Histopathological findings from the investigation of paediatric acute hepatitis of unknown aetiology, United Kingdom 2022.

In 2022, there were global reports of increased numbers of acute hepatitis not explained by hepatitis A-E virus infection in children. This manuscript summarises histopathology results from 20 patients in the United Kingdom who underwent liver transplant or had a liver biopsy as part of aetiological investigations. All available histopathological samples were reviewed centrally as part of the outbreak investigation. A working group comprised of infection specialists, hepatologists and histopathologists met virtually to review the cases, presentation, investigations and histopathology. All 20 liver samples had evidence of inflammation without significant interface activity, and submassive confluent pan-lobular or multilobular hepatocellular necrosis. Overall, the predominant histopathological findings were of acute nonspecific hepatitis with submassive hepatic necrosis and central vein perivenulitis and endothelitis. Histopathological findings were a poor indicator of aetiology.

The Reality of Antimicrobial Resistance and Antibiotic Usage Data in Asia: The CAPTURA Experience.

Antimicrobial resistance (AMR), particularly in low- and middle-income countries, is threatening to undermine advances in health and development. Scarce technical and human resources in these countries limit the collection of quality AMR data for evidence-based decision-making. The CAPTURA consortium, funded by the Fleming Fund, was implemented across 7 countries in the South and Southeast Asian region. The program focused on collating historical bacteriological data for qualitative and quantitative analyses. The team gathered standard data on the quality of laboratories and clinics and the quality and quantity of retrospective historical AMR data. In addition, retrospective data on antimicrobial use and consumption were analyzed. While standard protocols guided the project, a tailored approach for stakeholder engagement was implemented to work with countries and secure data-sharing agreements. The program also had to navigate the challenges of the COVID-19 pandemic, making some innovative adaptations to overcome logistical barriers. From 2018 through 2022, a large body of data was collected that was used to base a series of recommended key measures for strengthening the development of standardized national surveillance programs and to support alignment with international efforts.

Commentary: Profiling Children With Cerebral Visual Impairment (CVI) Using Multiple Methods of Assessment to Aid in Differential Diagnosis.

PROFILING CHILDREN WITH CEREBRAL VISUAL IMPAIRMENT USING MULTIPLE METHODS OF ASSESSMENT TO AID IN DIFFERENTIAL DIAGNOSIS: Amanda H. Lueck , Gordon N. Dutton , Sylvie Chokron Seminars in Pediatric Neurology Volume 31, October 2019, Pages 5-14 Cerebral (cortical) visual impairment (CVI), the primary cause of visual impairment in chil dren in high-income countries, is increasing globally due to improved life-saving measures for premature and full-term infants. Yet the consequences of this condition are only begin ning to be understood and addressed. According to the topography, site, and the extent of the pathology, the deficit may variably concern central visual functions, visual field, percep tion of movement, visual analysis, visual exploration, attention, or visual memory, as well as visual guidance of movement. Each affected child has a unique clinical picture, which needs to be identified and individually profiled. This is probably the underlying reason that CVI is commonly underdiagnosed or misdiagnosed, especially in children, and, as a consequence, the full range of potential behavioral outcomes are not identified and adequately addressed. The present paper shows how the use of multiple methods of assessment can improve understanding of children with CVI.

Properties of non-coding mutation hotspots as urinary biomarkers for bladder cancer detection.

Mutations at specific hotspots in non-coding regions of ADGRG6, PLEKHS1, WDR74, TBC1D12 and LEPROTL1 frequently occur in bladder cancer (BC). These mutations could function as biomarkers for the non-invasive detection of BC but this remains largely unexplored. Massively-parallel sequencing of non-coding hotspots was applied to 884 urine cell pellet DNAs: 591 from haematuria clinic patients (165 BCs, 426 non-BCs) and 293 from non-muscle invasive BC surveillance patients (29 with recurrence). Urine samples from 142 non-BC haematuria clinic patients were used to optimise variant calling. Non-coding mutations are readily detectable in the urine of BC patients and undetectable, or present at much lower frequencies, in the absence of BC. The mutations can be used to detect incident BC with 66% sensitivity (95% CI 58-75) at 92% specificity (95% CI 88-95) and recurrent disease with 55% sensitivity (95% CI 36-74) at 85% specificity (95% CI 80-89%) using a 2% variant allele frequency threshold. In the NMIBC surveillance setting, the detection of non-coding mutations in urine in the absence of clinically detectable disease was associated with an increased relative risk of future recurrence (RR = 4.62 (95% CI 3.75-5.48)). As urinary biomarkers, non-coding hotspot mutations behave similarly to driver mutations in BC-associated genes and could be included in biomarker panels for BC detection.

