Addressing Chronic Conditions and Social Determinants of Health During the COVID-19 Pandemic.

Chronic conditions or diseases are defined as persistent conditions lasting ≥ 1 year requiring either ongoing medical attention or limiting daily living or both (Agency for Healthcare Research and Quality (AHRQ) in Programs: SHARE approach workshop, Agency for Healthcare Research and Quality (AHRQ) (2016) Programs: SHARE approach workshop 2016. https://www.ahrq.gov/professionals/education/curriculum-tools/shareddecisionmaking/workshop/index.html . Accessed 20 Jan 2017). Physical chronic conditions, including diabetes, hypertension, heart disease, arthritis, and stroke, are prevalent, especially in the older population. Over 90% of older adults have at least 1 and 77% have ≥ 2 chronic conditions (American Diabetes Association (ADA) in Statistics about diabetes, American Diabetes Association (ADA) (2023) Statistics about diabetes. https://diabetes.org/about-us/statistics/about-diabetes . Accessed 20 Apr 2023). Chronic conditions account for $4.1 trillion of the nation's annual healthcare expenditure (Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion in Health and economic costs of chronic conditions, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion. Health and Economic Costs of Chronic Conditions (2022). https://www.cdc.gov/chronicdisease/about/costs/index.htm . Accessed 7 Jan 2023). There are marked disparities based on age, color, and income, with older people, people of color, and lower-income people having higher treatment costs or even lost wages in response to having chronic conditions. Chronic conditions are the on-the-top leading causes for death with diabetes being the top 7th in the USA in 2019 (Ferguson in Metabolic Syndrome Related Dis, Ferguson et al., Metab Syndr Relat Disord 21:177-187, 2023).

The Effects of Electroacupuncture via Chronically Implanted Electrodes on Alcohol Drinking and Withdrawal Signs in Rats.

BACKGROUND: In the United States, more than 14 million adults suffer from alcohol use disorder (AUD). We proposed a stress-free method of electroacupuncture (EA) using chronically implanted electrodes. We aimed to develop an effective method of EA for treating AUD by testing various stimulation locations and parameters, and then investigate the effects of the daily EA on alcohol consumption and withdrawal signs in rats. MATERIALS AND METHODS: Sprague-Dawley rats were trained to voluntarily drink ethanol under the intermittent access two-bottle choice procedure. By the end of four weeks, rats with ethanol consumption ≥1.5 g/kg/24 h were considered alcohol-dependent and included in an acute and prolonged experiments. The acute study was designed to investigate the effects of EA with different parameters and at different locations. EA treatment was applied at bilateral ST36 alone or bilateral ST36 and HT7 acupoints for 30 minutes. We investigated the effects of EA on 24-hour alcohol consumption, preference ratio (alcohol drink vs total drink), alcohol withdrawal signs (AWS), and prolonged alcohol consumption. Each animal served as its own control. RESULTS: 1) By the end of week 4, 70% of rats became alcohol-dependent. 2) Following ethanol withdrawal, there was a gradual increase in AWS over time that peaked at two hours and dropped at six hours. Among the tested stimulation parameters and locations: 3) The best stimulation location was ST36 alone, and the best stimulation parameters were a combination of 100 and 2 Hz. EA at best stimulation location and parameters reduced ethanol intake by 27% (p < 0.05 vs baseline) and marginally reduced preference ratio by 23% (p = 0.05 vs baseline). 4) EA reduced AWS at two- and four-hours following ethanol withdrawal (p ≤ 0.03 each vs no EA). 5) Daily EA (for five consecutive days) resulted in a substantial reduction in ethanol intake and preference ratio by 44% and 47%, respectively (p = 0.002 each). CONCLUSIONS: This work shows the potential of this novel method of EA for the treatment of AUD. Further studies are warranted to investigate the mechanisms through which EA exerts its effects.

Amelioration of hippocampal dysfunction by adipose tissue-targeted stem cell transplantation in a mouse model of type 2 diabetes.

