The last giants: New evidence for giant Late Triassic (Rhaetian) ichthyosaurs from the UK.

Giant ichthyosaurs with body length estimates exceeding 20 m were present in the latest Triassic of the UK. Here we report on the discovery of a second surangular from the lower jaw of a giant ichthyosaur from Somerset, UK. The new find is comparable in size and morphology to a specimen from Lilstock, Somerset, described in 2018, but it is more complete and better preserved. Both finds are from the uppermost Triassic Westbury Mudstone Formation (Rhaetian), but the new specimen comes from Blue Anchor, approximately 10 km west along the coast from Lilstock. The more complete surangular would have been >2 m long, from an individual with a body length estimated at ~25 m. The identification of two specimens with the same unique morphology and from the same geologic age and geographic location warrants the erection of a new genus and species, Ichthyotitan severnensis gen. et sp. nov. Thin sections of the new specimen revealed the same histological features already observed in similar giant ichthyosaurian specimens. Our data also supports the previous suggestion of an atypical osteogenesis in the lower jaws of giant ichthyosaurs. The geological age and giant size of the specimens suggest shastasaurid affinities, but the material is too incomplete for a definitive referral. Ichthyotitan severnensis gen. et sp. nov., is the first-named giant ichthyosaur from the Rhaetian and probably represents the largest marine reptile formally described.

Nasoenteric Tube Placement in Patients with Esophageal Varices: A Review of the Current Evidence and Society Guidelines.

Esophageal varices are a common complication of portal hypertension and variceal bleeding can be associated with significant morbidity and mortality. Hospitalized patients with cirrhosis might require nasoenteric tube (NET) placement, commonly for nutritional support and/or medication administration. However, the fear of causing massive variceal bleeding among clinicians might lead to hesitancy or complete avoidance of NET placement in patients who either have a known history of esophageal varices or are at risk to have them. Several experts and society guidelines addressed this concern with variable recommendations and degrees of evidence. In this article, we present an extensive review of the literature and latest society guidelines that address the safety of NET placement in patients with esophageal varices.

Pneumatic compression therapy using the EQ Press accelerates lymphatic flow in healthy equine forelimbs as determined by lymphoscintigraphy.

OBJECTIVE: Limb lymphedema in horses can be debilitating and painful. Pneumatic compression therapy has shown significant benefits for people suffering from lymphedema. The objective of this study was to determine the effect of a novel, equine-specific pneumatic compression device on the lymphatic flow of healthy horse forelimbs as determined by Tc-99m sulfur colloid lymphoscintigraphy. ANIMALS: 6 healthy Thoroughbreds. PROCEDURES: In a randomized crossover design, horses underwent bilateral forelimb lymphoscintigraphy following subcutaneous injection of Tc-99m sulfur colloid at the coronary band as untreated control or with pneumatic compression therapy using the EQ Press. Lateral, static images were obtained of the distal limb (time 0 to 60 minutes) and proximal limb (time 30 to 60 minutes) using a standard gamma camera. Lymphatic flow was determined by assigning a score to the time point at which Tc-99m sulfur colloid was first visualized at the level of the accessory carpal bone (1 to 7) in the distal limb and the cubital lymph node (1 to 4) in the proximal limb. RESULTS: EQ Press treatment led to a significantly faster lymphatic flow of Tc-99m sulfur colloid to the predetermined anatomic locations of the accessory carpal bone (P = .002) in the distal limb and the cubital lymph node (P = .001) in the proximal limb. CLINICAL RELEVANCE: Pneumatic compression therapy as provided by an equine-specific device encouraged lymphatic flow in healthy, nonedematous equine forelimbs. These data support further study of the EQ Press for pneumatic compression therapy in horses clinically affected by lymphedema and lymphatic drainage disorders.

Myosin II Adjusts Motility Properties and Regulates Force Production Based on Motor Environment.

