Managing myelodysplastic symptoms in elderly patients

Most patients with myelodysplastic syndromes (MDS) are elderly (median age range 65 to 70 years); as a consequence, the incidence and prevalence of these diseases are rising as the population ages. Physicians are often uncertain about how to identify patients who may benefit from specific treatment strategies. The International Prognostic Scoring System is a widely used tool to assess the risk of transformation to leukemia and to guide treatment decisions, but it fails to take into account many aspects of treating elderly patients, including comorbid illnesses, secondary causes of MDS, prior therapy for MDS, and other age-related health, functional, cognitive, and social problems that affect the outcome and managing of myelodysplastic symptoms. Patients with low-risk disease traditionally have been given only best supportive care, but evidence is increasing that treatment with novel non-conventional drugs such as lenalidomide or methyltransferase inhibitors may influence the natural history of the disease and should be used in conjunction with supportive-care measures. Supportive care of these patients could also be improved in order to enhance their quality of life and functional performance. Elderly patients commonly have multiple medical problems and use medications to deal with these. In addition, they are more likely to have more than one health care provider. These factors all increase the risk of drug interactions and the consequent treatment of toxicities. Manifestations of common toxicities or illnesses may be more subtle in the elderly, owing to age-associated functional deficits in multiple organ systems. Particularly important to the elderly MDS patient is the age-related decline in normal bone marrow function, including the diminished capacity of response to stressors such as infection or myelosuppressive treatments. Through the integration of geriatric and oncological strategies, a personalized approach toward this unique population may be applied. As with many diseases in the elderly, reliance on family members or friends to maintain the prescribed treatments, including travel to and from appointments, may place additional stressors on the patient and his/her support network. Careful evaluation and knowledge of functional status, ability to tolerate treatments, effect of disease progression, and general overall health conditions can provide the best opportunity to support these patients. Immediate assessment of daily living activities may detect deficiencies or deficits that often require early interventions

Invasive apocrine carcinoma of the breast: Myth or fact?

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Pre-surgery supportive and goal-oriented strategies are associated with lower post-surgery perceived distress in women diagnosed with breast cancer

Background: Psycho-oncology literature pointed out that individual health outcomes may depend on patients’ propensity to adopt approach or, conversely, avoidant coping strategies. Nevertheless, coping factors associated with postoperative distress remain unclear, unfolding the lack of tailored procedures to help breast cancer patients manage the psychological burden of scheduled surgery. In view of this, the present study aimed at investigating: 1. pre-/post-surgery distress variations occurring among women diagnosed with breast cancer; 2. the predictivity of approach and avoidant coping strategies and factors in affecting post-surgery perceived distress. Methods: N = 150 patients (mean age = 59.37; SD = ± 13.23) scheduled for breast cancer surgery were administered a screening protocol consisting of the Distress Thermometer (DT) and the Brief-COPE. The DT was used to monitor patients’ distress levels before and after surgery (± 7 days), whereas the Brief-COPE was adopted only preoperatively to evaluate patients’ coping responses to the forthcoming surgical intervention. Non-parametric tests allowed for the detection of pre-/post-surgery variations in patients’ perceived distress. Factor analysis involved the extraction and rotation of principal components derived from the Brief-COPE strategies. The predictivity of such coping factors was investigated through multiple regression (Backward Elimination). Results: The Wilcoxon Signed-Rank Test yielded a significant variation in DT mean scores (TW = -5,68 < -zα/2 = -1,96; p <.001) indicative of lower perceived distress following surgery. The four coping factors extracted and Varimax-rotated were, respectively: 1. cognitive processing (i.e., planning + acceptance + active coping + positive reframing); 2. support provision (i.e., instrumental + emotional support); 3. emotion-oriented detachment (i.e., self-blame + behavioral disengagement + humor + denial); 4. goal-oriented detachment (i.e., self-distraction). Among these factors, support provision (B =.458; β = −.174; t = − 2.03; p =.045), encompassing two approach coping strategies, and goal-oriented detachment (B =.446; β = −.176; t = − 2.06; p =.042), consisting of one avoidant strategy, were strongly related to post-surgery distress reduction. Conclusion: The present investigation revealed that the pre-surgery adoption of supportive and goal-oriented strategies led to postoperative distress reduction among breast cancer patients. These findings highlight the importance of timely psychosocial screening and proactive interventions in order to improve patients’ recovery and prognosis

Interactions between Primary Neurons and Graphene Films with Different Structure and Electrical Conductivity

