Temporal Immune Profiling in the CSF and Blood of Patients with Aneurysmal Subarachnoid Hemorrhage.

Background: Delayed cerebral ischemia (DCI) is a significant complication of aneurysmal subarachnoid hemorrhage (aSAH). This study profiled immune responses after aSAH and evaluated their association with DCI onset. Methods: Twelve aSAH patients were enrolled. Leukocyte populations and cytokine levels were analyzed in cerebrospinal fluid (CSF) and peripheral blood (PB) on days 3, 5, 7, 10, and 14 post-aSAH. Peripheral blood mononuclear cells (PBMCs) were collected and their cytokine production quantified following stimulation. Results: Mixed-effects models revealed distinct immune cell dynamics in CSF compared to blood. Natural killer T cell frequency increased over time in CSF only, while monocyte/macrophage numbers increased in both CSF and PBMCs. CD4+ HLA II+ T cells increased in circulation. Unstimulated PBMCs showed increased IL-1ß, IL-6, and TNFα production, peaking at 7 days post-aSAH, coinciding with typical DCI onset. Ex vivo stimulation of PBMCs showed that only IL-6 significantly changed over time. In CSF, cytokines peaked 5 days post-injury, preceding immune cell profile alterations. Conclusions: Our findings reveal a time-dependent immune response following aSAH, with distinct within-patient patterns in CSF and PB. The early CSF cytokine peak preceding immune cell changes suggests a potential mechanistic link and identifies the cytokine response as a promising therapeutic target. This cytokine surge may drive immune cell expansion and prime PBMCs for increased inflammatory activity, potentially contributing to DCI risk. Future studies should explore the importance and sources of specific cytokines in driving immune activation. These insights may inform the development of targeted immunomodulatory strategies for preventing or managing DCI in aSAH patients.

Pathogen effects on milk yield and composition in chronic subclinical mastitis in dairy cows.

This study aimed to evaluate the effects of chronic subclinical mastitis (CSM) on milk production and component yields in dairy cows. A total of six herds located in the Midwest area of São Paulo State, Brazil were selected. Herds were visited once every 2 weeks to measure milk yield and to collect milk samples from lactating Holstein cows. Milk samples were collected at two stages (1 and 2), and each stage comprised three milk samplings. In stage 1, a total of 117 of 647 cows were diagnosed with CSM based on at least two of three repeated somatic cell counts (SCC) > 2000,000 cells/mL and positive bacterial milk culture results (BC). Cows with CSM were selected for the second stage. In stage 2, selected cows had quarter sampling aseptically collected for BC analyses prior to milking, and quarter milk yield was measured. Milk components (total protein, fat, lactose, and total solids) were measured using mid-infrared spectroscopy. Mammary quarters were considered healthy if all three repeated SCC results were ≤ 200,000 cells/mL and no bacterial growth was detected on BC. All quarters with positive bacterial growth were classified as having (non-chronic) subclinical mastitis when only one of three SCC results were > 200,000 cells/mL, and CSM when at least two of three SCC results were > 200,000 cells/mL. The effects of CSM by type of pathogen on milk and components yield were assessed using a linear mixed model. Mammary quarters with CSM caused by major pathogens had milk loss of 1.1 kg/quarter milking in comparison to healthy quarters. Milk losses were 0.8 and 1.3 kg/quarter milking when CSM was caused by Staphylococcus aureus or environmental streptococci, respectively. In addition, healthy quarters produced more milk components than quarters with CSM caused by major pathogens. Minor pathogens causing CSM (non-aureus staphylococci and Corynebacterium spp.) had no effect on milk yield. Quarters with CSM had lower milk and component yields when compared with healthy quarters. Milk losses varied according to the type of pathogen and were higher when associated with major pathogens such as S. aureus and environmental streptococci compared with healthy quarters.

Comparison of standard and on-plate extraction protocols for identification of mastitis-causing bacteria by MALDI-TOF MS.