Introduction: Myosin II has been investigated with optical trapping, but single motor-filament assay arrangements are not reflective of the complex cellular environment. To understand how myosin interactions propagate up in scale to accomplish system force generation, we devised a novel actomyosin ensemble optical trapping assay that reflects the hierarchy and compliancy of a physiological environment and is modular for interrogating force effectors. Methods: Hierarchical actomyosin bundles were formed in vitro. Fluorescent template and cargo actin filaments (AF) were assembled in a flow cell and bundled by myosin. Beads were added in the presence of ATP to bind the cargo AF and activate myosin force generation to be measured by optical tweezers. Results: Three force profiles resulted across a range of myosin concentrations: high force with a ramp-plateau, moderate force with sawtooth movement, and baseline. The three force profiles, as well as high force output, were recovered even at low solution concentration, suggesting that myosins self-optimize within AFs. Individual myosin steps were detected in the ensemble traces, indicating motors are taking one step at a time while others remain engaged in order to sustain productive force generation. Conclusions: Motor communication and system compliancy are significant contributors to force output. Environmental conditions, motors taking individual steps to sustain force, the ability to backslip, and non-linear concentration dependence of force indicate that the actomyosin system contains a force-feedback mechanism that senses the local cytoskeletal environment and communicates to the individual motors whether to be in a high or low duty ratio mode. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-022-00731-1.

Anabolic Steroid-Induced Cholestatic Liver Injury: A Case Report.

Owing to performance-enhancing and cosmetic effects, illicit use of anabolic-androgenic steroids (AAS) has been well-described and can be associated with significant complications. We report a 27-year-old Caucasian male who self-medicated with AAS in the form of intramuscular injections and oral testosterone for a one-year duration. He complained of persistent jaundice and moderate generalized itching for one month. On admission, his total bilirubin level was 11.4 mg/dl (normal: 0-1.2 mg/dl), and liver enzymes were slightly elevated. On follow-up, the patient stated complete resolution of symptoms and near-normalization of lab results after one month of conservative management.

Multiomics assessment of dietary protein titration reveals altered hepatic glucose utilization.

Dietary protein restriction (PR) has rapid effects on metabolism including improved glucose and lipid homeostasis, via multiple mechanisms. Here, we investigate responses of fecal microbiome, hepatic transcriptome, and hepatic metabolome to six diets with protein from 18% to 0% of energy in mice. PR alters fecal microbial composition, but metabolic effects are not transferable via fecal transplantation. Hepatic transcriptome and metabolome are significantly altered in diets with lower than 10% energy from protein. Changes upon PR correlate with calorie restriction but with a larger magnitude and specific changes in amino acid (AA) metabolism. PR increases steady-state aspartate, serine, and glutamate and decreases glucose and gluconeogenic intermediates. 13C6 glucose and glycerol tracing reveal increased fractional enrichment in aspartate, serine, and glutamate. Changes remain intact in hepatic ATF4 knockout mice. Together, this demonstrates an ATF4-independent shift in gluconeogenic substrate utilization toward specific AAs, with compensation from glycerol to promote a protein-sparing response.

Advanced cancer patients in a randomized clinical trial of night-simulating eyeglasses observed to have a normal 24-h circadian rhythm during chemotherapy.

Objectives: Cancer patients routinely exhibit dysfunctional circadian organization. Indeed, a dysfunctional circadian organization is a hallmark of advanced cancer. A cohort of advanced cancer patients undergoing chemotherapy was recruited to investigate whether manipulating exposure to blue light could restore or ameliorate their circadian organization. Methods: Thirty advanced metastatic cancer patients participated in a randomized crossover trial to evaluate whether blue light-blocking night-simulating eyeglasses could ameliorate a disrupted circadian organization better than sham eyeglasses. Circadian organization was evaluated by actigraphy and patients' self-reports of sleep, fatigue, and quality of life. Kruskal-Wallis tests compared patients' outcomes in circadian organization with a cohort of non-cancer, disease-free individuals with normal sleep as a negative control, and with advanced cancer patients with disrupted circadian organization as a positive control. Quality-of-life outcomes of the patients were compared with population-based controls (negative controls) and with cohorts of advanced cancer patients (positive controls). Results: Actigraphy measurements, self-reported sleep, fatigue levels, and quality-of-life outcomes of trial participants were similar to those of negative controls with a normal circadian organization, in spite of the trial patients' concurrent chemotherapy. Night-simulating glasses did not improve circadian organization. The 24-h correlation of day-to-day rhythms of rest and activity was 0.455 for the experimental eyeglasses and 0.476 for the sham eyeglasses (p = 0.258). Actigraphic and patient-reported outcomes compared favorably to outcomes of positive controls. Conclusion: The circadian organization of patients in this study unexpectedly resembled that of healthy controls and was better than comparison populations with disrupted circadian organization. The study clinic implements chronomodulated chemotherapy and a systematic, supportive integrative treatment protocol. Results suggest a need for further research on interventions for circadian rhythm. Although the study intervention did not benefit the participants, this work highlights the value of supporting circadian time structure in advanced cancer patients.

