Effect of asthma and six-months high-intensity interval training on heart rate variability during exercise in adolescents.

Little is known regarding the influence of asthma and exercise, and their interaction, on heart rate variability (HRV) in adolescents. Thirty-one adolescents with asthma (13.7±0.9 years; 21.9±3.9 kg·m-2; 19 boys, 12 girls) and thirty-three healthy adolescents (13.8±0.9 years; 20.3±3.2 kg·m-2; 16 boys, 17 girls) completed an incremental ramp test and three heavy-intensity constant-work-rate cycle tests. Thirteen adolescents (7 boys, 6 girls; 6 asthma, 7 control) completed six-months high-intensity interval training (HIIT) and were compared to age- and sex-matched controls. Standard time-domain, frequency-domain and non-linear indices of HRV were derived at baseline, three- and six-months. Asthma did not influence HRV at baseline or following HIIT. Total power, low frequency and normalised low frequency power, and sympathovagal balance increased at three-months in HIIT, subsequently declining towards baseline at six-months. Normalised high frequency power was reduced at three-months in both groups, which was sustained at six-months. No effects of HIIT were observed in the time-domain nor in the non-linear indices. HRV was not influenced by asthma, potentially because such derangements are a function of disease progression, severity or duration. HIIT may be associated with a short-term shift towards greater sympathetic predominance during exercise, perhaps caused by physiological overload and fatigue.

Finite-time Lyapunov exponent-based analysis for compressible flows.

The finite-time Lyapunov exponent (FTLE) technique has shown substantial success in analyzing incompressible flows by capturing the dynamics of coherent structures. Recent applications include river and ocean flow patterns, respiratory tract dynamics, and bio-inspired propulsors. In the present work, we extend FTLE to the compressible flow regime so that coherent structures, which travel at convective speeds, can be associated with waves traveling at acoustic speeds. This is particularly helpful in the study of jet acoustics. We first show that with a suitable choice of integration time interval, FTLE can extract wave dynamics from the velocity field. The integration time thus acts as a pseudo-filter separating coherent structures from waves. Results are confirmed by examining forward and backward FTLE coefficients for several simple, well-known acoustic fields. Next, we use this analysis to identify events associated with intermittency in jet noise pressure probe data. Although intermittent events are known to be dominant causes of jet noise, their direct source in the turbulent jet flow has remained unexplained. To this end, a Large-Eddy Simulation of a Mach 0.9 jet is subjected to FTLE to simultaneously examine, and thus expose, the causal relationship between coherent structures and the corresponding acoustic waves. Results show that intermittent events are associated with entrainment in the initial roll up region and emissive events downstream of the potential-core collapse. Instantaneous acoustic disturbances are observed to be primarily induced near the collapse of the potential core and continue propagating towards the far-field at the experimentally observed, approximately 30° angle relative to the jet axis.

Recruitment of pregnant women to an exercise-intervention study.

We share here our experience of recruiting pregnant women into an exercise intervention study. Recruitment challenges were anticipated owing to the study design, which required four hospital visits for cardiovascular assessment, a long-term (nine-month) commitment, and adherence to a 20-week exercise programme. Fifty-three women were assigned to one of three groups (no-exercise, land exercise or water exercise) using a 2 × 2 × 2 flexible randomisation design. Seven hundred forty-four women were screened at an antenatal clinic, of whom 501 were eligible to participate in the study. One hundred forty-five women were subsequently approached: 46 (32%) of whom agreed to participate, 42 (29%) were interested but then declined and 57 (39%) declined outright. Our study design helped recruit pregnant women as it allowed them some choice of group membership. We also noted that the participant-researcher relationship is important in reducing attrition. Our experience provides indications of likely recruitment and attrition rates for future randomised controlled trials of this type.

Relationship between changes in pulmonary V̇O2 kinetics and autonomic regulation of blood flow.

