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  1. AU="Sanchez-Hernandez, A."
  2. AU="Schneemann, Andreas"
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  1. Article: Formalin fixation and paraffin embedding interfere with the preservation of optical metabolic assessments based on endogenous NAD(P)H and FAD two-photon excited fluorescence.

    Sánchez-Hernández, Adriana / Polleys, Christopher M / Georgakoudi, Irene

    Biomedical optics express

    2023  Volume 14, Issue 10, Page(s) 5238–5253

    Abstract: Endogenous NAD(P)H and FAD two-photon excited fluorescence (TPEF) images provide functional metabolic information with high spatial resolution for a wide range of living specimens. Preservation of metabolic function optical metrics upon fixation would ... ...

    Abstract Endogenous NAD(P)H and FAD two-photon excited fluorescence (TPEF) images provide functional metabolic information with high spatial resolution for a wide range of living specimens. Preservation of metabolic function optical metrics upon fixation would facilitate studies which assess the impact of metabolic changes in the context of numerous diseases. However, robust assessments of the impact of formalin fixation, paraffin embedding, and sectioning on the preservation of optical metabolic readouts are lacking. Here, we evaluate intensity and lifetime images at excitation/emission settings optimized for NAD(P)H and FAD TPEF detection from freshly excised murine oral epithelia and corresponding bulk and sectioned fixed tissues. We find that fixation impacts the overall intensity as well as the intensity fluctuations of the images acquired. Accordingly, the depth-dependent variations of the optical redox ratio (defined as FAD/(NAD(P)H + FAD)) across squamous epithelia are not preserved following fixation. This is consistent with significant changes in the 755 nm excited spectra, which reveal broadening upon fixation and additional distortions upon paraffin embedding and sectioning. Analysis of fluorescence lifetime images acquired for excitation/emission settings optimized for NAD(P)H TPEF detection indicate that fixation alters the long lifetime of the observed fluorescence and the long lifetime intensity fraction. These parameters as well as the short TPEF lifetime are significantly modified upon embedding and sectioning. Thus, our studies highlight that the autofluorescence products formed during formalin fixation, paraffin embedding and sectioning overlap highly with NAD(P)H and FAD emission and limit the potential to utilize such tissues to assess metabolic activity.
    Language English
    Publishing date 2023-09-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2572216-5
    ISSN 2156-7085
    ISSN 2156-7085
    DOI 10.1364/BOE.498297
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Formalin fixation and paraffin embedding interfere with preservation of optical metabolic assessments based on endogenous NAD(P)H and FAD two photon excited fluorescence.

    Sánchez-Hernández, Adriana / Polleys, Christopher M / Georgakoudi, Irene

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Endogenous NAD(P)H and FAD two-photon excited fluorescence (TPEF) images provide functional metabolic information with high spatial resolution for a wide range of living specimens. Preservation of metabolic function optical metrics upon fixation would ... ...

    Abstract Endogenous NAD(P)H and FAD two-photon excited fluorescence (TPEF) images provide functional metabolic information with high spatial resolution for a wide range of living specimens. Preservation of metabolic function optical metrics upon fixation would facilitate studies which assess the impact of metabolic changes in the context of numerous diseases. However, robust assessments of the impact of formalin fixation, paraffin embedding, and sectioning on the preservation of optical metabolic readouts are lacking. Here, we evaluate intensity and lifetime images at excitation/emission settings optimized for NAD(P)H and FAD TPEF detection from freshly excised murine oral epithelia and corresponding bulk and sectioned fixed tissues. We find that fixation impacts the overall intensity as well as the intensity fluctuations of the images acquired. Accordingly, the depth-dependent variations of the optical redox ratio (defined as FAD/(NAD(P)H + FAD)) across squamous epithelia are not preserved following fixation. This is consistent with significant changes in the 755 nm excited spectra, which reveal broadening upon fixation and additional distortions upon paraffin embedding and sectioning. Analysis of fluorescence lifetime images acquired for excitation/emission settings optimized for NAD(P)H TPEF detection indicate that fixation alters the long lifetime of the observed fluorescence and the long lifetime intensity fraction. These parameters as well as the short TPEF lifetime are significantly modified upon embedding and sectioning. Thus, our studies highlight that the autofluorescence products formed during formalin fixation, paraffin embedding and sectioning overlap highly with NAD(P)H and FAD emission and limit the potential to utilize such tissues to assess metabolic activity.
    Language English
    Publishing date 2023-06-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.06.16.545363
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Redefining QRS transition to confirm left bundle branch capture during left bundle branch area pacing.

