Marrow adipogenesis and bone loss that parallels estrogen deficiency is slowed by low-intensity mechanical signals.

UNLABELLED: Ovariectomized mice were used to assess the ability of low-intensity vibrations to protect bone microarchitecture and marrow composition. Results indicate that low-intensity vibrations (LIV), introduced 2 weeks postsurgery, slows marrow adipogenesis in OVX mice but does not restore the bone within the period studied. However, immediate application of LIV partially protects quality. INTRODUCTION: The aim of this study was to evaluate consequences of estrogen depletion on bone marrow (BM) phenotype and bone microarchitecture, and effects of mechanical signals delivered as LIV on modulating these changes. METHODS: LIV (0.3 g, 90 Hz) was applied to C57BL/6 mice immediately following ovariectomy or 2 weeks postestrogen withdrawal for 2 (ST-LIV) or 6 weeks (LT-LIV), respectively. Sham-operated age-matched controls (ST-AC, LT-AC) and ovariectomized controls (ST-OVX, LT-OVX) received sham LIV treatment. Bone microstructure was evaluated through µCT and BM adipogenesis through histomorphometry, serum markers, and genes expression analysis. RESULTS: LT-OVX increased BM adipogenesis relative to LT-AC (+136 %, p ≤ 0.05), while LT-LIV introduced for 6w suppressed this adipose encroachment (-55 %, p ≤ 0.05). In parallel with the fatty marrow, LT-OVX showed a marked loss of trabecular bone, -40 % (p ≤ 0.05) in the first 2 weeks following ovariectomy compared to LT-AC. Application of LT-LIV for 6w following this initial 2w bone loss failed to restore the lost trabeculae but did initiate an anabolic response as indicated by increased serum alkaline phosphatase (+26 %, p ≤ 0.05). In contrast, application of LIV immediately following ovariectomy was more efficacious in the protection of trabecular bone, with a +29 % (p > 0.05) greater BV/TV compared to ST-OVX at the 2w time period. CONCLUSIONS: LIV can mitigate adipocyte accumulation in OVX marrow and protect it by favoring osteoblastogenesis over adipogenesis. These data also emphasize the rapidity of bone loss with OVX and provide perspective in the timing of treatments for postmenopausal osteoporosis where sooner is better than later.

Effect of online diabetes training for hospitalists on inpatient glycaemia.

AIM: An online diabetes course for medical residents led to lower patient blood glucose, but also increased hypoglycaemia despite improved trainee confidence and knowledge. Based on these findings, we determined whether an optimized educational intervention delivered to hospitalists (corresponding to an Acute Physician or Specialist in Acute Hospital Medicine in the UK) improved inpatient glycaemia without concomitant hypoglycaemia. METHODS: All 22 hospitalists at an academic medical centre were asked to participate in an online curriculum on the management of inpatient dysglycaemia in autumn 2009 and a refresher course in spring 2010. RESULTS: All hospitalists completed the initial intervention. Median event blood glucose decreased from 9.3 mmol/l (168 mg/dl) pre-intervention to 7.8 mmol/l (141 mg/dl) post-intervention and 8.5 mmol/l (153 mg/dl) post-refresher (P < 0.001 for both). Hospitalizations categorized as hyperglycaemia decreased from 83.3 to 55.6% (P = 0.014), with a trend towards euglycaemia (10-28.9%, P = 0.08) and no change in hypoglycaemia. Hyperglycaemic patient-days decreased from 72.0 to 57.3% (P = 0.004), with greater target glycaemia (27.3-39.4%, P = 0.016) and no change in hypoglycaemia. CONCLUSIONS: An optimized online educational intervention delivered to hospitalists yielded significant improvements in inpatient glycaemia without increased hypoglycaemia.

Energized configurations of heart mitochondria in situ.

