Effect of Bacillus-direct-fed microbial on leaky gut, serum peptide YY concentration, bone mineralization, and ammonia excretion in neonatal female turkey poults fed with a rye-based diet.

Rye is high in nonstarch polysaccharides (NSP), a complex carbohydrate which cannot be digested by poultry as they lack the endogenous enzymes to do so. Exogenous carbohydrases must therefore be supplemented to avoid the antinutritional effects associated with a high NSP diet. The objectives of the present study were to evaluate the effects of a rye-based diet with and without supplementation of a Bacillus direct-fed microbial (DFM) on body weight, bone mineralization, and leaky gut, as well as its role on influencing serum concentrations of peptide YY (PPY) and the ammonia concentration in turkey manure. Two independent trials were conducted. In each experiment, day-of-hatch female turkey poults were neck tagged and randomly assigned to either a control rye-based diet or a rye-based diet supplemented with the DFM (n = 25 birds/group). At 10 days-of-age, poults in both groups were administered with an appropriate dose of fluorescein isothiocyanate-dextran (FITC-d) by oral gavage. One hour later, all poults were euthanized. Blood was collected to evaluate serum FITC-d and PPY concentrations. Furthermore, in Trial 2 only, both tibias were removed for assessment of bone parameters, and turkey manure was collected to evaluate physicochemical analysis. In both trials, poults treated with the DFM showed a significant increase (P < 0.05) in body weight and body weight gain as compared with control nontreated poults. Poults that received the DFM also had a significant reduction in serum levels of PPY and FITC-d when compared with control nontreated poults. In Trial 2, turkeys treated with the DFM had a substantial increase in tibia strength, tibia diameter, total ash, calcium, and phosphorus when compared with control nontreated turkeys. Their manure was also shown to have a significant reduction in the concentration of ammonia. This is the first report of a commercial DFM reducing the concentration of this compound in turkey manure. In summary, the results of the present study confirm that turkeys fed with a rye-based diet have a significant increase in gut permeability, a reduced body weight, and decreased bone mineralization when compared with turkeys fed with the DFM. Turkeys that received the rye-based diet supplemented with the Bacillus-DFM also had a significant reduction in the serum concentration of PPY when compared with control turkeys. This finding suggests a possible prebiotic effect of rye, warranting future studies to test this effect. Further studies to evaluate the microbiota diversity, as well as the concentration of ceca short-chain fatty acids, are also necessary to confirm the reliability of PPY as a potential metabolomic biomarker in poultry.

Imaging Appearance of SMARCB1 (INI1)-Deficient Sinonasal Carcinoma: A Newly Described Sinonasal Malignancy.

SMARCB1 (INI1)-deficient sinonasal carcinomas were first described in 2014, and this series of 17 cases represents the first imaging description. This tumor is part of a larger group of SMARCB1-deficient neoplasms, characterized by aggressive behavior and a rhabdoid cytopathologic appearance, that affect multiple anatomic sites. Clinical and imaging features overlap considerably with other aggressive sinonasal malignancies such as sinonasal undifferentiated carcinoma, which represents a common initial pathologic diagnosis in this entity. SMARCB1 (INI1)-deficient sinonasal tumors occurred most frequently in the nasoethmoidal region with invasion of the adjacent orbit and anterior cranial fossa. Avid contrast enhancement, intermediate to low T2 signal, and FDG avidity were frequent imaging features. Approximately half of the lesions demonstrated calcification, some with an unusual "hair on end" appearance, suggesting aggressive periosteal reaction.

PDE10A inhibitors stimulate or suppress motor behavior dependent on the relative activation state of the direct and indirect striatal output pathways.

The enzyme phosphodiesterase 10A (PDE10A) regulates the activity of striatal, medium spiny neurons (MSNs), which are divided into a behaviorally stimulating, Gs-coupled D1 receptor-expressing "direct" pathway and a behaviorally suppressant, Gi-coupled D2 receptor-expressing "indirect" pathway. Activating both pathways, PDE10A inhibitors (PDE10AIs) combine functional characteristics of D2 antagonists and D1 agonists. While the effects of PDE10AIs on spontaneous and stimulated behavior have been extensively reported, the present study investigates their effects on suppressed behavior under various conditions of reduced dopaminergic neurotransmission: blockade of D1 receptors with SCH-23390, blockade of D2 receptors with haloperidol, or depletion of dopamine with RO-4-1284 or reserpine. In rats, PDE10AIs displayed relatively low cataleptic activity per se. After blocking D1 receptors, however, they induced pronounced catalepsy at low doses close to those required for inhibition of apomorphine-induced behavior; slightly higher doses resulted in behavioral stimulant effects, counteracting the catalepsy. PDE10AIs also counteracted catalepsy and related behaviors induced by D2 receptor blockade or dopamine depletion; catalepsy was replaced by behavioral stimulant effects under the latter but not the former condition. Similar interactions were observed at the level of locomotion in mice. At doses close to those inhibiting d-amphetamine-induced hyperlocomotion, PDE10AIs reversed hypolocomotion induced by D1 receptor blockade or dopamine depletion but not hypolocomotion induced by D2 receptor blockade. It is concluded that PDE10AIs stimulate or inhibit motor behavior dependent on the relative activation state of the direct and indirect striatal output pathways.

