Germline GATA1s-generating mutations predispose to leukemia with acquired trisomy 21 and Down syndrome-like phenotype.

Individuals with Down syndrome are at increased risk of myeloid leukemia in early childhood, which is associated with acquisition of GATA1 mutations that generate a short GATA1 isoform called GATA1s. Germline GATA1s-generating mutations result in congenital anemia in males. We report on 2 unrelated families that harbor germline GATA1s-generating mutations in which several members developed acute megakaryoblastic leukemia in early childhood. All evaluable leukemias had acquired trisomy 21 or tetrasomy 21. The leukemia characteristics overlapped with those of myeloid leukemia associated with Down syndrome, including age of onset at younger than 4 years, unique immunophenotype, complex karyotype, gene expression patterns, and drug sensitivity. These findings demonstrate that the combination of trisomy 21 and GATA1s-generating mutations results in a unique myeloid leukemia independent of whether the GATA1 mutation or trisomy 21 is the primary or secondary event and suggest that there is a unique functional cooperation between GATA1s and trisomy 21 in leukemogenesis. The family histories also indicate that germline GATA1s-generating mutations should be included among those associated with familial predisposition for myelodysplastic syndrome and leukemia.

Clinical characteristics of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV2) patients in Hospital Tengku Ampuan Afzan.

BACKGROUND: The COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aims to describe the clinical characteristics of COVID-19 patients admitted to Hospital Tengku Ampuan Afzan (HTAA), Pahang, Malaysia and to identify the clinical and laboratory markers for severe disease, complications and virologic clearance according to clinical staging. METHODS: This was a single-centre, retrospective, descriptive study. All COVID-19 patients admitted to HTAA from March 9 to April 15, 2020, were included in the study. Patients were categorised according to clinical staging. Data obtained from the medical report includes baseline characteristics of patients, comorbidities, presenting symptoms, laboratory findings, treatments, complications, and outcomes. RESULTS: Of the total of 247 patients hospitalised, the majority consisted at clinical-stage 1 (43%) and stage 2 (39%) disease. Older patients, diabetes mellitus, hypertension, cardiovascular diseases, and chronic kidney disease were found more common among patients with severe disease. Fever was uncommon and the majority had normal haemoglobin levels, white cell counts, and platelet counts. C-reactive protein (CRP) was found statistically significant to predict pneumonia or hypoxia at a cut-off value of 14mg/L (sensitivity 73.8%, specificity 91.3%) and 50mg/L (sensitivity 100%, specificity 96.4%) respectively. Pneumonia was mostly diagnosed radiologically using chest radiography, especially among clinical stage 3. Acute kidney injury (AKI) was a significant complication, with 31% of clinical stage 3 and above developed AKI and 44% of them requiring haemodialysis. Median virologic clearance time was 15 days from onset of illness, and asymptomatic patients had longer clearance time. CONCLUSION: COVID-19 presented with a wide spectrum of clinical patterns. CRP was a valuable predictor of severe disease. In this study risk and severity of acute kidney injury were found to be higher. A longer duration of virologic clearance was observed among the asymptomatic patients.

Raman spectroscopic analysis of human remains from a seventh century cist burial on Anglesey, UK.

Specimens from human remains exhibiting unusual preservation excavated from a seventh century stone cist burial at Towyn y Capel in Anglesey, UK, have been analysed using Raman spectroscopy with near-infrared laser excitation at 1,064 and 785 nm. Specimens of hair and bone provided evidence for severe degradation and microbial colonisation. The deposits within the stone cist showed that some microbially mediated compounds had been formed. Analysis of crystals found at the interface between the hair and the skeletal neck vertebrae revealed a mixture of newberyite and haematite, associated with decomposition products of the hair and bone. An interesting differential degradation was noted in the specimens analysed which could be related to the air-void and the presence of plant root inclusions into the stone cist. This is the first time that Raman spectroscopy has been used in the forensic archaeological evaluation of burial remains in complex and dynamic environments.

Life in the sabkha: Raman spectroscopy of halotrophic extremophiles of relevance to planetary exploration.

The Raman spectroscopic biosignatures of halotrophic cyanobacterial extremophiles from sabkha evaporitic saltpans are reported for the first time and ideas about the possible survival strategies in operation have been forthcoming. The biochemicals produced by the cyanobacteria which colonise the interfaces between large plates of clear selenitic gypsum, halite, and dolomitized calcium carbonates in the centre of the salt pans are identifiably different from those which are produced by benthic cyanobacterial mats colonising the surface of the salt pan edges in the intertidal zone. The prediction that similar geological formations would have been present on early Mars and which could now be underlying the highly peroxidised regolith on the surface of the planet has been confirmed by recent satellite observations from Mars orbit and by localised traverses by robotic surface rovers. The successful adoption of miniaturised Raman spectroscopic instrumentation as part of a scientific package for detection of extant life or biomolecular traces of extinct life on proposed future Mars missions will depend critically on interpretation of data from terrestrial Mars analogues such as sabkhas, of which the current study is an example.

