Affinity-based covalent sialyltransferase probes enabled by ligand-directed chemistry.

Sialyltransferases (ST) are key enzymes found in, among others, mammals and bacteria that are responsible for producing sialylated glycans, which play critical roles in human health and disease. However, chemical tools to study sialyltransferases have been limited to non-covalent inhibitors and probes that do not allow isolation and profiling of these important enzymes. Here we report a new class of covalent affinity-based probes (AfBP) for ST by using ligand-directed chemistry (LDchem).

Senescence Accelerated Mouse-Prone 8: a Model of Neuroinflammation and Aging with Features of Sporadic Alzheimer's disease.

The large majority of Alzheimer's disease (AD) cases are sporadic with unknown genetic causes. In contrast, only a small percentage of AD cases are familial, with known genetic causes. Paradoxically, there are only few validated mouse models of sporadic AD but many of familial AD.

Volumetric printing and non-destructive drug quantification of water-soluble supramolecular hydrogels.

Vat photopolymerisation 3D printing is being actively explored for manufacturing personalised medicines due to its high dimensional accuracy and lack of heat application. However, several challenges have hindered its clinical translation, including the inadequate printing speeds, the lack of resins that give soluble matrices, and the need for non-destructive quality control measures. In this study, for the first time, a rapid approach to producing water-soluble vat photopolymerised matrices and a means of non-destructively verifying their drug content were investigated.

Glycoengineering with neuraminic acid analogs to label lipooligosaccharides and detect native sialyltransferase activity in gram-negative bacteria.

Lipooligosaccharides are the most abundant cell surface glycoconjugates on the outer membrane of Gram-negative bacteria. They play important roles in host-microbe interactions. Certain Gram-negative pathogenic bacteria cap their lipooligosaccharides with the sialic acid, N-acetylneuraminic acid (Neu5Ac), to mimic host glycans that among others protects these bacteria from recognition by the hosts immune system.

Rosemary extract activates oligodendrogenesis genes in mouse brain and improves learning and memory ability.

Rosemary (Rosmarinus officinalis L.) is a rich source of dietary bioactive compounds such as rosmarinic acid and carnosol with a large repertoire of pharmacological properties, including anti-inflammatory and neuroprotective activities. In the present study, we investigated rosemary as a potential new therapeutic agent for cognitive function and other symptoms of aging.

Fabrication of 3D printed mutable drug delivery devices: a comparative study of volumetric and digital light processing printing.

Mutable devices and dosage forms have the capacity to dynamically transform dimensionally, morphologically and mechanically upon exposure to non-mechanical external triggers. By leveraging these controllable transformations, these systems can be used as minimally invasive alternatives to implants and residence devices, foregoing the need for complex surgeries or endoscopies. 4D printing, the fabrication of 3D-printed structures that evolve their shape, properties, or functionality in response to stimuli over time, allows the production of such devices.

Emotional behavioral outcomes of children with unilateral and mild hearing loss.

Background: Deaf and hard-of hearing (DHH) children often experience emotional/behavioral difficulties. The impact of unilateral/mild hearing loss (HL) on children's emotion and behavior are unclear. We aimed to describe emotional/behavioral, health related quality-of-life (HRQoL) and parent psychological distress outcomes of school-age children with unilateral/mild HL, compared to children with moderate to profound HL, and in relation to population norms; and identify predictive factors of emotional/behavioral difficulties.

Supramolecular chemistry enables vat photopolymerization 3D printing of novel water-soluble tablets.

Vat photopolymerization has garnered interest from pharmaceutical researchers for the fabrication of personalised medicines, especially for drugs that require high precision dosing or are heat labile. However, the 3D printed structures created thus far have been insoluble, limiting printable dosage forms to sustained-release systems or drug-eluting medical devices which do not require dissolution of the printed matrix. Resins that produce water-soluble structures will enable more versatile drug release profiles and expand potential applications.

A case study on decentralized manufacturing of 3D printed medicines.

Pharmaceutical 3D printing (3DP) is one of the emerging enabling technologies of personalised medicines as it affords the ability to fabricate highly versatile dosage forms. In the past 2 years, national medicines regulatory authorities have held consultations with external stakeholders to adapt regulatory frameworks to embrace point-of-care manufacturing. The proposed concept of decentralized manufacturing (DM) involves the provision of feedstock intermediates (pharma-inks) prepared by pharmaceutical companies to DM sites for manufacturing into the final medicine.

Rifaximin potentiates clarithromycin against and in zebrafish.

Background: is a non-tuberculous mycobacterium (NTM) that causes chronic pulmonary infections. Because of its extensive innate resistance to numerous antibiotics, treatment options are limited, often resulting in poor clinical outcomes. Current treatment regimens usually involve a combination of antibiotics, with clarithromycin being the cornerstone of NTM treatments.

Predicting pharmaceutical inkjet printing outcomes using machine learning.

Inkjet printing has been extensively explored in recent years to produce personalised medicines due to its low cost and versatility. Pharmaceutical applications have ranged from orodispersible films to complex polydrug implants. However, the multi-factorial nature of the inkjet printing process makes formulation (e.

Advancing non-destructive analysis of 3D printed medicines.

