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Permanent URI for this collectionhttps://hdl.handle.net/1807/100050

This collection contains a copy of open access articles published by U of T authors in Karger journals since March 2020. These copies are provided by the publisher as part of the transformative open access agreement between the University of Toronto and Karger Publishers.

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Alcohol Use and Cancer in the European Union
(Karger, 2020-05-15) Rehm, Jürgen; Shield, Kevin D
Background: Cancers constitute a major non-communicable disease category globally and in the European Union (EU). Summary: Alcohol use has been established as a major cause of cancer in humans. Principal cancer agencies agree that the following cancer sites are causally impacted by alcohol: lip and oral cavity, pharynx (excluding nasopharynx), oesophagus, colon and rectum, liver, (female) breast, and larynx. For all of these cancer sites, there is a dose-response relationship with no apparent threshold: the higher the average level of consumption, the higher the risk of cancer incidence. In the EU in 2016, about 80,000 people died of alcohol-attributable cancer, and about 1.9 million years of life were lost due to premature mortality or due to disability. Key messages: Given the above-described impact of alcohol on cancer, public awareness about the alcohol-cancer link needs to be increased. In addition, effective alcohol policy measures should be implemented. As a large part of alcohol-attributable cancers are in low and moderate alcohol users, in particular for females, general population measures such as increases in taxation, restrictions on availability, and bans on marketing and advertisement are best suited to reduce the alcohol-attributable cancer burden.
Alpha-Fetoprotein-Producing Early Gastric Cancer with Intramucosal Hepatoid and Fetal Enteric Differentiation
(Karger, 2020-08-26) Iwaya, Mai; Riddell, Robert; Asano, Koji; Kobayashi, Kazuo; Uehara, Takeshi; Ota, Hiroyoshi
Alpha-fetoprotein (AFP)-producing gastric carcinomas (AFPGCs) are relatively rare tumors known to have a poor prognosis and commonly found as advanced lesions. Histologically, AFPGCs have been described as having hepatoid and fetal enteric (enteroblastic) morphology and are associated with conventional adenocarcinomas. Prior studies reported a hepatoid component present only in invasive areas and hypothesized that AFPGCs may develop hepatoid features during the process of tumor invasion. We report three cases of AFP-producing early gastric cancer which had an intramucosal hepatoid component. Immunohistochemistry showed that the hepatoid component was diffusely immunoreactive for SALL4, AFP, arginase-1, and HepPar1, and focally for CDX2 and PDX1. An intramucosal transition between the hepatoid component and conventional intramucosal adenocarcinoma was identified. Two patients also had a coexistent fetal enteric component, which was admixed with a hepatoid component. Although at an early stage one patient subsequently developed liver metastasis and a second patient was suspected of having liver metastasis, these were not biopsy-proven. The latter patient had a previous history of hepatocellular carcinoma (HCC) and SALL4 was used on the HCC to distinguish metastatic/further HCC from a gastric metastatic primary with hepatoid differentiation.
Alternating Hypotropia with Pseudoptosis: A New Phenotype of Congenital Cranial Dysinnervation Disorder
(2018) Sedarous, Fady; Chan, Toby Y B; Makar, Inas
Congenital cranial dysinnervation disorders, also known as CCDDs, are characterized by aberrant innervation to extraocular and facial muscles resulting in unusual forms of incomitant strabismus. Anomalous innervation to extraocular muscles can result in a wide variety of phenotypes causing various clinical conditions such as Duane syndrome, congenital fibrosis of the extraocular muscles, and Möbius syndrome. We report a case of bilateral dysinnervation disorder causing atypical ocular movements in both eyes as the patient changes fixation from one eye to the other and from right gaze to left gaze that fits with the wider diagnosis of CCDDs.
