Evaluating the Quality of Narrative Feedback for Entrustable Professional Activities in a Surgery Residency Program.

OBJECTIVE: We assessed the quality of narrative feedback given to surgical residents during the first five years of Competency-Based Medical Education (CBME) implementation. SUMMARY BACKGROUND DATA: CBME requires ongoing formative assessments and feedback on learners' performance. METHODS: We conducted a retrospective cross-sectional study using assessments of Entrustable Professional Activities (EPAs) in the Surgical Foundations curriculum at Queen's University from 2017-2022. Two raters independently evaluated quality of narrative feedback using the Quality of Assessment of Learning (QuAL) Score (0-5). RESULTS: A total of 3,900 EPA assessments were completed over 5 years. Fifty-seven percent (2229/3900) of assessments had narrative feedback documented with a mean QuAL score of 2.16±1.49. Of these, 1614 (72.4%) provided evidence about the resident's performance, 951 (42.7%) provided suggestions for improvement, and 499/2229 (22.4%) connected suggestions to the evidence. There was no meaningful change in narrative feedback quality over time (r=0.067, P=0.002). Variables associated with lower quality of narrative feedback include: Attending role (2.04±1.48) compared to medical student (3.13±1.12, P<0.001) and clinical fellow (2.47±1.54, P<0.001), concordant specialties between the assessor and learner (2.06±1.50 vs. 2.21±1.49, P=0.025), completion of the assessment one month or more after the encounter versus one week (1.85±1.48 vs. 2.23±1.49, P<0.001), and resident entrustment versus not entrusted to perform the assessed EPA (2.13±1.45 vs. 2.35±1.66; P=0.008). The quality of narrative feedback was similar for assessments completed under direct and indirect observation (2.18±1.47 vs. 2.06±1.54; P=0.153). CONCLUSIONS: Just over half of the EPA assessments of surgery residents contained narrative feedback with overall fair quality. There was no meaningful change in the quality of feedback over 5 years. These findings prompt future research and faculty development.

Association of Body Mass Index with Multiple Organ Failure in Hospitalized Patients with COVID-19: A Multicenter Retrospective Cohort Study.

Purpose: This study examines whether excessive adipose tissue, as measured by the body mass index (BMI), is associated with higher systemic markers of inflammation and higher risk of severe acute organ failure among patients with coronavirus disease 2019 (COVID-19). Methods: This was a multicenter retrospective cohort study of 1370 hospitalized adults (18 years or older) with COVID-19 during the first wave of the pandemic. Patient-level variables were extracted from the electronic medical record. The primary predictor variable was the BMI at time of hospital admission, in accordance with the World Health Organization classification. Multivariable logistic regression analyses examined the association of BMI with the composite of acute respiratory distress syndrome (ARDS), as defined by the use of high-flow nasal canula, non-invasive ventilation, or mechanical ventilation, severe acute kidney injury (AKI), as defined by acute dialysis requirement, or in-hospital death. Results: After adjustment for important cofounders, the BMI stratum of > 40 kg/m2 (compared to the BMI < 25 kg/m2 reference group) was associated with higher odds for the composite of ARDS, severe AKI, or in-hospital death (adjusted odds ratio [ORadj] 1.69; 95% confidence interval [CI]1.03, 2.78). As a continuous variable, BMI (per 5-kg/m2 increase) remained independently associated with the composite outcome (ORadj 1.13; 95% CI 1.03, 1.23); patients in higher BMI categories exhibited significantly higher peak levels of C-reactive protein (CRP), a systemic marker of inflammation (P = .01). In a sub-cohort of 889 patients, the association of BMI with the composite outcome was no longer significant after adjustment for the peak level of CRP. Conclusions: Among hospitalized patients with COVID-19, a higher BMI is associated with higher risk of severe organ failure or in-hospital death, which dissipates after adjustment for CRP level. This supports the hypothesis that inflammation is a downstream mediator of adipose tissue on acute organ dysfunction.

In vitro and in vivo remediation of per- and polyfluoroalkyl substances by processed and amended clays and activated carbon in soil.

