Quantitative MALDI-MS and Imaging of Fungicide Pyrimethanil in Strawberries with 2-Nitrophloroglucinol as an Effective Matrix.

This work explores the use of 2-nitrophloroglucinol (2-NPG) as a matrix for quantitative analysis of the fungicide Pyrimethanil (PYM) in strawberries using matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and imaging. 2-NPG was selected for PYM analysis for optimum sensitivity and precision compared to common matrices α-cyano-4-hydroxylcinnamic acid (CHCA) and 2,5-dihydroxybenzoic acid (DHB). PYM-sprayed strawberries were frozen 0, 1, 3, and 4 days after treatment and sectioned for MALDI imaging. The remaining part of each strawberry was processed using quick easy cheap effective rugged and safe (QuEChERS) extraction and analyzed by MALDI-MS and ultraperformance liquid chromatography multireaction-monitoring (UPLC-MRM). MALDI-MS showed comparable performance to UPLC-MRM in calibration, LOD/LOQ, matrix effect, and recovery, with the benefit of fast analysis. The MALDI imaging results demonstrated that PYM progressively penetrated the interior of the strawberry over time and the PYM concentration on tissue measured by MALDI imaging correlated linearly with MALDI-MS and UPLC-MRM measurements and accounts for 79% MALDI-MS and 85% UPLC-MRM values on average. Additionally, quartz crystal microbalance (QCM) was introduced as a new approach to determine strawberry tissue mass per area for MALDI imaging absolute quantitation with sensitive, direct, and localized measurements. This work demonstrates the first example of absolute quantitative MALDI imaging of pesticides in a heterogeneous plant tissue. The novel use of the 2-NPG matrix in quantitative MALDI-MS and imaging could be applied to other analytes, and the new QCM tissue mass per area method is potentially useful for quantitative MALDI imaging of heterogeneous tissues in general.

Bone biochemistry in children with fractures presenting with non-accidental injury.

BACKGROUND: In cases of fractures in children with suspicion of non-accidental injury (NAI), biochemical markers of calcium homeostasis should be performed. OBJECTIVES: To describe the pattern of biochemistry in children with fractures NAI is suspected. PARTICIPANTS AND SETTING: Children ≤2 years of age who had undergone a skeletal survey as part of a child protection investigation where 1/+ fracture was identified over a ten-year period (2012-2021) at the Royal Hospital for Children, Glasgow. METHODS: A retrospective review of case notes was conducted. Established criteria to classify NAI were used to distinguish confirmed NAI from non-NAI. Biochemical markers of calcium homeostasis were classified as normal or abnormal using local reference ranges. Vitamin D deficiency was classified as Vitamin D < 25 nmol/L and insufficiency as 25-50 nmol/L. RESULTS: One hundred and twenty-seven children were identified, of whom 107 (84 %) had bone biochemistry performed. Twenty-nine children (24 %) had injuries that were classified as confirmed NAI. In cases where NAI was confirmed either at case conference or by criminal conviction 14/29 (48 %) had one or more abnormal bone biochemical markers. None of the children displayed clinical or radiological evidence of rickets. Alkaline phosphatase (ALP) was higher in children with confirmed NAI (median 296 vs. 261, p = 0.01) but there were no other statistically significant differences in biochemical levels between those with confirmed NAI compared to those without. Those with confirmed NAI were from areas with lower SIMD score (2.0 vs. 3.0 p = 0.01) but no other differences were found between the groups. CONCLUSION: No clear predictors of NAI are demonstrated on biochemistry alone in young children with fractures.

The impact of a rosemary containing drink on event-related potential neural markers of sustained attention.

