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Abstract We describe our initial studies in the development of an orthotopic, genetically defined, large animal model of pancreatic cancer. Primary pancreatic epithelial cells were isolated from pancreatic duct of domestic pigs. A transformed cell line was generated from these primary cells with oncogenic KRAS and SV40T. The transformed cell lines outperformed the primary and SV40T immortalized cells in terms of proliferation, population doubling time, soft agar growth, transwell migration and invasion. The transformed cell line grew tumors when injected subcutaneously in nude mice, forming glandular structures and staining for epithelial markers. Future work will include implantation studies of these tumorigenic porcine pancreatic cell lines into the pancreas of allogeneic and autologous pigs. The resultant large animal model of pancreatic cancer could be utilized for preclinical research on diagnostic, interventional, and therapeutic technologies.

Oxygen is a necessary component of normal wound healing and is required for multiple cell functions, including the killing of bacteria by leukocytes. A new oxygen-generating dressing has been developed that provides intermittent periods of hyperoxia interspersed with periods in which the wound oxygen tension is allowed to autoregulate. Materials and Methods: The effects of an oxygen-generating dressing on healing of infected wounds were examined in 2 experiments using a rodent model of a chronically infected (>10[5] bacteria/g of tissue) granulating wound. Serial wound area measurements were compared among animals treated with the oxygen-generating dressing, the growth factor KGF-2, a vehicle control, a negative dressing control, and a positive dressing control. Serial biopsies of the wound for quantitative bacteriology were performed throughout both experiments. Results In both experiments, infected wounds healed fastest when topically treated with an oxygen-generating dressing (P< 0.05). Although KGF-2 treated wounds healed faster than the vehicle control wounds in experiment 1, the oxygen-generating dressing was statistically better than KGF-2 (P<0.05). The oxygengenerating dressing decreased the bacterial burden in the granulating wounds 100-fold greater than did all other treatments. Conclusions: The oxygen-generating dressing used in these experiments decreased the number of tissue bacteria in these infected wounds to less than 10[5] colony forming units (CFU) per gram of tissue. This, plus the stimulatory effect of oxygen on numerous healing processes, facilitated more rapid healing of the infected granulating wounds. [ABSTRACT FROM AUTHOR]

This study sought to describe speaking fundamental frequency characteristics of elderly Euro-American and African-American individuals and to explore the effects of ethnicity and ageing on vocal parameters of speech production. Speech samples from 42 elderly Euro-American and 37 elderly African-American individuals (age range: 70-80 years) were compared on measures of mean speaking fundamental frequency (F[o]), maximum and minimum speaking F[o], speaking F[o] standard deviation (F[o] SD), and speaking F[o] range (in semitones). Elderly African-American females had significantly lower mean speaking F[o] and speaking F[o] SD than their Euro-American cohorts. Results indicate that researchers need to improve the clinical database for speakers from non-Euro-American backgrounds, and speech-language pathologists must exercise discretion when assessing the speaking F[o] and other speech characteristics of elderly individuals from different ethnic groups. [ABSTRACT FROM AUTHOR]

Menopause in human females and subsequent ovarian hormone deficiency, particularly concerning 17β-estradiol (E2), increase the risk for metabolic dysfunctions associated with obesity, diabetes type 2, cardiovascular diseases, and dementia. Several studies indicate that these disorders are also strongly associated with compositional changes in the intestinal microbiota; however, how E2 deficiency and hormone therapy affect the gut microbial community is not well understood. Using a rat model, we aimed to evaluate how ovariectomy (OVX) and subsequent E2 administration drive changes in metabolic health and the gut microbial community, as well as potential associations with learning and memory. Findings indicated that OVX-induced ovarian hormone deficiency and E2 treatment had significant impacts on several health-affecting parameters, including (a) the abundance of some intestinal bacterial taxa (e.g., Bifidobacteriaceae and Porphyromonadaceae ), (b) the abundance of microbial short-chain fatty acids (SCFAs) (e.g., isobutyrate), (c) weight/BMI, and (d) high-demand spatial working memory following surgical menopause. Furthermore, exploratory correlations among intestinal bacteria abundance, cognition, and BMI underscored the putative influence of surgical menopause and E2 administration on gut-brain interactions. Collectively, this study showed that surgical menopause is associated with physiological and behavioral changes, and that E2-linked compositional changes in the intestinal microbiota might contribute to some of its related negative health consequences. Overall, this study provides novel insights into interactions among endocrine and gastrointestinal systems in the post-menopausal life stage that collectively alter the risk for the development and progression of cardiovascular, metabolic, and dementia-related diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zeibich, Koebele, Bernaud, Ilhan, Dirks, Northup-Smith, Neeley, Maldonado, Nirmalkar, Files, Mayer, Bimonte-Nelson and Krajmalnik-Brown.)