Various regulatory mechanisms of pulmonary oxygen uptake (V̇O2) kinetics have been postulated. The purpose of this study was to investigate the relationship between vagal withdrawal, measured using RMSSDRR, the root mean square of successive differences in cardiac interval (RR) kinetics, a mediator of oxygen delivery, and V̇O2 kinetics. Forty-nine healthy adults (23 ± 3 years; 72 ± 13 kg; 1.80 ± 0.08 m) performed multiple repeat transitions to moderate- and heavy-intensity exercise. Electrocardiography, impedance cardiography, and pulmonary gas exchange parameters were measured throughout; time domain measures of heart rate variability were subsequently derived. The parameters describing the dynamic response of V̇O2, cardiac output (Q) and RMSSDRR were determined using a mono-exponential model. During heavy-intensity exercise, the phase II τ of V̇O2 was significantly correlated with the τ of RR (r = 0.36, P < 0.05), Q (r = 0.67, P < 0.05), and RMSSDRR (r = 0.38, P < 0.05). The τ describing the rise in Q explained 47% of the variation in V̇O2 τ, with 30% of the rate of this rise in Q explained by the τ of RR and RMSSDRR. No relationship was evident between V̇O2 kinetics and those of Q, RR, or RMSSDRR during moderate exercise. Vagal withdrawal kinetics support the concept of a centrally mediated oxygen delivery limitation partly regulating V̇O2 kinetics during heavy-, but not moderate-, intensity exercise.

Potential sources of mouth drying in beverages fortified with dairy proteins: A comparison of casein- and whey-rich ingredients.

Oral nutritional supplement drinks (ONS) are beverages high in dairy proteins that are prescribed to individuals at risk of malnutrition. Consumption of ONS is poor in elderly care facilities, with patients commenting that the sensory attributes of these drinks reduce their enjoyment and willingness to consume. Mouth drying is an attribute of ONS found to build with repeated consumption, which may further limit liking of these products. This study investigated the sources of drying sensations by sequential profiling, with a trained sensory panel rating a range of model milk systems and ONS over repeated sips and during after-effects. Sequential profiling found that fortification of milk with both caseinate and whey protein concentrate significantly increased the perception of mouth drying over repeated consumption, increasing by between 35 and 85% over consumption of 40mL. Enrichment of ONS with either whey protein concentrate or milk protein concentrate to a total protein content of 8.7% (wt/wt) resulted in whey and casein levels of 4.3:4.4% and 1.7:7.0% respectively. The product higher in whey protein was substantially more mouth drying, implying that whey proteins may be the most important contributor to mouth drying in ONS. However, efforts to mask mouth drying of protein-fortified milk by increasing sweetness or fat level were unsuccessful at the levels tested. Increasing the viscosity of protein-fortified milk led to a small but significant reduction in mouth drying. However, this approach was not successful when tested within complete ONS. Further analysis is required into the mechanism of protein-derived mouth drying to mask negative sensations and improve the enjoyment and consumption of protein-rich ONS.

Electrodiagnostic testing in dogs with disorders of the spinal cord or cauda equina.

Electrodiagnostic (EDX) testing is uncommonly utilized in dogs other than for investigation of disorders of the neuromuscular system. In dogs with diseases affecting the spinal cord or cauda equina, EDX testing can provide functional data complementary to imaging information that together can guide therapeutic and management approaches. Additionally, in some clinical scenarios, EDX testing prior to advanced imaging is integral to identifying if there is spinal cord or cauda equina involvement and can aid in determining the appropriate diagnostic path. This review will outline EDX testing methods that have been reported in dogs relating to the diagnosis, monitoring or prognosis of various conditions affecting the spinal cord and cauda equina. The various tests will be briefly outlined regarding how they are performed and what information is provided. The main focus will be on clinical applications including highlighting situations where EDX testing is useful for differentiating between neurologic and non-neurologic presentations. Additional ways these EDX techniques could be incorporated in the management of diseases of the spinal cord and cauda equina in dogs will be presented.

Quantification of metallic artifact on CT associated with titanium pedicle screws.

