Diabetes management in cancer patients. An Italian Association of Medical Oncology, Italian Association of Medical Diabetologists, Italian Society of Diabetology, Italian Society of Endocrinology and Italian Society of Pharmacology multidisciplinary consensus position paper.

Cancer management has significantly evolved in recent years, focusing on a multidisciplinary team approach to provide the best possible patient care and address the various comorbidities, toxicities, and complications that may arise during the patient's treatment journey. The co-occurrence of diabetes and cancer presents a significant challenge for health care professionals worldwide. Management of these conditions requires a holistic approach to improve patients' overall health, treatment outcomes, and quality of life, preventing diabetes complications and cancer treatment side-effects. In this article, a multidisciplinary panel of experts from different Italian scientific societies provide a critical overview of the co-management of cancer and diabetes, with an increasing focus on identifying a novel specialty field, 'diabeto-oncology', and suggest new co-management models of cancer patients with diabetes to improve their care. To better support cancer patients with diabetes and ensure high levels of coordinated care between oncologists and diabetologists, 'diabeto-oncology' could represent a new specialized field that combines specific expertise, skills, and training.

Quantitative Time-Course Analysis of Osmotic and Salt Stress in Arabidopsis thaliana Using Short Gradient Multi-CV FAIMSpro BoxCar DIA.

A major limitation when undertaking quantitative proteomic time-course experimentation is the tradeoff between depth-of-analysis and speed-of-analysis. In high complexity and high dynamic range sample types, such as plant extracts, balance between resolution and time is especially apparent. To address this, we evaluate multiple compensation voltage (CV) high field asymmetric waveform ion mobility spectrometry (FAIMSpro) settings using the latest label-free single-shot Orbitrap-based DIA acquisition workflows for their ability to deeply quantify the Arabidopsis thaliana seedling proteome. Using a BoxCarDIA acquisition workflow with a -30 -50 -70 CV FAIMSpro setting, we were able to consistently quantify >5000 Arabidopsis seedling proteins over a 21-min gradient, facilitating the analysis of ∼42 samples per day. Utilizing this acquisition approach, we then quantified proteome-level changes occurring in Arabidopsis seedling shoots and roots over 24 h of salt and osmotic stress, to identify early and late stress response proteins and reveal stress response overlaps. Here, we successfully quantify >6400 shoot and >8500 root protein groups, respectively, quantifying nearly ∼9700 unique protein groups in total across the study. Collectively, we pioneer a short gradient, multi-CV FAIMSpro BoxCarDIA acquisition workflow that represents an exciting new analysis approach for undertaking quantitative proteomic time-course experimentation in plants.

Parallel convolutional processing using an integrated photonic tensor core.

With the proliferation of ultrahigh-speed mobile networks and internet-connected devices, along with the rise of artificial intelligence (AI)1, the world is generating exponentially increasing amounts of data that need to be processed in a fast and efficient way. Highly parallelized, fast and scalable hardware is therefore becoming progressively more important2. Here we demonstrate a computationally specific integrated photonic hardware accelerator (tensor core) that is capable of operating at speeds of trillions of multiply-accumulate operations per second (1012 MAC operations per second or tera-MACs per second). The tensor core can be considered as the optical analogue of an application-specific integrated circuit (ASIC). It achieves parallelized photonic in-memory computing using phase-change-material memory arrays and photonic chip-based optical frequency combs (soliton microcombs3). The computation is reduced to measuring the optical transmission of reconfigurable and non-resonant passive components and can operate at a bandwidth exceeding 14 gigahertz, limited only by the speed of the modulators and photodetectors. Given recent advances in hybrid integration of soliton microcombs at microwave line rates3-5, ultralow-loss silicon nitride waveguides6,7, and high-speed on-chip detectors and modulators, our approach provides a path towards full complementary metal-oxide-semiconductor (CMOS) wafer-scale integration of the photonic tensor core. Although we focus on convolutional processing, more generally our results indicate the potential of integrated photonics for parallel, fast, and efficient computational hardware in data-heavy AI applications such as autonomous driving, live video processing, and next-generation cloud computing services.

