Diversities of Mechanism in Patients with VHL Syndrome and diabetes: A Report of Two Cases and Literature Review.

Background: Von Hippel-Lindau (VHL) syndrome is characterized by tumorous lesions affecting multiple organs. Pancreatic involvement in VHL syndrome can present as endocrine tumors and pancreatic cysts, which can interfere with both exocrine and endocrine functions of the pancreas. Diabetes is an uncommon complication of VHL syndrome. Purpose: This study aims to summarize the various mechanisms of diabetes in VHL syndrome by reporting two cases and conducting a literature review. Methods: We analyzed the clinical and imaging data of two patients with VHL syndrome and diabetes. Additionally, we reviewed the existing literature to explore the clinical diversities and management strategies for VHL syndrome complicated with diabetes. Results: The first patient presented with liver metastasis of pancreatic neuroendocrine tumor and multiple pheochromocytoma. After surgery, the patient's diabetic control improved, as evidenced by a significant reduction in insulin dosage. This indicates a potential insulin resistance due to elevated metanephrine levels prior to surgery and partial insulin deficiency caused by distal pancreatectomy. The second patient had multiple hemangioblastomas, as well as multiple pancreatic cysts and positive pancreatic islet autoantibodies. Diabetes in this case may be attributed to pancreatic lesions and the coexistence of autoimmune insulitis. A literature review of other patients with VHL combined with diabetes revealed multiple mechanisms, including increased catecholamine levels, pancreatic lesions, surgical removal of pancreatic tissue, endocrine treatment, and possibly the coexistence of autoimmune insulitis. Conclusion: VHL syndrome complicated with diabetes involves diverse mechanisms.

Pituitary stalk interruption syndrome and liver cirrhosis associated with diabetes and an inactivating KCNJ11 gene mutation: a case report and literature review.

Background: Pituitary stalk interruption syndrome (PSIS) is a congenital disease commonly found in patients with combined pituitary hormone deficiency (CPHD). Most PSIS patients manifest growth retardation and delayed puberty. We report a rare case of PSIS with tall stature, liver cirrhosis and diabetes, possibly caused by an inactivating KCNJ11 gene mutation. Case presentation: A 37-year-old female patient initially presented with liver cirrhosis and diabetes, without any secondary sexual characteristics. Endocrine investigation indicated CPHD. Small anterior pituitary, invisible pituitary stalk and no eutopic posterior lobe hypersignal in the sella turcica viewed in magnetic resonance imaging (MRI) confirmed the diagnosis of PSIS. Despite receiving no growth hormone or sex hormone therapy, she reached a final height of 186 cm. Liver histopathology revealed nonalcoholic fatty cirrhosis. Genetic testing identified a heterozygous p.Arg301Cys mutation in the KCNJ11 gene. Conclusion: This is a rare case of PSIS with liver cirrhosis and diabetes associated with an inactivating KCNJ11 gene mutation. It's supposed that early hyperinsulinism caused by the KCNJ11 gene mutation, as well as delayed epiphyseal closure due to estrogen deficiency, contributed to the patient's exceptionally tall stature. Untreated growth hormone deficiency (GHD) resulted in increased visceral fat, leading to nonalcoholic fatty liver disease (NAFLD) and cirrhosis. The decline in ß cell function with age, combined with NAFLD, may have played a role in the development of diabetes.

Interface-Confined Channels Facilitating Water Transport through an IL-Enriched Nanocomposite Membrane.

Improving the permeance of the polyamide (PA) membrane while maintaining the rejection is crucial for promoting the development of membrane separation technology in the practical water-treatment industry. Herein, a novel metal-ionic liquid (Zn-IL) coordination compound was synthesized by in situ growth to improve the water permeance of PA nanofiltration membranes, using an amine-functionalized IL (1-aminopropyl-3-methylimidazolium chloride, [AEMIm][Cl]) as a ligand to react with Zn(NO3)2·6H2O. Piperazine (PIP) and trimesoyl chloride (TMC) were adopted to prepare the PA layer covering the Zn-IL complex. Due to the unique property of the Zn-IL complex, the Zn-IL/PIP-TMC absorbing force to water was increased, enabling the fast transport of water molecules through the membrane pore channels in the form of free water. The resulting Zn-IL/PIP-TMC nanocomposite membrane exhibited a high permeance of up to 26.5 L m-2 h-1 bar-1, which is 3 times that of the PIP-TMC membrane (8.8 L m-2 h-1 bar-1), combined with rejection above 99% for dyes such as methyl blue.

Euglycaemic Ketoacidosis Due to Extremely Low-Calorie Intake and Dehydration After Laparoscopic Sleeve Gastrectomy in a Patient with Type 2 Diabetes.

