Cold stress protein RBM3 responds to temperature change in an ultra-sensitive manner in young neurons.

Extremely mild hypothermia to 36.0 °C is not thought to appreciably differ clinically from 37.0 °C. However, it is possible that 36.0 °C stimulates highly sensitive hypothermic signaling mechanism(s) and alters biochemistry. To the best of our knowledge, no such ultra-sensitive pathway/mechanisms have been described. Here we show that cold stress protein RNA binding motif 3 (RBM3) increases in neuron and astrocyte cultures maintained at 33 °C or 36 °C for 24 or 48 h, compared to 37 °C controls. Neurons cultured at 36 °C also had increased global protein synthesis (GPS). Finally, we found that melatonin or fibroblast growth factor 21 (FGF21) augmented RBM3 upregulation in young neurons cooled to 36 °C. Our results show that a 1 °C reduction in temperature can induce pleiotropic biochemical changes by upregulating GPS in neurons which may be mediated by RBM3 and that this process can be pharmacologically mimicked and enhanced with melatonin or FGF21.

Anthraquinone-2-sulfonic acid (AQ2S) is a novel neurotherapeutic agent.

Anthraquinone derivatives such as emodin have recently been shown to protect in models of beta amyloid ß (Aß) and tau aggregation-induced cell death. The mechanisms of action possibly involve preconditioning effects, anti-aggregation properties, and/or enhancing the phosphatidylinositol-3-kinase (PI3K)/AKT survival mechanism. We studied several natural (emodin, rhein, and aloin) and synthetic (AQ2S) anthraquinones, to screen for post-treatment therapeutic benefit in two models of neuronal death, namely hydrogen peroxide (H(2)O(2)) and staurosporine (STS)-induced injury. Treatment with emodin, rhein, or aloin failed to reduce H(2)O(2) injury. Moreover, consistent with emodin behaving like a mild toxin, it exacerbated oxidative injury at the highest concentration used (50 µM) in our post-treatment paradigm, and potently inhibited AKT. In contrast, AQ2S was neuroprotective. It reduced H(2)O(2) injury at 50 and 75 µM. In addition, AQ2S potently inhibited staurosporine (STS)-induced injury. The mechanisms of action involve caspase inhibition and AKT activation. However, blockade of AKT signaling with LY294002 failed to abolish AQ2S-mediated protection on the STS assay. This is the first study to report that AQ2S is a new neuroprotective compound and a novel caspase inhibitor.

Cellular and molecular characterization of a feline insulinoma.

BACKGROUND: Insulinoma is an autonomous insulin-secreting islet cell neoplasm that is rarely diagnosed in cats. The clinical and pathological aspects of feline insulinoma have been described previously, but the molecular characteristics of these tumors have not been investigated. OBJECTIVES: The study objectives were to characterize peptide hormone production and determine expression of selected genes involved in glucose metabolism and insulin secretion in a feline insulinoma. METHODS: Immunohistochemistry and RT-PCR were used to examine hormone and gene expression, respectively, by insulinoma cells. RESULTS: Immunohistochemistry examination indicated that the tumor cells expressed insulin, chromogranin A, and somatostatin but not glucagon or pancreatic polypeptide. The tumor expressed several genes characteristic of pancreatic beta cells (beta cells) including insulin (INS), glucose transporter 2 (GLUT2), and glucokinase (GCK). The tumor also expressed hexokinase 1 (HK1), a glycolytic enzyme not normally expressed in beta cells. GCK expression was higher in the insulinoma than in normal pancreas from the same cat. The GCK : HK1 ratio was >20-fold higher in insulinoma tissue than in normal pancreas. CONCLUSIONS AND CLINICAL IMPORTANCE: The feline insulinoma produced several peptide hormones and expressed genes consistent with a beta-cell phenotype. The pattern of hexokinase gene expression in tumor cells differed from that of normal pancreas. These findings suggest insulinoma cells may have an increased sensitivity to glucose that could contribute to the abnormal insulin secretory response observed at low serum glucose concentrations.