Analysis of Geographic and Environmental Factors and Their Association with Cutaneous Melanoma Incidence in Canada
(2022-11) Berman-Rosa, Melissa; Logan, James; Ghazawi, Feras M; Le, Michelle; Conte, Santina; Netchiporouk, Elena; Mukovozov, Ilya M; Cyr, Janelle; Mourad, Ahmed; Miller, Wilson H; Claveau, Joël; Salopek, Thomas G; Gniadecki, Robert; Sasseville, Denis; Rahme, Elham; Lagacé, François; Litvinov, Ivan V
Background: Over 90% of skin cancers including cutaneous melanoma (CM) are related directly to sun exposure. Despite extensive knowledge on ultraviolet radiation’s (UVR) detrimental impact, many still fail to implement sun protection/sun avoidance. Human behavior, attitudes, and cultural norms of individuals and communities heavily depend on the surrounding climate/environment. In many instances, the climate shapes the culture/norms of the society. Canada has vast geographic/environmental differences. Methods: In the current ecological study, we sought to examine the relationship between various geographic and environmental factors and the distribution of CM incidence by Forward Sortation Area (FSA) postal code across Canada. CM incidence data were extracted from the Canadian Cancer Registry, while environmental data were extracted from the Canadian Urban Environmental Health Research Consortium (greenspace, as measured by the normalized difference vegetation index; annual highest temperature; absolute number and average length of yearly heat events; annual total precipitation [rain and snow]; absolute number and average length of events with precipitation [rain and snow]; and summer UVR index). The above geographic/environmental data by FSA were correlated with the respective CM incidence employing negative binomial regression model. Results: Our analysis highlights that increases in annual average temperature, summer UVR, and greenspace were associated with higher expected incidence of CM cases, while higher number of annual heat events together with highest annual temperature and higher average number of annual rain events were associated with a decrease in CM incidence rate. This study also highlights regional variation in environmental CM risk factors in Canada. Conclusions: This national population-based study presents clinically relevant conclusions on weather/geographic variations associated with CM incidence in Canada and will help refine targeted CM prevention campaigns by understanding unique weather/geographic variations in high-risk regions.
Analytical Validation of a Webcam-Based Assessment of Speech Kinematics: Digital Biomarker Evaluation following the V3 Framework
(Karger, 2023-04-28) Simmatis, Leif; Alavi Naeini, Saeid; Jafari, Deniz; Xie, Michael (Kai Yue); Tanchip, Chelsea; Taati, Niyousha; McKinlay, Scotia; Sran, Rupinder; Truong, Justin; Guarin, Diego L; Taati, Babak; Yunusova, Yana
Kinematic analyses have recently revealed a strong potential to contribute to the assessment of neurological diseases. However, the validation of home-based kinematic assessments using consumer-grade video technology has yet to be performed. In line with best practices for digital biomarker development, we sought to validate webcam-based kinematic assessment against established, laboratory-based recording gold standards. We hypothesized that webcam-based kinematics would possess psychometric properties comparable to those obtained using the laboratory-based gold standards.
Anti-Inflammatory Effects of Japanese Herbal Medicine Hochuekkito in a Mouse Model of Acute Exacerbation of Chronic Obstructive Pulmonary Disease
(Karger, 2024-04) Fukuda, Kensuke; Matsuzaki, Hirotaka; Hiraishi, Yoshihisa; Miyashita, Naoya; Ishii, Takashi; Yuki, Masaaki; Isago, Hideaki; Tamiya, Hiroyuki; Mitani, Akihisa; Saito, Akira; Jo, Taisuke; Nagase, Takahide
Introduction: The traditional Japanese herbal medicine hochuekkito (TJ-41) has been reported to ameliorate systemic inflammation and malnutrition in patients with chronic obstructive pulmonary disease (COPD). TJ-41 has also been known to have preventive effects against influenza virus infection. However, its role in the acute exacerbation of COPD (AECOPD) remains to be elucidated. Our previous study established a murine model of viral infection-associated AECOPD that was induced by intratracheal administration of porcine pancreatic elastase (PPE) and polyinosinic-polycytidylic acid [poly(I:C)]. Here, we used this model and investigated the effects of TJ-41 in AECOPD. Methods: Specific pathogen-free C57BL/6J mice were used. A COPD model was induced by treating mice intratracheally with PPE on day 0. To generate the murine model of AECOPD, poly(I:C) was administered intratracheally following PPE treatment on days 22–24. Mice were sacrificed and analyzed on day 25. Mice were fed a diet containing 2% TJ-41 or a control diet. Results: Daily oral intake of TJ-41 significantly decreased the numbers of neutrophils and lymphocytes in the bronchoalveolar lavage fluid (BALF), which was accompanied by decreased transcripts of CXC chemokines involved in neutrophil migration, viz., Cxcl1 and Cxcl2, in whole lung homogenates and reduced Cxcl2 concentration in BALF. Conclusion: This study demonstrates the anti-inflammatory effects of TJ-41 in a mouse model of AECOPD, suggesting the effectiveness of TJ-41 for the management of COPD. Clinical investigations evaluating the therapeutic efficacy of TJ-41 in AECOPD would be meaningful.
