Experimental Analysis of Energy Transfers between a Quantum Emitter and Light Fields.

Energy can be transferred between two quantum systems in two forms: unitary energy-that can be used to drive another system-and correlation energy-that reflects past correlations. We propose and implement experimental protocols to access these energy transfers in interactions between a quantum emitter and light fields. Upon spontaneous emission, we measure the unitary energy transfer from the emitter to the light field and show that it never exceeds half the total energy transfer and is reduced when introducing decoherence. We then study the interference of the emitted field and a coherent laser field at a beam splitter and show that the nature of the energy transfer quantitatively depends on the quantum purity of the emitted field.

Role of genetic investigation in the diagnosis of short stature in a cohort of Italian children.

BACKGROUND: Short stature (SS) is defined as height more than 2 standard deviations below the mean for age and sex. Hypothyroidism, celiac disease, growth hormone deficiency, hormonal abnormalities, and genetic conditions are among its causes. A wide range of conditions often due to largely unknown genetic variants can elude conventional diagnostic workup. AIM: We used next-generation sequencing (NGS) to better understand the etiology of SS in a cohort of Italian children. PATIENTS AND METHODS: The study sample was 125 children with SS of unknown origin referred to our Institute between 2015 and 2021. All had undergone complete auxological and hormonal investigations to exclude common causes of SS. Genetic analysis was performed using a NGS panel of 104 genes. Clinical data were reviewed to clarify the pathogenicity of the variants detected. RESULTS: In this cohort, 43 potentially causing variants were identified in 38 children. A syndromic genetic condition was diagnosed in 7: Noonan syndrome in 3, Leri-Weill syndrome in 3, and hypochondroplasia in 1. Moreover, 8 benign variants and other 37 like benign variants were found. In 88 children, 179 variants of uncertain significance (VUS) were identified. No variant was found in 16 children. CONCLUSION: Genetic analysis is a useful tool in the diagnostic workup of patients with SS, in adapting management and treatment, and in identifying syndromes with mild atypical clinical features. The role of VUS should not be underestimated, particularly when multiple VUS with possible mutual worsening effects are present in the same child.

Vinorelbine in bladder-preserving multimodality treatment for muscle-invasive bladder cancer-a valid option for cisplatin-unfit patients?

PURPOSE: Treatment of muscle-invasive bladder cancer (MIBC) remains challenging, especially for elderly and/or comorbid patients. Patients who are unfit for or refuse surgery should receive bladder-preserving multimodality treatment (BPMT), consisting of transurethral resection of the bladder tumor (TURB) followed by combined chemoradiotherapy (CRT). We aimed to investigate the effectiveness of vinorelbine, a chemotherapeutic agent not routinely used for MIBC, in patients referred to CRT who are unfit for standard chemotherapy and would thus rely solely on radiotherapy (RT). METHODS: We retrospectively analyzed 52 consecutive patients with MIBC who received standard CRT with cisplatin (n = 14), CRT with vinorelbine (n = 26), or RT alone (n = 12). Primary endpoints were median overall survival (OS) and median cancer-specific survival (CSS). Secondary endpoints were median local control (LC), median distant control (DC), and OS, CSS, LC, and DC after 1, 2, and 3 years, respectively. RESULTS: Median OS and CSS were significantly higher for patients who received vinorelbine as compared to RT alone (OS 8 vs. 22 months, p = 0.003; CSS 11 months vs. not reached, p = 0.001). Median LC and DC did not differ significantly between groups. Vinorelbine was well tolerated with no reported side effects >grade II. CONCLUSION: Our results suggest that CRT with vinorelbine is well tolerated and superior to RT alone in terms of OS and CSS. Therefore, this treatment regime might constitute a new treatment option for patients with MIBC who are unfit for or refuse surgery or standard chemotherapy. This study encourages a randomized controlled trial to compare this new regime to current standard therapies.

Energetics of a Single Qubit Gate.

Qubits are physical, a quantum gate thus not only acts on the information carried by the qubit but also on its energy. What is then the corresponding flow of energy between the qubit and the controller that implements the gate? Here we exploit a superconducting platform to answer this question in the case of a quantum gate realized by a resonant drive field. During the gate, the superconducting qubit becomes entangled with the microwave drive pulse so that there is a quantum superposition between energy flows. We measure the energy change in the drive field conditioned on the outcome of a projective qubit measurement. We demonstrate that the drive's energy change associated with the measurement backaction can exceed by far the energy that can be extracted by the qubit. This can be understood by considering the qubit as a weak measurement apparatus of the driving field.