Mujer de 25 años con lesión seudotumoral talámica posvacunal / A 25 years-old woman with a postvaccine thalamic pseudotumoral lesion

No disponible

Postoperative infections after cytoreductive surgery and HIPEC for peritoneal carcinomatosis: proposal and results from a prospective protocol study of prevention, surveillance and treatment.

The incidence of infectious complications due to several contributory causes is particularly elevated and life-threatening in patients undergoing peritonectomy and HIPEC procedure for peritoneal carcinomatosis. Following a previous experience, we started a prospective protocol study of preoperative screening, perioperative prophylaxis and postoperative surveillance and treatment. A total of 111 patients with peritoneal carcinomatosis of various origin underwent CRS with HIPEC between April 2004 and December 2012. The group was divided into a pilot group of 30 patients (04/04 to 05/08) and a main group of 81 patients (06/08 to 12/12). Overall postoperative morbidity rate was 44%, with 35.8% of symptomatic infections. No post-operative mortality was observed. Microorganisms were isolated in 24 patients (80.0%) in the first group and 54 (66.7%) in the second. They were symptomatic in 18 cases (75.0%) and 25 (46.3%) cases respectively. In addition, 7 invasive candidosis were recorded (25.9%). Colon resection (P = 0.01) and duration of surgery (P = 0.0008) were associated with infection at logistic regression model. Concerning symptomatic infections, only Infection Risk Index (P = 0.009) showed significance at multivariate analysis. Despite a significant incidence of infectious complications, establishment of a prevention, surveillance and treatment protocol lead to a zero mortality rate in the observed patients of our experience. Owing to the obtained results, we suggest the use of a standardized protocol for the prevention, monitoring and treatment in all patients enrolled for cytoreductive surgery and HIPEC.

Chronic kidney disease is still present after renal transplantation with excellent function.

According to a k/DOQI work group, chronic kidney disease (CKD) can be present also in subjects with glomerular filtration rate (GFR) >90 mL/min or a serum creatinine (sCr) below 1.3 mg/dL. The aim of this study was to document the prevalence of clinical or biologic abnormalities among 190 cadaveric renal transplant patients with excellent and stable renal function at 6 months after transplantation as well as 5 years later. The recipients were 82 women and 108 men of mean age at transplantation of 44.56 +/- 11.73 years. All patients were on Neoral-based immunosuppression with at least 5-year follow-up. Mean sCr was 1.18 +/- 0.2 mg/dL. Mean GFR was 78.57 +/- 27.06 mL/min. Systolic blood pressure was >130 mm Hg in 56.6%, although 78.3% of patients were on antihypertensive therapy; 34.3% were anemic; 75.4% had serum cholesterol >200 mg/dL; 62.2% had serum triglyceride levels >170 mg/dL. Serum intact parathyroid hormone >100 pg/mL was observed in 38% of patients and 43% were on vitamin D supplementation, and 11.4% had developed posttransplant diabetes mellitus. With respect to controls, von Willebrand factor was higher in 81.2% (P < .0001; RR = 11); serum homocysteine levels in 75% (P < 0.001; RR = 7.61); PAI-1 in 37.5% (P = .0009; RR = 4). At 5 years posttransplantation we observed an overall improvement in these abnormalities. The vast majority of renal transplant patients with excellent graft function belong to stage 1 of CKD being affected by hypertension, dyslipidemia, anemia, and residual hyperparathyroidism. Markers of endothelial dysfunction were largely abnormal, a condition that could predispose to cardiovascular events.

Cardiovascular risk factors in severe chronic renal failure: the role of dietary treatment.

