Ketogenic Diet in the Treatment of Gliomas and Glioblastomas

In recent years, scientific interest in the use of the ketogenic diet (KD) as a complementary approach to the standard cancer therapy has grown, in particular against those of the central nervous system (CNS). In metabolic terms, there are the following differences between healthy and neoplastic cells: neoplastic cells divert their metabolism to anaerobic glycolysis (Warburg effect), they alter the normal mitochondrial functioning, and they use mainly certain amino acids for their own metabolic needs, to gain an advantage over healthy cells and to lead to a pro-oncogenetic effect. Several works in literature speculate which are the molecular targets of KD used against cancer. The following different mechanisms of action will be explored in this review: metabolic, inflammatory, oncogenic and oncosuppressive, ROS, and epigenetic modulation. Preclinical and clinical studies on the use of KD in CNS tumors have also increased in recent years. An interesting hypothesis emerged from the studies about the possible use of a ketogenic diet as a combination therapy along with chemotherapy (CT) and radiotherapy (RT) for the treatment of cancer. Currently, however, clinical data are still very limited but encouraging, so we need further studies to definitively validate or disprove the role of KD in fighting against cancer

Drug resistance in B and non-B subtypes amongst subjects recently diagnosed as primary/recent or chronic HIV-infected over the period 2013–2016: Impact on susceptibility to first-line strategies including integrase strand-transfer inhibitors

Objectives To characterize the prevalence of transmitted drug resistance mutations (TDRMs) by plasma analysis of 750 patients at the time of HIV diagnosis from January 1, 2013 to November 16, 2016 in the Veneto region (Italy), where all drugs included in the recommended first line therapies were prescribed, included integrase strand transfer inhibitors (InNSTI). Methods TDRMs were defined according to the Stanford HIV database algorithm. Results Subtype B was the most prevalent HIV clade (67.3%). A total of 92 patients (12.3%) were expected to be resistant to one drug at least, most with a single class mutation (60/68–88.2% in subtype B infected subjectsand 23/24–95.8% in non-B subjects) and affecting mainly NNRTIs. No significant differences were observed between the prevalence rates of TDRMs involving one or more drugs, except for the presence of E138A quite only in patients with B subtype and other NNRTI in subjects with non-B infection. The diagnosis of primary/recent infection was made in 73 patients (9.7%): they had almost only TDRMs involving a single class. Resistance to InSTI was studied in 484 subjects (53 with primary-recent infection), one patient had 143C in 2016, a total of thirteen 157Q mutations were detected (only one in primary/recent infection). Conclusions Only one major InSTI-TDRM was identified but monitoring of TDRMs should continue in the light of continuing presence of NNRTI-related mutation amongst newly diagnosed subjects, sometime impacting also to modern NNRTI drugs recommended in first-line therapy

Lactic acid bacteria adjunct cultures exert a mitigation effect against spoilage microbiota in fresh cheese

Lactic acid bacteria (LAB) have a strong mitigation potential as adjunct cultures to inhibit undesirable bacteria in fermented foods. In fresh cheese with low salt concentration, spoilage and pathogenic bacteria can affect the shelf life with smear on the surface and packaging blowing. In this work, we studied the spoilage microbiota of an Italian fresh cheese to find tailor-made protective cultures for its shelf life improvement. On 14-tested LAB, three of them, namely Lacticaseibacillus rhamnosus LRH05, Latilactobacillus sakei LSK04, and Carnobacterium maltaromaticum CNB06 were the most effective in inhibiting Gram-negative bacteria. These cultures were assessed by the cultivation-dependent and DNA metabarcoding approach using in vitro experiments and industrial trials. Soft cheese with and without adjunct cultures were prepared and stored at 8 and 14 \ub0C until the end of the shelf life in modified atmosphere packaging. Data demonstrated that the use of adjunct cultures reduce and/or modulate the growth of spoilage microbiota at both temperatures. Particularly, during industrial experiments, C. maltaromaticum CNB06 and Lcb. rhamnosus RH05 lowered psychrotrophic bacteria of almost 3 Log CFU/g in a 5-week stored cheese. On the contrary, Llb. sakei LSK04 was able to colonize the cheese but it was not a good candidate for its inhibition capacity. The combined approach applied in this work allowed to evaluate the protective potential of LAB strains against Gram-negative communities

Conceptual design of the Gas Injection and Vacuum System for DTT NBI

The Divertor Tokamak Test (DTT) is a new experimental facility whose construction is starting in Frascati, Rome, Italy; its main goals are improving the understanding of plasma-wall interactions and supporting the development of ITER and DEMO. DTT will be equipped with a Neutral Beam Injector (NBI) based on negative deuterium ions, designed to inject 10 MW of power to the tokamak. A fundamental system for the good operations of the DTT NBI will be its Gas injection and Vacuum System (GVS). Indeed, the efficiency of the entire NBI strongly depends on the good performance of its GVS. The GVS for DTT NBI will be composed of two systems working in parallel: a grounded section connected to the main vacuum vessel, and a high voltage part connected to the ion source vessel and working at -510 kV voltage. The grounded part will feature a fore vacuum system (given by screw and roots pumps) plus a high vacuum system based on turbo-molecular pumps located on the side walls of the vessel and Non-Evaporable Getter (NEG) pumps located inside the vessel on the upper and lower surfaces. On the other hand, the high voltage part will feature a fore vacuum system (given by two compact screw pumps mounted on the external surface for the ion source vessel) plus a high vacuum system based on turbo-molecular pumps also located on the sidewalls of the ion source vessel. A dedicated deuterium gas injection will feed the process gas to the ion source and the neutralizer. This paper gives a description of the conceptual design of the GVS for DTT NBI, and of the procedure followed to optimize this system considering the operational requirements and the other constraints of the DTT NBI.Comment: 12 pages, 8 figures, presented at the SOFT 2022 conferenc

