Glycemic control and cancer outcomes in oncologic patients with diabetes: an Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), Italian Society of Pharmacology (SIF) multidisciplinary critical view.

BACKGROUND:  Increasing evidence suggests that diabetes increases the risk of developing different types of cancer. Hyperinsulinemia, hyperglycemia and chronic inflammation, characteristic of diabetes, could represent possible mechanisms involved in cancer development in diabetic patients. At the same time, cancer increases the risk of developing new-onset diabetes, mainly caused by the use of specific anticancer therapies. Of note, diabetes has been associated with a ∼10% increase in mortality for all cancers in comparison with subjects who did not have diabetes. Diabetes is associated with a worse prognosis in patients with cancer, and more recent findings suggest a key role for poor glycemic control in this regard. Nevertheless, the association between glycemic control and cancer outcomes in oncologic patients with diabetes remains unsettled and poorly debated. PURPOSE:  The current review seeks to summarize the available evidence on the effect of glycemic control on cancer outcomes, as well as on the possibility that timely treatment of hyperglycemia and improved glycemic control in patients with cancer and diabetes may favorably affect cancer outcomes.

Cocoa by-product inclusion in dairy sheep diet: effect on sensory, volatile and antioxidant properties of cheese.

The possibility of inclusion of agro-industrial by-products in the diet of small ruminants represents both an economical and an environmental strategy for reducing waste management by industries and the cost of feeding as well as the impact of livestock farming. Large amounts of wastes from the cocoa industry are annually produced with a considerable part represented by cocoa bean shells, considered a suitable ingredient to be included in the diet of ruminants within the limits established by European legislation. The aim of this study was to assess the effect of including cocoa bean shells in the diet of dairy sheep on the sensory, volatile, and antioxidant properties of cheese. To this purpose, 20 Comisana lactating ewes were randomly assigned to 2 experimental groups: control (CTRL) and cocoa bean shells (CBS), and received alfalfa hay ad libitum and 800g of conventional (CTRL) or experimental (CBS) concentrate containing 11.7% CBS to partially replace corn and barley of the CTRL concentrate. Bulk milk collected from each group was used to produce a total of 15 cheeses per group, obtained in 5 different days of cheese-making (3 cheeses a day per group). After 60 d of aging, each cheese of each experimental group was sampled for the analyses. The results on chemical composition revealed a greater monounsaturated fatty acids content and an increase in the nutritional indices suggesting a favorable role of cocoa bean shells dietary inclusion on the nutritive value of the cheese. The cheese sensory profile was affected by the cocoa bean shells inclusion, with more pronounced appearance, odor, aroma, and taste attributes in the product. The volatile profile showed only a few significant differences, mainly related to the cheese ripening process, and no differences were found in α-tocopherol contents in cheese fat between the 2 groups. Therefore, the coca bean shells inclusion in the diet of dairy sheep allowed to obtain a good quality cheese, without altering the characteristics associated with the typical profiles of sheep cheese. Furthermore, the use of this by-product could contribute to decrease feed costs and waste management, representing a good practice for increasing the sustainability of dairy products.

Search for the Lepton Flavor Violating Decays B

We present a search for the lepton flavor violating decays B^{+}→K^{+}τ^{±}ℓ^{∓}, with ℓ=(e,µ), using the full data sample of 772×10^{6} BB[over ¯] pairs recorded by the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We use events in which one B meson is fully reconstructed in a hadronic decay mode. We find no evidence for B^{±}→K^{±}τℓ decays and set upper limits on their branching fractions at the 90% confidence level in the (1-3)×10^{-5} range. The obtained limits are the world's best results.

First Simultaneous Determination of Inclusive and Exclusive |V_{ub}|.

