Impact of Different e-Cigarette Generation and Models on Cognitive Performances, Craving and Gesture: A Randomized Cross-Over Trial (CogEcig)

Introduction: Most electronic-cigarettes (e-cigarette) are designed to look like traditional cigarettes and simulate the visual, sensory, and behavioral aspects of smoking traditional cigarettes. This research aimed to explore whether different e-cigarette models and smokers' usual classic cigarettes can impact on cognitive performances, craving and gesture.  Methods: The study is randomized cross-over trial designed to compare cognitive performances, craving, and gesture in subjects who used first generation electronic cigarettes, second generation electronic cigarettes with their usual cigarettes. (Trial registration: ClinicalTrials.gov number NCT01735487).  Results: Cognitive performance was not affected by “group condition.” Within-group repeated measures analyses showed a significant time effect, indicating an increase of participants' current craving measure in group “usual classic cigarettes (group C),” “disposable cigalike electronic cigarette loaded with cartridges with 24 mg nicotine (group H), second generation electronic cigarette, personal vaporizer model Ego C, loaded with liquid nicotine 24 mg (group E). Measures of gesture not differ over the course of the experiment for all the products under investigation  Conclusion: All cognitive measures attention, executive function and working memory are not influenced by the different e-cigarette and gender showing that in general electronics cigarettes could become a strong support also from a cognitive point of view for those who decide to quit smoking. It seems that not only craving and other smoke withdrawal symptoms but also cognitive performance is not only linked to the presence of nicotine; this suggests that the reasons behind the dependence and the related difficulty to quit smoking needs to be looked into also other factors like the gesture

Imaging features of perineural and perivascular spread in rapidly progressive rhino-orbital-cerebral mucormycosis: A case report and brief review of the literature

Background: Rhinocerebral mucormycosis (ROCM) is an opportunistic fungal infection originating from the paranasal sinuses with extension to the brain. A delayed diagnosis can rapidly result in a poor prognosis. ROCM commonly affects patients with diabetes or immunocompromised states with a variable progression. Case description: We report the case of a 59-year old patient with an untreated diabetes who developed a ROCM with rapidly progressive neurological symptoms. From the onset of sinus pain, nasal congestion, he rapidly developed facial swelling and masticatory dysfunction. The patient underwent sinus surgery which allowed Rhizopus oryzae to be isolated. Accordingly, a systemic therapy by intensive intravenous amphotericin B was started. Nevertheless, the infection rapidly resulted in bilateral cavernous sinuses thrombosis and occlusion of the left internal carotid artery providing the subsequent patient death. Conclusion: Mucormycosis is a life-threatening fungal infection in diabetic and/or immunosuppressed patients. Our case demonstrates the three main mechanisms for infection spreading that are direct, perineural, and perivascular diffusion. Clear identification of the main risk factors, proper assessment of clinical features, and radiological findings may improve the chance for an early diagnosis and patient survival

LDOC1 expression in fibroblasts of patients with Down syndrome

Abstract Down syndrome (DS) is characterised by intellectual disability and is caused by trisomy 21. Apoptosis is a programmed cell death process and is involved in neurodegenerative diseases such as Alzheimer. People with DS can develop some traits of Alzheimer disease at an earlier age than subjects without trisomy 21. The leucine zipper, down regulated in cancer 1 (LDOC1) appears to be involved in the apoptotic pathways. The aim of the present work was to detect the presence of intracellular synthesis of LDOC1 protein and LDOC1 mRNA in fibroblast cultures from DS subjects. The western blot shows the presence of LDOC1 protein in fibroblasts of DS subjects but no evidence of LDOC1 protein in fibroblasts of normal subjects. LDOC1 gene mRNA expression is increased in fibroblasts from DS subjects compared to fibroblasts from normal subjects. The data obtained from this study strengthen the hypothesis that the over-expression of LDOC1 gene could play a role in determining the phenotype of individuals with DS but does not exclude that this results from apoptotic mechanisms

Impact of Different e-Cigarette Generation and Models on Cognitive Performances, Craving and Gesture: A Randomized Cross-Over Trial (CogEcig)

Introduction: Most electronic-cigarettes (e-cigarette) are designed to look like traditional cigarettes and simulate the visual, sensory, and behavioral aspects of smoking traditional cigarettes. This research aimed to explore whether different e-cigarette models and smokers' usual classic cigarettes can impact on cognitive performances, craving and gesture.Methods: The study is randomized cross-over trial designed to compare cognitive performances, craving, and gesture in subjects who used first generation electronic cigarettes, second generation electronic cigarettes with their usual cigarettes. (Trial registration: ClinicalTrials.gov number NCT01735487).Results: Cognitive performance was not affected by “group condition.” Within-group repeated measures analyses showed a significant time effect, indicating an increase of participants' current craving measure in group “usual classic cigarettes (group C),” “disposable cigalike electronic cigarette loaded with cartridges with 24 mg nicotine (group H), second generation electronic cigarette, personal vaporizer model Ego C, loaded with liquid nicotine 24 mg (group E). Measures of gesture not differ over the course of the experiment for all the products under investigationConclusion: All cognitive measures attention, executive function and working memory are not influenced by the different e-cigarette and gender showing that in general electronics cigarettes could become a strong support also from a cognitive point of view for those who decide to quit smoking. It seems that not only craving and other smoke withdrawal symptoms but also cognitive performance is not only linked to the presence of nicotine; this suggests that the reasons behind the dependence and the related difficulty to quit smoking needs to be looked into also other factors like the gesture.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01735487