Anti-Vascular Endothelial Growth Factor Therapy Regimens for Polypoidal Choroidal Vasculopathy: A Systematic Review
(Karger, 2023-08-17) Mihalache, Andrew; Hatamnejad, Amin; Patil, Nikhil S; Popovic, Marko M; Muni, Rajeev H; Kertes, Peter J; Wong, David T
Introduction: There are no guidelines on the optimal anti-vascular endothelial growth factor (anti-VEGF) monotherapy regimen for patients with polypoidal choroidal vasculopathy (PCV). In this study, we aimed to assess the comparative safety and efficacy of different treatment regimens of anti-VEGF monotherapy for PCV. Methods: We conducted a systematic literature search on Ovid MEDLINE, Embase, and Cochrane Library from January 2000 to May 2023 for comparative articles reporting on different treatment regimens of anti-VEGF agents in PCV. Our primary outcomes were the final best-corrected visual acuity (BCVA) and the change in BCVA from baseline. Secondary outcomes were the final retinal thickness (RT), the change in RT from baseline, the rate of polyp closure, and the incidence of adverse events. Results: A total of 10,440 studies were screened, and seven studies reporting on 636 eyes with PCV at baseline were included in this systematic review. One RCT of 53 eyes found a similar final BCVA, change in BCVA from baseline, final RT, and complete polyp closure rate between a treat-and-extend (T&E) regimen and a bimonthly fixed-dosing regimen of aflibercept. This trial also found superiority of T&E for change in RT from baseline. One observational study of 33 eyes found a similar BCVA at last study observation between a pro re nata (PRN) regimen and bimonthly fixed-dosing regimen of aflibercept. One observational study of 42 eyes found a similar change in BCVA from baseline and complete polyp closure rate between a PRN regimen and bimonthly fixed-dosing regimen of aflibercept. One RCT of 249 eyes found a similar change in BCVA and RT from baseline, as well as polyp closure, between a T&E regimen and fixed 12-week dosing regimen of conbercept. One observational study of 30 eyes found a superiority of T&E aflibercept for change in BCVA and risk of polyp recurrence, compared to a PRN regimen. Conclusion: Overall, there is a paucity of evidence comparing various treatment regimens of anti-VEGF therapy in patients with PCV. This limited evidence suggests that current treatment regimens are similarly efficacious, though T&E aflibercept achieved superior outcomes when compared to bimonthly dosing or PRN in some individual studies. Further trials are needed to confirm or refute these findings.
Anti-Vascular Endothelial Growth Factor Treatment Compared with Steroid Treatment for Retinal Vein Occlusion: A Meta-Analysis
(2022-11) Patil, Nikhil S; Hatamnejad, Amin; Mihalache, Andrew; Popovic, Marko M; Kertes, Peter J; Muni, Rajeev H
Background: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) and steroid treatment are both used for macular edema (ME) secondary to retinal vein occlusion (RVO), however a continual reevaluation of their comparative efficacy is required. Objectives: This meta-analysis aimed to compare the efficacy and safety of intravitreal anti-VEGF agents and intravitreal steroids for the treatment of ME secondary to RVO. Methods: A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and the Cochrane Controlled Register of Trials for studies published between January 2005 and November 2021. Randomized controlled trials (RCTs) reporting on patients with ME secondary to RVO who were treated with intravitreal steroids or anti-VEGF agents were included. A random effects meta-analysis was performed. Results: 879 eyes from 11 RCTs were included. At the last study observation, intravitreal anti-VEGF agents were associated with a significantly better best corrected visual acuity (WMD = −0.14 logMAR, 95% CI = [−0.19, −0.09], p < 0.00001) and lower retinal thickness (WMD = −38.01 µm, 95% CI = [−56.17, −19.85], p < 0.0001) relative to intravitreal steroids. Similar findings were found at 3–12 month time points. Intravitreal anti-VEGF agents were associated with a significantly lower incidence of IOP-related adverse events (RR = 0.28, 95% CI = [0.15, 0.51], p < 0.0001), cataract development/progression (RR = 0.22, 95% CI = [0.09, 0.49], p = 0.0003), and conjunctival hemorrhage (RR = 0.52, 95% CI = [0.32, 0.86], p = 0.01). Conclusions: Our meta-analysis found superiority of intravitreal anti-VEGF agents relative to intravitreal steroids for the treatment of ME secondary to RVO with regards to visual acuity, anatomic outcomes, and safety endpoints.