BACKGROUND: Lipoprotein abnormalities and increased oxidized LDL (OxLDL) are often observed in uremia and are reported to play a central role in the development of cardiovascular disease (CVD). Vegan diet, known for its better lipoprotein profile and antioxidant vitamins content, could protect against CVD. Aim of this study was to investigate the influence of vegan diet supplemented with essential amino acids (EAA) and ketoanalogues (VSD) on both traditional and non-traditional cardiovascular risk factors (CVRF). METHODS: Twenty-nine patients (18 M, 11 F) aged 55 years (range 29-79 years) with advanced chronic renal failure (median sCr: 5.6 mg/dl) on very low protein vegetarian diet (0.3 g/kg/day) supplemented with a mixture of EAA and ketoacids (VSD) and 31 patients (20 M, 11 F) aged 65 years (range 29 - 82 years) on conventional low-protein diet (CD: 0.6 g/kg/day) with a similar renal function (median sCr: 5.2 mg/dl), were investigated for lipids and apolipoprotein parameters (traditional CVRF) as well as for oxidative stress (oxidized LDL, antibodies against OxLDL and thiobarbituric acid-reactive substances (TBARS)), total homocysteine (tHcy), lipoprotein(a) (Lp(a)), albumin and c-reactive protein (CRP) (non-traditional CVRF) including vitamins A, E, B12 and folic acid. RESULTS: Compared to patients on CD, those on VSD showed increased HDL cholesterol levels (p < 0.005) with a reduction of LDL cholesterol (p < 0.01) and an increase of apoA1/apoB ratio (p < 0.02). Among non-traditional CVRF, a mild but significant reduction of OxLDL (p < 0.05) with lower TBARS concentrations (p < 0.01) and a significant reduction of total homocysteine (p < 0.002), Lp(a) (p < 0.002) and CRP levels (p < 0.05) were also observed in these patients. Concentrations of vitamin E and A were not different between the two groups while vitamin B12 and folic acid resulted markedly increased in patients on VSD. OxLDL significantly correlated with total and LDL cholesterol, triglycerides and Apo B in CD but not in VSD patients. Patients on CD also showed a significant correlation between urea and CRP. After a multivariate analysis, only urea (p < 0.001) and OxLDL (p < 0.006) were associated to a risk of CRP > 0.3 mg/dl. CONCLUSIONS: These results indicate a better lipoprotein profile in patients on vegan diet including non-traditional CVRF. In particular, these patients show a reduced oxidative stress with a reduced acute-phase response (CRP) as compared to patients on conventional diet. We hypothesize that urea, significantly lower in patients on VSD, may account, possibly together with the reduction of other protein breakdown products, for the decreased acute-phase response observed in these patients. Our findings suggest that low-protein diets, and vegan in particular, may exert a beneficial effect on the development of cardiovascular disease in patients with end-stage renal disease (ESRD).

Can herbal products be used safely during pregnancy? Focus on echinacea.

QUESTION: Many of my patients are now using herbal medicines; some even use them during pregnancy. As we enter the "cold and flu" season, many are inquiring about use of the herb echinacea to prevent these ailments. Is there any evidence to suggest that use of echinacea during pregnancy is safe? ANSWER: Although herbal products have been used in the past during pregnancy and delivery, there is little evidence showing they are safe. Many authoritative reviews of echinacea report that its safety for use during pregnancy has not been established. A recent Motherisk study showed that use of echinacea during the first trimester of pregnancy was not associated with increased risk of major malformations.

Detección de aversiones gustativas inducidas por estímulos incondicionados débiles como la rotación / Detection of taste aversions induced by weak unconditioned stimuli like body rotarion

El objetivo principal de este estudio fue el desarrollo de un procedimiento conductual suficientemente potente para detectar aversiones inducidas en un único ensayo por estímulos aversivos débiles, concretamente rotación corporal y dosis bajas de LiCl, en ratas wistar. Dicho procedimiento implica el uso de una prueba de elección entre estímulos con diferentes preferencias previas. El experimento 1a demostró que utilizando una solución de café descafeinado y otra de vinagre de sidra, la aversión adquirida a la solución preferida (café) mediante rotación corporal sólo aparece en una prueba de elección posterior entre ambos estímulos, cuando se anula la neofobia al estímulo menos preferido (vinagre). Una única preexposición antes de la prueba de elección, es suficiente para anular el efecto de neofobia a dicho sabor (experimento 1b). En el experimento 2 el mismo procedimiento permitió detectar consistentemente aversiones inducidas por inyecciones intraperitoneales (i.p.) de cloruro de litio (LiCl) cuando se aplican dosis reducidas (0.2 por cientop.c., peso corporal, 0.15Molar). La importancia de este procedimiento reside en que permite un mejor estudio de los procesos psicobiológicos implicados en el aprendizaje aversivo gustativo y por ello se propone como una herramienta comportamental especialmente sensible para la detección de aversiones inducidas por estímulos incondicionados débiles de distinta naturaleza (AU)

Pregnancy outcome following gestational exposure to echinacea: a prospective controlled study.

