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Article ; Online: Ventral Hippocampal Input to Infralimbic Cortex Is Necessary for the Therapeutic-Like Effects of Extinction in Stressed Rats.

Paredes, Denisse / Morilak, David A

The international journal of neuropsychopharmacology

2023 Volume 26, Issue 8, Page(s) 529–536

Abstract: Background: Posttraumatic stress disorder is characterized by deficits in cognitive flexibility related to dysfunction of the medial prefrontal cortex (mPFC). Exposure therapy can effectively reverse these deficits. Fear extinction in rodents bears ... ...

Abstract	Background: Posttraumatic stress disorder is characterized by deficits in cognitive flexibility related to dysfunction of the medial prefrontal cortex (mPFC). Exposure therapy can effectively reverse these deficits. Fear extinction in rodents bears similarity to exposure therapy. Extinction reverses chronic stress-induced deficits in cognitive flexibility on the attentional set-shifting test (AST), an mPFC-mediated process. This therapeutic effect requires activity of pyramidal neurons and brain derived neurotrophic factor (BDNF) signaling in infralimbic cortex (IL). However, the circuit mechanisms governing BDNF-mediated plasticity initiated by extinction in IL are unknown. The ventral hippocampus (vHipp) plays a role in regulating IL activity during extinction, and plasticity in vHipp is necessary for extinction memory consolidation. Therefore, we investigated the role of vHipp input to IL in the effects of extinction in reversing stress-induced cognitive deficits. Methods: vHipp input to IL was silenced using a Gi-Designer Receptors Exclusively Activated by Designer Drugs (DREADD) via local infusion of clozapine-N-oxide (CNO) into IL before extinction. A day later, rats were tested on AST. In a separate experiment, we tested whether vHipp input to the IL induces BDNF signaling to exert therapeutic effects. We activated the vHipp using a Gq-DREADD, and injected an anti-BDNF neutralizing antibody into IL. Rats were tested on the AST 24 hours later. Results: Silencing the vHipp input to IL prevented the beneficial effects of extinction in reversing stress-induced cognitive deficits. Activating vHipp input to IL in the absence of extinction was sufficient to reverse stress-induced deficits in set-shifting. The beneficial effects were blocked by local infusion of a neutralizing anti-BDNF antibody into IL. Conclusions: vHipp-driven BDNF signaling in IL is critical for extinction to counteract the deleterious cognitive effects of chronic stress.
MeSH term(s)	Rats ; Animals ; Extinction, Psychological ; Fear ; Cerebral Cortex ; Hippocampus ; Pyramidal Cells
Language	English
Publishing date	2023-07-21
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1440129-0
ISSN	1469-5111 ; 1461-1457
ISSN (online)	1469-5111
ISSN	1461-1457
DOI	10.1093/ijnp/pyad043
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Article ; Online: Empathy in family medicine postgraduate education: A mixed studies systematic review.

Ortiz-Paredes, David / Adam Henet, Peterson / Desseilles, Martin / Rodríguez, Charo

Medical teacher

2024 , Page(s) 1–17

Abstract: Purpose: Empathy is an important construct in patient-physician relationships, particularly critical in family physicians' daily practice. We aimed to understand how empathy has been conceived and integrated into family medicine postgraduate training.!## ...

Abstract	Purpose: Empathy is an important construct in patient-physician relationships, particularly critical in family physicians' daily practice. We aimed to understand how empathy has been conceived and integrated into family medicine postgraduate training. Materials and methods: Medline, PsyINFO, and Embase were searched in this systematic mixed studies systematic review. Two independent reviewers screened abstracts and full texts. Disagreements were solved through research team consensus-based discussion. Included studies were synthesized thematically. Results: A total of 18 studies were included. Four themes were identified. Conclusions: Studies mostly measured the cognitive component of empathy. The moral component of empathy was underrepresented in the conceptualization of empathy and the development of educational interventions. Conflicting evidence exists regarding the decline of empathy levels during the family medicine residency. Longitudinal designs should be privileged when exploring the evolution of empathy levels across the continuum of medical education.
Language	English
Publishing date	2024-03-31
Publishing country	England
Document type	Journal Article
ZDB-ID	424426-6
ISSN	1466-187X ; 0142-159X
ISSN (online)	1466-187X
ISSN	0142-159X
DOI	10.1080/0142159X.2024.2328324
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Article ; Online: 15-min Cities: the Potential of a Medium-Sized Polycentric Latin American City.

