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Thermodynamics and kinetics of ion translocation in the human wild-type and E-1' A α7 nicotinic receptor
No full textWe use an all-atom model of the human nicotinic acetylcholine receptor α7 in a conductive conformation, to provide the first available mapping of the potential of mean force for the ion translocation across the channel. The modeling is based on MD simulations combined with the milestoning method with Voronoi tessellation. The quality of the protein model and description is confirmed by the agreement with experimental data for proteins of the same family. The specific mutation E-1' A at the cytoplasmatic filter is here shown to strongly affect both sodium and chloride permeation, leading to a complete inversion of selectivit
In vivo validation of time domain optical mammograph with high-sensitivity detection chain
No full textOptical mammography is an application of diffuse optics that combines the advantages of cost-effectiveness, non-invasiveness, no significant dependence on breast density and capability to derive information about breast composition. Literature reports promising preliminary results when employed for breast cancer risk assessment, lesion characterisation, therapy monitoring and prediction
of therapy outcome. In view of a clinical trial on the monitoring of neoadjuvant chemotherapy, we upgraded our time domain multi-wavelength optical mammograph
exploiting new technology based on silicon photomultipliers and high throughput time-to-digital conversion. The setup is presented, together with the validation of its performances via laboratory and in vivo test
Collagen micro-architecture investigation in tumor sections by means of second-harmonic generation signal multiphasor analysis coupled with non-supervised machine learning techniques
No full textCollagen organization changes with the tissue pathological conditions, like cancer, and can be monitored through Second-Harmonic Generation imaging, a label-free method sensitive to the fibrils microstructure. As a consequence,
collagen can be exploited as an early-tumor diagnosis marker. Coupling a phasorbased method with a non-supervised machine learning algorithm, our protocol is
able to map pixel by pixel crucial features of the collagen fibrils and enlighten different collagen organizations. Basing on these maps, our protocol can automatically
discriminate, on fixed tumor sections, tumor area from the surrounding tissue with an accuracy of ∼ 90%, opening the possibility to effectively assist histopathologists
in cancer diagnosis
PAPRICA: The PAir PRoduction Imaging ChAmber
No full textIn the treatment of tumours with charged particle beams, several factors introduce uncertainties in predicting the beam range in the biological tissue. In the treatment planning, safety margins of several millimetres are added to the volume to be treated in order to avoid under-dosage of the tumour. Beam range monitoring techniques have been proposed and studied in order to reduce safety margins and ensure safer treatments. Some of these techniques detect secondary radiation emitted during beam-tissue interaction. The aim of the PAir PRoduction Imaging ChAmber project is to demonstrate the feasibility of a range monitoring technique based on secondary prompt-gamma radiation, detected by means of the pair production mechanism. The project results presented at the SIF Congress 2020 were deepened and updated with new Monte Carlo simulations
Intercostal Muscle Cavernous Haemangioma: A Chest Wall Pandora’s Box
Get PDFBackground: Haemangiomas are uncommon chest wall tumours arising outside the rib cage. Their occurrence in intercostal muscle is extremely rare.Aim: We describe a case of intercostal muscle cavernous haemangioma as a differential diagnosis for chest wall swelling.Case description: We describe an 18-year-old male patient with an asymptomatic left-sided chest wall swelling. Contrast-enhanced computed tomography revealed a well-defined homogenously non-enhancing mass lesion arising from the seventh intercostal muscle with differential diagnoses of various chest wall tumours. Clinical presentation and imaging findings were inconclusive, but histopathological examination following excision biopsy revealed a cavernous haemangioma. The present case emphasizes the importance of histopathological diagnosis when clinical and radiological examination is inconclusive. Hence, it is necessary to consider intercostal muscle haemangiomas as a differential diagnosis for chest wall tumours in the absence of a feeding vessel. Conclusion: Despite its rare occurrence, intercostal muscle haemangioma must be considered as a differential diagnosis in chest wall tumours even in the absence of a feeding vessel. We believe that histopathology can provide a definitive diagnosis when most investigative procedures are inconclusive
Ceftriaxone-induced Agranulocytosis
Get PDFCeftriaxone is a widely used antibiotic regarded as safe and effective. Drug-induced agranulocytosis is a life-threatening adverse reaction and few reports related to ceftriaxone were found in a review of the literature. The authors present a case of ceftriaxone-induced agranulocytosis, in which a brain abscess was diagnosed and ceftriaxone was commenced. Neutropenic fever occurred on the 29th day of therapy with a cumulative dose of 116 g ceftriaxone and a neutrophil nadir of 0.1×109/l. Ceftriaxone was withheld, filgrastim was administered for 3 days and neutrophil normalization was achieved. Although rare, ceftriaxone-induced agranulocytosis may occur in patients on a long course of ceftriaxone therapy. Prompt recognition and drug withdrawal are required
Should CD4 Levels be Monitored in a Patient on Temozolomide?