Probing Myosin Ensemble Mechanics in Actin Filament Bundles using Optical Tweezers.

Myosins are motor proteins that hydrolyze ATP to step along actin filament (AF) tracks and are essential in cellular processes such as motility and muscle contraction. To understand their force-generating mechanisms, myosin II has been investigated both at the single-molecule (SM) level and as teams of motors in vitro using biophysical methods such as optical trapping. These studies showed that myosin force-generating behavior can differ greatly when moving from the single-molecule level in a three-bead arrangement to groups of motors working together on a rigid bead or coverslip surface in a gliding arrangement. However, these assay constructions do not permit evaluating the group dynamics of myosin within viscoelastic structural hierarchy as they would within a cell. We have developed a method using optical tweezers to investigate the mechanics of force generation by myosin ensembles interacting with multiple actin filaments. These actomyosin bundles facilitate investigation in a hierarchical and compliant environment that captures motor communication and ensemble force output. The customizable nature of the assay allows for altering experimental conditions to understand how modifications to the myosin ensemble, actin filament bundle, or the surrounding environment result in differing force outputs.

Epidural anesthesia needle guidance by forward-view endoscopic optical coherence tomography and deep learning.

Epidural anesthesia requires injection of anesthetic into the epidural space in the spine. Accurate placement of the epidural needle is a major challenge. To address this, we developed a forward-view endoscopic optical coherence tomography (OCT) system for real-time imaging of the tissue in front of the needle tip during the puncture. We tested this OCT system in porcine backbones and developed a set of deep learning models to automatically process the imaging data for needle localization. A series of binary classification models were developed to recognize the five layers of the backbone, including fat, interspinous ligament, ligamentum flavum, epidural space, and spinal cord. The classification models provided an average classification accuracy of 96.65%. During puncture, it is important to maintain a safe distance between the needle tip and the dura mater. Regression models were developed to estimate that distance based on the OCT imaging data. Based on the Inception architecture, our models achieved a mean absolute percentage error of 3.05% ± 0.55%. Overall, our results validated the technical feasibility of using this novel imaging strategy to automatically recognize different tissue structures and measure the distances ahead of the needle tip during the epidural needle placement.

Computer-aided Veress needle guidance using endoscopic optical coherence tomography and convolutional neural networks.

During laparoscopic surgery, the Veress needle is commonly used in pneumoperitoneum establishment. Precise placement of the Veress needle is still a challenge for the surgeon. In this study, a computer-aided endoscopic optical coherence tomography (OCT) system was developed to effectively and safely guide Veress needle insertion. This endoscopic system was tested by imaging subcutaneous fat, muscle, abdominal space, and the small intestine from swine samples to simulate the surgical process, including the situation with small intestine injury. Each tissue layer was visualized in OCT images with unique features and subsequently used to develop a system for automatic localization of the Veress needle tip by identifying tissue layers (or spaces) and estimating the needle-to-tissue distance. We used convolutional neural networks (CNNs) in automatic tissue classification and distance estimation. The average testing accuracy in tissue classification was 98.53 ± 0.39%, and the average testing relative error in distance estimation reached 4.42 ± 0.56% (36.09 ± 4.92 µm).

Total protein, not amino acid composition, differs in plant-based versus omnivorous dietary patterns and determines metabolic health effects in mice.

Plant-based dietary patterns are associated with improved cardiometabolic health, but causal dietary components are unclear. Protein has been proposed to play a role, but the importance of protein quantity versus quality remains unknown. We investigated the contributions of total protein amount, amino acid (AA) composition, and plant versus animal source. Analysis of total protein and AA composition of food items and dietary patterns revealed differences between individual food items, but few differences between AA profiles of vegan versus omnivorous dietary patterns. Effects of protein quantity, but not quality, on cardiometabolic health markers were observed in mice using semi-purified diets with crystalline AAs in plant versus animal-based ratios and naturally sourced diets with whole-food ingredients. Our data show relatively little difference in protein quality between plant-based and omnivorous dietary patterns and that reduced total protein intake in plant-based dietary patterns may be a contributor to the benefits of plant-based diets.