There is growing evidence that type 2 diabetes or insulin resistance is linked to cognitive impairment. We recently confirmed altered lipid composition, down-regulation of insulin receptor expression and impaired basal synaptic transmission in the hippocampus of our transgenic murine model of adipocyte insulin resistance (AtENPP1-Tg). Here we evaluated whether the correction of adipose tissue dysfunction [via the subcutaneous transplantation of mesenchymal stem cells (MSC)] can improve the hippocampal synaptic transmission in AtENPP1-Tg mice versus their wildtype littermates. Animals were simply randomized to receive MSC, then weighed weekly for 12 weeks. At euthanasia, we assessed leptin in the collected serum and hippocampal synaptic high-frequency stimulation long-term potentiation (HFS-LTP) using brain slices. MSC transplantation normalized AtENPP1-Tg body and epididymal fat weights and was associated with increased leptin levels, a sign of adipocyte maturation. More importantly, transplantation restored the deficiency observed in AtENPP1-Tg HFS-LTP, the cellular readout of memory. Our results further corroborate the role of adipocyte maturation arrest in adipose tissue and highlight a role for the adipose tissue in modulating hippocampal cellular mechanisms. Further studies are warranted to explore the mechanisms for the MSC-induced improvement of hippocampal HFS-LTP.

Peripheral adipose tissue insulin resistance alters lipid composition and function of hippocampal synapses.

Compelling evidence indicates that type 2 diabetes mellitus, insulin resistance (IR), and metabolic syndrome are often accompanied by cognitive impairment. However, the mechanistic link between these metabolic abnormalities and CNS dysfunction requires further investigations. Here, we evaluated whether adipose tissue IR and related metabolic alterations resulted in CNS changes by studying synapse lipid composition and function in the adipocyte-specific ecto-nucleotide pyrophosphate phosphodiesterase over-expressing transgenic (AtENPP1-Tg) mouse, a model characterized by white adipocyte IR, systemic IR, and ectopic fat deposition. When fed a high-fat diet, AtENPP1-Tg mice recapitulate essential features of the human metabolic syndrome, making them an ideal model to characterize peripherally induced CNS deficits. Using a combination of gas chromatography and western blot analysis, we found evidence of altered lipid composition, including decreased phospholipids and increased triglycerides (TG) and free fatty acid in hippocampal synaptosomes isolated from high-fat diet-fed AtENPP1-Tg mice. These changes were associated with impaired basal synaptic transmission at the Schaffer collaterals to hippocampal cornu ammonis 1 (CA1) synapses, decreased phosphorylation of the GluN1 glutamate receptor subunit, down-regulation of insulin receptor expression, and up-regulation of the free fatty acid receptor 1.

Electroacupuncture via Chronically Implanted Electrodes: Potential Treatment for Chemotherapy-Induced Delayed Emesis.

OBJECTIVES: We proposed a novel method of chronic electroacupuncture (EA) using implanted electrodes for the treatment of chronic chemotherapy-induced nausea and vomiting (CINV). We aimed to establish a rodent model of delayed emesis and explore EA effects on kaolin intake. MATERIALS AND METHODS: Saline-treated and cisplatin-treated rats underwent chronic placement of electrodes at bilateral PC6 and ST36 acupoints. Tested EA parameters included sham EA; EA at frequency of 10, 20, or 40 Hz; duration of one, three, or six hours; pulse width of 0.3, 0.6, or 1.2 msec; and amplitude of 0.4-2.0 mA. Kaolin intake was measured following each treatment. RESULTS: 1) Cisplatin increased kaolin intake (p ≤ 0.01 vs. saline). 2) In terms of reduction of kaolin intake vs. sham EA: a) EA at a frequency of 10 Hz was effective only when given for three hours (p = 0.0004). b) EA at a frequency of 20 Hz was effective when given for either one or three hours, with three hours being most effective (p = 0.007 and 0.005, respectively). c) EA at a frequency of 40 Hz was effective at six hours only (p = 0.04). 3) All different pulse widths significantly reduced kaolin intake, with 0.3 msec being most effective. 4) Using EA on both acupoints is superior to using EA on PC6 only (p = 0.005). CONCLUSION: EA with parameters of 20 Hz, 0.3 msec for three hours on both PC6 and ST36 acupoints was found to be the best in reducing kaolin intake. Chronic EA with appropriate parameters is effective in reducing pica in a rodent model of CINV.