The objective was to compare standard versus on-plate sample preparation protocols for identification of mastitis bacteria by MALDI-TOF MS. A total of 186 bacterial isolates from cows with subclinical mastitis were identified by MALDI-TOF MS after preparation using two extraction protocols. On-plate protocol was performed by applying the bacterial colony directly from the culture plate onto the plate spot. For the standard protocol, lysis of bacterial colonies using reagents was performed in a cryotube, and the resulting extract was applied onto the plate spot for analysis. The on-plate protocol showed a similar bacteria identification rate (91.4%, n = 170/186) in comparison to the standard (94.6%, n = 176/186). Identification was higher for both protocols when scores used for species-level identification (≥ 2.0) was reduced to genus-level (≥ 1.7); genus-level identification score rate increased from 94.6 to 100% when using the standard protocol, and from 91.4 to 94.6% when using the on-plate protocol. However, when compared standard (as gold standard) versus on-plate protocol, genus-level identification score rate ranged from 87.1 to 89.8%. Therefore, when the on-plate protocol fails to identify any specie, the standard extraction may be more suitable as a reference protocol for use. Strategy for increasing identification with the on-plate protocol may include upgrading the reference database library. Choice of protocol for preparation may be influenced by the bacterial type to be identified. Standard and on-plate extraction protocols of bacterial ribosomal proteins associated with MALDI-TOF MS might be alternatives to conventional microbiology methods for identification of subclinical mastitis pathogens.

Expression of a Constitutively Active Human Insulin Receptor in Hippocampal Neurons Does Not Alter VGCC Currents.

Memory and cognitive decline are the product of numerous physiological changes within the aging brain. Multiple theories have focused on the oxidative, calcium, cholinergic, vascular, and inflammation hypotheses of brain aging, with recent evidence suggesting that reductions in insulin signaling may also contribute. Specifically, a reduction in insulin receptor density and mRNA levels has been implicated, however, overcoming these changes remains a challenge. While increasing insulin receptor occupation has been successful in offsetting cognitive decline, alternative molecular approaches should be considered as they could bypass the need for brain insulin delivery. Moreover, this approach may be favorable to test the impact of continued insulin receptor signaling on neuronal function. Here we used hippocampal cultures infected with lentivirus with or without IRß, a constitutively active, truncated form of the human insulin receptor, to characterize the impact continued insulin receptor signaling on voltage-gated calcium channels. Infected cultures were harvested between DIV 13 and 17 (48 h after infection) for Western blot analysis on pAKT and AKT. These results were complemented with whole-cell patch-clamp recordings of individual pyramidal neurons starting 96 h post-infection. Results indicate that while a significant increase in neuronal pAKT/AKT ratio was seen at the time point tested, effects on voltage-gated calcium channels were not detected. These results suggest that there is a significant difference between constitutively active insulin receptors and the actions of insulin on an intact receptor, highlighting potential alternate mechanisms of neuronal insulin resistance and mode of activation.

Short communication: Effect of 3 phytoceutical products on elimination of bacteria in experimentally induced Streptococcus uberis clinical mastitis.

Our objective was to assess the ability of 3 herbal products to eliminate experimentally induced Streptococcus uberis mastitis. These herbal products, also known as phytoceuticals, are used in organically managed dairy cattle to maintain or promote udder health. The products tested were an intramammary product, a topical product, and a product applied to the vulvar area. These products are not approved by the US Food and Drug Administration for treatment of mastitis but they are sold to enhance milk quality or for maintenance or improvement of udder health. Each of the products contains at least one component shown to have antibacterial activity. In this study, we successfully challenge-inoculated 25 lactating dairy cows maintained under organic conditions with an isolate of S. uberis. All challenged cows were positive for S. uberis by milk culture after challenge. When cows met predefined criteria indicating the presence of clinical mastitis, treatment with 1 of the 3 products was initiated based upon a predetermined random allocation. Culture of aseptically collected quarter milk samples was performed before, during, and following challenge with S. uberis. Eight, 8, and 9 cows received the intravulvar, intramammary, and topical treatments, respectively. Milk from all cows that were treated with phytoceuticals were culture-positive for S. uberis at every time point following treatment through 168 h following the last phytoceutical treatment. Based upon the presence of clinical signs and for humane reasons, 2 intravulvar-treated cows, 1 topical-treated, and 4 intramammary-treated cows received intramammary antibiotic therapy. We concluded that the phytoceuticals tested, as dosed and used in this trial, did not produce bacterial cures in S. uberis-induced mastitis.