Down-Regulation of a Profibrotic Transforming Growth Factor-ß1/Cellular Communication Network Factor 2/Matrix Metalloprotease 9 Axis by Triamcinolone Improves Idiopathic Subglottic Stenosis.

Idiopathic subglottic stenosis (iSGS) is a progressive fibrotic disease characterized by life-threatening airway narrowing. Although the molecular underpinnings are unknown, previous reports showing that subglottic serial intralesional steroid injections (SILSIs) improve clinical outcomes suggest a steroid-sensitive pathway in iSGS. Herein, a prospective study was conducted to determine the changes in profibrotic markers during SILSI to identify steroid-sensitive profibrotic drivers. Seven newly diagnosed patients with iSGS were recruited for SILSI. Subglottic biopsies before and after SILSI treatments were evaluated for histologic and molecular markers by confocal microscopy and RT-qPCR. At baseline, iSGS subglottises contained abundant vimentin-positive/α-smooth muscle actin-negative fibroblasts, intermingled with a matrix of fibronectin and types I and VI collagen. Transforming growth factor (TGF)-ß1 was up-regulated primarily in glandular epithelium. Cellular communication network factor 2 (CCN2) was mainly up-regulated in stromal fibroblasts surrounding TGF-ß1-positive glandular structures. SILSI improved iSGS by reducing fibroblast infiltration and increasing matrix remodeling. Mechanistically, SILSI counteracted the effects of TGF-ß1 by inducing matrix metalloprotease 9 (MMP9) expression while repressing CCN2 expression, without affecting TGFß1 levels. Treatment of primary iSGS-derived fibroblasts with TGF-ß1 recapitulated aspects of the disease in vivo, demonstrating that the induction in CCN2 and repression of MMP9 are caused by changes in histone acetylation induced by TGF-ß1. Triamcinolone counteracted the coregulation of these genes by impairing SMAD2/3 binding to promoter regions, and not through histone acetylation. In conclusion, this study shows that SILSI counteracts a dysregulated TGF-ß1/CCN2/MMP9 axis involved in iSGS development.

Adipose tissue parasite sequestration drives leptin production in mice and correlates with human cerebral malaria.

Circulating levels of the adipokine leptin are linked to neuropathology in experimental cerebral malaria (ECM), but its source and regulation mechanism remain unknown. Here, we show that sequestration of infected red blood cells (iRBCs) in white adipose tissue (WAT) microvasculature increased local vascular permeability and leptin production. Mice infected with parasite strains that fail to sequester in WAT displayed reduced leptin production and protection from ECM. WAT sequestration and leptin induction were lost in CD36KO mice; however, ECM susceptibility revealed sexual dimorphism. Adipocyte leptin was regulated by the mechanistic target of rapamycin complex 1 (mTORC1) and blocked by rapamycin. In humans, although Plasmodium falciparum infection did not increase circulating leptin levels, iRBC sequestration, tissue leptin production, and mTORC1 activity were positively correlated with CM in pediatric postmortem WAT. These data identify WAT sequestration as a trigger for leptin production with potential implications for pathogenesis of malaria infection, prognosis, and treatment.

Determination of vibrational band positions in the E-hook of ß-tubulin.

Raman spectral characterization of the ß-TUBB2A E-hook hexapeptide, EGEDEA, is determined through experimental analysis combined with full geometry optimizations and corresponding harmonic vibrational frequency computations employing DFT methods. The hexapeptide is first broken down into di- and tetrapeptide fragments which are analyzed both quantum chemically and experimentally, and then combined to achieve an energetic minimum of the large EGEDEA hexapeptide. The Raman spectral characterization of EGEDEA band positions are then verified via the literature and comparison to the small fragment's similarly located band positions. The approach employed provides further evidence for the use of fragments as a helpful tool in characterization of the vibrational band positions of large peptides. STATEMENT OF SIGNIFICANCE: To investigate ß-TUBB2A E-hook hexapeptide, a unique approach is employed whereby the hexapeptide is broken into fragments, EG, ED, EA, EGED, and EDEA and analyzed via experimental Raman spectroscopy of the crystalline solids. The experimentally observed vibrational band positions are compared to those computed using and scaled from DFT methods and Pople's 6-311+G(2df,2pd) basis set. The reported vibrational band positions are also confirmed by previously reported bands of similar peptides in the literature. This methodology facilitates differentiation between the behaviors of various side chains and their influence on the structure of the hexapeptide, providing insight into not only the nature of the peptide but also defining regions for potential protein and cytoplasmic interactions, without requiring excessive computing resources or overly-sensitive experimental methods.