Racial Disparities in Selected Complications and Comorbidities among People with Type 2 Diabetes.

Type 2 diabetes (T2D) is a growing public health concern, disproportionately impacting racial and ethnic minorities. Assessing disparities is the first step towards achieving the translation goal to reduce disparities in diabetes outcomes, according to the Centers for Disease Control and Prevention (CDC)'s Division of Diabetes. We analyzed the data of patients (18+ years) diagnosed with T2D between 1 January 2012 and 31 March 2017, using the electronic health records of the University of Texas Medical Branch at Galveston. We compared the crude rate and age-standardized rate (using direct method) of selected micro- and macrovascular complication rates, associated obesity, and insulin dependence among racial and ethnic groups. Our sample included 20,680 patients who made 394,106 visits (9922 non-Hispanic White patients, 4698 non-Hispanic Black patients, and 6060 Hispanic patients). Our results suggest a higher risk of acquiring macrovascular (hypertension, ischemic disease, and stroke) and microvascular (renal, ophthalmic, and neurological) complications in Black patients compared to non-Hispanic White and Hispanic patients. The rates of stage I or II obesity were higher in Black patients compared with White and Hispanic patients. The rates of insulin use rather than oral hypoglycemics were also higher in Black patients than White and Hispanic patients. The disparities in terms of the higher susceptibility to complications among Black patients are possibly linked to the socioeconomic disadvantages of this population, leading to poorer management. Prevention strategies are warranted to reduce the incidence of T2D complications in racial minorities.

Prolonged treatment with transcutaneous electrical nerve stimulation (TENS) modulates neuro-gastric motility and plasma levels of vasoactive intestinal peptide (VIP), motilin and interleukin-6 (IL-6) in systemic sclerosis.

PURPOSE: We assessed the effects of transcutaneous electrical nerve stimulation (TENS) on neurogastric functioning in scleroderma patients. METHODS: Seventeen SSc patients underwent 30 min TENS treatment >10Hz at GI acupuncture points PC6 and ST36, once (acute TENS) and then after two weeks of TENS sessions for 30 min twice daily (prolonged TENS). Data collected at Visits 1 and 2 included gastric myoelectrical activity (GMA) by surface electrogastrography (EGG), heart rate variability (HRV) by surface electrocardiography (EKG), GI specific symptoms and health related SF-36 questionnaires. Plasma VIP, motilin and IL-6 levels were determined. Statistical analyses were performed by Student's t-test, Spearman Rank and p-values <0.05 were considered significant. RESULTS: 1. Only after prolonged TENS, the percentages of normal slow waves and average slow wave coupling (especially channels 1, 2 reflecting gastric pacemaker and corpus regions) were significantly increased; 2. the percentage of normal slow waves was significantly correlated to sympathovagal balance; 3. Mean plasma VIP and motilin levels were significantly decreased after acute TENS, (vs. baseline), generally maintained in the prolonged TENS intervals. Compared to baseline, mean plasma IL-6 levels were significantly increased after acute TENS, but significantly decreased after prolonged TENS. 4. After prolonged TENS, the frequency of awakening due to abdominal pain and abdominal bloating were significantly and modestly decreased, respectively. CONCLUSIONS: In SSc patients, two weeks of daily TENS improved patient GMA scores, lowered plasma VIP, motilin and IL-6 levels and improved association between GMA and sympathovagal balance. This supports the therapeutic potential of prolonged TENS to enhance gastric myoelectrical functioning in SSc.

Outcomes of Medicare-covered diabetes self-management training for cancer survivors with diabetes.