Long-term adherence to topical psoriasis treatment can be abysmal: a 1-year randomized intervention study using objective electronic adherence monitoring.

BACKGROUND: Most people with psoriasis have limited disease that could be treated with topicals, but topical efficacy is limited by low short-term adherence. Psoriasis is a chronic disease, and long-term adherence is an even bigger problem. OBJECTIVES: To determine how well medication is used in the long-term topical treatment of psoriasis and to assess the potential of an internet-based reporting intervention to improve treatment adherence and outcomes. METHODS: An investigator-blinded, prospective study evaluated topical fluocinonide adherence in 40 patients with mild-to-moderate psoriasis over 12 months. Subjects were randomized in a 1 : 1 ratio to standard-of-care or internet-based reporting group. Adherence was objectively monitored with Medication Event Monitoring System® caps. RESULTS: Fifty per cent of subjects discontinued the treatment. Greater adherence was seen in the intervention group compared with the standard-of-care group (50% vs. 35%, P = 0·08). Psoriasis Area and Severity Index improved more in the intervention group at month 1 (1·61 vs. -0·12, P = 0·003), month 3 (2·50 vs. 0·79, P = 0·025) and month 12 (3·32 vs. 0·34, P = 0·038) than in the standard-of-care group. CONCLUSIONS: This study likely underestimates the challenge of long-term adherence, as adherence tends to be better in research studies than in clinical practice. This study also did not fully account for primary nonadherence. Adherence to topical treatment is low in the short term and decreased further in the long term, a considerable challenge for dermatologists to address. A reporting intervention may be one of the ways we can improve our patients' treatment outcomes.

Inhibition of the virulence, antibiotic resistance, and fecal shedding of multiple antibiotic-resistant Salmonella Typhimurium in broilers fed Original XPC™.

Salmonella carriage is an insidious problem for the poultry industry. While most Salmonella serotypes are avirulent in poultry, these bacteria can contaminate chicken meat during processing, leading to one of the most important food safety hazards. In this study, we examined the anti-Salmonella effects of Diamond V Original XPC™ (XPC) included in the finisher diet fed to commercial broilers. On 3 occasions between day one (D1) and D20, broilers were experimentally infected with multiple antibiotic-resistant Salmonella Typhimurium. After confirming that the chicks were shedding Salmonella in the feces on D21, broiler chicks were fed a diet containing XPC (n = 57 birds; 1.25 kg/MT) or an XPC-free control diet (CON) (n = 57 birds) to D49. Fecal samples were obtained weekly and subjected to selective culture for enumerating and determining the antibiotic resistance of the Salmonella Salmonella isolates were then subjected to an in vitro virulence assay, which predicts the ability of Salmonella to cause illness in a mammalian host. Broilers were euthanized on D49 and a segment of the large intestine was removed and subjected to the same assays used for the fecal samples. When compared to the birds fed the CON diet, Salmonella fecal shedding, virulence (invasion and invasion gene expression), and antibiotic resistance were significantly decreased in birds fed XPC (5-fold, 7.5-fold, 6-fold, and 5.3-fold decreases, respectively). Birds fed XPC exhibited heavier body weight (BW) and greater BW gains than those fed the CON diet. The decrease in virulence was associated with a decreased expression of a genetic regulator of Salmonella invasion into cells (hilA), while the decrease in antibiotic resistance was due to a loss of an integron (SGI1) from the input strain. This study revealed that Original XPC™ inhibits the shedding, downstream virulence, and antibiotic resistance of Salmonella residing in broilers.

The oxytocin-CD38-vitamin A axis in pregnant women involves both hypothalamic and placental regulation.