The first simultaneous determination of the absolute value of the Cabibbo-Kobayashi-Maskawa matrix element V_{ub} using inclusive and exclusive decays is performed with the full Belle data set at the ϒ(4S) resonance, corresponding to an integrated luminosity of 711 fb^{-1}. We analyze collision events in which one B meson is fully reconstructed in hadronic modes. This allows for the reconstruction of the hadronic X_{u} system of the semileptonic b→uℓν[over ¯]_{ℓ} decay. We separate exclusive B→πℓν[over ¯]_{ℓ} decays from other inclusive B→X_{u}ℓν[over ¯]_{ℓ} and backgrounds with a two-dimensional fit that utilizes the number of charged pions in the X_{u} system and the four-momentum transfer q^{2} between the B and X_{u} systems. Combining our measurement with information from lattice QCD and QCD calculations of the inclusive partial rate as well as external experimental information on the shape of the B→πℓν[over ¯]_{ℓ} form factor, we determine |V_{ub}^{excl}|=(3.78±0.23±0.16±0.14)×10^{-3} and |V_{ub}^{incl}|=(3.88±0.20±0.31±0.09)×10^{-3}, respectively, with the uncertainties being the statistical error, systematic errors, and theory errors. The ratio of |V_{ub}^{excl}|/|V_{ub}^{incl}|=0.97±0.12 is compatible with unity.

Hematocolpos due to imperforate hymen: a case report and literature systematic review.

INTRODUCTION AND HYPOTHESIS: Hematocolpos is a rare condition, where menstrual blood fills the vagina, instead of being expelled, due to a series of uterovaginal pathologies, the most frequent of which is the imperforate hymen. To date, few cases of hematocolpos have been reported in the literature. METHODS: We report a case of hematometrocolpos due to imperforate hymen initially misdiagnosed as constipation and subsequently as ovarian mass; moreover, the present study undertakes a systematic review of studies on hematometrocolpos due to imperforate hymen to synthesize available knowledge on epidemiology, diagnosis, and management about this rare condition. RESULTS: A total of 35 studies, describing 61 patients, were identified. The presence of hematocolpos should be suspected in premenarchal patients complaining of low abdominal pain, abdominal swelling, and urinary retention. Genital examination disclosing a tender, pale hymen and ultrasound represent a useful tool for diagnosis. The goal of the management is to timely perform hymenotomy to drain the hematocolpos, followed by hymenectomy to prevent recurrence. Follow-up is needed to diagnose possible recurrences. CONCLUSIONS: In the case of an adolescent girl complaining of genital pain associated with primary amenorrhea, hematocolpos due to imperforate hymen should be suspected.

Striatal glutamatergic hyperactivity in Parkinson's disease.

Glutamatergic hyperactivity in the nucleus striatum, the main basal ganglia input, has been involved in the progression of Parkinson's disease (PD) and the onset of L-Dopa-induced dyskinesias (LIDs). Abnormalities in the spiny projection neurons excitability and firing, and in the overactivity of glutamate transmission found in animal models of PD, pointed to the synaptic dysfunctions as a primary target to counteract alterations before overt neurodegeneration, conferring a key role to striatal glutamatergic transmission in the early phases of the disease. The present paper provides an overview of the evidence that glutamatergic overactivity is a critical mechanism underlying different PD-associated striatal alterations in early and advanced symptomatic stages of the disease. These aberrant changes, under L-Dopa therapy, lead to a more complex synaptopathy that involves other neurotransmitter systems and persistent modifications to generate LIDs. The review discusses the main changes in glutamatergic functions found in PD preclinical models and clinical studies and an update of the current pharmacological strategies to modulate the glutamatergic systems at the pre- and postsynaptic levels will be provided.

Bipolar seesaw control on last interglacial sea level.