MET inhibition sensitizes rhabdomyosarcoma cells to NOTCH signaling suppression

Rhabdomyosarcoma (RMS) is a pediatric myogenic soft tissue sarcoma. The Fusion-Positive (FP) subtype expresses the chimeric protein PAX3-FOXO1 (P3F) while the Fusion-Negative (FN) is devoid of any gene translocation. FP-RMS and metastatic FN-RMS are often unresponsive to conventional therapy. Therefore, novel therapeutic approaches are needed to halt tumor progression. NOTCH signaling has oncogenic functions in RMS and its pharmacologic inhibition through gamma-secretase inhibitors blocks tumor growth in vitro and in vivo. Here, we show that NOTCH signaling blockade resulted in the up-regulation and phosphorylation of the MET oncogene in both RH30 (FP-RMS) and RD (FN-RMS) cell lines. Pharmacologic inhibition of either NOTCH or MET signaling slowed proliferation and restrained cell survival compared to control cells partly by increasing Annexin V and CASP3/7 activation. Co-treatment with NOTCH and MET inhibitors significantly amplified these effects and enhanced PARP1 cleavage in both cell lines. Moreover, it severely hampered cell migration, colony formation, and anchorage-independent growth compared to single-agent treatments in both cell lines and significantly prevented the growth of FN-RMS cells grown as spheroids. Collectively, our results unveil the overexpression of the MET oncogene by NOTCH signaling targeting in RMS cells and show that MET pathway blockade sensitizes them to NOTCH inhibition

Highly specific memory B cells generation after the 2nd dose of BNT162b2 vaccine compensate for the decline of serum antibodies and absence of mucosal IgA

Specific memory B cells and antibodies are a reliable read-out of vaccine efficacy. We analysed these biomarkers after one and two doses of BNT162b2 vaccine. The second dose significantly increases the level of highly specific memory B cells and antibodies. Two months after the second dose, specific antibody levels decline, but highly specific memory B cells continue to increase, thus predicting a sustained protection from COVID-19. We show that although mucosal IgA is not induced by the vaccination, memory B cells migrate in response to inflammation and secrete IgA at mucosal sites. We show that the first vaccine dose may lead to an insufficient number of highly specific memory B cells and low concentration of serum antibodies, thus leaving vaccinees without the immune robustness needed to ensure viral elimination and herd immunity. We also clarify that the reduction of serum antibodies does not diminish the force and duration of the immune protection induced by vaccination. The vaccine does not induce sterilizing immunity. Infection after vaccination may be caused by the lack of local preventive immunity because of the absence of mucosal IgA

High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections

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

Hirayama disease – Early MRI diagnosis of subacute medullary ischemia: A case report

Background: Hirayama disease (HD) is a rare, benign, and self-limiting motor neuron disorder that results in selective motor impairment of the C7-T1 myotomes. It is characterized by progressive, unilateral, or bilateral asymmetric muscle atrophy of the distal upper extremities and myelopathy. Case Description: A 23-year-old male presented with bilateral atrophy of the thenar/hypothenar eminences/interosseous muscles, plus left-hand weakness. The cervical MRI documented subacute ischemic damage of the distal cervical cord. To rule out a tumor and reduce questionable cord compression, the patient underwent a C5–C6 anterior cervical discectomy and fusion (ACDF) immediately followed by a laminectomy with durotomy and to obtain a spinal cord biopsy. When the histology confirmed focal cord ischemia consistent with HD, it was clear that both operations were unnecessary. Conclusion: Establishing the diagnosis of HD is based on clinical findings and MRI/flexion MR features which include the demonstration of an increased T2-weighted intramedullary cord signal, enlargement of the posterior epidural space, and segmental spinal cord atrophy. The presence of HD should be recognized as a “nonsurgical entity,” and conservative nonsurgical management should be employed

Impact of different e-cigarette generation and models on cognitive performances, craving and gesture. A randomized cross-over trial (CogEcig)

Introduction: Most electronic-cigarettes (e-cigarette) are designed to look like traditional cigarettes and simulate the visual, sensory, and behavioral aspects of smoking traditional cigarettes. This research aimed to explore whether different e-cigarette models and smokers' usual classic cigarettes can impact on cognitive performances, craving and gesture. Methods: The study is randomized cross-over trial designed to compare cognitive performances, craving, and gesture in subjects who used first generation electronic cigarettes, second generation electronic cigarettes with their usual cigarettes. (Trial registration: ClinicalTrials.gov number NCT01735487). Results: Cognitive performance was not affected by "group condition." Within-group repeated measures analyses showed a significant time effect, indicating an increase of participants' current craving measure in group "usual classic cigarettes (group C)," "disposable cigalike electronic cigarette loaded with cartridges with 24 mg nicotine (group H), second generation electronic cigarette, personal vaporizer model Ego C, loaded with liquid nicotine 24 mg (group E). Measures of gesture not differ over the course of the experiment for all the products under investigation Conclusion: All cognitive measures attention, executive function and working memory are not influenced by the different e-cigarette and gender showing that in general electronics cigarettes could become a strong support also from a cognitive point of view for those who decide to quit smoking. It seems that not only craving and other smoke withdrawal symptoms but also cognitive performance is not only linked to the presence of nicotine; this suggests that the reasons behind the dependence and the related difficulty to quit smoking needs to be looked into also other factors like the gestur