Tumorigenic effect mediated by ROS/eicosanoids and their regulation on TP53 expression in a murine mammary gland adenocarcinoma.

The aim of this study was to investigate the in vivo and in vitro effects of dietary ω-6 and ω-3 polyunsaturated fatty acids (PUFAs) and their derivatives on the expression of TP53 and their relationship with cellular proliferation and death in a murine mammary adenocarcinoma model. BALB/c mice were divided in three diet groups: chia oil (ChO) rich in ω-3, corn oil (CO) rich in ω-6/ω-3 and safflower oil (SO) rich in ω-6 and subcutaneously inoculated with LMM3 mammary tumor cell line. Results demonstrated that diets with higher concentration of omega-6 PUFAs induced an increment of linoleic and arachidonic acid on tumor cell membranes increasing ROS liberation, 12(S)-HHT generation, TP53, Ki67 expression and cell proliferation. However, diets enriched with high content in omega-3 PUFAs induced higher tumor cell apoptosis and tumor infiltration of CD3+ lymphocytes, lowest cell viability and proliferation. Dietary omega-3 PUFAs nutritional intervention can be used as a potential preventative strategy to inhibit the molecular signaling pathways involved in the mammary tumor growth process as the TP53.

Rehabilitations with immediate loading of one-piece implants stabilized with intraoral welding.

The authors present an implant prosthesis procedure that uses screws on one-piece implants connected with a titanium pin at their abutment level and one supporter titanium bar in order to guarantee immediate stabilization. These can be implanted and fitted with customized temporary crowns in a single surgical procedure, restoring function and aesthetics and consenting recovery of the bone deficit with reduced healing times and limited patient discomfort. One-piece wide-diameter titanium screw implants with thread measurements of 2.1 and 2.6 mm (smaller diameter) up to diameter of 4.5 mm with one abutment of 2.0 and 2.5 mm respectively, were positioned and splinted by intraoral welding. One-piece titanium implants were used together with a pin (needle) titanium implant as supporting structure to achieve deep stabilization. The Scialom-like pin has a diameter of 1.2 mm and it is long enough to reach deep cortical bone that is “bicorticalism”. The One-piece implant is tightly connected to the needle implant by means of Mondani intra-oral welding technique. In severely atrophic anterior maxilla, the use of this method allows the immediate loading of a fixed resin prosthesis soon after surgery. These implants yielded satisfactory functional and aesthetic outcome in bone-deficient upper anterior sectors, without invasive regenerative procedures. The low invasiveness of this approach also consents rapid healing, reduced biological burden and greater patient benefit.

The importance of occlusal trauma in the primary etiology of periodontal disease.

The presence of periodontal disease can be ascertained by clinical examination (redness, edema and probe depth, bleeding-on-probing). Occlusal adjustment can lead to a marked, stable improvement in periodontal health in terms of bacterial profile and clinical appearance, presumably by obviating tissue distress caused by occlusal dysfunction, thereby providing unfavorable conditions for bacterial growth. Therefore, occlusal trauma can be an essential indicator of the periodontal disease and, if not corrected, could lead to a relapse.

Mondani intraoral welding: historical process and main practical applications.

The intraoral welder was invented by Dr. Pierluigi Mondani during the early 70’s to weld titanium needle implants to a titanium bar in patient’s mouth and to load them immediately by means of resin prosthesis. The clinical use documented dates back to 1972. Over the years, many practical applications have been added to the initial one, which have expanded the use of this device. In this scientific work, main applications are described. The aim of the work was to trace the historical process of intra-oral welding according to Mondani and describe the main practical applications. Intra-oral welding is a process introduced by dr. Pier Luigi Mondani of Genova (Italy) which allows to firmly conjoin titanium implants of any shape by means of a titanium bar or also directly between them in the mouth during surgery. The immediate stabilization achieved by intraoral welding increases implants success rate, allows immediate loading even in situations of bone atrophy, saves implants that are running into failure, re-evaluates fractured implants, allows to stabilize submerged implants postponing prosthesis management, allows to achieve efficient rehabilitation protocols to deal with difficult cases. The 40-years’ experience with intra-oral welding described in this article, confirms the ease of use and efficiency in providing immediate stabilization of titanium implants of all types.

