The Onset and Solidification Path of a Basaltic Melt by in situ Differential Scanning Calorimetry (DSC) and ex situ Investigations

The in situ differential scanning calorimetry (DSC) technique has been applied to investigate the solidification paths of a basaltic liquid. The starting glass was heated up to 1300°C, kept at this superliquidus temperature for 2 h and cooled at rates (ΔT/Δt) of 7, 60, 180, 1000, and 1800°C/h, down to 800 and 600°C. Glass transition temperature (Tg), crystallization temperature (Tx_HR) and melting temperature (Tm) were measured by in situ DSC spectra on heating. Tx measured along the cooling paths (Tx_CR) shows exothermic peaks that change from a single symmetric shape (7 and 60°C/h) to multi-component patterns (180, 1000, and 1800°C/h). The recovered products characterized by field emission gun source of the scanning electron microscopy and electron probe micro-analyzer-wavelength dispersive spectrometers show a phase assemblage of spinel (sp), clinopyroxene (cpx), melilite (mel), plagioclase (plg), and glass. Moreover, crystal size distributions (CSDs) and growth rates (Gmax and GCSD) were also determined. The crystal content slightly increases from 7 to 1800°C/h. Faceted sp are present in all the run products with an amount always <2 area%. Cpx increases from 7 to 1800°C/h, changing its texture from almost faceted to dendritic between 60 and 180°C/h. The area% of mel follows an asymmetric Gaussian trend, while plg nucleates only at 7°C/h with a content <2 area%. The coupling of DSC and SEM outcomes indicate that sp nucleate first, followed by cpx and mel (and/or plg). The increment of ΔT/Δt causes an increase of the CSD slope (m) and crystal population density per size (n0), as well as a decrease of the crystal size, for both cpx and sp. The log-linear CSD segments with different slopes at 7 and 60°C/h suggest multiple nucleation events and crystal growth by coarsening. Gmax and GCSD for cpx and sp directly measured on the actual crystallization time by DSC spectra, both increase with the increasing of ΔT/Δt. The onset temperature of crystallization (Txi) decreases as ΔT/Δt increases, following an exponential trend that defines the uppermost portion of a time-transformation-temperature-like curve. This analytical model allows us to quantitatively model the kinetic crystallization paths of dry basalts

Assessment of Human Papillomavirus in Lung Tumor Tissue

Background Lung cancer kills more than 1 million people worldwide each year. Whereas several human papillomavirus (HPV)-associated cancers have been identified, the role of HPV in lung carcinogenesis remains controversial. Methods We selected 450 lung cancer patients from an Italian population-based case-control study, the Environment and Genetics in Lung Cancer Etiology. These patients were selected from those with an adequate number of unstained tissue sections and included all those who had never smoked and a random sample of the remaining patients. We used real-time polymerase chain reaction (PCR) to test specimens from these patients for HPV DNA, specifically for E6 gene sequences from HPV16 and E7 gene sequences from HPV18. We also tested a subset of 92 specimens from all never-smokers and a random selection of smokers for additional HPV types by a PCR-based test for at least 54 mucosal HPV genotypes. DNA was extracted from ethanol- or formalin-fixed paraffin-embedded tumor tissue under strict PCR clean conditions. The prevalence of HPV in tumor tissue was investigated. Results Specimens from 399 of 450 patients had adequate DNA for analysis. Most patients were current (220 patients or 48.9%) smokers, and 92 patients (20.4%) were women. When HPV16 and HPV18 type-specific primers were used, two specimens were positive for HPV16 at low copy number but were negative on additional type-specific HPV16 testing. Neither these specimens nor the others examined for a broad range of HPV types were positive for any HPV type. Conclusions When DNA contamination was avoided and state-of-the-art highly sensitive HPV DNA detection assays were used, we found no evidence that HPV was associated with lung cancer in a representative Western population. Our results provide the strongest evidence to date to rule out a role for HPV in lung carcinogenesis in Western populations

The Polycomb BMI1 Protein Is Co-expressed With CD26+ in Leukemic Stem Cells of Chronic Myeloid Leukemia

