Quadriceps weakness may be present in patients who have osteoarthritis but do not have knee pain or muscle atrophy; this suggests that the weakness may be due to muscle dysfunction. The data are consistent with the possibility that quadriceps weakness is a primary risk factor for knee pain, disability, and progression of joint damage in persons with osteoarthritis of the knee.

No abstract

In short-term, symptomatic treatment of osteoarthritis of the knee, the efficacy of acetaminophen was similar to that of ibuprofen, whether the latter was administered in an analgesic or an antiinflammatory dose.

BackgroundThe natural history of mild traumatic brain injury (TBI) or concussion remains poorly defined and no objective biomarker of physiological recovery exists for clinical use. The National Collegiate Athletic Association (NCAA) and the US Department of Defense (DoD) established the Concussion Assessment, Research and Education (CARE) Consortium to study the natural history of clinical and neurobiological recovery after concussion in the service of improved injury prevention, safety and medical care for student-athletes and military personnel.ObjectivesThe objectives of this paper were to (i) describe the background and driving rationale for the CARE Consortium; (ii) outline the infrastructure of the Consortium policies, procedures, and governance; (iii) describe the longitudinal 6-month clinical and neurobiological study methodology; and (iv) characterize special considerations in the design and implementation of a multicenter trial.MethodsBeginning Fall 2014, CARE Consortium institutions have recruited and enrolled 23,533 student-athletes and military service academy students (approximately 90% of eligible student-athletes and cadets; 64.6% male, 35.4% female). A total of 1174 concussions have been diagnosed in participating subjects, with both concussion and baseline cases deposited in the Federal Interagency Traumatic Brain Injury Research (FITBIR) database.ConclusionsChallenges have included coordinating regulatory issues across civilian and military institutions, operationalizing study procedures, neuroimaging protocol harmonization across sites and platforms, construction and maintenance of a relational database, and data quality and integrity monitoring. The NCAA–DoD CARE Consortium represents a comprehensive investigation of concussion in student-athletes and military service academy students. The richly characterized study sample and multidimensional approach provide an opportunity to advance the field of concussion science, not only among student athletes but in all populations at risk for mild TBI.

Objective. To confirm preclinical data suggesting that doxycycline can slow the progression of osteoarthritis (OA). The primary outcome measure was joint space narrowing (JSN) in the medial tibiofemoral compartment.Methods. In this placebo-controlled trial, obese women (n ‫؍‬ 431) ages 45-64 years with unilateral radiographic knee OA were randomly assigned to receive 30 months of treatment with 100 mg doxycycline or placebo twice a day. Tibiofemoral JSN was measured manually in fluoroscopically standardized radiographic examinations performed at baseline, 16 months, and 30 months. Severity of joint pain was recorded at 6-month intervals.Results. Seventy-one percent of all randomized subjects completed the trial. Radiographs were obtained from 85% of all randomized subjects at 30 months. Adherence to the dosing regimen was 91.8% among subjects who completed the study per protocol. After 16 months of treatment, the mean ؎ SD loss of joint space width in the index knee in the doxycycline group was 40% less than that in the placebo group (0.15 ؎ 0.42 mm versus 0.24 ؎ 0.54 mm); after 30 months, it was 33% less (0.30 ؎ 0.60 mm versus 0.45 ؎ 0.70 mm). Doxycycline did not reduce the mean severity of joint pain, although pain scores in both treatment groups were low at baseline and remained low throughout the trial, suggesting the presence of a floor effect. However, the frequency of followup visits at which the subject reported a >20% increase in pain in the index knee, relative to the previous visit, was reduced among those receiving doxycycline. In contrast, doxycycline did not have an effect on either JSN or pain in the contralateral knee. In both treatment groups, subjects who reported a >20% increase in knee pain at the majority of their followup visits had more rapid JSN than those whose pain did not increase.Conclusion. Doxycycline slowed the rate of JSN in knees with established OA. Its lack of effect on JSN in the contralateral knee suggests that pathogenetic mechanisms in that joint were different from those in the index knee.In the present report, we describe the results of a randomized, placebo-controlled, double-blind trial of the tetracycline antibiotic, doxycycline, in subjects with knee osteoarthritis (OA). Selection of doxycycline as a potential disease-modifying OA drug was based not on the premise that OA is an infectious disease, but rather on results of in vitro studies showing 1) that doxycycline inhibited the degradation of type XI collagen, one of the minor collagens of articular cartilage, by 72-kd gelati-