BACKGROUND: Research suggests that the ingestion or aroma of rosemary enhances cognitive ability in both rodents and humans. However, how rosemary facilitates cognition and the precise therapeutic impacts on information processing remains unclear. HYPOTHESIS/PURPOSE: This pilot study used the temporal precision of event-related potentials (ERPs) to examine the cognitive-enhancing benefits of a rosemary drink. Neural markers of sustained attention were used as indices to explore whether rosemary facilitates concentration in general or the allocation of resources to task-relevant information only. STUDY DESIGN AND METHODS: In a between-subject design (rosemary vs water control drink), 48 adults performed a 3-stimulus visual oddball task. Participants differentiated between rare target stimuli (index of task-relevant attentional processes; P3b ERP) embedded in a train of frequent stimuli. The presentation of an infrequent novel stimulus was also included (index of task-irrelevant stimulus processing; P3a ERP). Throughout the session, electroencephalograms (EEG) were collected and time-locked to the presentation of the target (P3b) and novel (P3a) stimulus types. RESULTS: The primary analyses revealed facilitation of the P3a in particular with a medium Cohen's effect size reported. The investigation of the P3b component, although less reliable, also had a medium effect. The subsidiary consideration of the association between behaviour and the ERPs provided a further level of explanation regarding the therapeutic effect of rosemary on cognition. Indeed, the pattern of associations was suggestive of strategy differences during the performance of the task across the treatment group., although these data should be treated with caution. CONCLUSIONS: These pilot data provide critical insights into the utility of rosemary to facilitate different aspects of attention. In particular, data are consistent with rosemary providing additional attentional resources to enhance the processing of stimuli we encounter, irrespective of task relevance. Indeed, the enhancement of both P3a and P3b components following rosemary administration may indicate that the herb enhances the processing of all stimuli in the environment. We argue for the use of both behavioural and EEG methods to explore the therapeutic effects of herbal compounds.

The free bilamellar autograft (FBA) procedure: A comprehensive case series of an alternative surgical approach to reconstruction of large eyelid defects.

Purpose: The free bilamellar autograft (FBA) procedure involves harvesting a free, full-thickness section of eyelid tissue from one of the patient's healthy eyelids to reconstruct a large defect of the involved eyelid. No vascular augmentation is employed. The purpose of this study was to determine the structural and cosmetic results of this procedure. Methods: A case series was performed, looking at patients who underwent the FBA procedure for large, full-thickness eyelid defects (>50% eyelid length) between 2009 and 2020 at a single oculoplastic surgical centre. Basal cell carcinomas most frequently met criteria for the procedure. OHSN-REB waived ethics approval. All surgeries were performed by one surgeon. A single operation, with surgical steps reported in detail, was completed with follow-up documentation at ideally 1 day, 1 week, 1 month, 3 months, 6 months, and 1 year. The mean follow-up period was 28 months. Results: Thirty-one patients (17 males, 14 females, mean age 78-years-old) were included in the case series. Comorbidities included diabetes and smoking. Most patients had known basal cell carcinomas removed from the upper or lower eyelid. The mean widths of the recipient and donor sites were 18.8 and 11.5 mm, respectively. All 31 FBA surgeries resulted in structurally functional, cosmetically pleasing, and viable eyelids. Six patients developed minor graft dehiscence, 3 developed an ectropion, and 1 developed mild superficial graft necrosis secondary to frostbite, which fully recovered. Three healing phases were identified. Conclusion: This case series adds to the currently sparse data on the free bilamellar autograft procedure. The surgical technique is clearly articulated and illustrated. The FBA procedure is a simple and efficient alternative to current surgical techniques in the reconstruction of full-thickness upper and lower eyelid defects. The FBA provides functional and cosmetic success, despite the absence of an intact blood supply, with decreased operative time and faster recovery.

WAS IT LEUCONOSTOC SPECIES? A CASE OF DELAYED-ONSET ENDOPHTHALMITIS PRESENTING 14 YEARS AFTER CATARACT SURGERY.