BACKGROUND: Echinacea products are among the most popular phytomedicines on the North American market. Since at least half of all pregnancies are unplanned, many women inadvertently use echinacea in their first trimester. Presently, there is a paucity of information regarding the gestational safety of this herb. The primary objective of this study was to evaluate the safety of echinacea in pregnancy when used for upper respiratory tract ailments. PATIENTS AND METHODS: The study group consisted of women who were prospectively followed up after contacting the Motherisk Program regarding the gestational use of echinacea. This cohort was disease-matched to women exposed to nonteratogenic agents by maternal age, alcohol, and cigarette use. Rates of major and minor malformations between the groups were compared. RESULTS: A total of 206 women were enrolled in the study group after using echinacea products during pregnancy; 112 women used the herb in the first trimester. There were a total of 195 live births, including 3 sets of twins, 13 spontaneous abortions, and 1 therapeutic abortion. Six major malformations were reported, including 1 chromosomal abnormality, and 4 of these malformations occurred with echinacea exposure in the first trimester. In the control group, there were 206 women with 198 live births, 7 spontaneous abortions, and 1 therapeutic abortion. Seven major malformations were reported. There were no statistical differences between the study and control groups for any of the end points analyzed. CONCLUSIONS: This first prospective study suggests that gestational use of echinacea during organogenesis is not associated with an increased risk for major malformations.

Attitudes and practices of physicians and naturopaths toward herbal products, including use during pregnancy and lactation.

BACKGROUND: The popularity of complementary therapies continues to grow, and physicians are asked increasingly by their patients for information regarding these modalities. PURPOSE: To assess the impact of these trends on physicians and medical students, and compare their attitudes and practices with those of the naturopaths and their students, with particular interest in the use of herbal products during pregnancy and breastfeeding. MATERIALS AND METHODS: A detailed questionnaire was distributed by a medical student and a naturopathic student to a randomly selected group of physicians, medical students, naturopaths and naturopathic students. They were asked a variety of questions about their background, attitudes and practices concerning herbal products. RESULTS: Thirty-eight per cent of the questionnaires were returned, with a total of 242 respondents. Fifty-four per cent of physicians discussed complementary therapies with their patients, whereas 100% of naturopaths discussed conventional medicines with their patients. The most popular product recommended by both medical doctors and naturopaths was echinacea, followed by St John's Wort. Eighty-six per cent of physicians, 74% of medical students, 66% of naturopaths and 50% of naturopathic students think that complementary medical education should be incorporated into the standard medical curriculum. Only one physician actually recommended a herbal product to a pregnant patient compared with 49% of the naturopaths who felt comfortable doing so. CONCLUSIONS: Complementary medicine has become a reality, and physicians are recommending herbal products to their patients, although on a smaller scale than are naturopaths. However, the two most popular herbal products are the same in each group. Physicians are less likely to recommend herbal products to pregnant and breastfeeding women than are naturopaths.

Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer.

BACKGROUND: Herbal mixtures are popular alternatives to demonstrated therapies. PC-SPES, a commercially available combination of eight herbs, is used as a nonestrogenic treatment for cancer of the prostate. Since other herbal medicines have estrogenic effects in vitro, we tested the estrogenic activity of PC-SPES in yeast and mice and in men with prostate cancer. METHODS: We measured the estrogenic activity of PC-SPES with transcriptional-activation assays in yeast and a biologic assay in mice. We assessed the clinical activity of PC-SPES in eight patients with hormone-sensitive prostate cancer by measuring serum prostate-specific antigen and testosterone concentrations during and after treatment. RESULTS: In complementary yeast assays, a 1:200 dilution of an ethanol extract of PC-SPES had estrogenic activity similar to that of 1 nM estradiol, and in ovariectomized CD-1 mice, the herbal mixture increased uterine weights substantially. In six of six men with prostate cancer, PC-SPES decreased serum testosterone concentrations (P<0.05), and in eight of eight patients it decreased serum concentrations of prostate-specific antigen. All eight patients had breast tenderness and loss of libido, and one had venous thrombosis. High-performance liquid chromatography, gas chromatography, and mass spectrometry showed that PC-SPES contains estrogenic organic compounds that are distinct from diethylstilbestrol, estrone, and estradiol. CONCLUSIONS: PC-SPES has potent estrogenic activity. The use of this unregulated mixture of herbs may confound the results of standard or experimental therapies and may produce clinically significant adverse effects.

