Predicting biological invasions in marine habitats through eco-physiological mechanistic models: a case study with the bivalve Brachidontes pharaonis

Aim We used a coupled biophysical ecology (BE)-physiological mechanistic modelling approach based on the Dynamic Energy Budget theory (DEB, Dynamic energy budget theory for metabolic organisation, 2010, Cambridge University Press, Cambridge; DEB) to generate spatially explicit predictions of physiological performance (maximal size and reproductive output) for the invasive mussel, Brachidontes pharaonis. Location We examined 26 sites throughout the central Mediterranean Sea. Methods We ran models under subtidal and intertidal conditions; hourly weather and water temperature data were obtained from the Italian Buoy Network, and monthly CHL-a data were obtained from satellite imagery. Results Mechanistic analysis of the B. pharaonis fundamental niche shows that subtidal sites in the Central Mediterranean are generally suitable for this invasive bivalve but that intertidal habitats appear to serve as genetic sinks. Main conclusions A BE-DEB approach enabled an assessment of how the physical environment affects the potential distribution of B. pharaonis. Combined with models of larval dispersal, this approach can provide estimates of the likelihood that an invasive species will become established

Information sources and knowledge on vaccination in a population from southern Italy: The ESCULAPIO project

Vaccine knowledge of the general population is shaped by different information sources and strongly influences vaccination attitudes and uptake. The CCM-Italian Ministry of Health ESCULAPIO project attempted to identify the role of such information sources, in order to address adequate strategies to improve information on vaccines and vaccine preventable diseases. In the present study, data on 632 adults from Southern Italy regarding information sources were collected, and their perceived and actual knowledge on vaccinations were compared and analyzed in relation to socio-demographic characteristics and information sources. The main reported reference sources were general practitioners (GPs) (42.5%) and pediatricians (33.1%), followed by mass media (24.1%) and the Internet (17.6%). A total of 45.4% reported they believed to be informed (45.4%), while those estimated to be truly informed were 43.8%. However, as showed in the multivariate logistic regression, people having the perception to be correctly informed ascribed their good knowledge to their profession in the health sector (Adj OR 2.28, CI 1.09–4.77, p < 0.05) and to friends/relatives/colleagues (AdjOR 6.25, CI 2.38–16.44, p < 0.001), while the non-informed population thought the responsibility had to be attributed to mass media (AdjOR 0.45, CI 0.22–0.92, p < 0.05). Those showing the real correct information, instead, were younger (AdjOR 1.64, CI 1.04–2.59, p < 0.05), and their main reference sources were pediatricians (AdjOR 1.63, CI 1.11–2.39, p < 0.05) and scientific magazines (Adj OR 3.39, CI 1.51–7.59, p < 0.01). Only 6% knew the “VaccinarSì” portal, developed to counter the widespred antivaccine websites in Italy. The post-survey significant increase of connections to “VaccinarSi” could be ascribed to the counselling performed during questionnaire administration. Strategies to improve information about vaccination should be addressed to fortifying healthcare workers knowledge in order to make them public health opinion leaders. General population should be provided with correct indications on trustworthy websites on vaccines to contrast false information supplied by anti-vaccinists on their own websites or social networks pages and on the mass media

LTP and memory impairment caused by extracellular A\u3b2 and Tau oligomers is APP-dependent

The concurrent application of subtoxic doses of soluble oligomeric forms of human amyloid-beta (oA\u3b2) and Tau (oTau) proteins impairs memory and its electrophysiological surrogate long-term potentiation (LTP), effects that may be mediated by intra-neuronal oligomers uptake. Intrigued by these findings, we investigated whether oA\u3b2 and oTau share a common mechanism when they impair memory and LTP in mice. We found that as already shown for oA\u3b2, also oTau can bind to amyloid precursor protein (APP). Moreover, efficient intra-neuronal uptake of oA\u3b2 and oTau requires expression of APP. Finally, the toxic effect of both extracellular oA\u3b2 and oTau on memory and LTP is dependent upon APP since APP-KO mice were resistant to oA\u3b2- and oTau-induced defects in spatial/associative memory and LTP. Thus, APP might serve as a common therapeutic target against Alzheimer's Disease (AD) and a host of other neurodegenerative diseases characterized by abnormal levels of A\u3b2 and/or Tau

Targeting prohibitins induces apoptosis in acute myeloid leukemia cells

Fluorizoline is a new synthetic molecule that induces apoptosis by selectively targeting prohibitins (PHBs). In this study, the pro-apoptotic effect of fluorizoline was assessed in two cell lines and 21 primary samples from patients with debut of acute myeloid leukemia (AML). Fluorizoline induced apoptosis in AML cells at concentrations in the low micromolar range. All primary samples were sensitive to fluorizoline irrespectively of patients' clinical or genetic features. In addition, fluorizoline inhibited the clonogenic capacity and induced differentiation of AML cells. Fluorizoline increased the mRNA and protein levels of the pro-apoptotic BCL-2 family member NOXA both in cell lines and primary samples analyzed. These results suggest that targeting PHBs could be a new therapeutic strategy for AM

A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation

We previously described diaryl trifluorothiazoline compound 1a (hereafter referred to as fluorizoline) as a first-in-class small molecule that induces p53-independent apoptosis in a wide range of tumor cell lines. Fluorizoline directly binds to prohibitin 1 and 2 (PHBs), two proteins involved in the regulation of several cellular processes, including apoptosis. Here we demonstrate that fluorizoline-induced apoptosis is mediated by PHBs, as cells depleted of these proteins are highly resistant to fluorizoline treatment. In addition, BAX and BAK are necessary for fluorizoline-induced cytotoxic effects, thereby proving that apoptosis occurs through the intrinsic pathway. Expression analysis revealed that fluorizoline induced the upregulation of Noxa and Bim mRNA levels, which was not observed in PHB-depleted MEFs. Finally, Noxa-/-/Bim-/- MEFs and NOXA-downregulated HeLa cells were resistant to fluorizoline-induced apoptosis. All together, these findings show that fluorizoline requires PHBs to execute the mitochondrial apoptotic pathway

Sindrome della morte improvvisa del lattante (SIDS) in Sicilia: una valutazione dei principali determinanti di accudimento

Aim: to evaluate certain caring behaviors associated with the onset of sudden infant death syndrome (SIDS). Methods: a telephone questionnaire was administered between May and July 2017 to a sample of 1055 Sicilian mothers within 30 days of delivery. A multivariate logistic analysis was conducted considering outcome variables: the sleeping position of the children, exclusive breastfeeding and passive smoking. Results: 62% of the participants place their children in the supine position, 37.9% practice exclusive breastfeeding and 89.0% are not smokers. Being aged &lt; 32 years, having a low level of education and limited economic resources are risk factors for the non-supine positioning of children during sleep. A low level of education, primiparity, non-participation to an antenatal course expose mothers to a greater risk of not practicing exclusive breastfeeding at one month. Postpartum smoking is positively associated with a low level of education. Conclusions: the assessment of the main caring behaviors towards newborns and infants is essential for an effective campaign for reducing the risk of SIDS

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

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Performance of the ALICE experiment at the CERN LHC

ALICE is the heavy-ion experiment at the CERN Large Hadron Collider. The experiment continuously took data during the first physics campaign of the machine from fall 2009 until early 2013, using proton and lead-ion beams. In this paper we describe the running environment and the data handling procedures, and discuss the performance of the ALICE detectors and analysis methods for various physics observables