Urrutia-Mosquera, Jorge / Flórez-Calderón, Luz / Paredes, Dusan

Journal of urban health : bulletin of the New York Academy of Medicine

2023 Volume 100, Issue 4, Page(s) 725–744

Abstract: Urban sustainability and sustainable mobility have become the central focus of sustainable development initiatives. The city of 15 models seeks to ensure that urban development is sustainable. This paper evaluates the current state of mobility and the ... ...

Abstract	Urban sustainability and sustainable mobility have become the central focus of sustainable development initiatives. The city of 15 models seeks to ensure that urban development is sustainable. This paper evaluates the current state of mobility and the use of sustainable transport in the specific context of the city of Antofagasta, which, due to its characteristics of urban expansion and its mining activity, has been considered an international reference case. In particular, we study how the current urban structure shapes the city's travel patterns and identify opportunities for public policy actions to focus their investment and urban intervention efforts on the essential aspects that make it possible to achieve 15- or 20-min territories. The results reveal the need for urban development initiatives to focus on improving the supply of goods and services in areas with low installed capacity, promoting the culture of micro-neighbourhoods, and encouraging cycling. In particular, only 10% of trips, for all purposes and all modes of transport, are completed in less than 15 min. And about 58% of trips, for all purposes and all modes, are completed in less than 30 min. In the marginal effects of the multinomial logit model, a one-unit increase in travel time increases the probability of choosing to travel by public transport by 63% and decreases the probability of walking by 41%.
MeSH term(s)	Humans ; Cities ; Latin America ; Sustainable Growth ; Walking ; Transportation
Language	English
Publishing date	2023-08-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	1435288-6
ISSN	1468-2869 ; 1099-3460
ISSN (online)	1468-2869
ISSN	1099-3460
DOI	10.1007/s11524-023-00749-4
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Article ; Online: 'I created my own access:' understanding mental healthcare access experiences among LGTBQ + youth who use cannabis in Canada.

Ortiz-Paredes, David / Chanady, Tara / Wassef, Kinda / Knight, Rod / Ferlatte, Olivier

Culture, health & sexuality

2024 , Page(s) 1–20

Abstract: In North America, LGBTQ+ youth have high rates of cannabis use and face mental health issues. We conducted a photovoice study to describe the perspectives, needs, and motivations of forty-six LGBTQ+ youth who use cannabis as they access mental healthcare ...

Abstract	In North America, LGBTQ+ youth have high rates of cannabis use and face mental health issues. We conducted a photovoice study to describe the perspectives, needs, and motivations of forty-six LGBTQ+ youth who use cannabis as they access mental healthcare services. Participants' photographs were discussed in individual semi-structured interviews conducted by peer researchers. Following a thematic analysis of the interview transcripts, we first found that, beyond medication, LGBTQ+ youth sought mental health services facilitating introspection to better understand their sexual and gender identities and mental health. Second, participants sought affirming health professionals but often felt judged by providers. Third, access to desired services was often described as uncertain and taxing, which impacted their mental health. Fourth, participants' agency was determined by their experience with mental health services, which translated into resilience to tackle access challenges and cannabis use to mitigate their mental health struggles. Our findings point to the need for mental healthcare delivery that goes beyond medication provision but which in addition foster therapeutic processes based on a holistic understanding of mental health. A trusting dynamic between health professionals and LGBTQ+ youth is imperative to counteract the feelings of stigma experienced by LGBTQ+ youth using cannabis in Canada.
Language	English
Publishing date	2024-04-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2023577-X
ISSN	1464-5351 ; 1369-1058
ISSN (online)	1464-5351
ISSN	1369-1058
DOI	10.1080/13691058.2024.2340090
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Article: The causes and consequences of pest population variability in agricultural landscapes.

