The molecular chaperone function of alpha-crystallin in the lens prevents the aggregation and insolubilization of lens proteins that occur during the process of aging. We found that chemical modification of alpha-crystallin by a physiological alpha-dicarbonyl compound, methylglyoxal (MG), enhances its chaperone function. Protein-modifying sugars and ascorbate have no such effect and actually reduce chaperone function. Chaperone assay after immunoprecipitation or with immunoaffinity-purified argpyrimidine-alpha-crystallin indicates that 50-60% of the increased chaperone function is due to argpyrimidine-modified protein. Incubation of alpha-crystallin with DL-glyceraldehyde and arginine-modifying agents also enhances chaperone function, and we believe that the increased chaperone activity depends on the extent of arginine modification. Far- and near-UV circular dichroism spectra indicate modest changes in secondary and tertiary structure of MG-modified alpha-crystallin. LC MS/MS analysis of MG-modified alpha-crystallin following chymotryptic digestion revealed that R21, R49, and R103 in alphaA-crystallin were converted to argpyrimidine. 1,1'-Bis(4-anilino)naphthalene-5,5'-disulfonic acid binding, an indicator of hydrophobicity of proteins, increased in alpha-crystallin modified by low concentrations of MG (2-100 microM). MG similarly enhances chaperone function of another small heat shock protein, Hsp27. Our results show that posttranslational modification by a metabolic product can enhance the chaperone function of alpha-crystallin and Hsp27 and suggest that such modification may be a protective mechanism against environmental and metabolic stresses. Augmentation of the chaperone function of alpha-crystallin might have evolved to protect the lens from deleterious protein modifications associated with aging.

IntroductionRisk factors of adverse outcomes in COVID-19 are defined but stratification of mortality using non-laboratory measured scores, particularly at the time of prehospital SARS-CoV-2 testing, is lacking.MethodsMultivariate regression with bootstrapping was used to identify independent mortality predictors in patients admitted to an acute hospital with a confirmed diagnosis of COVID-19. Predictions were externally validated in a large random sample of the ISARIC cohort (N=14 231) and a smaller cohort from Aintree (N=290).Results983 patients (median age 70, IQR 53–83; in-hospital mortality 29.9%) were recruited over an 11-week study period. Through sequential modelling, a five-predictor score termed SOARS (SpO2, Obesity, Age, Respiratory rate, Stroke history) was developed to correlate COVID-19 severity across low, moderate and high strata of mortality risk. The score discriminated well for in-hospital death, with area under the receiver operating characteristic values of 0.82, 0.80 and 0.74 in the derivation, Aintree and ISARIC validation cohorts, respectively. Its predictive accuracy (calibration) in both external cohorts was consistently higher in patients with milder disease (SOARS 0–1), the same individuals who could be identified for safe outpatient monitoring. Prediction of a non-fatal outcome in this group was accompanied by high score sensitivity (99.2%) and negative predictive value (95.9%).ConclusionThe SOARS score uses constitutive and readily assessed individual characteristics to predict the risk of COVID-19 death. Deployment of the score could potentially inform clinical triage in preadmission settings where expedient and reliable decision-making is key. The resurgence of SARS-CoV-2 transmission provides an opportunity to further validate and update its performance.

This case report highlights an unusual presentation of acute adrenal infarction in a Covid-19 patient who presented with abdominal symptoms and hyponatraemia. We discuss the recent literature reviewing how Covid-19 creates a hypercoaguable state, with acute adrenal infarction as a possible prothrombotic complication.

Melanoma is uncommon in the pediatric age range, but is increasing in frequency and often presents with atypical features compared to the classic ABCDE criteria common to adult melanoma cases. Moreover, many melanocytic neoplasms in childhood pose diagnostic challenges to the pathologist, and sometimes cannot be unequivocally classified as benign nevi or melanoma. This chapter addresses the evaluation and management of pediatric patients with melanoma and atypical melanocytic neoplasms, including the roles of and unresolved questions surrounding sentinel lymph node biopsy, completion lymphadenectomy, adjuvant therapy, and treatment of advanced disease.

TCA are commonly used for children, honey in particular for respiratory tract symptoms. Parents and some PHPs appear unaware of the risk of botulism from honey use in infants. Healthcare practitioners should ask routinely about the use of honey and other TCA, and consider different parental belief systems in ethnically diverse populations. Further research is required on the use and efficacy of honey for infants, to raise awareness of its benefits and risks.

Pulsatile tinnitus (PT) can be a mild or debilitating symptom. Following clinical examination and otoscopy, when the underlying aetiology is not apparent, radiological imaging can be used to evaluate further. CT arteriographyvenography (CT A-V) of the head and neck has recently been introduced as a single 'one catch' modality for identifying the many causes of PT including those which are treatable and potentially serious whilst also providing reassurance through negative studies or studies with benign findings.CT A-V is performed as a single phase study allowing both arterial and venous assessment, hence limiting radiation exposure. Additional multiplanar reformats and bone reconstructions are desirable. Understanding the limitations of CT A-V is also required, with an awareness of the scenarios where other imaging modalities should be considered.The causes of PT can be divided into systemic and non-systemic categories. Non-systemic aetiologies in the head and neck should be carefully reviewed on CT A-V and include a variety of vascular causes (arteriovenous malformations/fistulas, venous or arterial aetiologies) and non-vascular causes (tumours and bony dysplasias). Venous causes (dominant, aberrant, stenosed or thrombosed venous vessels) are more common than arterial aetiologies (aberrant or stenosed internal carotid artery, aneurysms or a persistent stapedial artery). Glomus tumours that are not visible on otoscopy and osseous pathologies such as bony dehiscence and otospongiosis should also be excluded.Careful assessment of all the potential vascular and non-vascular causes should be reviewed in a systematic approach, with correlation made with the clinical history. A structured reporting template for the reporting radiologist is provided in this review to ensure all the potential causes of PT are considered on a CT A-V study. This will help in providing a comprehensive radiological evaluation, hence justifying the radiation dose and for patient assessment and prognostication.

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Primary testicular lymphoma is a rare testicular neoplasm that mainly affects elderly patients, with Human Immunodeficiency Virus (HIV) being a known risk factor in the younger population. Approximately 20% of patients will have disseminated disease with extra-nodal involvement at clinical presentation. Rarely, direct spread along the spermatic cord and gonadal vessels can occur and has been described in the literature. We present two cases of this phenomenon where the primary testicular tumour has spread along the gonadal vein to its origin at the inferior vena cava.