Monkeypox encephalitis with transverse myelitis in a female patient.

The 2022 monkeypox outbreak has affected 110 countries worldwide, outside of classic endemic areas (ie, west Africa and central Africa). On July 23, 2022, the outbreak was classified by WHO as a public health emergency of international concern. Clinical presentation varies from mild to life-changing symptoms; neurological complications are relatively uncommon and there are few therapeutic interventions for monkeypox disease. In this Grand Round, we present a case of monkeypox with encephalitis complicated by transverse myelitis in a previously healthy woman aged 35 years who made an almost complete recovery from her neurological symptoms after treatment with tecovirimat, cidofovir, steroids, and plasma exchange. We describe neurological complications associated with orthopoxvirus infections and laboratory diagnosis, the radiological features in this case, and discuss treatment options.

From vision to cognition: potential contributions of cerebral visual impairment to neurodevelopmental disorders.

Vision has a crucial role to play in human development and functioning. It is, therefore, not surprising that vision plays a fundamental role in the development of the child. As a consequence, an alteration in visual function is, therefore, likely to hinder the child's development. Although ocular disorders are well known, diagnosed and taken into account, cerebral visual impairments (CVI) resulting from post-chiasmatic damage are largely underdiagnosed. However, among the disorders resulting from an episode of perinatal asphyxia and/or associated with prematurity, or neonatal hypoglycaemia, CVIs are prominent. In this article, we focus on the role of the possible effects of CVI on a child's learning abilities, leading to major difficulty in disentangling the consequences of CVI from other neurodevelopmental disorders (NDD) such as dyslexia, dyscalculia, dysgraphia, attention-deficit/hyperactivity disorder (ADHD), developmental coordination disorder (DCD) and autism spectrum disorders (ASD). Although we focus here on the possible overlap between children with CVI and children with other NDD, De Witt et al. (Wit et al. Ear Hear 39:1-19, 2018) have raised exactly the same question regarding children with auditory processing disorders (the equivalent of CVI in the auditory modality). We underline how motor, social and cognitive development as well as academic success can be impaired by CVI and raise the question of the need for systematic evaluation for disorders of vision, visual perception and cognition in all children presenting with a NDD and/or previously born under adverse neurological conditions.

The PhanSST global database of Phanerozoic sea surface temperature proxy data.

Paleotemperature proxy data form the cornerstone of paleoclimate research and are integral to understanding the evolution of the Earth system across the Phanerozoic Eon. Here, we present PhanSST, a database containing over 150,000 data points from five proxy systems that can be used to estimate past sea surface temperature. The geochemical data have a near-global spatial distribution and temporally span most of the Phanerozoic. Each proxy value is associated with consistent and queryable metadata fields, including information about the location, age, and taxonomy of the organism from which the data derive. To promote transparency and reproducibility, we include all available published data, regardless of interpreted preservation state or vital effects. However, we also provide expert-assigned diagenetic assessments, ecological and environmental flags, and other proxy-specific fields, which facilitate informed and responsible reuse of the database. The data are quality control checked and the foraminiferal taxonomy has been updated. PhanSST will serve as a valuable resource to the paleoclimate community and has myriad applications, including evolutionary, geochemical, diagenetic, and proxy calibration studies.

Development of a competency-based clinical assessment instrument for exit level Oral Hygiene students at the University of Western Cape.