Paredes, Daniel / Rosenheim, Jay A / Karp, Daniel S

Ecological applications : a publication of the Ecological Society of America

2022 Volume 32, Issue 5, Page(s) e2607

Abstract: Variability in population densities is key to the ecology of natural systems but also has great implications for agriculture. Farmers' decisions are heavily influenced by their risk aversion to pest outbreaks that result in major yield losses. However, ... ...

Abstract	Variability in population densities is key to the ecology of natural systems but also has great implications for agriculture. Farmers' decisions are heavily influenced by their risk aversion to pest outbreaks that result in major yield losses. However, the need for long-term pest population data across many farms has prevented researchers from exploring the drivers and implications of pest population variability (PV). Here, we demonstrate the critical importance of PV for sustainable farming by analyzing 13 years of pest densities across >1300 Spanish olive groves and vineyards. Variable populations were more likely to cause major yield losses, but also occasionally created temporal windows when densities fell below insecticide spray thresholds. Importantly, environmental factors regulating pest variability were very distinct from factors regulating mean density, suggesting variability needs to be uniquely managed. Finally, we found diversifying landscapes may be a win-win situation for conservation and farmers, as diversified landscapes promote less abundant and less variable pest populations. Therefore, we encourage agricultural stakeholders to increase the complexity of the landscapes surrounding their farms through conserving/restoring natural habitat and/or diversifying crops.
MeSH term(s)	Agriculture ; Crops, Agricultural ; Ecosystem ; Farms ; Insecticides ; Pest Control, Biological
Chemical Substances	Insecticides
Language	English
Publishing date	2022-05-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1074505-1
ISSN	1939-5582 ; 1051-0761
ISSN (online)	1939-5582
ISSN	1051-0761
DOI	10.1002/eap.2607
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Article ; Online: The enzymatic properties of Arabidopsis thaliana DNA polymerase λ suggest a role in base excision repair.

Morales-Ruiz, T / Beltrán-Melero, C / Ortega-Paredes, D / Luna-Morillo, J A / Martínez-Macías, M I / Roldán-Arjona, T / Ariza, R R / Córdoba-Cañero, D

Plant molecular biology

2024 Volume 114, Issue 1, Page(s) 3

Abstract: Base excision repair (BER) generates gapped DNA intermediates containing a 5'-terminal 2-deoxyribose-5-phosphate (5'-dRP) group. In mammalian cells, gap filling and dRP removal are catalyzed by Pol β, which belongs to the X family of DNA polymerases. In ... ...

Abstract	Base excision repair (BER) generates gapped DNA intermediates containing a 5'-terminal 2-deoxyribose-5-phosphate (5'-dRP) group. In mammalian cells, gap filling and dRP removal are catalyzed by Pol β, which belongs to the X family of DNA polymerases. In higher plants, the only member of the X family of DNA polymerases is Pol λ. Although it is generally believed that plant Pol λ participates in BER, there is limited experimental evidence for this hypothesis. Here we have characterized the biochemical properties of Arabidopsis thaliana Pol λ (AtPol λ) in a BER context, using a variety of DNA repair intermediates. We have found that AtPol λ performs gap filling inserting the correct nucleotide, and that the rate of nucleotide incorporation is higher in substrates containing a C in the template strand. Gap filling catalyzed by AtPol λ is most efficient with a phosphate at the 5'-end of the gap and is not inhibited by the presence of a 5'-dRP mimic. We also show that AtPol λ possesses an intrinsic dRP lyase activity that is reduced by mutations at two lysine residues in its 8-kDa domain, one of which is present in Pol λ exclusively and not in any Pol β homolog. Importantly, we also found that the dRP lyase activity of AtPol λ allows efficient completion of uracil repair in a reconstituted short-patch BER reaction. These results suggest that AtPol λ plays an important role in plant BER.
MeSH term(s)	Animals ; Arabidopsis/genetics ; Arabidopsis/metabolism ; Excision Repair ; DNA-Directed DNA Polymerase/genetics ; DNA-Directed DNA Polymerase/chemistry ; DNA-Directed DNA Polymerase/metabolism ; DNA Repair ; Nucleotides ; Phosphates ; Mammals/metabolism ; DNA Polymerase beta
Chemical Substances	DNA polymerase beta2 (EC 2.7.7.-) ; DNA-Directed DNA Polymerase (EC 2.7.7.7) ; Nucleotides ; Phosphates ; DNA Polymerase beta (EC 2.7.7.7)
Language	English
Publishing date	2024-01-13
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	778032-1
ISSN	1573-5028 ; 0167-4412
ISSN (online)	1573-5028
ISSN	0167-4412
DOI	10.1007/s11103-023-01407-8
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Zs.A 3458: Show issues

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Article: The causes and consequences of pest population variability in agricultural landscapes

Paredes, Daniel / Rosenheim, Jay A. / Karp, Daniel S.