PURPOSE: To report a case of delayed-onset endophthalmitis presenting 14 years after an uncomplicated cataract surgery. METHODS: Case report. RESULTS: An 89-year-old pseudophakic man complained of redness and reduced visual acuity in his right eye. He had no history of trauma or systemic infection, and his only surgery on the right eye was an uncomplicated cataract surgery 14 years before. On physical examination, he was found to have keratic precipitates and a white posterior capsular plaque in the right eye. He was treated with a right pars plana vitrectomy and intraocular lens removal. Microbiological classification of the samples revealed the presence of a Leuconostoc species within the vitreous humor and coagulase-negative staphylococci on the lens. Two months after placement of the intraocular lens, he achieved a best-corrected visual acuity of 20/200 in his right eye. CONCLUSION: To the best of our knowledge, this is the first reported case of delayed-onset endophthalmitis occurring more than 10 years after an uncomplicated cataract surgery. This case highlights a highly unusual presentation of delayed-onset endophthalmitis and reports a potential novel microbiological cause of plaque formation.

Leber Hereditary Optic Neuropathy in Southwestern Ontario: A Growing List of Mutations.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is a rare but bilaterally blinding disease. Three characteristic disease-causing point mutations, and other less common mutations, are most often found on the mitochondrially encoded genes of NADH-ubiquinone oxidoreductase core subunits (MT-ND). The purpose of this study is to provide an overview of LHON mutations in Southwestern Ontario and to describe the associated demographic and clinical characteristics. METHODS: A retrospective genetic and clinical chart review was performed from January 2015 to 2020. Patients were identified within a mitochondrial mutation database and included if a mutation was detected on the MT-ND1, -ND4, or -ND6 genes. A clinical chart review was done on all available patients. RESULTS: Forty-five of 63 patients identified had classic disease-causing mutations (6.7% m.3460G>A, 44.4% m.11778G>A, and 48.9% m.14484T>C). Several of the remaining 18 patients had rare mutations previously documented in association with LHON. Of the 14 patients with clinical charts accessible for review, 12 had symptomatic disease, and all but one had bilateral optic neuropathies. Nine patients had classic LHON mutations and 3 had possible novel mutations; 7 were males; 9 had final visual acuity ≤ 20/200 in at least one eye; and 6 of those had ≤20/400 in both eyes. CONCLUSIONS: This study adds to the literature on LHON in Canada, and specifically Southwestern Ontario. The demographic and clinical data regarding LHON in this geographic location, as well as possible novel disease-causing mutations, provide important information to aid clinicians in recognizing cases of LHON that may otherwise be disregarded.

Ophthalmology on Call: Evaluating the Volume, Urgency, and Type of Pages Received at a Tertiary Care Center.

BACKGROUND: A significant proportion of on-call resident workload is related to answering and managing pages. Ophthalmology residents see high volumes of patients on call, but little is known about the profile of pages they receive. The objective of this study is to characterize the volume, type, and urgency of pages received by the ophthalmology on-call service. METHODS: A retrospective review of on-call pager log sheets and patient charts was performed at a single academic institution. Data were collected from July to December 2019, sampling the first seven days of each month. Data collected for each page included date/time of day, source, and primary concern. For each page leading to a patient encounter, time from page to patient assessment, patient demographics, and final diagnosis were recorded. Continuous variables were reported as mean values, whereas categorical variables were presented as percentages. A two-sample t-test and single-factor analysis of variance were employed. RESULTS: Over 42 days, 1108 pages were received. Over half of these calls required patient assessment, 71% of which were seen the same day. On average, 26 pages were received in 24 hours. Daytime weekday hours were significantly more busy than weekday nights or weekends (p<0.001). Patients and the emergency department each accounted for almost one-third of calls received. Retina- and cornea-related consults were most common. CONCLUSIONS: Pager volumes in ophthalmology are high and on-call patient volumes are rising. Answering pages increases the on-call resident's workload and has a negative impact on clinic flow. These data can be used to inform resident curriculum development, hospital system changes, patient education regarding appropriate paging, and medical school teaching.

A DnaK(Hsp70) Chaperone System Connects Type IV Pilus Activity to Polysaccharide Secretion in Cyanobacteria.