Our current understanding of ocean-atmosphere-cryosphere interactions at ice-age terminations relies largely on assessments of the most recent (last) glacial-interglacial transition, Termination I (T-I). But the extent to which T-I is representative of previous terminations remains unclear. Testing the consistency of termination processes requires comparison of time series of critical climate parameters with detailed absolute and relative age control. However, such age control has been lacking for even the penultimate glacial termination (T-II), which culminated in a sea-level highstand during the last interglacial period that was several metres above present. Here we show that Heinrich Stadial 11 (HS11), a prominent North Atlantic cold episode, occurred between 135 ± 1 and 130 ± 2 thousand years ago and was linked with rapid sea-level rise during T-II. Our conclusions are based on new and existing data for T-II and the last interglacial that we collate onto a single, radiometrically constrained chronology. The HS11 cold episode punctuated T-II and coincided directly with a major deglacial meltwater pulse, which predominantly entered the North Atlantic Ocean and accounted for about 70 per cent of the glacial-interglacial sea-level rise. We conclude that, possibly in response to stronger insolation and CO2 forcing earlier in T-II, the relationship between climate and ice-volume changes differed fundamentally from that of T-I. In T-I, the major sea-level rise clearly post-dates Heinrich Stadial 1. We also find that HS11 coincided with sustained Antarctic warming, probably through a bipolar seesaw temperature response, and propose that this heat gain at high southern latitudes promoted Antarctic ice-sheet melting that fuelled the last interglacial sea-level peak.

Boron isotope evidence for oceanic carbon dioxide leakage during the last deglaciation.

Atmospheric CO2 fluctuations over glacial-interglacial cycles remain a major challenge to our understanding of the carbon cycle and the climate system. Leading hypotheses put forward to explain glacial-interglacial atmospheric CO2 variations invoke changes in deep-ocean carbon storage, probably modulated by processes in the Southern Ocean, where much of the deep ocean is ventilated. A central aspect of such models is that, during deglaciations, an isolated glacial deep-ocean carbon reservoir is reconnected with the atmosphere, driving the atmospheric CO2 rise observed in ice-core records. However, direct documentation of changes in surface ocean carbon content and the associated transfer of carbon to the atmosphere during deglaciations has been hindered by the lack of proxy reconstructions that unambiguously reflect the oceanic carbonate system. Radiocarbon activity tracks changes in ocean ventilation, but not in ocean carbon content, whereas proxies that record increased deglacial upwelling do not constrain the proportion of upwelled carbon that is degassed relative to that which is taken up by the biological pump. Here we apply the boron isotope pH proxy in planktic foraminifera to two sediment cores from the sub-Antarctic Atlantic and the eastern equatorial Pacific as a more direct tracer of oceanic CO2 outgassing. We show that surface waters at both locations, which partly derive from deep water upwelled in the Southern Ocean, became a significant source of carbon to the atmosphere during the last deglaciation, when the concentration of atmospheric CO2 was increasing. This oceanic CO2 outgassing supports the view that the ventilation of a deep-ocean carbon reservoir in the Southern Ocean had a key role in the deglacial CO2 rise, although our results allow for the possibility that processes operating in other regions may also have been important for the glacial-interglacial ocean-atmosphere exchange of carbon.

Sea-level and deep-sea-temperature variability over the past 5.3 million years.

Ice volume (and hence sea level) and deep-sea temperature are key measures of global climate change. Sea level has been documented using several independent methods over the past 0.5 million years (Myr). Older periods, however, lack such independent validation; all existing records are related to deep-sea oxygen isotope (δ(18)O) data that are influenced by processes unrelated to sea level. For deep-sea temperature, only one continuous high-resolution (Mg/Ca-based) record exists, with related sea-level estimates, spanning the past 1.5 Myr. Here we present a novel sea-level reconstruction, with associated estimates of deep-sea temperature, which independently validates the previous 0-1.5 Myr reconstruction and extends it back to 5.3 Myr ago. We find that deep-sea temperature and sea level generally decreased through time, but distinctly out of synchrony, which is remarkable given the importance of ice-albedo feedbacks on the radiative forcing of climate. In particular, we observe a large temporal offset during the onset of Plio-Pleistocene ice ages, between a marked cooling step at 2.73 Myr ago and the first major glaciation at 2.15 Myr ago. Last, we tentatively infer that ice sheets may have grown largest during glacials with more modest reductions in deep-sea temperature.

Nutraceutical Properties of Herbal Infusions from Six Native Plants of Argentine Patagonia.