PURPOSE: This study aimed to examine the impact of utilization of the Medicare-covered Diabetes Self-Management Training (DSMT) on the likelihood of receiving preventive care and on outcomes among cancer survivors with diabetes. METHODS: We conducted a retrospective cohort study using 1999-2019 Texas Cancer Registry-Medicare linkage data for beneficiaries diagnosed with prostate, colorectal, or breast cancer for ≥5 years. We used propensity score matching to estimate the beneficiaries' probability of receiving DSMT and matched it with non-users. The observed DSMT outcomes were hospitalization, ER visit, eye exam, HbA1c test, foot exam, nephropathy, and all-cause mortality. DSMT utilization was set at attending 1, 2, and 3 or more sessions. Conditional Cox proportional hazard regression was built to determine the association between DSMT use and each respective outcome, unadjusted and adjusted for patients' covariates. RESULTS: A total of 79,271 beneficiaries (65% had diabetes-related complications, and 41% were either prostate or breast cancer survivors) were included. We found that (1) DSMT users had more eye exams (HR=1.27), HbA1c tests (HR=1.47), foot exams (HR=1.21), and nephropathy visits (HR=1.11), and less hospitalization (HR=0.86) and overall mortality (HR=0.70) (p≤0.01 each vs. non-users); (2) among DSMT users, 56% attended one session, 24% attended 2 sessions, and 20% attended 3 or more sessions; (3) attending 2 or ≥3 DSMT sessions was associated with more eye exams (HR=1.14), HbA1c tests (HR=1.12), and foot exams (HR=1.24). CONCLUSIONS: DSMT is instrumental to preventing or delaying complications of diabetes in cancer survivors and reducing their overall mortality. The findings may inform future efforts to promote the value of DSMT for cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Medicare-covered DSMT offers a great value to cancer survivors with diabetes.

Coronavirus Disease 2019, Diabetes, and Inflammation: A Systemic Review.

People with cardiometabolic diseases [namely type 2 diabetes (T2D), obesity, or metabolic syndrome] are more susceptible to coronavirus disease 2019 (COVID-19) infection and endure more severe illness and poorer outcomes. Hyperinflammation has been suggested as a common pathway for both diseases. To examine the role of inflammatory biomarkers shared between COVID-19 and cardiometabolic diseases, we reviewed and evaluated published data using PubMed, SCOPUS, and World Health Organization COVID-19 databases for English articles from December 2019 to February 2022. Of 248 identified articles, 50 were selected and included. We found that people with diabetes or obesity have (i) increased risk of COVID-19 infection; (ii) increased risk of hospitalization (those with diabetes have a higher risk of intensive care unit admissions) and death; and (iii) heightened inflammatory and stress responses (hyperinflammation) to COVID-19, which worsen their prognosis. In addition, COVID-19-infected patients have a higher risk of developing T2D, especially if they have other comorbidities. Treatments controlling blood glucose levels and or ameliorating the inflammatory response may be valuable for improving clinical outcomes in these patient populations. In conclusion, it is critical for health care providers to clinically evaluate hyperinflammatory states to drive clinical decisions for COVID-19 patients.

Gastric emptying and intestinal transit of various enteral feedings following severe burn injury.

BACKGROUND: Burn-induced delayed gastric emptying and intestinal transit limits enteral feeding/resuscitation. AIMS: To study (1) the effects of burn injury on gastric emptying and intestinal transit at different time points following enteral feeding/fluids, and (2) the effects of enteral resuscitative fluids on gastric emptying, intestinal transit, and plasma volume expansion. METHODS: Rats were randomized into sham-burn and burn groups. They were either enterally untreated or treated by a gavage of one or multiple doses of oral rehydration solution (ORS) or, Vivonex(®), all mixed with phenol red as a marker, at different time points from 1 to 6 h after burn. Gastric emptying, intestinal transit and hematocrit values were assessed. Gastric emptying of a semi-solid methylcellulose meal served as a standard control for gastric emptying studies. RESULTS: We found that (1) burn did not alter the gastric emptying of ORS, but delayed its intestinal transit at all time points; (2) burn delayed the gastric emptying of both methylcellulose or Vivonex and the intestinal transit of Vivonex, 6 h after burn; and (3) multiple doses of ORS normalized the elevated post-burn hematocrit values. The percentage of plasma volume expansion at 6 h resulting from the multiple-dose ORS was superior to that of Vivonex by 50%. Addition of Erythromycin to Vivonex improved its gastric emptying, intestinal transit, and plasma volume expansion. CONCLUSIONS: Burn delays the gastric emptying of semi-solids, but not the ORS. Enteral electrolyte solution (ORS) and feeding (Vivonex) provided plasma volume expansion. Prokinetic drugs may be able to maximize the effectiveness of early post-burn feeding.

Combined Treatment of Adipose Derived-Mesenchymal Stem Cells and Pregabalin Is Superior to Monotherapy for the Treatment of Neuropathic Pain in Rats.

AIMS: Neuropathic pain following nerve injury does not respond well to most available pharmacological remedies. We aimed to compare the outcome of the addition of adipose-derived mesenchymal stem cells (ADMSCs) to pregabalin for neuropathic pain treatment. METHODS: Adult female albino rats (n = 100) were randomized to receive traumatic sciatic nerve injury or sham. Animals were then randomized to ADMSC treatment with or without pregabalin. We conducted a battery of neurobehavioral and electrophysiological to assess neuropathic pain. Following sacrifice, we evaluated the histological changes and gene expression of brain-derived neurotrophic factor (BDNF) in the sciatic nerve. Serum and sciatic nerve tissue pro- and inflammatory cytokine levels were also assessed. RESULTS: (1) All treatments significantly improved thermal withdrawal latency, sciatic nerve conduction velocity, and proinflammatory cytokine levels in injured animals, with no significant effect of the combined treatments compared to pregabalin monotherapy (p < 0.05 each). (2) Combined treatment significantly improved medial gastrocnemius electromyographic amplitude and sciatic function index compared to pregabalin monotherapy (p < 0.05 each). (3) Combined treatment significantly increased the BDNF expression, decreased anti-inflammatory cytokine (p < 0.05 each), and restored the structural nerve damage, compared to pregabalin monotherapy. CONCLUSIONS: Combined treatment is associated with greater improvement of the sciatic nerve structure and function. Further studies are warranted to study the mechanism of action of the combined treatment to improve neuropathic pain.

Lycopene is superior to moringa in improving fertility markers in diet-induced obesity male rats.

Obesity is a condition of chronic tissue inflammation and oxidative stress that poses as a risk factor for male infertility. Moringa oleifera oil extract is known to have cholesterol-lowering properties and a potential to treat obesity, while lycopene is a potent antioxidant. We hypothesize that Moringa or lycopene may improve male fertility markers in an animal model of diet-induced obesity. Male Albino rats (n = 60) were randomized to receive regular chow (RC) or high-fat diet (HFD) for 12 weeks (n = 30 each). Animals in each arm were further randomized to receive gavage treatment with corn oil (vehicle), lycopene (10 mg/kg), or Moringa (400 mg/kg) for four weeks starting on week 9 (n = 10 each). Animals were sacrificed at 12 weeks, and blood was collected to assess lipid profile, serum testosterone, and gonadotropin levels. The testes and epididymides were removed for sperm analysis, oxidative stress and inflammatory markers, and histopathological assessment. In comparison to their RC littermates, animals on HFD showed an increase in body weights, serum lipids, testosterone and gonadotrophin levels, testicular oxidative stress and inflammatory markers, as well as sperm abnormalities and disrupted testicular histology. Moringa or lycopene reduced body weight, improved oxidative stress, and male fertility markers in HFD-fed animals with lycopene exhibiting better anti-antioxidant and anti-lipidemic effects. Lycopene is superior to Moringa in improving male fertility parameters, possibly by attenuating oxidative stress.

Mechanisms of burn-induced impairment in gastric slow waves and emptying in rats.