Surface motility powered by type IV pili (T4P) is widespread among bacteria, including the photosynthetic cyanobacteria. This form of movement typically requires the deposition of a motility-associated polysaccharide, and several studies indicate that there is complex coregulation of T4P motor activity and polysaccharide production, although a mechanistic understanding of this coregulation is not fully defined. Here, using a combination of genetic, comparative genomic, transcriptomic, protein-protein interaction, and cytological approaches in the model filamentous cyanobacterium N. punctiforme, we provided evidence that a DnaK-type chaperone system coupled the activity of the T4P motors to the production of the motility-associated hormogonium polysaccharide (HPS). The results from these studies indicated that DnaK1 and DnaJ3 along with GrpE comprised a chaperone system that interacted specifically with active T4P motors and was required to produce HPS. Genomic conservation in cyanobacteria and the conservation of the protein-protein interaction network in the model unicellular cyanobacterium Synechocystis sp. strain PCC 6803 imply that this system is conserved among nearly all motile cyanobacteria and provides a mechanism to coordinate polysaccharide secretion and T4P activity in these organisms. IMPORTANCE Many bacteria, including photosynthetic cyanobacteria, exhibit type IV pili (T4P) driven surface motility. In cyanobacteria, this form of motility facilitates dispersal, phototaxis, the formation of supracellular structures, and the establishment of nitrogen-fixing symbioses with eukaryotes. T4P-powered motility typically requires the deposition of motility-associated polysaccharides, and previous studies indicate that T4P activity and polysaccharide production are intimately linked. However, the mechanism by which these processes are coupled is not well defined. Here, we identified and characterized a DnaK(Hsp70)-type chaperone system that coordinates these two processes in cyanobacteria.

Multifocal germinoma masquerading as avoidant restrictive food intake disorder: a case of severely decreased food intake and malnutrition.

A young woman presented with significant weight loss and malnutrition secondary to decreased food intake. Her presentation was felt to be consistent with a psychiatric diagnosis of avoidant restrictive food intake disorder (ARFID). She received 3 years of treatment for ARFID, but failed to make significant progress and ultimately required a feeding tube. Incidentally, she noted severe visual field changes at this time, which triggered further workup including an MRI of the head. This revealed the true diagnosis of a suprasellar and pineal germinoma. There are several cases in the literature of germinomas presenting with decreased food intake that were misdiagnosed as anorexia nervosa. However, this is the first reported case of a multifocal germinoma presenting as ARFID. Criteria for the diagnosis of ARFID do not include body image distortion, potentially making this eating disorder more prone to misdiagnosis.

Positive schizotypy and the experience of creativity: The distinctive roles of suspiciousness and dispositional mindfulness.

Positive schizotypy has been shown to predict emergence of schizophrenia-spectrum disorders, with suspiciousness/paranoia regarded a key risk factor. However, magical thinking and unusual perceptual experiences, other aspects of positive schizotypy, are associated with creativity. We investigated whether suspiciousness attenuates the relationship of magical thinking and unusual experiences with creative experience, and explored the interaction of dispositional mindfulness with positive schizotypy and creative experience. 342 (256 females) healthy adults (mean age: 25.9; SD 8.4) completed online self-report measures of schizotypy, creative experience, and dispositional mindfulness. Moderation analysis showed that suspiciousness attenuated the positive relationship of magical thinking (b = -0.29, p = .03) and unusual perceptual experiences (b = -0.23, p = .01) with an aspect of creative experience related to positive affect - power/pleasure. This effect was not present for 4 other aspects of creative experience. Multiple linear regressions revealed higher dispositional mindfulness to interact with aspects of positive schizotypy associated with heightened creative experience of power/pleasure (b = 0.06, p = .03), clarity/preparation (b = 0.03, p = .004), and differing levels of anxiety associated with creative engagement (b = -0.06, p = .003; b = 0.03, p = .047). Higher dispositional mindfulness was also associated with lower suspiciousness (rs = -0.33, p < .001). The study highlights the importance of considering the role of suspiciousness/paranoia when investigating the relationship between positive schizotypy and creativity. The findings provide support for the application of mindfulness-based interventions for mitigating psychosis-risk associated with suspiciousness, whilst supporting the otherwise favourable association of positive schizotypy with creativity.