Remediation methods for soil contaminated with poly- and perfluoroalkyl substances (PFAS) are needed to prevent their leaching into drinking water sources and to protect living organisms in the surrounding environment. In this study, the efficacy of processed and amended clays and carbons as soil amendments to sequester PFAS and prevent leaching was assessed using PFAS-contaminated soil and validated using sensitive ecotoxicological bioassays. Four different soil matrices including quartz sand, clay loam soil, garden soil, and compost were spiked with 4 PFAS congeners (PFOA, PFOS, GenX, and PFBS) at 0.01-0.2 µg/mL and subjected to a 3-step extraction method to quantify the leachability of PFAS from each matrix. The multistep extraction method showed that PFAS leaching from soil was aligned with the total carbon content in soil, and the recovery was dependent on concentration of the PFAS. To prevent the leaching of PFAS, several sorbents including activated carbon (AC), calcium montmorillonite (CM), acid processed montmorillonite (APM), and organoclays modified with carnitine, choline, and chlorophyll were added to the four soil matrices at 0.5-4 % w/w, and PFAS was extracted using the LEAF method. Total PFAS bioavailability was reduced by 58-97 % by all sorbents in a dose-dependent manner, with AC being the most efficient sorbent with a reduction of 73-97 %. The water leachates and soil were tested for toxicity using an aquatic plant (Lemna minor) and a soil nematode (Caenorhabditis elegans), respectively, to validate the reduction in PFAS bioavailability. Growth parameters in both ecotoxicological models showed a dose-dependent reduction in toxicity with value-added growth promotion from the organoclays due to added nutrients. The kinetic studies at varying time intervals and varying pHs simulating acidic rain, fresh water, and brackish water suggested a stable sorption of PFAS on all sorbents that fit the pseudo-second-order for up to 21 days. Contaminated soil with higher than 0.1 µg/mL PFAS may require reapplication of soil amendments every 21 days. Overall, AC showed the highest sorption percentage of total PFAS from in vitro studies, while organoclays delivered higher protection in ecotoxicological models (in vivo). This study suggests that in situ immobilization with soil amendments can reduce PFAS leachates and their bioavailability to surrounding organisms. A combination of sorbents may facilitate the most effective remediation of complex soil matrices containing mixtures of PFAS and prevent leaching and uptake into plants.

Outcomes of endovascular thrombectomy for ischaemic stroke among nonagenarians with and without pre-existing dependency.

BACKGROUND: Our aim was to compare the outcomes of treatment with endovascular thrombectomy for pre-stroke dependent versus pre-stroke independent among the very elderly ≥90 years. METHODS: A retrospective cohort study was performed on 106 patients ≥90 years who underwent endovascular thrombectomy for ischaemic stroke in Western Australia between June 2016 and September 2021. Patient, stroke and procedural details along with inpatient progress and outcome at 90 days were recorded. Patients were divided into Group A (pre-stroke modified Rankin Scale 0-2) and Group B (pre-stroke modified Rankin Scale >2). Primary outcome measure was functional status at 90 days post-stroke, with favourable clinical outcome defined as a 90-day mRS category equal to the patients' respective pre-stroke mRS category. Secondary outcome measures include successful reperfusion, symptomatic intracranial haemorrhage, hospital length-of-stay, change in accommodation to an aged care facility, and mortality during admission, at 90 days and one year. RESULTS: 61 patients were allocated to Group A and 45 to Group B. There was none with pre-stroke mRS 5. Group B had more pre-existing cognitive impairment, aged care facility residents, higher median age and lower Alberta Stroke Program Early CT Score. For primary outcome measure, 38 % of patients in Group A and 49 % in Group B achieved a favourable clinical outcome. The difference was not significant (p=0.3408). For secondary outcome measures, Group B had a significantly higher 90-day mortality rate at 47 % versus 24 % in Group A (p=0.03). All other secondary outcome measures were similar between the two groups. These include the rate of successful reperfusion and symptomatic intracranial haemorrhage, hospital length-of-stay, new transition into an aged care facility, inpatient mortality rate and 1-year mortality rate. CONCLUSION: When treated with endovascular thrombectomy for ischaemic stroke, nonagenarians with pre-existing dependency achieved a rate of favourable functional outcome comparable with their independent peers, although they also had higher 90-day mortality rate.

Kinetics of glyphosate and aminomethylphosphonic acid sorption onto montmorillonite clays in soil and their translocation to genetically modified corn.

