Proteomic and functional comparison between human induced and embryonic stem cells.

Human induced pluripotent stem cells (hiPSCs) have great potential to be used as alternatives to embryonic stem cells (hESCs) in regenerative medicine and disease modelling. In this study, we characterise the proteomes of multiple hiPSC and hESC lines derived from independent donors and find that while they express a near-identical set of proteins, they show consistent quantitative differences in the abundance of a subset of proteins. hiPSCs have increased total protein content, while maintaining a comparable cell cycle profile to hESCs, with increased abundance of cytoplasmic and mitochondrial proteins required to sustain high growth rates, including nutrient transporters and metabolic proteins.

A CDK1 phosphorylation site on PAR-3 regulates neuroblast polarisation and sensory organ formation.

The generation of distinct cell fates during development depends on asymmetric cell division of progenitor cells. In the central and peripheral nervous system of progenitor cells respectively called neuroblasts or sensory organ precursors use PAR polarity during mitosis to control cell fate determination in their daughter cells. How polarity and the cell cycle are coupled, and how the cell cycle machinery regulates PAR protein function and cell fate determination is poorly understood.

Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders.

Human developmental disorders encompass a wide range of debilitating physical conditions and intellectual disabilities. Perturbation of protein kinase signalling underlies the development of some of these disorders. For example, disrupted SRPK signalling is associated with intellectual disabilities, and the gene dosage of DYRKs can dictate the pathology of disorders including Down's syndrome.

The Role of Airway Management on Feeding Difficulties in Children With Pfeiffer Syndrome.

Background: Pfeiffer syndrome is characterized by craniosynostosis, mid-face hypoplasia, broad thumbs, and often multilevel airway obstruction. Airway management is often required, including the use of positive airway ventilation, nasopharyngeal airway (NPA), or tracheostomy.

Objective: The objective of this study was to assess the impact an airway adjunct can have on feeding difficulties in children with Pfeiffer syndrome.

Towards a Better Understanding of Texturization during High-Moisture Extrusion (HME)-Part II: Characterization of Thermophysical Properties of High-Moisture Meat Analogues.

It is crucial to determine the thermophysical properties of high-moisture extruded samples (HMESs) to properly understand the texturization process of high-moisture extrusion (HME), especially when the primary objective is the production of high-moisture meat analogues (HMMAs). Therefore, the study's aim was to determine thermophysical properties of high-moisture extruded samples made from soy protein concentrate (SPC ALPHA 8 IP). Thermophysical properties such as the specific heat capacity and the apparent density were experimentally determined and further investigated to obtain simple prediction models.

Towards a Better Understanding of Texturization during High-Moisture Extrusion (HME)-Part I: Modeling the Texturability of Plant-Based Proteins.

This study focused on predicting high-moisture texturization of plant-based proteins (soy protein concentrate (SPC), soy protein isolate (SPI), pea protein isolate (PPI)) at different water contents (57.5%, 60%, 65%, 70%, and 72.5% (/ db)) to optimize and guarantee the production of high-moisture meat analogs (HMMA).

Personalised interventions for subgroups of children with conduct problems.

Background: Conduct problems are a range of disruptive behaviours in childhood that are associated with long-term adverse outcomes in adolescence and adulthood, including antisocial behaviour, substance misuse, and poor academic achievement. Children with conduct problems can vary according to age of onset, comorbidities, and environmental factors, and it has been suggested that certain groups of children may have different treatment outcomes. Therefore, it is important to assess the extent to which personalised interventions for different groups of children with conduct problems may affect outcomes.

Hearing outcomes in children with single sided deafness: Our experience at a tertiary paediatric otorhinolaryngology unit.

Introduction: Hearing rehabilitation options for single sided deafness (SSD) include contralateral routing of sound (CROS) aids and bone conduction devices (BCDs). This study aimed to review the management of children with SSD at our tertiary paediatric otolaryngology unit over the last 15 years.

Material And Methods: A retrospective cohort study was performed.

