Anticoagulant treatment in COVID-19: a narrative review

Journal of Thrombosis and Thrombolysis - The actual Coronavirus Disease (COVID 19) pandemic is due to Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a member of the coronavirus...     

Phagocytosis of Hemozoin (Native and Synthetic Malaria Pigment), and Plasmodium falciparum Intraerythrocyte-Stage Parasites by Human and Mouse Phagocytes

Hemozoin, the detoxification product of hemoglobin heme, piles up as electron-dense material in the food vacuole (FV) of intraerythrocytic malaria parasites (malaria pigment). In infected individuals, pigment is internalized by both circulating and resident phagocytes, thus modulating their functions. Synthetic beta-hematin, prepared in vitro from hematin (ferriprotoporphyrin IX hydroxide) in acidic condition, is spectroscopically identical to hemozoin. In this electron microscopy study, native and synthetic hemozoin also prove to be morphologically indistinguishable (large polygonal crystals with apparent transverse banding) and to undergo the same process when internalized by phagocytes (primarily a direct uptake of crystals, similar to what is described for asbestos fibers). On the contrary,whole parasites appear to follow a classical endocytic pathway. This suggests that there may be differences between the ingestion of free particles and whole parasites in terms of modulation of phagocytes' functions.     

Spontaneous and pronase‐induced HER2 truncation increases the trastuzumab binding capacity of breast cancer tissues and cell lines

A subgroup of HER2‐overexpressing breast tumours co‐expresses p95 $^{{\rm{HER2}}}$ , a truncated HER2 receptor that retains a functional HER2 kinase domain but lacks the extracellular domain, thus impairing trastuzumab binding. We evaluated p95 $^{{\rm{HER2}}}$ expression in 99 frozen breast carcinoma samples by western blot analysis. The HER2‐positive cell line BT474 treated with pervanadate or pronase was used as a positive control for p95 $^{{\rm{HER2}}}$ expression. Immunohistochemistry was performed on parallel formalin‐fixed, paraffin‐embedded sections of the same case series using antibodies directed against either the intra‐ or extra‐cellular binding domain of HER2. In particular, biotinylated trastuzumab (BiotHER) was used to evaluate the binding capacity of the humanized antibody. To avoid a subjective evaluation of the score values and the percentage of immunostained cells, the slides were scanned and automatically analysed. The number of cases with HER2 overexpression (score 3+) and HER2 gene amplification was higher in the p185 $^{{\rm{HER2}}}$ ‐positive/p95 $^{{\rm{HER2}}}$ ‐positive samples than in the p185 $^{{\rm{HER2}}}$ ‐positive/p95 $^{{\rm{HER2}}}$ ‐negative group. Automated analysis confirmed a significantly higher percentage of 3+ scored cells in p95 $^{{\rm{HER2}}}$ ‐positive cases. Conversely, the percentage of 2+ scored cells was higher in p95 $^{{\rm{HER2}}}$ ‐negative cases. The status of the HER2 extracellular domain was then studied using flow cytometry on BT474 cells after pronase enzymatic digestion using trastuzumab and pertuzumab, while the presence of HER2‐HER3 dimers was studied using a proximity‐ligation assay. In vitro experiments showed that short‐term pronase digestion of BT474 cells produced two HER2 fragments (of 95 and 150 kDa, detectable in tissue specimens as well), increased the binding affinity of trastuzumab, reduced the rate of HER2–HER3 dimers, and did not interfere with pertuzumab‐binding capacity. In conclusion, the presence of p95 $^{{\rm{HER2}}}$ as detected by western blot analysis does not compromise the immunohistochemical detection of HER2. Our data suggest that a reduction of the receptor steric hindrance as induced by enzymatic shedding may facilitate the binding capacity of trastuzumab. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Y-chromosome polymorphisms and ethnic group – a combined STR and SNP approach in a population sample from northern Italy

Aim

To find an association between Y chromosome polymorphisms and some ethnic groups.

Methods

Short tandem repeats (STR) and single-nucleotide polymorphisms (SNP) on the Y chromosome were typed in 311 unrelated men from four different ethnic groups – Italians from northern Italy, Albanians, Africans from the Maghreb region, and Indo-Pakistanis, using the AmpFlSTR^® Yfiler PCR Amplification Kit and the SNaPshot Multiplex Kit.

Results

STRs analysis found 299 different haplotypes and SNPs analysis 11 different haplogroups. Haplotypes and haplogroups were analyzed and compared between different ethnic groups. Significant differences were found among all the population groups, except between Italians and Indo-Pakistanis and between Albanians and Indo-Pakistanis.

Conclusions

Typing both STRs and SNPs on the Y chromosome could become useful in determining ethnic origin of a potential suspect.Determining the ethnic origin of a suspect through DNA analysis of biological stains left at the crime scene is an important part of criminal investigations. To discriminate between different ethnic groups, short tandem repeat (STR) autosomal marker analysis (1-6) can be complemented by single-nucleotide polymorphism (SNP) assays, which have have been demonstrated to be more useful for this purpose (7,8). The introduction of new markers, mostly from the Y chromosome, offers a better power of discrimination to define even sub-populations of different ethnic groups (9-11). This study aims to compare a sample of Italian men from Brescia (northern Italy) with a sample of men from each of three main ethnic groups living in Brescia county (Albanians, North Africans, Indo-Pakistanis), through STRs and SNPs Y chromosome typing, in order to find the data useful in defining the ethnic origin.     

Open-source open-access reaction time test (OORTT): an easy tool to assess reaction times

Neurological Sciences - The speed of information processing is one of the most reliable indices of cognitive efficiency. The most common way to evaluate this ability is to assess reaction times...     

Panencephalopathic Creutzfeldt‐Jakob Disease with Distinct Pattern of Prion Protein Deposition in a Patient with D178N Mutation and Homozygosity for Valine at Codon 129 of the Prion Protein Gene

Prion diseases include sporadic, acquired and genetic forms linked to mutations of the prion protein (PrP) gene (PRNP). In subjects carrying the D178N PRNP mutation, distinct phenotypes can be observed, depending on the methionine/valine codon 129 polymorphism. We present here a 53‐year‐old woman with D178N mutation in the PRNP gene and homozygosity for valine at codon 129. The disease started at age 47 with memory deficits, progressive cognitive impairment and ataxia. The clinical picture slowly worsened to a state of akinetic mutism in about 2 years and the disease course was 6 years. The neuropathologic examination demonstrated severe diffuse cerebral atrophy with neuronal loss, spongiosis and marked myelin loss and tissue rarefaction in the hemispheric white matter, configuring panencephalopathic Creutzfeldt‐Jakob disease. PrP deposition was present in the cerebral cortex, basal ganglia and cerebellum with diffuse synaptic‐type pattern of immunoreactivity and clusters of countless, small PrP deposits, particularly evident in the lower cortical layers, in the striatum and in the molecular layer of the cerebellum. Western blot analysis showed the presence of type 1 PrP^Sc (Parchi classification). These findings underline the clear‐cut distinction between the neuropathological features of Creutzfeldt‐Jakob disease associated with D178N PRNP mutation and those of fatal familial insomnia.