with 8.3% (n=553) having metabolic syndrome. Patients with metabolic syndrome were more likely to have renal comorbidity (P=0.042), bleeding disorder (P=0.011), American Society of Anesthesiology classification ≥3 (P<0.001), and undergo a long fusion (P=0.009). Patients with metabolic syndrome had higher rates of 30-day mortality (P=0.042), superficial surgical site infection (P=0.006), sepsis (P=0.003), cardiac complications (P<0.001), pulmonary complications (P=0.003), pulmonary embolism (P=0.050), prolonged hospitalization (P=0.010), nonhome discharge (P=0.007), and reoperation (P=0.003). Metabolic syndrome was an independent risk factor for cardiac complications [odds ratio (OR)=4.2; 95% confidence interval (CI): 1.7-10.2; P=0.001], superficial surgical site infection (OR=2.8; 95% CI: 1.4-5.7; P=0.004), sepsis (OR=2.2, 95% CI: 1.2-3.9; P=0.009), reoperation (OR=1.7; 95% CI: 1.2-2.5; P=0.006), pulmonary complications (OR=1.7; 95% CI: 1.1-2.5; P=0.017), and prolonged hospitalization (OR=1.4; 95% CI: 1.0-1.9; P=0.039). CONCLUSIONS: Recognition and awareness of the relationship between metabolic syndrome and postoperative complications following ASD surgery is important for preoperative optimization and perioperative care.

Applications of Machine Learning Using Electronic Medical Records in Spine Surgery.

Developments in machine learning in recent years have precipitated a surge in research on the applications of artificial intelligence within medicine. Machine learning algorithms are beginning to impact medicine broadly, and the field of spine surgery is no exception. Electronic medical records are a key source of medical data that can be leveraged for the creation of clinically valuable machine learning algorithms. This review examines the current state of machine learning using electronic medical records as it applies to spine surgery. Studies across the electronic medical record data domains of imaging, text, and structured data are reviewed. Discussed applications include clinical prognostication, preoperative planning, diagnostics, and dynamic clinical assistance, among others. The limitations and future challenges for machine learning research using electronic medical records are also discussed.

Optimization of Degradation Profile for New Scaffold in Cartilage Repair.

Objective To establish whether a novel biomaterial scaffold with tunable degradation profile will aid in cartilage repair of chondral defects versus microfracture alone in vitro and in a rat model in vivo. Design In vitro-Short- and long-term degradation scaffolds were seeded with culture expanded articular chondrocytes or bone marrow mesenchymal stem cells. Cell growth and differentiation were evaluated with cell morphological studies and gene expression studies. In vivo-A microfracture rat model was used in this study to evaluate the repair of cartilage and subchondral bone with the contralateral knee serving as the empty control. The treatment groups include (1) empty osteochondral defect, (2) polycaprolactone copolymer-based polyester polyurethane-urea (PSPU-U) caffold short-term degradative profile, and (3) PSPU-U scaffold long-term degradative profile. After placement of the scaffold, the rats were then allowed unrestricted activity as tolerated, and histological analyses were performed at 4, 8, and 16 weeks. The cartilage defect was measured and compared with the contralateral control side. Results In vitro-Long-term scaffolds showed statistically significant higher levels of aggrecan and type II collagen expression compared with short-term scaffolds. In vivo-Within 16 weeks postimplantation, there was new subchondral bone formation in both scaffolds. Short-term scaffolds had a statistically significant increase in defect filling and better qualitative histologic fill compared to control. Conclusions The PSPU short-term degradation scaffold may aid in cartilage repair by ultimately incorporating the scaffold into the microfracture procedure.

Prevention of lung cancer recurrence using cisplatin-loaded superhydrophobic nanofiber meshes.

For early stage lung cancer patients, local cancer recurrence after surgical resection is a significant concern and stems from microscopic disease left behind after surgery. Here we apply a local drug delivery strategy to combat local lung cancer recurrence after resection using non-woven, biodegradable nanofiber meshes loaded with cisplatin. The meshes are fabricated using a scalable electrospinning process from two biocompatible polymers--polycaprolactone and poly(glycerol monostearate-co-caprolactone)--to afford favorable mechanical properties for use in a dynamic tissue such as the lung. Owing to their rough nanostructure and hydrophobic polymer composition, these meshes exhibit superhydrophobicity, and it is this non-wetting nature that sustains the release of cisplatin in a linear fashion over ∼90 days, with anti-cancer efficacy demonstrated using an in vitro Lewis Lung carcinoma (LLC) cell assay. The in vivo evaluation of cisplatin-loaded superhydrophobic meshes in the prevention of local cancer recurrence in a murine model of LLC surgical resection demonstrated a statistically significant increase (p = 0.0006) in median recurrence-free survival to >23 days, compared to standard intraperitoneal cisplatin therapy of equivalent dose. These results emphasize the importance of supplementing cytoreductive surgery with local drug delivery strategies to improve prognosis for lung cancer patients undergoing tumor resection.