Higher Dose Oral Fluconazole for the Treatment of AIDS-related Cryptococcal Meningitis (HIFLAC)-report of A5225, a multicentre, phase I/II, two-stage, dose-finding, safety, tolerability and efficacy randomised, amphotericin B-controlled trial of the AIDS Clinical Trials Group.

Background: The WHO recommended 1200mg/day of fluconazole (FCZ) in the induction phase of cryptococcal meningitis (CM) in HIV prior to 2018 in regions where amphotericin-B (AMB) was unavailable. A 2-stage AMB-controlled, dose-escalation study to determine the maximum tolerated dose and the safety/efficacy of an induction-consolidation strategy of higher doses FCZ (1200mg-2000mg/day), adjusted for weight and renal function (eGFR)in adults with CM was undertaken.

Methods: In Stage-1, three induction doses of FCZ (1200mg/day, 1600mg/day and 2000mg/day) were tested in sequential cohortsand compared with AMB in a 3:1 ratio.

Predictors of virologic outcome among people living with HIV who continue a protease inhibitor-based antiretroviral regimen following virologic failure with no or limited resistance.

Background: Treatment management after repeated failure of antiretroviral therapy (ART) is difficult due to resistance and adherence challenges. For people who have failed non-nucleoside reverse transcriptase inhibitor-(NNRTI-) and protease inhibitor-(PI-) based regimens with no or limited resistance, remaining on PI-based ART is an option. Using data from an ART strategy trial (A5288) in low/middle-income countries which included this option, we explored whether predictors can be identified distinguishing those who experienced further virologic failure from those who achieved and maintained virologic suppression.

The MK2 cascade mediates transient alteration in mGluR-LTD and spatial learning in a murine model of Alzheimer's disease.

A key aim of Alzheimer disease research is to develop efficient therapies to prevent and/or delay the irreversible progression of cognitive impairments. Early deficits in long-term potentiation (LTP) are associated with the accumulation of amyloid beta in rodent models of the disease; however, less is known about how mGluR-mediated long-term depression (mGluR-LTD) is affected. In this study, we have found that mGluR-LTD is enhanced in the APP /PS1dE9 mouse at 7 but returns to wild-type levels at 13 months of age.

Third-line antiretroviral therapy, including raltegravir (RAL), darunavir (DRV/r) and/or etravirine (ETR), is well tolerated and achieves durable virologic suppression over 144 weeks in resource-limited settings: ACTG A5288 strategy trial.

Introduction: ACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second-line protease inhibitor (PI)-based antiretroviral therapy (ART) from 10 low- and middle-income countries (LMICs). Participants resistant to lopinavir (LPV) and/or multiple nucleotide reverse transcriptase inhibitors started on third-line regimens that included raltegravir (RAL), darunavir/ritonavir (DRV/r) and/or etravirine (ETR) according to their resistance profiles. At 48 weeks, 87% of these participants achieved HIV-1 RNA ≤200 copies/ml.

Isoniazid Adherence Reduces Mortality and Incident Tuberculosis at 96 Weeks Among Adults Initiating Antiretroviral Therapy With Advanced Human Immunodeficiency Virus in Multiple High-Burden Settings.

Background: People with human immunodeficiency virus (HIV) and advanced immunosuppression initiating antiretroviral therapy (ART) remain vulnerable to tuberculosis (TB) and early mortality. To improve early survival, isoniazid preventive therapy (IPT) or empiric TB treatment have been evaluated; however, their benefit on longer-term outcomes warrants investigation.

Methods: We present a 96-week preplanned secondary analysis among 850 ART-naive outpatients (≥13 years) enrolled in a multicountry, randomized trial of efavirenz-containing ART plus either 6-month IPT ( = 426) or empiric 4-drug TB treatment ( = 424).

Cold-season freeze frequency is a pervasive driver of subcontinental forest growth.