The co-occurrence of glyphosate (GLP) and aminomethylphosphonic acid (AMPA) in contaminated water, soil, sediment and plants is a cause for concern due to potential threats to the ecosystem and human health. A major route of exposure is through contact with contaminated soil and consumption of crops containing GLP and AMPA residues. However, clay-based sorption strategies for mixtures of GLP and AMPA in soil, plants and garden produce have been very limited. In this study, in vitro soil and in vivo genetically modified corn models were used to establish the proof of concept that the inclusion of clay sorbents in contaminated soils will reduce the bioavailability of GLP and AMPA in soils and their adverse effects on plant growth. Effects of chemical concentration (1-10 mg/kg), sorbent dose (0.5%-3% in soil and 0.5%-1% in plants) and duration (up to 28 days) on sorption kinetics were studied. The time course results showed a continuous GLP degradation to AMPA. The inclusion of calcium montmorillonite (CM) and acid processed montmorillonite (APM) clays at all doses significantly and consistently reduced the bioavailability of both chemicals from soils to plant roots and leaves in a dose- and time-dependent manner without detectable dissociation. Plants treated with 0.5% and 1% APM inclusion showed the highest growth rate (p ≤ 0.05) and lowest chemical bioavailability with up to 76% reduction in roots and 57% reduction in leaves. Results indicated that montmorillonite clays could be added as soil supplements to reduce hazardous mixtures of GLP and AMPA in soils and plants.

Approach to sialadenitis.

OBJECTIVE: To provide family physicians with a practical evidence-based approach to the management of patients with sialadenitis. SOURCES OF INFORMATION: MEDLINE and PubMed databases were searched for English-language research on sialadenitis and other salivary gland disorders, as well as for relevant review articles and guidelines published between 1981 and 2021. MAIN MESSAGE: Sialadenitis refers to inflammation or infection of the salivary glands and is a condition that can be caused by a broad range of processes including infectious, obstructive, and autoimmune. History and physical examination play important roles in directing management, while imaging is often useful to establish a diagnosis. Red flags such as suspected abscess formation, signs of respiratory obstruction, facial paresis, and fixation of a mass to underlying tissue should prompt urgent referral to head and neck surgery or a visit to the emergency department. CONCLUSION: Family physicians can play an important role in the diagnosis and management of sialadenitis. Prompt recognition and treatment of the condition can prevent the development of complications.

Montmorillonite clay-based sorbents decrease the bioavailability of per- and polyfluoroalkyl substances (PFAS) from soil and their translocation to plants.

Consumption of food and water contaminated with per- and polyfluoroalkyl substances (PFAS) presents a significant risk for human exposure. There is limited data on high affinity sorbents that can be used to reduce the bioavailability of PFAS from soil and translocation to plants and garden produce. To address this need, montmorillonite clay was amended with the nutrients carnitine and choline to increase the hydrophobicity of the sorbent and the interlayer spacing. In this study, the binding of PFOA (perfluorooctanoic acid) and PFOS (perfluorooctanesulfonic acid) to parent and amended clays was characterized. Isothermal analyses were conducted at pH 7 and ambient temperature to simulate environmentally-relevant conditions. The data for all tested sorbents fit the Langmuir model indicating saturable binding sites with high capacities and affinities under neutral conditions. Amended montmorillonite clays had increased capacities for PFOA and PFOS (0.51-0.71 mol kg-1) compared to the parent clay (0.37-0.49 mol kg-1). Molecular dynamics (MD) simulations suggested that hydrophobic and electrostatic interactions at the terminal fluorinated carbon chains of PFAS compounds were major modes of surface interaction. The safety and efficacy of the clays were confirmed in a living organism (Lemna minor), where clays (at 0.1% inclusion) allowed for increased growth compared to PFOA and PFOS controls (p ≤ 0.01). Importantly, soil studies showed that 2% sorbent inclusion could significantly reduce PFAS bioavailability from soil (up to 74%). Studies in plants demonstrated that inclusion of 2% sorbent significantly reduced PFAS residues in cucumber plants (p ≤ 0.05). These results suggest that nutrient-amended clays could be included in soil to decrease PFAS bioavailability and translocation of PFAS to plants.

Aflatoxin Exposure Among Mothers and Their Infants from the Western Highlands of Guatemala.