Six native plants of South America traditionally consumed in the Patagonian region (southern Argentina and Chile), namely: Adesmia boronioides Hook. f., Apium australe Thouars, Buddleja globosa Hope, Drimys andina (Reiche) R. Rodr. & Quezada, Dysphania multifida L. and Solidago chilensis Meyen were investigated to determine the nutraceutical properties of infusions of their aerial parts. The infusions were characterized in terms of their antioxidant activity, phenolic and flavonoid content, profile of phenolic compounds, general toxicity and cytotoxicity on two different human cell lines: T84 (derived from colon cancer) and HTR8/SVneo (not derived from cancer). Twenty-nine compounds, mainly phenolic acids and flavonoids, were identified. This is the first analysis of phenolic compounds in infusions from native plants of Patagonia. D. andina, B. globosa and S. chilensis showed high levels of antioxidants, even higher than those of Green Tea. The content of phenolic compounds correlated significantly with the antioxidant activity of the samples analyzed. The toxicity test indicated that the use of A. australe, B. globosa and D. multifida seems safe, but a moderate consumption is suggested for A. boronioides, D. andina and S. chilensis until more exhaustive and long-term results are available. Moreover, A. boronioides and S. chilensis showed anticancer potential due to their antiproliferative activity on human cancer cell lines.

TMS of supplementary motor area (SMA) facilitates mental rotation performance: Evidence for sequence processing in SMA.

In the present study we applied online transcranial magnetic stimulation (TMS) bursts at 10Hz to the supplementary motor area (SMA) and primary motor cortex to test whether these regions are causally involved in mental rotation. Furthermore, in order to investigate what is the specific role played by SMA and primary motor cortex, two mental rotation tasks were used, which included pictures of hands and abstract objects, respectively. While primary motor cortex stimulation did not affect mental rotation performance, SMA stimulation improved the performance in the task with object stimuli, and only for the pairs of stimuli that had higher angular disparity between each other (i.e., 100° and 150°). The finding that the effect of SMA stimulation was modulated by the amount of spatial orientation information indicates that SMA is causally involved in the very act of mental rotation. More specifically, we propose that SMA mediates domain-general sequence processes, likely required to accumulate and integrate information that are, in this context, spatial. The possible physiological mechanisms underlying the facilitation of performance due to SMA stimulation are discussed.

Controlling second-harmonic generation at the nanoscale with monolithic AlGaAs-on-AlOx antennas.

We review recent achievements in the field of nanoscale nonlinear AlGaAs photonics based on all-dielectric optical antennas. After discussing the motivation and main technological challenges for the development of an AlGaAs monolithic platform for χ (2) nonlinear nanophotonics, we present numerical and experimental investigations of the second-order nonlinear response and physical reasons for high efficiency of second-order nonlinear interactions in the AlGaAs nano-antennas. In particular, we emphasize the role of the dipolar resonances at the fundamental frequency and the multipolar resonances at the second harmonic wavelength. We also discuss second-harmonic generation directionality and show possible strategies to engineer the radiation pattern of nonlinear antennas.

Bioimpedance analysis, metabolic effects and safety of the association Berberis aristata/Bilybum marianum: a 52-week double-blind, placebo-controlled study in obese patients with type 2 diabetes.

Berberine, a quaternary isoquinoline alkaloid present in Berberis aristata, is well known in terms of cholesterol-lowering, hypoglycemic, and insulin sensitizing effects. Because of its low oral bioavailability, to improve intestinal absorption it has been recently combined with silymarin (Silybum marianum). The aim of our placebo controlled study was to evaluate the effects of its association with silymarin on abdominal fat in overweight/obese patients with type 2 diabetes mellitus (T2DM). To do so, 136 obese subjects with T2DM and metabolic syndrome were analyzed for fasting blood glucose and insulin, Insulin Resistance index according to the Homeostatic Model Assessment (HOMA-R), total, HDL and LDL cholesterol, triglycerides, uric acid, BMI, waist circumference, waist to hip ratio and underwent bioelectrical impedance to assess % of abdominal fat. All the above-mentioned parameters, as recorded at enrollment, after 6 months and at the end of the study, had significantly improved in the BBR-treated group in respect to baseline and to the control group. A validated national cardiovascular risk score also improved significantly after BBR treatment in respect to placebo. Our results point to a clinically significant effect in obese people with T2DM and metabolic syndrome. Moreover, for the first time, they provide evidence of a significant uric acid lowering activity as an additive beneficial effect of the association BBR + silymarin.

