Child Neurology: Hemiconvulsion-Hemiplegia-Epilepsy Syndrome in the Setting of COVID-19 Infection and Multisystem Inflammatory Syndrome.

Hemiconvulsion-Hemiplegia-Epilepsy (HHE) syndrome is a rare pediatric epilepsy syndrome characterized by prolonged focal febrile convulsive status epilepticus with unilateral hemispheric cerebral edema and followed by the subsequent development of hemiplegia, global atrophy of the affected hemisphere, and epilepsy. The pathophysiology of HHE syndrome remains poorly understood though is clearly multifactorial. Factors thus far implicated are hyperthermia, pro-inflammatory state, and cytotoxic edema from prolonged ictal activity. Prognosis is variable, from the resolution of hemiplegia and seizures to permanent hemiparesis and refractory epilepsy. We describe a 2-year-old boy who presented with super-refractory focal status epilepticus in the setting of acute Coronavirus Infectious Disease-2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C). He had right-sided hemiplegia on neurological examination, and an MRI of the brain showed left cerebral hemispheric edema consistent with HHE syndrome. Our case represents the first report in the literature on HHE syndrome in the setting of acute COVID-19 and MIS-C.

Post-traumatic Headache in Children and Adolescents.

PURPOSE OF REVIEW: Post-traumatic headache is a common disorder in the pediatric age group, seen both by child neurologists and by non-neurologists. The current review of post-traumatic headache in children and adolescents aims to review the pathophysiology, risk factors, clinical features, neuroimaging, and both acute and preventive treatment options. RECENT FINDINGS: Recent literature provides insight into specific risk factors in the pediatric age group for developing post-traumatic headache as well as unique pathophysiologic changes seen in neuroimaging and neurometabolic pathways. It also elucidates common treatment options and novel treatments being currently explored, such as with monoclonal antibodies to CGRP. Finally, current evidence and guidelines recommend the benefit of a gradual return to normal activity based on symptom stability rather than a specific time period. Review of literature on pediatric post-traumatic headache reveals a growing understanding of the factors involved in developing headache after head trauma and the diagnosis/treatment of headache though future research will help further elucidate these areas.

Robust composite-shell microcapsules via pickering emulsification.

Microencapsulation technology has been increasingly applied toward the development of self-healing paints. Added to paint as a dry powder prior to spraying, the microcapsules store a liquid that can repair the protective barrier layer if released into a scratch. However, self-healing will not occur unless the microcapsules can withstand spray-painting, aggressive solvents in the paint, and long-term exposure to the elements. We have therefore developed a one-pot synthesis for the production of Pickering microcapsules with outstanding strength, solvent resistance, and barrier properties. Octadecyltrimethoxysilane-filled (OTS) microcapsules form via standard interfacial polycondensation, except that silica nanopowder (10-20 nm diameter) replaces the conventional surfactant or hydrocolloid emulsifier. Isophorone diisocyanate (IPDI) in the OTS core reacts with diethylenetriamine, polyethylenimine, and water to form a hard polymer shell along the interface. Compared to pure polyurea, the silica-polyurea composite improves the shelf life of the OTS by 10 times. The addition of SiO2 prevents leaching of OTS into xylenes and hexanes for up to 80 days, and the resulting microcapsules survive nebulization through a spray gun at 620 kPa in a 500 cSt fluid.

Synthesis of mercapto-(+)-methamphetamine haptens and their use for obtaining improved epitope density on (+)-methamphetamine conjugate vaccines.

This study reports the synthesis of the mercapto-hapten (S)-N-(2-(mercaptoethyl)-6-(3-(2-(methylamino)propyl)phenoxy)hexanamide [3, (+)-METH HSMO9] and its use to prepare METH-conjugated vaccines (MCV) from maleimide-activated proteins. MALDI-TOF mass spectrometry analysis of the MCV synthesized using 3 showed there was a high and controllable epitope density on two different carrier proteins. In addition, the MCV produced a substantially greater immunological response in mice than previous METH haptens, and a monoclonal antibody generated from this MCV in mice showed a very high affinity for (+)-METH (K(D) = 6.8 nM). The efficient covalent coupling of (+)-METH HSMO9 to the activated carrier proteins suggests that this approach could be cost-effective for large-scale production of MCV. In addition, the general methods described for the synthesis of (+)-METH HSMO9 (3) and its use to synthesize MCV will be applicable for conjugated vaccines of small molecules and other substances of abuse such as morphine, nicotine, and cocaine.

The synthesis of haptens and their use for the development of monoclonal antibodies for treating methamphetamine abuse.

In addition to addiction, the repeated use of (+)-methamphetamine [(+)-METH], (+)-amphetamine [(+)-AMP], or (+/-)-3,4-methylenedioxymethamphetamine ((+/-)-MDMA, commonly called ecstasy) can lead to life-threatening medical problems including cardiovascular injury, severe depression, and psychosis. Currently, there are no specific pharmacotherapies to treat these medical problems. In this study, we report the design and synthesis of two haptens, (S)-(+)-3-(9-carboxynonyloxy)methamphetamine (3a, (+)-METH MO10) and (S)-(+)-3-(5-carboxypentyloxy)methamphetamine (3b, (+)-METH MO6), and their use in generating high affinity (low K(D) value) monoclonal antibodies (mAbs) against (+)-METH, (+)-AMP, and/or (+)-MDMA. On the basis of results from the determination of mAb K(D) values and ligand specificity, the mAbs generated from hapten 3a showed the greatest promise for generating active and passive immunotherapies for treating overdose or addiction from (+)-METH-like stimulants.

Synthesis, monoamine transporter binding, properties, and functional monoamine uptake activity of 3beta-[4-methylphenyl and 4-chlorophenyl]-2 beta-[5-(substituted phenyl)thiazol-2-yl]tropanes.

Synthetic methods were developed for the synthesis of the 3beta-(4-substituted phenyl)-2 beta-[5-(substituted phenyl)thiazol-2-yl]tropanes (4a-s). The compounds were evaluated for their monoamine transporter binding and monoamine uptake inhibition properties using both rat brain tissue and cloned transporter assays. In general, the compounds showed higher dopamine transporter (DAT) affinity relative to the serotonin and norepinephrine transporters (SERT and NET, respectively) and greater [3H]dopamine uptake inhibition potency relative to [3H]serotonin and [3H]norepinephrine uptake inhibition. Several compounds were DAT selective relative to the SERT and NET in the monoamine transporter binding assays. The most potent and selective analog in the functional monoamine uptake inhibition test was 3beta-(4-methylphenyl-2 beta-[5-(3-nitrophenyl)thiazol-2-yl]tropane (4p).

Stereochemical study of phosphonothioate cleavage by a metallomicelle.

[reaction: see text] The copper metallomicellar hydrolysis of O-methyl O-4-nitrophenyl phenylphosphonothioate to O-methyl phenylphosphonothioic acid takes place with effectively complete inversion at phosphorus.