Brain glucose hypometabolism and hippocampal inflammation in Goto-Kakizaki rats.

Brain glucose hypometabolism and neuroinflammation are early pathogenic manifestations in neurological disorders. Neuroinflammation may also disrupt leptin signaling, an adipokine that centrally regulates appetite and energy balance by acting on the hypothalamus and exerting neuroprotection in the hippocampus. The Goto-Kakizaki (GK) rat is a non-obese type 2 diabetes mellitus (T2DM) animal model used to investigate diabetes-associated molecular mechanisms without obesity jeopardizing effects. Wistar and GK rats received the maintenance adult rodent diet. Also, an additional control group of Wistar rats received a high-fat and high-sugar diet (HFHS) provided by free consumption of condensed milk. All diets and water were provided ad libitum for eight weeks. Brain glucose uptake was evaluated by 2-deoxy-2-[fluorine-18] fluoro-D-glucose under basal (saline administration) or stimulated (CL316,243, a selective ß3-AR agonist) conditions. The animals were fasted for 10-12 h, anesthetized, and euthanized. The brain was quickly dissected, and the hippocampal area was sectioned and stored at -80°C in different tubes for protein and RNA analyses on the same animal. GK rats exhibited attenuated brain glucose uptake compared to Wistar animals and the HFHS group under basal conditions. Also, the hippocampus of GK rats displayed upregulated leptin receptor, IL-1ß, and IL-6 gene expression and IL-1ß and the subunit of the transcription factor NF-κB (p-p65) protein expression. No significant alterations were detected in the hippocampus of HFHS rats. Our data indicated that a genetic predisposition to T2DM has significant brain deteriorating features, including brain glucose hypometabolism, neuroinflammation, and leptin signaling disruption in the hippocampal area.

Brain glucose hypometabolism and hippocampal inflammation in Goto-Kakizaki rats

Brain glucose hypometabolism and neuroinflammation are early pathogenic manifestations in neurological disorders. Neuroinflammation may also disrupt leptin signaling, an adipokine that centrally regulates appetite and energy balance by acting on the hypothalamus and exerting neuroprotection in the hippocampus. The Goto-Kakizaki (GK) rat is a non-obese type 2 diabetes mellitus (T2DM) animal model used to investigate diabetes-associated molecular mechanisms without obesity jeopardizing effects. Wistar and GK rats received the maintenance adult rodent diet. Also, an additional control group of Wistar rats received a high-fat and high-sugar diet (HFHS) provided by free consumption of condensed milk. All diets and water were provided ad libitum for eight weeks. Brain glucose uptake was evaluated by 2-deoxy-2-[fluorine-18] fluoro-D-glucose under basal (saline administration) or stimulated (CL316,243, a selective β3-AR agonist) conditions. The animals were fasted for 10-12 h, anesthetized, and euthanized. The brain was quickly dissected, and the hippocampal area was sectioned and stored at -80°C in different tubes for protein and RNA analyses on the same animal. GK rats exhibited attenuated brain glucose uptake compared to Wistar animals and the HFHS group under basal conditions. Also, the hippocampus of GK rats displayed upregulated leptin receptor, IL-1β, and IL-6 gene expression and IL-1β and the subunit of the transcription factor NF-κB (p-p65) protein expression. No significant alterations were detected in the hippocampus of HFHS rats. Our data indicated that a genetic predisposition to T2DM has significant brain deteriorating features, including brain glucose hypometabolism, neuroinflammation, and leptin signaling disruption in the hippocampal area.

Reviewing physical exercise in non-obese diabetic Goto-Kakizaki rats.

There is a high incidence of non-obese type 2 diabetes mellitus (non-obese-T2DM) cases, particularly in Asian countries, for which the pathogenesis remains mainly unclear. Interestingly, Goto-Kakizaki (GK) rats spontaneously develop insulin resistance (IR) and non-obese-T2DM, making them a lean diabetes model. Physical exercise is a non-pharmacological therapeutic approach to reduce adipose tissue mass, improving peripheral IR, glycemic control, and quality of life in obese animals or humans with T2DM. In this narrative review, we selected and analyzed the published literature on the effects of physical exercise on the metabolic features associated with non-obese-T2DM. Only randomized controlled trials with regular physical exercise training, freely executed physical activity, or skeletal muscle stimulation protocols in GK rats published after 2008 were included. The results indicated that exercise reduces plasma insulin levels, increases skeletal muscle glycogen content, improves exercise tolerance, protects renal and myocardial function, and enhances blood oxygen flow in GK rats.