Background: In dogs undergoing vertebral column stabilization, post-operative computed tomography (CT) evaluates implant placement. The impact on the interpretation of metallic artifact associated with titanium implants in dogs remains to be established. Our objective was to quantify metallic artifact on CT associated with titanium pedicle screws. Methods: The study design included an in vitro model and a retrospective review of 11 dogs with vertebral column stabilization. Twenty four titanium pedicle screws (6 each: 2.0 mm, 2.7 mm, 3.5 mm, and 4.5 mm) were inserted into a 20% ballistic gel, and CT scan of the construct was performed. Three blinded raters used a bone window to measure the maximum width (effective size) of each screw, one rater measured effective size using an ultrawide window and 45 titanium pedicle screws (3×2.0 mm, 5×2.7 mm, 30×3.5 mm, and 7×4.5 mm) in 11 clinical cases. Effective size measurements were compared to actual screw sizes. Results: The effective size was 26.9-43.8%, 9.2-18.5%, and 21.1-30.5% larger than the actual size for the in vitro system (bone window), in vitro system (ultrawide window), and clinical cases, respectively. The mean gross difference for the in vitro measurements varied by implant size (p < 0.001) and was positively correlated with implant size (r = 0.846), but the mean percentage difference was negatively correlated with implant size (p < 0.001). Overestimation was larger for the in vitro model bone window compared to the ultrawide window (p < 0.001) and clinical cases (p = 0.001). Conclusion: Metallic artifact associated with titanium pedicle screws on CT resulted in an overestimation of screw size. This information might aid in the interpretation of implant placement on post-operative imaging.

Use of levetiracetam for the successful treatment of suspected myoclonic seizures: five dogs (2016-2022).

OBJECTIVES: Myoclonic seizures are considered a type of generalised seizure characterised by brief, jerking movements of the body. The aim of this study is to describe cases of suspected canine myoclonic seizure of idiopathic aetiology and to discuss the successful use of the anticonvulsant levetiracetam as treatment in each of these cases. MATERIALS AND METHODS: Dogs with epileptic myoclonus suspected to be idiopathic in aetiology were considered for inclusion. Medical records were reviewed for physical and neurologic examination findings, clinicopathologic results, and diagnostic imaging results. All included dogs were treated with levetiracetam, and their response was reported. RESULTS: Five dogs were included, all of which had suspected myoclonic seizures either observed in-person or on video recording by a board-certified veterinary neurologist. The duration of myoclonic seizures preceding treatment ranged from one day to one year. One dog also experienced a generalised tonic-clonic seizure. All dogs were treated with levetiracetam. Two dogs experienced long-term myoclonic seizure freedom (duration seizure-free of at least 1 year), and two dogs experienced marked decreased myoclonic seizure frequency. One dog experienced immediate abatement of myoclonic seizures, although levetiracetam was only utilised for 1 month following onset of myoclonic seizures in this patient. CLINICAL SIGNIFICANCE: Myoclonic seizures can be idiopathic in aetiology. Levetiracetam can be used effectively to rapidly stop myoclonic seizures and to decrease the frequency of myoclonic seizures.

Alcohol administration blocks stress-induced impairments in memory and anxiety, and alters hippocampal neurotransmitter receptor expression in male rats.

Chronic exposure to stress has many deleterious effects on behavior, which can often lead to self-medication with anxiolytics, antidepressants, or alcohol. We determined the effects of alcohol administration following a stressor on established behavioral, physiological, and neural responses to stress. Male Sprague-Dawley rats received: No alcohol/No stress (CON), Alcohol alone (ALC), Stress alone (STR), or Stress plus Alcohol (STR+ALC). For seven consecutive days, two cohorts received an oral dose of 2.0 g/kg of either 20% ethanol or saline. In Cohort 1, behavioral testing began after the final treatment (day-8). Memory was tested using the object recognition (OR) and Y-maze, anxiety on the plus maze, and depression on the forced swim task. Memory on OR and Y-maze tasks was impaired in the ALC and STR groups. This deficit was reversed in the STR+ALC group, which performed not differently from the CON group. Stress alone was associated with increased anxiety, which was alleviated with alcohol treatment. No treatment effects were found in the forced swim task. In Cohort 2, hippocampal GABAα4 was upregulated in the STR+ALC group and GluN2B was upregulated in the ALC and STR+ALC groups. The STR+ALC group in Cohort 1 showed enhanced corticosterone levels after forced swim. The STR+ALC group in Cohort 2 showed increased corticosterone levels on day-1 of treatment and a habituation by day-7. In conclusion, this study found a reversal of stress-induced deficits in cognition and anxiety when alcohol was given post-stress, and changes in neurotransmitter receptor expression may contribute to these behavioral effects.

