Dual enteric and respiratory tropisms of winter dysentery bovine coronavirus in calves

Summary Although winter dysentery (WD), which is caused by the bovine coronavirus (BCoV) is characterized by the sudden onset of diarrhea in many adult cattle in a herd, the pathogenesis of the WD-BCoV is not completely understood. In this study, colostrum-deprived calves were experimentally infected with a Korean WD-BCoV strain and examined for viremia, enteric and nasal virus shedding as well as for viral antigen expression and virus-associated lesions in the small and large intestines and the upper and lower respiratory tract from 1 to 8 days after an oral infection. The WD-BCoV-inoculated calves showed gradual villous atrophy in the small intestine and a gradual increase in the crypt depth of the large intestine. The WD-BCoV-infected animals showed epithelial damage in nasal turbinates, trachea and lungs, and interstitial pneumonia. The WD-BCoV antigen was detected in the epithelium of the small and large intestines, nasal turbinates, trachea and lungs. WD-BCoV RNA was detected in the serum from post-inoculation day 3. These results show that the WD-BCoV has dual tropism and induces pathological changes in both the digestive and respiratory tracts of calves. To our knowledge, this is the first detailed report of dual enteric and respiratory tropisms of WD-BCoV in calves. Comprehensive studies of the dual tissue pathogenesis of the BCoV might contribute to an increased understanding of similar pneumoenteric CoV infections in humans.     

3D-printed spine surgery implants: a systematic review of the efficacy and clinical safety profile of patient-specific and off-the-shelf devices

Three-dimensional printing (3DP), or additive manufacturing, is an emergent fabrication technology for surgical devices. As a production method, 3DP enables physical realisation of surgical implants from geometrically complex digital-models in computer-aided design. Spine surgery has been an innovative adopter of 3DP technology for both patient-specific (PS) and market-available ‘Off-The-Shelf’ (OTS) implants. The present study assessed clinical evidence for efficacy and safety of both PS and OTS 3DP spinal implants through review of the published literature. The aim was to evaluate the clinical utility of 3DP devices for spinal surgery. A systematic literature review of peer-reviewed papers featured on online medical databases evidencing the application of 3DP (PS and OTS) surgical spine implants was conducted in accordance with PRISMA guidelines. Twenty-two peer-reviewed articles and one book-chapter were eligible for systematic review. The published literature was limited to case reports and case series, with a predominant focus on PS designs fabricated from titanium alloys for surgical reconstruction in cases where neoplasia, infection, trauma or degenerative processes of the spine have precipitated significant anatomical complexity. PS and 3DP OTS surgical implants have demonstrated considerable utility for the surgical management of complex spine pathology. The reviewed literature indicated that 3DP spinal implants have also been used safely, with positive surgeon- and patient-reported outcomes. However, these conclusions are tentative as the follow-up periods are still relatively short and the number of high-powered studies was limited. Single case and small case series reporting would benefit greatly from more standardised reporting of clinical, radiographic and biomechanical outcomes. These slides can be retrieved under Electronic Supplementary Material.     

A comparison between orthogonal and parallel plating methods for distal humerus fractures: a prospective randomized trial

With the continuing improvements in implants for distal humerus fractures, it is expected that newer types of plates, which are anatomically precontoured, thinner and less irritating to soft tissue, would have comparable outcomes when used in a clinical study. The purpose of this study was to compare the clinical and radiographic outcomes in patients with distal humerus fractures who were treated with orthogonal and parallel plating methods using precontoured distal humerus plates. Sixty-seven patients with a mean age of 55.4 years (range 22–90 years) were included in this prospective study. The subjects were randomly assigned to receive 1 of 2 treatments: orthogonal or parallel plating. The following results were assessed: operating time, time to fracture union, presence of a step or gap at the articular margin, varus–valgus angulation, functional recovery, and complications. No intergroup differences were observed based on radiological and clinical results between the groups. In our practice, no significant differences were found between the orthogonal and parallel plating methods in terms of clinical outcomes, mean operation time, union time, or complication rates. There were no cases of fracture nonunion in either group; heterotrophic ossification was found 3 patients in orthogonal plating group and 2 patients in parallel plating group. In our practice, no significant differences were found between the orthogonal and parallel plating methods in terms of clinical outcomes or complication rates. However, orthogonal plating method may be preferred in cases of coronal shear fractures, where posterior to anterior fixation may provide additional stability to the intraarticular fractures. Additionally, parallel plating method may be the preferred technique used for fractures that occur at the most distal end of the humerus.     

Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis: a randomized,double-blind,placebo-controlled,dose-escalation trial

OBJECTIVE: To investigate the safety and efficacy of MRA, a recombinant human anti-interleukin-6 (anti-IL-6) receptor monoclonal antibody of the IgG1 subclass that inhibits the function of IL-6, in patients with established rheumatoid arthritis (RA). METHODS: A randomized, double-blind, placebo-controlled, dose-escalation trial was conducted in 45 patients with active RA, as defined by the American College of Rheumatology (ACR) revised criteria. Patients were sequentially allocated to receive a single intravenous dose of either 0.1, 1, 5, or 10 mg/kg of MRA or placebo. The primary efficacy end point was meeting the ACR 20% response criteria at week 2 after treatment. RESULTS: Demographic features were similar between treatment groups. At week 2, a significant treatment difference was observed between the 5 mg/kg of MRA and placebo, with 5 patients (55.6%) in the MRA cohort and none in the placebo cohort achieving ACR 20% improvement. There was no statistically significant difference in the ACR 20% response between the other 3 MRA cohorts and placebo at week 2. The mean disease activity score at week 2 in those who received 5 mg/kg and 10 mg/kg of MRA was 4.8 and 4.7 (P < 0.001 and P < 0.001 by analysis of variance), respectively. These mean scores were statistically significantly lower than those in the 0.1- and 1-mg/kg MRA and the placebo cohorts (6.4, 6.2, and 7.0, respectively). The erythrocyte sedimentation rate and C-reactive protein values fell significantly in the 5- and 10-mg/kg MRA cohorts and normalized 2 weeks after treatment. Seventeen patients (5, 4, 6, 2, and 0 patients in the placebo, 0.1-, 1-, 5-, and 10-mg/kg MRA cohorts, respectively) required corticosteroid or disease-modifying antirheumatic drug treatment because of active disease before study end. They were regarded as nonresponders from the time they received these treatments. Diarrhea was the most common adverse event, occurring in 8% of patients. Seven patients (15.6%) reported a severe adverse event (3, 1, 2, and 2 patients in the placebo, 0.1-, 1-, and 10-mg/kg MRA cohorts). There were no serious adverse events that were thought to be related to the study drug. CONCLUSION: This is the first randomized controlled trial showing that inhibition of IL-6 significantly improved the signs and symptoms of RA and normalized the acute-phase reactants. Further research with multiple dosing is necessary to define the most appropriate therapeutic regimen of MRA in RA.     

Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial

OBJECTIVE: Adalimumab, a fully human, anti-tumor necrosis factor monoclonal antibody, was evaluated for its safety and efficacy compared with placebo in the treatment of active psoriatic arthritis (PsA). METHODS: Patients with moderately to severely active PsA and a history of inadequate response to nonsteroidal antiinflammatory drugs were randomized to receive 40 mg adalimumab or placebo subcutaneously every other week for 24 weeks. Study visits were at baseline, weeks 2 and 4, and every 4 weeks thereafter. The primary efficacy end points were the American College of Rheumatology 20% improvement (ACR20) response at week 12 and the change in the modified total Sharp score of structural damage at week 24. Secondary end points were measures of joint disease, disability, and quality of life in all patients, as well as the severity of skin disease in those patients with psoriasis involving at least 3% of body surface area. RESULTS: At week 12, 58% of the adalimumab-treated patients (87 of 151) achieved an ACR20 response, compared with 14% of the placebo-treated patients (23 of 162) (P < 0.001). At week 24, similar ACR20 response rates were maintained and the mean change in the modified total Sharp score was -0.2 in patients receiving adalimumab and 1.0 in those receiving placebo (P < 0.001). Among the 69 adalimumab-treated patients evaluated with the Psoriasis Area and Severity Index (PASI), 59% achieved a 75% PASI improvement response at 24 weeks, compared with 1% of the 69 placebo-treated patients evaluated (P < 0.001). Disability and quality of life measures were also significantly improved with adalimumab treatment compared with placebo. Adalimumab was generally safe and well-tolerated. CONCLUSION: Adalimumab significantly improved joint and skin manifestations, inhibited structural changes on radiographs, lessened disability due to joint damage, and improved quality of life in patients with moderately to severely active PsA.     

A pilot study of urine cytokines in ketamine-associated lower urinary tract symptoms

Introduction and hypothesis

The aim of this study was to investigate urine cytokine and chemokine levels in symptomatic ketamine abusers compared with age-matched controls.

Methods

Midstream urine specimens were collected in a prospective study of 23 ketamine abusers and 27 controls who had never used ketamine. Their basic demographic and urinary symptoms were compared. The urine was analyzed by a multiplex panel screen for 19 cytokines/chemokines: EGF, GM-CSF, GRO, IL-1Ra, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p40, IL-12p70, IP-10, MCP-1, MIP-1b, sCD40L, sIL-2Ra, VEGF, MCP-4, and TARC using Luminex? xMAP® technology. Protein concentration values were normalized to urine creatinine concentrations.

Results

Mean age of the control group was 21.1?±?4.3 years (n?=?27) and of the ketamine group was 20.6?±?3.7 years (n?=?23). All participants were women. The urine cytokine analysis showed a significant elevation in EGF levels in the ketamine group with lower urinary tract symptoms (LUTS) compared with the control group (p?Conclusions Urinary EGF levels were increased among symptomatic ketamine abusers. This suggests inflammation and epithelial repair may play a role in ketamine-associated LUTS, and this may in turn help in understanding the pathophysiology of this disease entity, leading to better treatment options.     

Piloting a food photo sorting activity in Samoa to assess maternal beliefs and their role in child diet

Eating habits begin forming early in life when parental beliefs and behaviours often play a major role in shaping dietary intake. We aimed to assess maternal beliefs about the cost, social status, and nutritional value of foods in Samoa—a setting with an alarming burden of childhood obesity—and to determine how those beliefs may be related to child dietary intake. Samoan mothers (n = 44) sorted photographs of 26 foods commonly consumed in children in Samoa by cost, social status, and nutritional value (healthfulness). Responses were then assessed for their association with child dietary intake (reported using a food frequency questionnaire) using Pearson correlations. Mothers indicated that traditional Samoan foods were healthier, of higher social status, and lower cost compared with non‐traditional/imported food items. Compared with nutritional experts and a market survey of food prices, mothers demonstrated strong nutritional (r = .87, 95% CI [0.68, 0.95], p < .001) and consumer (r = .84, 95% CI [0.68, 0.93], p < .001) knowledge. The perceived cost of food was more strongly associated (r = ?.37, 95% CI [?0.66, 0.02], p = .06) with child dietary intake than either healthfulness or social status, with decreasing consumption reported with increasing food cost. Our findings contradicted the notion that the high social status of imported foods may be contributing to increased intake and rising prevalence of childhood obesity in this developing country setting. Despite their nutritional knowledge, Samoan mothers may need additional support in applying their knowledge/beliefs to provide a healthy child diet, including support for access to reasonably priced healthy foods.