The miR-28-5p Targetome Discovery Identified SREBF2 as One of the Mediators of the miR-28-5p Tumor Suppressor Activity in Prostate Cancer Cells

miR-28-5p is downregulated in some tumor tissues in which it has been demonstrated to have tumor suppressor (TS) activity. Here, we demonstrate that miR-28-5p acts as a TS in prostate cancer (PCa) cells affecting cell proliferation/survival, as well as migration and invasion. Using the miRNA pull out assay and next generation sequencing, we collected the complete repertoire of miR-28-5p targets, obtaining a data set (miR-28-5p targetome) of 191 mRNAs. Filtering the targetome with TargetScan 7, PITA and RNA22, we found that 61% of the transcripts had miR-28-5p binding sites. To assign a functional value to the captured transcripts, we grouped the miR-28-5p targets into gene families with annotated function and showed that six transcripts belong to the transcription factor category. Among them we selected SREBF2, a gene with an important role in PCa. We validated miR-28-5p/SREBF2 interaction, demonstrating that SREBF2 inhibition affects almost all the tumor processes altered by miR-28-5p re-expression, suggesting that SREBF2 is an important mediator of miR-28-5p TS activity. Our findings support the identification of the targetome of cancer-related miRNAs as a tool to discover genes and pathways fundamental for tumor development, and potential new targets for anti-tumor therapy

The Dust-to-Gas Ratio in the Small Magellanic Cloud Tail

The Tail region of the Small Magellanic Cloud (SMC) was imaged using the MIPS instrument on the Spitzer Space Telescope as part of the SAGE-SMC Spitzer Legacy. Diffuse infrared emission from dust was detected in all the MIPS bands. The Tail gas-to-dust ratio was measured to be 1200 +/- 350 using the MIPS observations combined with existing IRAS and HI observations. This gas-to-dust ratio is higher than the expected 500-800 from the known Tail metallicity indicating possible destruction of dust grains. Two cluster regions in the Tail were resolved into multiple sources in the MIPS observations and local gas-to-dust ratios were measured to be ~440 and ~250 suggests dust formation and/or significant amounts of ionized gas in these regions. These results support the interpretation that the SMC Tail is a tidal tail recently stripped from the SMC that includes gas, dust, and young stars.Comment: 6 pages, 3 figures, ApJ Letters, in press, (version with full resolution figures at http://www.stsci.edu/~kgordon/papers/PS_files/sage-smc_taildust_v1.62.pdf

Evidence for dust evolution within the Taurus Complex from Spitzer images

We present Spitzer images of the Taurus Complex (TC) and take advantage of the sensitivity and spatial resolution of the observations to characterize the diffuse IR emission across the cloud. This work highlights evidence of dust evolution within the translucent sections of the archetype reference for studies of quiescent molecular clouds. We combine Spitzer 160 um and IRAS 100 um observations to produce a dust temperature map and a far-IR dust opacity map at 5' resolution. The average dust temperature is about 14.5K with a dispersion of +/-1K across the cloud. The far-IR dust opacity is a factor 2 larger than the average value for the diffuse ISM. This opacity increase and the attenuation of the radiation field (RF) both contribute to account for the lower emission temperature of the large grains. The structure of the TC significantly changes in the mid-IR images that trace emission from PAHs and VSGs. We focus our analysis of the mid-IR emission to a range of ecliptic latitudes where the zodiacal light residuals are small. Within this cloud area, there are no 8 and 24 um counterparts to the brightest 160 um emission features. Conversely, the 8 and 24 um images reveal filamentary structure that is strikingly inconspicuous in the 160 um and extinction maps. The IR colors vary over sub-parsec distances across this filamentary structure. We compare the observed colors with model calculations quantifying the impact of the RF intensity and the abundance of stochastically heated particles on the dust SED. To match the range of observed colors, we have to invoke variations by a factor of a few of both the interstellar RF and the abundance of PAHs and VSGs. We conclude that within this filamentary structure a significant fraction of the dust mass cycles in and out the small size end of the dust size distribution.Comment: 43 pages, 13 figures, accepted for publication in Ap