Rituximab in the treatment of resistant lupus nephritis: therapy failure in rapidly progressive crescentic lupus nephritis.

OBJECTIVE: The objective of this paper is to report the clinical outcome of B cell depletion therapy in 18 patients with refractory lupus nephritis (LN). METHODS: Eighteen patients received rituximab on an open-label basis with prospective evaluations. All patients had renal disease refractory to conventional immunosuppressive therapy, including intravenous cyclophosphamide (CyC). All patients fulfilled the revised ACR classification criteria for SLE. Rituximab was given as 2 × 1 g infusions with 500 mg iv CyC and 500 mg iv methylprednisolone, two weeks apart. Complete remission (CR) of nephritis at six months was defined as normal serum creatinine and serum albumin levels, inactive urine sediment, and proteinuria < 0.5 g/day; partial remission (PR) was defined as a ≥50% improvement in all renal parameters that were abnormal at baseline. Clinical response was assessed by the British Isles Lupus Assessment Group (BILAG) score pre- and post-rituximab treatment, and efficacy was recorded by extent and duration of B lymphocyte depletion (normal range 0.100-0.500 × 10(9)/l). Follow-up data were collected at six months, one year post-treatment and at the most recent clinic visit. RESULTS: At six months, 11/18 patients reached renal CR and two of 18 PR. The mean global BILAG scores for responders decreased from 15 (SD 10) to 5 (SD 3), and a total of ten A scores disappeared. Five patients failed to show complete or partial renal response despite peripheral B lymphocyte count depletion, and progressed to end-stage renal failure (ESRF) and dialysis. Four of these patients had severe proliferative, crescentic nephritis, of whom three had Class IV-G, one Class III and one late membranous glomerulonephritis. One patient died six years after rituximab therapy from overwhelming sepsis while on long-term haemodialysis. CONCLUSION: Rituximab therapy achieved a response in 13/18 patients with refractory LN. However, in patients with rapidly progressive crescentic LN, when there is already evidence of significant renal impairment, rituximab therapy may not prevent progression to ESRF and dialysis. Our data also suggest that severe Class IV-G LN may be associated with a poor response to therapy.

Adaptation of land treadmill scoring system for underwater treadmill in dogs with thoracolumbar intervertebral disc extrusion.

The underwater treadmill (UWTM) is utilized in dogs recovering from thoracolumbar intervertebral disc extrusion (TL-IVDE). Gait scoring is validated for dogs with TL-IVDE walking on the land treadmill (LT) but has not been reported for the UWTM. Our objective was to investigate if LT gait analysis could be applied to the UWTM and if non-ambulatory dogs walking unassisted on the UWTM, at a standardized water level, would be more likely to generate gait scores compared to on the LT. This was a prospective, observational study in dogs with TL-IVDE managed surigcally. At 0, 2, 4, 8 and 12 weeks post-operatively, paired video footage of dogs walking on the LT and UWTM (water level at the greater trochanter) was used to generate 0-100 stepping (SS) and coordination (regularity index, RI) scores. Scores were compared between treadmill type and over time. Twenty dogs were enrolled and seventy-eight paired recordings were available for review. Median gait scores increased over time but did not differ by treadmill type (P = 0.262 for SS, P = 0.533 for RI). Combining SS and RI, more recordings received scores of 0 for the LT (n = 58/156; 37.2 %) compared to the UWTM (n = 44/156; 28.2 %; P = 0.043). Scores of 0, at visits when there was at least movement present at multiple joints, was more common on the LT (n = 11/108; 10.2 %) compared to the UWTM (n = 2/108, 1.9 %; P = 0.026). In dogs recovering from TL-IVDE, LT-based gait scoring was feasible in dogs walking on the UWTM and might complement other gait analysis methods, especially for non-ambulatory dogs.