Deep neural network improves the estimation of polygenic risk scores for breast cancer.

Polygenic risk scores (PRS) estimate the genetic risk of an individual for a complex disease based on many genetic variants across the whole genome. In this study, we compared a series of computational models for estimation of breast cancer PRS. A deep neural network (DNN) was found to outperform alternative machine learning techniques and established statistical algorithms, including BLUP, BayesA, and LDpred. In the test cohort with 50% prevalence, the Area Under the receiver operating characteristic Curve (AUC) were 67.4% for DNN, 64.2% for BLUP, 64.5% for BayesA, and 62.4% for LDpred. BLUP, BayesA, and LPpred all generated PRS that followed a normal distribution in the case population. However, the PRS generated by DNN in the case population followed a bimodal distribution composed of two normal distributions with distinctly different means. This suggests that DNN was able to separate the case population into a high-genetic-risk case subpopulation with an average PRS significantly higher than the control population and a normal-genetic-risk case subpopulation with an average PRS similar to the control population. This allowed DNN to achieve 18.8% recall at 90% precision in the test cohort with 50% prevalence, which can be extrapolated to 65.4% recall at 20% precision in a general population with 12% prevalence. Interpretation of the DNN model identified salient variants that were assigned insignificant p values by association studies, but were important for DNN prediction. These variants may be associated with the phenotype through nonlinear relationships.

TREAT AF (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation): A Randomized Clinical Trial.

OBJECTIVES: This study was a sham-controlled, double-blind, randomized clinical trial to examine the effect of chronic low level tragus stimulation (LLTS) in patients with paroxysmal AF. BACKGROUND: Low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve at the tragus (LLTS) acutely suppresses atrial fibrillation (AF) in humans, but the chronic effect remains unknown. METHODS: LLTS (20 Hz, 1 mA below the discomfort threshold) was delivered using an ear clip attached to the tragus (active arm) (n = 26) or the ear lobe (sham control arm) (n = 27) for 1 h daily over 6 months. AF burden over 2-week periods was assessed by noninvasive continuous electrocardiogram monitoring at baseline, 3 months, and 6 months. Five-minute electrocardiography and serum were obtained at each visit to measure heart rate variability and inflammatory cytokines, respectively. RESULTS: Baseline characteristics were balanced between the 2 groups. Adherence to the stimulation protocol (≤4 sessions lost per month) was 75% in the active arm and 83% in the control arm (p > 0.05). At 6 months, the median AF burden was 85% lower in the active arm compared with the control arm (ratio of medians: 0.15; 95% confidence interval: 0.03 to 0.65; p = 0.011). Tumor necrosis factor-alpha was significantly decreased by 23% in the active group relative to the control group (ratio of medians: 0.77; 95% confidence interval: 0.63 to 0.94; p = 0.0093). Frequency domain indices of heart rate variability were significantly altered with active versus control stimulation (p < 0.01). No device-related side effects were observed. CONCLUSIONS: Chronic, intermittent LLTS resulted in lower AF burden than did sham control stimulation, supporting its use to treat paroxysmal AF in selected patients. (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation [TREAT-AF]; NCT02548754).

Natural Killer-Like T-Cell Lymphoma: A Rare Cause of Acute Liver Failure.

Acute liver failure is characterized by encephalopathy and disruption of hepatic function, often requiring liver transplantation to prevent fatal consequences. We present a 33-year-old man with recurrent lymphoma presenting with acute liver failure, which was initially thought to be from drug-induced liver injury associated with his chemotherapy medication, asparaginase. However, liver biopsy revealed malignant infiltration by lymphoma. The subtype of lymphoma was natural killer-like T-cell lymphoma, which is an uncommon variant, and has rarely been associated with hepatic infiltration. His condition rapidly worsened with development of multiorgan failure leading to death.