Serogroup C meningococci in Italy in the era of conjugate menC vaccination

<p>Abstract</p> <p>Background</p> <p>To assess changes in the pattern of Invasive Meningococcal Disease (IMD) in Italy after the introduction of conjugate menC vaccine in the National Vaccine Plan 2005–2007 and to provide information for developing timely and appropriate public health interventions, analyses of microbiological features of isolates and clinical characteristics of patients have been carried out. In Italy, the number of serogroup C meningococci fell progressively following the introduction of the MenC conjugate vaccine, recommended by the Italian Ministry of Health but implemented according to different regional strategies.</p> <p>Methods</p> <p>IMD cases from January 2005 through July 2008 reported to the National Meningococcal Surveillance System were considered for this study. Serogrouping and sero/subtyping were performed on 179 serogroup C strains received at the National Reference Laboratory of the Istituto Superiore di Sanità. Antibiotic susceptibility testing was possible for 157 isolates. MLST (Multilocus sequence typing), <it>por</it>A VRs (Variable Region) typing, PFGE (Pulsed Field Gel Electrophoresis), VNTR (Variable Number Tandem Repeats) analyses were performed on all C:2a and C:2b meningococci (n = 147), following standard procedures.</p> <p>Results</p> <p>In 2005 and 2008, IMD showed an incidence of 0.5 and 0.3 per 100,000 inhabitants, respectively. While the incidence due to serogroup B remained stable, IMD incidence due to serogroup C has decreased since 2006. In particular, the decrease was significant among infants. C:2a and C:2b were the main serotypes, all C:2a strains belonged to ST-11 clonal complex and all C:2b to ST-8/A4. Clinical manifestations and outcome of infections underlined more severe disease caused by C:2a isolates. Two clusters due to C:2a/ST-11 meningococci were reported in the North of Italy in December 2007 and July 2008, respectively, with a high rate of septicaemia and fatal outcome.</p> <p>Conclusion</p> <p>Public health surveillance of serogroup C invasive meningococcal disease and microbiological/molecular characterization of the isolates requires particular attention, since the hyper-invasive ST-11 predominantly affected adolescents and young adults for whom meningococcal vaccination was not recommended in the 2005–2007 National Vaccine Plan.</p

Physical Conditions in the Ionized Gas of 30 Doradus

We present a mid-infrared spectroscopic data cube of the central part of 30 Doradus, observed with Spitzer's IRS and MIPS/SED mode. Aromatic dust emission features and emission lines from molecular and atomic hydrogen are detected but not particularly strong. The dominant spectral features are emission lines from moderately ionized species of argon, neon, and sulphur, which are used to determine the physical conditions in the ionized gas. The ionized gas excitation shows strong variations on parsec scales, some of which can plausibly be associated with individual hot stars. We fit the ionic line strengths with photoionization and shock models, and find that photoionization dominates in the region. The ionization parameter U traces the rim of the central bubble, as well as highlighting isolated sources of ionization, and at least one quiescent clump. The hardness of the ionizing radiation field T_rad reveals several "hot spots" that are either the result of individual very hot stars or trace the propagation of the diffuse ionizing field through the surrounding neutral cloud. Consistent with other measurements of giant molecular hydrogen regions, log(U) ranges between -3 and -0.75, and T_rad between 30000 and 85000K.Comment: 32 pages, 26 figures, ApJ accepted. A version with high-resolution images can be found at http://www.astro.virginia.edu/~ged3j/indebetouw20090125.pd

Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p &lt; 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p &lt; 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p &lt; 0.0001) or urgent (20.4% vs. 38.5%; p &lt; 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p &lt; 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. Methods: The STAR Network \u201cDepot Study\u201d was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS &lt; 41 or BPRS 65 41). Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions\u2014conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently\u2014showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline. Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders