Diet shapes the metabolite profile in the intact human ileum, which affects PYY release.

The human ileum contains a high density of enteroendocrine L-cells, which release the appetite-suppressing hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) in response to food intake. Recent evidence highlighted the potential role of food structures in PYY release, but the link between food structures, ileal metabolites, and appetite hormone release remains unclear owing to limited access to intact human ileum. In a randomized crossover trial (ISRCTN11327221; isrctn.com), we investigated the role of human ileum in GLP-1 and PYY release by giving healthy volunteers diets differing in fiber and food structure: high-fiber (intact or disrupted food structures) or low-fiber disrupted food structures. We used nasoenteric tubes to sample chyme from the intact distal ileum lumina of humans in the fasted state and every 60 min for 480 min postprandially. We demonstrate the highly dynamic, wide-ranging molecular environment of the ileum over time, with a substantial decrease in ileum bacterial numbers and bacterial metabolites after food intake. We also show that high-fiber diets, independent of food structure, increased PYY release compared with a low-fiber diet during 0 to 240 min postprandially. High-fiber diets also increased ileal stachyose, and a disrupted high-fiber diet increased certain ileal amino acids. Treatment of human ileal organoids with ileal fluids or an amino acid and stachyose mixture stimulated PYY expression in a similar profile to blood PYY concentrations, confirming the role of ileal metabolites in PYY release. Our study demonstrates the diet-induced changes over time in the metabolite environment of intact human ileum, which play a role in PYY release.

Successful utilization of high frequency spinal cord stimulation for HIV and chemotherapy induced polyneuropathy.

We present a case of a 53-year-old male who presented with functionally limiting bilateral lower extremity neuropathic pain secondary to multiple subtypes of small fiber neuropathy. He had failed management with multiple conservative measures including oral medications, physical therapy and desensitization techniques. He ultimately underwent placement of a spinal cord stimulator and continued to experience 80% improvement of his pain, as well as improved function and quality of life at 5 month follow-up. To our knowledge, this is the first reported case of successful treatment of multiple subtypes of small fiber neuropathy with spinal cord stimulator.

We report a case of a 53-year-old male who presented with multiple subtypes of small fiber neuropathy, characterized by abnormal sensation and nerve pain in his distal lower extremities, which was making performing his activities of daily living challenging. He had failed multiple conservative measures including oral medications, physical therapy and desensitization techniques. The patient then underwent a trial with a spinal cord stimulator, which includes placing a device in the spinal canal that can alleviate pain by providing low levels of electrical current. At the 5 month follow-up, he continued to report 80% improvement of his pain as well as improved function and quality of life. This is the first reported use of spinal cord stimulator in a patient with multiple subtypes of small fiber neuropathy.

Successful application of spinal cord stimulation in a patient with refractory bilateral meralgia paresthetica.

We present a 38-year-old morbidly obese male who presented with functionally limiting bilateral anterior thigh pain consistent with meralgia paresthetica. His symptoms had been unresponsive to conservative measures which included physical therapy, oral medications and multiple nerve blocks. Patient underwent a trial of spinal cord stimulation (SCS), experiencing 70% of pain relief. He then underwent permanent SCS implant. At subsequent follow-ups 3 and 6 months later, he continued to report 70% improvement of his pain, as well as improved function and quality of life. To our knowledge, this is only the second reported case of successful treatment of meralgia paresthetica with SCS, and the first in a morbidly obese patient.

We report a case of a 38-year-old obese male who presented with meralgia paresthetica, a condition characterized by abnormal sensation and nerve pain to the outer aspect of the thigh, limiting his ability to perform activities of daily living. His pain was unresponsive to multiple treatment options such as physical therapy, oral medications and a series of injections with local anesthetic and corticosteroid medications. We then proceeded with spinal cord stimulation, which consists of implanting a device that provides low levels of electrical current to the spinal cord, in hopes of alleviating his pain. After implantation of the device, at 3- and 6-month follow-ups, he was able to achieve 70% improvement of his pain, with the ability to perform his daily activities. This is the second case reported of the use of spinal cord stimulation for this type of condition.

Local electrophilicity.

In this work some possibilities for deriving a local electrophilicity are studied. First, we consider the original definition proposed by Chattaraj, Maiti, and Sarkar (J Phys Chem A 107:4973, 2003), in which the local electrophilicity is given by the product of the global electrophilicity, and the Fukui function for charge acceptance is derived by two different approaches, making use of the chain rule for functional derivatives. We also modify the proposals based on the electron density so as to have a definition with the same units of the original definition, which also introduces a dependence in the Fukui function for charge donation. Additionally, we also explore other possibilities using the tools of information theory and the temperature dependent reactivity indices of the density functional theory of chemical reactivity. The poor results obtained from the last two approaches lead us to conjecture that this is due to the fact that the global electrophilicity is not a derivative, like most of the other reactivity indices. The conclusion is that Chattaraj's suggestion seems to be the simplest, but at the same time a very reliable approach to this important property.