ICH3, a selective alpha7 nicotinic acetylcholine receptor agonist, modulates adipocyte inflammation associated with obesity.

PURPOSE: The alpha7 nicotinic acetylcholine receptor (α7nAChR), involved in the modulation of inflammation and insulin sensitivity, is downregulated in white adipose tissue (WAT) of obese patients. This study aims to test the ability of a selective synthetic α7nAChR agonist, the spirocyclic Δ2-isoxazoline derivative (R)-(-)-ICH3 (ICH3), to counteract acute inflammation and obesity-associated modifications in WAT. METHODS: We employed the LPS-septic shock murine model, human primary adipocytes and diet-induced obese (DIO) mice. Inflammatory factor expression was assessed by ELISA and quantitative real-time PCR. Flow cytometry was employed to define WAT inflammatory infiltrate. Insulin signaling was monitored by quantification of AKT phosphorylation. RESULTS: In the septic shock model, ICH3 revealed antipyretic action and reduced the surge of circulating cytokines. In vitro, ICH3 stimulation (10 µM) preserved viability of human adipocytes, decreased IL-6 mRNA (P < 0.05) and blunted LPS-induced peak of TNFα (P < 0.05) and IL-6 (P < 0.01). Chronic administration of ICH3 to DIO mice was associated with lower numbers of CD8+ T cells (P < 0.05) and to changed WAT expression of inflammatory factors (Hp, P < 0.05; CD301/MGL1, P < 0.01; Arg-1, P < 0.05). As compared to untreated, ICH3 DIO mice exhibited improved insulin signaling in the skeletal muscle (P < 0.01) mirrored by an improved response to glucose load (ipGTT: P < 0.05 at 120 min). CONCLUSIONS: We proved that ICH3 is an anti-inflammatory drug, able to reduce inflammatory cytokines in human adipocytes and to blunt the effects of obesity on WAT inflammatory profile, on glucose tolerance and on tissue insulin sensitivity.

Lipodystrophy and obesity are associated with decreased number of T cells with regulatory function and pro-inflammatory macrophage phenotype.

BACKGROUND/OBJECTIVES: In lipodystrophy (LD) adipose tissue function to store lipids is impaired, leading to metabolic syndrome, similar to that found in obesity. Emerging evidence links dysmetabolism with disorders of the immune system. Our aim is to investigate whether T-cell populations with regulatory function and monocyte-derived macrophages (MDMs) are affected by LD and obesity. SUBJECTS/METHODS: Blood was collected from 16 LD, 16 obese (OB, BMI>30 kg m-2) and 16 healthy normal-weight women (CNT). Physical parameters, plasma lipid profile, glucose, HbA1c, leptin levels were determined. Flow cytometry was employed to assess the number of circulating CD4+/CD25hi regulatory T cells (Tregs) and invariant natural killer T (iNKT) cells. Characterization of MDMs included: 1. morphological/oil-Red-O staining analyses to define two morphotypes: lipid laden (LL) and spindle-like (sp) MDM; 2. gene expression studies; 3. use of conditioned medium from MDMs (MDMs CM) on human SGBS cells. RESULTS: As compared to CNT, LD and, to a lesser extent, obesity were associated with reduced Tregs and iNKTs (P<0.001 and P<0.01 for LD and OB, respectively), higher number of LL-MDMs (P<0.001 and P<0.01 for LD and OB, respectively), lower number of sp-MDMs (P<0.001 for both LD and OB), which correlated with increased paracrine stimulation of lipid accumulation in cells (P<0.001 and P<0.01 for LD and OB, respectively). LD MDMs showed decreased and increased expression for anti-inflammatory (IL10 and CD163) and pro-inflammatory (CD68 and CCL20) marker genes, respectively. Analysis of correlation indicated that Tregs are directly related with HDL (P<0.01) and inversely related with LL-MDM (P<0.001) and that LL-MDM are directly related with triglycerides (P<0.01) and oxidized LDL (P<0.01). CONCLUSIONS: LD and obesity are associated with changes in the immune system: a significant reduction in the number of T cells with regulatory function and a shift of MDM towards lipid accumulation. Lipid profile of the patients correlates with these changes.