Poor prognosis indicators of type-2 diabetic COVID-19 patients.

Diabetes is associated with a worse prognosis and a high risk of morbidity and mortality in COVID-19 patients. We aimed to evaluate the main factors involved in the poor prognosis in diabetic patients. A total of 984 patients diagnosed with COVID-19 admitted to the hospital were included in this study. Patients were first divided into type-2 diabetic (DM+) and non-diabetic (DM-) groups. The participants were analyzed based on the National Early Warning Score (NEWS) and on the Quick-Sequential Organ Failure Assessment (qSOFA) to find the best prognostic risk score for our study. The DM+ and DM- groups were divided into non-severe and severe groups. Comparative and correlative analyses were used to identify the physiological parameters that could be employed for creating a potential risk indicator for DM+ COVID-19 patients. We found a poorer prognosis for the DM+ COVID-19 patients with a higher ICU admission rate, mechanical ventilation rate, vasopressor use, dialysis, and longer treatment times compared with the DM- group. DM+ COVID-19 patients had increased plasma glucose, lactate, age, urea, NEWS, and D-dimer levels, herein referred to as the GLAUND set, and worse prognosis and outcomes when compared with infected DM- patients. The NEWS score was a better indicator for assessing COVID-19 severity in diabetic patients than the q-SOFA score. In conclusion, diabetic COVID-19 patients should be assessed with the NEWS score and GLAUND set for determining their prognosis COVID-19 prognosis.

Multicenter retro-prospective observational study on chronic hypoparathyroidism and rhPTH (1-84) treatment.

PURPOSE: The main purpose of this study was to investigate the effects of 12 months of rhPTH (1-84) (Natpar®) treatment in a cohort of patients selected according to the indications of hypoparathyroidism guidelines. The use of recombinant human PTH (1-84) [rhPTH (1-84)] is approved as hormonal replacement therapy in patients with hypoparathyroidism not adequately controlled with conventional therapy. METHODS: It is a multicenter, observational, retro-prospective, open label study. Eleven Italian Endocrinological centers, members of Hypoparathyroidism Working Group of the Italian Society of Endocrinology (HypoparaNET) were involved. Main outcome measures were serum and urinary calcium and phosphate concentration, calcium-phosphate product, renal function, oral calcium and vitamin D doses, and clinical manifestations. RESULTS: Fourteen adult subjects, affected by chronic hypoparathyroidism, were treated with rhPTH (1-84) for 12 months. At 12 months of rhPTH (1-84) treatment, 61.5% of patients discontinued calcium supplement and 69.2% calcitriol. Mean albumin-adjusted total serum calcium levels quickly normalized after initiation of rhPTH (1-84) treatment compared to baseline (p = 0.009), remaining in the normal range until 12 months. Rare hypo-hypercalcemia episodes were reported. Renal function was maintained normal and no renal complications were reported. Serum and urinary phosphate and urinary calcium were maintained in the normal range. Mean phosphatemia levels linearly decreased from 3 months up to 12 months compared to baseline (p = 0.014). No severe adverse events were described. CONCLUSIONS: Biochemical and clinical results confirm the efficacy and safety of rhPTH (1-84) therapy, which represents an important option for hypoparathyroid patients unresponsive to conventional therapy.

Stereotactic Re-irradiation in Recurrent Prostate Cancer after Previous Postoperative or Definitive Radiotherapy: Long-term Results after a Median Follow-up of 4 Years.

AIMS: In 2018, we published early results from a cohort of patients treated with stereotactic body radiotherapy (SBRT) after previous radiotherapy with definitive or postoperative intent. We sought to provide extended follow-up of this cohort to confirm the safety and efficacy of this approach in a real-world scenario. MATERIALS AND METHODS: Fifty patients affected by local relapse after previous definitive or postoperative radiotherapy were treated with SBRT. Treatment provided a total dose of 30 Gy in five fractions. Data about biochemical relapse-free survival (BRFS) and metastasis-free survival (MFS), together with adverse events, were analysed. Toxicity was reported according to Common Terminology Criteria for Adverse Events (CTCAE) score v.4.03. RESULTS: After a median follow-up of 48.2 months, the median BRFS was 43 months. A Gleason score >7 and concomitant androgen deprivation therapy were shown to be predictors of the worst BRFS (hazard ratio 2.42, 95% confidence interval 1.09-5.41, P = 0.02; hazard ratio 2.83, 95% confidence interval 1.17-6.8, P = 0.02, respectively). The median MFS was not reached; concomitant androgen deprivation therapy was confirmed to be predictive of the worst MFS (hazard ratio 4.75, 95% confidence interval 1.52-14.8, P = 0.007). Late grade 1 and 2 rectal and bladder toxicity occurred in three (6%) and 13 (26%) patients, respectively. One patient experienced both grade 3 acute and chronic bladder toxicity. CONCLUSION: Salvage SBRT re-irradiation after previous postoperative or definitive radiotherapy for local prostate cancer recurrence confirmed promising results in terms of oncological outcomes and the safety of this approach.