Regional hippocampal differences in AKT survival signaling across the lifespan: implications for CA1 vulnerability with aging.

Distinct neuronal populations differ by the degree of damage caused from cellular stress. Hippocampal neurons of area CA1 are especially vulnerable to several stressors that increase as age advances. We show here that survival signaling, as measured by activated protein kinase B (AKT), was significantly reduced in the nuclear CA1 region across the lifespan compared with CA3. In agreement with these findings, the pro-apoptotic protein and AKT nuclear substrate, forkhead box O3a transcription factor (FOXO3a), were significantly higher in CA1. Further, regional differences in PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1), a recently discovered inhibitor of AKT, inversely correlated with nuclear phosphorylated AKT at Ser473. Altogether, our data suggest that regional differences in nuclear levels of activated AKT may contribute to regional differences in hippocampal vulnerability and implicate PHLPP1 as a potential target for therapeutic intervention to improve hippocampal health.

Heat resistance of Escherichia coli O157:H7 in a nutrient medium and in ground beef patties as influenced by storage and holding temperatures.

Stationary-phase cultures of Escherichia coli O157:H7 were inoculated into tryptic soy broth, sealed in vials, and stored at -18 degrees C for 1, 8, and 15 days, or 3 or 15 degrees C for 3, 6, and 9 h. Thermal resistance was determined at 55 degrees C. Each storage treatment was repeated with additional holding at 23 or 30 degrees C for 1, 2, 3, or 4 h prior to heating to simulate potential temperature abuse during handling. Cultures under treatments enabling the growth of E. coli O157:H7 were generally more heat sensitive than those held at temperatures which restricted growth or enabled growth to stationary phase. Cultures stored frozen (-18 degrees C) without holding at elevated temperatures had greater heat resistance than those stored under refrigeration (3 degrees C) or at 15 degrees C. Subsequent holding of frozen cultures at 23 or 30 degrees C resulted in a decrease in heat resistance. To determine whether these responses would be observed under typical commercial preparation procedures, ground beef patties were inoculated with E. coli O157:H7 and stored at 3 or 15 degrees C for 9 h or at -18 degrees C for 8 d and then held at 21 or 30 degrees C for 0 or 4 h. Patties were grilled to an internal temperature of 54.4 degrees C (130 degrees F), 62.8 degrees C (145 degrees F), or 68.3 degrees C (155 degrees F). Cultures were most resistant in frozen patties, while cultures in patties stored at 15 degrees C were the most heat sensitive. Holding patties at 21 or 30 degrees C prior to grilling resulted in increased sensitivity. Storage and holding temperatures similar to those encountered in food service may influence the ability of E. coli O157:H7 to survive heat treatments.

Effect of utilization review in a fee-for-service health insurance plan.

BACKGROUND: Although utilization review is widely used to control health care costs, its effect on patterns of health care is uncertain. METHODS: In 1989, New York City and its unions temporarily replaced actual utilization review with sham review for half the participants in the city's fee-for-service health insurance plan. We compared the health services provided to 3702 enrollees whose requests were subjected to utilization review (the review group) with the services provided to 3743 enrollees whose requests received sham review and were automatically approved for insurance coverage (the nonreview group). The enrollees, physicians, and hospitals were all unaware of the group assignments. RESULTS: During the study period (mean duration, eight months), the members of the review group underwent 1255 procedures in 20 categories of procedures for which second opinions were required (such as breast, cataract, foot, hernia, and hip-replacement surgery, as well as hysterectomy and coronary bypass surgery), and the members of the nonreview group underwent 1365 procedures (P = 0.02). The members of the review group had 124 fewer procedures in doctors' offices and hospital outpatient departments (P = 0.002). In the following year, the members of the review group underwent 248 procedures from the 20 categories, and the members of the nonreview group underwent 234 (P = 0.46). No other differences in patterns of care were found between the groups, including rates of hospital admission to medical-surgical, substances-abuse, or psychiatric units; average lengths of hospital stay; the percentage of enrollees who received preadmission testing; or rates of use of home care. During the study period, the mean age-adjusted insurance payments per person were $7,355 in the review group and $6,858 in the nonreview group (P = 0.06). CONCLUSIONS: The utilization-review program reduced the performance of diagnostic and surgical procedures for which second opinions were required and did not merely delay them until the following year. Otherwise, the program had little effect. Alternatively, actual review and sham review may both have decreased the use of hospital services, with patients or their physicians choosing more efficient treatment when they believed that care would be reviewed.