Outcomes of Rhegmatogenous Retinal Detachment Repair With Nonrestricted Postoperative Positioning.

Purpose: To investigate the anatomical success rate associated with rhegmatogenous retinal detachment (RRD) repair without postoperative head positioning. Methods: Data on 182 individuals undergoing pars plana vitrectomy (PPV) with or without phacoemulsification or scleral buckle for primary RRD with intraocular tamponade were retrospectively reviewed. The primary outcome was the initial anatomical success rate. Secondary outcome measures were the change in best-corrected visual acuity and the final reattachment rate. Results: A total of 122 eyes from 122 patients who underwent RRD repair without postoperative positioning were included in this study. PPV alone was performed in 39% of cases, whereas the remaining patients had PPV combined with phacoemulsification (35%), with scleral buckle (19%), or both (7%). Inferior breaks between the 4 o'clock and 8 o'clock positions were present in 47% of cases. Primary and final anatomical success was achieved in 86% and 98% of cases, respectively. The most common cause for redetachment was proliferative vitreoretinopathy. Age and combined inferior retinal and superior breaks were predictive of recurrence in the logistic regression model. The mean baseline best-corrected visual acuity improved from 1.2 (Snellen equivalent, 20/320) to 0.76 (Snellen, 20/125) logarithm of the minimum angle of resolution after retinal reattachment (P < .001). Conclusions: PPV combined with or without phacoemulsification or scleral buckle for primary RRD in pseudophakic eyes or those rendered pseudophakic is associated with good anatomical outcomes without restricted postoperative head positioning. Retinal detachment in eyes with combined retinal inferior and superior breaks may have a lower success rate, and whether this is due to lack of postoperative positioning needs further evaluation in prospective, controlled studies.

Periadventitial tissue examination in temporal artery biopsies for suspected giant cell arteritis: a case series and literature review.

OBJECTIVE: Giant cell arteritis (GCA) is a systemic vasculitis, affecting medium- and large-sized vessels. Temporal artery biopsies (TABs) are currently the benchmark for diagnosing suspected cases of GCA. Often, the temporal artery is "skeletonized," and surrounding soft tissue is discarded at the time of biopsy. The purpose of this study was to identify cases in which diagnoses were made through examination of periadventitial soft tissue in nonskeletonized TABs. DESIGN: Retrospective observational case series and literature review. PARTICIPANTS: Six patients were recruited on a case-by-case basis. INCLUSION CRITERIA: bilateral TABs for suspected GCA and periadventitial findings leading to appropriate diagnosis. EXCLUSION CRITERIA: none. METHODS: A retrospective chart review was performed to collect patient demographics and clinical information in 2 academic institutions in Ontario, Canada. The primary outcome measure was identification of histopathological diagnoses made through examination of periadventitial soft tissue in TABs performed for suspected GCA. RESULTS: Two patients were diagnosed with GCA, one of which had a concurrent diagnosis of chronic lymphocytic leukemia. Four patients were diagnosed with small vessel vasculitis, 3 of which were antineutrophil cytoplasmic antibody-related vasculitides. All patients had evidence of a disease limited to the periadventitial tissue of the TAB. The results are limited by the study's size. CONCLUSIONS: This case series demonstrates that other serious conditions may declare themselves with symptoms similar to that of GCA. We recommend that surgeons perform a nonskeletonized TAB in all cases of suspected GCA and that pathologists adequately examine the periadventitial tissue in these biopsies to ensure appropriate diagnosis.

A Systematic Review of the Impact of Surgical Special Care Units on Patient Outcomes and Health Care Resource Utilization.