Reviewing physical exercise in non-obese diabetic Goto-Kakizaki rats

There is a high incidence of non-obese type 2 diabetes mellitus (non-obese-T2DM) cases, particularly in Asian countries, for which the pathogenesis remains mainly unclear. Interestingly, Goto-Kakizaki (GK) rats spontaneously develop insulin resistance (IR) and non-obese-T2DM, making them a lean diabetes model. Physical exercise is a non-pharmacological therapeutic approach to reduce adipose tissue mass, improving peripheral IR, glycemic control, and quality of life in obese animals or humans with T2DM. In this narrative review, we selected and analyzed the published literature on the effects of physical exercise on the metabolic features associated with non-obese-T2DM. Only randomized controlled trials with regular physical exercise training, freely executed physical activity, or skeletal muscle stimulation protocols in GK rats published after 2008 were included. The results indicated that exercise reduces plasma insulin levels, increases skeletal muscle glycogen content, improves exercise tolerance, protects renal and myocardial function, and enhances blood oxygen flow in GK rats.

Poor prognosis indicators of type-2 diabetic COVID-19 patients

Diabetes is associated with a worse prognosis and a high risk of morbidity and mortality in COVID-19 patients. We aimed to evaluate the main factors involved in the poor prognosis in diabetic patients. A total of 984 patients diagnosed with COVID-19 admitted to the hospital were included in this study. Patients were first divided into type-2 diabetic (DM+) and non-diabetic (DM-) groups. The participants were analyzed based on the National Early Warning Score (NEWS) and on the Quick-Sequential Organ Failure Assessment (qSOFA) to find the best prognostic risk score for our study. The DM+ and DM- groups were divided into non-severe and severe groups. Comparative and correlative analyses were used to identify the physiological parameters that could be employed for creating a potential risk indicator for DM+ COVID-19 patients. We found a poorer prognosis for the DM+ COVID-19 patients with a higher ICU admission rate, mechanical ventilation rate, vasopressor use, dialysis, and longer treatment times compared with the DM- group. DM+ COVID-19 patients had increased plasma glucose, lactate, age, urea, NEWS, and D-dimer levels, herein referred to as the GLAUND set, and worse prognosis and outcomes when compared with infected DM- patients. The NEWS score was a better indicator for assessing COVID-19 severity in diabetic patients than the q-SOFA score. In conclusion, diabetic COVID-19 patients should be assessed with the NEWS score and GLAUND set for determining their prognosis COVID-19 prognosis.

Spatial Bloch Oscillations of a Quantum Gas in a "Beat-Note" Superlattice.

We report the experimental realization of a new kind of optical lattice for ultracold atoms where arbitrarily large separation between the sites can be achieved without renouncing to the stability of ordinary lattices. Two collinear lasers, with slightly different commensurate wavelengths and retroreflected on a mirror, generate a superlattice potential with a periodic "beat-note" profile where the regions with large amplitude modulation provide the effective potential minima for the atoms. To prove the analogy with a standard large spacing optical lattice we study Bloch oscillations of a Bose Einstein condensate with negligible interactions in the presence of a small force. The observed dynamics between sites separated by ten microns for times exceeding one second proves the high stability of the potential. This novel lattice is the ideal candidate for the coherent manipulation of atomic samples at large spatial separations and might find direct application in atom-based technologies like trapped-atom interferometers and quantum simulators.

Polymorphic variants of alkaline phosphatase gene correlate with clinical signs of adult hypophosphatasia?