TMIGD1 is a novel adhesion molecule that protects epithelial cells from oxidative cell injury.

Oxidative damage to renal tubular epithelial cells is a fundamental pathogenic mechanism implicated in both acute kidney injury and chronic kidney diseases. Because epithelial cell survival influences the outcome of acute kidney injury and chronic kidney diseases, identifying its molecular regulators could provide new insight into pathobiology and possible new therapeutic strategies for these diseases. We have identified transmembrane and immunoglobulin domain-containing 1 (TMIGD1) as a novel adhesion molecule, which is highly conserved in humans and other species. TMIGD1 is expressed in renal tubular epithelial cells and promotes cell survival. The extracellular domain of TMIGD1 contains two putative immunoglobulin domains and mediates self-dimerization. Our data suggest that TMIGD1 regulates transepithelial electric resistance and permeability of renal epithelial cells. TMIGD1 controls cell migration, cell morphology, and protects renal epithelial cells from oxidative- and nutrient-deprivation-induced cell injury. Hydrogen peroxide-induced oxidative cell injury downregulates TMIGD1 expression and targets it for ubiquitination. Moreover, TMIGD1 expression is significantly affected in both acute kidney injury and in deoxy-corticosterone acetate and sodium chloride (deoxy-corticosterone acetate salt)-induced chronic hypertensive kidney disease mouse models. Taken together, we have identified TMIGD1 as a novel cell adhesion molecule expressed in kidney epithelial cells that protects kidney epithelial cells from oxidative cell injury to promote cell survival.

Glucose-dependent insulinotropic polypeptide-mediated signaling pathways enhance apical PepT1 expression in intestinal epithelial cells.

We have shown recently that glucose-dependent insulinotropic polypeptide (GIP), but not glucagon-like peptide 1 (GLP-1) augments H(+) peptide cotransporter (PepT1)-mediated peptide absorption in murine jejunum. While we observed that inhibiting cAMP production decreased this augmentation of PepT1 activity by GIP, it was unclear whether PKA and/or other regulators of cAMP signaling pathway(s) were involved. This study utilized tritiated glycyl-sarcosine [(3)H-glycyl-sarcosine (Gly-Sar), a relatively nonhydrolyzable dipeptide] uptake to measure PepT1 activity in CDX2-transfected IEC-6 (IEC-6/CDX2) cells, an absorptive intestinal epithelial cell model. Similar to our earlier observations with mouse jejunum, GIP but not GLP-1 augmented Gly-Sar uptake (control vs. +GIP: 154 ± 22 vs. 454 ± 39 pmol/mg protein; P < 0.001) in IEC-6/CDX2 cells. Rp-cAMP (a PKA inhibitor) and wortmannin [phosophoinositide-3-kinase (PI3K) inhibitor] pretreatment completely blocked, whereas neither calphostin C (a potent PKC inhibitor) nor BAPTA (an intracellular Ca(2+) chelator) pretreatment affected the GIP-augmented Gly-Sar uptake in IEC-6/CDX2 cells. The downstream metabolites Epac (control vs. Epac agonist: 287 ± 22 vs. 711 ± 80 pmol/mg protein) and AKT (control vs. AKT inhibitor: 720 ± 50 vs. 75 ± 19 pmol/mg protein) were shown to be involved in GIP-augmented PepT1 activity as well. Western blot analyses revealed that both GIP and Epac agonist pretreatment enhance the PepT1 expression on the apical membranes, which is completely blocked by wortmannin in IEC-6/CDX2 cells. These observations demonstrate that both cAMP and PI3K signaling pathways augment GIP-induced peptide uptake through Epac and AKT-mediated pathways in intestinal epithelial cells, respectively. In addition, these observations also indicate that both Epac and AKT-mediated signaling pathways increase apical membrane expression of PepT1 in intestinal absorptive epithelial cells.

Sonographic evaluation of knee cartilage defects implanted with preconditioned scaffolds.