Background Repeated C. trachomatis infections are common among young sexually active women. The relative frequency of re-infection and antibiotic treatment failure is undefined. Methods Adolescent women enrolled in a longitudinal cohort had behavioral and sexually transmitted infection assessment every 3 months, including amplification tests for C. trachomatis, ompA genotyping and interviews and diary entries to document partner-specific coitus and event-specific condom use. Repeated infections were classified as re-infection or treatment failure using an algorithm. All infections with treatment outcomes were used to estimate antibiotic use-effectiveness. Results We observed 478 infection episodes among 210 participants; 176 women remained uninfected. Incidence rate was 34 per 100-woman years. Of those infected, 121 had ≥1 repeat infections forming 268 episode pairs; 183 pairs had complete data and were classified with the algorithm. Of repeated infections, 84.2% were definite, probable or possible re-infections, 13.7% were probable or possible treatment failures and 2.2% persisted without documented treatment. For 318 evaluable infections, we estimated a 92.2% treatment use-effectiveness. Conclusions Most repeat chlamydial infections in this high incidence cohort were re-infections, but treatment failures occurred as well. Our results have implications for male screening and partner notification programs and suggest the need for improved antibiotic therapies.

We have developed a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome (H-ARS) for efficacy testing of medical countermeasures (MCM) against radiation according to the FDA Animal Rule. Ten to 12 week old male and female C57BL/6 mice were exposed to the LD50/30-LD70/30 dose of total body irradiation (TBI, 137Cs, 0.62-0.67 Gy min-1) in the morning hours when mice were determined to be most radiosensitive, and assessed for 30 day survival and mean survival time (MST). Antibiotics were delivered in the drinking water on days 4-30 post-TBI at a concentration based on the amount of water that lethally-irradiated mice were found to consume. The fluoroquinolones, ciprofloxacin and levofloxacin, and the tetracycline doxycycline and aminoglycoside neomycin, all significantly increased MST of decedent mice, while ciprofloxacin (p=0.061) and doxycycline + neomycin (p=0.005) showed at least some efficacy to increase 30 day survival. Blood sampling (30uL/mouse every 5th day) was found to negatively impact 30 day survival. Histopathology of tissues harvested from non-moribund mice showed expected effects of lethal irradiation, while moribund mice were largely septicemic with a preponderance of enteric organisms. Kinetics of loss and recovery of peripheral blood cells in untreated mice and those treated with two MCM, granulocyte-colony stimulating factor and Amifostine, further characterized and validated our model for use in screening studies and pivotal efficacy studies of candidate MCM for licensure to treat irradiated individuals suffering from H-ARS.

Lactobacillus-dominated vaginal microbiotas are associated with reproductive health and STI resistance in women, whereas altered microbiotas are associated with bacterial vaginosis (BV), STI risk and poor reproductive outcomes. Putative vaginal taxa have been observed in male first-catch urine, urethral swab and coronal sulcus (CS) specimens but the significance of these observations is unclear. We used 16 S rRNA sequencing to characterize the microbiota of the CS and urine collected from 18 adolescent men over three consecutive months. CS microbiotas of most participants were more stable than their urine microbiotas and the composition of CS microbiotas were strongly influenced by circumcision. BV-associated taxa, including Atopobium, Megasphaera, Mobiluncus, Prevotella and Gemella, were detected in CS specimens from sexually experienced and inexperienced participants. In contrast, urine primarily contained taxa that were not abundant in CS specimens. Lactobacilllus and Streptococcus were major urine taxa but their abundance was inversely correlated. In contrast, Sneathia, Mycoplasma and Ureaplasma were only found in urine from sexually active participants. Thus, the CS and urine support stable and distinct bacterial communities. Finally, our results suggest that the penis and the urethra can be colonized by a variety of BV-associated taxa and that some of these colonizations result from partnered sexual activity.