Oxygen free radical scavenger properties of dehydroepiandrosterone.

The microsomes from dehydroepiandrosterone (DHEA)-supplemented animals are good hydroxyl radical scavengers, as demonstrated through electron spin resonance and deoxyribose degradation. The ability of DHEA-supplemented microsomes to react with superoxide radical was also demonstrated through the inhibition of nitroblue-tetrazolium reduction determined by superoxide radicals produced in a hypoxanthine-xanthine oxidase system. DHEA-enriched microsomes, obtained from acutely DHEA-treated rats, become resistant to iron-dependent lipid peroxidation triggered by H2O2/FeSO4 and ascorbate/FeSO4. The direct addition of DHEA to microsomes from untreated rats failed to prevent iron-dependent lipid peroxidation, even if the microsomes were preincubated with DHEA for up to 15 min, indicating that in vivo transformation is required before antioxidant action can be exerted.

Key components of patient education for pelvic floor stimulation in the treatment of urinary incontinence.

A thorough patient education plan promotes motivation and compliance and is essential to insuring successful outcomes with pelvic floor stimulation therapy. A pyramid forms the conceptual framework for an education program and for nurse-patient interactions. The introduction, goal-setting, education, achievement, and outcome stages are parts of this pyramid. Clinical discussion of the process as applied to pelvic-floor stimulation is detailed. Use of the pyramid approach contributes to three nurse-patient goals; facilitating home management of pelvic floor stimulation equipment, increasing patient knowledge about causes and treatments for urinary incontinence, and establishing mutual goals and outcome measurements for pelvic floor stimulation home therapy.

Effects of yew alkaloids and related compounds on guinea-pig isolated perfused heart and papillary muscle.

The mechanical and electrical effects of selected yew alkaloids were studied on two different cardiac preparations: the isolated coronary perfused heart and the isolated papillary muscle of the guinea-pig. In the isolated heart, the Winterstein acid type alkaloids 1, 2 and 3 induced electrical and mechanical effects similar to those reported after yew intoxication (negative inotropic effect, block of atrio-ventricular conduction), but the coronary flow was unchanged. Taxine B (1), the most potent compound of this group, reduced cardiac contractility and the maximum rate of depolarisation of the action potential in the isolated papillary muscle, acting as a class I antiarrhythmic drug. In the isolated heart, the cinnamates 4 and 5, corresponding to the degradation products of 1 and 3, exerted arrhythmogenic effect due to a reduction of coronary flow. No alterations in electrical and contractile activities were in fact recorded after perfusion of the isolated papillary muscle with 4. Taxine A (6) and the taxane alcohol 7, corresponding to the terpenoid core of 3 had no significant cardiac effect. Our results suggest that the poisonous properties of the yew tree are probably due to the combined activity of alkaloids of the Winterstein acid type and their corresponding cinnamtes, which can reduce both the excitability and the coronary flow of the heart.

[Mineral metabolism in young beef cattle during the period of changing from winter feed rations to grazing]. / Minerálny metabolizmus mladého výkrmového dobytka v období prechodu zo zimnej krmnej dávky na pasu.