    Briongos-Figuero, Sem / Estévez Paniagua, Álvaro / Sánchez Hernández, Ana / Muñoz-Aguilera, Roberto

    Frontiers in cardiovascular medicine

    2023  Volume 10, Page(s) 1217133

    Abstract: Background: QRS transition criteria during dynamic manoeuvers are the gold-standard for non-invasive confirmation of left bundle branch (LBB) capture, but they are seen in <50% of LBB area pacing (LBBAP) procedures.: Objective: We hypothesized that ... ...

    Abstract Background: QRS transition criteria during dynamic manoeuvers are the gold-standard for non-invasive confirmation of left bundle branch (LBB) capture, but they are seen in <50% of LBB area pacing (LBBAP) procedures.
    Objective: We hypothesized that transition from left ventricular septal pacing (LVSP) to LBB pacing (LBBP), when observed during lead penetration into the deep interventricular septum (IVS) with interrupted pacemapping, can suggest LBB capture.
    Methods: QRS transition during lead screwing-in was defined as shortening of paced V6-R wave peak time (RWPT) by ≥10 ms from LVSP to non-selective LBBP (ns-LBBP) obtained during mid to deep septal lead progression at the same target area, between two consecutive pacing manoeuvres. ECG-based criteria were used to compared LVSP and ns-LBBP morphologies obtained by interrupted pacemapping.
    Results: Sixty patients with demonstrated transition from LVSP to ns-LBBP during dynamic manoeuvers were compared to 44 patients with the same transition during lead screwing-in. Average shortening in paced V6-RWPT was similar among study groups (17.3 ± 6.8 ms vs. 18.8 ± 4.9 ms for transition during dynamic manoeuvres and lead screwing-in, respectively;
    Conclusions: During LBBAP procedure, QRS transition from LVSP to ns-LBBP can be observed as the lead penetrates deep into the IVS with interrupted pacemapping. Shortening of at least 10 ms in paced V6-RWPT may serve as marker of LBB capture.
    Language English
    Publishing date 2023-07-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2781496-8
    ISSN 2297-055X
    ISSN 2297-055X
    DOI 10.3389/fcvm.2023.1217133
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Combination of current and new electrocardiographic-based criteria: a novel score for the discrimination of left bundle branch capture.

    Briongos-Figuero, Sem / Estévez-Paniagua, Álvaro / Sánchez-Hernández, Ana / Muñoz-Aguilera, Roberto

    Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology

    2023  Volume 25, Issue 3, Page(s) 1051–1059

    Abstract: Aims: Most of the criteria used to diagnose direct capture of the left bundle branch (LBB) have never been validated in an external sample. We hypothesized that lead aVL might add relevant information, and the combination of several electrocardiograph ( ... ...

    Abstract Aims: Most of the criteria used to diagnose direct capture of the left bundle branch (LBB) have never been validated in an external sample. We hypothesized that lead aVL might add relevant information, and the combination of several electrocardiograph (ECG)-based criteria might discriminate better LBB capture from left ventricular septal (LVS) capture, than each criterion separately.
    Methods and results: Single-centre study involving all consecutive patients who received LBB area pacing. LBB capture was defined according to QRS morphology transition criteria during decremental pacing. Multivariate logistic regression analysis was performed to develop a predictive score for LBB capture. A total of 71 patients with confirmed LBB capture were analysed. The optimal cut-off values of R wave peak time (RWPT) in lead V6 (V6-RWPT) and V6-V1 interpeak interval for the discrimination of LBB capture were <83 ms and ≥33 ms, respectively. The RWPT in lead aVL (aVL-RWPT) showed a good discrimination power for the differential diagnosis of LBB capture and LVS capture. The optimal value for aVL-RWPT was 79 ms [sensitivity (SN) and specificity (SP) of 71.2% and 88.4%, respectively]. A new score, with a good diagnostic performance (area under the curve of 0.976), was constructed gathering the information from V6-RWPT, aVL-RWPT, and V6-V1 interpeak interval. The optimal score of 3 points showed a SN and SP of 89.2% and 100%, respectively for the differentiation of LBB capture.
    Conclusions: ECG-based criteria are useful to confirm the capture of the LBB. The combination of V6-RWPT, aVL-RWPT, and V6-V1 interpeak interval values demonstrated better diagnostic performance than isolated measurements.
    MeSH term(s) Humans ; Heart Conduction System ; Electrocardiography/methods ; Ventricular Septum ; Sensitivity and Specificity ; Bundle of His ; Cardiac Pacing, Artificial
    Language English
    Publishing date 2023-05-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 1449879-0
    ISSN 1532-2092 ; 1099-5129
    ISSN (online) 1532-2092
    ISSN 1099-5129
    DOI 10.1093/europace/euac276
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Simultaneous determination of favipiravir and surrogates of its metabolites by means of heart-cutting bidimensional liquid chromatography (2D-LC).

