Functional assessment of cancer therapy questionnaire for breast cancer (FACT-B+4): Italian version validation

BACKGROUND: Improvements in breast cancer diagnosis and treatment led to an increased incidence of survivors' rate. The healthcare system has to face new problems related not only to the treatment of the disease, but also to the management of the quality of life after the diagnosis. The aim of this study was to validate the Italian version of the Functional Assessment of Cancer Therapy - Breast (FACT-B+4) questionnaire and to evaluate its reliability. METHODS: The questionnaire was administered twice, with an interval of three days between each administration, to a cohort of women of the Breast Surgical Unit, PoliclincoUmberto I. Cronbach's alpha was used as a measure of the internal consistency of the Italian version. RESULTS: The Italian version of the tool was administered to 55 subjects. The Cronbach's alpha for most scores registered values >0.7, both at baseline and at the follow-up analysis, therefore the subscale showed good internal consistency. CONCLUSIONS: The Italian version of FACT-B+4 demonstrated acceptable reliability properties in the Breast Unit patients. The use of this questionnaire seemed to be effective and in line with the results derived from the English and Spanishversions. Internal consistency and validity had similar performance results

Tablet splitting in elderly patients with dementia: The case of quetiapine

Quetiapine is an atypical antipsychotic approved for treating schizophrenia, bipolar depression, and mania but is frequently used in an off-label manner to control the behavioral and psychological symptoms of dementia in elderly patients with dementia. Due to the need to personalize doses for elderly patients with dementia, quetiapine tablet manipulation is widespread in hospital settings, long-term care facilities, and patient homes. The aim of this study was to assess the impact of the different splitting techniques on quetiapine fumarate tablets by analysing the obtained sub-divided tablets and to discuss compliance with the European Pharmacopoeia limits on whole and split tablets. Quetiapine fumarate tablets of two dose strengths were taken at random (in a number able to assure a power of 0.8 during statistical comparison) and were split with a kitchen knife or tablet cutter. The weight and the drug content were determined for each half tablet. The obtained data were compared to the European Pharmacopoeia limits. The differences between the different splitting techniques were statistically tested. Data showed that split tablets, independently of the dose strength and the technique employed, were not compliant with the European Pharmacopoeia specifications for both entire and subdivided tablets in terms of weight and content uniformity. Thus, such a common practice could have potential effects on treatment efficacy and toxicity, especially when also considering the fragility of the elderly target population in which polypharmacotherapy is very common. These results indicate a compelling need for flexible quetiapine formulations that can assure more accurate dose personalization

Cytoprotective effect of preparations from various parts of Punica granatum L. fruits in oxidatively injured mammalian cells in comparison with their antioxidant capacity in cell free systems

none9Pomegranate (Punica granatum L.) juice (PJ) is being increasingly proposed as a nutritional supplement to prevent atherosclerosis in humans. This therapeutically valuable potential has been attributed to PJ antioxidant capacity which has been mostly tested by means of cell-free assays: indeed, to the best of our knowledge, no study has focused on the direct antioxidant capacity of PJ in cultured cells. Here, the antioxidant capacity in cell free-systems of preparations from various parts of pomegranate has been compared with their cytoprotective – bona fide antioxidant – activity in cultured human cells (U937 promonocytes and HUVEC endothelial cells) exposed to an array of oxidizing agents. Pomegranate derivatives were PJ, arils only juice (AJ) and aqueous rinds extract (RE). In cell-free assays – 1,1-diphenyl-2-picrylhydrazyl (DPPH), chemiluminescence luminol/xanthine/xanthine oxidase and lipoxygenase assays – all the preparations displayed good antioxidant capacity, the relative potency order being RE > PJ > AJ. On the contrary, only RE was capable of preventing the deleterious effects – cytotoxicity, DNA damage and depletion of non protein sulphydrils (NPSH) pool – caused by treatment of cells with H2O2, tert-butylhydroperoxide (tB-OOH) or oxidized lipoproteins (Ox-LDL) via a mechanism which is likely to involve both direct scavenging of radical species and iron chelation. Surprisingly, AJ and PJ slightly sensitized cells to the cytotoxic effects of the three agents. Then it would appear that AJ, the major and tasty part of PJ, does not contain ellagic acid and punicalagin (i.e. the polyphenols highly represented in RE which are reputed to be responsible for the antioxidant capacity) in amounts sufficient to exert cytoprotection in oxidatively injured, living cells. Based on these results, the development and evaluation of rinds-only based derivatives for antiatherogenic preventive purposes in humans should be encouraged.openSESTILI P; MARTINELLI C; RICCI D; FRATERNALE D; BUCCHINI A; GIAMPERI L; CURCIO R; PICCOLI G; STOCCHI V.Sestili, Piero; Martinelli, Chiara; Ricci, Donata; Fraternale, Daniele; Bucchini, ANAHI ELENA ADA; Giamperi, Laura; Curcio, R; Piccoli, Giovanni; Stocchi, Vilbert