Spontaneous lateral sphenoid cephaloceles: anatomic factors contributing to pathogenesis and proposed classification.

SUMMARY: Spontaneous lateral sphenoid cephaloceles arise from bony defects in the lateral sphenoid, in the absence of predisposing factors such as trauma, surgery, mass, or congenital skull base malformation. We reviewed CT and MR imaging findings and clinical data of 26 patients with spontaneous lateral sphenoid cephaloceles to better understand anatomic contributions to pathogenesis, varying clinical and imaging manifestations, and descriptive terminology. Two types of spontaneous lateral sphenoid cephaloceles were identified. In 15 of 26 patients, a type 1 spontaneous lateral sphenoid cephalocele was noted, herniating into a pneumatized lateral recess of the sphenoid sinus, and typically presenting with CSF leak and/or headache. In 11 of 26 patients, a type 2 spontaneous lateral sphenoid cephalocele was noted, isolated to the greater sphenoid wing without extension into the sphenoid sinus, presenting with seizures, headaches, meningitis, cranial neuropathy, or detected incidentally. All patients had sphenoid arachnoid pits, and 61% of patients had an empty or partially empty sella, suggesting that altered CSF dynamics may play a role in their genesis.

Characterization of DNA-protein complexes by capillary electrophoresis-single molecule fluorescence correlation spectroscopy.

A high-speed capillary electrophoresis mobility shift assay (CEMSA) for determining the binding ratios of DNA-protein complexes in solution is demonstrated. Single molecule fluorescence correlation spectroscopy (FCS) was used to resolve the bound and unbound fluorescently labeled DNA molecules as they flowed continuously through a fused silica capillary under the influence of an applied electric field. Resolution of the bound and unbound complexes was based on the difference in their electrophoretic mobilities, and was accomplished without the need to perform a chemical separation. Data sufficient to perform the analysis was acquired in less than 10 s, compared to the minutes that are normally needed to carry out such measurement via CE separation. The binding ratios were determined with 5 to 10% precision and agreed with the results obtained by CE separation within experimental error. The resolution of the CEMSA based FCS analysis (CEMSA-FCS) was significantly higher than for the analysis performed by conventional diffusional FCS, due to the higher mass sensitivity of the electrophoretic mobility compared to the translational diffusion coefficient. Fluorescently labeled 39-mer single stranded DNA (ssDNA) and the single stranded binding protein (SSB) from Escherichia coli was used as the model system. The dissociation constant of the ssDNA-SSB complex was estimated to be approximately 2 nM based on the CEMSA-FCS analysis.

Correlates of vascular access occlusion in hemodialysis.

Vascular access occlusion results in significant morbidity in hemodialysis patients. Age, diabetes, and synthetic grafts (polytetrafluoroethylene [PTFE]) have been associated with vascular access occlusion in univariate analysis. However, the independent risk associated with each of these factors has not been assessed adjusting for confounding among the factors or by other variables, such as blood pressure (BP) or hematocrit. The influence of serum lipoprotein(a) [Lp(a)] and fibronectin on vascular access occlusion has not been widely studied despite their theoretical or demonstrated importance in vascular bypass occlusion. In a cohort study of 124 hemodialysis patients monitored for up to 14 months, we reported that Lp(a) values in the upper tertile (> or = 57 mg/dL) were associated with vascular access occlusion risk in white and Hispanic patients, but not in black patients. We now report an expanded analysis of this data set to determine the independent correlates of vascular access occlusion. Variables tested included age, race, gender, diabetes, access type (PTFE v endogenous), treatment time, systolic BP, hematocrit, heparin and erythropoietin dosage, and serum levels of Lp(a) and fibronectin. In univariate analysis, access occlusion was associated with age, diabetes, PTFE, Lp(a) > or = 57 mg/dL, serum fibronectin, and reduced BP. The independent correlates of first access occlusion were determined with the Cox proportional hazards model. Since the overall model included a significant race x Lp(a) interaction term, we stratified by race. In black patients, risk correlated directly with PTFE (P < 0.01) and inversely with systolic BP (P < 0.001), whereas for white and Hispanic patients, age (P = 0.04) and Lp(a) > or = 57 mg/dL (P = 0.05) were associated with increased risk. In summary, vascular access occlusion was found to be associated with a number of factors. Important independent correlates were PTFE and lower BP in black patients, and age and serum Lp(a) > or = 57 mg/dL in white and Hispanic patients. Diabetes mellitus and increased serum fibronectin may contribute additional risk.

