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Head and neck cancers represent a significant portion of cancer diagnoses, with head and neck cancer incidence increasing in some parts of the world. Typical treatment of early-stage head and neck cancers includes either surgery or radiotherapy; however, advanced cases often require surgery followed by radiation and chemotherapy. Salivary gland damage following radiotherapy leads to severe and chronic hypofunction with decreased salivary output, xerostomia, impaired ability to chew and swallow, increased risk of developing oral mucositis, and malnutrition. There is currently no standard of care for radiation-induced salivary gland dysfunction, and treatment is often limited to palliative treatment that provides only temporary relief. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an enzyme that activates catabolic processes and has been shown to influence the cell cycle, proliferation, and autophagy. In the present study, we found that radiation (IR) treatment decreases tissue levels of phosphorylated AMPK following radiation and decreases intracellular NAD+ and AMP while increasing intracellular adenosine triphosphate. Furthermore, expression of sirtuin 1 (SIRT1) and nicotinamide phosphoribosyl transferase (NAMPT) was lower 5 d following IR. Treatment with AMPK activators, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and metformin, attenuated compensatory proliferation (days 6, 7, and 30) following IR and reversed chronic (day 30) salivary gland dysfunction post-IR. In addition, treatment with metformin or AICAR increased markers of apical/basolateral polarity (phosphorylated aPKCζT560-positive area) and differentiation (amylase-positive area) within irradiated parotid glands to levels similar to untreated controls. Taken together, these data suggest that AMPK may be a novel therapeutic target for treatment of radiation-induced salivary damage.

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BACKGROUND: Deaf and hard of hearing (DHH) people are an underserved population and underrepresented among healthcare professionals. A major barrier to success for DHH healthcare professionals is obtaining effective accommodations during education and employment. Our objective: describe DHH individuals' experiences with accommodations in healthcare education. METHODS: We used an online survey and multipronged snowball sampling to recruit participants who identify as DHH and who had applied to a U.S. health professional school (regardless of acceptance status). One hundred forty-eight individuals representing multiple professions responded; 51 had completed their training. Over 80% had been accepted to, were currently enrolled, or had completed health professions schools or residency programs, and/or were employed. The survey included questions addressing experiences applying to health professions programs and employment; satisfaction with accommodations in school and training; having worked with a disability resource professional (DRP); and depression screening. RESULTS: Use and type of accommodation varied widely. While in school, respondents reported spending a mean of 2.1 h weekly managing their accommodations. Only 50% were highly satisfied with the accommodations provided by their programs. Use of disability resource providers (DRPs) for accommodations was highest during school (56%) and less frequent during post-graduate training (20%) and employment (14%). Respondents who transitioned directly from school to employment (versus via additional training) were more satisfied with their accommodations during school and were more likely to find employment (p = 0.02). Seventeen respondents screened positive for risk of depression; a positive screen was statistically associated with lower school accommodation satisfaction. CONCLUSIONS: DHH people study and practice across many health professions. While respondents were mostly successful in entering health professions programs, accommodation experiences and satisfaction varied. Satisfaction with accommodations was related to successful employment and wellness. Low satisfaction was associated with higher likelihood of depression symptoms. To increase representation in the workforce, healthcare professional schools, training programs, and employers should enhance support for the learning and working climates for people with disabilities.

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Poly(A) polymerases are centrally involved in the process of mRNA 3' end formation in eukaryotes. In animals and yeast, this enzyme works as part of a large multimeric complex to add polyadenylate tracts to the 3' ends of precursor RNAs in the nucleus. Plant nuclear enzymes remain largely uncharacterized. In this report, we describe an initial analysis of plant nuclear poly(A) polymerases (nPAPs). An enzyme purified from pea nuclear extracts possesses many features that are seen with the enzymes from yeast and mammals. However, the pea enzyme possesses the ability to polyadenylate RNAs that are associated with polynucleotide phosphorylase (PNP), a chloroplast-localized enzyme involved in RNA turnover. Similar behavior is not seen with the yeast poly(A) polymerase (PAP). A fusion protein consisting of glutathione-S-transferase and the active domain of an Arabidopsis-encoded nuclear poly(A) polymerase was also able to utilize PNP, indicating that the activity of the pea enzyme was due to an interaction between the pea nPAP and PNP, and not to other factors that might copurify with the pea enzyme. These results suggest the existence, in plant nuclei, of factors related to PNP, and an interaction between such factors and poly(A) polymerases.

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In Part 1 (July/August 1999), the authors reviewed the evolution of patient classification systems over four generations of progress, discussed issues of system credibility, and presented a third-generation patient classification system (3PCS) to address the shortcomings of current systems. In this article, an actual implementation of a 3PCS is presented by the authors in collaboration with system users. The development, implementation, and evaluation of the 3PCS, as well as the overall advantages, are discussed. Finally, the authors share lessons learned and thoughts for the future.

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Surgical reconstructions of anterior-inferior shoulder instabilities and rotator cuff injuries require secure fixation of soft tissue to bone. Sutures are inserted directly through transosseous tunnels in current techniques, which are surgically complex and not always adequate for fixation strength. Using fresh-frozen cadaveric human specimens, our objectives were 1) to compare immediate pull-out strength of two versions of polyacetal suture anchors (wedge and rod) with conventional suture-only attachment techniques in Bankart lesion and rotator cuff repairs, and 2) to compare pull-out strength of the two polyacetal suture anchors with a metallic suture anchor. Our results indicate no significant differences in fixation strength of Bankart lesions or rotator cuff repairs using sutures only, or using wedge or rod polyacetal suture anchors (P = 0.70). Pull-out force did not differ significantly (P = 0.37) between the two polyacetal anchors. Polyacetal anchors exhibited higher pull-out forces than metallic anchors when inserted into metaphyseal regions of the tibia and significantly higher pull-out forces (P < 0.001) when inserted into metaphyseal regions with thicker cortical walls. Our results indicate that both polyacetal suture anchors provide adequate immediate fixation for soft tissue repairs in the human shoulder.