The Polycomb gene BMI1 expression exerts a negative predictive impact on several hematological malignancies, such as acute and chronic myeloid leukemia (CML), myelofibrosis, and follicular lymphoma. As already demonstrated in CML, BMI1 is responsible for the resistance to the tyrosine kinase inhibitors (TKIs) in a BCR-ABL1-independent way. Even if, it is unknown where BMI1 in CML is expressed (in progenitors or more mature cells). We decided, therefore, to evaluate if and where the BMI1 protein is located, focusing mainly on the CD34+/CD38-/CD26+ CML progenitors. To begin we measured, by flow cytometry, the proportion of CD34+/CD26+ cells in 31 bone marrow samples from 20 CML patients, at diagnosis and during treatment with imatinib. After that the bone marrow blood smears were stained with antibodies anti-CD26, BCR-ABL1, and BMI1. These smears were observed by a confocal laser microscope and a 3D reconstruction was then performed. At diagnosis, CD34+/CD26+ cells median value/μL was 0.48; this number increased from diagnosis to the third month of therapy and then reduced during treatment with imatinib. The number and behavior of the CD26+ progenitors were independent from the BCR-ABL1 expression, but they summed up what previously observed about the BMI1 expression modulation. In this work we demonstrate for the first time that in CML the BMI1 protein is co-expressed with BCR-ABL1 only in the cytoplasm of the CD26+ precursors; on the contrary, in other hematological malignancies where BMI1 is commonly expressed (follicular lymphoma, essential thrombocytemia, acute myeloid leukemia), it was not co-localized with CD26 or, obviously, with BCR-ABL1. Once translated into the clinical context, if BMI1 is a marker of stemness, our results would suggest the combination of the BMI1 inhibitors with TKIs as an interesting object of research, and, probably, as a promising way to overcome resistance in CML patients

Induction of apoptosis of human primary osteoclasts treated with extracts from the medicinal plant Emblica officinalis

<p>Abstract</p> <p>Background</p> <p>Osteoclasts (OCs) are involved in rheumatoid arthritis and in several pathologies associated with bone loss. Recent results support the concept that some medicinal plants and derived natural products are of great interest for developing therapeutic strategies against bone disorders, including rheumatoid arthritis and osteoporosis. In this study we determined whether extracts of <it>Emblica officinalis </it>fruits display activity of possible interest for the treatment of rheumatoid arthritis and osteoporosis by activating programmed cell death of human primary osteoclasts.</p> <p>Methods</p> <p>The effects of extracts from <it>Emblica officinalis </it>on differentiation and survival of human primary OCs cultures obtained from peripheral blood were determined by tartrate-acid resistant acid phosphatase (TRAP)-positivity and colorimetric MTT assay. The effects of <it>Emblica officinalis </it>extracts on induction of OCs apoptosis were studied using TUNEL and immunocytochemical analysis of FAS receptor expression. Finally, <it>in vitro </it>effects of <it>Emblica officinalis </it>extracts on NF-kB transcription factor activity were determined by gel shift experiments.</p> <p>Results</p> <p>Extracts of <it>Emblica officinalis </it>were able to induce programmed cell death of mature OCs, without altering, at the concentrations employed in our study, the process of osteoclastogenesis. <it>Emblica officinalis </it>increased the expression levels of Fas, a critical member of the apoptotic pathway. Gel shift experiments demonstrated that <it>Emblica officinalis </it>extracts act by interfering with NF-kB activity, a transcription factor involved in osteoclast biology. The data obtained demonstrate that <it>Emblica officinalis </it>extracts selectively compete with the binding of transcription factor NF-kB to its specific target DNA sequences. This effect might explain the observed effects of <it>Emblica officinalis </it>on the expression levels of interleukin-6, a NF-kB specific target gene.</p> <p>Conclusion</p> <p>Induction of apoptosis of osteoclasts could be an important strategy both in interfering with rheumatoid arthritis complications of the bone skeleton leading to joint destruction, and preventing and reducing osteoporosis. Accordingly, we suggest the application of <it>Emblica officinalis </it>extracts as an alternative tool for therapy applied to bone diseases.</p

