Comparison of Meat Composition from Offspring of Cloned and Conventionally Produced Boars

This study compares the meat composition of the offspring from boars produced by somatic cell nuclear transfer (n = 4) to that of the offspring from conventionally produced boars (n = 3). In total, 89 commercial gilts were artificially inseminated and 61 progressed to term and farrowed. All of the resulting piglets were housed and raised identically under standard commercial settings and slaughtered upon reaching market weight. Loin samples were taken from each slaughtered animal and shipped offsite for meat composition analysis. In total, loin samples from 404 animals (242 from offspring of clones and 162 from controls) were analyzed for 58 different parameters generating 14,036 and 9396 data points from offspring of clones and the controls, respectively. Values for controls were used to establish a range for each parameter. Ten percent was then added to the maximum and subtracted from the minimum of the control range, and all results within this range were considered clinically irrelevant. Of the 14,036 data points from the offspring of clones, only three points were found outside the clinically irrelevant range, two of which were within the range established by the USDA National Nutrient Database for Standard Reference, Release 18, 2005. The only outlier was the presence of Eicosadienoic acid (C20:2) in one sample which is typically present in minute quantities in pork; no reference data were found regarding this fatty acid in the USDA National Nutrient Database. In conclusion, these data indicated that meat from the offspring of clones was not chemically different than meat from controls and therefore supported the case for the safety of meat from the offspring of clones

Comparison of Meat Composition from Offspring of Cloned and Conventionally Produced Boars

This study compares the meat composition of the offspring from boars produced by somatic cell nuclear transfer (n = 4) to that of the offspring from conventionally produced boars (n = 3). In total, 89 commercial gilts were artificially inseminated and 61 progressed to term and farrowed. All of the resulting piglets were housed and raised identically under standard commercial settings and slaughtered upon reaching market weight. Loin samples were taken from each slaughtered animal and shipped offsite for meat composition analysis. In total, loin samples from 404 animals (242 from offspring of clones and 162 from controls) were analyzed for 58 different parameters generating 14,036 and 9396 data points from offspring of clones and the controls, respectively. Values for controls were used to establish a range for each parameter. Ten percent was then added to the maximum and subtracted from the minimum of the control range, and all results within this range were considered clinically irrelevant. Of the 14,036 data points from the offspring of clones, only three points were found outside the clinically irrelevant range, two of which were within the range established by the USDA National Nutrient Database for Standard Reference, Release 18, 2005. The only outlier was the presence of Eicosadienoic acid (C20:2) in one sample which is typically present in minute quantities in pork; no reference data were found regarding this fatty acid in the USDA National Nutrient Database. In conclusion, these data indicated that meat from the offspring of clones was not chemically different than meat from controls and therefore supported the case for the safety of meat from the offspring of clones

Challenges in conducting trials for pediatric tuberculous meningitis: lessons from the field

SETTING: TBM-KIDS is a phase I/II trial enrolling children with tuberculous meningitis (TBM) in three tertiary referral centers in India and Malawi. OBJECTIVE: To describe the challenges encountered in conducting the first randomized clinical trial of antimicrobial agents in pediatric TBM. DESIGN: The sources of the data were primarily monthly trial reports, non-enrollment case report forms, study diaries and registers maintained for recruitment, experiences shared by key team members during regular study calls and comments from site review visits. We reviewed, broadly categorized, and describe in detail the challenges encountered by study teams in trial implementation. RESULTS: Over 17 months, 3371 children with clinical presentations consistent with meningoencephalitis or undergoing lumbar puncture were assessed for eligibility; 21 (<1%) met enrollment criteria. We encountered challenges related to diagnosis, management of sick children, large catchment areas, adverse event attribution, concomitant medications, infrastructure requirements, expensive pediatric formulations with short expiry, and detection of treatment response in a highly variable disease across the age continuum. Training and adaptation of tools for neurocognitive and neurologic function assessment were necessary. Special care was undertaken to explain study participation to distraught caregivers and manage children longitudinally. CONCLUSION: Interventional trials in pediatric TBM are challenging but are critically important for improving the treatment of a disease that disables children physically, cognitively and emotionally. Sharing these challenges may help to address them more effectively as a TB research community and to advance treatments for this at-risk population

Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Neurocognitive and functional impairment in adult and paediatric tuberculous meningitis [version 1; peer review: 2 approved]

In those who survive tuberculous meningitis (TBM), the long-term outcome is uncertain; individuals may suffer neurocognitive, functional and psychiatric impairment, which may significantly affect their ability to lead their lives as they did prior to their diagnosis of TBM. In children who survive, severe illness has occurred at a crucial timepoint in their development, which can lead to behavioural and cognitive delay. The extent and nature of this impairment is poorly understood, particularly in adults. This is in part due to a lack of observational studies in this area but also inconsistent inclusion of outcome measures which can quantify these deficits in clinical studies. This leads to a paucity of appropriate rehabilitative therapies available for these individuals and their caregivers, as well as burden at a socioeconomic level. In this review, we discuss what is known about neurocognitive impairment in TBM, draw on lessons learnt from other neurological infections and discuss currently available and emerging tools to evaluate function and cognition and their value in TBM. We make recommendations on which measures should be used at what timepoints to assess for impairment, with a view to optimising and standardising assessment of neurocognitive and functional impairment in TBM research