We analyzed polymorphism of the ALPL gene in patients with low serum levels of tissue-nonspecific alkaline phosphatase (TNAP). The presence of three or more of the less frequent alleles of ALPL polymorphisms was associated with significantly lower TNAP serum level and higher frequencies of metatarsal fractures, which may help confirm a clinical suspicion of adult hypophosphatasia. INTRODUCTION: Alkaline phosphatases (ALPs) are membrane-bound enzymes that hydrolyze monophosphate esters at a high pH (pH 8-10). Inorganic pyrophosphate, pyridoxal 5-phosphate, the activated form of vitamin B6 (PLP), and phosphoethanolamine (PEA), are natural substrates of ALPs. Hypophosphatasia (HPP, OMIM 146300, 241500, 241510) is a heterogeneous rare metabolic bone disease caused by loss-of-function mutations in the tissue-nonspecific alkaline phosphatase gene (ALPL; MIM 171760) with a deficiency of TNAP. Clinical presentation of HPP in adults demonstrated a wide range of manifestations, many of which are nonspecific. In the present study, we screened the polymorphic genetic variants of ALPL in 56 subjects presenting low serum levels of TNAP and/or other clinical signs of adult HPP in order to evaluate a possible role of polymorphic variants in the diagnosis and management of HPP in adults. METHODS: Genomic DNA was extracted from peripheral blood and ALPL gene was sequenced by PCR-based Sanger technique. RESULTS: Fourteen different polymorphic variants were found in the study population. A lower serum level of TNAP and higher frequencies of metatarsal fractures were observed in patients bearing three or more of the minor frequency alleles (MFAs) of the ALPL polymorphic variants. The presence of some MFAs, mostly as a contemporary presence of three or more of them, was found to be mainly represented in patients having both a significantly lower level of TNAP and a higher level of vitamin B6. CONCLUSION: The genetic analysis and presence of some polymorphic variants may be an instrument to confirm clinical and biochemical data, consider adult HPP, and help clinicians be cautious in the administration of anti-reabsorption drugs.

Bone fragility in patients affected by congenital diseases non skeletal in origin.

BACKGROUND: Bone tissue represents a large systemic compartment of the human body, with an active metabolism, that controls mineral deposition and removal, and where several factors may play a role. For these reasons, several non-skeletal diseases may influence bone metabolism. It is of a crucial importance to classify these disorders in order to facilitate diagnosis and clinical management. This article reports a taxonomic classification of non-skeletal rare congenital disorders, which have an impact on bone metabolism METHODS: The International Osteoporosis Foundation (IOF) Skeletal Rare Diseases Working Group (SRD-WG), comprised of basic and clinical scientists, has decided to review the taxonomy of non-skeletal rare disorders that may alter bone physiology. RESULTS: The taxonomy of non-skeletal rare congenital disorders which impact bone comprises a total of 6 groups of disorders that may influence the activity of bone cells or the characteristics of bone matrix. CONCLUSIONS: This paper provides the first comprehensive taxonomy of non-skeletal rare congenital disorders with impact on bone physiology.

A high-carbohydrate diet induces greater inflammation than a high-fat diet in mouse skeletal muscle.

We previously reported that both the high-carbohydrate diet (HCD) and high-fat diet (HFD) given for two months promote lipid deposition and inflammation in the liver and brain of mice. The results obtained indicate a tissue-specific response to both diets. Herein, we compared the effects of HCD and HFD on fatty acid (FA) composition and inflammation in the gastrocnemius muscle. Male Swiss mice were fed with HCD or HFD for 1 or 2 months. Saturated FA (SFA), monounsaturated FA (MUFA), n-3 polyunsaturated FA (n-3 PUFA), and n-6 PUFA were quantified. The activities of stearoyl-CoA desaturase 1 (SCD-1), Δ-6 desaturase (D6D), elongase 6, and de novo lipogenesis (DNL) were estimated. As for indicators of the inflammatory tissue state, we measured myeloperoxidase (MPO) activity and gene expression of F4/80, tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, and IL-10. The HCD led to a lower deposition of SFA, MUFA, n-3 PUFA, and n-6 PUFA compared to HFD. However, the HCD increased arachidonic acid levels, SFA/n-3 PUFA ratio, DNL, SCD-1, D6D, and MPO activities, and expression of IL-6, contrasting with the general idea that increased lipid deposition is associated with more intense inflammation. The HCD was more potent to induce skeletal muscle inflammation than the HFD, regardless of the lower lipid accumulation.