OBJECTIVES: We examined breast milk of mothers and urine of infants before and after introduction of supplementary foods for aflatoxin M1 (AFM1) and the association between AFM1 with maternal and infant diet. METHODS: A prospective cohort study was conducted among mothers and infants ages 0-6 months and 7-12 months from June-October 2014. Sociodemographic, dietary, birth, and health data were collected. A breast milk sample was collected from each mother and a urine sample from each infant at baseline (time point 1) and monthly for 2 time points thereafter; samples collected at baseline and time point 3 were tested for AFM1. RESULTS: Almost 5% of breast milk and 15.7% of urine samples tested AFM1-positive. The median AFM1 in breast milk was 0.020 ng/mL and in urine 0.077 ng/mg creatinine. At time point 3, infants of 5 of the 6 mothers in each group who were AFM1-positive in breast milk were also AFM1-positive in urine. Mothers' consumption of cooked maize/maize dough ≥ 3 days per week (OR 2.96, 95% CI = 1.19-7.34) and mothers' consumption of tamales made from maize ≥ 3 days per week (OR 0.28, 95% CI = 0.10-0.73) were significantly associated with AFM1 in infant urine. CONCLUSION: This is the first study in Guatemala documenting aflatoxin exposure in both breast milk of lactating mothers and infants´ urine during the first year of life. This may have important implications in understanding the multicausality of the high rates of stunting among children < 5 years old in Guatemala.

Decreased bioavailability of aminomethylphosphonic acid (AMPA) in genetically modified corn with activated carbon or calcium montmorillonite clay inclusion in soil.

The widespread use of pesticides has resulted in detectable residues throughout the environment, sometimes at concentrations well above regulatory limits. Therefore, the development of safe, effective, field-practical, and economically feasible strategies to mitigate the effects of pesticides is warranted. Glyphosate is an organophosphorus herbicide that is degraded to aminomethylphosphonic acid (AMPA), a toxic and persistent metabolite that can accumulate in soil and sediment and translocate to plants. In this study, we investigated the binding efficacy of activated carbon (AC) and calcium montmorillonite (CM) clay to decrease AMPA bioavailability from soil and AMPA translocation to plants. Adsorption isotherms and thermodynamic studies on AC and CM were conducted and showed tight binding (enthalpy values >-20 kJ/mol) for AMPA with high capacities (0.25 mol/kg and 0.38 mol/kg, respectively), based on derivations from the Langmuir model. A hydra assay was utilized to indicate toxicity of AMPA and the inclusion of 1% AC and CM both resulted in 90% protection of the hydra (**p ≤ 0.01). Further studies in glyphosate-contaminated soil showed that AC and CM significantly reduced AMPA bioavailability by 53% and 44%, respectively. Results in genetically modified (GM) corn showed a conversion of glyphosate to AMPA in roots and sprouts over a 10-day exposure duration. Inclusion of AC and CM reduced AMPA residues in roots and sprouts by 47%-61%. These studies collectively indicate that AC and CM are effective sorbents for AMPA and could be used to reduce AMPA bioavailability from soil and AMPA residues in GM corn plants.

Insights into the interactions of bisphenol and phthalate compounds with unamended and carnitine-amended montmorillonite clays.

Montmorillonite clays could be promising sorbents to mitigate toxic compound exposures. Bisphenols A (BPA) and S (BPS) as well as phthalates, dibutyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP), are ubiquitous environmental contaminants linked to adverse health effects. Here, we combined computational and experimental methods to investigate the ability of montmorillonite clays to sorb these compounds. Molecular dynamics simulations predicted that parent, unamended, clay has higher binding propensity for BPA and BPS than for DBP and DEHP; carnitine-amended clay improved BPA and BPS binding, through carnitine simultaneously anchoring to the clay through its quaternary ammonium cation and forming hydrogen bonds with BPA and BPS. Experimental isothermal analysis confirmed that carnitine-amended clay has enhanced BPA binding capacity, affinity and enthalpy. Our studies demonstrate how computational and experimental methods, combined, can characterize clay binding and sorption of toxic compounds, paving the way for future investigation of clays to reduce BPA and BPS exposure.

Development of broad-acting clays for the tight adsorption of benzo[a]pyrene and aldicarb.