Background: Bariatric surgery is an effective therapy for type 2 diabetes mellitus (T2DM) and obesity. Euglycaemic ketoacidosis (EKA) has been reported in patients taking sodium-glucose cotransporter 2 (SGLT2) inhibitors after bariatric surgery. Cases of T2DM complicated with EKA without SGLT2 inhibitors after bariatric surgery are rarely reported. Purpose: To present a case report of a T2DM patient (without SGLT2 inhibitor use) who developed EKA soon after laparoscopic sleeve gastrectomy. Methods: Clinical records and interviews were used. Results: A 35-year-old female patient was diagnosed with T2DM and obesity. The patient underwent laparoscopic sleeve gastrectomy to lose weight and control her blood glucose levels. Her daily fluid intake was 800-1000 mL, and her daily caloric intake was less than 500 kcal during the first days after the surgery. She was prescribed degludec insulin, metformin and dulaglutide and her blood sugar was lower than 13.9 mmol/L. On postoperative Day 6, the patient complained of fatigue and vomiting. Blood gas analysis and urine analysis supported the diagnosis of ketoacidosis. Fluid resuscitation, insulin and glucose were administered to the patient immediately. On postoperative Day 8, the patient recovered without any symptoms. Conclusion: We report an extremely rare case of T2DM in which the patient developed EKA after laparoscopic sleeve gastrectomy owing to extremely low-calorie intake and dehydration. Physicians should be on alert for ketoacidosis in patients with T2DM after bariatric surgery with an euglycaemic status, even without the use of SGLT2 inhibitors or the presence of stresses, such as infection.Level V: Opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

Rule-based learning explains visual perceptual learning and its specificity and transfer.

Visual perceptual learning models, as constrained by orientation and location specificities, propose that learning either reflects changes in V1 neuronal tuning or reweighting specific V1 inputs in either the visual cortex or higher areas. Here we demonstrate that, with a training-plus-exposure procedure, in which observers are trained at one orientation and either simultaneously or subsequently passively exposed to a second transfer orientation, perceptual learning can completely transfer to the second orientation in tasks known to be orientation-specific. However, transfer fails if exposure precedes the training. These results challenge the existing specific perceptual learning models by suggesting a more general perceptual learning process. We propose a rule-based learning model to explain perceptual learning and its specificity and transfer. In this model, a decision unit in high-level brain areas learns the rules of reweighting the V1 inputs through training. However, these rules cannot be applied to a new orientation/location because the decision unit cannot functionally connect to the new V1 inputs that are unattended or even suppressed after training at a different orientation/location, which leads to specificity. Repeated orientation exposure or location training reactivates these inputs to establish the functional connections and enable the transfer of learning.

Decoupling location specificity from perceptual learning of orientation discrimination.

Perceptual learning of orientation discrimination is reported to be precisely specific to the trained retinal location. This specificity is often taken as evidence for localizing the site of orientation learning to retinotopic cortical areas V1/V2. However, the extant physiological evidence for training improved orientation turning in V1/V2 neurons is controversial and weak. Here we demonstrate substantial transfer of orientation learning across retinal locations, either from the fovea to the periphery or amongst peripheral locations. Most importantly, we found that a brief pretest at a peripheral location before foveal training enabled complete transfer of learning, so that additional practice at that peripheral location resulted in no further improvement. These results indicate that location specificity in orientation learning depends on the particular training procedures, and is not necessarily a genuine property of orientation learning. We suggest that non-retinotopic high brain areas may be responsible for orientation learning, consistent with the extant neurophysiological data.

Complete transfer of perceptual learning across retinal locations enabled by double training.

Practice improves discrimination of many basic visual features, such as contrast, orientation, and positional offset. Perceptual learning of many of these tasks is found to be retinal location specific, in that learning transfers little to an untrained retinal location. In most perceptual learning models, this location specificity is interpreted as a pointer to a retinotopic early visual cortical locus of learning. Alternatively, an untested hypothesis is that learning could occur in a central site, but it consists of two separate aspects: learning to discriminate a specific stimulus feature ("feature learning"), and learning to deal with stimulus-nonspecific factors like local noise at the stimulus location ("location learning"). Therefore, learning is not transferable to a new location that has never been location trained. To test this hypothesis, we developed a novel double-training paradigm that employed conventional feature training (e.g., contrast) at one location, and additional training with an irrelevant feature/task (e.g., orientation) at a second location, either simultaneously or at a different time. Our results showed that this additional location training enabled a complete transfer of feature learning (e.g., contrast) to the second location. This finding challenges location specificity and its inferred cortical retinotopy as central concepts to many perceptual-learning models and suggests that perceptual learning involves higher nonretinotopic brain areas that enable location transfer.

Stimulus coding rules for perceptual learning.

Perceptual learning of visual features occurs when multiple stimuli are presented in a fixed sequence (temporal patterning), but not when they are presented in random order (roving). This points to the need for proper stimulus coding in order for learning of multiple stimuli to occur. We examined the stimulus coding rules for learning with multiple stimuli. Our results demonstrate that: (1) stimulus rhythm is necessary for temporal patterning to take effect during practice; (2) learning consolidation is subject to disruption by roving up to 4 h after each practice session; (3) importantly, after completion of temporal-patterned learning, performance is undisrupted by extended roving training; (4) roving is ineffective if each stimulus is presented for five or more consecutive trials; and (5) roving is also ineffective if each stimulus has a distinct identity. We propose that for multi-stimulus learning to occur, the brain needs to conceptually "tag" each stimulus, in order to switch attention to the appropriate perceptual template. Stimulus temporal patterning assists in tagging stimuli and switching attention through its rhythmic stimulus sequence.