Comparison of heat stability of goat milk subjected to ultra-high temperature and in-container sterilization.

Goat milk with and without stabilizing salt was subjected to in-container and UHT sterilization. Heat stability was assessed by measuring the amount of sediment in the milk. Without stabilizing salts, goat milk usually produced less sediment when subjected to in-container sterilization compared with UHT processing. Addition of stabilizing salts up to 12.8mM resulted in a progressive increase in sediment for in-container sterilization. In contrast, adding stabilizing salts at 6.4mM initially reduced sediment formation in UHT-treated milk but addition of stabilizing salts at 12.8mM increased sediment formation. Adding stabilizing salts to goat milk increased pH, decreased ionic calcium, and increased ethanol stability. Adding up to 2mM calcium chloride increased sediment formation more after UHT treatment than after in-container sterilization. These results suggest that no single mechanism or set of reactions causes milk to produce sediment during heating and that the favored pathway is different for UHT and in-container sterilization processes. Poor heat stability could be induced both by increasing ionic calcium and by decreasing it. Ethanol stability is not a good indicator of heat stability for in-container sterilization, but it may be for UHT sterilization, if milk does not enter the region of poor heat stability found at low concentrations of ionic calcium.

Heat stability of milk supplemented with calcium chloride.

Calcium chloride (0-25 mM) was added to skim milk powder that was reconstituted to 9% total solids. Heat stability was evaluated between 60 and 120°C for different times by observing whether samples had coagulated, and by measuring the amount of sediment and residual protein in the centrifuged supernatant. Milk samples were also dialyzed during their respective heat treatments to recover the soluble phase at different temperatures to measure pH and ionic calcium. The transition conditions between good and poor heat stability were established for different calcium chloride concentrations and temperatures. As temperature increased, coagulation occurred at lower levels of added calcium chloride. The transition was quite distinct at higher temperatures but less so at lower temperatures; it was initiated by an increase in sediment formation before a firm coagulum was formed. Both pH and ionic calcium decreased in dialysates as temperature increased. No coagulation was observed if Ca(2+) was <0.5 mM and pH was >6.3 in dialysates taken at their respective coagulation temperatures. Being able to measure pH and ionic calcium at high temperatures will allow better understanding of factors affecting heat stability. Electrophoresis of the supernatants permitted identification of the protein fractions participating in the coagulation process. When coagulation was observed below 80°C, substantial amounts of undenatured ß-lactoglobulin and α-lactalbumin were found in the supernatant, as well as some soluble casein fractions. All the major whey protein and casein fractions were found in the sediment.

Short communication: Evaluation of bulk tank milk microbiological quality of nine dairy farms in Tennessee.

The purpose of this study was to evaluate the bulk tank milk (BTM) quality of 9 East Tennessee dairy farms and to determine its relationship with selected quality milk parameters. Bulk tank milk samples (n=1,141) were collected over a 42-mo period (June 2006 through November 2009) from farms, based on their preliminary incubation count (PIC) history. Parameters of BTM quality evaluated in this study included somatic cell count (SCC), standard plate count (SPC), PIC, laboratory pasteurization count (LPC), Staphylococcus spp. count, Streptococcus spp. count, and coliform count. Strong correlations between SPC and Streptococcus spp. counts (0.72) and between SPC and PIC (0.70) were found. However, moderate correlations were seen among other milk quality parameters. In addition, seasonal variations for some milk quality parameters were noted. For example, milk quality parameters such as SCC, SPC, LPC, and coliform count were significantly higher in summer, whereas Streptococcus spp. counts were significantly higher in winter. No seasonal variation in PIC or Staphylococcus spp. counts was observed. Summarizing, results from this investigation showed the importance of using several bacterial counts (SCC, SPC, PIC, LPC, Streptococcus spp. count, Staphylococcus spp. count, and coliform counts) as simultaneous indicators of milk quality.