OBJECTIVE: Oxytocin, a hypothalamic hormone secreted upon release of ectoenzyme CD38, plays a vital role in interpersonal bonding behaviors. Reduced plasma oxytocin characterizes autistic individuals. CD38 levels, which were found to be low in LBCs derived from autistic patients, is upregulated upon the addition of a vitamin A derivative. During pregnancy, oxytocin is also secreted by placenta. Recent controversial studies have suggested an increased risk for autism when oxytocin is used during induction and augmentation of labor. We aimed to examine the tripartite relationship between oxytocin, CD38 and vitamin A in pregnant women and their newborns. METHODS: Thirty-one healthy expectant mothers were enlisted for this study. Levels of oxytocin, CD38 and ATRA were measured in both maternal peripheral and newborn cord blood, and the tripartite relationship between these parameters examined. Estrogen and progesterone levels of the mothers were also recorded. Several clinical measures were also noted. RESULTS: Mean maternal oxytocin and vitamin A levels were approximately 8- and 4-fold higher, respectively, than neonatal levels. CD38 expression, however, was 9 times higher in neonates than in the maternal group. Positive correlation was found between maternal and cord blood for both oxytocin and CD38. CONCLUSIONS: This establishment of normative values for oxytocin, CD38 and vitamin A in healthy pregnant women and newborns may serve as a reference in the investigation of developing pathologies of disorders such as autism.

Short communication: an in vitro assessment of the antibacterial activity of plant-derived oils.

Nonantibiotic treatments for mastitis are needed in organic dairy herds. Plant-derived oils may be useful but efficacy and potential mechanisms of action of such oils in mastitis therapy have not been well documented. The objective of the current study was to evaluate the antibacterial activity of the plant-derived oil components of Phyto-Mast (Bovinity Health LLC, Narvon, PA), an herbal intramammary product, against 3 mastitis-causing pathogens: Staphylococcus aureus, Staphylococcus chromogenes, and Streptococcus uberis. Plant-derived oils evaluated were Thymus vulgaris (thyme), Gaultheria procumbens (wintergreen), Glycyrrhiza uralensis (Chinese licorice), Angelica sinensis, and Angelica dahurica. Broth dilution testing according to standard protocol was performed using ultrapasteurized whole milk instead of broth. Controls included milk only (negative control), milk + bacteria (positive control), and milk + bacteria + penicillin-streptomycin (antibiotic control, at 1 and 5% concentrations). Essential oil of thyme was tested by itself and not in combination with other oils because of its known antibacterial activity. The other plant-derived oils were tested alone and in combination for a total of 15 treatments, each replicated 3 times and tested at 0.5, 1, 2, and 4% to simulate concentrations potentially achievable in the milk within the pre-dry-off udder quarter. Thyme oil at concentrations ≥2% completely inhibited bacterial growth in all replications. Other plant-derived oils tested alone or in various combinations were not consistently antibacterial and did not show typical dose-response effects. Only thyme essential oil had consistent antibacterial activity against the 3 mastitis-causing organisms tested in vitro. Further evaluation of physiological effects of thyme oil in various preparations on mammary tissue is recommended to determine potential suitability for mastitis therapy.

Effect of 2 herbal intramammary products on milk quantity and quality compared with conventional and no dry cow therapy.

Dry cow therapy, administered at the end of lactation, is aimed at eliminating current and preventing future intramammary (IMM) bacterial infections and typically involves intramammary administration of antibiotics. Certified organic dairies in the United States are restricted from using antibiotics and must consider an alternative therapy or no dry cow therapy. The current study compared 2 herbal products to conventional dry cow therapy and no treatment for a total of 5 treatments over 2 trials. Trial 1 was conducted over 3 yr on 1 research farm and trial 2 included 4 commercial farms plus the research herd over 2 yr. Treatments included (1) a conventional IMM antibiotic and internal teat sealant (penicillin-dihydrostreptomycin and bismuth subnitrate; CON); (2) an herbal IMM product purported to act as a teat sealant (Cinnatube, New AgriTech Enterprises, Locke, NY; CIN); (3) an herbal IMM product (Phyto-Mast, Bovinity Health LLC, Narvon, PA; P-M); (4) Phyto-Mast and Cinnatube (PC); or (5) no dry cow therapy (NT). Each treatment group was balanced by breed, lactation number, due date, herd, and year. However, the CON treatment was used only in the research herd because of the intent to avoid antibiotic usage on the other 4 farms. Comparisons among treatments included the difference between pre- and posttreatment 305-d mature equivalent milk production (trial 1), somatic cell score change from dry-off to freshening at the cow and quarter levels (trials 1 and 2), and milk microbiology change over the dry period (trial 2). We detected no significant differences among treatments for milk yield differences between the lactation following treatment and the lactation preceding treatment. Changes in somatic cell score from one lactation to the next also did not differ significantly among treatments in either trial. Cure rates were not significantly different among treatments; only 19.6% of all quarters were infected at dry off. The proportion of quarters with new infections at 3 to 5d postcalving did not significantly differ among treatments, except between CIN and NT. Percentages (least squares means ± standard error) of quarters with new infections were 24 ± 21% for CON, 15 ± 7% for CIN, 30 ± 10% for P-M, 32 ± 11% for PC, and 35 ± 11% for NT. The efficacy of the herbal products was similar to that of conventional therapy, and the herbal products had no apparent adverse effects.

