Systemic inhibition or global deletion of CaMKK2 protects against post-traumatic osteoarthritis.

OBJECTIVE: To investigate the role of Ca2+/calmodulin-dependent protein kinase 2 (CaMKK2) in post-traumatic osteoarthritis (PTOA). METHODS: Destabilization of the medial meniscus (DMM) or sham surgeries were performed on 10-week-old male wild-type (WT) and Camkk2-/- mice. Half of the DMM-WT mice and all other cohorts (n = 6/group) received tri-weekly intraperitoneal (i.p.) injections of saline whereas the remaining DMM-WT mice (n = 6/group) received i.p. injections of the CaMKK2 inhibitor STO-609 (0.033 mg/kg body weight) thrice a week. Study was terminated at 8- or 12-weeks post-surgery, and knee joints processed for microcomputed tomography imaging followed by histology and immunohistochemistry. Primary articular chondrocytes were isolated from knee joints of 4-6-day-old WT and Camkk2-/- mice, and treated with 10 ng/ml interleukin-1ß (IL)-1ß for 24 or 48 h to investigate gene and protein expression. RESULTS: CaMKK2 levels and activity became elevated in articular chondrocytes following IL-1ß treatment or DMM surgery. Inhibition or absence of CaMKK2 protected against DMM-associated destruction of the cartilage, subchondral bone alterations and synovial inflammation. When challenged with IL-1ß, chondrocytes lacking CaMKK2 displayed attenuated inflammation, cartilage catabolism, and resistance to suppression of matrix synthesis. IL-1ß-treated CaMKK2-null chondrocytes displayed decreased IL-6 production, activation of signal transducer and activator of transcription 3 (Stat3) and matrix metalloproteinase 13 (MMP13), indicating a potential mechanism for the regulation of inflammatory responses in chondrocytes by CaMKK2. CONCLUSIONS: Our findings reveal a novel function for CaMKK2 in chondrocytes and highlight the potential for its inhibition as an innovative therapeutic strategy in the prevention of PTOA.

Ecosystem services in vineyard landscapes: a focus on aboveground carbon storage and accumulation.

BACKGROUND: Organic viticulture can generate a range of ecosystem services including supporting biodiversity, reducing the use of conventional pesticides and fertilizers, and mitigating greenhouse gas emissions through long-term carbon (C) storage. Here we focused on aboveground C storage rates and accumulation using a one-year increment analysis applied across different winegrape varietals and different-aged vineyard blocks. This produced a chronosequence of C storage rates over what is roughly the productive lifespan of most vines (aged 2-30 years). To our knowledge, this study provides the first estimate of C storage rates in the woody biomass of vines. Additionally, we assessed C storage in wildland buffers and adjacent oak-dominated habitats over a 9-year period. RESULTS: Carbon storage averaged 6.5 Mg/Ha in vines. We found the average annual increase in woody C storage was 43% by mass. Variation correlated most strongly with vine age, where the younger the vine, the greater the relative increase in annual C. Decreases in C increment rates with vine age were more than offset by the greater overall biomass of older vines, such that C on the landscape continued to increase over the life of the vines at 18.5% per year on average. Varietal did not significantly affect storage rates or total C stored. Carbon storage averaged 81.7 Mg/Ha in native perennial buffer vegetation; we found an 11% increase in mass over 9 years for oak woodlands and savannas. CONCLUSIONS: Despite a decrease in the annual rate of C accumulation as vines age, we found a net increase in aboveground C in the woody biomass of vines. The results indicate the positive role that older vines play in on-farm (vineyard) C and overall aboveground accumulation rates. Additionally, we found that the conservation of native perennial vegetation as vineyard buffers and edge habitats contributes substantially to overall C stores. We recommend that future research consider longer time horizons for increment analysis, as this should improve the precision of C accumulation rate estimates, including in belowground (i.e., soil) reservoirs.

Spinal cord syndromes in patients with systemic lupus erythematosus: differentiating lupus myelitis, neuromyelitis optica, and multiple sclerosis.