Antithrombotic Management in Ischemic Stroke with Essential Thrombocythemia: Current Evidence and Dilemmas
(Karger, 2021-10) Das, Shubhabrata; Deb, Anasua; Pal, Tanmoy
Thrombotic diseases like ischemic stroke are common complications of essential thrombocythemia (ET) due to abnormal megakaryopoiesis and platelet dysfunction. Ischemic stroke in ET can occur as a result of both cerebral arterial and venous thrombosis. Management of ET is aimed at preventing vascular complications including thrombosis. Acute management of ischemic stroke in ET is the same as that in the general population without myeloproliferative disorders. However, an ET patient with ischemic stroke is at high risk for rethrombosis and is therefore additionally managed with cytoreductive therapy and antithrombotic agents. Given abnormal platelet production in ET, there is suboptimal suppression of platelets with the standard recommended dose of aspirin for cardiovascular (CV) prevention. Hence, for optimal CV protection in ET, low-dose aspirin is recommended twice daily in an arterial thrombotic disease like atherothrombotic ischemic stroke in presence of the following risk factors: age >60 years, Janus kinase2 V617F gene mutation, and presence of CV risk factors. In the presence of the same risk factors, concurrent antiplatelet and anticoagulant therapy is suggested for venous thrombosis. However, increased risk of bleeding with dual antithrombotic agents poses a significant challenge in their use in cerebral venous thromboembolism or atrial fibrillation in presence of the above-mentioned risk factors. We discuss these dilemmas regarding antithrombotic management in ischemic stroke in ET in this case-based review of literature in the light of current evidence.
The Association between Evidence-Based Healthcare Practices and Outcomes among Preterm Births in China
(2022-02) Jin, Di; Gu, Xinyue; Jiang, Siyuan; Wang, Yanchen; Yang, Tongling; Lu, Yulan; Cao, Yun; Lee, Shoo K; Wu, Hui
Introduction: Very preterm infants are at high risk of early death or severe brain injury, with potential for impaired long-term neurodevelopmental function and physical health. There are evidence-based healthcare practices that can reduce the incidence. Materials and Methods: Infants born at 24–316 weeks gestational age and admitted within 24 h to NICUs participating in the Chinese Neonatal Network in 2019 were included. We examined the association between 4 evidence-based practices: inborn (born in a tertiary hospital in the Chinese Neonatal Network), ACS (any antenatal corticosteroid), MgSO4 (prenatal magnesium sulfate), and NT (normothermic temperature [36.0–37.5°C] at admission) and early death and/or severe brain injury in the study population. Results: Of 6,035 eligible infants, the incidence of early death and/or severe brain injury was 10.6%. Exposure to ACS only was associated with significant lower incidence of death and/or severe brain injury than none (aOR, 0.71; 95% CI: 0.57–0.88), but not MgSO4 only (aOR, 0.97; 95% CI: 0.81–1.17), NT only (aOR, 0.91; 95% CI: 0.76–1.08), or inborn only (aOR, 0.91; 95% CI: 0.72–1.15). The association between number of practices and incidence of early death and/or severe brain injury is as follows: none = 23% (31/138), any 1 = 14% (84/592), any 2 = 12% (185/1,538), any 3 = 9% (202/2,285), and all 4 = 9% (140/1,482). Discussion/Conclusion: More comprehensive use of evidence-based practices was associated with improved survival without severe brain injury among very preterm infants born at <32 weeks gestational age.