Canine intracranial gliomas: relationship between magnetic resonance imaging criteria and tumor type and grade.

Limited information is available to assist in the ante-mortem prediction of tumor type and grade for dogs with primary brain tumors. The objective of the current study was to identify magnetic resonance imaging (MRI) criteria related to the histopathological type and grade of gliomas in dogs. A convenience sample utilizing client-owned dogs (n=31) with gliomas was used. Medical records of dogs with intracranial lesions admitted to two veterinary referral hospitals were reviewed and cases with a complete brain MRI and definitive histopathological diagnosis were retrieved for analysis. Each MRI was independently interpreted by five investigators who were provided with standardized grading instructions and remained blinded to the histopathological diagnosis. Mild to no contrast enhancement, an absence of cystic structures (single or multiple), and a tumor location other than the thalamo-capsular region were independently associated with grade II tumors compared to higher grade tumors. In comparison to oligodendrogliomas, astrocytomas were independently associated with the presence of moderate to extensive peri-tumoral edema, a lack of ventricular distortion, and an isointense or hyper-intense T1W-signal. When clinical and MRI features indicate that a glioma is most likely, certain MRI criteria can be used to inform the level of suspicion for low tumor grade, particularly poor contrast enhancement. Information obtained from the MRI of such dogs can also assist in predicting an astrocytoma or an oligodendroglioma, but no single imaging characteristic allows for a particular tumor type to be ruled out.

Comparisons of milk quality on North Carolina organic and conventional dairies.

The organic dairy industry is growing rapidly across the United States and has recently expanded into the southeastern states. To date, no published comparisons of milk quality exist between organic and conventional dairies in the Southeastern United States. Maintaining high milk quality is challenging in this region due to the longer periods of high heat and humidity. The objective of this observational study was to compare milk quality on organic and conventional dairies in North Carolina during the warm summer months of the year. Data were compared from 7 organically and 7 conventionally managed herds in North Carolina. To assess milk quality, milk samples were aseptically collected from each functional quarter of each cow in the milking herds at the time of sampling and linear somatic cell scores (SCS) were obtained for individual cows. A total of 4,793 quarter milk samples (2,526 conventional and 2,267 organic) were collected from 1,247 cows (652 conventional and 595 organic). Milk samples were cultured and bacterial growth was identified using protocols consistent with those of the National Mastitis Council (Verona, WI). Subclinical mastitis was defined as the presence of SCS ≥ 4 and also a microbiological infection in at least 1 quarter. The proportion of cows with subclinical mastitis did not differ between conventional (20.8%) and organic (23.3%) herds. No significant difference was observed between herd management types in the proportion of cows without microbiological growth in milk samples. Also, no significant differences were observed between organic and conventional herds for cow-level prevalence of Staphylococcus aureus, coagulase-negative Staphylococcus spp., Streptococcus spp., or Corynebacterium spp. Two of the organic herds had a notably higher prevalence of Corynebacterium spp. and higher SCS. Coliforms were found in 5 of 7 conventional herds and in only 1 of 7 organic herds. Mean SCS did not differ between conventional (3.3±0.2) and organic (3.5±0.2) herds. Despite differences in herd management, milk quality was remarkably similar between the organic and conventional dairies compared for this study.

Involvement of a putative intercellular signal-recognizing G protein-coupled receptor in the engulfment of Salmonella by the protozoan Tetrahymena.