A novel synthetic medium and expression system for subzero growth and recombinant protein production in Pseudoalteromonas haloplanktis TAC125.

The Antarctic bacterium Pseudoalteromonas haloplanktis TAC125 is a model organism of cold-adapted bacteria. The interest in the study of this psychrophilic bacterium stems from its capability either as a non-conventional system for production of recombinant protein and as a rich source of bioactive compounds. To further explore the biotechnological ability of P. haloplanktis TAC125, we have developed a synthetic medium, containing D-gluconate and L-glutamate (GG), which allows the bacterium to grow even at subzero temperatures. P. haloplanktis TAC125 growing in GG medium at low temperature displays growth kinetic parameters which confirm its spectacular adaptation to cold environment and subzero lifestyle, paving the way to the definition of the underlying molecular strategies. Moreover, in this paper, we report the setup of a finely regulated gene expression system inducible by D-galactose to produce recombinant protein in GG synthetic medium at temperatures as low as -2.5 °C. Thanks to the combination of the novel medium and the new expression system, we obtained for the first time the production of a recombinant protein at subzero temperature, thus providing an innovative strategy for the recombinant production of "difficult" proteins.

The stress response of Ragusano donkey (Equus asinus) to different semen collection techniques.

The aim of the present study was to characterize the stress response of donkeys to different semen collection techniques, comparing the physiological patterns of hormonal (adrenocorticotropic hormone: ACTH, cortisol) and biochemical variables (creatinine, total protein, urea, aspartate aminotransferase: AST, alanine aminotransferase: ALT), and routine seminal parameters and sexual behaviour. Twenty two healthy Ragusano donkeys were used and were randomly assigned to one of 2 groups based on different semen collection techniques. Group A was designated as the experimental group and included 16 donkeys submitted to semen collection by an artificial vagina (AV) "on the ground"; group B was designated as the control group, and included 6 donkeys submitted to semen collection by AV during the mount. The semen collection was performed in October, once a day for 10 consecutive days. Blood samples were collected in baseline conditions, before the onset of the treatments and within 30 min after, from the jugular vein of each subject. Two-way ANOVA showed a significant effect of semen collection technique and time points in group A for ACTH (p=0.0084), cortisol (p=0.0004) and creatinine (p=0.0131), with lower values after semen collection than before. A significant effect of semen collection technique and time points in group B for ACTH (p<0.0001) and cortisol (p<0.0001) was observed, with higher values after semen collection than before. The comparison between groups A and B values over different time points showed a significant effect after semen collection for ACTH (p<0.0001), cortisol (p<0.0001) and creatinine (p<0.0001), with the highest values in group B. This study provides the physiological evidence that semen collection on the ground in healthy donkeys could be used as an alternative strategy to induce a positive animal approach and economical advantages.

A proteomic approach for the rapid, multi-informative and reliable identification of blood.

Blood evidence is frequently encountered at the scene of violent crimes and can provide valuable intelligence in the forensic investigation of serious offences. Because many of the current enhancement methods used by crime scene investigators are presumptive, the visualisation of blood is not always reliable nor does it bear additional information. In the work presented here, two methods employing a shotgun bottom up proteomic approach for the detection of blood are reported; the developed protocols employ both an in solution digestion method and a recently proposed procedure involving immobilization of trypsin on hydrophobin Vmh2 coated MALDI sample plate. The methods are complementary as whilst one yields more identifiable proteins (as biomolecular signatures), the other is extremely rapid (5 minutes). Additionally, data demonstrate the opportunity to discriminate blood provenance even when two different blood sources are present in a mixture. This approach is also suitable for old bloodstains which had been previously chemically enhanced, as experiments conducted on a 9-year-old bloodstain deposited on a ceramic tile demonstrate.