OBJECTIVE: Non-infectious myelitis in systemic lupus erythematosus (SLE) may be due to SLE myelitis, comorbid multiple sclerosis (MS), or neuromyelitis optica (NMO). We compared characteristics of these three conditions in SLE patients at a large academic institution. METHODS: We searched for neurologic diagnoses of SLE myelitis, NMO myelitis, and MS myelitis among 2297 patients with at least four 1997 American College of Rheumatology revised criteria for SLE between 2000 and 2015. Each subject was reviewed by a neurologist to confirm the underlying neurologic diagnosis. Demographic, clinical, laboratory, and radiographic data were extracted and compared using Fisher's exact test, analysis of variance, and Wilcoxon rank-sum test. RESULTS: Fifteen of the 2297 subjects with SLE (0.7%) met criteria for a spinal cord syndrome: seven had SLE myelitis, three had AQP4 seropositive NMO, and five had MS. The median SLE Disease Activity Index 2000 score at time of neurologic syndrome presentation was higher in SLE myelitis subjects (8, interquartile range (IQR) 7-16) compared with subjects with NMO (6, IQR 0-14) or MS (2, IQR 0-4), p = 0.02. Subjects with SLE myelitis were also more likely to have elevated anti-dsDNA antibodies at presentation (86%) compared with subjects with NMO (33%) or MS (0%), p = 0.03. CONCLUSION: Myelitis occurs rarely among patients with SLE. Compared with subjects with SLE + NMO and subjects with SLE + MS, subjects with SLE myelitis had higher SLE disease activity at presentation.

Pesticide exposure and risk of systemic lupus erythematosus in an urban population of predominantly African-American women.

OBJECTIVE: Past studies have reported associations between pesticide exposure and the risk of systemic lupus erythematosus (SLE). Residential pesticide exposure has been less well studied than agricultural exposure. The purpose of this study was to assess SLE risk associated with residential pesticide exposure in an urban population of predominantly African-American women. METHODS: Adult women with SLE were identified from six hospital databases and community screening in three neighborhoods in Boston, Massachusetts, USA. Controls were adult women volunteers from the same neighborhoods who were screened for the absence of connective tissue disease and anti-nuclear antibodies. Subjects were considered exposed to pesticides if they had ever had an exterminator for an ant, cockroach, or termite problem prior to SLE diagnosis or corresponding reference age in controls. Risks associated with pesticide exposure were analyzed using multivariable logistic regression models, adjusted for sociodemographic factors. RESULTS: We identified 93 SLE subjects and 170 controls with similar baseline characteristics. Eighty-three per cent were African-American. Pesticide exposure was associated with SLE, after controlling for potential confounders (odds ratio 2.24, 95% confidence interval 1.28-3.93). CONCLUSION: Residential exposure to pesticides in an urban population of predominantly African-American women was associated with increased SLE risk. Additional studies are needed to corroborate these findings.

Myocardial tumor necrosis factor-alpha expression does not correlate with clinical indices of heart failure in patients on left ventricular assist device support.

BACKGROUND: Mechanical unloading with a left ventricular assist device (LVAD) can improve clinical indices of heart failure and alter myocardial tumor necrosis factor-alpha (TNFalpha) expression, but a correlation between clinical and molecular indices has not been established. METHODS: We enrolled 14 patients with end-stage heart failure treated with drugs and mechanical unloading in a protocol including the collection of myocardial tissue samples at LVAD implantation and explantation. Ten nonfailing donor hearts served as controls. TNFalpha expression was measured by quantitative reverse transcription polymerase chain reaction. Clinical indices of heart failure were retrospectively analyzed and correlated with myocardial TNFalpha expression. RESULTS: Left ventricular end-diastolic dimension decreased (p < 0.01) and cardiac index (p < 0.001) increased with unloading. Abnormal values of serum sodium, creatinine, blood urea nitrogen, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, and albumin showed a trend toward normalization with mechanical unloading. TNFalpha expression was increased in 5 of 14 patients and decreased with mechanical unloading in 4 of them. Surprisingly, there was no correlation between mRNA levels of TNFalpha and any of the clinical indices studied. CONCLUSIONS: Although clinical indices of heart failure improve and elevated levels of myocardial TNFalpha expression decrease with mechanical unloading, there is no correlation between the two. Thus, clinical and molecular indices of heart failure in LVAD-supported patients do not always correlate.

The ethics of placebo-controlled trials in developing countries to prevent mother-to-child transmission of HIV.