Interest of an auto-adjustable nighttime compression sleeve (MOBIDERM® Autofit) in maintenance phase of upper limb lymphedema: the MARILYN pilot RCT.

PURPOSE: Breast cancer-related lymphedema (BCRL) is a debilitating condition. The recommended treatment is based on decongestive lymphedema therapy (DLT) with two separate phases: a short-term intensive phase to reduce lymphedema volume and a long-term maintenance phase to stabilize it. Optimizing compression therapy and compliance during maintenance phase are key factors for long-term control of lymphedema. The primary objective of this pilot prospective open-label randomized study was to assess the benefit of a new auto-adjustable nighttime arm sleeve (MOBIDERM® Autofit) on lymphedema volume during the maintenance phase after the intensive phase. METHODS: Forty women with BRCL were consecutively enrolled and randomized (D0) for 1 month in 1:1 ratio either in night-use group: with MOBIDERM® Autofit (on top of a daytime compression hosiery), or in no night-use group: without MOBIDERM® Autofit (daytime hosiery alone). From Day 31 to Day 90, all patients were fitted with MOBIDERM® Autofit. Primary endpoint was lymphedema volume variation between Day 0 and Day 30. Secondary endpoints were compliance, quality of life (LYMQOL arm questionnaire), functional symptoms (heaviness, limb use limitation, pain), sleep quality, and safety. RESULTS: In ITT population, between Day 0 and Day 30, mean lymphedema volume increase was higher in no night-use group with 92.9 mL (i.e., 3.2%) than in night-use group with 46.7 mL (i.e., 1.80%), p = 0.757. Between Day 30 and Day 90, all patients fitted with MOBIDERM® Autofit, lymphedema volume remained stable in both groups. The device improved functional symptoms and function domain of the LYMQOL arm questionnaire. MOBIDERM® Autofit was worn overnight almost 85% of the nights. It was well accepted by the patients and no adverse reaction leading to permanent device discontinuation occurred. CONCLUSIONS: Our results suggest that MOBIDERM® Autofit offers clinical benefits during maintenance phase of lymphedema treatment and enhances patient's self-management.

Correlation between dysfunctional occlusion and periodontal bacterial profile.

The aim of this study is to compare the evolution in bacterial profile at evident periodontitis sites following two types of treatment - oral hygiene procedures alone (Group 1) and oral hygiene plus occlusal adjustment through selective grinding (Group 2). The presence of periodontal disease was ascertained by clinical examination (redness, oedema, probe depth, bleeding-on-probing). Bacterial profiling was carried out via phase contrast microscopy on plaque samples taken from periodontitis sites in both patient groups. Bacterial populations were characterized in terms of coccus content before (T0) and at monthly intervals after treatment (T1-6) over a period of six months. Static and dynamic occlusion was evaluated only in Group 2 patients. Whereas the poor pre-treatment bacterial profile was re-established progressively over the evaluation period in Group 1 patients, coccus populations flourished in Group 2 patients, reaching healthy levels (>70%) two months after occlusal adjustment, and clinical examination confirmed an absence of periodontal inflammation in these patients. Occlusal adjustment can lead to a marked, stable improvement in periodontal health in terms of bacterial profile and clinical appearance, presumably by obviating tissue distress caused by occlusal dysfunction, thereby providing unfavourable conditions for bacterial growth. Bacterial profiling is an effective indicator of periodontal health.

Residence registration to cope with homelessness: evidence from a qualitative research study in Milan.