Ecological applications. 2022 July, v. 32, no. 5

2022

Abstract	Variability in population densities is key to the ecology of natural systems but also has great implications for agriculture. Farmers' decisions are heavily influenced by their risk aversion to pest outbreaks that result in major yield losses. However, the need for long‐term pest population data across many farms has prevented researchers from exploring the drivers and implications of pest population variability (PV). Here, we demonstrate the critical importance of PV for sustainable farming by analyzing 13 years of pest densities across >1300 Spanish olive groves and vineyards. Variable populations were more likely to cause major yield losses, but also occasionally created temporal windows when densities fell below insecticide spray thresholds. Importantly, environmental factors regulating pest variability were very distinct from factors regulating mean density, suggesting variability needs to be uniquely managed. Finally, we found diversifying landscapes may be a win–win situation for conservation and farmers, as diversified landscapes promote less abundant and less variable pest populations. Therefore, we encourage agricultural stakeholders to increase the complexity of the landscapes surrounding their farms through conserving/restoring natural habitat and/or diversifying crops.
Keywords	habitats ; insecticides ; olives ; pests ; risk ; stakeholders
Language	English
Dates of publication	2022-07
Publishing place	John Wiley & Sons, Inc.
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	1074505-1
ISSN	1939-5582 ; 1051-0761
ISSN (online)	1939-5582
ISSN	1051-0761
DOI	10.1002/eap.2607
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Infralimbic BDNF signaling is necessary for the beneficial effects of extinction on set shifting in stressed rats.

Paredes, Denisse / Knippenberg, Anna R / Morilak, David A

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2021 Volume 47, Issue 2, Page(s) 507–515

Abstract: Current pharmacotherapies for posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are ineffective for many patients, and often do not restore cognitive dysfunction associated with these disorders. Behavioral therapies, such as ... ...

Abstract	Current pharmacotherapies for posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are ineffective for many patients, and often do not restore cognitive dysfunction associated with these disorders. Behavioral therapies, such as exposure therapy, can be effective for treatment-resistant patients. The mechanisms underlying exposure therapy are not well-understood. Fear extinction as an intervention after chronic stress can model the beneficial effects of exposure therapy in rats. Extinction requires neuronal activity and protein synthesis in the infralimbic (IL) cortex for its beneficial effects. We hypothesized that extinction requires Brain-Derived Neurotrophic Factor (BDNF) activity in the IL cortex to reverse stress-induced cognitive flexibility impairments. Extinction learning reversed set-shifting deficits induced by Chronic Unpredictable Stress (CUS), tested 24 h after extinction. Blocking BDNF signaling in the IL cortex during extinction by local administration of a neutralizing antibody prevented the beneficial effects of extinction on set shifting after stress. Extinction induced activation of the BDNF TrkB receptor, and signaling pathways associated with BDNF (Akt and Erk). Administration of exogenous BDNF into IL cortex in the absence of extinction was sufficient to reverse the effects of stress on set shifting. The effects of extinction were prevented by blocking either Erk or Akt signaling in the IL cortex, whereas the effects of exogenous BDNF were dependent on Erk, but not Akt, signaling. Our observations suggest that BDNF-Erk signaling induced by extinction underlies plastic changes that can reverse or counteract the effects of chronic stress in the IL cortex.
MeSH term(s)	Animals ; Brain-Derived Neurotrophic Factor/metabolism ; Depressive Disorder, Major ; Extinction, Psychological ; Fear/physiology ; Implosive Therapy ; Rats
Chemical Substances	Bdnf protein, rat ; Brain-Derived Neurotrophic Factor
Language	English
Publishing date	2021-09-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/s41386-021-01171-7
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Zs.A 2379: Show issues

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Article ; Online: Translational considerations for the design of untethered nanomaterials in human neural stimulation.