Seminal to the process of a health sciences curriculum evaluation is the periodic review of clinical assessment instruments that measure competency. An assessment of quality is facilitated by using a well-structured, authentic and reliable instrument. This process rests on designing and measuring the instrument against a sound framework and validating it for scientific merit. This paper documents the pedagogy and the process taken in developing an improved formative competency-based assessment instrument for the final year students of the Bachelor of Oral Health program (BOH) at the University of the Western Cape (UWC). METHODS: A qualitative research study design employing the Nominal Group Technique (NGT) was used as a method for gaining small group consensus on the clinical assessment instrument for exit level Oral Hygiene (BOH3) students within the parameters of assessment principles. The key contributors to the instrument development process were the academic staff of the Department of Oral Hygiene, involved in clinical teaching and assessment of student competency. RESULTS: The domains of ethics and professionalism, patient assessment, diagnosis, treatment planning and implementation was identified as the core elements in the assessment. The principles of assessment, which include, alignment with outcomes, feedback, transparency and validity, were used to guide the instrument development. The assessment criteria were cross examined for alignment to the learning outcomes of the module and the program whilst formative feedback was foregrounded as a central feature to support student learning and progress monitoring. Transparency was obtained by providing students access to the instrument before and after the assessment including the written feedback on their performance. The instrument embodied a range of criteria to be assessed rather than on the awarding of a cumulative score. This allowed for the identification of the criteria or domain within which a student is struggling or excelling. Consensus on the instrument design was achieved using the NGT phases throughout the instrument development process including the weighting of the domains and grading. This level of engagement together with the application of scientifically sound assessment principles contributed to the validation of the instrument. CONCLUSION: The development of a competency-based assessment instrument was the result of a structured, collaborative and scientifically engaged process framed around specific assessment principles. The process culminated in the development of a formative competency-based clinical assessment instrument that was fit for purpose in the Bachelor of Oral Health program.The Nominal Group Technique served to be a valuable approach for small group consensus in developing the instrument. It served to promote individual perspectives and to generate debate and group discussion between academics that were proficient in clinical teaching and, finally to facilitate group consensus on the instrument structure and system for administration.

African Hydroclimate During the Early Eocene From the DeepMIP Simulations.

The early Eocene (∼56-48 Myr ago) is characterized by high CO2 estimates (1,200-2,500 ppmv) and elevated global temperatures (∼10°C-16°C higher than modern). However, the response of the hydrological cycle during the early Eocene is poorly constrained, especially in regions with sparse data coverage (e.g., Africa). Here, we present a study of African hydroclimate during the early Eocene, as simulated by an ensemble of state-of-the-art climate models in the Deep-time Model Intercomparison Project (DeepMIP). A comparison between the DeepMIP pre-industrial simulations and modern observations suggests that model biases are model- and geographically dependent, however, these biases are reduced in the model ensemble mean. A comparison between the Eocene simulations and the pre-industrial suggests that there is no obvious wetting or drying trend as the CO2 increases. The results suggest that changes to the land sea mask (relative to modern) in the models may be responsible for the simulated increases in precipitation to the north of Eocene Africa. There is an increase in precipitation over equatorial and West Africa and associated drying over northern Africa as CO2 rises. There are also important dynamical changes, with evidence that anticyclonic low-level circulation is replaced by increased south-westerly flow at high CO2 levels. Lastly, a model-data comparison using newly compiled quantitative climate estimates from paleobotanical proxy data suggests a marginally better fit with the reconstructions at lower levels of CO2.

The latitudinal temperature gradient and its climate dependence as inferred from foraminiferal δ18O over the past 95 million years.

SignificanceThe temperature difference between low and high latitudes is one measure of the efficiency of the global climate system in redistributing heat and is used to test the ability of models to represent the climate system through time. Here, we show that the latitudinal temperature gradient has exhibited a consistent inverse relationship with global mean sea-surface temperature for at least the past 95 million years. Our results help reduce conflicts between climate models and empirical estimates of temperature and argue for a fundamental consistency in the dynamics of heat transport and radiative transfer across vastly different background states.

A new look at the safety and tolerability of prostaglandin analogue eyedrops in glaucoma and ocular hypertension.

INTRODUCTION: In the last 25 years, topical prostaglandin analogues (PGAs) have emerged to become first line and first choice therapeutic options in the management of glaucoma and ocular hypertension (OHT). Although the short-term efficacy and safety of PGAs has been extensively investigated, less is known about their long term safety and tolerability. This gap in current knowledge is clinically relevant, because treatment-related adverse events and long-term tolerability issues are key determinants of the overall success of long-term therapy and the final outcome of a lifelong, symptomless disease like glaucoma. AREAS COVERED: We include selected evidence pertaining to the safety and tolerability of available and emerging PGA formulations. We also outline PGA formulations with different concentrations of the active ingredient, different preservatives, and preservative-free (PF) options. EXPERT OPINION: Undoubtedly PGAs will continue to play a major role in the medical therapy of glaucoma and OHT. Despite extensive literature and prolonged clinical experience with these agents worldwide, a number of areas that warrant further research have been identified in the present review. Recently launched novel PGAs, or those still in development offer new opportunities and future challenges.