Homeless people are one of the most vulnerable and marginalized groups in developed countries, and their homelessness situation often persists over the long term. However, so far, no studies have explained the specific role played by residence registration as it relates to deprivation amongst the homeless population and its contribution to improving the lives of homeless people. This paper investigates the paths homeless people in Milan use to access residence registration, via a case study in the city of Milan. Home to Italy's largest homeless population, the city of Milan has implemented the innovative ResidenzaMi project to improve access to residence registration for homeless people. The study considers official statistics and individual interviews with service providers involved in the registration process. It further investigates the main factors impeding the registration process and outlines the consequences of the COVID-19 pandemic. Results from our study indicate that a residence certificate plays a critical role in helping homeless people exercise their rights and access the services they need to escape homelessness. Our findings suggest the importance of a holistic, multidimensional approach to ensure access to residence registration for homeless persons.

[Association of hypertension and antihypertensive agents and the severity of COVID-19 pneumonia. A monocentric French prospective study]. / Association entre l'hypertension artérielle, les traitements inhibiteurs du système rénine angiotensine et les formes graves de COVID-19. Étude prospective monocentrique française.

BACKGROUND AND AIM: Angiotensin converting enzyme (ACE) type 2 is the receptor of SARSCoV-2 for cell entry into lung cells. Because ACE-2 may be modulated by ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), there are concern that patients treated with ACEIs and ARBs are at higher risk for COVID-19 infection or severity. This study sought to analyse the association of severe forms of COVID-19 and mortality with hypertension and a previous treatment with ACEI and ARB. METHODS: Prospective follow-up of 433 consecutive patients hospitalised for COVID-19 pneumonia confirmed by PCR or highly probable on clinical, biological, and radiological findings, and included in the COVHYP study. Mortality and severe COVID-19 (criteria: death, intensive care unit, or hospitalisation >30 days) were compared in patients receiving or not ACEIs and ARBs. Follow-up was 100% at hospital discharge, and 96.5% at >1month. RESULTS: Age was 63.6±18.7 years, and 40%) were female. At follow-up (mean 78±50 days), 136 (31%) patients had severity criteria (death, 64 ; intensive care unit, 73; hospital stay >30 days, 49). Hypertension (55.1% vs 36.7%, P<0.001) and antihypertensive treatment were associated with severe COVID-19 and mortality. The association between ACEI/ARB treatment and COVID-19 severity criteria found in univariate analysis (Odds Ratio 1.74, 95%CI [1.14-2.64], P=0.01) was not confirmed when adjusted on age, gender, and hypertension (adjusted OR1.13 [0.59-2.15], P=0.72). Diabetes and hypothyroidism were associated with severe COVID-19, whereas history of asthma was not. CONCLUSION: This study suggests that previous treatment with ACEI and ARB is not associated with hospital mortality, 1- and 2-month mortality, and severity criteria in patients hospitalised for COVID-19. No protective effect of ACEIs and ARBs on severe pneumonia related to COVID-19 was demonstrated.

How much and why does the mum matter? Mechanisms explaining the intergenerational transmission of smoking.

Offspring whose mother smokes during pregnancy have higher risk of smoking themselves. In this study, epigenetics, antisocial behaviours, and social learning were investigated as potential mechanisms of mother-to-child transmission of smoking among a population sample drawn from the Birth Cohort Study 1970. Findings on daughters showed that the direct epigenetic hypothesis was mediated by social learning mechanisms, suggesting that exposure to maternal smoking across childhood and adolescence strongly explained why the smoking habits of mother and daughter correlate. However, prenatal smoking effects on sons were only partially explained by observational learning of mother smoking habits. Our estimates provided evidence concerning the potential role also played by the child's persistent antisocial behaviours. These results were confirmed after controlling for early life circumstances and current socioeconomic conditions. Policy implications of the results are discussed.

Parents who exit and parents who enter. Family structure transitions, child psychological health, and early drinking.