People and animals can be unintentionally exposed to complex mixtures of hazardous chemicals that can threaten the safety of food and water supplies following natural and man-made disasters and emergencies. Our research has focused on the development of broad-acting adsorbents that will tightly bind environmental contaminants in the gastrointestinal tract and decrease their bioavailability to humans and animals during these events. In this study, benzo[a]pyrene (BaP) and aldicarb were used as representative chemicals due to their high toxicity and extensive distribution in the environment. Both chemicals have been commonly detected in water and sediments in the US, and their distribution and concentrations can be enhanced during disasters. To address this problem, we have amended and functionalized montmorillonite clays with the nutrients, L-carnitine and choline to enhance their attraction for lipophilic toxins, such as BaP and aldicarb. Based on equilibrium isothermal analyses, we have demonstrated a significantly increased binding capacity (Qmax) and affinity (Kd) for BaP and aldicarb compared to the parent clay. Adsorption isotherms also showed that talc bound strongly to BaP with the highest Qmax, which was twice that of activated carbon. Additionally, cultures of adult hydra with a metabolism activation package were used as an in vivo toxicity indicator to confirm the ability of test adsorbents to protect against toxicity at low inclusion levels. We anticipate that the optimal adsorbents developed can be delivered in food and flavored water, or administered by sachet or capsule during emergencies and disasters to decrease human and animals exposures to environmental toxins.

Development of enterosorbents that can be added to food and water to reduce toxin exposures during disasters.

Humans and animals can be exposed to mixtures of chemicals from food and water, especially during disasters such as extended droughts, hurricanes and floods. Drought stress facilitates the occurrence of mycotoxins such as aflatoxins B1 (AfB1) and zearalenone (ZEN), while hurricanes and floods can mobilize toxic soil and sediments containing important pesticides (such as glyphosate). To address this problem in food, feed and water, we developed broad-acting, clay-based enterosorbents that can reduce toxin exposures when included in the diet. In this study, we processed sodium and calcium montmorillonite clays with high concentrations of sulfuric acid to increase surface areas and porosities, and conducted equilibrium isothermal analyses and dosimetry studies to derive binding parameters and gain insight into: (1) surface capacities and affinities, (2) potential mechanisms of sorption, (3) thermodynamics (enthalpy) of toxin/surface interactions and (4) estimated dose of sorbent required to maintain toxin threshold limits. We have also used a toxin-sensitive living organism (Hydra vulgaris) to predict the safety and efficacy of newly developed sorbents. Our results indicated that acid processed montmorillonites were effective sorbents for AfB1, ZEN and glyphosate, with high capacity and tight binding, and effectively protected hydra against individual toxins, as well as mixtures of mycotoxins.

RNA Recognition-like Motifs Activate a Mitogen-Activated Protein Kinase.

Smk1 is a mitogen-activated protein kinase (MAPK) family member in the yeast Saccharomyces cerevisiae that controls the postmeiotic program of spore formation. Ssp2 is a meiosis-specific protein that activates Smk1 and triggers the autophosphorylation of its activation loop. A fragment of Ssp2 that is sufficient to activate Smk1 contains two segments that resemble RNA recognition motifs (RRMs). Mutations in either of these motifs eliminated Ssp2's ability to activate Smk1. In contrast, deletions and insertions within the segment linking the RRM-like motifs only partially reduced the activity of Ssp2. Moreover, when the two RRM-like motifs were expressed as separate proteins in bacteria, they activated Smk1. We also find that both motifs can be cross-linked to Smk1 and that at least one of the motifs binds near the ATP-binding pocket of the MAPK. These findings demonstrate that motifs related to RRMs can directly activate protein kinases.

Approche de la sialadénite.

OBJECTIF: Proposer aux médecins de famille une approche pratique fondée sur des données probantes pour la prise en charge de patients souffrant de sialadénite. SOURCES DE L'INFORMATION: Une recension a été effectuée dans les bases de données MEDLINE et PubMed pour trouver des recherches publiées en anglais sur la sialadénite et d'autres troubles des glandes salivaires, ainsi que des revues et des lignes directrices pertinentes, publiées entre 1981 et 2021. MESSAGE PRINCIPAL: La sialadénite désigne une inflammation ou une infection des glandes salivaires; elle peut être causée par un large éventail de processus de nature infectieuse, obstructive et auto-immune. L'anamnèse et l'examen physique jouent un rôle important pour orienter la prise en charge, tandis que l'imagerie est souvent utile pour établir un diagnostic. Des signaux d'alerte comme la formation suspectée d'un abcès, des signes d'obstruction respiratoire, une parésie faciale et la fixation d'une masse aux tissus sous-jacents devraient inciter à faire une demande de consultation urgente en chirurgie de la tête et du cou, ou à recommander une visite au service d'urgence. CONCLUSION: Les médecins de famille peuvent jouer un rôle important dans le diagnostic et la prise en charge de la sialadénite. Une reconnaissance et un traitement rapides du problème peuvent prévenir la survenance de complications.

