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Objective: We determined secular changes in the incidence of hospitalizations due to herpes zoster (HZh) and assessed the validity of HZ International Classification of Diseases (ICD) code algorithms for identifying HZh in a region of Quebec, Canada., Methods: We performed a validation study as part of a retrospective cohort study of adult HZ patients hospitalized at Centre Hospitalier Universitaire de Sherbrooke during 2000-2017. Cases were identified using ICD codes from an inpatient administrative database. HZ cases identified by ICD-9 (053.xx) and ICD-10 (B02.x) codes were chart-confirmed, and performance characteristics of ICD code algorithms were calculated (positive predictive value [PPV] and sensitivity)., Results: Overall, 1314 hospitalizations with HZ diagnosis (HZh) with or without complications were identified during 2000-2017. Among the hospitalizations, 526 (44.4%) were due to active HZ disease or a complication related to a recent or previous HZ episode. These hospitalizations were due to active disease at the time of admission (340/526, 64.6%), HZ that developed during hospitalization (120/526, 22.8%), or a complication directly related to a recent or previous HZ episode (66/526, 12.6%). PPV was significantly higher when HZ was the primary diagnosis (276/310, 89%, 95% confidence interval [CI]: 85-92%) than when HZ was a secondary diagnosis (254/928, 27%, 95% CI: 25-30%) (p < 0.0001), and the PPV of a first secondary diagnosis (84/140, 60.0%, 95% CI: 51.3-68.2%) was higher than that of other secondary diagnoses (203/794, 25.6%, 95% CI: 22.6-28.8%) (p < 0.0001). An algorithm combining ICD codes and antiviral usage demonstrated the best sensitivity (86.3%, 95% CI: 83.1-89.1%) and PPV to identify HZh (100%, 95% CI: 99.2-100%). Poisson regression revealed no significant changes in HZh over time (incidence rate ratio: 0.98, 95% CI: 0.92-1.04%; p = 0.5)., Conclusion: HZh incidence was stable over time. Prescription of antivirals might be a useful addition to ICD codes to identify HZh cases from administrative databases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

This study aimed at better understanding the neurochemistry underlying transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS) measurements as it pertains to GABAergic activity following administration of allosteric GABA A receptor agonist lorazepam. Seventeen healthy adults (8 females, 26.0 ± 5.4 years old) participated in a double-blind, crossover, placebo-controlled study, where participants underwent TMS and MRS two hours after drug intake (placebo or lorazepam; 2.5 mg). Neuronavigated TMS measures reflecting cortical inhibition and excitation were obtained in the left primary motor cortex. Sensorimotor cortex and occipital cortex MRS data were acquired using a 3T scanner with a MEGA-PRESS sequence, allowing water-referenced [GABA] and [Glx] (glutamate + glutamine) quantification. Lorazepam administration decreased occipital [GABA], decreased motor cortex excitability and increased GABA A -receptor mediated motor cortex inhibition (short intracortical inhibition (SICI)). Lorazepam intake did not modulate sensorimotor [GABA] and TMS measures of intra-cortical facilitation, long-interval cortical inhibition, cortical silent period, and resting motor threshold. Furthermore, higher sensorimotor [GABA] was associated with higher cortical inhibition (SICI) following lorazepam administration, suggesting that baseline sensorimotor [GABA] may be valuable in predicting pharmacological or neuromodulatory treatment response. Finally, the differential effects of lorazepam on MRS and TMS measures, with respect to GABA, support the idea that TMS measures of cortical inhibition reflect synaptic GABAergic phasic inhibitory activity while MRS reflects extrasynaptic GABA., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Production of chemicals in microorganisms is no longer restricted to products arising from native metabolic potential. In this review, we highlight the evolution of metabolic engineering studies, from the production of natural chemicals fermented from biomass hydrolysates, to the engineering of microorganisms for the production of non-natural chemicals. Advances in synthetic biology are accelerating the successful development of microbial cell factories to directly produce value-added chemicals. Here we outline the emergence of novel computational tools for the creation of synthetic pathways, for designing artificial enzymes for non-natural reactions and for re-wiring host metabolism to increase the metabolic flux to products. We also highlight exciting opportunities for applying directed evolution of enzymes, dynamic control of growth and production, growth-coupling strategies as well as decoupled strategies based on orthogonal pathways in the context of non-natural chemicals., (Copyright © 2019 Elsevier Inc. All rights reserved.)