The new phylogenesis of the genus Mycobacterium

Abstract Phylogenetic knowledge of the genus Mycobacterium is based on comparative analysis of their genetic sequences. The 16S rRNA has remained for many years the only target of such analyses, but in the last few years, other housekeeping genes have been investigated and the phylogeny based on their concatenated sequences become a standard. It is now clear that the robustness of the phylogenetic analysis is strictly related to the size of the genomic target used. Whole genome sequencing (WGS) is nowadays becoming widely accessible and comparatively cheap. It was decided, therefore, to use this approach to reconstruct the ultimate phylogeny of the genus Mycobacterium . Over 50 types of strains of the same number of species of Mycobacterium were sequenced using the Illumina HiSeq platform. The majority of the strains of which the whole sequence was already available in GenBank were excluded from this panel with the aim of maximizing the number of the species with genome available. Following assembling and annotation with proper software, the phylogenetic analysis was conducted with PhyloPhlAn and the pan-genome analysis pipeline. The phylogenetic three which emerged was characterized by a clear-cut distinction of slowly and rapidly growing species with the latter being more ancestral. The species of the Mycobacterium terrae complex occupied an intermediate position between rapid and slow growers. Most of the species revealed clearly related and occupied specific phylogenetic branches. Thanks to the WGS technology, the genus Mycobacterium is finally approaching its definitive location

Heterogeneity in circulating tumor cells : the relevance of the stem-cell subset

The release of circulating tumor cells (CTCs) into vasculature is an early event in the metastatic process. The analysis of CTCs in patients has recently received widespread attention because of its clinical implications, particularly for precision medicine. Accumulated evidence documents a large heterogeneity in CTCs across patients. Currently, the most accepted view is that tumor cells with an intermediate phenotype between epithelial and mesenchymal have the highest plasticity. Indeed, the existence of a meta-stable or partial epithelial⁻mesenchymal transition (EMT) cell state, with both epithelial and mesenchymal features, can be easily reconciled with the concept of a highly plastic stem-like state. A close connection between EMT and cancer stem cells (CSC) traits, with enhanced metastatic competence and drug resistance, has also been described. Accordingly, a subset of CTCs consisting of CSC, present a stemness profile, are able to survive chemotherapy, and generate metastases after xenotransplantation in immunodeficient mice. In the present review, we discuss the current evidence connecting CTCs, EMT, and stemness. An improved understanding of the CTC/EMT/CSC connections may uncover novel therapeutic targets, irrespective of the tumor type, since most cancers seem to harbor a pool of CSCs, and disclose important mechanisms underlying tumorigenicity

explorative study on the use of omalizumab in patients suffering from interstitial cystitis bladder pain syndrome

The aim of this study was to evaluate the efficacy of omalizumab in the treatment of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS), evaluated by visual analogue score for pain and urgency- frequency, O'Leary-Sant IC symptom and problem index questionnaire, Pain Urgency Frequency questionnaire and Patient Global Assessment questionnaire. Four female patients with a diagnosis of IC/BPS were included in the study, with an age between 20 and 39 years. In the first patient the subjective final evaluation was of a marked improvement. The second patient had a moderate improvement of the subjective final evaluation. The third patient considered her overall clinical situation to have slightly improved after treatment. One 32-year-old patient, with multiple allergies, discontinued treatment after 3 months and could not complete the study due to side effects. Omalizumab was subcutaneously administered to patients with IC/PBS; it induced both a subjective and objective improvement of symptoms in 2 patients enrolled in the study

Loss of miR-204 expression is a key event in melanoma

Cutaneous melanoma (CM) is a malignancy with increasing occurrence. Its microRNA repertoire has been defined in a number studies, leading to candidates for biological and clinical relevance: miR-200a/b/c, miR-203, miR-205, miR-204, miR-211, miR-23b and miR-26a/b. Our work was aimed to validate the role of these candidate miRNAs in melanoma, using additional patients cohorts and in vitro cultures. miR-26a, miR-204 and miR-211 were more expressed in normal melanocytes, while miR-23b, miR-200b/c, miR-203 and miR-205 in epidermis and keratinocytes. None of the keratinocyte-related miRNAs was associated with any known mutation or with clinical covariates in melanoma. On the other hand, the loss of miR-204 was enriched in melanomas with NRAS sole mutation (Fisher exact test, P = 0.001, Log Odds = 1.67), and less frequent than expected in those harbouring CDKN2A mutations (Fisher exact test, P = 0.001, Log Odds − 1.09). Additionally, miR-204 was associated with better prognosis in two independent melanoma cohorts and its exogenous expression led to growth impairment in melanoma cell lines. Thus, miR-204 represents a relevant mechanism in melanoma, with potential prognostic value and its loss seems to act in the CDKN2A pathway, in cooperation with NRAS