Changes in the configurational state of the cristal membranes of rat heart mitochondria within the living cell can be induced by imposing energizing conditions. An exact correlation has been established between the configurational states of the cristal membrane and the energy states of the mitochondrion. The configurational changes observed in mitochondria in situ are comparable to those established for beef heart mitochondria in vitro and are consistent with the postulate of the conformational basis of energy transductions in membrane systems. The formation of paracrystalline arrays is one of the noteworthy features of configurational changes of mitochondria in situ.

AlphaB-crystallin in lens development and muscle integrity: a gene knockout approach.

PURPOSE: To study the role of alphaB-crystallin (alphaB) in the developing lens and its importance in lens structure and function. METHODS: Gene targeting in embryonic stem cells was used to generate mouse lines in which the alphaB gene and its protein product were absent. Gene structure and expression were characterized by genomic Southern blot, immunoblot, and Northern blot analyses, and two-dimensional gel electrophoresis. The gene knockout mice were screened for cataract with slit lamp biomicroscopy, and dissected lenses were examined with dark-field microscopy. Lenses and other tissues were analyzed by standard histology and immunohistochemistry. Chaperone activity was determined by heating lens homogenate supernatants and measuring absorbance changes. RESULTS: In an unexpected result, lenses in the alphaB gene knockout mice developed normally and were remarkably similar to wild-type mouse lenses. All the other crystallins were present. The thermal stability of a lens homogenate supernatant was mildly compromised, and when oxidatively stressed in vivo with hyperbaric oxygen, the knockout lenses reacted similarly to wild type. In targeting the alphaB gene, the adjacent HSPB2 gene, which is not expressed in the lens, was also disrupted. Loss of alphaB and/or HSPB2 function leads to degeneration of some skeletal muscles. CONCLUSIONS: AlphaB is not essential for normal development of a transparent lens in the mouse, and therefore is more dispensable to the lens than the closely related alphaA-crystallin. It may play a small role in maintaining transparency throughout life. alphaB and/or the closely related HSPB2 is required to maintain muscle cell integrity in some skeletal muscles.

Molecular characterization of iridoviruses isolated from sympatric amphibians and fish.

Iridoviruses infect invertebrates (primarily insects and crustaceans) and ectothermic vertebrates (fish, amphibians, and reptiles). Identical, or nearly identical viruses, have been isolated from different animals within the same taxonomic class, indicating that infection by a given virus is not limited to a single species. Although inter-class infections have been documented following experimental infection with vertebrate iridoviruses, it is not clear whether such infections occur in nature. Here we report the isolation of apparently identical iridoviruses from wild sympatric fish (the threespine stickleback, Gasterostelus aculeatus) and amphibians (the red-legged frog, Rana aurora). Viruses isolated from sticklebacks (stickleback virus, SBV) and from a red-legged frog tadpole (tadpole virus 2, TV2) replicated in fathead minnow (FHM) cells and synthesized proteins which co-migrated with those of frog virus 3 (FV3). Following restriction endonuclease digestion of viral DNA with Hind III and Xba I, gel analysis showed that the profiles of SBV and TV2 were identical to each other and distinct from FV3. Using oligonucleotide primers specific for a highly conserved region of the iridovirus major capsid protein, an approximately 500 nucleotide DNA fragment was amplified from SBV and TV2. Sequence analysis showed that within this 500 nucleotide region SBV and TV2 were identical to each other and to FV3. Taken together these results provide the first evidence that iridoviruses naturally infect animals belonging to different taxonomic classes, and strengthen the suggestion that fish may serve as a reservoir for amphibian viruses or vice versa.

Massive tracheal necrosis complicating endotracheal intubation.

There are significant complications associated with endotracheal intubation. Massive tracheal necrosis secondary to tracheoesophageal space abscess developed in a 71-year-old man during mechanical ventilation. Elevated endotracheal tube cuff pressures, sepsis, hypotension, and other risk factors predispose to this disastrous consequence.

Pharyngeal volume in asymptomatic snorers compared with nonsnoring volunteers.