This paper seeks to extend prior research by exploring whether family structure transition is associated with an increase in early alcohol consumption and whether this association is mediated by; children's socio-emotional problems, providing information on whether the effects of the transition; differ according to the number of changes, the family's initial status, or the time of exposure. The; data have been drawn from the UK Millennium Cohort Study to explore associations framed with; a life-course approach. Our findings suggest that types of family transitions (such as distinguishing; parental exits from and parental entrances to the family) are more important than the number of; family changes during childhood. The results show that moving from a two-parent household to a single-parent household directly increased the probability of being a frequent alcohol consumer among early adolescent boys, whereas the indirect effect on girls was found via socio-emotional difficulties. Our findings also show an increase in socio-emotional and behavioural difficulties in boys due to the entrance of a step-parent only if the transition occurred in the earliest childhood. Indeed, a sensitivity analysis of the time to which the children were exposed to the transition to a new family structure showed stronger effects for those who experienced a family structure change in the early life course, consistent with the cumulative disadvantage process.

Effect of Chia oil (Salvia Hispanica) rich in omega-3 fatty acids on the eicosanoid release, apoptosis and T-lymphocyte tumor infiltration in a murine mammary gland adenocarcinoma.

We investigated the effects of certain dietary polyunsaturated fatty acids (PUFAs) and related eicosanoids on the growth and metastasis formation of a murine mammary gland adenocarcinoma. Salvia hispanica (ChO) and Carthamus tinctorius (SaO) vegetable oil sources of omega-3 and -6 PUFAs and a commercial diet as control (CO), were used. We analysed fatty acids of neoplastic cells (NC) membranes by GLC; the eicosanoids 12- HETE and 12-HHT (LOX and COX metabolites) by HPLC and apoptosis and T-lymphocyte infiltration by flow cytometry and microscopy. NC from ChO groups showed lower levels of arachidonic acid and of both eicosanoids compared to SaO and CO (p<0.05). The ChO diet decreased the tumor weight and metastasis number (p<0.05). Apoptosis and T-lymphocyte infiltration were higher and mitosis decreased with respect to the other diets (p<0.05). Present data showed that ChO, an ancient and almost unknown source of omega-3, inhibits growth and metastasis in this tumor model.

Health and income inequalities in Europe: What is the role of circumstances?

Equality of opportunity theories distinguish between inequalities due to individual effort and those due to external circumstances. Recent research has shown that half of the variability in income of World population was determined by country of birth and income distribution. Since health and income are generally strictly related, the aim of this paper is to estimate how much variability in income and health is determined by external circumstances. We use data from the Survey of Health, Ageing and Retirement (SHARE) and the English Longitudinal Survey on Ageing (ELSA), two comparable multidisciplinary surveys that provide micro-level data on health and financial resources among the elderly for a large number of European countries. Our baseline estimation shows that about 20% of the variability in income is explained by current country-specific circumstances, while health outcomes range from 12% using BMI to 19% using self-rated health. By including early-life circumstances, the explained variability increases almost 20 percentage points for income and for self-rated health but less for other health outcomes. Finally, by controlling for endogeneity issues linked with effort, our estimates indicate that circumstances better explain variability in health outcomes. Results are robust to some tests, and the implications of these findings are discussed.

The effects of ω-6 and ω-3 fatty-acids on early stages of mice DMBA submandibular glands tumorigenesis.

The aim of this work was: to assess the impact of diets enriched in polyunsaturated fatty acids ω-3 and ω-6 families on the lipid profile of cell membrane and their effect on cycle regulation and apoptosis, evaluated by TP53 and Ki-67 expression in 9,10-dimethyl-1,2-benzanthracene (DMBA) induced tumor development in submandibular glands (SMG) in murine models. To generate tumorigenic changes, SMG mice in the experimental group were injected with 50µl of 0.5% of DMBA. Both control (no DMBA) and experimental groups of BALB/c mice were fed with: chia oil (ChO), rich in ω-3 fatty acid; corn oil (CO), rich in ω-6/ω-3 fatty acid; and safflower (SO) oil, rich in ω-6fatty acid. Results demonstrate novel differential effects of ω-3 and ω-6 PUFAs on the regulation of early tumorigenesis events in murine SMG injected with DMBA. This knowledge may help to develop chemoprotective treatments, therapeutic agents and health promotion and prevention activities in humans.

Implant Dentistry: Monitoring of Bacteria Along the Transmucosal Passage of the Healing Screw in Absence of Functional Load.