Association between Hidradenitis Suppurativa and Inflammatory Arthritis: A Systematic Review and Meta-Analysis
(2021-09) Almuhanna, Nouf; Finstad, Alexandra; Alhusayen, Raed
Background: Several studies report a high prevalence of inflammatory arthritis among hidradenitis suppurativa (HS) patients. Objectives: To study the association between HS and inflammatory arthritis. Methods: The systematic review and meta-analysis were performed according to the PRISMA guidelines to identify the association between HS and inflammatory arthritis, spondyloarthritis, ankylosing spondylitis (AS), and rheumatoid arthritis (RA). Results: Seven studies were entered in the analysis, with 200,361 HS patients and 385,599 controls. Pooled analysis illustrated a significantly increased risk of inflammatory arthritis in HS patients compared to controls (odds ratio [OR] 3.44; 95% confidence interval [CI] 1.92–6.17). There was also a statistically significant association between HS and spondyloarthritis (OR 2.10; 95% CI 1.40–3.15), and between HS and AS (OR 1.89; 95% CI 1.14–3.12). Moreover, pooled analysis showed a statistically significant association between HS and RA (OR 1.96; 95% CI 1.28–2.98). Conclusions: Our findings show that HS patients have a 3-fold increased risk of developing inflammatory arthritis. HS patients are specifically at a higher risk for spondyloarthritis, its subtype AS, and RA.
The Association between Retinal Thickness Fluctuations and Visual Outcomes under Anti-Vascular Endothelial Growth Factor Therapy: A Systematic Review and Meta-Analysis
(Karger, 2024-10) Pandya, Bhadra; Mihalache, Andrew; Hatamnejad, Amin; Grad, Justin; Popovic, Marko M; Wong, David T W
Introduction: The objective of this study was to examine the association between retinal thickness (RT) fluctuations and best corrected visual acuity (BCVA) in eyes with neovascular AMD, macular edema secondary to RVO, and DME treated with anti-VEGF therapy. Methods: A systematic search of Ovid MEDLINE, EMBASE, and the Cochrane Library was performed from January 2006 to March 2024. Studies comparing visual or anatomic outcomes of patients treated with anti-VEGF therapy, stratified by magnitudes of RT fluctuation, were included. ROBINS-I and Cochrane RoB 2 tools were used to assess risk of bias, and certainty of evidence was evaluated with GRADE criteria. Meta-analysis was performed with a random-effects model. Primary outcomes were final BCVA and change in BCVA relative to baseline. Results: 15,725 articles were screened; 15 studies were identified in the systematic review and 5 studies were included in the meta-analysis. Final ETDRS VA was significantly worse in eyes with the highest level of RT fluctuation (weighted mean difference [WMD] = 7.86 letters; 95% CI, 4.97, 10.74; p < 0.00001; I2 = 81%; 3,136 eyes). RT at last observation was significantly greater in eyes with high RT fluctuations (WMD = −27.35 μm; 95% CI, −0.04, 54.75; p = 0.05; I2 = 88%; 962 eyes). Conclusions: Final visual outcome is associated with magnitude of RT fluctuation over the course of therapy. It is unclear whether minimizing RT fluctuations would help optimize visual outcomes in patients treated with anti-VEGF therapy. These findings are limited by a small set of studies, risk of bias, and considerable heterogeneity.
Atypical Central Retinal Artery Occlusion following COVID-19 Infection: A Case Report
(Karger, 2023-08-30) Heidarzadeh, Hamid Reza; Abrishami, Mojtaba; Motamed Shariati, Mehrdad; Ghavami Shahri, Seyed Hossein; Ansari Astaneh, Mohammad Reza
Herein, we report a patient with atypical central retinal artery occlusion (CRAO) following COVID-19 recovery. A 44-year-old male was referred to the emergency room with a history of diplopia and sudden-onset painless visual loss in his left eye. He had a history of 1-week hospitalization for severe COVID-19 infection with pneumonia 3 weeks before, with positive real-time reverse transcription polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a nasopharyngeal sample. His visual acuity in the left eye was light perception which became no light perception later. Relative afferent pupillary defect was positive in the left eye. He had anterior chamber and anterior vitreous cells due to spillover and white cotton-wool-like patches in the left eye. He was diagnosed with atypical CRAO with uveitis-like features. After 3 weeks, he developed neovascular glaucoma and was treated with panretinal photocoagulation. In conclusion, SARS-CoV-2-induced vasculopathy and hypercoagulopathy conditions may be involved in the progression of CRAO in our patient. COVID-19 could be a considerable predisposing factor for CRAO.
