Alzheimer's Proteins, Oxidative Stress, and Mitochondrial Dysfunction Interplay in a Neuronal Model of Alzheimer's Disease

In this paper, we discuss the interplay between beta-amyloid (Aβ) peptide, Tau fragments, oxidative stress, and mitochondria in the neuronal model of cerebellar granule neurons (CGNs) in which the molecular events reminiscent of AD are activated. The identification of the death route and the cause/effect relationships between the events leading to death could be helpful to manage the progression of apoptosis in neurodegeneration and to define antiapoptotic treatments acting on precocious steps of the death process. Mitochondrial dysfunction is among the earliest events linked to AD and might play a causative role in disease onset and progression. Recent studies on CGNs have shown that adenine nucleotide translocator (ANT) impairment, due to interaction with toxic N-ter Tau fragment, contributes in a significant manner to bioenergetic failure and mitochondrial dysfunction. These findings open a window for new therapeutic strategies aimed at preserving and/or improving mitochondrial function

Diagnosis and treatment delay of head and neck cancers during COVID-19 era in a tertiary care academic hospital: what should we expect?

Background Since the spreading of SARS-CoV-2 from China, all deferrable medical activities have been suspended, to redirect resources for the management of COVID patients. The goal of this retrospective study was to investigate the impact of COVID-19 on head and neck cancers' diagnosis in our Academic Hospital. Methods A retrospective analysis of patients treated for head and neck cancers between March 12 and November 1, 2020 was carried out, and we compared these data with the diagnoses of the same periods of the 5 previous years. Results 47 patients were included in this study. We observed a significative reduction in comparison with the same period of the previous 5 years. Conclusions Our findings suggest that the COVID-19 pandemic is associated with a decrease in the number of new H&N cancers diagnoses, and a substantial diagnostic delay can be attributable to COVID-19 control measures

Impact of the COVID-19 Pandemic on Otolaryngology Residency: A Real-Life Experience

The coronavirus disease (COVID-19) pandemic as been rapidly spreading worldwide. In our country, the entire Italian Healthcare System has been forced to adapt to this unprecedented condition in this century. The Head and Neck Department clinical and surgical activity was substantially reduced. In this situation, the Ear, Nose and Throat (ENT) residents in University Hospitals find themselves in an uncertain position; we are physicians, facing a deadly disease about which much remains unknown, but we are also trainees, and there is a high risk for our residency training to be affected. With this Letter, we would like to give a testimony of our experience and give some advices to bridge the training gap

Voluntary lung function screening to reveal new COPD cases in southern Italy

Background: Underdiagnosis of COPD is a relevant issue, and most frequently involves patients at early stages of the disease. Physicians do not routinely recommend smokers to undergo spirometry, unless they are symptomatic. Aims: To investigate the effectiveness of voluntary lung function screening in bringing to light patients with previously unknown COPD and to evaluate the relationships among symptoms, smoking status, and airway obstruction. Methods: A voluntary screening study for COPD was conducted during two editions of the annual Fiera del Levante (2014 and 2015), an international trade fair in Bari. Subjects were eligible for the study if they fulfilled the following inclusion criteria: age â¥35 years, smoker/ex-smoker â¥5 pack-years (PYs), or at least one chronic respiratory symptom (cough, sputum production, shortness of breath, and wheezing). A free post-β2-agonist spirometry test was performed by trained physicians for each participant using portable spirometers. Post-β2-agonist forced expiratory volume in 1 second (FEV1):forced vital capacity ratio <0.7 was chosen to establish the diagnosis of COPD. Sensitivity, specificity, and negative and positive predictive values (NPVs and PPVs) of symptoms for the presence of obstruction were calculated. Results: A total of 1,920 individuals were eligible for the study; 188 subjects (9.8%) met COPD criteria. There was a 10.4% prevalence of COPD in subjects with one or more symptoms who had never smoked or smoked â¤5 PYs. Among COPD patients, prevalence of symptoms increased in the presence of FEV1<80%. COPD smokers were more symptomatic than smokers without COPD. Sensitivity and specificity in all subjects with one or more symptoms were 87% and 32%, respectively, whereas in smoker subgroups, sensitivity and specificity were 71% and 41% (â¥5 PYs) and 74% and 35% (â¥10 PYs), respectively. In all subjects, the presence of at least one symptom was associated with a low PPV for COPD of 11%, but a very high NPV (96%). These data did not change if the analysis was limited to smokers. Conclusion: Voluntary public lung function screening programs in Italy are effective, and may detect a large number of undiagnosed subjects with COPD in early stages. In our population, COPD symptoms had low specificity and PPV, even considering smokers only