Delayed gastric emptying is common following severe large cutaneous burns; however, the mechanisms of burn-induced delayed gastric emptying remain unknown. The aim of this study was to explore the possible involvement of hyperglycemia and cyclooxygenase-2 receptors in the burn-induced gastric dysrhythmias. Gastric slow waves and gastric emptying were assessed in rats 6 h following sham or burn injury. Animals were randomized to one sham-burn and seven burn groups: untreated; two groups of saline treated (control); insulin treated (5 IU/kg); cyclooxygenase-2 inhibitor treated (10 mg/kg); ghrelin treated (2 nmol/rat); and gastric electrical stimulation treated. It was found that 1) severe burn injury impaired gastric slow waves postprandially and delayed gastric emptying; 2) the impairment in gastric slow waves included a decrease in the slow-wave frequency and in the percentage of normal slow waves, and an increase in the percentage of bradygastria (P = 0.001, 0.01, and 0.01, respectively vs. preburn values). None of the gastric slow-wave parameters was significantly correlated with gastric emptying; 3) cyclooxygenase-2 inhibitor normalized burn-induced delayed gastric emptying (P = 0.3 vs. sham-burn), but not gastric dysrhythmias (P < 0.002 vs. sham), whereas insulin normalized both gastric emptying (P = 0.4 vs. sham-burn) and gastric dysrhythmias (P = 0.3 vs. sham-burn); 4) both gastric electrical stimulation and ghrelin accelerated burn-induced delayed gastric emptying (P = 0.002 and 0.04, respectively, vs. untreated burn). In conclusion, hyperglycemia alters gastric slow-wave activity and delayed gastric emptying, while cyclooxygenase-2 inhibition delays gastric emptying without altering gastric slow-wave activity.

Colorectal and rectocolonic reflexes in canines: involvement of tone, compliance, and anal sphincter relaxation.

Distention of the proximal colon may have inhibitory or excitatory effects on the rectum and vice versa. The reflexes between the proximal colon and the rectum have not been well studied due to difficulties in accessing the proximal colon. The aim of this study was to investigate the reflex responses and their mechanisms between the proximal colon and the rectum in consideration of distention-related changes in tone and compliance of these regions as well as anal sphincter relaxation in a canine model. Proximal colon/rectal tone, compliance, and anal sphincter relaxation were investigated in six dogs chronically implanted with a proximal colon cannula while in the fasting state and during proximal colon distention or rectal distention. It was found that: 1) both rectal distention and proximal colon distention significantly and substantially decreased the compliance of the opposite regions, and guanethidine abolished proximal colon distention-induced changes in rectal compliance; 2) rectal/proximal colon distension decreased proximal colonic/rectal tone, and guanethidine abolished both of these inhibitory effects; 3) the anal sphincter was more sensitive to rectal distention than proximal colon distention; and 4) the minimal distention pressure required to induce anal inhibitory reflex was lower for rectal distention than proximal colon distention. It was concluded that distention-related changes in tone and compliance suggest the long inhibitory reflexes between the proximal colon and the rectum with the sympathetic involvement in rectal responses. The anal sphincter is more sensitive to the distention of the rectum than that of the proximal colon.

Therapeutic lifestyle change intervention improved metabolic syndrome criteria and is complementary to amlodipine/atorvastatin.

AIMS: To examine whether addition of amlodipine (5 mg)/atorvastatin (10 mg) A/A to Therapeutic Lifestyle change intervention (TLC) would beneficially modulate Metabolic Syndrome (MetS) and oxidized low-density lipoprotein (Ox-LDL) levels. METHODS: Patients with MetS (n = 53) were randomized to TLC + placebo or TLC + A/A for 12 months. Anthropometric measurements, blood pressure (BP), lipid profile, plasma Ox-LDL, and area under the curve of free fatty acid (AUCFFA) during oral glucose tolerance test, a marker of adipose tissue health, were assessed before and after the intervention. RESULTS: Twenty-six patients completed the study with an overall improvement of MetS (p = 0.02). TLC + placebo was beneficial in reversing MetS comparable to TLC + A/A (54% vs. 39%; p = 0.08). Both treatments decreased systolic BP (p ≤ 0.01). TLC + A/A also decreased diastolic BP and triglyceride levels. The changes in Ox-LDL levels directly correlated with changes in weight in the TLC-placebo group (r = 0.64; p = 0.04). AUCFFA determined the loss of fat mass (r = 0.472, p = 0.03). CONCLUSIONS: 1) Addition of A/A has the advantage of improving the lipid profile and BP; but TLC alone was comparable to TLC + A/A in improving MetS; 2) weight change determines the TLC-associated change in Ox-LDL levels; and 3) AT metabolic health is a significant predictor of TLC-associated loss of body fat mass.

Ghrelin abates bacterial translocation following burn injury by improving gastric emptying.