Clinical characteristics of non-infectious inflammatory myopathy in the boxer dog.

OBJECTIVES: To evaluate the clinical characteristics, treatment, outcome and potential association between non-infectious inflammatory myopathy and malignancy in boxer dogs. MATERIALS AND METHODS: Boxer dogs histologically diagnosed with non-infectious inflammatory myopathy at the Comparative Neuromuscular Laboratory, University of California San Diego from 2010 to 2018 and with complete medical records were included in this retrospective study. Signalment, history, clinical signs, clinicopathologic findings, treatment and outcome were documented. RESULTS: Twenty-eight boxer dogs with non-infectious inflammatory myopathy, aged 1 to 11 years, were included. Eighteen were male (16 neutered; two entire) and 10 were female (seven spayed; three entire). Clinical signs included generalised weakness (n=17), dysphagia (n=11) and weight loss (n=10). Serum creatine kinase activity was elevated in all 20 cases tested (range 908 to 138,000 IU/L). One dog had undifferentiated round cell neoplastic infiltration within the muscle at the time of inflammatory myopathy diagnosis. Five dogs historically had mast cell tumours and 21 dogs were not diagnosed with neoplasia prior, at the time of or after inflammatory myopathy diagnosis. Treatment included glucocorticoid monotherapy (n=12), cyclosporine monotherapy (n=1) or multiple immune-suppressive medications (n=14). Six dogs neurologically improved, 11 improved but relapsed while on treatment, seven did not improve. Eight dogs were euthanased, one died, four were lost to follow-up. CLINICAL SIGNIFICANCE: Boxer dogs with non-infectious inflammatory myopathy can present for generalised weakness and dysphagia; long-term successful outcome is uncommon. The relationship between neoplasia and non-infectious inflammatory myopathy in boxer dogs remains unclear; future prospective studies evaluating a larger cohort are warranted.

Exercise and cardiac regulation: what can electrocardiographic time series tell us?

Electrocardiographic (ECG) monitoring allows temporal analysis of cardiac rhythm. We are usually interested in the variability of two components of the ECG: RR interval (a surrogate marker of cardiac interval) and QT interval (the duration of ventricular depolarization/repolarization). Quantification of RR rhythm, called heart rate variability (HRV) analysis, reflects the cardiac influences of the autonomic nervous system. QT variability provides insight regarding the risk of ventricular arrhythmia, and is at least partially independent of HRV. In this review, we consider the analysis of ECG time series during physical exercise. Our objectives were to show the variety of methods that can be used to characterize these time series data and to demonstrate "normal" changes in these characteristics during exercise and recovery. Attaining a comprehensive understanding of cardiac electrical conduction changes during exercise is not straightforward: analysis methods are numerous and results require careful interpretation. However, we recommend that assessment of both HRV and QT properties yields the most valuable information, the utility of which can be appreciated from the viewpoints of the athlete (e.g. providing feedback on the cardiac effects of training), the clinician (assisting in cardiovascular screening and exercise therapy evaluation) and the exercise physiologist (providing data for physiological process modelling).

Measurement of ionic calcium, pH, and soluble divalent cations in milk at high temperature.

Dialysis and ultrafiltration were investigated as methods for measuring pH and ionic calcium and partitioning of divalent cations of milk at high temperatures. It was found that ionic calcium, pH, and total soluble divalent cations decreased as temperature increased between 20 and 80 degrees C in both dialysates and ultrafiltration permeates. Between 90 and 110 degrees C, ionic calcium and pH in dialysates continued to decrease as temperature increased, and the relationship between ionic calcium and temperature was linear. The permeabilities of hydrogen and calcium ions through the dialysis tubing were not changed after the tubing was sterilized for 1h at 120 degrees C. There were no significant differences in pH and ionic calcium between dialysates from raw milk and those from a range of heat-treated milks. The effects of calcium chloride addition on pH and ionic calcium were measured in milk at 20 degrees C and in dialysates collected at 110 degrees C. Heat coagulation at 110 degrees C occurred with addition of calcium chloride at 5.4mM, where pH and ionic calcium of the dialysate were 6.00 and 0.43mM, respectively. Corresponding values at 20 degrees C were pH 6.66 and 2.10mM.