The Novel Mouse Mutation Oblivion Inactivates the PMCA2 Pump and Causes Progressive Hearing Loss

Progressive hearing loss is common in the human population, but we have few clues to the molecular basis. Mouse mutants with progressive hearing loss offer valuable insights, and ENU (N-ethyl-N-nitrosourea) mutagenesis is a useful way of generating models. We have characterised a new ENU-induced mouse mutant, Oblivion (allele symbol Obl), showing semi-dominant inheritance of hearing impairment. Obl/+ mutants showed increasing hearing impairment from post-natal day (P)20 to P90, and loss of auditory function was followed by a corresponding base to apex progression of hair cell degeneration. Obl/Obl mutants were small, showed severe vestibular dysfunction by 2 weeks of age, and were completely deaf from birth; sensory hair cells were completely degenerate in the basal turn of the cochlea, although hair cells appeared normal in the apex. We mapped the mutation to Chromosome 6. Mutation analysis of Atp2b2 showed a missense mutation (2630C→T) in exon 15, causing a serine to phenylalanine substitution (S877F) in transmembrane domain 6 of the PMCA2 pump, the resident Ca2+ pump of hair cell stereocilia. Transmembrane domain mutations in these pumps generally are believed to be incompatible with normal targeting of the protein to the plasma membrane. However, analyses of hair cells in cultured utricular maculae of Obl/Obl mice and of the mutant Obl pump in model cells showed that the protein was correctly targeted to the plasma membrane. Biochemical and biophysical characterisation showed that the pump had lost a significant portion of its non-stimulated Ca2+ exporting ability. These findings can explain the progressive loss of auditory function, and indicate the limits in our ability to predict mechanism from sequence alone

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Demanding Diagnosis of Splenic Angiosarcoma as Cause of Delayed Treatment of Spontaneous Splenic Rupture: A Case Report and Literature Review

Background. Primary splenic angiosarcoma is a very rare mesenchymal malignant tumor associated with a poor prognosis due to its high metastatic potential. This disease can be easily neglected and spontaneous splenic rupture is a frequent manifestation at the time of diagnosis leading to a poor outcome because of peritoneal dissemination. Case Presentation. We describe the case of a 49-year-old man who presented with asthenia, left upper quadrant abdominal pain, and anemia. Computerized tomography scan showed an enlarged spleen with no nodules and a nontraumatic rupture of the splenic capsule. Splenectomy was performed on account of the severe anemia and histopathology examination showed a primary angiosarcoma. Conclusions. Splenic angiosarcoma should be considered as one of the differential diagnoses in patients with nontraumatic spleen rupture and a specific previous medical history. Regrettably, splenectomy allows for a definitive diagnosis but not a curative treatment

Demanding Diagnosis of Splenic Angiosarcoma as Cause of Delayed Treatment of Spontaneous Splenic Rupture: A Case Report and Literature Review

Background. Primary splenic angiosarcoma is a very rare mesenchymal malignant tumor associated with a poor prognosis due to its high metastatic potential. This disease can be easily neglected and spontaneous splenic rupture is a frequent manifestation at the time of diagnosis leading to a poor outcome because of peritoneal dissemination. Case Presentation. We describe the case of a 49-year-old man who presented with asthenia, left upper quadrant abdominal pain, and anemia. Computerized tomography scan showed an enlarged spleen with no nodules and a nontraumatic rupture of the splenic capsule. Splenectomy was performed on account of the severe anemia and histopathology examination showed a primary angiosarcoma. Conclusions. Splenic angiosarcoma should be considered as one of the differential diagnoses in patients with nontraumatic spleen rupture and a specific previous medical history. Regrettably, splenectomy allows for a definitive diagnosis but not a curative treatment