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Abstract Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed neurobehavioural disorder in childhood, affecting over 5% of children worldwide. As well as the core symptoms of inattention, hyperactivity and impulsivity, patients often exhibit learning difficulties and impairment in social functioning. The frequency of referral is higher for boys than for girls (about 2:1), and girls are generally older at the time of referral. Pharmacological therapy is considered the first-line treatment for patients with severe ADHD and severe impairment. Stimulant medications are licensed in the UK for the management of ADHD in school-age children and young people, and are effective in controlling ADHD symptoms. While immediate-release preparations of methylphenidate (MPH) have proven effective in the treatment of ADHD, there are a number of problems associated with their use, most notably compliance, stigma and medication diversion. Modified release preparations are now available that overcome the need for multiple daily dosing, and which offer different MPH release profiles, thereby enabling the physician to match the medication to the patient's particular requirements. This review describes the diagnosis, referral and treatment pathways for patients with ADHD in the UK and the practical considerations when initiating pharmacological treatment. The clinical experience of treating ADHD with a modified-release MPH preparation (Equasym XL®) is illustrated with case studies.

Downstream processing is a significant part of a production process and accounts for 50-90% of the production cost of biotechnological products. Post-fermentation localization of a microbial metabolite contributes significantly to the recovery cost of the product. Enterobacter cloacae produced naturally, acidic lipase with a 0.023:1 extracellular localization ratio. This research aimed to re-direct the localization of lipase to the extracellular milieu to reduce recovery costs using multi-objective response surface optimization (MO-RSM). The approach resulted in a 1:0.32 extracellular: intracellular lipase ratio, with product formation kinetics of Luedeking-Piret function showing a significant switch from a completely growth-associated intracellular production to a predominantly non-growth-associated extracellular localization. The enzyme was purified by an aqueous two-phase system which extracted 95.22% lipase with 72.36 purity. Characterization of the enzyme showed a molecular weight of 55.7 kDa, kcat of 68.59 s -1 , and a K m of 0.63 mmol. Lipase activity occurred optimally at pH 2.5-3.5 and 50 °C, and was stable in most organic solvents tested. The acidic lipase demonstrated pH-dependent enantioselective esterification in resolving (R, S)-ibuprofen ( E  = 14, pH 4.5) and (R, S)-Naproxen ( E  = 13, pH 2.5), with an enantioselective preference for (S)-enantiomer in both drugs thus underpinning its potential for pharmaceutical applications.

As physiological impairments that require replacement therapy continue to increase, so also does the need for improved production of acidic lipase from new microbial sources. Enterobacter cloacae strain UCCM 00116 produced a novel acidic lipase in kernel oil-processing waste-basal broth with 0.023:1 extracellular: intracellular localization ratio. This research re-directed enzyme localization to the extracellular milieu to reduce recovery cost using multi-objective response surface optimization of medium parameters. Results revealed a 1:0.32 extracellular:intracellular lipase ratio. Product formation kinetics, modeled by the Luedeking-Piret function, showed a significant switch from a completely growth-associated intracellular production to a predominantly non-growth-associated extracellular localization through medium optimization. Aqueous two-phase system purification conditions extracted 95.22% lipase with 72.36 purity, a V max of 370.37 µmolmin -1 , and a K m of 0.63 mmol. Enzyme activity was enhanced by K + and Ca 2+ ions, stable in many organic solvents, except acetone, and had pH and temperature optima at 2.5-3.5 and 50 °C, respectively., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Bacterial alkaline peptidases, especially from Bacillus species, occupy the frontline in global enzyme market, albeit with poor production economics. Here, we report the deployment of response surface methodology approximations to optimize fermentation parameters for enhanced yield of alkaline peptidase by the non-Bacillus bacterium; Stenotrophomonas acidaminiphila. Shake flask production under optimized conditions was scaled up in a 5-L bench-scale bioreactor. Logistic and modified Gompertz models revealed significant fits for biomass formation, total protein, and substrate consumption models. Maximum specific growth rate (µ max  = 0.362 h -1 ) of the bacterium in the optimized medium did not differ significantly from those in Luria-Bertani and trypticase soy broths. The aqueous two-phase system-purified 45.7 kDa alkaline protease retained 83% activity which improved with increasing sodium dodecyl sulfate concentration thus highlighting potential laundry application. Maximum enzyme activity occurred at 75ºC and pH 10.5 but was inhibited by 5 mM phenyl-methyl-sulfonyl fluoride suggesting a serine-protease nature., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A strain of Stenotrophomonas acidaminiphila , isolated from fermenting bean-processing wastewater, produced alkaline protease in pretreated cassava waste-stream, but with low yield. Strain improvement by alternate combinatorial random mutagenesis and bioprocess optimization using comparative statistical and neural network methods enhanced yield by 17.8-fold in mutant kGy-04-UV-25. Kinetics of production by selected mutant modeled by logistic and modified Gompertz functions revealed higher specific growth rate in mutant than in the parent strain, likewise volumetric and specific productivities. Purification by PEG/Na + citrate aqueous two-phase system recovered 73.87% yield and 52.55-fold of protease. Its activity was stable at 5-35% NaCl, 45-75°C, and was significantly enhanced by 1-15 mM sodium dodecyl sulfate (SDS). The protease was inhibited by low concentrations of phenyl-methyl-sulfonyl fluoride but was activated by 1-5 mM Mn 2+ suggesting a manganese-dependent serine‑protease. The 45.7 kDa thermo-halo-stable alkaline protease demonstrated keratinolytic and blood-stain removal potentials showing prospects in textile and detergent industries, respectively., Competing Interests: 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. 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., (© 2022 The Authors. Published by Elsevier B.V.)

Background: The association of attention deficit/hyperactivity disorder (ADHD) and fetal alcohol spectrum disorders (FASD) results in a complex constellation of symptoms that complicates the successful diagnosis and treatment of the affected individual. Current literature lacks formal guidelines, randomized control trials, and evidence-based treatment plans for individuals with ADHD and associated FASD. Therefore, a meeting of professional experts was organized with the aim of producing a consensus on identification and treatment guidelines that will aid clinicians in caring for this unique patient population., Methods: Experts from multiple disciplines in the fields of ADHD and FASD convened in London, United Kingdom, for a meeting hosted by the United Kingdom ADHD Partnership (UKAP; www.UKADHD.com ) in June 2015. The meeting provided the opportunity to address the complexities of ADHD and FASD from different perspectives and included presentations, discussions, and group work. The attendees worked towards producing a consensus for a unified approach to ADHD and associated FASD., Results: The authors successfully came to consensus and produced recommended guidelines with specific regards to identification and assessment, interventions and treatments, and multiagency liaisons and care management, highlighting that a lifespan approach to treatment needs to be adopted by all involved. Included in the guidelines are: 1) unique 'red flags', which when identified in the ADHD population can lead to an accurate associated FASD diagnosis, 2) a treatment decision tree, and 3) recommendations for multiagency care management., Conclusions: While clinically useful guidelines were achieved, more research is still needed to contribute to the knowledge base about the diagnosis, treatment, and management of those with ADHD and associated FASD.