Increasing the amylose content of durum wheat through silencing of the SBEIIa genes

<p>Abstract</p> <p>Background</p> <p>High amylose starch has attracted particular interest because of its correlation with the amount of Resistant Starch (RS) in food. RS plays a role similar to fibre with beneficial effects for human health, providing protection from several diseases such as colon cancer, diabetes, obesity, osteoporosis and cardiovascular diseases. Amylose content can be modified by a targeted manipulation of the starch biosynthetic pathway. In particular, the inactivation of the enzymes involved in amylopectin synthesis can lead to the increase of amylose content. In this work, genes encoding starch branching enzymes of class II (SBEIIa) were silenced using the RNA interference (RNAi) technique in two cultivars of durum wheat, using two different methods of transformation (biolistic and Agrobacterium). Expression of RNAi transcripts was targeted to the seed endosperm using a tissue-specific promoter.</p> <p>Results</p> <p>Amylose content was markedly increased in the durum wheat transgenic lines exhibiting <it>SBEIIa </it>gene silencing. Moreover the starch granules in these lines were deformed, possessing an irregular and deflated shape and being smaller than those present in the untransformed controls. Two novel granule bound proteins, identified by SDS-PAGE in SBEIIa RNAi lines, were investigated by mass spectrometry and shown to have strong homologies to the waxy proteins. RVA analysis showed new pasting properties associated with high amylose lines in comparison with untransformed controls. Finally, pleiotropic effects on other starch genes were found by semi-quantitative and Real-Time reverse transcription-polymerase chain reaction (RT-PCR).</p> <p>Conclusion</p> <p>We have found that the silencing of <it>SBEIIa </it>genes in durum wheat causes obvious alterations in granule morphology and starch composition, leading to high amylose wheat. Results obtained with two different methods of transformation and in two durum wheat cultivars were comparable.</p

CRISPR-Cas9 Multiplex Editing of the &#945;-Amylase/Trypsin Inhibitor Genes to Reduce Allergen Proteins in Durum Wheat

Wheat and its derived foods are widespread, representing one of the main food sources globally. During the last decades, the incidence of disorders related to wheat has become a global issue for the human population, probably linked to the spread of wheat-derived foods. It has been ascertained that structural and metabolic proteins, like \u3b1-amylase/trypsin inhibitors (ATI), are involved in the onset of wheat allergies (bakers' asthma) and probably Non-Coeliac Wheat Sensitivity (NCWS). The ATI are a group of exogenous protease inhibitors, which are encoded by a multigene family dispersed over several chromosomes in durum and bread wheat. WTAI-CM3 and WTAI-CM16 subunits are considered among the main proteins involved in the onset of bakers' asthma and probably NCWS. A CRISPR-Cas9 multiplexing strategy was used to edit the ATI subunits WTAI-CM3 and WTAI-CM16 in the grain of the Italian durum wheat cultivar Svevo with the aim to produce wheat lines with reduced amount of potential allergens involved in adverse reactions. Using a marker gene-free approach, whereby plants are regenerated without selection agents, homozygous mutant plants without the presence of CRISPR vectors were obtained directly from T0 generation. This study demonstrates the capability of CRISPR technology to knock out immunogenic proteins in a reduced time compared to conventional breeding programmes. The editing of the two target genes was confirmed either at molecular (sequencing and gene expression study) or biochemical (immunologic test) level. Noteworthy, as a pleiotropic effect, is the activation of the ATI 0.28 pseudogene in the edited lines