Development of High Capacity Enterosorbents for Aflatoxin B1 and Other Hazardous Chemicals.

Previously, a calcium montmorillonite clay (NovaSil) included in the diet of animals has been shown to bind aflatoxin B1 (AfB1) and reduce the symptoms of aflatoxicosis. To investigate and improve the capacity and efficacy of clay-based materials as aflatoxin sorbents, we developed and tested calcium and sodium montmorillonite clays amended with nutrients including l-carnitine and choline. Also, we determined the sorption of AfB1 by isothermal analysis and tested the ability of these amended sorbents to protect adult hydra from AfB1 toxicity. The results showed that exchanging montmorillonite clays with l-carnitine and choline inhibited swelling of the clays and increased the sorption capacity and efficacy of clay surfaces for AfB1. Results from dehydroxylated and heat-collapsed clays suggested that AfB1 was primarily adsorbed in the clay interlayer, as predicted from thermodynamic calculations and computational modeling. The hydra bioassay further indicated that the modified clays can significantly protect adult hydra from AfB1 with as low as 0.005% clay inclusion. This enterosorbent therapy may also be applied to screen hazardous chemicals such as pesticides and PAHs based on similar sorption mechanisms. Taken together, enterosorbent therapy could be delivered in nutritional supplements, foods that are vulnerable to aflatoxin contamination, flavored liquids and animal feeds during emergencies and outbreaks of acute aflatoxicosis, and as a screening model for hazardous environmental chemicals.

1H-Pyrazolo[3,4-g]hexahydro-isoquinolines as potent GR antagonists with reduced hERG inhibition and an improved pharmacokinetic profile.

We report the further optimization of our series 1H-pyrazolo[3,4-g]hexahydro-isoquinoline sulfonamides as GR antagonists. By incorporating a heteroaryl ketone group at the ring junction, we have obtained compounds with excellent functional GR antagonism. Optimization of the sulfonamide substituent has provided compounds with a very desirable overall profile, including minimal hERG activity, good bioavailability and in vivo efficacy.

Mitigation of colitis with NovaSil clay therapy.

BACKGROUND/AIMS: Five million people currently live with Crohn's disease (CD) or ulcerative colitis, the two major forms of inflammatory bowel disease. Available treatments frequently result in side effects that compromise the immune health of the patient. Consequently, alternative therapies that cause fewer systemic effects are needed. Dioctahedral smectite clays have been utilized to treat medical conditions, including diarrheal and enteric disease. Herein, we report the ability of a refined dioctahedral smectite (NovaSil, NS) to sorb inflammatory proteins and reduce inflammation in a TNBS (2,4,6-trinitrobenzenesulfonic acid) mouse model of CD. We also investigated whether NS could rescue gut microbial diversity in TNBS-induced mice. METHODS: ELISA, X-ray diffraction, and transmission electron microscopy were employed to characterize the NS-cytokine interaction in vitro. A TNBS mouse colitis model was utilized to study the efficacy of NS supplementation for 4 weeks. The three treatment groups included control, TNBS, and TNBS + NS. DNA was extracted from feces and sorted for bacterial phylogenetic analysis. RESULTS: Results suggest that NS binds TNFα in vitro. In TNBS-treated mice, supplementation with NS significantly reduced weight loss, and serum proinflammatory cytokine levels (IL-2, IL-6, and IL-12, TNFα, IFNγ) compared with the TNBS group. TNBS-treated mice demonstrated a significant reduction in gut microbiota species richness when compared with the TNBS + NS group and control group. CONCLUSIONS: NovaSil mitigated the effects of TNBS-induced colitis based on reduction in systemic markers of inflammation, significant improvement in weight gain, and intestinal microbial profile.

Reversible cerebral vasoconstriction syndrome as a cause of thunderclap headache: a retrospective case series study.