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OBJECTIVE: To identify the source of metallic artifacts observed on cervical spine MR studies following anterior cervical diskectomy and fusion (ACD&F), preoperative and postoperative MR studies were done on cadavers using standard spin echo T1, T2, and GRASS imaging. MATERIALS AND METHODS: An ACD&F was performed on each cadaver at various levels using different combinations of drill burrs, curettes, and suction tips. RESULTS: Results showed that contact between the drill burr and suction tip produced the worst artifacts; however, artifacts still occurred in cases in which the suction tip was not introduced. CONCLUSION: This observation suggests that metal flakes from the curettes also produced artifacts. Image distortion was greater on GRASS imaging than on the spin echo imaging.

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We were able to confirm previous studies demonstrating that administration of thyroxine is capable of ameliorating the severity of acute nephrotoxic renal failure in the rat. Nephrotoxic acute renal failure was induced by the subcutaneous injection of potassium dichromate (6.25 mg/kg) into Sprague-Dawley rats. Twenty-four hours after this injection, rats received an intraperitoneal injection of either thyroxine (80 micrograms/kg body wt) or normal saline. Forty-eight hours after the potassium dichromate injection, renal clearance studies were performed. Inulin clearance was significantly higher in the thyroxine-treated than in the saline-treated acute renal failure rats: 1.12 +/- 0.13 (SEM) mL/g versus 0.75 +/- 0.07 mL/min/g kidney wt (P = 0.025). Thyroxine treatment also effected an increase of p-aminohippuric acid extraction from 0.23 +/- 0.03 to 0.33 +/- 0.02 (P = 0.011) and a decrease in the fractional excretion of sodium from 0.38 +/- 0.21 to 0.11 +/- 0.03% (P = 0.037 by Mann-Whitney U test). In order to investigate one potential mechanism of the beneficial effect of thyroxine we studied renal tubular regeneration in this model of acute renal failure. Renal cortical uptake of labeled thymidine into DNA was significantly increased 48 h after the injection of potassium dichromate, and thyroxine administration further enhanced this repair process: 53.9 +/- 3.6 versus 81.4 +/- 5.3 dpm/200 pg of DNA (P = 0.0033).

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We have previously demonstrated an abnormal renal response to chronic acid loading in the hypothyroid rat. The present study was designed to characterize further this defect by examining the renal response to bicarbonate loading. Hypothyroidism was induced by the intraperitoneal injection of Na131I and animals were studied 10 or more weeks thereafter under anesthesia and compared with their age-matched littermates. Insulin clearance of hypothyroid animals was lower and fractional urine flow and sodium excretion rates were higher than in the control rats. At the time of maximal urinary bicarbonate levels, the urine PCO2 exceeded blood values (U - B PCO2) by 41 plus or minus 2 (mean plus or minus SE) mmHg (1 mmHg equals 133.22 Pa) in the controls and 25 plus or minus mmHg in the hypothyroid rats (p less than 0.001). Although maximal urinary bicarbonate concentrations achieved during bicarbonate loading were lower in the hypothyroid animals. U - B PCO2 was consistently less in controls when compared at similar urine bicarbonate concentrations. Thus, the difference in U - B PCO2 was not explained by lower urinary bicarbonate concentrations in the hypothyroid animals. Maximal U - B PCO2 during neutral phosphate loading was significantly less in the hypothyroid rats (38 plus or minus 2 mmHg) than in the controls (68 plus or minus 5 mmHg), p less than 0.001, arguing against a gradient defect of distal hydrogen ion handling. These data indicate that hypothyroid rats exhibit an impairment of distal hydrogen ion secretion.

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The mechanisms of the abnormal renal tubular handling of sodium and water in hypothyroidism are still unexplained. Since prostaglandins (PG) have been shown to diminish the tubular reabsorption of both sodium and water, this study was undertaken to examine the possibility that the tubular abnormalities observed in hypothyroidism are prostaglandin mediated. Renal clearance studies were performed in rats before and after administration of two prostaglandin synthetase inhibitors. There was no significant difference in the PG-inhibitor induced absolute and percentage decrease of sodium and fluid excretion between the normal and hypothyroid rats during mild volume expansion. This indicates that prostaglandins are not responsible for the increased fractional sodium and water excretion in hypothyroid animals.

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In these experiments, two groups of animals were studies to evaluate the effect of altering renal tubular sodium-handling on the excretion of acute HCl load. In group, I, normal salt animals hypotonically expanded with antidiuretic hormone (ADH) (using a protocol known to stimulate aldosterone) presented large amounts of sodium to the distal tubule and excreted an acute HCl load much more efficiently than did animals pretreated with either a normal (NL) or low (LO) salt diet alone. In group II, 24 hr after acid-loading, the plasma bicarbonate concentrations were significantly lower in animals pretreated with sodium restriction plus furosemide (F) than in those maintained on a normal (NL) or high (HI) salt diet alone. Acid excretion was maximized (ADH) when distal sodium avidity was stimulated in the presence of adequate distal sodium delivery and minimized (F) when distal sodium delivery was limited (despite possible augmentation of distal sodium avidity). Alterations in urinary sodium excretion alone (LO, NL, HI) did not affect the rate of acid excretion. These data are compatible with the hypothesis that the excretion of an acute HCl load is mediated by existing levels of distal sodium delivery and distal sodium avidity.

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