Ostrich slaughter and fabrication: 1. Slaughter yields of carcasses and effects of electrical stimulation on post-mortem pH.

A commercial ostrich slaughter protocol was developed. Ostriches (n = 7 males and n = 7 females) averaged 95.54 kg live weight and yielded 55.91-kg carcasses. By-product yields were measured. The most significant by-products by weight were full viscera (8.29 kg), hide (6.71 kg), full gizzard and crop (5.80 kg), and abdominal fat (4.11 kg). Sex had no effect on slaughter yields. Post-mortem temperature declines were measured on five separate muscles and showed that chilling for 24 h was sufficient to adequately chill the deep muscle temperature to under 4 C. The effect of electrical stimulation on post-mortem pH decline also was investigated and had no effect.

Educational characteristics of ambulatory morning report.

The educational characteristics of ambulatory morning report were compared with those of the inpatient morning report sessions over a five-month period. Ambulatory morning report had fewer total participants and was more likely to cover general internal medicine topics (p < 0.05), the medical interview (6.8% vs 1.2%, p = 0.02), and social issues (9.6% vs 1.2%, p = 0.02). Morning report conference can be replicated in the ambulatory setting, thus providing an opportunity to discuss general medicine topics not usually addressed in the inpatient setting.

What do senior internal medicine residents do in their continuity clinics?

OBJECTIVE: To describe the activities of second- and third-year internal medicine residents during their outpatient continuity clinics. DESIGN: Descriptive observational study. SETTING: Medical school-affiliated community hospital primary care clinic. PATIENTS/PARTICIPANTS: All second-year (n = 15) and third-year (n = 14) residents enrolled in the internal medicine training program were observed at one-minute intervals during their routine half-day continuity clinics. MEASUREMENTS AND MAIN RESULTS: An average of 203 observations were recorded for each resident. The distribution of resident activities was as follows: 1) direct interaction with patients (29.5%); 2) charting or writing prescriptions (24.0%); 3) social interactions with staff (13.7%); 4) attending conferences or reviewing medical literature (9.4%); 5) waiting or transiting (8.2%); 6) ward responsibilities (4.9%); 7) reviewing cases with attending physicians (4.4%); and 8) miscellaneous activities (4.9%). Analysis of variance procedures revealed that the following variables significantly (p < 0.05) affected the residents' activities: 1) the actual number of patients seen produced predictable increases in direct and indirect patient care activities; and 2) the year of training had an impact on the mean number of observations of interactions with the supervising attending physician (PGY-2 = 11.4, PGY-3 = 3.8). CONCLUSIONS: These results suggest that this senior resident continuity experience is clinically intensive, yet provides surprisingly infrequent direct resident supervision. Further analysis of the educational activities occurring on these half-days is necessary to judge whether they are quantitatively and qualitatively adequate.

Survey of Residential Refrigerators for the Presence of Listeria monocytogenes.

One hundred and ninety-five residential refrigerators in Brazos and Robertson counties of Texas were examined for the presence of Listeria monocytogenes . Surfaces on which meat and vegetables were usually stored, as well as other storage areas, were sampled. L. monocytogenes was not recovered from any of the refrigerators sampled. The organism, if introduced, may only be a transient inhabitant of refrigerator surfaces, as long-term colonization of such surfaces does not seem to be a common occurrence.

Identification and evaluation of volatile compounds of vacuum and modified atmosphere packaged beef strip loins.