Bacterial Skin Dysbiosis in Darier Disease
(Karger, 2024-06) Reiter, Ofer; Leshem, Avner; Alexander-Shani, Rivka; Brandwein, Michael; Cohen, Yotam; Yeshurun, Algit; Ziv, Michael; Elinav, Eran; Hodak, Emmilia; Dodiuk-Gad, Roni P
Introduction: Darier disease is a rare inherited disease with dominant skin manifestations including keratotic papules and plaques on sebaceous and flexural areas. Secondary infection of skin lesions is common, and Staphylococcus aureus commonly colonizes these lesions. The aim of the study was to characterize the bacterial microbiome of cutaneous Darier lesions compared to normal-looking skin and disease severity. Methods: All patients with a history of Darier followed up at Emek Medical Center were invited to participate in the study. Patients that did not use antibiotics in the past month and signed informed consent had four skin sites sampled with swabs: scalp, chest, axilla, and palm. All samples were analyzed for bacterial microbiome using 16S rDNA sequencing. Results: Two hundred and eighty microbiome samples obtained from lesional and non-lesional skin of the scalp, chest, axilla, and palm of 42 Darier patients were included in the analysis. The most abundant bacterial genera across all skin sites were Propionibacterium, Corynebacterium, Paracoccus, Micrococcus, and Anaerococcus. Scalp and chest lesions featured a distinct microbiome configuration that was mainly driven by an overabundance of Staphylococci species. Patients with more severe disease exhibited microbiome alterations in the chest, axilla, and palm compared with patients with only mild disease, driven by Peptoniphilus and Moryella genera in scalp and palmar lesions, respectively. Conclusion:Staphylococci were significantly associated with Darier lesions and drove Darier-associated dysbiosis. Severity of the disease was associated with two other bacterial genera. Whether these associations also hold a causative role and may serve as a therapeutic target remains to be determined and requires further investigation.
Benzodiazepine Use and Morbidity-Mortality Outcomes in a Geriatric Palliative Care Unit: A Retrospective Review
(Karger, 2021-03) Senderovich, Helen; Gardner, Sandra; Berall, Anna; Ganion, Michael; Zhang, Dennis; Vinoraj, Danusha; Waicus, Sarah
Introduction: Patients often experience delirium at the end of life. Benzodiazepine use may be associated with an increased risk of developing delirium. Alternate medications used in conjunction with benzodiazepines may serve as an independent precipitant of delirium. The aim is to understand the role of benzodiazepines in precipitating delirium and advanced mortality in palliative care population at the end of life. Methods: A retrospective medical chart review was conducted at a hospice and palliative care inpatient unit between the periods of June 2017–December 2017 and October 2017–November 2018. It included patients in hospice and palliative care inpatient units who received a benzodiazepine and those who did not. Patient characteristics, as well as Palliative Performance Scale score, diagnosis, and occurrence of admission, terminal, and/or recurrent delirium, were collected and analyzed. Results: Use of a benzodiazepine was not significantly associated with overall mortality nor cause-specific death without terminal delirium rate. However, it was significantly associated with higher cause-specific death with terminal delirium rate and a higher recurrent delirium rate. Discussion: This retrospective chart review suggests an association between benzodiazepine use and specific states of delirium and cause-specific death. However, it does not provide strong evidence on the use of this drug, especially at the end of life, as it pertains to the overall mortality rate. Suggested is a contextual approach to the use of benzodiazepines and the need to consider Palliative Performance Scale score and goals of care in the administration of this drug at varying periods during patient length of stay.
Bisphenol A Induces Agrp Gene Expression in Hypothalamic Neurons through a Mechanism Involving ATF3
(Karger, 2021-06-23) Loganathan, Neruja; McIlwraith, Emma K; Belsham, Denise D
Background: Bisphenol A (BPA) is a ubiquitous endocrine disrupting chemical and obesogen. Although limited evidence exists of the effects of BPA on hypothalamic agouti- related peptide (AgRP) levels, the mechanisms underlying these effects remain unknown. Given that AgRP is a potent orexigenic neuropeptide, determining the mechanism by which BPA increases AgRP is critical to preventing the progression to metabolic disease. Methods: Using quantitative reverse transcriptase polymerase chain reaction, we investigated the response of Agrp-expressing mouse hypothalamic cell lines to BPA treatment. The percentage of total BPA entering hypothalamic cells in culture was quantified using an enzyme-linked immunosorbent assay. In order to identify the mechanism underlying BPA-mediated changes in Agrp, siRNA knockdown of transcription factors, FOXO1, CHOP, ATF3, ATF4, ATF6, and small-molecule inhibitors of endoplasmic reticulum stress, JNK or MEK/ERK were used. Results: BPA increased mRNA levels of Agrp in six hypothalamic cell lines (mHypoA-59, mHypoE-41, mHypoA-2/12, mHypoE-46, mHypoE-44, and mHypoE-42). Interestingly, only 18% of the total BPA in the culture medium entered the cells after 24 h, suggesting that the exposure concentration is much lower than the treatment concentration. BPA increased pre-Agrp mRNA levels, indicating increased Agrp transcription. Knockdown of the transcription factor ATF3 prevented BPA-mediated increase in Agrp, pre-Agrp, and in part Npy mRNA levels. However, chemical chaperone, sodium phenylbutyrate, JNK inhibitor, SP600125, or the MEK/ERK inhibitor PD0352901 did not block BPA-induced Agrp upregulation. Conclusion: Overall, these results indicate that hypothalamic Agrp is susceptible to dysregulation by BPA and implicate ATF3 as a common mediator of the orexigenic effects of BPA in hypothalamic neurons.