Giant endometrial cyst of the liver: a case report and review of the literature.

Endometriosis is a benign condition described as the presence of endometrial- like tissue found outside the uterine cavity. Hepatic endometriosis is one of the rarest localization of extrapelvic endometriosis, only 22 cases have been reported in the literature. The preoperative diagnosis of hepatic endometriosis is rather difficult because in about the half of the patient affected they had no history of endometriosis. Moreover radiological images reveal no characteristic findings for hepatic endometriosis. It is often described as cystic mass with or without solid component, difficult to distinguish from hepatic abscess, hematoma, cystoadenoma or malignant neoplasia. We report a case of a 27-year-old female with a large cystic mass involving the left lobe of the liver. The patient underwent laparoscopic exploration and converted to laparotomy for resection of giant hepatic endometriosis.

Deslorelin implants in pre-pubertal female dogs: short- and long-term effects on the genital tract.

Deslorelin acetate is a GnRH agonist used for contraception in dogs. This study aimed to evaluate the treatment of pre-pubertal female dogs with deslorelin acetate implants, to better investigate the primary stimulatory effect of the drug and the long-term effects on the genital tract, throughout repeated treatments. Sicilian hound female dogs (24) were randomly assigned to treated group, control group 1 and control group 2. First group bitches were implanted at 4.5, 9.0 and 13.5 months and monitored clinically, ultrasonographically and endocrinologically, throughout the study period (13.5 months). Control group 1 bitches were not implanted and clinically monitored for the same period. At 18 months, the animals underwent ovariohysterectomy, thus allowing evaluation of the internal genitalia. Control group 2 bitches were ovariohysterectomized at the age of 4.5 months. The suppression of oestrus was obtained in the treated group despite the fact that the first implant caused a modest increase in plasmatic levels of 17-beta estradiol and an evident cornification of the vaginal mucosa cells (50-80%). Estradiol and progesterone were at baseline levels for the remaining study period, in which no other oestrous manifestations were observed. The external genitalia maintained a juvenile appearance. The ovaries, ultrasonographically, showed no follicular structures and stayed the same size. At 18 months, the genital tract was still juvenile with inactive small ovaries and a thin filiform uterus. Deslorelin suppressed ovarian activity in pre-pubertal bitches, and oestrous induction was not observed despite the presence of the primary stimulatory effect of the drug. Juvenile genitalia were an expected side effect of the treatment.

Galectin-3 expression in thyroid fine needle cytology (t-FNAC) uncertain cases: validation of molecular markers and technology innovation.

Thyroid cancer is not very common, accounting for 1-2% of all cancers, with a population incidence of about 0.004%. Currently, the ability to discriminate between follicular adenoma and carcinoma represents the major challenge in preclinical diagnosis of thyroid proliferative lesions. Better discrimination between the two would help avoid unnecessary thyroidectomy and save valuable resources. Over the years, galectin-3 (Gal-3) has been proposed as a diagnostic marker with varied success. In this paper, we used Environmental Scanning Electron Microscopy Immunogold Labelling (ESEM-IGL) to investigate the expression of Gal-3 on Thin-Prep fine needle aspiration cytology (FNAC). We optimized the ESEM-IGL method on thyroid cell lines (RO-82 and FTC-133) comparing our membrane Gal-3 labeling data with Western blot. We evaluated 183 thyroid FNAC from Italian patients with a uncertain pre-surgical diagnosis. ESEM-IGL method marker sensitivity is 71.2%, while specificity is 53.3% and diagnostic efficacy is 61.2%. Our results confirmed that Gal-3 expression is associated with situations of hypertrophy and/or cellular hyperproliferation, pathophysiological situations common both to adenomas and to thyroid carcinomas. The innovation of thyroid FNAC Thin-Prep ESEM-IGL shows the levels of Gal-3 immunolabeling clearly, even through the individual cells of a thyroid nodule. However, Gal-3 alone, as a molecular marker of thyroid cancer, can still have a limited application in pre-surgery diagnosis.