In an effort to investigate the molecular basis of protozoa engulfment-mediated hypervirulence of Salmonella in cattle, we evaluated protozoan G protein-coupled receptors (GPCRs) as transducers of Salmonella engulfment by the model protozoan Tetrahymena. Our laboratory previously demonstrated that non-pathogenic protozoa (including Tetrahymena) engulf Salmonella and then exacerbate its virulence in cattle, but the mechanistic details of the phenomenon are not fully understood. GPCRs were investigated since these receptors facilitate phagocytosis of particulates by Tetrahymena, and a GPCR apparently modulates bacterial engulfment for the pathogenic protozoan Entamoeba histolytica. A database search identified three putative Tetrahymena GPCRs, based on sequence homologies and predicted transmembrane domains, that were the focus of this study. Salmonella engulfment by Tetrahymena was assessed in the presence of suramin, a non-specific GPCR inhibitor. Salmonella engulfment was also assessed in Tetrahymena in which expression of putative GPCRs was knocked-down using RNAi. A candidate GPCR was then expressed in a heterologous yeast expression system for further characterization. Our results revealed that Tetrahymena were less efficient at engulfing Salmonella in the presence of suramin. Engulfment was reduced concordantly with a reduction in the density of protozoa. RNAi-based studies revealed that knock-down of one the Tetrahymena GPCRs caused diminished engulfment of Salmonella. Tetrahymena lysates activated this receptor in the heterologous expression system. These data demonstrate that the Tetrahymena receptor is a putative GPCR that facilitates bacterial engulfment by Tetrahymena. Activation of the putative GPCR seemed to be related to protozoan cell density, suggesting that its cognate ligand is an intercellular signaling molecule.

Non-typhoidal Salmonella encephalopathy involving lipopolysaccharide in cattle.

This study assessed the involvement of lipopolysaccharide (LPS) in the non-typhoidal Salmonella encephalopathy (NTSE) caused by a unique isolate of Salmonella enterica serovar Saint-paul (SstpNPG). NTSE was prevented by genetic (deletion of murE) or pharmacologic (polymyxin) disruption of LPS on SstpNPG although the disruption of LPS did not deter brain penetration of the strain. This is the first study to demonstrate that LPS is involved in the manifestations of NTSE.

Molecular epidemiology of Staphylococcus aureus mastitis in dairy heifers.

The specific purpose was to investigate the possible interrelationships of genotypes of Staphylococcus aureus found in mammary glands, horn flies, and extramammary sites on 3 southeastern US dairies. A total of 1,228 samples were obtained from various sources on the 3 dairy herds, each of which had a history of Staph. aureus mastitis. Dairy herds studied had access to pasture, and samples were collected during the summer when horn flies (Haematobia irritans) were active. Samples collected included milk samples from all lactating herd cows, colostrum samples from heifers calving during the study period, heifer body sites (mouth, nostrils, and teats), the heifer environment (water, feed, and soil/vegetation/pasture), horn flies, and humans (hands and nostrils). Isolation of Staph. aureus was attempted from all samples, with isolates subjected to genotypic analysis using pulsed-field gel electrophoresis. A total of 244/1228 (or 19.9%) of all samples were positive for Staph. aureus. For milk samples, 52/383 (or 13.6%) of samples were Staph. aureus positive, and 70/411 (or 17.0%) of heifer quarter colostrum samples were positive. Horn fly samples were frequently positive, with over one-half (29/52, or 55.8%) of samples positive for Staph. aureus. Staphylococcus aureus obtained during the study comprised isolates from 12 different genotype groups as defined in this study. Identical genotypes were obtained from horn flies, heifer colostrum samples, and cow milk samples. Group B genotypes were shared among flies, heifer colostrum samples, body sites, and cow milk samples, whereas group A genotypes were common to the same sample locations and body sites but rarely (once) found in horn flies. We conclude, based upon the finding of identical pulsed-field gel electrophoresis genotypes in flies, heifer body sites, and heifer colostrum samples, that flies and heifer body sites could be important sources of Staph. aureus for heifer intramammary infections.

The effect of topiramate plasma concentration on linguistic behavior, verbal recall and working memory.