Get PDFIntroduction:
Temozolomide is an alkylating agent, indicated in the treatment of refractory anaplastic astrocytoma and newly diagnosed glioblastoma. We describe a case of Salmonella typhimurium bacteraemia associated with septic arthritis in the setting of concurrent temozolomide use.
Case:
A 67-year-old woman presented with acute onset of bilateral knee pain and swelling. She had a medical history of glioblastoma multiforme treated with temozolomide. Synovial fluid analysis and blood cultures revealed S. typhimurium, confirming a diagnosis of S. typhimurium bacteraemia associated with septic arthritis.
Conclusion:
We conclude that chemotherapy with temozolomide and corticosteroid use will increase an individual’s susceptibility to a wide variety of opportunistic infections akin to HIV-associated acquired immunodeficiency syndrome (AIDS). Furthermore, we hypothesize a possible benefit of monitoring CD4 levels and prophylaxis against opportunistic infections (based on the CD4 levels) in individuals receiving temozolomide-based chemotherapy, similar to HIV-AIDS
A 29-year-old Bodybuilder with Liothyronine-induced Thyrotoxic Hypokalaemic Periodic Paralysis
Get PDFWe describe a 29-year-old male bodybuilder with recurrent attacks of myalgia and muscle weakness associated with hypokalaemia and thyrotoxicosis due to abuse of liothyronine. The attacks quickly resolved after potassium supplementation and liothyronine cessation. We concluded that the patient had thyrotoxic hypokalaemic periodic paralysis (TPP). Although muscle weakness and hypokalaemia are
prominent symptoms of TPP, underlying thyrotoxicosis may be overlooked. Up to 25% of androgen abusers also abuse thyroid hormone. Lack of recognition of thyroid hormone abuse as a cause of hypokalaemic periodic paralysis may result in unnecessary, potentially harmful
medical investigations and improper treatment and advice
Disseminated Blastomycosis Presenting with Spontaneous Coronary Artery Dissection
Get PDFSpontaneous coronary artery dissection (SCAD) is increasingly recognized as an important cause of acute coronary syndrome (ACS) and myocardial infarction (MI) in individuals with few or no known atherosclerotic risk factors. While systemic autoimmune inflammatory disorders are associated with precipitating SCAD, the role of infection-induced systemic inflammation in SCAD is not well defined. We present the case of a 49-year-old Caucasian woman with ST-elevation myocardial infarction (STEMI) diagnosed as SCAD from a severe systemic inflammatory response related to disseminated blastomycosis. Punch biopsy of a skin lesion and synovial fluid culture confirmed Blastomyces dermatitidis. This case suggests the possibility of systemic infection-induced inflammation as a precipitating factor in SCAD pathogenesis similar to autoimmune inflammatory disorders
IgG4-Related Disease Affecting Testicle and Myelodysplastic Syndrome: Just a Coincidence?
Get PDFImmunoglobulin G4-related disease (IgG4-RD) is progressive immune-mediated fibrotic condition characterised by a tendency to form tumefactive lesions in different organs and by elevated IgG4 serum concentrations. Urological manifestations are rare and normally occur together with other systemic affections. Myelodysplastic syndromes (MDS) are hematopoietic stem cell neoplasms, with different subtypes based on the type of blood cells involved. MDS can be associated with other pathologies or medical treatments. We present an uncommon case of testicular manifestation associated with myelodysplastic syndrome here