Voluntary lung function screening to reveal new COPD cases in southern Italy

Background: Underdiagnosis of COPD is a relevant issue, and most frequently involves patients at early stages of the disease. Physicians do not routinely recommend smokers to undergo spirometry, unless they are symptomatic. Aims: To investigate the effectiveness of voluntary lung function screening in bringing to light patients with previously unknown COPD and to evaluate the relationships among symptoms, smoking status, and airway obstruction. Methods: A voluntary screening study for COPD was conducted during two editions of the annual Fiera del Levante (2014 and 2015), an international trade fair in Bari. Subjects were eligible for the study if they fulfilled the following inclusion criteria: age â¥35 years, smoker/ex-smoker â¥5 pack-years (PYs), or at least one chronic respiratory symptom (cough, sputum production, shortness of breath, and wheezing). A free post-Î22-agonist spirometry test was performed by trained physicians for each participant using portable spirometers. Post-Î22-agonist forced expiratory volume in 1 second (FEV1):forced vital capacity ratio <0.7 was chosen to establish the diagnosis of COPD. Sensitivity, specificity, and negative and positive predictive values (NPVs and PPVs) of symptoms for the presence of obstruction were calculated. Results: A total of 1,920 individuals were eligible for the study; 188 subjects (9.8%) met COPD criteria. There was a 10.4% prevalence of COPD in subjects with one or more symptoms who had never smoked or smoked â¤5 PYs. Among COPD patients, prevalence of symptoms increased in the presence of FEV1<80%. COPD smokers were more symptomatic than smokers without COPD. Sensitivity and specificity in all subjects with one or more symptoms were 87% and 32%, respectively, whereas in smoker subgroups, sensitivity and specificity were 71% and 41% (â¥5 PYs) and 74% and 35% (â¥10 PYs), respectively. In all subjects, the presence of at least one symptom was associated with a low PPV for COPD of 11%, but a very high NPV (96%). These data did not change if the analysis was limited to smokers. Conclusion: Voluntary public lung function screening programs in Italy are effective, and may detect a large number of undiagnosed subjects with COPD in early stages. In our population, COPD symptoms had low specificity and PPV, even considering smokers only

THE ITALIAN QUATERNARY VOLCANISM

The peninsular and insular Italy are punctuated by Quaternary volcanoes and their rocks constitute an important aliquot of the Italian Quaternary sedimentary successions. Also away from volcanoes themselves, volcanic ash layers are a common and frequent feature of the Quaternary records, which provide us with potential relevant stratigraphic and chronological markers at service of a wide array of the Quaternary science issues. In this paper, a broad representation of the Italian volcano-logical community has joined to provide an updated comprehensive state of art of the Italian Quaternary volcanism. The eruptive history, style and dynamics and, in some cases, the hazard assessment of about thirty Quaternary volcanoes, from the north-ernmost Mt. Amiata, in Tuscany, to the southernmost Pantelleria and Linosa, in Sicily Channel, are here reviewed in the light of the substantial improving of the methodological approaches and the overall knowledge achieved in the last decades in the vol-canological field study. We hope that the present review can represent a useful and agile document summarising the knowledege on the Italian volcanism at the service of the Quaternary community operating in central Mediterranean area

The italian quaternary volcanism

The peninsular and insular Italy are punctuated by Quaternary volcanoes and their rocks constitute an important aliquot of the Italian Quaternary sedimentary successions. Also away from volcanoes themselves, volcanic ash layers are a common and frequent feature of the Quaternary records, which provide us with potential relevant stratigraphic and chronological markers at service of a wide array of the Quaternary science issues. In this paper, a broad representation of the Italian volcano logical community has joined to provide an updated comprehensive state of art of the Italian Quaternary volcanism. The eruptive history, style and dynamics and, in some cases, the hazard assessment of about thirty Quaternary volcanoes, from the north ernmost Mt. Amiata, in Tuscany, to the southernmost Pantelleria and Linosa, in Sicily Channel, are here reviewed in the light of the substantial improving of the methodological approaches and the overall knowledge achieved in the last decades in the vol canological field study. We hope that the present review can represent a useful and agile document summarising the knowledege on the Italian volcanism at the service of the Quaternary community operating in central Mediterranean area

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 < .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

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)