Concentrations of calcium, inorganic phosphorus, magnesium, sodium and potassium were observed in the blood serum of beef bullocks after their transfer from winter feed ration to grazing and in the successive grazing cycles within two years. Blood samples were taken by puncture from the vena jugularis from the identical six bullocks. In the first year of observation, blood collection took place a week before transfer to grazing while in the second year of observation twice in weekly intervals before grazing. In the period of grazing, the biological material was sampled in weekly intervals from week 1 to week 5 (May--Ist cycle, June--IInd cycle), then in week 10 (July--IIIrd cycle) and in week 14 (August--IVth cycle of grazing). Calcium concentrations in the blood serum of beef bullocks (Fig. 1) decreased after transfer from stable feeding to grazing while this drop was significant in the second year of observation (P < 0.05). That period was followed by an increase in serum calcium concentrations in both target groups. The concentrations of inorganic phosphorus in the serum of beef bullocks (Fig. 2) dropped after transfer to grazing but a gradual increase in the values was recorded in week 4 in the first year of observation and in week 5 of grazing in the 2nd year of observation. These changes were not statistically significant. The concentrations of serum magnesium in beef bullocks (Fig. 3) statistically significantly dropped (P < 0.05) after transfer from stable feeding to grazing in week 3 in the first year of observation and in week 4 of grazing in the second year of observation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alteration of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by estradiol and tamoxifen.

We have hypothesized that part of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is mediated by interaction with the estrogen receptor complex. The experiments reported here investigate the interactions of TCDD with agonists and antagonists of the estrogen receptor. CD-1 female mice were observed for 2 months after treatment with various combinations of corn oil, estradiol, or tamoxifen, and/or TCDD in corn oil on 3 consecutive days. Estradiol had little effect on acute TCDD lethality but increased severity of TCDD-induced ascites and antagonized TCDD-induced uterine suppression. Severe liver damage did occur in TCDD and estradiol:TCDD treatment groups. Tamoxifen, a competitive inhibitor and a mixed agonist of the mouse estrogen receptor, antagonized the estrogenic effects of estradiol and estradiol:TCDD. Tamoxifen or tamoxifen:TCDD treatment greatly slowed body weight gain in comparison to controls and estrogen-treated animals. While the dose of tamoxifen used was otherwise non-toxic, tamoxifen greatly increased toxicity of TCDD as measured by time to death and percent lethality while having no effect on relative liver weight or relative uterine weight changes induced by TCDD. These findings are consistent with the hypothesis that a portion of the toxicity of TCDD is manifest through activity of the estrogen receptor complex.

[Carnitine and Down's syndrome]. / Carnitina e sindrome di Down.

The present study revealed a degree of carnitine deficiency in a large percentage of Down's syndrome children. In fact below average carnitine levels were noted in 39.1% of the cases examined with severe deficiency in 4. On the basis of these data supplementary carnitine is recommended in cases of deficiency particularly in view of the value of carnitine in the prevention of cell aging.

A possible mechanism of psoralen phototoxicity not involving direct interaction with DNA.

Psoralens in combination with ultraviolet light (UVA; 320-400 nm) are used in the photochemical treatment of a variety of skin diseases including vitiligo, a skin depigmentational disorder, and psoriasis, a disease of accelerated epidermal cell proliferation. Although it is generally assumed that the major site of action of the psoralens is DNA, we have obtained evidence that another site may be the primary target for these compounds. We have identified specific, saturable, high-affinity binding sites for 8-methoxypsoralen on HeLa cells and have detected specific binding of 8-methoxypsoralen to four other human cell lines and five mouse cell lines. In HeLa cells, specific binding is reversible and independent of the ability of the compound to intercalate into DNA. In addition, binding sites become covalently modified by the psoralen after UVA exposure. Specific binding of 8-[methoxy-3H]methoxypsoralen constitutes 79% of the label bound to the cells. Scatchard analysis indicated two classes of psoralen binding sites: high-affinity sites with a Kd of 19 X 10(-9) M (1.8 X 10(5) sites per cell) and low-affinity sites with a Kd of 4 X 10(-6) M (7.1 X 10(6) sites per cell). Four structurally related psoralen analogs block 8-methoxypsoralen binding in a manner that parallels their biological activity. Based on these findings, we hypothesize that specific binding sites for psoralens on mammalian cells mediate, at least in part, psoralen-induced phototoxicity.