Proteomic changes and molecular effects associated with Cr(III) and Cr(VI) treatments on germinating kiwifruit pollen

The present study is aimed at identifying molecular changes elicited by Cr(III) and Cr(VI) on germinating kiwifruit pollen. To address this question, comparative proteomic and DNA laddering analyses were performed. While no genotoxic effect was detected, a number of proteins whose accumulation levels were altered by treatments were identified. In particular, the upregulation of some proteins involved in the scavenging response, cell redox homeostasis and lipid synthesis could be interpreted as an oxidative stress response induced by Cr treatment. The strong reduction of two proteins involved in mitochondrial oxidative phosphorylation and a decline in ATP levels were also observed. The decrease of pollen energy availability could be one of the causes of the severe inhibition of the pollen germination observed upon exposure to both Cr(III) and Cr(VI). Finally, proteomic and biochemical data indicate proteasome impairment: the consequential accumulation of misfolded/damaged proteins could be an important molecular mechanism of Cr(III) toxicity in pollen

No effect of creatine supplementation on oxidative stress and cardiovascular parameters in spontaneously hypertensive rats

Background: Exacerbated oxidative stress is thought to be a mediator of arterial hypertension. It has been postulated that creatine (Cr) could act as an antioxidant agent preventing increased oxidative stress. The aim of this study was to investigate the effects of nine weeks of Cr or placebo supplementation on oxidative stress and cardiovascular parameters in spontaneously hypertensive rats (SHR). Findings: Lipid hydroperoxidation, one important oxidative stress marker, remained unchanged in the coronary artery (Cr: 12.6 +/- 1.5 vs. Pl: 12.2 +/- 1.7 nmol.mg(-1); p = 0.87), heart (Cr: 11.5 +/- 1.8 vs. Pl: 14.6 +/- 1.1 nmol.mg(-1); p = 0.15), plasma (Cr: 67.7 +/- 9.1 vs. Pl: 56.0 +/- 3.2 nmol.mg(-1); p = 0.19), plantaris (Cr: 10.0 +/- 0.8 vs. Pl: 9.0 +/- 0.8 nmol.mg(-1); p = 0.40), and EDL muscle (Cr: 14.9 +/- 1.4 vs. Pl: 17.2 +/- 1.5 nmol.mg(-1); p = 0.30). Additionally, Cr supplementation affected neither arterial blood pressure nor heart structure in SHR (p &gt; 0.05). Conclusions: Using a well-known experimental model of systemic arterial hypertension, this study did not confirm the possible therapeutic effects of Cr supplementation on oxidative stress and cardiovascular dysfunction associated with arterial hypertension.FAPES

Effects of a commercially available branched-chain amino acid-alanine-carbohydrate-based sports supplement on perceived exertion and performance in high intensity endurance cycling tests

Background:Sports nutritional supplements containing branched-chain amino acids (BCAA) have been widelyreported to improve psychological and biological aspects connected to central fatigue and performance inendurance exercise, although the topic is still open to debate. The aim of the present study was to determinewhether the intake of a commercially available BCAA-based supplement, taken according to the manufacturer’srecommendations, could affect the rating of perceived exertion (RPE) and performance indexes at the beginning(1d) and end of a 9-week (9w) scheduled high intensity interval training program, with an experimental approachintegrating the determination of psychometric, performance, metabolic and blood biochemical parameters.Methods:This was a randomized double-blind placebo-controlled study. Thirty-two untrained, healthy young adults(20 males and 12 female) were enrolled. A high-intensity endurance cycling (HIEC) test was used to induce fatigue inthe participants: HIEC consisted in ten 90 s sprints interspersed by ten 3 min recovery phases and followed by a finalstep time to exhaustion was used. In parallel with RPE, haematological values (creatine kinase, alanine, BCAA,tryptophan, ammonia and glucose levels), and performance indexes (maximal oxygen consumption - VO2max,powerassociated with lactate thresholds - WLT1,WLT2and time to exhaustion - TTE) were assessed. All subject took thesupplement (13.2 g of carbohydrates; 3.2 g of BCAA and 1.6 g of L-alanine per dose) or placebo before each test andtraining session. Dietary habits and training load were monitored during the entire training period.Results:The administration of the supplement (SU) at 1d reduced RPE by 9% during the recovery phase, as comparedto the placebo (PL); at 9w the RPE scores were reduced by 13 and 21% during the sprint and recovery phase,respectively; at 9w, prolonged supplement intake also improved TTE and TRIMP. SU intake invariably promoted a rapidincrease (within 1 h) of BCAA serum blood levels and prevented the post-HIEC tryptophan: BCAA ratio increase foundin the PL group, at both 1d and 9w. There was no difference in dietary habits between groups and those habits didnot change over time; no difference in glycemia was found between SU and PL. VO2max,WLT1and WLT2valuesimproved over time, but were unaffected by supplement intake. Conclusions:On the whole, these results suggest that i) the intake of the BCAA-based commercially availablesupplement used in this study reduces RPE as a likely consequence of an improvement in the serum tryptophan: BCAAratio; ii) over time, reduced RPE allows subjects to sustain higher workloads, leading to increased TRIMP and TTE