Cortical Visual Impairments and Learning Disabilities.

Medical advances in neonatology have improved the survival rate of premature infants, as well as children who are born under difficult neurological conditions. As a result, the prevalence of cerebral dysfunctions, whether minimal or more severe, is increasing in all industrialized countries and in some developing nations. Whereas in the past, ophthalmological diseases were considered principally responsible for severe visual impairment, today, all recent epidemiological studies show that the primary cause of blindness and severe visual impairment in children in industrialized countries is now neurological, with lesions acquired around the time of birth currently comprising the commonest contributor. The resulting cortical or cerebral visual impairments (CVIs) have long been ignored, or have been confused either with other ophthalmological disorders causing low vision, or with a range of learning disabilities. We present here the deleterious consequences that CVI can have upon learning and social interaction, and how these can be given behavioral labels without the underlying visual causes being considered. We discuss the need to train and inform clinicians in the identification and diagnosis of CVI, and how to distinguish the diagnosis of CVI from amongst other visual disorders, including the specific learning disorders. This is important because the range of approaches needed to enhance the development of children with CVI is specific to each child's unique visual needs, making incorrect labeling or diagnosis potentially detrimental to affected children because these needs are not met.

Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the healthcare environment: a bacterial genome-wide association study.

Staphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease. To investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage. All major global lineages were represented in both bacteraemia and carriage, with no evidence for different infection rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (P=10-8.9-10-9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10-5.3) as well as the presence of SCCmec (HMP=10-4.4). Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (P=10-7.1-10-19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (P=10-7.2). In an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment. Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and healthcare-associated carriage, suggesting that AMR increases the propensity not only to survive in healthcare environments, but also to cause invasive disease.

Perceptual visual dysfunction in children - An Indian perspective.

Perceptual visual dysfunction (PVD) comprises a group of vision disorders resulting from dysfunction of the posterior parietal and/or temporal lobes. Often, affected children have normal/near normal visual acuities and/or visual fields, but have difficulties in activities of daily living involving the use of vision. PVDs are known to be common among children with risk factors such as a history of prematurity and/or neurodevelopmental disorders. The inferior temporal lobes and ventral stream transform visual signals into perception, while the posterior parietal lobes and dorsal stream transform visual signals to non-consciously map the scene to guide action and facilitate attention. Dysfunction of these can lead to specific visual impairments that need to be identified during history taking, triggering ascertainment of further details by a structured inventory approach. Clinical tests to elicit dorsal and ventral stream visual dysfunctions have good specificity but low sensitivity. Neuropsychologists are rarely available in the developing world to perform detailed assessments, but there are a few tests that can be used by eye care professionals with some training. Optical coherence tomography (OCT) showing thinning of the ganglion cell layer and retinal nerve fiber layer is being explored as a potential tool for rapid assessment in the clinic. The behavioral outcomes of PVD can mimic psychological conditions including autism spectrum disorder, attention deficit hyperactivity disorder, specific learning disability, and intellectual impairment, and one needs to be aware of overlap among these differential diagnoses. A practical functional approach providing working solutions for each child's set of difficulties in day-to-day activities is needed.

The treatment of glaucoma using topical preservative-free agents: an evaluation of safety and tolerability.

Introduction: Preservative-free (PF) medications represent a valuable treatment strategy in the lifelong management of glaucoma. By removing preservative toxicity, PF formulations provide tangible clinical benefits to glaucoma patients worldwide. They improve tolerability and adherence, leading to a positive impact in long-term intraocular pressure (IOP) control.Areas covered: A critical review of the subject is provided, including selected evidence on the safety and tolerability of currently available topical PF formulations. Cumulative evidence confirms that topical PF medications are at least equally efficacious to their preserved equivalents. There is convincing short-term evidence for superior tolerability and safety of PF formulations compared to preserved medications. The long-term benefits and success of PF therapy requires further elucidation.Expert opinion: Successful stepwise administration of medical therapy for glaucoma remains elusive. There is a greater risk for ocular toxicity and therapy failure with preserved topical glaucoma therapy. Currently available and emerging PF therapy options potentially optimize lifelong stepwise glaucoma therapy and may enhance outcome. To avert complications from preservatives leading to poor adherence, ideally, future antiglaucoma therapy should become 100% PF. There are still key aspects of PF therapy that warrant further investigation.