Effects of timing of food intake and fat/carbohydrate ratio on insulin sensitivity and preconditioning against renal ischemia reperfusion injury by calorie restriction.

BACKGROUND: Dietary restriction (DR) improves lifespan, metabolic fitness and resilience in many organisms, but the role of dietary macronutrient composition and timing of food intake in specific benefits remains unclear. OBJECTIVE: We sought to compare the effects of two isocaloric DR regimes differing in the timing of food intake - every other day (EOD) fasting/feeding vs. daily calorie restriction (CR) - at two different fat/carbohydrate ratios on two well-established DR benefits, improved glucose homeostasis and protection from renal ischemia reperfusion injury in mice. We hypothesized that both EOD fasting and isocaloric CR would result in similar improvements in glucose homeostasis and stress resistance independent of macronutrient composition. METHODS: Six groups of mice were fed either semi-purified low-fat diet (LFD, 10% calories from fat) or high-fat diet (HFD, 60% calories from fat) and randomized into one of three dietary regimens: 1) ad libitum (AL), 2) EOD feeding/fasting, or 3) pair-fed daily to the average daily EOD intake within LFD or HFD feeding group resulting in daily CR. After 6 weeks, the following assessments were made: fasting blood glucose, glucose and insulin tolerance, and resistance to bilateral renal ischemia reperfusion injury using serum urea as a marker of renal function. Within the EOD group, the effects of prior day feeding (EODfed vs. EODfast) were also assessed. RESULTS: EOD mice ate ∼20-25% less food over time than AL mice on the corresponding LFD or HFD. EOD and CR mice displayed changes in body weight, fasting blood glucose levels and glucose tolerance commensurate with total calorie intake. No significant differences were observed in circulating IGF-1 levels. Insulin sensitivity improved independent of fat/carbohydrate ratio on daily CR and EODfast regimens, but not EODfed. HFD increased susceptibility to renal ischemia reperfusion in AL mice, while CR and EOD regimens gave significant protection independent of dietary fat content or fed or fasted day in the EOD group. CONCLUSIONS: Reduced food intake protects mice against renal ischemia reperfusion injury within 6 weeks independent of timing of food intake (CR, EODfast, EODfed) or fat content of diet (10% vs. 60%). Neither circulating IGF-1 levels (unchanged) nor whole-body insulin sensitivity (improved upon daily CR and EODfast but not EODfed) correlated with protection, so are unlikely to be involved mechanistically.

Gabapentin Improves Symptoms of Functional Dyspepsia in a Retrospective, Open-label Cohort Study.

GOALS: We sought to determine the efficacy of gabapentin in the treatment of functional dyspepsia among an observational cohort of patients. BACKGROUND: Gabapentin has an established role in the treatment of neuropathic pain, with evidence supporting a benefit in visceral hypersensitivity. There is currently no data on the use of gabapentin for the treatment of functional dyspepsia. STUDY: Consecutive patients presenting to a tertiary motility clinic for the evaluation of functional dyspepsia without concurrent gastric emptying delay completed a baseline Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) before evaluation and were started on gabapentin for functional dyspepsia by their providers. The primary endpoint was change in total PAGI-SYM score between initial and subsequent visits. RESULTS: Of 110 patients enrolled, 62 patients with functional dyspepsia completed pregabapentin and postgabapentin surveys. Subjects' mean PAGI-SYM score decreased by 0.44 (P<0.0001) with significant changes in all subscales (including upper abdominal pain, lower abdominal pain, postprandial fullness) except for bloating. Multivariable analysis showed that worsening pretreatment symptom severity was independently associated with improvement. Seven (11.3%) patients discontinued gabapentin with 5 (71.4%) discontinuing due to side effects. Using the minimum significant PAGI-SYM score change threshold, ≥50% of the cohort had significant improvement in their overall, postprandial fullness, and upper abdominal pain subscores. CONCLUSIONS: In a retrospective, open-label cohort of patients treated with gabapentin for functional dyspepsia, there were significant improvements in dyspeptic symptoms interpreted within the limitations of an open-label study design. Further studies are needed to place gabapentin in the functional dyspepsia treatment algorithm.