A high-carbohydrate diet induces greater inflammation than a high-fat diet in mouse skeletal muscle

We previously reported that both the high-carbohydrate diet (HCD) and high-fat diet (HFD) given for two months promote lipid deposition and inflammation in the liver and brain of mice. The results obtained indicate a tissue-specific response to both diets. Herein, we compared the effects of HCD and HFD on fatty acid (FA) composition and inflammation in the gastrocnemius muscle. Male Swiss mice were fed with HCD or HFD for 1 or 2 months. Saturated FA (SFA), monounsaturated FA (MUFA), n-3 polyunsaturated FA (n-3 PUFA), and n-6 PUFA were quantified. The activities of stearoyl-CoA desaturase 1 (SCD-1), Δ-6 desaturase (D6D), elongase 6, and de novo lipogenesis (DNL) were estimated. As for indicators of the inflammatory tissue state, we measured myeloperoxidase (MPO) activity and gene expression of F4/80, tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, and IL-10. The HCD led to a lower deposition of SFA, MUFA, n-3 PUFA, and n-6 PUFA compared to HFD. However, the HCD increased arachidonic acid levels, SFA/n-3 PUFA ratio, DNL, SCD-1, D6D, and MPO activities, and expression of IL-6, contrasting with the general idea that increased lipid deposition is associated with more intense inflammation. The HCD was more potent to induce skeletal muscle inflammation than the HFD, regardless of the lower lipid accumulation.

Stereotactic radiotherapy in oligoprogressive and oligorecurrent urothelial cancer patients: A retrospective experience.

Urothelial cancer is one of the most common malignancies; after relapse or disease progression available therapeutic options are limited. We analyze efficacy and toxicity of local treatment on metastases using stereotactic body radiation therapy (SBRT) in selected patients with oligometastatic disease from urothelial cancer. A significant percentage of treated lesions achieved local control, with a promising overall response rate. OBJECTIVES: to analyze efficacy and toxicity of local treatment on metastases using stereotactic body radiation therapy (SBRT) in selected patients with oligometastatic disease from urothelial cancer. MATERIALS AND METHODS: Data from clinical records of 19 patients treated in our institution since May 2011 to October 2017 with SBRT for oligometastatic/oligoprogressive urothelial carcinoma were retrospectively collected. Clinical outcomes in terms of local control (LC), response rate, symptoms control, progression free and overall survival (PFS and OS), and adverse events were analyzed and reported. RESULTS: Nineteen patients were treated on 25 metastatic lesions; 5 of them received treatment on multiple sites. After an average follow up of 11.5 months, LC was achieved in 17 lesions (68%) and there was no local recurrence in lesions with complete or partial response. OS was 13.8 months. Adverse events were reported only in 3 patients (5 overall events). No late toxicity was reported. CONCLUSIONS: An approach consisting in SBRT for local treatment of oligometastatic or persistent disease can be effective and safe in selected patients. Prospective studies are needed, to find correct selection criteria and optimal dose and fractionation.

Adipose tissue is less responsive to food restriction anti-inflammatory effects than liver, muscle, and brain in mice

High caloric intake promotes chronic inflammation, insulin resistance, and chronic diseases such as type-2 diabetes, which may be prevented by food restriction (FR). The effect of FR on expression of pro-inflammatory and anti-inflammatory genes in adipose tissue, liver, muscle, and brain was compared. Male Swiss mice were submitted to FR (FR group) or had free access to food (control group) during 56 days. The liver, gastrocnemius muscle, brain, and epididymal white adipose tissue (WAT) were collected for analysis of gene expressions. FR attenuated inflammation in the liver, brain, and gastrocnemius muscle but did not markedly change inflammatory gene expression in epididymal WAT. We concluded that adipose tissue was less responsive to FR in terms of gene expression of pro-inflammatory and anti-inflammatory genes.

Adipose tissue is less responsive to food restriction anti-inflammatory effects than liver, muscle, and brain in mice.

High caloric intake promotes chronic inflammation, insulin resistance, and chronic diseases such as type-2 diabetes, which may be prevented by food restriction (FR). The effect of FR on expression of pro-inflammatory and anti-inflammatory genes in adipose tissue, liver, muscle, and brain was compared. Male Swiss mice were submitted to FR (FR group) or had free access to food (control group) during 56 days. The liver, gastrocnemius muscle, brain, and epididymal white adipose tissue (WAT) were collected for analysis of gene expressions. FR attenuated inflammation in the liver, brain, and gastrocnemius muscle but did not markedly change inflammatory gene expression in epididymal WAT. We concluded that adipose tissue was less responsive to FR in terms of gene expression of pro-inflammatory and anti-inflammatory genes.