Fuel homeostasis and locomotor behavior: role of leptin and melanocortin pathways.

BACKGROUND: While it is now accepted that genes and their products affect food intake, the concept that locomotor behavior or the propensity for physical activity is controlled by neuro hum oral regulators is frequently underappreciated. In mammals, complex interactions have developed to allow the cross-talk between fuel homeostasis and physical activity. AIM: The aim of this review is to provide a synopsis of the influence of the leptin-melanocortin pathway, a well-studied pivotal player in body weight regulation, on locomotor behaviors. CONCLUSIONS: In rodents, reductions in leptin levels that physiologically occur following acute food deprivation or a reduction of the fat mass consequent to prolonged caloric restrictions are associated with a decrease in total locomotor activity and simultaneous increase in food-anticipatory activity, a locomotor behavior which reflects a foraging attitude. These actions can be prevented by leptin administration and are at least partially mediated by the neurons of the melanocortin pathway. In humans, twin studies have attributed to genetic factors approximately 50% of the variance of physical activity. An elevated number of the genes or loci which may affect physical activity are involved in body weight homeostasis. Polymorphisms of the melanocortin-4 and leptin receptors have repeatedly been associated with the level of physical activity. Unraveling the complexity of the regulation of locomotor behavior and the interconnections with the pathways involved in energy homeostasis may help explain the substantial individual variability in physical activities in humans and disentangle the harmful effects of sedentary lifestyle, which may be distinct from the detrimental effects of obesity.

Permanence of molecular features of obesity in subcutaneous adipose tissue of ex-obese subjects.

OBJECTIVE: Bariatric surgery represents a powerful tool for morbid obesity treatment. However, after stabilization of weight loss that follows surgical interventions, ex-obese patients face the problem of residual tissues removal. Actually, it is unknown whether the characteristics of this residual subcutaneous adipose tissue (SAT) are 'restored' with regard to molecular and morphological features. DESIGN: To clarify this issue, we compared the SAT gene expression profile of ex-obese patients (ExOB-SAT, mean body mass index (BMI): 27.2±1.3 kg m(-2)) with that of lean (normal weight, NW-SAT, mean BMI: 22.6±1.1 kg m(-2)), overweight (OW-SAT, BMI: 27.65±0.2 kg m(-2)) and obese patients, according to BMI classes (OB1-SAT: 30 > or = BMI < or = 34.9, OB2-SAT: 35 > or = BMI < or = 39.9, OB3-SAT: BMI > or = 40). SUBJECTS AND METHODS: A total of 58 samples of SAT were collected during surgical interventions. Gene expression levels were assessed by microarrays and significant genes were validated by RT-qPCR. Adipocyte hypertrophy, inflammatory infiltration and fibrosis were assessed by morphological techniques. RESULTS: Global gene expression in ExOB-SAT was closely related to gene expression of OB3-SAT by hierarchical clustering procedures, in spite of different BMI. Metallothioneins (MT1A and MT2A) were the key over-expressed genes in both groups. At morphologic level, adipocyte hypertrophy and inflammatory infiltration improved after weight loss in ExOB-SAT, despite a persistence of fibrosis. CONCLUSIONS: Taken together, these results demonstrate that SAT gene expression is not fully restored, even after an extensive and stable weight loss. The persistence of 'obesity molecular features' in ExOB-SAT suggests that the molecular signature of adipose tissue is not solely dependent on weight loss and may need longer time period to completely disappear.

Frequency of the GPR7 Tyr135Phe allelic variant in lean and obese subjects.

BACKGROUND: GPR7, the endogenous coupled receptor for neuropeptide B and neuropeptide W, is expressed in several regions of the central nervous system, which are involved in the regulation of feeding behavior. GPR7 affects the regulation of energy balance through a mechanism independent of leptin and melanocortin pathways. AIM: Aim of this study was to investigate whether GPR7 gene mutations can be detected in human subjects and, in that event, if they are differently distributed among lean and obese subjects. SUBJECTS AND METHODS: The coding region of GPR7 were sequenced in 150 obese patients and 100 normal-weight unrelated controls. Functional studies of the allelic variants were performed. RESULTS: One genetic GPR7 variant was found (Tyr135Phe - rs33977775) in obese subjects (13.3%) and lean control (25%). Functional studies did not reveal significant differences between the wild type and the Tyr135Phe allelic variants in their NPW-mediated capacity to inhibit forskolin-induced cAMP production. CONCLUSIONS: Screening of GPR7 gene mutations among lean and obese subjects revealed a Tyr135Phe allelic variant that was fairly common in the study population. As indicated by in vitro and in silico studies, this variant is unlikely to cause a functional derangement of the receptor.