Background: Traditionally, total shoulder arthroplasty (TSA) involves detaching the subscapularis tendon through either tenotomy or lesser tuberosity osteotomy. A subscapularis-sparing approach avoids detachment but may make re-creation of the anatomy more difficult because of limited exposure. The primary aim of this study was to evaluate the ability to re-create the proximal humeral geometry and assess for osteophyte removal with this technique. The secondary aim was to assess for complications or an inability to complete the procedure with this technique., Methods: We performed a retrospective review of a consecutive series of 47 patients (100% with osteoarthritis; 59% Walch type A and 41% Walch type B; 50% male and 50% female patients; and average body mass index, 28.21 ± 4.6) who underwent the subscapularis-sparing windowed anterior technique for TSA. The ability to reconstruct the proximal humeral geometry and remove the inferior osteophytes was assessed by 2 independent observers using the center-of-rotation difference (ΔCOR) between the native and prosthetic humeral heads. The ability to complete the procedure was recorded, and a chart review was performed to assess for complications., Results: The procedure was successfully completed in 44 of the 47 patients. Radiographic review demonstrated an average ΔCOR of 2.28 mm (range, 0.2-6.05 mm; intraclass correlation coefficient, 0.971), below the previously reported acceptable ΔCOR of 3 mm. The ΔCOR was >3 mm in 31.8% of patients (14 of 44; 8 Walch type A and 6 Walch type B; 9 male and 5 female patients). There was no difference in ΔCOR based on Walch type (P = .824). Male patients on average showed a higher ΔCOR (2.62 mm) than female patients (1.94 mm) (P = .099) and more commonly had a ΔCOR > 3 mm (P = .195). Body mass index was not significantly correlated with ΔCOR (r = 0.077, P = .619). For all cases in which the ΔCOR was >3 mm, the prosthetic humeral head was undersized. Osteophytes were successfully removed in 75% of cases (33 of 44) and had no effect on average ΔCOR (P = .468). No revisions or mechanical failures in the early postoperative period were identified in the treatment group of 44 patients (range, 3-15 months). In the group with unsuccessful treatment, there was 1 case of infection treated with 1-stage revision reverse TSA., Discussion: The subscapularis-sparing windowed anterior technique is an effective approach to TSA that allows for early unrestricted motion. Over 90% of cases can be completed using this technique. Radiographic analysis demonstrated that this approach can be used successfully without compromising anatomic reconstruction of the proximal humerus. Further study is necessary to identify patient factors that would favor a traditional deltopectoral approach and to assess the functional outcomes of this technique., (Copyright © 2021 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

This is a case series of 10 patients who had staphylococcal biofilm infections that were treated with adjuvant rifabutin therapy instead of rifampin therapy. In these cases, rifampin was contraindicated secondary to drug-drug interactions with the patients' chronic medications. Rifabutin therapy was well tolerated with no side effects. As well, no patients had recurrence of their staphylococcal infections. This case series shows that rifabutin can be a beneficial adjuvant therapy in Staphylococcus biofilm infections when drug-drug interactions limit the use of rifampin.