Prealbumin and lipoprotein(a) in hemodialysis: relationships with patient and vascular access survival.

The high morbidity and mortality of hemodialysis patients has led to a search for early markers of risk. Because cardiovascular and nutritional risk are prevalent in this population, we examined the prognostic value of the serum levels of two markers of risk in the general population: (1) lipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle linked to myocardial infarction and coronary bypass stenosis, and (2) prealbumin, a marker of visceral protein status, with a shorter half-life than that of serum albumin. Baseline demographics, clinical information, dialysis prescription, and serum biochemistry measurements of 125 hemodialysis patients followed for up to 14 months were recorded on enrollment. Vascular access events and deaths were recorded prospectively. The hypotheses tested were that increased serum Lp(a) levels would predict cardiovascular mortality and vascular access stenosis and thrombosis, and that reduced serum prealbumin levels would predict mortality risk independently of established risk predictors. Cross-sectional analysis of serum Lp(a) demonstrated a skewed distribution with a median value of 38.3 mg/dL (upper tertile, > or = 57 mg/dL). Lipoprotein(a) was significantly higher in black patients (P < 0.001) and was significantly correlated (P < 0.005) with total cholesterol and apoprotein B (apoB), but not with a history of prior coronary disease. Serum prealbumin was strongly correlated with serum albumin (r = 0.49, P < 0.001). However, prealbumin correlated (P < 0.001) more strongly with other serum nutrition markers (total cholesterol, apoB, creatinine, urea) than did serum albumin. Fourteen-month cumulative survival was 80%. Age, diabetes, and serum levels of albumin, prealbumin, creatinine, total cholesterol and apoB, but not Lp(a), were correlated with survival in univariate analysis. Using the Cox proportional hazards model, independent predictors of mortality risk were prealbumin less than 15 mg/dL versus higher values (relative risk [RR] = 4.48, P < 0.01), apoB (RR = 0.97 per 1 mg/dL increase, P < 0.02), creatinine less than 10 mg/dL versus higher values (RR = 3.51, P = 0.04), and age (RR = 1.04 per year, P = 0.10). Thirty-eight patients experienced at least one vascular access thrombosis (n = 33) or stenosis (n = 5) during the study. Patients with Lp(a) > or = 57 mg/dL had decreased vascular access event-free survival compared with patients with Lp(a) less than 57 mg/dL (56% v 73%, P < 0.06). This trend was increased in magnitude and statistically significant for white and Hispanic patients (31% v 79%, P < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Predictors of mortality in hemodialysis patients.

Serum biochemical measures suggestive of undernutrition have been reported to correlate with 1-yr mortality risk in prevalent groups of hemodialysis patients. The predictive power of these variables has not been reported in newly diagnosed patients or in patients whose dialysis prescription is guided by urea kinetics. The relationship of these predictors to mortality over periods of longer than 1 yr is also unreported. Therefore, the survival of 184 hemodialysis patients was examined for up to 44 months (1987 to 1991) with the Cox proportional hazards model. Baseline demographic, clinical, and biochemical parameters were used as independent variables. To adjust for bias in patient selection, the survival of patients with 12 months or less of prior dialysis at the time of enrollment ("new cases") was analyzed separately from that of patients with more than 1 yr of prior treatment ("long-standing cases"). Serum albumin was less than 3.5 g/dL in 31% of new cases and in 12% of long-standing cases. Adjusting for the other variables, low serum albumin was the strongest mortality risk predictor in both new and long-standing cases. Low serum cholesterol was an independent risk predictor in both groups. Diabetes and race were not significant predictors. Mean age at enrollment was nearly a decade higher for nonsurvivors than for survivors, in both new and long-standing groups. Yet, age was not an independent risk predictor in the Cox model for the new group because of an unexpectedly high death rate among young black men. Female gender, which was confounded by increased age, took the place of age in the model for the new group. For each model, there was good agreement between observed and predicted mortality for up to 24 months. To assess the influence of dialysis treatment time and dose (measured as pre-to-post treatment urea ratio) on risk, survival was examined in a subset of 139 patients monitored for up to 22 months, from 1989 to 1991, a period when the urea ratio was used routinely. Adjusting for the other variables, low serum albumin and cholesterol again independently increased risk. The urea ratio was also a significant independent predictor. The pattern of mortality by urea ratio was U shaped, with minimum risk for values between 2.5 and 3.4 Treatment time did not influence risk. It was concluded that baseline serum values of albumin and cholesterol strongly influence survival for up to 2 yr in new and long-standing hemodialysis patients.(ABSTRACT TRUNCATED AT 400 WORDS)