Pharmaceutical 3D printing (3DP) has attracted significant interest over the past decade for its ability to produce personalised medicines on demand. However, current quality control (QC) requirements for traditional large-scale pharmaceutical manufacturing are irreconcilable with the production offered by 3DP. The US Food and Drug Administration (FDA) and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) have recently published documents supporting the implementation of 3DP for point-of-care (PoC) manufacturing along with regulatory hurdles.

Simultaneous fabrication of multiple tablets within seconds using tomographic volumetric 3D printing.

3D printing is driving a shift in patient care away from a generalised model and towards personalised treatments. To complement fast-paced clinical environments, 3D printing technologies must provide sufficiently high throughputs for them to be feasibly implemented. Volumetric printing is an emerging 3D printing technology that affords such speeds, being capable of producing entire objects within seconds.

Inkjet drug printing onto contact lenses: Deposition optimisation and non-invasive dose verification.

Inkjet printing has the potential to advance the treatment of eye diseases by printing drugs on demand onto contact lenses for localised delivery and personalised dosing, while near-infrared (NIR) spectroscopy can further be used as a quality control method for quantifying the drug but has yet to be demonstrated with contact lenses. In this study, a glaucoma therapy drug, timolol maleate, was successfully printed onto contact lenses using a modified commercial inkjet printer. The drug-loaded ink prepared for the printer was designed to match the properties of commercial ink, whilst having maximal drug loading and avoiding ocular inflammation.

Integrating pressure sensor control into semi-solid extrusion 3D printing to optimize medicine manufacturing.

Semi-solid extrusion (SSE) is a three-dimensional printing (3DP) process that involves the extrusion of a gel or paste-like material via a syringe-based printhead to create the desired object. In pharmaceuticals, SSE 3DP has already been used to manufacture formulations for human clinical studies. To further support its clinical adoption, the use of a pressure sensor may provide information on the printability of the feedstock material in situ and under the exact printing conditions for quality control purposes.

A Standardized Approach to Extra-Oral and Intra-Oral Digital Photography.

Contemporary dentistry mandates a more comprehensive and personalized analysis of each patient. Technological advances in digital photography have played vital roles in diagnostic accuracy, treatment planning, execution of therapies, and outcome evaluations, including esthetic enhancement. Digital photography also provides an excellent platform for patient education, communication, and co-management of cases with other healthcare providers.

Selective Exoenzymatic Labeling of Lipooligosaccharides of Neisseria gonorrhoeae with α2,6-Sialoside Analogues.

The interactions between bacteria and their host often rely on recognition processes that involve host or bacterial glycans. Glycoengineering techniques make it possible to modify and study the glycans on the host's eukaryotic cells, but only a few are available for the study of bacterial glycans. Here, we have adapted selective exoenzymatic labeling (SEEL), a chemical reporter strategy, to label the lipooligosaccharides of the bacterial pathogen Neisseria gonorrhoeae, using the recombinant glycosyltransferase ST6Gal1, and three synthetic CMP-sialic acid derivatives.

To infinity and beyond: Strategies for fabricating medicines in outer space.

Recent advancements in next generation spacecrafts have reignited public excitement over life beyond Earth. However, to safeguard the health and safety of humans in the hostile environment of space, innovation in pharmaceutical manufacturing and drug delivery deserves urgent attention. In this review/commentary, the current state of medicines provision in space is explored, accompanied by a forward look on the future of pharmaceutical manufacturing in outer space.

A bio-functional polymer that prevents retinal scarring through modulation of NRF2 signalling pathway.

One common cause of vision loss after retinal detachment surgery is the formation of proliferative and contractile fibrocellular membranes. This aberrant wound healing process is mediated by epithelial-mesenchymal transition (EMT) and hyper-proliferation of retinal pigment epithelial (RPE) cells. Current treatment relies primarily on surgical removal of these membranes.

Food and fluid intake and hydration status does not affect ultrasound measurements of subcutaneous adipose tissue in active adults.

Objectives: To investigate the impact of acute food and fluid intake or hydration status on the standardised brightness-mode ultrasound measurement of subcutaneous adipose tissue thickness.

Design: Thirty active adults (female n = 10) participated in a randomised cross over study.

Methods: Participants completed three body composition assessment sessions via standardised brightness-mode ultrasound and Dual-energy X-ray absorptiometry.

Psychotropic medication prescribing trends in a developmental-behavioural clinic during the COVID-19 pandemic.

Aim: Psychotropic medication prescribing among children with developmental-behavioural and mental health problems appears to be rising globally. We aim to examine the effects of the COVID-19 pandemic and rapid introduction of telehealth consultations on the prescribing trends and medication change in a large paediatric public hospital developmental-behavioural outpatient service.

Methods: Data for developmental-behavioural outpatient encounters from 23 March 2019 to 22 March 2021 were extracted from the electronic medical record; representing the 12 months following the conversion to telehealth consultations during the onset of COVID-19 pandemic and the 12 months prior to this change.

Malaria in Pregnancy: From Placental Infection to Its Abnormal Development and Damage.

Malaria remains a global health burden with accounting for the highest mortality and morbidity. Malaria in pregnancy can lead to the development of placental malaria, where -infected erythrocytes adhere to placental receptors, triggering placental inflammation and subsequent damage, causing harm to both mother and her infant. Histopathological studies of -infected placentas revealed various placental abnormalities such as excessive perivillous fibrinoid deposits, breakdown of syncytiotrophoblast integrity, trophoblast basal lamina thickening, increased syncytial knotting, and accumulation of mononuclear immune cells within intervillous spaces.