STUDY OBJECTIVE: to determine if asymptomatic snorers have smaller pharyngeal volumes than age- and height-matched nonsnorers. DESIGN: we recruited asymptomatic heavy snorers and nonsnorers for a study. Each snorer was matched by age (+/- 3 years) and height (+/- 2 inches) with a nonsnorer. The nonsnorers were required to be near ideal body weight. All volunteers underwent overnight polysomnography, pulmonary function testing, and magnetic resonance imaging of the pharynx while awake. The volume of the pharynx was determined by a computer with data input from a digitizing instrument. SETTING: Veterans Administration Hospital and University of Florida Teaching Hospital PARTICIPANTS: Nine volunteers were recruited for both the snorer and nonsnorer groups. Each participant was paid $50. There were no interventions. MEASUREMENTS AND RESULTS: There were no differences in sleep variables between the two groups. There was also no significant difference between pharyngeal volumes for the two groups. CONCLUSIONS: The volume of the pharynx in asymptomatic snorers is similar to the volume in age- and height-matched nonsnorers.

Cutaneous mastocytomas in the neotenic caudate amphibians Ambystoma mexicanum (axolotl) and Ambystoma tigrinum (tiger salamander).

Spontaneous mastocytomas studied in 18 axolotls (Ambystoma mexicanum) and six tiger salamanders (Ambystoma tigrinum) were gray-white, uni- to multilobular cutaneous protrusions from 2 mm to 2 cm in diameter. Tumors were moderately cellular unencapsulated masses that usually infiltrated the dermis and hypodermis with the destruction of intervening tissues. Some tumors were invading superficial bundles of the underlying skeletal muscle. Tumors consisted of mitotically active cells derived from a single lineage but showing a range of differentiation. Immature cells had nearly smooth to lightly cleft or folded basophilic nuclei bordered by a band of cytoplasm with few cytoplasmic processes and containing a few small uniform eccentric granules. Mature cells had basophilic nuclei with deep clefts or folds and abundant eosinophilic cytoplasm with multiple long intertwining cytoplasmic extensions packed with metachromatic granules. The axolotls were old individuals from an inbred laboratory colony. The tiger salamanders were wild animals from a single polluted pond. They could have been old and inbred. Both groups were neotenic. These are the first mastocytomas discovered in cold-blooded animals.

Role of ionophores in energy coupling.

If, as we deem inevitable, the principles of energy coupling are universal, then the necessity for charge-separating devices will apply across the board to all bioenergetic systems. Since, apart from the elctron transfer chain, ionophores are the only charge-separating devices available in bioenergetic systems, model of energy coupling that does not feature this central role of ionophores can be taken seriously. The ionophore approach thus opens the royal highway to the ultimate solution of all bioenergetic problems.

Studies of the coagulation system in arenaviral hemorrhagic fever: experimental infection of strain 13 guinea pigs with Pichinde virus.

Significant coagulation abnormalities were associated with experimental infection of strain 13 guinea pigs with Pichinde virus, an arenavirus related to the virulent human pathogens Junin, Machupo, and Lassa viruses. Infected animals developed decreased activity of multiple coagulation factors, decreased antithrombin III levels, high levels of fibrin-fibrinogen degradation products, impaired platelet function, and thrombocytopenia. Testing for the presence of a coagulation inhibitor revealed a pattern consistent with factor deficiency. Fibrin thrombi were not found at necropsy. The findings of high fibrin-fibrinogen degradation product levels and decreased antithrombin III levels, in association with decreased activity of multiple coagulation factors and thrombocytopenia, suggest that intravascular coagulation is a feature of this experimental infection. The demonstration of abnormal platelet function is also significant, as this could contribute to defective hemostasis despite the moderate thrombocytopenia which usually occurs in arenaviral disease.

Maturation of humoral immune response determines the susceptibility of guinea-pigs to leptospirosis.

Baby guinea-pigs were susceptible to infection with Leptospira interrogans serovar pomona, but rapidly became resistant as they matured. Increased resistance with increasing weight of guinea-pigs was correlated with the development of ability to produce agglutinating antibodies to leptospires and with maturation of B-cell dependent (but not T-cell dependent) areas in lymphoid organs. These observations can explain the basis of species-resistance of adult guinea-pigs to infection with serovar pomona.