Graphene-based materials represent a useful tool for the realization of novel neural interfaces. Several studies have demonstrated the biocompatibility of graphene-based supports, but the biological interactions between graphene and neurons still pose open questions. In this work, the influence of graphene films with different characteristics on the growth and maturation of primary cortical neurons is investigated. Graphene films are grown by chemical vapor deposition progressively lowering the temperature range from 1070 to 650 °C to change the lattice structure and corresponding electrical conductivity. Two graphene-based films with different electrical properties are selected and used as substrate for growing primary cortical neurons: i) highly crystalline and conductive (grown at 1070 °C) and ii) highly disordered and 140-times less conductive (grown at 790 °C). Electron and fluorescence microscopy imaging reveal an excellent neuronal viability and the development of a mature, structured, and excitable network onto both substrates, regardless of their microstructure and electrical conductivity. The results underline that high electrical conductivity by itself is not fundamental for graphene-based neuronal interfaces, while other physico–chemical characteristics, including the atomic structure, should be also considered in the design of functional, bio-friendly templates. This finding widens the spectrum of carbon-based materials suitable for neuroscience applications

Pengendalian Frekuensi Dengan Menggunakan Kontrol Fuzzy Prediktif Pada Simulator Plant Turbin-Generator Pada PLTU

Sistem pembangkit dirasakan sangat perlu guna memenuhi kebutuhan tenaga listrik yang semakin meningkat, kestabilan sangat dibutuhkan pada proses pembangkit sehingga sistem pengendalian digunakan untuk menjaga variabel proses tersebut tetap stabil. Salah satunya adalah dengan melakukan pengendali frekuensi pada tubin-generator suatu pembangkit listik, contohnya PLTU (Pembangkit Listrik Tenaga Uap). Frekuensi dari turbin uap harus dijaga kestabilannya agar keluaran daya listrik di generator berjalan dengan baik. Fluktuasi frekuensi adalah salah satu kendala penyampaian daya listrik ke beban, juga waktu kembali yang tidak segera ke kondisi normal akan mengakibatkan kerusakan pada sistem seperti patahnya poros turbin-generator dan kemungkinan terjadi gangguan pada jaringan listrik, sehingga perlu dilakukan pengaturan laju aliran uap yang masuk ke turbin. Kontroler yang digunakan untuk menjaga Perubahan frekuensi adalah kontrol fuzzy prediktif, dengan penambahan gain K1 pada kontrol fuzzy prediktif sebesar 42.35 yang bekerja secara sucsessive kontroler ini dapat mengurangi error sebesar 1,04% jika sistem hanya menggunakan kontroler fuzzy pada saat terjadi Perubahan beban

Protocol of the Long-term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) randomized trial.

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Uridine and pyruvate protect T cells’ proliferative capacity from mitochondrial toxic antibiotics: a clinical pilot study

Antibiotics that inhibit bacterial protein or nucleic acid synthesis and function can exert an off-target action on mitochondria (mitotoxic antibiotics), making actively dividing mammalian cells dependent on uridine and pyruvate supplementation. Based on this rationale, we carried out, for the first time, a randomized pilot study in 55 patients with asymptomatic bacteriuria or positive sperm culture, each treated with a single mitotoxic antibiotic with or without oral supplementation of uridine + pyruvate (Uripyr, Mitobiotix, Italy). The in vivo and ex vivo data show a a 3.4-fold higher value in the differential (before and after the antibiotic treatment) lymphocytes count and a 3.7-fold increase in the percentage of dividing T cells, respectively, in the Uripyr vs the control group. Our findings lay the groundwork to enhance the synergy between antibiotics and the immune system in order to optimize the administration protocols and widen the application potentials of antibiotic therapies as well as to re-evaluate old “forgotten” molecules to fight bacterial infections in the antibiotics resistance era

Endothelial Dysfunction in Patients with Severe Mitral Regurgitation

Mitral valve prolapse (MVP) is the most common cause of severe mitral regurgitation. It has been reported that MVP patients-candidates for mitral valve repair (MVRep)-showed an alteration in the antioxidant defense systems as well as in the L-arginine metabolic pathway. In this study, we investigate if oxidative stress and endothelial dysfunction are an MVP consequence or driving factors. Forty-five patients undergoing MVRep were evaluated before and 6 months post surgery and compared to 29 controls. Oxidized (GSSG) and reduced (GSH) forms of glutathione, and L-arginine metabolic pathway were analyzed using liquid chromatography-tandem mass spectrometry methods while osteoprotegerin (OPG) through the ELISA kit and circulating endothelial microparticles (EMP) by flow cytometry. Six-month post surgery, in MVP patients, the GSSG/GSH ratio decreased while symmetric and asymmetric dimethylarginines levels remained comparable to the baseline. Conversely, OPG levels significantly increased when compared to their baseline. Finally, pre-MVRep EMP levels were significantly higher in patients than in controls and did not change post surgery. Overall, these results highlight that MVRep completely restores the increased oxidative stress levels, as evidenced in MVP patients. Conversely, no amelioration of endothelial dysfunction was evidenced after surgery. Thus, therapies aimed to restore a proper endothelial function before and after surgical repair could benefit MVP patients