Non-adherence to Mediterranean diet and synergy with lifestyle habits in the occurrence of breast cancer: a case-control study in Italy

Objective: The aim of this study was to assess the synergistic effect of non-adherence to the Mediterranean Diet (MD) and lifestyle habits on the occurrence of breast cancer (BC). Patients and methods: A case-control study was carried out from September 2018 to February 2019 at the Teaching Hospital "Umberto I" in Rome. A Food Frequency Questionnaire was used for assessing the level of adherence to MD, the IPAQ Questionnaire to measure physical activity, and AUDIT-C to estimate alcohol consumption. The possible interaction between risk factors was tested using the synergism index. Results: A total of 94 cases and 88 controls were enrolled (median age 55.8 for cases and 57.9 for controls). The MD Score over 6 was associated with low odds of having breast cancer (OR = 0.29; 95% CI: 0.12-0.69). There is a clear indication for the additivity and synergism between non-adherence to MD and many risk factors on the occurrence of BC: current smoker (S = 2.02; 95% CI 0.62-8.07), physical inactivity (S = 2.14; 95% CI 0.71 2-8.28) and alcohol consumption (S = 3.02; 95% CI 0.91-12.95). Conclusions: Primary prevention of BC can benefit from intervention targeting nutritional and lifestyle factors that act synergistically

Covid-19 disease, women’s predominant non-heparin vaccine-induced thrombotic thrombocytopenia and kounis syndrome: A passepartout cytokine storm interplay

Coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitute one of the deadliest pandemics in modern history demonstrating cardiovascular, gastrointestinal, hematologic, mucocutaneous, respiratory, neurological, renal and testicular manifestations and further complications. COVID-19-induced excessive immune response accompanied with uncontrolled release of cytokines culminating in cytokine storm seem to be the common pathogenetic mechanism of these complications. The aim of this narrative review is to elucidate the relation between anaphylaxis associated with profound hypotension or hypoxemia with pro-inflammatory cytokine release. COVID-19 relation with Kounis syndrome and post-COVID-19 vaccination correlation with heparin-induced thrombocytopenia with thrombosis (HITT), especially serious cerebral venous sinus thrombosis, were also reviewed. Methods: A current literature search in PubMed, Embase and Google databases was performed to reveal the pathophysiology, prevalence, clinical manifestation, correlation and treatment of COVID-19, anaphylaxis with profuse hypotension, Kounis acute coronary syndrome and thrombotic events post vaccination. Results: The same key immunological pathophysiology mechanisms and cells seem to underlie COVID-19 cardiovascular complications and the anaphylaxis-associated Kounis syndrome. The myocardial injury in patients with COVID-19 has been attributed to coronary spasm, plaque rupture and microthrombi formation, hypoxic injury or cytokine storm disposing the same pathophysiology with the three clinical variants of Kounis syndrome. COVID-19-interrelated vaccine excipients as polysorbate, polyethelene glycol (PEG) and trometamol constitute potential allergenic substances. Conclusion: Better acknowledgement of the pathophysiological mechanisms, clinical similarities, multiorgan complications of COVID-19 or other viral infections as dengue and human immunodeficiency viruses along with the action of inflammatory cells inducing the Kounis syndrome could identify better immunological approaches for prevention, treatment of the COVID-19 pandemic as well as post-COVID-19 vaccine adverse reactions