Placebo-trials on HIV-infected pregnant women in developing countries like Thailand and Uganda have provoked recent controversy. Such experiments aim to find a treatment that will cut the rate of vertical transmission more efficiently than existing treatments like zidovudine. This scenario is first stated as generally as possible, before three ethical principles found in the Belmont Report, itself a sharpening of the Helsinki Declaration, are stated. These three principles are the Principle of Utility, the Principle of Autonomy and the Principle of Justice. These are taken as voices of moral imperative. But although each has intuitive appeal, it can be shown that there are possible scenarios in which they give conflicting prescriptions. To achieve consistency, one must be subordinate to the others. The voice of utility is taken as subordinate to those of justice and autonomy and it is shown that given plausible assumptions about the level of poverty and education in the developing country targeted, the experiment is ruled morally wrong in the name of both justice and autonomy. Moreover, it is argued that no justification can be found for the inclusion of a placebo group, when strictly defined. By contrast, a 'no-treatment' control arm might be justified, but only when the demands of autonomy are satisfied, demands that are more stringent than they might appear. A utilitarian defence of the experiment is examined, namely that the would-be participants are in a no-loss situation, and it is shown that this defence is seriously flawed. Finally, it is concluded that there is no justification for amending the Declaration of Helsinki.

Lack of immunity in university students before an outbreak of serogroup C meningococcal infection.

Immunity to meningococci was determined in infected and uninfected students before and during an outbreak of serogroup C meningococcal infection at a university in the United Kingdom. No immunity against the outbreak strain was detected in serum taken from infected students prior to the outbreak or at the time of admission; bactericidal activity developed during convalescence. Carriage of all strains of serogroup C meningococci in asymptomatic students was low (0.9%), and no carriage of the outbreak strain could be detected. Immunity in the at-risk student population before the outbreak was low: 90% of students had no significant bactericidal activity against the outbreak strain. A low prevalence of carriage of the outbreak strain, together with a low prevalence of protective immunity within the student population, was associated with a high incidence of invasive disease in those who acquired the outbreak strain.

Root trunk dimensions of 5 different tooth types.

The primary purpose of this study was to document mean, standard deviation, and range of root trunk dimensions of multirooted tooth types. A total of 412 extracted teeth were examined and classified as: maxillary first molars, maxillary second molars, maxillary first premolars, mandibular first molars, and mandibular second molars. The distance from the cementoenamel junction (CEJ) to the root groove and from the CEJ to the root division was measured. Mean CEJ to root groove distances ranged from 1.35 to 1.65 mm for maxillary first molars, from 1.49 to 1.89 mm for maxillary second molars, from 1.71 to 1.73 mm for maxillary first premolars, from 1.16 to 1.22 mm for mandibular first molars, and from 1.53 to 1.76 mm for mandibular second molars.

Why is short-term sentence recall verbatim? An evaluation of the role of lexical priming.

By showing that short-term sentence recall can be significantly affected by words encountered in an intervening distractor task, Potter and Lombardi (1990, Journal of Memory and Language, 29, 633-654) argue that short-term sentence recall is often verbatim because of the availability of recently activated lexical entries during the regeneration of the sentence from its conceptual representation. We show that similar effects can be obtained even when bilinguals perform an intervening task in a different language from that of sentence recall, or when monolinguals perform an intervening task upon pictures. Furthermore, we show that the presentation of a word in P&L's distractor task does not, in any case, affect subsequent retrieval of a semantically related word as measured in a picture-naming task. We suggest that the effects on recall reported here and by P&L should be explained in terms of conceptual level interference at the time of recall. We also discuss the implications of our suggestion for the issue of the verbatimness of short-term sentence recall.

Sociodemographics of homebound people in Kentucky.

In this report, selected results are presented from the 1987 Kentucky Oral Health Survey, which acquired statewide data on the oral health status and practices of the noninstitutionalized population of Kentucky. In the 1987 epidemiological survey, information about persons who were homebound was also gathered through telephone and in-person interviews. The results of that survey provided a relatively accurate estimate of the number of persons homebound in the state of Kentucky. Although the majority of this population was older than age 60, almost 21% were between the ages of 35 and 59. Household income for persons who are homebound and the amount of money spent on dental care is significantly less than in households not reporting the presence of a person who is homebound. These findings provide baseline data for dentists and health planners interested in serving this population. Also, this data is pertinent to the formation of health policies to create accessible, affordable care for this growing segment of the population.

Quality assessment/assurance activities in U.S. dental schools.

Quality of health care services has become a major social issue. Accordingly, activities directed toward the assessment and assurance of quality are receiving increased attention in dentistry and dental education. The purpose of this study was to determine the status of quality assessment/assurance (QA) programs in U.S. dental schools. Responses from 48 U.S. schools identify a range of institutional QA activities currently being conducted in dental education. The evaluation and remedial action elements of the QA process are being addressed in a majority of schools; however, the establishment of criteria delineating those elements of a given QA activity area that should be measured is lacking.