Effect of physiological exercise on osteocalcin levels in subjects with adrenal incidentaloma.

AIM: In the present study, we have evaluated whether physical exercise affect low osteocalcin concentrations observed in patients with subclinical hypercortisolism. SUBJECTS AND METHODS: Sixteen patients (10 men and 6 women, age 38-55 yr) with adrenal incidentaloma were studied. Fifteen healthy volunteers matched for age (range 35-47 yr) were used as controls. Subjects were submitted to a 8-week exercise-training program with cycle-ergometer for 1 h/day 3-4 days/week at 60% of their individual VO2 max. Before and after this period, resting venous serum osteocalcin and GH concentrations were measured in the same batch. The blood sampling after 8 weeks of the training program were performed after resting for one day. All patients and controls underwent also the following endocrine evaluation: serum cortisol, plasma ACTH. RESULTS: Our results demonstrate a significant increase of osteocalcin after physical exercise and a positive correlation between osteocalcin and GH. This later might suggest a role of GH in the increased osteocalcin secretion. CONCLUSIONS: The data of the present study suggest a positive effect of physical exercise on bone metabolism in patients with adrenal incidentaloma.

Somatostatin reduces neuropeptide Y rise induced by physical exercise.

The effect of an i. v. infusion of somatostatin (SRIH) 4.1 µg/min×90 min on the basal secretion of NPY and on the NPY response to physical exercise was studied in normal men. Basal NPY secretion was not modified by SRIH infusion, whereas the NPY response to physical exercise was significantly lower in the presence of SRIH. These data suggest the involvement of a somatostatinergic mechanism in the regulation of NPY response to physical exercise.

Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects.

Leptin, the gene product of the obese gene, may play an important role in regulating body weight by signalling the size of the adipose tissue mass. Plasma leptin was found to be highly correlated with body mass index (BMI) in rodents and in 87 lean and obese humans. In humans, there was variability in plasma leptin at each BMI suggesting that there are differences in its secretion rate from fat. Weight loss due to food restriction was associated with a decrease in plasma leptin in samples from mice and obese humans.

Relatively low plasma leptin concentrations precede weight gain in Pima Indians.

Leptin, the product of the ob gene, is a hormone, produced by adipose cells, that inhibits food intake and increases energy expenditure in rodents. In humans, plasma leptin concentrations correlate closely with the size of the adipose tissue depot; however, there is considerable variation in plasma leptin concentrations at any given degree of fatness. To investigate whether individuals prone to weight gain are hypoleptinemic, we measured fasting plasma leptin concentrations in two groups of weight-matched nondiabetic Pima Indians followed for approximately 3 years, 19 of whom subsequently gained weight and 17 of whom maintained their weight. After we adjusted for initial percent body fat, mean plasma leptin concentration was lower in those who gained weight than in those whose weight was stable. These data indicate that relatively low plasma leptin concentrations may play a role in the development of obesity in Pima Indians, a population prone to obesity.

Weight-reducing effects of the plasma protein encoded by the obese gene.

The gene product of the ob locus is important in the regulation of body weight. The ob product was shown to be present as a 16-kilodalton protein in mouse and human plasma but was undetectable in plasma from C57BL/6J ob/ob mice. Plasma levels of this protein were increased in diabetic (db) mice, a mutant thought to be resistant to the effects of ob. Daily intraperitoneal injections of either mouse or human recombinant OB protein reduced the body weight of ob/ob mice by 30 percent after 2 weeks of treatment with no apparent toxicity but had no effect on db/db mice. The protein reduced food intake and increased energy expenditure in ob/ob mice. Injections of wild-type mice twice daily with the mouse protein resulted in a sustained 12 percent weight loss, decreased food intake, and a reduction of body fat from 12.2 to 0.7 percent. These data suggest that the OB protein serves an endocrine function to regulate body fat stores.

Naloxone decreases the inhibitory effect of ethanol on the release of arginine-vasopressin induced by physical exercise in man.