Four major approaches to total knee arthroplasty (TKA) exist: standard parapatellar, subvastus, midvastus, and mini-parapatellar. Research has shown that there may be some benefit to patients when minimally invasive approaches are employed. However, research has not shown whether the minimally invasive approaches are beneficial for restoring patients' gait when compared against those of healthy age-matched subjects. This study has compared the effect of the four surgical approaches using computer navigation on recovery of gait at 2, 4, and 6 months. Although some statistically significant differences exist among surgical approaches at specific points of the gait cycle, results demonstrate that no approach is superior to another in restoring patients' gait across the entire gait cycle., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Recent changes in legislation for persons with disabilities have led to an increased focus on Central Auditory Processing problems. Test scores from the Clinical Evaluation of Language Functioning-Revised (CELF-R), Test of Nonverbal Intelligence (TONI), and the Slosson Intelligence Test (SIT) obtained from folders of 40 clients referred for auditory processing problems were analyzed to ascertain the validity of using these tests with a population on which these tests were not normed. All tests and subscales were correlated significantly. Even so, mean differences were present, with one exception, on comparisons of test scores. Moreover, females obtained significantly higher scores on the TONI than did males. Our findings generally support the validity of using these tests with a Central Auditory Processing sample.

12-Oxo-9(11)-dehydroestradiol-17 beta (12-oxo-E2) was used to assay estrogen receptor binding in uterine cytosol preparations by an indirect fluorescence assay. In alkaline solution, 12-oxo-E2 has a fluorescence excitation maximum at 402 nm (epsilon = 24,000) and an emission maximum at 480 nm (phi f = 0.57), and its fluorescence can be observed down to 5 X 10(-11) M. The minimum detection limit of 12-oxo-E2 is 25 fmol by spectrofluorometry and 5 fmol by HPLC-fluorometry. Although this compound is not appreciably fluorescent at neutral pH (i.e., at conditions under which it binds to the estrogen receptor), receptor binding by fluorometry can be measured indirectly: After equilibration of 12-oxo-E2 with the receptor preparation and removal of excess free ligand, the receptor-12-oxo-E2 complex is disrupted, and fluorescence measurements are made on the dissociated 12-oxo-E2 in alkaline medium. This fluorometric assay was validated quantitatively by performing simultaneously, on the same receptor preparation, radiometric and fluorometric assays with [3H]E2 and [3H]-12-oxo-E2. The radiometric determinations with both compounds gave nearly equivalent estimates of receptor site concentrations, but the fluorometric estimate of binding site concentration was somewhat less (70-85%) than that expected on the basis of the [3H]E2 radiometric assay. The use of 12-oxo-E2 in an indirect spectro- or HPLC-fluorometric assay provides a means for assaying estrogen receptor concentrations by fluorescence with a sensitivity approaching that of radiometric techniques.

Steroidal and nonsteroidal estrogens substituted with halogens ortho to the phenolic hydroxyl group in the D ring at C-16 have been prepared as potential estrogen receptor-based imaging agents for human breast tumors. Estrogens bearing an aromatic fluorine ortho to a phenolic hydroxyl group were prepared by the Schiemann reaction on the corresponding methyl esters; other ortho-halogenated estrogens were prepared by direct halogenation. Steroidal estrogens substituted at the 16 alpha position were prepared by halogenation of estrone 3-acetate (17-enol acetate) followed by hydride reduction, and those substituted at the 16 beta position were prepared by epimerization prior to reduction. The binding affinity of these halogenated estrogens to the uterine estrogen receptor was measured relative to that of [3H]estradiol by a competitive binding assay. All of the monosubstituted ortho-fluorinated estrogens show very high binding affinity for the receptor (64--250% that of estradiol). The monosubstituted and symmetrically disubstituted bromo- and iodohexestrols and 2- and 4-substituted estradiols have binding affinities considerably lower than those of the fluoro compounds, the 4-substituted estradiols have affinities greater than the corresponding 2-substituted isomers. Introduction of a halogen (Cl, Br, I) at the 16 alpha position of 17 beta-estradiol results in compounds with receptor affinities comparable to that of 17 beta-estradiol itself; the 16 beta-epimers and the estrone derivatives are bound less well. Thus, provided that they can be labeled with suitable gamma-emitting radioisotopes at sufficiently high specific activity, it appears that the A-ring fluoroestrogens and 16 alpha-bromo- and 16 alpha-iodoestradiol-17 beta are excellent candidates for receptor-based imaging of human breast tumors.