Dominguez-Paredes, David / Jahanshahi, Ali / Kozielski, Kristen L

Brain stimulation

2021 Volume 14, Issue 5, Page(s) 1285–1297

Abstract: Neural stimulation is a powerful tool to study brain physiology and an effective treatment for many neurological disorders. Conventional interfaces use electrodes implanted in the brain. As these are often invasive and have limited spatial targeting, ... ...

Abstract	Neural stimulation is a powerful tool to study brain physiology and an effective treatment for many neurological disorders. Conventional interfaces use electrodes implanted in the brain. As these are often invasive and have limited spatial targeting, they carry a potential risk of side-effects. Smaller neural devices may overcome these obstacles, and as such, the field of nanoscale and remotely powered neural stimulation devices is growing. This review will report on current untethered, injectable nanomaterial technologies intended for neural stimulation, with a focus on material-tissue interface engineering. We will review nanomaterials capable of wireless neural stimulation, and discuss their stimulation mechanisms. Taking cues from more established nanomaterial fields (e.g., cancer theranostics, drug delivery), we will then discuss methods to modify material interfaces with passive and bioactive coatings. We will discuss methods of delivery to a desired brain region, particularly in the context of how delivery and localization are affected by surface modification. We will also consider each of these aspects of nanoscale neurostimulators with a focus on their prospects for translation to clinical use.
MeSH term(s)	Brain ; Electrodes ; Humans ; Nanostructures ; Nervous System Diseases
Language	English
Publishing date	2021-08-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2394410-9
ISSN	1876-4754 ; 1935-861X
ISSN (online)	1876-4754
ISSN	1935-861X
DOI	10.1016/j.brs.2021.08.001
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Article ; Online: Extracting Thyroid Nodules Characteristics from Ultrasound Reports Using Transformer-based Natural Language Processing Methods.

Pathak, Aman / Yu, Zehao / Paredes, Daniel / Monsour, Elio Paul / Rocha, Andrea Ortiz / Brito, Juan P / Ospina, Naykky Singh / Wu, Yonghui

AMIA ... Annual Symposium proceedings. AMIA Symposium

2024 Volume 2023, Page(s) 1193–1200

Abstract: The ultrasound characteristics of thyroid nodules guide the evaluation of thyroid cancer in patients with thyroid nodules. However, the characteristics of thyroid nodules are often documented in clinical narratives such as ultrasound reports. Previous ... ...

Abstract	The ultrasound characteristics of thyroid nodules guide the evaluation of thyroid cancer in patients with thyroid nodules. However, the characteristics of thyroid nodules are often documented in clinical narratives such as ultrasound reports. Previous studies have examined natural language processing (NLP) methods in extracting a limited number of characteristics (<9) using rule-based NLP systems. In this study, a multidisciplinary team of NLP experts and thyroid specialists, identified thyroid nodule characteristics that are important for clinical care, composed annotation guidelines, developed a corpus, and compared 5 state-of-the-art transformer-based NLP methods, including BERT, RoBERTa, LongFormer, DeBERTa, and GatorTron, for extraction of thyroid nodule characteristics from ultrasound reports. Our GatorTron model, a transformer-based large language model trained using over 90 billion words of text, achieved the best strict and lenient F1-score of 0.8851 and 0.9495 for the extraction of a total number of 16 thyroid nodule characteristics, and 0.9321 for linking characteristics to nodules, outperforming other clinical transformer models. To the best of our knowledge, this is the first study to systematically categorize and apply transformer-based NLP models to extract a large number of clinical relevant thyroid nodule characteristics from ultrasound reports. This study lays ground for assessing the documentation quality of thyroid ultrasound reports and examining outcomes of patients with thyroid nodules using electronic health records.
MeSH term(s)	Humans ; Thyroid Nodule/diagnostic imaging ; Natural Language Processing ; Electronic Health Records ; Ultrasonography ; Narration
Language	English
Publishing date	2024-01-11
Publishing country	United States
Document type	Journal Article
ISSN	1942-597X
ISSN (online)	1942-597X
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