Beef strip loins were packaged and stored for up to 28 days at 3°C in high-oxygen barrier film under vacuum and in 100% CO(2), 40% CO(2)/60% N(2) and 20% CO(2)/80% O(2). As storage progressed, loins packaged and stored in 20% CO(2)/80% O(2) developed strong off-odors. 1-hexene, methyl thiirane, ethyl acetate, benzene and 1-heptene were detected in these packaged loins beginning at 7 to 14 days of storage. With the exception of 1-hexene, these compounds were not consistently detected in loins stored in vacuum, in 100% CO(2), or in 40% CO(2)/60% N(2), and these packaged loins developed much less off-odor during storage than loins packaged and stored in 20% CO(2)/80% O(2). A large number of volatile compounds from the headspace of the packaged loins originated from the packaging material. Lactobacillus plantarum became the dominant flora on loins stored under vacuum and under 40% CO(2)/60% N(2) while Leuconostoc mesenteroides subsp. mesenteroides predominated in loins stored in 100% CO(2). Pseudomonas putida eventually dominated on loins stored in 20% CO(2)/80% O(2).

Have you been taking your pills? The adherence-monitoring sequence in the medical interview.

This paper employs qualitative, sociolinguistic techniques to identify and describe the kinds of conversational strategies that primary care physicians use to assess patient adherence to antihypertensive regimens. Three general approaches are described: indirect inquiry, simple direct questions, and information-intensive inquiry. The strengths and weaknesses inherent in these discourse categories are discussed. Qualitative assessment, coupled with the results of a pilot study investigating the effectiveness of naturally occurring instances of these three general styles, leads to the conclusion that how one asks "Have you been taking your medications?" is consequential for the accurate diagnosis and management of adherence problems.

Essential thrombocythemia in pregnancy.

A 32-year-old women with essential thrombocythemia and a history of bleeding completed a full-term pregnancy. During pregnancy, the platelet count declined markedly to near-normal levels, but returned to prepregnancy levels within two weeks after delivery. The clinical course was uneventful, except for two brief episodes of vaginal bleeding during the second trimester. Possible etiologic mechanisms for pregnancy-related reduction of platelet levels in thrombocythemia include increased platelet consumption or down-regulation of platelet production by a placental or fetal factor.

The activated patient: dogma, dream, or desideratum?

In this paper we critically review the active patient concept and place it in a broader social and historical context. We argue that as a reflection of core, Western European values, the active patient concept has not been adequately scrutinized. Very little research has been done that explicitly tests the claims that have been advanced on behalf of this ideal model of the clinician-patient relationship. The research that is available is far from definitive and does not support many of the assertions made by advocates of this approach to patienthood. We urge investigators to substitute theory driven research programs for those motivated by advocacy of a particular ideological stance.

Determinants of three stages of delay in seeking care at a medical clinic.

Factors affecting delay were studied in patients seeking treatment for the first time for a particular symptom at clinics in a major, innercity hospital. On the basis of the patients' retrospective report, the total time from first noticing a symptom to the seeking of treatment was divided into three sequential stages: 1) appraisal delay--the time the patient takes to appraise a symptom as a sign of illness; 2) illness delay--the time taken from deciding one is ill until deciding to seek professional medical care; and 3) utilization delay--the time from the decision to seek care until the patient goes to the clinic and uses its services. The variables used to predict the length of delay for each of the three stages and for total delay included reports on concrete, sensory perceptions and abstract, conceptual beliefs about one's symptoms, behavioral factors such as strategies for self-appraisal and techniques for coping with illness, emotional reactions, negative imagery elicited by the illness threat, situational barriers, and socio-demographic factors. Patients experiencing a very painful symptom and patients who did not read about their symptom had a short appraisal delay. Patients with old symptoms and those who imagined possible, severe consequences of their illness had long illness delays. Utilization delay was shortest for persons who were not concerned about the cost of treatment, who had a painful symptom, and who were certain that their symptom could be cured. Patients who had short total delays were persons who did not have a competing personal problem and who had a painful symptom. All of these predictors were significantly correlated with the measure of delay at or beyond the p = .01 level. It was concluded that different factors mediate delay in each of the three stages and that studies which use only a single measure of total delay are likely to be of limited value in understanding delay.