PURPOSE: To assess the changes in bacterial profile along the transmucosal path of healing screws placed immediately after insertion of two-piece endosseus implants during the 4-month osseointegration phase, in absence of functional load. MATERIALS AND METHODS: Two site-specific samples were collected at the peri-implant mucosa of the healing screws of 80 two-piece implants, for a total of 640 samples. Implants placement was performed following a single protocol with flapless technique, in order to limit bacterial contamination of the surgical site. Identical healing screws (5 mm diameter/4 mm height) were used for each of the 80 implants. During the 4 months of the study, the patients followed a standard oral care regimen with no special hygiene maneuvers at the collection sites. RESULTS: The present research documents that during the 4-month period prior to application of function load the bacterial profile of all sites exhibited a clear prevalence of cocci at the interface between implant neck and osteoalveolar crest margin. CONCLUSIONS: A potentially pathogenic bacterial flora developed only along the peri-implant transmucosal path.

Estimating mean pulmonary wedge pressure in patients with chronic atrial fibrillation from transthoracic Doppler indexes of mitral and pulmonary venous flow velocity.

OBJECTIVES: We sought to obtain a noninvasive estimation of mean pulmonary wedge pressure (MPWP) in patients with chronic atrial fibrillation (AF). BACKGROUND: It has previously been demonstrated that MPWP can be reliably estimated from Doppler indexes of mitral and pulmonary venous flow (PVF) in patients with sinus rhythm. Doppler estimation of MPWP has not been validated in patients with AF. METHODS: MPWP was correlated with variables of mitral and pulmonary venous flow velocity as assessed by Doppler transthoracic echocardiography in 35 consecutive patients. The derived algorithm was prospectively tested in 23 additional patients. RESULTS: In all patients the mitral flow pattern showed only a diastolic forward component. A significant but relatively weak correlation (r = -0.50) was observed between MPWP and mitral deceleration time. In 12 (34%) of 35 patients, the pulmonary vein flow tracing demonstrated only a diastolic forward component; a diastolic and late systolic forward flow was noted in the remaining 23 patients (66%). A strong negative correlation was observed between MPWP and the normalized duration of the diastolic flow (r = -0.80) and its initial deceleration slope time (r = -0.91). Deceleration time > 220 ms predicted MPWP < or = 12 mm Hg with 100% sensitivity and 100% specificity. When estimating MPWP by using the equation MPWP = -94.261 PVF deceleration time -9.831 Interval QRS to onset of diastolic PVF -16.337 Duration of PVF + 44.261, the measured and predicted MPWP closely agreed with a mean difference of -0.85 mm Hg. The 95% confidence limits were 4.8 and -6.1 mm Hg. CONCLUSIONS: In patients with chronic AF, MPWP can be estimated from transthoracic Doppler study of PVF velocity signals.

Dietary lipids modulate eicosanoid release and apoptosis of cells of a murine lung alveolar carcinoma.

Dietary arachidonic acid (AA) and eicosanoids influence neoplastic cell (NC) growth, differentiation and apoptosis. Plasma membrane fatty acid and cyclooxygenase (COX) and lipoxygenase (LOX) products were investigated in lung alveolar carcinoma cells from mice fed on different diets. Two groups were fed on a basic diet plus 6% of: corn oil (rich in 18:2n-6; CO) and on olein oil (rich in 18:1n-9; O), respectively. Control group (C) received commercial diet. NC fatty acids were analyzed by GLC, and apoptosis by flow cytometry and microscopy. In NC from CO group AA levels and LOX metabolites were increased, whereas COX metabolites decreased. NC from CO compared to O group diet showed a higher count of apoptosis and increased LOX:COX ratio. High levels of AA and decreased COX eicosanoids has been involved in anti-tumoral mechanisms by increasing tumor cell apoptosis. Present data emphasizes the implications of the dietary fatty acids on the neoplastic process in this tumoral model.

Synthesis and biological evaluation of NAD analogs as human pyridine nucleotide adenylyltransferase inhibitors.