BACKGROUND: In severe burns, increased intestinal permeability facilitates bacterial translocation, resulting in systemic endotoxemia and multi- organ failure. We investigated the role of burn-induced gastrointestinal dysmotility (BIGD) in promoting bacterial translocation following burn injury, and the protective effect of ghrelin in this process. METHODS: We assessed gastric emptying (GE%) and intestinal transit (IT by geometric center "GC") in a 60% total body surface area scald burn rat model and measured bacterial counts in mesenteric lymph nodes (MLN) and distal small intestine by colony-forming unit per gram of tissue (CFU/g). A group of animals was treated with ghrelin or saline after burn. KEY RESULTS: Scald burn was associated with a significant delay in GE (62% ± 4% vs 74% ± 4%; P = .02) and a trend of delay in intestinal transit (GC: 5.5 ± 0.1 vs 5.8 ± 0.2; P = .09). Concurrently, there was a marginal increase in small intestinal bacterial overgrowth (6 × 105 vs 2 × 105  CFU/g; P = .05) and significant translocation to MLN (2 × 102 vs 4 × 101 ; P = .03). We observed a negative correlation between GE and intestinal bacterial overgrowth (rs  = -0.61; P = .002) and between IT and translocation (rs  = -0.63; P = .004). Ghrelin administration significantly accelerated GE following burn injury (91% ± 3% vs 62% ± 4; P = .03), reduced small intestinal bacterial overgrowth, and completely inhibited translocation to MLN (0.0 vs 5 × 102 ; P = .01). CONCLUSIONS & INFERENCES: Burn-induced gastrointestinal dysmotility is correlated with the systemic translocation of gram-negative gut bacteria that are implicated in multiple organ failure in burn patients. Therapeutic interventions to restore BIGD are warranted (Neurogastroenterol Motil, 2012, 24, 78).

Feasibility of gastric electrical stimulation by percutaneous endoscopic transgastric electrodes.

BACKGROUND: Gastric electrical stimulation has been used for the treatment of drug refractory GI motility disorders and for the treatment of obesity. Both these indications have involved surgical placement of gastric electrodes, which adds to the complexity and cost of the procedure. Endoscopic placement is therefore an attractive alternative approach for this therapy. OBJECTIVE: Our purpose was to investigate the feasibility, safety, and efficacy of percutaneous endoscopic electrodes for gastric electrical stimulation. DESIGN AND SETTING: Experimental animal study in hound dogs. INTERVENTIONS: Percutaneous endoscopic transgastric electrode (PETE) placement was carried out by using a pair of gastric pacing wires attached to a percutaneous endoscopic gastrostomy tube. In addition, 4 pairs of gastric serosal electrodes were implanted surgically for comparison. The efficacy of the percutaneous endoscopic electrodes was defined by their ability to entrain gastric slow waves and the induction of dysrhythmia. RESULTS: (1) The PETE recorded gastric slow waves comparable to the serosal electrodes. (2) Gastric electrical stimulation with long pulses delivered by the PETE, at a frequency of 10% higher than the intrinsic gastric slow wave frequency, entrained gastric slow waves. (3) Gastric electrical stimulation delivered by the PETE, at a tachygastric frequency, induced gastric dysrhythmia. LIMITATIONS: This was an animal study; however, its results are expected to be reproducible in humans, with PETE kept in place for even a longer duration than 6 to 8 weeks. CONCLUSION: PETE placement is both feasible and safe. PETEs are effective, having a potential for use in treatment of both gastroparesis and obesity.

Clinical significance of quantitative assessment of rectoanal inhibitory reflex (RAIR) in patients with constipation.