Phosphate wasting disorders in adults.

A cause of hypophosphatemia is phosphate wasting disorders. Knowledge concerning mechanisms involved in phosphate wasting disorders has greatly increased in the last decade by the identification of phosphatonins, among them FGF-23. FGF-23 is a primarily bone derived factor decreasing renal tubular reabsorption of phosphate and the synthesis of calcitriol. Currently, pharmacological treatment of these disorders offers limited efficacy and is potentially associated to gastrointestinal, renal, and parathyroid complications; therefore, efforts have been directed toward newer pharmacological strategies that target the FGF-23 pathway. This review focuses on phosphate metabolism, its main regulators, and phosphate wasting disorders in adults, highlighting the main issues related to diagnosis and current and new potential treatments.

Self-Bound Quantum Droplets of Atomic Mixtures in Free Space.

Self-bound quantum droplets are a newly discovered phase in the context of ultracold atoms. In this Letter, we report their experimental realization following the original proposal by Petrov [Phys. Rev. Lett. 115, 155302 (2015)PRLTAO0031-900710.1103/PhysRevLett.115.155302], using an attractive bosonic mixture. In this system, spherical droplets form due to the balance of competing attractive and repulsive forces, provided by the mean-field energy close to the collapse threshold and the first-order correction due to quantum fluctuations. Thanks to an optical levitating potential with negligible residual confinement, we observe self-bound droplets in free space, and we characterize the conditions for their formation as well as their size and composition. This work sets the stage for future studies on quantum droplets, from the measurement of their peculiar excitation spectrum to the exploration of their superfluid nature.

Robotic Stereotactic Retreatment for Biochemical Control in Previously Irradiated Patients Affected by Recurrent Prostate Cancer.

AIMS: Robotic stereotactic body radiotherapy (rSBRT) to local recurrences emerged as a valuable option for exclusive local failure after prior external beam radiation therapy (EBRT) for localised prostate cancer. The aim of this study was to assess the efficacy and safety of rSBRT in patients experiencing locally recurrent prostate cancer after prior definitive or postoperative radiotherapy using the Cyberknife. MATERIALS AND METHODS: Data from 50 patients were retrospectively reviewed. Local recurrence was assessed by 18F-choline positron emission tomography and pelvic magnetic resonance imaging; a dose of 30 Gy was delivered in five fractions. Prostate-specific antigen (PSA) was assessed at 2 months, 6 months and every 4 months thereafter. Toxicity was assessed according to CTCAE v.4.03. RESULTS: All patients received prior EBRT. The median EQD2 total dose was 74 Gy (60-80 Gy). Eleven patients were receiving androgen deprivation after prior biochemical failure. At 6 months, 41 patients showed a median PSA decline of -77.1% (14.3-99.3%), whereas nine patients experienced a median PSA elevation of +58.7% (0-2300.0%). Biochemical relapse-free survival (BRFS) was 80.0%. Impaired BRFS was correlated with the high-risk category at diagnosis (P = 0.014, hazard ratio 5.61) and ongoing androgen deprivation (P = 0.025, hazard ratio 2.98). Neither clinical variables nor dosimetric parameters were found to be predictive for toxicity. CONCLUSION: Focal rSBRT can achieve durable remission in locally relapsing patients and systemic treatment can be postponed with acceptable toxicity. Accurate patient selection is mandatory to maximise disease control.

Crossing Over from Attractive to Repulsive Interactions in a Tunneling Bosonic Josephson Junction.

We explore the interplay between tunneling and interatomic interactions in the dynamics of a bosonic Josephson junction. We tune the scattering length of an atomic ^{39}K Bose-Einstein condensate confined in a double-well trap to investigate regimes inaccessible to other superconducting or superfluid systems. In the limit of small-amplitude oscillations, we study the transition from Rabi to plasma oscillations by crossing over from attractive to repulsive interatomic interactions. We observe a critical slowing down in the oscillation frequency by increasing the strength of an attractive interaction up to the point of a quantum phase transition. With sufficiently large initial oscillation amplitude and repulsive interactions, the system enters the macroscopic quantum self-trapping regime, where we observe coherent undamped oscillations with a self-sustained average imbalance of the relative well population. The exquisite agreement between theory and experiments enables the observation of a broad range of many body coherent dynamical regimes driven by tunable tunneling energy, interactions and external forces, with applications spanning from atomtronics to quantum metrology.