Anatase--a pigment in ancient artwork or a modern usurper?

Fragments of wall-paintings from Roman villas in Easton Maudit, which date from ca 150 AD have been studied by Raman spectroscopy. An intact ancient Roman paint pot discovered in the remains of a villa in Castor, Cambridgeshire, still containing a mixture of white and red pigment was also analysed and the pigments identified as haematite and anatase. The discovery of anatase in the intact artist's paint pot, particularly, and also on fragments of broken paint pots from the Easton Maudit villa site, is a unique contribution to current knowledge of ancient European pigment history, because the presence of this mineral has not hitherto been recognised fully in an ancient artist's palette. The relative spectral response of anatase and haematite in the Raman data is compared with that of anatase and other red pigments such as minium, cinnabar, and litharge.

Ancient biodeterioration: an FT-Raman spectroscopic study of mammoth and elephant ivory.

Raman spectra of mammoth ivory specimens have been recorded using near-infrared excitation, and comparisons made with modern Asian and African elephant ivories. Whereas the most ancient mammoth ivory (60-65 ky) showed no evidence for an organic collagen component, more recent samples of mammoth ivory indicated that some preservation had occurred, although with biodeterioration of the protein structure exhibited by the amide I and III bands in the 1200-1700 cm(-1) region of the Raman spectrum. The consequent difficulties encountered when applying chemometrics methods to ancient ivory analysis (which are successful for modern specimens) are noted. In the most ancient mammoth ivory specimens, which are extensively fragmented, evidence of mineralization is seen, with the production of gypsum, calcite and limonite; Raman microscopic analysis of crystalline material inside the fissures of the mammoth ivory shows the presence of gypsum as well as cyanobacterial colonisation. The application of Raman spectroscopy to the nondestructive analysis of archaeological materials in order to gain information of relevance to their preservation or restoration is highlighted.

Raman spectroscopic analyses of preserved historical specimens of human hair attributed to Robert Stephenson and Sir Isaac Newton.

The Raman spectra of two historical specimens of human hair attributed to the engineer Robert Stephenson and scientist Sir Isaac Newton, preserved in private collections are reported. Comparisons are made with the Raman spectra of modern hair specimens and with hair from archaeological excavations. The hair spectra collected with a laser excitation of 785 nm are of a better quality than those collected using 1064 nm. The historical hair specimens are remarkably well-defined spectroscopically in terms of the amide I vibrational mode and the [small nu](SS), ascribed to a predominantly gauche-gauche-gauche CSSC conformation. The contrast with degraded hair specimens recovered from archaeological excavations is striking. The presence of a weak feature near 2590 cm(-1) in the hair samples attributed to a [small nu](SH) vibration could be indicative of a reduction process operative on the CSSC cystine keratotic linkages and a possible origin of this is bacterial biodegradation identified histologically. This study demonstrates the molecular information available from non-destructive Raman spectroscopic analysis from single hair shafts or small bundles of fibres which complements information available from histological and destructive analytical techniques for rare biological specimens subjected to conservation or curation procedures in museums or private collections.

[The CT-stereotaxic neutron brachytherapy of brain tumors with californium sources on the ANET-B apparatus]. / KT-stereotaksicheskaia neitronnaia brakhiterapiia opukholei golovnogo mozga kalifornievymi istochnikami na apparate "ANET-B".

A method for stereotaxic intratissue radiotherapy of brain tumors based on the findings of computed tomography is described. Radiosurgical implantation of sources with increased 252Cf content emitting mixed neutron + gamma-radiation was accomplished by means of an ANET-B apparatus by the afterloading method. Neutron irradiation is particularly effective in patients with malignant tumors possessing a large fraction of cells in a state of deep anoxia. Dosimetric planning was conducted by means of an original computer system. Devices and radiation-technical equipment for adaptation of the ANET-B apparatus for irradiation of neurosurgical patients are described. The indications for the use of this method and its place among the complex of measures for the treatment of patients with new growths of the brain are discussed. The first experience in using CT-stereotaxic neutron brachytherapy with californium sources on the ANET-B apparatus for the treatment of 6 patients with malignant glial tumors of the brain is dwelt on.

[Computerized system of dosimetric planning of interstitial multiposition stereotaxic irradiation in neutron therapy of brain tumors]. / Kompiuternaia sistema dozimetricheskogo planirovaniia vnutritkanevogo mnogopozitsionnogo stereotaksicheskogo oblucheniia pri neitronnoi terapii opukholei golovnogo mozga.

A computerized system PLUT-B intended for a dosimetric design of stereotaxic neutron brachytherapy of brain tumors, was developed. It is capable of simulating dose distribution in various parameters of irradiation, manipulating them, retaining the surgical aspects within the field of vision, and arriving at an acceptable dosimetric plan. The system permits visualization of a target with an applied dose field in the multiwindow mode, layer-by-layer vision in any direction, displaying a scheme of implantation, and drawing up of maps of isodose distributions. It is intended to be used by a physician, convenient in operation, the time at the design stage is 35-40 minutes.