Book Review - Fast Facts: Digital Medicine - Measurement
(Karger, 2020-07-02) Kapur, Ritu
Brain Structures and Networks Underlying Treatment Response to Deep Brain Stimulation Targeting the Inferior Thalamic Peduncle in Obsessive-Compulsive Disorder
(2022) Germann, Jürgen; Boutet, Alexandre; Elias, Gavin J B; Gouveia, Flavia Venetucci; Loh, Aaron; Giacobbe, Peter; Bhat, Venkat; Kucharczyk, Walter; Lozano, Andres M
Background: Obsessive-compulsive disorder (OCD) is a debilitating disease with a lifetime prevalence of 2–3%. Neuromodulatory treatments have been successfully used in severe cases. Deep brain stimulation (DBS) targeting the inferior thalamic peduncle (ITP) has been shown to successfully alleviate symptoms in OCD patients; however, the brain circuits implicated remain unclear. Here, we investigate the efficacious neural substrates following ITP-DBS for OCD. Methods: High-quality normative structural and functional connectomics and voxel-wise probabilistic mapping techniques were applied to assess the neural substrates of OCD symptom alleviation in a cohort of 5 ITP-DBS patients. Results: The region of most efficacious stimulation was located in the regions of the ITP and bed nucleus of the stria terminalis. Both functional and structural connectomics analyses demonstrated that successful symptom alleviation involved a brain network encompassing the bilateral amygdala and prefrontal regions. Limitations: The main limitation is the small size of the ITP-DBS cohort. While the findings are highly consistent and significant, these should be validated in larger studies. Conclusions: These results identify a tripartite brain network – composed of the bilateral amygdala and prefrontal regions 24 and 46 – whose engagement is associated with greater symptom improvement. They also provide information for optimizing targeting and identifying network components critically involved in ITP-DBS treatment response. Amygdala engagement in particular seems to be a key component for clinical benefits and could constitute a biomarker for treatment optimization.
Bringing the "Place" to Life-Space in Gerontology Research
(Karger, 2021-06) Bayat, Sayeh; Widener, Michael J; Mihailidis, Alex
Understanding older adults' relationships with their environments and the way this relationship evolves over time have been increasingly acknowledged in gerontological research. This relationship is often measured in terms of life-space, defined as the spatial area through which a person moves within a specific period of time. Life-space is traditionally reported using questionnaires or travel diaries and is, thus, subject to inaccuracies. More recently, studies are using a global positioning system to accurately measure life-space. Although life-space provides useful insights into older adults' relationships with their environment, it does not capture the inherent complexities of environmental exposures. In the fields of travel behaviour and health geography, a substantial amount of research has looked at people's spatial behaviour using the notion of "Activity Space," allowing for increasing sophistication in understanding older adults' experience of their environment. This manuscript discusses developments and directions for extending the life-space framework in environmental gerontology by drawing on the advancements in the activity space framework.
Cannabis-Induced Gastrointestinal Tract Symptoms in the Adult Population: A Systematic Review
(Karger, 2024) Senderovich, Helen; Meaney, Christopher; Vashishtha, Srishti
Cannabinoid usage is widespread in the self-management of various medical ailments. However, adverse effects have been reported with use, especially pertaining to the gastrointestinal system in adults and aged patients. These range from nausea, vomiting, bloating, or abdominal pain. This systematic review of previously reported cannabis-induced gastrointestinal symptoms in the adult population from the literature provides an analysis of relevant data to enhance knowledge and awareness of this topic.

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