This is the first study of the effect of topiramate on linguistic behavior and verbal recall using a computational linguistics system for automated language and speech analysis to detect and quantify drug-induced changes in speech recorded during discourse-level tasks. Healthy volunteers were administered a single, 100-mg oral dose of topiramate in two double-blind, randomized, placebo-controlled, crossover studies. Subjects' topiramate plasma levels ranged from 0.23 to 2.81 µg/mL. We found a significant association between topiramate levels and impairment on measures of verbal fluency elicited during a picture description task, correct number of words recalled on a paragraph recall test, and reaction time recorded during a working memory task. Using the tools of clinical pharmacology and computational linguistics, we elucidated the relationship between the determinants of a drug's disposition as reflected in plasma concentrations and their impact on cognitive functioning as reflected in spoken language discourse.

Milk and plasma disposition of thymol following intramammary administration of a phytoceutical mastitis treatment.

Despite the recent growth of the organic dairy industry, organic producers and veterinarians have limited information when choosing mastitis treatments for animals in organic dairy production. Organic producers commonly administer homeopathic or other plant-based products without having research evaluating the efficacy of these products and using estimated or no withholding times to treat mastitis and other health problems in their herds. In this pilot study, we attempted to identify several active ingredients of Phyto-Mast (Penn Dutch Cow Care, Narvon, PA), a plant-based mastitis treatment used on organic dairy farms, and to quantify the product residue in milk and plasma after intramammary administration. We developed an assay to quantify thymol (one of the active ingredients in Phyto-Mast) in milk and plasma using gas chromatography and mass spectrometry (GC-MS). Thymol is a volatile aromatic compound with antiinflammatory properties. As a model for dairy cows, 5 healthy, lactating alpine dairy goats were given 5 mL of Phyto-Mast per udder half. For 10 d following treatment, we analyzed blood and milk samples for thymol residues using GC-MS. The GC-MS assay was very sensitive for thymol detection, to a concentration of 0.01 µg/mL in plasma. Using thymol as a marker, Phyto-Mast was detectable and quantifiable in plasma beginning with the 15-min posttreatment sample, but was no longer detectable in the 4-h posttreatment sample. Thymol residues were only detected in the 12-h posttreatment milk sample. An inflammatory response was not evident in the udder following phytoceutical administration. Although this study provides information about the elimination of thymol, the product contains several other active chemicals, which may have different pharmacokinetic behaviors. Further analysis and additional study animals will help to determine a milk withholding time for Phyto-Mast. Given the recent growth of the organic dairy industry, understanding the pharmacokinetics of therapeutics used in organic production and developing accurate withholding recommendations will help to ensure milk safety.

Attentional modulation of the somatosensory mu rhythm.

Neural oscillations with a frequency of around 10 Hz are thought to be a ubiquitous phenomenon in sensory cortices, and it has been hypothesized that the level of 10 Hz activity is related to local cortical excitability. During spatial attention, the visual alpha rhythm has been found to be modulated according to the direction of attention. Specifically, the alpha rhythm desynchronizes over visual cortex contralateral to the direction of attention and synchronizes over visual cortex ipsilateral to the direction of attention, and these modulations have been associated with facilitation and inhibition of sensory processing. In the somatosensory domain, the reactivity of a similar rhythm, known as the mu rhythm, during attention tasks is a current topic of inquiry and somatotopic modulation of the mu rhythm by directed attention have been reported. In this paper, we investigate how lateralized spatial attention modulates the ongoing somatosensory mu rhythm, and how such modulation impacts sensory information processing. 128 channel EEG was recorded while subjects performed a somatosensory spatial attention task. In addition to analyses on scalp recorded data, a spatial filtering method was utilized to investigate spatial attention effects in the source space. The direction of spatial attention was found to have a significant somatotopic effect on the ongoing mu rhythm occurring in primary somatosensory cortex. Concurrently, the visual alpha rhythm was significantly elevated above the baseline level during somatosensory attention, demonstrating a cross-modal effect. Lastly, an analysis was performed to investigate the correlation between the level of prestimulus mu activity and subsequent stimulus evoked activity in primary somatosensory cortex.