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

We-Measure: Toward a low-cost portable posturography for patients with multiple sclerosis using the commercial Wii balance board

This study was aimed at investigating whether postural sway measures derived from a standard force platform were similar to those generated by a custom-written software (“We-Measure”) acquiring and processing data from a commercial Nintendo balance board (BB). For this purpose, 90 patients with multiple sclerosis (MS) and 50 healthy controls (HC) were tested in a single-day session with a reference standard force platform and a BB-based system. Despite its acceptable between-device agreement (tested by visual evaluation of Bland–Altman plot), the low-cost BB-based system tended to overestimate postural sway when compared to the reference standard force platform in both MS and HC groups (on average +30% and +54%, respectively). Between-device reliability was just adequate (MS: 66%, HC: 47%), while test–retest reliability was excellent (MS: 84%, HC: 88%). Concurrent validity evaluation showed similar performance between the reference standard force platform and the BB-based system in discriminating fallers and non-fallers among patients with MS. All these findings may encourage the use of this balance board-based new device in longitudinal study, rather than in cross-sectional design, thus providing a potential useful tool for multicenter settings

OXA-46, a New Class D β-Lactamase of Narrow Substrate Specificity Encoded by a bla(VIM-1)-Containing Integron from a Pseudomonas aeruginosa Clinical Isolate

A novel OXA-type enzyme, named OXA-46, was found to be encoded by a gene cassette inserted into a class 1 integron from a multidrug-resistant Pseudomonas aeruginosa clinical isolate. The variable region of the integron also contained a bla(VIM-1) metallo-β-lactamase cassette and a duplicated aacA4 aminoglycoside acetyltransferase cassette. OXA-46 belongs to the OXA-2 lineage of class D β-lactamases. It exhibits 78% sequence identity with OXA-2 and the highest similarity (around 92% identity) with another OXA-type enzyme detected in clinical isolates of Burkholderia cepacia and in unidentified bacteria from a wastewater plant. Expression of bla(OXA-46) in Escherichia coli decreased susceptibility to penicillins and narrow-spectrum cephalosporins but not to extended-spectrum cephalosporins, cefsulodin, aztreonam, or carbapenems. The enzyme was overproduced in E. coli and purified by two anion-exchange chromatography steps (approximate yield, 6 mg/liter). OXA-46 was made of a 28.5-kDa polypeptide and exhibited an alkaline pI (7.8). In its native form OXA-46 appeared to be dimeric, and the oligomerization state was not affected by EDTA. Kinetic analysis of OXA-46 revealed a specificity for narrow-spectrum substrates, including oxacillin, other penicillins (but not temocillin), and narrow-spectrum cephalosporins. The enzyme apparently did not interact with temocillin, oxyimino-cephalosporins, or aztreonam. OXA-46 was inactivated by tazobactam and carbapenems and, although less efficiently, also by clavulanic acid. Enzyme activity was not affected either by EDTA or by divalent cations and exhibited low susceptibility to NaCl. These findings underscore the functional and structural diversity that can be encountered among class D β-lactamases

Investigation into the Allylation Reactions of Aldehydes Promoted by CeCl3·7H2O-NaI System as a Lewis Acid

The Lewis acid promoted allylation of aldehydes has become an important carbon−carbon bond forming reaction in organic chemistry. In this context, we have developed an alternative over existing catalytic processes, wherein aldehydes are subject in acetonitrile to reaction of allylation with allyltributylstannane in the presence of 1.0 equiv of cerium(III) chloride heptahydrate (CeCl3·7H2O), an inexpensive and mild Lewis acid. The allylation has been accelerated by using an inorganic iodide as a cocatalyst, and various iodide salts were examined. The procedure must use allylstannane reagent instead of allylsilane reagent, desirable for environmental reasons, but high chemoselectivity was observed, and this is opposite the results obtained with other classical Lewis acids such as TiCl4 and Et2O·BF3