BACKGROUND: Rectoanal inhibitory reflex (RAIR) is routinely assessed in anorectal manometry and is of clinical value in the diagnosis of patients with constipation. However, no quantitative analysis is currently available for the assessment of RAIR. The aim of this study was to evaluate the diagnostic value of quantitative assessment of RAIR in patients with constipation. METHODS: Nine healthy subjects, 22 constipation patients (CO) and 26 fecal incontinence patients (FI) were enrolled in this study. RAIR was solicited by inflating the balloon with various volumes from 10 to 50 mL. The percentage of relaxation was determined on the basis of the rectal resting sphincter pressure and residual pressure with the balloon distention. RESULTS: Percentage of internal sphincter relaxation induced by rectal distention in constipation patients was significantly lower with distention of 20, 30, 40, and 50 mL in comparison with that in healthy subjects (Mixed model, P<0.05). The volume of distention required to achieve a relaxation of 50% was significantly higher in patients with CO (37.3+/-3.1 mL) than that in healthy subjects (27.8+/-2.6 mL, P<0.03) or FI (26.3+/-2.3 mL, P<0.05). It was also found that the percentage of relaxation could be used to differentiate the patients with constipation with a specificity of 64% and a sensitivity of 67%. CONCLUSIONS: Patients with CO have impaired RAIR in comparison with healthy subjects and patients with FI. Quantitative assessment of RAIR is valuable in the diagnosis of patients with CO and may be incorporated in the clinical anorectal manometric test.

Adipose Tissue Insulin Resistance in Gestational Diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by insulin resistance (IR) and altered glucose-lipid metabolism. We propose that ectonucleotide pyrophosphate phosphodiesterase-1 (ENPP1), a protein known to induce adipocyte IR, is a determinant of GDM. Our objective was to study ENPP1 expression in adipose tissue (AT) of obese pregnant women with or without GDM, as well as glucose tolerance in pregnant transgenic (Tg) mice with AT-specific overexpression of human ENPP1. METHODS: AT biopsies and blood were collected from body mass index-matched obese pregnant women non-GDM (n = 6), GDM (n = 7), and nonpregnant controls (n = 6) undergoing cesarian section or elective surgeries, respectively. We measured the following: (1) Expression of key molecules involved in insulin signaling and glucose-lipid metabolism in AT; (2) Plasma glucose and insulin levels and calculation of homeostasis model assessment of IR (HOMA-IR); (3) Intraperitoneal glucose tolerance test in AtENPP1 Tg pregnant mice. RESULTS: We found that: (1) Obese GDM patients have higher AT ENPP1 expression than obese non-GDM patients, or controls (P = 0.01-ANOVA). (2) ENPP1 expression level correlated negatively with glucose transporter 4 (GLUT4) and positively with insulin receptor substrate-1 (IRS-1) serine phosphorylation, and to other adipocyte functional proteins involved in glucose and lipid metabolism (P < 0.05 each), (3) AT ENPP1 expression levels were positively correlated with HOMA-IR (P = 0.01-ANOVA). (4) Pregnant AT ENPP1 Tg mice showed higher plasma glucose than wild type animals (P = 0.046-t test on area under curve [AUC]glucose). CONCLUSIONS: Our results provide evidence of a causative link between ENPP1 and alterations in insulin signaling, glucose uptake, and lipid metabolism in subcutaneous abdominal AT of GDM, which may mediate IR and hyperglycemia in GDM.

Acupuncture-based modalities: novel alternative approaches in the treatment of gastrointestinal dysmotility in patients with systemic sclerosis.

BACKGROUND: The gastrointestinal (GI) dysmotility of systemic sclerosis (SSc, scleroderma) patients requires careful evaluation and intervention. The lack of effective prokinetic drugs motivate researchers to search for alternative treatments. OBJECTIVES: We present an overview of the pathophysiology of SSc GI dysmotility and the advances in its management, with particular focus on acupuncture-related modalities and innovative therapies. DATA SOURCES: Original research articles were identified based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline methodology. We have searched the MEDLINE database using Medical Subject Heading (MeSH) for all English and non-English articles with an English abstract from 2005 to October 2012. RESULTS: Only four original articles of various study designs were found studying Complementary and Alternative Medicine (CAM) therapies for SSc patients. Despite the small patient study numbers, CAM treatments, acupressure, and transcutaneous electroacupuncture, showed self-reported and physiologic evidence of improvement of GI functioning and/or symptoms in SSc patients. CONCLUSIONS: CAM therapies include experimental modalities with the potential to offer relief of symptoms from GI dysmotility. Larger studies are needed to investigate their optimal use in patient subsets to tailor therapies to patient needs.