Steroids Alone or as Adjunctive Therapy with Doxycycline Fail To Improve Oviduct Damage in Mice Infected with Chlamydia muridarum

In women, Chlamydia trachomatis can ascend from the cervix to the fallopian tubes, where an overly aggressive host inflammatory response can cause scarring that leads to chronic pelvic pain, infertility, or ectopic pregnancy. Although screening and treatment programs for women have resulted in decreased rates of sequelae, morbidities associated with oviduct scarring continue to occur. Since corticosteroids have anti-inflammatory and antifibrotic effects, we tested the ability of dexamethasone to inhibit inflammation and prevent oviduct scarring in mice genitally infected with Chlamydia muridarum. The administration of 1 or 2.5 mg/kg of body weight of dexamethasone on days 7 to 21 of infection resulted in reduced accumulation of inflammatory cells in the oviducts compared to that in controls. However, a concomitant increase in bacterial burden was observed, and chronic oviduct disease was not reduced. Adjunctive administration of a prolonged (21-day) or short (3-day) course of dexamethasone in combination with the antibiotic doxycycline also failed to reduce chronic oviduct pathology compared to antibiotic treatment alone. Steroids administered alone or adjunctively with antibiotics failed to prevent oviduct damage in this murine model of C. trachomatis infection.     

Cholinergic receptor gene (CHRM2) variation and familial loading for alcohol dependence predict childhood developmental trajectories of P300

P300 amplitude in childhood predicts substance use disorders by young adulthood. Trajectories of visual P300 amplitude show an association between low amplitude P300 and familial risk for alcohol dependence (AD). Variation in the cholinergic muscarinic receptor gene (CHRM2) has previously been associated with P300 amplitude and AD. The present study used group based trajectory modeling of auditory P300 data collected longitudinally from offspring in families with and without familial loading for AD to determine if specific trajectories would be associated with familial risk and CHRM2 variation. Trajectory modeling confirms previous reports of an association between the low visual P300 trajectory with high familial risk in male offspring. This association was detected in offspring in the 8–12 age range, but not in 13–18 or 19–29 year olds or in high-risk female offspring. CHRM2 association analysis with P300 finds 8–12 year olds who are homozygous for the T allele of rs1824024 are 2.6 times more likely to follow a P300 trajectory characterized by lower and slower change regardless of familial loading. Combining the odds for being male and having a TT genotype results in odds of 6.5 that individuals will follow the low P300 trajectory.     

Development and characterization of 22 microsatellite loci for the ringed salamander (Ambystoma annulatum) using paired-end Illumina shotgun sequencing

We isolated and screened 150 microsatellite loci from the ringed salamander, Ambystoma annulatum, an ambystomatid salamander endemic to the Interior Highlands. Twenty-two polymorphic loci were identified and pooled into two multiplex reactions. These loci will be valuable tools for assessing population genetic structure and connectivity across the landscape, and informing management of this species.     

Furlong Hydroxyapatite-Coated Hip Prosthesis vs the Charnley Cemented Hip Prosthesis

We report the results of a prospective trial comparing uncemented Furlong hydroxyapatite-coated total hip arthroplasty and cemented Charnley total hip arthroplasty. One hundred ninety-one patients were allocated into 2 groups depending on their year of birth. One group received a Furlong hydroxyapatite-coated total hip arthroplasty and the other group received a cemented Charnley total hip arthroplasty. At a mean follow-up of 14 years (12-16 years), Harris hip scores showed no difference between the 2 groups. The longitudinal multilevel model analysis shows that the mean slope of the change in the Harris hip score was −0.02 for the Furlong group and −0.05 for the Charnley group; the difference is 0.03 (P = .002). The survival analysis using Kaplan-Meier regression analysis (the log-rank test λ²₁ = 0.031, P = .58) does not show a significant difference between the 2 groups. Overall survival was 93.6% in the Furlong group and 94.8% in the Charnley group.     

Cannabinoids and Bone: Friend or Foe?

The endocannabinoid system is recognized to play an important role in regulating a variety of physiological processes, including appetite control and energy balance, pain perception, and immune responses. The endocannabinoid system has also recently been implicated in the regulation of bone metabolism. Endogenously produced cannabinoids are hydrophobic molecules derived from hydrolysis of membrane phospholipids. These substances, along with plant-derived and synthetic cannabinoids, interact with the type 1 (CB₁) and 2 (CB₂) cannabinoid receptors and the GPR55 receptor to regulate cellular function through a variety of signaling pathways. Endocannabinoids are produced in bone, but the mechanisms that regulate their production are unclear. Skeletal phenotyping of mice with targeted inactivation of cannabinoid receptors and pharmacological studies have shown that cannabinoids play a key role in the regulation of bone metabolism. Mice with CB₁ deficiency have high peak bone mass as a result of an osteoclast defect but develop age-related osteoporosis as a result of impaired bone formation and accumulation of bone marrow fat. Mice with CB₂ deficiency have relatively normal peak bone mass but develop age-related osteoporosis as a result of increased bone turnover with uncoupling of bone resorption from bone formation. Mice with GPR55 deficiency have increased bone mass as a result of a defect in the resorptive activity of osteoclasts, but bone formation is unaffected. Cannabinoids are also produced within synovial tissues, and preclinical studies have shown that cannabinoid receptor ligands are effective in the treatment of inflammatory arthritis. These data indicate that cannabinoid receptors and the enzymes responsible for ligand synthesis and breakdown play important roles in bone remodeling and in the pathogenesis of joint disease.     

Adverse clinical phenotype in inflammatory bowel disease: A cross sectional study identifying factors potentially amenable to change

Background and Aim: A significant proportion with inflammatory bowel disease (IBD) exhibit an adverse clinical phenotype reflected in endpoints like surgery and hospitalizations. We sought to identify clinico‐demographic factors associated with these adverse consequences that may be amenable to change. Methods: Over 6 months IBD patients visiting a metropolitan center were prospectively identified and given a comprehensive survey addressing patient knowledge, mental health and satisfaction with medical care along with other clinical data. Logistic regression analyses assessed for associations between clinico‐demographic variables and adverse clinical endpoints (previous surgery [ever] and/or recent inpatient admission over a 16 month observation period). Results: Of 256 IBD patients, 162 responded (response rate 63%); 95 (59%) had Crohn's disease (CD), 63 (40%) ulcerative colitis (UC), four indeterminate colitis; 53% were female. Factors associated with a greater likelihood of hospitalization included moderate/severe disease activity, psychological co‐morbidity, numbers of medications and outpatient visits (odds ratio [OR] 7.09 [2.83–17.76], 4.13 [1.25–13.61], 1.26 [1.03–1.54], 1.17 [1.00–1.37] respectively; all P < 0.05). Post‐surgical patients were more likely to have CD, more currently active disease and longer disease duration (OR 8.55 [2.43–29.4], 3.52 [1.26, 9.87], 1.14 [1.08, 1.21] respectively; all P < 0.02), yet were less likely to have previously seen a gastroenterologist, OR 0.25 [0.08–0.76] (P = 0.01). Conclusions: ‘At risk’ patients (those previously operated, with ongoing disease activity, dissatisfaction and/or psychological comorbidities) may benefit from early identification and more intensive management. Specialist gastroenterology care appears to be under‐utilized in operated patients yet may reduce future IBD morbidity.