Attitudes to AIDS: a comparative analysis of a new and negative stereotype.

Two propositions about attitudes, which have previously been supported with respect to the mentally ill, were examined with respect to AIDS patients. The first, that people attach a stigma to the AIDS patient, was strongly supported, and two quite independent components of the stigma were found. One of these components identified as dependence, was closely related to the attributes of typical cancer patients and coronary heart patients, while the other, identified as low moral worth, clearly distinguished the AIDS patient from the other two groups of patients. The second proposition, that attitudes to AIDS are not strongly related to age, sex and occupational background, was largely supported. However there was some evidence that males rated AIDS patients lower on moral worth than did females.

Community attitudes to mental illness in New Zealand twenty-two years on.

Three propositions about attitudes to mental illness derived from Nunnally (Popular Conceptions of Mental Health. Holt, Rinehart & Winston, New York, 1961) were examined with the semantic differential technique as it was used originally by Olmsted and Ordway (Final Report to National Institutes of Mental Health, 1963). Attitudes were compared between several studies using the same measures, that ranged over 22 years from 1962 to 1984. The results were remarkably consistent across all studies, indicating that the community had persistently negative attitudes towards the mentally ill and was no more likely today to want to play a major role in the care of the mentally ill than was the case more than 20 years ago. As a consequence it appears that there will need to be substantial and permanent attitude change, of a kind fleetingly observed over the period of the study, before the professional care of the mentally ill in the community may be expected to have maximum impact.

Synthesis, isolation, and characterization of two stereoisomeric ring sulfoxides of thioridazine.

A selective oxidation of thioridazine to give exclusively its ring sulfoxides and a separation of the resulting products as diastereoisomeric pairs of enantiomers (DL, LD and DD, LL) are reported. These pairs were characterized by TLC, high-performance liquid chromatographic, IR, UV, 1H-NMR, 13C-NMR, GC-MS, and elemental analyses, and by reduction to thioridazine by lithium aluminum hydride. Structural data for the separated diastereoisomeric pairs or their nitric acid salts were obtained from NMR and IR studies. Gram quantities of each of the two diastereoisomeric pairs of enantiomers were isolated in better than 99% purity.

Comparative perceptions of driver ability--a confirmation and expansion.

This study aimed to investigate earlier Swedish and United States research which has shown that drivers tend to rate themselves as more skillful and less risky than the average driver, and to extend the range of driver characteristics on which such ratings are made. A total of 178 male and female drivers rated "me as a driver," "an average driver" and "a very good driver" on the following eight relevant bipolar semantic differential scales: foolish-wise, unpredictable-predictable, unreliable-reliable, inconsiderate-considerate, dangerous-safe, tense-relaxed, worthless-valuable, irresponsible-responsible. The results confirmed expectations that a substantial majority of drivers, up to 80%, would rate themselves above average on a number of important characteristics, but also showed that they rated themselves below "a very good driver." The ratings did not vary significantly across demographic categories. Implications for road safety are briefly discussed.

Components of Resistance to Rhizoctonia solani Associated with Two Tall Fescue Cultivars.

Components of resistance to Rhizoctonia solani in the tall fescue cultivars Kentucky 31 (moderately resistant) and Mojave (susceptible) were evaluated under controlled environmental conditions. Size and expansion rate of foliar lesions were recorded on 100 individual plants of each cultivar. Lesions on the first fully expanded leaves of 6- to 10-month-old inoculated plants covered a significantly greater proportion of the leaf width on cv. Mojave compared to Kentucky 31. Rate of lesion expansion was also greater on cv. Mojave than on Kentucky 31. Lesion size and rate of expansion were greater on the second compared to the first fully expanded leaf of both cultivars. Wider leaves and slower lesion expansion are two components responsible for the greater level of resistance to R. solani in cv. Kentucky 31 compared to Mojave tall fescue.