As northern latitudes experience rapid winter warming, there is an urgent need to assess the effect of varying winter conditions on tree growth and forest carbon sequestration potential. We examined tree growth responses to variability in cold-season (November–April) frequency of freeze days (FFD) over 1951 to 2018 using tree-ring data from 35,217 trees and 57 species at 4,375 sites distributed across Canada. We found that annual radial growth responses to FFD varied by species, with some commonalities across genera and clades.

The effect on the T-14 paediatric throat disorders outcome score of delaying adenotonsillectomy surgery due to COVID-19.

Introduction: Adenotonsillectomy is commonly performed for recurrent tonsillitis and obstructive sleep apnoea. These conditions may improve with age. The COVID-19 pandemic led to all UK elective surgery being suspended.

Variations in Paranasal Sinus Anatomy in Children With Apert Syndrome: A Radiological Analysis.

Background: Apert syndrome is a genetic disorder characterized by craniofacial abnormalities and premature closure of the coronal sutures. The restriction of cranial development may have a subsequent effect on paranasal anatomy development.

Aim: The aim of the study was to gain an understanding of paranasal sinus anatomical variations seen in children with Apert syndrome.

Participant Perspectives and Experiences Following an Intensively Monitored Antiretroviral Pause in the United States: Results from the AIDS Clinical Trials Group A5345 Biomarker Study.

The AIDS Clinical Trials Group A5345 study (NCT03001128) included an intensively monitored antiretroviral pause (IMAP), during which participants living with HIV temporarily stopped antiretroviral treatment (ART) in an effort to identify biomarkers that could predict HIV rebound. We evaluated the potential impact of the IMAP on A5345 study participants in the United States by questioning them immediately after the IMAP and at the end of the study. We administered longitudinal sociobehavioral questionnaires to participants following the IMAP when they resumed ART and at the end of the study.

Sustained chemogenetic activation of locus coeruleus norepinephrine neurons promotes dopaminergic neuron survival in synucleinopathy.

Dopaminergic neuron degeneration in the midbrain plays a pivotal role in motor symptoms associated with Parkinson's disease. However, non-motor symptoms of Parkinson's disease and post-mortem histopathology confirm dysfunction in other brain areas, including the locus coeruleus and its associated neurotransmitter norepinephrine. Here, we investigate the role of central norepinephrine-producing neurons in Parkinson's disease by chronically stimulating catecholaminergic neurons in the locus coeruleus using chemogenetic manipulation.

Inner Ear Anomalies in Children With Apert Syndrome: A Radiological and Audiological Analysis.

Introduction: Apert syndrome is a multisystem genetic disorder typically characterized by craniosynostosis and syndactyly. Studies also report an increased incidence of hearing loss in children with Apert syndrome in comparison to the general population. The aim of this study was to gain an understanding of the inner ear radiological anatomical variations seen in children with Apert syndrome and correlate these with audiological outcomes.

Adding Tree Rings to North America's National Forest Inventories: An Essential Tool to Guide Drawdown of Atmospheric CO2.

Tree-ring time series provide long-term, annually resolved information on the growth of trees. When sampled in a systematic context, tree-ring data can be scaled to estimate the forest carbon capture and storage of landscapes, biomes, and-ultimately-the globe. A systematic effort to sample tree rings in national forest inventories would yield unprecedented temporal and spatial resolution of forest carbon dynamics and help resolve key scientific uncertainties, which we highlight in terms of evidence for forest greening (enhanced growth) versus browning (reduced growth, increased mortality).

Urinary Tract Infection in Parkinson's Disease.

Urinary tract infection (UTI) is a common precipitant of acute neurological deterioration in patients with Parkinson's disease (PD) and a leading cause of delirium, functional decline, falls, and hospitalization. Various clinical features of PD including autonomic dysfunction and altered urodynamics, frailty and cognitive impairment, and the need for bladder catheterization contribute to an increased risk of UTI. Sepsis due to UTI is a feared consequence of untreated or undertreated UTI and a leading cause of morbidity in PD.