Perioperative intermediate care units (termed surgical special care units) have been widely implemented across health systems because they are believed to improve surveillance and management of high-risk surgical patients. Our objective was to conduct a systematic review to investigate the effects of a 3-level model of perioperative care delivery (ie, ward, surgical special care unit, or intensive care unit) compared to a 2-level model of care (ie, ward, intensive care unit) on postoperative outcomes. Our protocol was registered with PROSPERO, the international prospective register of systematic reviews (CRD42015025155). Randomized controlled studies and nonrandomized comparator studies were included. We performed a systematic search of Medline, Cumulative Index to Nursing and Allied Health Literature, Embase, and the Cochrane library (inception - 11/2017). The primary outcome was mortality; secondary outcomes included length of stay and hospital costs. We identified 1995 citations with our search, and 21 studies met eligibility criteria (2 randomized controlled studies and 19 nonrandomized comparator studies; 44,134 patients in total). Surgical special care units were characterized by continuous monitoring (12 studies), the absence of mechanical ventilation (8 studies), nurse-to-patient ratios (range, 1:2-1:4), and number of beds (median: 5; range: 3-33). Thirteen studies reported on mortality. Notable findings included no observed difference in overall in-hospital mortality, but an apparent increase in intensive care unit mortality in a 3-level model of care. This may reflect a decanting of lower acuity patients from the intensive care unit to the surgical special care unit. No significant difference was found in hospital length of stay; however, 2 studies demonstrated reductions in hospital costs with the implementation of a surgical special care unit. Significant clinical and methodological heterogeneity precluded pooled analysis. Given the prevalence of surgical special care units, the results of our review suggest that additional methodologically rigorous investigations are needed to understand the effect of these units on the surgical population.

MedsOnCall Pager App: A Pilot Project for Practicing Safe Clinical Decision-making.

Errors in clinical decision-making contribute to approximately half of in-hospital adverse events. The steep learning curve when students transition to residents is particularly susceptible to increased errors. Decision-making skills are a major contributor to preparedness for residency and educators agree that decision-making should be purposefully taught and tested. Despite this, little structured assessment of decision-making currently exists. This innovation report describes the development and piloting of the MedsOnCall (MOC) Pager App, a simulated pager program designed as a learning and assessment tool for senior medical students and junior residents to practice safe clinical decision-making as they transition between these two roles. Learners are randomly "paged" by the app about a list of virtual patients. To answer, they must integrate pertinent patient information efficiently. Learners then receive a page-management question that further probes their decision-making skills by asking them to consider the urgency and their level of confidence when determining the virtual patient's needs. The pilot version of the app was successfully alpha-tested in 2016 and 2017 with twenty fourth year medical students at our institution. Subjectively, students greatly enjoyed using the MOC Pager app to practice answering pages in a safe environment. The app was then adapted for the National Cardiac Surgery Bootcamp in 2017 for use by first-year residents. With demonstrated success as a pilot project, our group aims to rebuild the app for customizable use by multidisciplinary learners anywhere in the world simultaneously. We also plan to collect validity evidence, integrate in-app feedback capability, and disseminate the app on multiple platforms.

Cognitive biases in orbital mass lesions - Lessons learned.

PURPOSE: A patient's presentation and clinical diagnosis can at times be clouded by their past medical history. Clinicians' anchoring bias towards initial information, such as a history of cancer, may lead them astray when creating a differential diagnosis for a patient who presents with new signs and symptoms of a mass lesion, assuming metastatic disease without seeking tissue confirmation. METHODS: The presentation, workup, diagnosis, and treatment of two patients who presented with orbital masses in the context of a primary prostate cancer are presented in this report. RESULTS: In both cases, prostate cancer metastasis to the orbit was top on the differential. Ultimately, histopathological examination of biopsies taken from the orbital masses revealed orbital lymphoma in both patients. CONCLUSION: With mounting rates of patients who have survived a previous cancer, multiple primary cancers within one patient are becoming increasingly common. While prostate cancer metastasis to the orbit is a relatively rare event, orbital lymphoma is a more common diagnosis in orbital masses. Therefore, when patients present with orbital masses in the context of prostate cancer, the conclusion should not immediately be metastasis and a tissue diagnosis should be sought; especially given that the treatment of these entities is different.