Bulas de medicamentos e a informação adequada ao paciente

OBJECTIVE: To investigate the adequacy of the content and format of the patient information section in package inserts of commonly prescribed drugs at the internal medicine service of a school hospital. METHODS: Forty eight package inserts were collected from six pharmacies of the city of Porto Alegre in June 1998. The presence of mandatory notification and other information required by Brazilian laws that regulate inserts content was examined. RESULTS: No one package inserts contained all the notification required by law. Warnings about medication storage and expiration date were the most frequently information found in package inserts analyzed. CONCLUSION: Important information for the drug user was not presented in package inserts analyzed, limiting the purpose of inserts as an instrument for patient education.OBJETIVO: Avaliar a adequação da forma e conteúdo da seção de "informações ao paciente" das bulas de medicamentos, freqüentemente prescritos no ambulatório de medicina interna de um hospital universitário. MÉTODOS: Foram selecionadas 48 bulas disponíveis em três redes de farmácia e três farmácias de pequeno porte de Porto Alegre, em junho de 1998. Por meio de um formulário, foi verificada a presença de frases de formato padronizado e outras informações exigidas pela Portaria 110, que regulamenta o conteúdo das bulas de medicamentos. RESULTADOS: Em nenhuma das bulas analisadas foi verificada a presença de todas as frases e demais informações exigidas pela legislação. Cuidados com o armazenamento e com o prazo de validade dos medicamentos foram as informações mais freqüentemente apresentadas nas bulas analisadas. CONCLUSÕES: Ausência de informações importantes para o usuário, sobre o medicamento nas bulas, reduz o seu valor enquanto material educativo para o paciente

Increasing the heme-dependent respiratory efficiency in Lactococcus lactis by inhibition of lactate dehydrogenase

The discovery of heme-induced respiration in Lactococcus lactis has radically improved the industrial processes used for the biomass production of this species. Here, we show that inhibition of the lactate dehydrogenase activity of L. lactis during growth under respiration-permissive conditions can stimulate aerobic respiration, thereby increasing not only growth efficiency but also the robustness of this organism

Exercise Therapy for Fibromyalgia

Fibromyalgia syndrome, a chronic condition typically characterized by widespread pain, nonrestorative sleep, fatigue, cognitive dysfunction, and other somatic symptoms, negatively impacts physical and emotional function and reduces quality of life. Exercise is commonly recommended in the management of people with fibromyalgia, and interest in examining exercise benefits for those with the syndrome has grown substantially over the past 25 years. Research supports aerobic and strength training to improve physical fitness and function, reduce fibromyalgia symptoms, and improve quality of life. However, other forms of exercise (e.g., tai chi, yoga, Nordic walking, vibration techniques) and lifestyle physical activity also have been investigated to determine their effects. This paper highlights findings from recent randomized controlled trials and reviews of exercise for people with fibromyalgia, and includes information regarding factors that influence response and adherence to exercise to assist clinicians with exercise and physical activity prescription decision-making to optimize health and well-being

Enabling ultra-high dose rate electron beams at a clinical linear accelerator for isocentric treatments

BACKGROUND AND PURPOSE Radiotherapy delivery with ultra-high dose rates (UHDR) has consistently produced normal tissue sparing while maintaining efficacy for tumour control in preclinical studies, known as the FLASH effect. Modified clinical electron linacs have been used for pre-clinical studies at reduced source-surface distance (SSD) and novel intra-operative devices are becoming available. In this context, we modified a clinical linac to deliver 16 MeV UHDR electron beams with an isocentric setup. MATERIALS AND METHODS The first Varian TrueBeam (SN 1001) was clinically operative between 2009-2022, it was then decommissioned and converted into a research platform. The 18 MeV electron beam was converted into the experimental 16 MeV UHDR. Modifications were performed by Varian and included a software patch, thinner scattering foil and beam tuning. The dose rate, beam characteristics and reproducibility were measured with electron applicators at SSD = 100 cm. RESULTS The dose per pulse at isocenter was up to 1.28 Gy/pulse, corresponding to average and instantaneous dose rates up to 256 Gy/s and 3⋅10$^{5}$ Gy/s, respectively. Beam characteristics were equivalent between 16 MeV UHDR and conventional for field sizes up to 10x10cm$^{2}$ and an overall beam reproducibility within ± 2.5% was measured. CONCLUSIONS We report on the first technical conversion of a Varian TrueBeam to produce 16 MeV UHDR electron beams. This research platform will allow isocenter experiments and deliveries with conventional setups up to field sizes of 10x10 cm$^{2}$ within a hospital environment, reducing the gap between preclinical and clinical electron FLASH investigations