NAD analogs modified at the ribose adenylyl moiety, named N-2'-MeAD and Na-2'-MeAD, were synthesized as ligands of pyridine nucleotide (NMN/NaMN) adenylyltransferase (NMNAT). Both dinucleotides resulted selective inhibitors against human NMNAT-3 isoenzyme.

Association between E-cadherin expression by human colon, bladder and breast cancer cells and the 13-HODE:15-HETE ratio. A possible role of their metastatic potential.

The relationship between 15(S)-HETE and 13(S)-HODE from different human tumor cells exposed to n-6 and n-3 essential fatty acids (EFAs) and E-cadherin expression was studied. Colon cancer cells (HRT-18) exposed to gamma linoleic acid (18:3n-6, GLA) and eicosapentaenoic (20:5n-3, EPA) (50microM) showed an increased expression of E-cadherin. Breast cancer (MCF-7) exposed to EPA showed an increment whereas GLA had no effect on E-cadherin expression. No expression of E-cadherin was observed for urothelial cancer (T-24) after GLA or EPA treatment. Significant levels of 15(S)-HETE and 13(S)-HODE were detected after GLA or EPA treatment for all tumor lines. E-cadherin expression was inversely proportional to the 13(S)-HODE:15(S)-HETE ratio when cells were pretreated with GLA or EPA. Nevertheless, the liberation of these metabolites seems to be independent of the E-cadherin expression. The increase in the13(S)-HODE:15(S)-HETE correlates to a decrease in the expression of E-cadherin. Both factors may play a role in metastasis development.

COX and LOX eicosanoids modulate platelet activation and procoagulation induced by two murine cancer cells.

Involvement of arachidonic acid cyclooxygenase (COX) and lipoxygenase (LOX) metabolites in platelet aggregation and coagulation induced by two varieties of cancer cells of murine transplantable tumors was studied. A lung alveolar carcinoma (LAC) and a fibrosarcoma (FS), induced platelet aggregation and plasma coagulation (P<0.05). Pretreatment of both tumor lines with a COX inhibitor did not block the tumor cell induced platelet aggregation (TCIPA). COX [12(S)-HTT] and LOX [12(S)-HETE], metabolites of washed platelets (WP), alone or co-incubated with LAC or FS cells, were analyzed. We observed higher 12(S)-HETE release with respect to 12(S)HHT when WP were co-incubated with LAC cells. With both neoplastic cell (NC) lines prothrombin time (PT) was shortened. Pretreatment of NC with iodoacetic acid, soybean trypsin inhibitor or Factor X-deficient plasma increased the PT. These results indicate that AA metabolites play a role on the procoagulation and platelet aggregation induced by mesenchymal and epithelial murine cancers.

Inhibition of HIV-1 replication in macrophages by red blood cell-mediated delivery of a heterodinucleotide of azidothymidine and 9-(R)-2-(phosphono methoxypropyl)adenine.

Monocyte-derived macrophages (M/M) are considered important in vivo reservoirs for different kinds of viruses, including HIV. Hence, therapeutic strategies are urgently needed to protect these cells from virus infection or to control viral replication. In this paper, we report the synthesis, target delivery and in vitro efficacy of a new heterodinucleotide (AZTpPMPA), able to inhibit HIV-1 production in human macrophages. AZTpPMPA consists of two established anti-HIV drugs [zidovudine (AZT) and tenofovir (PMPA)] chemically coupled together by a phosphate bridge. This drug is not able to prevent p24 production when administered for 18 h to M/M experimentally infected with HIV-1 Bal (inhibition 27%), but can almost completely suppress virus production when given encapsulated into autologous erythrocytes (inhibition of p24 production 97%). AZTpPMPA is slowly converted to PMPA, AZT monophosphate and AZT (36 h half-life at 37 degrees C) by cell-resident enzymes. Thus AZTpPMPA should be considered a new prodrug of AZT and PMPA that is able to provide stechiometric amounts of both nucleoside analogues to macrophage cells and to overcome the low phosphorylating activity of M/M for AZT and the modest permeability of PMPA.