B Cell Synovitis and Clinical Phenotypes in Rheumatoid Arthritis: Relationship to Disease Stages and Drug Exposure.

OBJECTIVE: To define the relationship of synovial B cells to clinical phenotypes at different stages of disease evolution and drug exposure in rheumatoid arthritis (RA). METHODS: Synovial biopsy specimens and demographic and clinical data were collected from 2 RA cohorts (n = 329), one of patients with untreated early RA (n = 165) and one of patients with established RA with an inadequate response to tumor necrosis factor inhibitors (TNFi-IR; n = 164). Synovial tissue was subjected to hematoxylin and eosin and immunohistochemical staining and semiquantitative assessment for the degree of synovitis (on a scale of 0-9) and of CD20+ B cell infiltrate (on a scale of 0-4). B cell scores were validated by digital image analysis and B cell lineage-specific transcript analysis (RNA-Seq) in the early RA (n = 91) and TNFi-IR (n = 127) cohorts. Semiquantitative CD20 scores were used to classify patients as B cell rich (≥2) or B cell poor (<2). RESULTS: Semiquantitative B cell scores correlated with digital image analysis quantitative measurements and B cell lineage-specific transcripts. B cell-rich synovitis was present in 35% of patients in the early RA cohort and 47.7% of patients in the TNFi-IR cohort (P = 0.025). B cell-rich patients showed higher levels of disease activity and seropositivity for rheumatoid factor and anti-citrullinated protein antibody in early RA but not in established RA, while significantly higher histologic synovitis scores in B cell-rich patients were demonstrated in both cohorts. CONCLUSION: We describe a robust semiquantitative histologic B cell score that closely replicates the quantification of B cells by digital or molecular analyses. Our findings indicate an ongoing B cell-rich synovitis, which does not seem to be captured by standard clinimetric assessment, in a larger proportion of patients with established RA than early RA.

Localization of Sed5, a putative vesicle targeting molecule, to the cis-Golgi network involves both its transmembrane and cytoplasmic domains.

The yeast Sed5 protein, which is required for vesicular transport between ER and Golgi complex, is a membrane protein of the syntaxin family. These proteins are thought to provide the specific targets that are recognized by transport vesicles. We have investigated the mechanism by which Sed5 protein is itself localized. Expression of epitope-tagged versions of the yeast, Drosophila and rat Sed5 homologues in COS cells results in a perinuclear distribution; immuno-EM reveals that the majority of the protein is in a tubulo-vesicular compartment on the cis side of the Golgi apparatus. A similar distribution was obtained with a chimeric molecule consisting of a plasma membrane syntaxin with the Drosophila Sed5 transmembrane domain. This indicates that the membrane-spanning domain contains targeting information, as is the case with resident Golgi enzymes. However, alterations to the transmembrane domain of Drosophila Sed5 itself did not result in its mistargeting, implying that an additional targeting mechanism exists which involves only the cytoplasmic part of the protein. This was confirmed by modifying the transmembrane domain of the yeast Sed5 protein: substitution with the corresponding region from the Sso1 protein (a plasma membrane syntaxin homologue) did not affect yeast Sed5 function in vivo.

beta-Endorphin is associated with overeating in genetically obese mice (ob/ob) and rats (fa/fa).

Small doses of the opiate antagonist naloxone selectively abolished overeating in genetically obese mice (ob/ob) and rats (fa/fa). Elevated concentrations of the naturally occurring opiate beta-endorphin were found in the pituitaries of both obese species and in the blood plasma of the obese rats. Brain levels of beta-endorphin and Leu-enkephalin were unchanged. These data suggest that excess pituitary beta-endorphin may play a role in the development of the overeating and obesity syndrome.