To establish whether ethanol and/or endogenous opioids play a role in the control of arginine-vasopressin (AVP) response to physical exercise, six healthy men underwent six bicycle-ergometer tests until exhaustion [exercise control test; exercise plus ethanol (50 of 110 ml proof whiskey orally), exercise plus naloxone (2 mg injected plus 5 mg infused or 4 mg injected plus 10 mg infused intravenously] or exercise plus ethanol plus naloxone). Plasma AVP levels, physiological and biochemical variables were measured during tests. Physiological and biochemical variables were similar in all tests. During the control test, exercise significantly increased plasma AVP levels, with a peak value five times higher than baseline. The AVP response to exercise was similar in the presence of naloxone, whereas it was abolished by ethanol. When ethanol tests were repeated in the presence of naloxone, at both lower and higher dose, ethanol inhibition on AVP secretion was only partial, with mean peak responses 2.5 times higher than basal values. Results indicate an ethanol involvement in regulation of the AVP response to physical exercise. Furthermore, naloxone-sensitive endogenous opioids appear to play a role in the mechanism underlying ethanol inhibitory action, but not in mediation of the AVP response to physical exercise.

Consumerism in prenatal diagnosis? A local Italian study.

AIM: To assess the causes of excessive use of prenatal diagnosis. MATERIAL AND METHODS: 304 questionnaires were completed anonymously by puerperae in a Siena (Italy) hospital in May-August 2006. The questionnaires contained 24 questions about the women, examinations performed during pregnancy and the reasons for them. RESULTS: The mean number of ultrasound examinations per woman was 6.5 +/- 2.5. Forty-two percent of the women in our sample (29.3% of women under 35 and 68.9% of women over 35 years of age) reported that amniocentesis/CVS had been performed; the mean age of these women was 34.1 +/- 4.5 years. Eighty-five percent of the women under 36 years of age who had amniocentesis declared that it was performed as a personal choice and 15% for the presence of risk factors. Among 131 women who performed amniocentesis, 32 performed it with a normal blood screening for Down syndrome (DS), and 76 declared to have performed no blood screening for DS. Only 45% of women stated that they thought age above 35 years was a risk factor for pregnancy, but most of them (75%) were aware that amniocentesis was performed to detect chromosomal anomalies. In 89% of the cases a source of information about prenatal testing was the woman's gynecologist. CONCLUSION: This study shows that the high use of prenatal examinations is often not justified by the presence of clinical risk factors and that both national health system and caregivers should find new strategies to inform women about the aims of prenatal tests, and promote a more serene approach to pregnancy. A broader study is needed to confirm these data.

Metabolic findings on 3T 1H-MR spectroscopy in peritumoral brain edema.

BACKGROUND AND PURPOSE: Little is known about the metabolic properties of brain edema associated with tumors. This work was conducted on the basis of the assumption that, in the presence of intra-axial and extra-axial brain tumors, the white matter involved by the edema is a site of metabolic change that involves the structure of the myelin sheath. MATERIALS AND METHODS: Thirteen patients comprised our cohort affected by intra-axial and extra-axial cerebral tumors with a peritumoral T2-weighted MR signal hyperintensity as a result of edema, where MR spectroscopy showed no increase in choline-containing compounds. Measurements on proton MR spectroscopy (1H-MR spectroscopy) were performed with a 3T whole-body scanner with use of a point-resolved spectroscopy sequence for localization (TR, 2000 ms; TE, 35 ms), and the metabolites were quantified with the SAGE method. Peak intensities of the main metabolites were expressed as ratios of one another and were compared with values obtained in the white matter of the left frontal region in a control group of 16 healthy volunteers. RESULTS: Choline-to-creatine (Cho/Cr) and myo-inositol-to-creatine (mIns/Cr) signal intensity ratios were normal in all patients. N-acetylaspartate-to-creatine (NAA/Cr) and N-acetylaspartate-to-choline (NAA/Cho) ratios decreased in 4 patients. Glutamate plus glutamine-to-creatine (Glx/Cr) was increased in 10 patients. A resonance peak at 3.44 ppm, strongly suggesting the presence of glucose, was detected in all but 1 patient. Lactate was detected in 12 patients and lipids in 5. Moreover, the resonances that pertained to the aliphatic amino acids valine, leucine, and isoleucine were present in 12 patients. CONCLUSIONS: Our findings on MR spectroscopy confirmed the hypothesis that in the edema surrounding brain tumors, an energy-linked metabolic alteration was associated with injury to the myelin sheath.