Thunderclap headache is a common emergency department presentation. Although subarachnoid hemorrhage (SAH) should be the first diagnosis to exclude, reversible cerebral vasoconstriction syndrome (RCVS) is an important alternative cause, which may be commoner than appreciated. Reversible cerebral vasoconstriction syndrome is characterized by multifocal narrowing of cerebral arteries, typically manifested by acute, severe headache with or without neurologic deficits. To compare and discuss the clinical and radiologic characteristics of patients with RCVS. We report 4 cases of RCVS, presenting at a single unit in 1 year. All presented with thunderclap headache, whereas half of them had additional neurologic symptoms such as right homonymous hemianopia, right-sided weakness, and slurred speech. Brain computed tomography was normal in 2 of our patients, but subsequent cerebrospinal fluid analysis revealed xanthochromia consistent with SAH. The remaining 2 patients demonstrated intracerebral hemorrhage on computed tomography. All of our patients underwent digital subtraction angiography that showed segmental narrowing and dilatation of one or more cerebral arteries without any signs of aneurysm. Repeat digital subtraction angiography after 3 months was entirely normal prompting the diagnosis of RCVS. Thunderclap headache requires urgent workup to identify the underlying cause. Although SAH is the most important diagnosis to exclude in the first instance, emergency physicians should be aware of other causes and how they present, such as RCVS. Early recognition of this condition is important in order to remove precipitants, avoid unnecessary investigations, and inform patients about their prognosis.

Comparative effect of thymol or its glucose conjugate, thymol-ß-D-glucopyranoside, on Campylobacter in avian gut contents.

Campylobacter jejuni is an important human food-borne pathogen that can contaminate meat and poultry during processing. Consequently, strategies are sought to reduce the carriage of C. jejuni in food animals before they arrive at the abattoir. Thymol is a natural product that reduces survivability of Campylobacter in vitro, but its rapid absorption from the proximal alimentary tract limits its bactericidal efficacy in vivo. Thymol-ß-D-glucopyranoside is more resistant to absorption than free thymol, but its administration to chickens has not been reported. In the present studies, 1 mM thymol-ß-D-glucopyranoside was shown to exhibit near equal anti-Campylobacter activity as 1 mM thymol when incubated anaerobically in avian crop or cecal contents in vitro, resulting in reductions of 1.10-2.32 log10 colony forming units mL(-1) in C. jejuni concentrations after 24 h incubation. In a follow-up live animal study, oral administration of thymol-ß-D-glucopyranoside, but not free thymol, significantly lowered (>10-fold) recovery of Campylobacter from the crop of market-aged broilers when compared to placebo-treated controls (n = 6 broilers/treatment). Neither thymol-ß-D-glucopyranoside nor thymol affected recovery of Campylobacter from cecal contents of the treated broilers. These results indicate that rapid absorption or passage of free thymol from the crop precluded its anti-Campylobacter activity at this site and throughout the entire gastrointestinal tract. Conversely, lower recovery of Campylobacter from the crop of birds treated with thymol-ß-D-glucopyranoside indicates this conjugate was retained and able to be hydrolyzed to biologically active free thymol at this site as intended, yet was not sufficiently protected to allow passage of efficacious amounts of the intact glycoside to the lower gut. Nevertheless, these results warrant further research to see if higher doses or encapsulation of thymol-ß-D-glucopyranoside or similar glycosides may yield an efficacious additive to reduce carriage of Campylobacter as well as other pathogens throughout the avian gut.

Aflatoxin B1 modulates the expression of phenotypic markers and cytokines by splenic lymphocytes of male F344 rats.

Aflatoxin B1 (AFB1) is immunotoxic to animals and a suspected immunosuppressant in humans. In this study, we investigated the effects of AFB1 on splenic lymphocyte phenotypes and the inflammatory cytokine expression in male F344 rats. Exposure of animals to AFB1 [5-75 µg kg(-1) body weight (BW)] for 1 week showed dose-dependent decreases in the percentage of splenic CD8(+) T cells and CD3(-) CD8a(+) NK cells. A general inhibition of the expression of interleukin (IL)-4 and interferon (IFN)-γ by CD4(+) T cells, IL-4 and IFN-γ by CD8a(+) cells, and tumor necrosis factor (TNF)-α expression by natural killer (NK) cells was also found; however, no concurrent histological changes in spleen tissue were present, suggesting acute immunosuppression without overt toxicity. Five-week exposure with AFB1 significantly increased the percentages of CD3(+) and CD8(+) T cells, especially at low doses (≤ 25 µg kg(-1)). AFB1 treatment significantly decreased the anti-inflammatory cytokine IL-4 expression by CD4(+) T cells and significantly increased the pro-inflammatory cytokine IFN-γ expression by CD4(+) T cells and TNF-α expression by NK cells. These results indicated that repeated AFB1 exposure promotes inflammatory responses by regulating cytokine expression. Our data provides novel insights into the mechanisms by which AFB1 exposure differentially modulates the cell-mediated immune responses and suggests the involvement of an inflammatory response upon repeated exposure.