OBJECTIVES: The purpose of this study was to develop a novel method for creating an acellular bioactive scaffold, to prove its efficacy in vivo and in vitro for the augmentation of biological repair, and to confirm that sonographic microscopy is a viable modality for monitoring the healing process of osteochondral defects implanted with preconditioned bioactive scaffolds. METHODS: Rabbit marrow stromal cells were retrovirally transduced with either bone morphogenetic protein 7 (BMP-7) or insulinlike growth factor 1 (IGF-1) genes, cultured for 9 weeks in nonwoven poly-L-lactic acid scaffolds, and then frozen and lyophilized. The knees were evaluated at 3, 6, and 12 weeks after surgery using 20-MHz ultrasound and then prepared for routine histologic analysis. B-scans of the extracellular matrix defects were compared to histologic results. RESULTS: Control defects showed a void or a mixture of fibrocartilage tissue. Both types of scaffolds resulted in a higher percentage (both P< .001) of primarily hyaline cartilage tissue with intact articular surfaces. The osteochondral defects were clearly observed in each sonographic signature. There were no differences between images of scaffolds treated with IGF-1 or BMP-7. Extracellular matrix regrowth was found to closely parallel (R(2) = 0.968; P < .003) the histologic images. A 3-mm defect depth and a 2.5-mm scaffold thickness were measured on the sonograms, comparing well to actual dimensions. CONCLUSIONS: There was a gradual increase in healing bordering the defects for the 3-, 6-, and 12-week samples. Also, we have shown that sonography can aid in monitoring implantation of preconditioned scaffolds in osteochondral defects and thus assessing the healing process and cartilage/bone quality.

Glucose-dependent insulinotropic polypeptide regulates dipeptide absorption in mouse jejunum.

Glucose-dependent insulinotropic polypeptide (GIP) secreted from jejunal mucosal K cells augments insulin secretion and plays a critical role in the pathogenesis of obesity and Type 2 diabetes mellitus. In recent studies, we have shown GIP directly activates Na-glucose cotransporter-1 (SGLT1) and enhances glucose absorption in mouse jejunum. It is not known whether GIP would also regulate other intestinal nutrient absorptive processes. The present study investigated the effect of GIP on proton-peptide cotransporter-1 (PepT1) that mediates di- and tripeptide absorption as well as peptidomimetic drugs. Immunohistochemistry studies localized both GIP receptor (GIPR) and PepT1 proteins on the basolateral and apical membranes of normal mouse jejunum, respectively. Anti-GIPR antibody detected 50-, 55-, 65-, and 70-kDa proteins, whereas anti-PepT1 detected a 70-kDa proteins in mucosal homogenates of mouse jejunum. RT-PCR analyses established the expression of GIPR- and PepT1-specific mRNA in mucosal cells of mouse jejunum. Absorption of Gly-Sar (a nondigestible dipeptide) measured under voltage-clamp conditions revealed that the imposed mucosal H(+) gradient-enhanced Gly-Sar absorption as an evidence for the presence of PepT1-mediated H(+):Gly-Sar cotransport on the apical membranes of mouse jejunum. H(+):Gly-Sar absorption was completely inhibited by cephalexin (a competitive inhibitor of PepT1) and was activated by GIP. The GIP-activated Gly-Sar absorption was completely inhibited by RP-cAMP (a cAMP antagonist). In contrast to GIP, the ileal L cell secreting glucagon-like peptide-1 (GLP-1) did not affect the H(+):Gly-Sar absorption in mouse jejunum. We conclude from these observations that GIP, but not GLP-1, directly activates PepT1 activity by a cAMP-dependent signaling pathway in jejunum.

Segmental testicular infarction: sonographic findings and pathologic correlation.

Segmental testicular infarction can mimic testicular carcinoma on sonography and can lead to unnecessary orchiectomy. This case series describes and correlates sonographic and histologic findings of 7 pathologically proven segmental testicular infarction cases. Segmental testicular infarction should be suspected on sonography when a geographic lesion with low or mixed echogenicity has absent or near-absent flow in a patient with scrotal pain. A hyperechoic rim and peripheral hyperemia correspond to interstitial hemorrhage and inflammatory changes. As an infarct evolves, it becomes more discrete and hypoechoic as ghost outlines replace seminiferous tubules. Follow-up or contrast-enhanced magnetic resonance imaging or sonography can increase diagnostic confidence in suspected cases and prevent unnecessary orchiectomy.

Widespread tuberculosis including renal involvement.

Renal and urogenital disease is a prevalent finding of extrapulmonary Mycobacterium tuberculosis. Patients can present with unusual complaints not immediately suspicious for tuberculosis. We describe a 38-year-old man who presented with vomiting and an acute kidney injury. Imaging studies showed nodules throughout the lungs, retroperitoneum, abdominal viscera, and kidneys. Asymmetrical hydronephrosis was found on renal imaging. A classic beaded ureteral appearance (ureteritis cystica) was found during retrograde pyelography. The patient was screened and found to have a negative purified protein derivative skin test, negative acid-fast bacilli of sputum in three samples, and an indeterminate QuantiFERON Gold test. Evaluation of the urine for acid-fast bacilli was negative in four separate samples. A fifth urine sample for acid-fast bacilli was positive. A renal biopsy showed granulomatous interstitial nephritis with multiple areas of caseous necrosis. The patient was diagnosed with active tuberculosis and started on traditional four-drug antituberculous medical therapy. Kidney function remained marginal but did mildly improve with volume expansion and urinary drainage.