    Sánchez-Hernández, Aitana / García-Gómez, Diego / Pérez Pavón, José Luis / Rodríguez-Gonzalo, Encarnación

    Analytical biochemistry

    2023  Volume 684, Page(s) 115375

    Abstract: Therapeutic monitoring of drugs, particularly those with multiple metabolites, can be time-consuming and labor-intensive due to the need for different analytical methods depending on the specific metabolite or matrix of interest. In this study, we ... ...

    Abstract Therapeutic monitoring of drugs, particularly those with multiple metabolites, can be time-consuming and labor-intensive due to the need for different analytical methods depending on the specific metabolite or matrix of interest. In this study, we employed a heart-cutting 2D-LC separation method based on the coupling of reversed-phase and mixed-mode mechanisms to determine Favipiravir and surrogates of five main metabolites. This approach was applied to serum, plasma, urine, and human peripheral blood mononuclear cells. The method underwent validation to ensure its reliability. The findings highlight the potential of 2D-LC as a practical and efficient approach for therapeutic drug monitoring.
    MeSH term(s) Humans ; Reproducibility of Results ; Leukocytes, Mononuclear ; Chromatography, Liquid/methods
    Chemical Substances favipiravir (EW5GL2X7E0)
    Language English
    Publishing date 2023-11-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1110-1
    ISSN 1096-0309 ; 0003-2697
    ISSN (online) 1096-0309
    ISSN 0003-2697
    DOI 10.1016/j.ab.2023.115375
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Quality indicators and excellence requirements for a multidisciplinary lung cancer tumor board by the Spanish Lung Cancer Group.

    Guirado, M / Sanchez-Hernandez, A / Pijuan, L / Teixido, C / Gómez-Caamaño, A / Cilleruelo-Ramos, Á

    Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico

    2021  Volume 24, Issue 3, Page(s) 446–459

    Abstract: Multidisciplinary care is needed to decide the best therapeutic approach and to provide optimal care to patients with lung cancer (LC). Multidisciplinary teams (MDTs) are optimal strategies for the management of patients with LC and have been associated ... ...

    Abstract Multidisciplinary care is needed to decide the best therapeutic approach and to provide optimal care to patients with lung cancer (LC). Multidisciplinary teams (MDTs) are optimal strategies for the management of patients with LC and have been associated with better outcomes, such as an increase in quality of life and survival. The Spanish Lung Cancer Group has promoted this review about the current situation of the existing national LC-MDTs, which also offers a set of excellence requirements and quality indicators to achieve the best care in any patient with LC. Time and sufficient resources; leadership; administrative and institutional support; and recording of activity are key factors for the success of LC-MDTs. A set of excellence requirements in terms of staff, resources and organization of the LC-MDT have been proposed. At last, a list of quality indicators has been agreed to achieve and measure the performance of current LC-MDTs.
    MeSH term(s) Humans ; Lung Neoplasms/therapy ; Patient Care Team ; Quality Indicators, Health Care ; Spain
    Language English
    Publishing date 2021-10-19
    Publishing country Italy
    Document type Journal Article ; Review
    ZDB-ID 2397359-6
    ISSN 1699-3055 ; 1699-048X
    ISSN (online) 1699-3055
    ISSN 1699-048X
    DOI 10.1007/s12094-021-02712-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Role of Perineuronal nets in the cerebellar cortex in cocaine-induced conditioned preference, extinction, and reinstatement.

    Guarque-Chabrera, Julian / Sanchez-Hernandez, Aitor / Ibáñez-Marín, Patricia / Melchor-Eixea, Ignasi / Miquel, Marta

    Neuropharmacology

    2022  Volume 218, Page(s) 109210

    Abstract: Perineuronal nets (PNNs) are cartilage-like structures of extracellular matrix molecules that enwrap in a net-like manner the cell-body and proximal dendrites of special subsets of neurons. PNNs stabilize their incoming connections and restrict ... ...

    Abstract Perineuronal nets (PNNs) are cartilage-like structures of extracellular matrix molecules that enwrap in a net-like manner the cell-body and proximal dendrites of special subsets of neurons. PNNs stabilize their incoming connections and restrict plasticity. Consequently, they have been proposed as a candidate mechanism for drug-induced learning and memory. In the cerebellum, PNNs surround Golgi inhibitory interneurons and both inhibitory and excitatory neurons in the deep cerebellar nuclei (DCN). Previous studies from the lab showed that cocaine-induced conditioned memory increased PNN expression in the granule cell layer of the posterior vermis. The present research aimed to investigate the role of cerebellar PNNs in cocaine-induced conditioned preference. For this purpose, we use the enzyme chondroitinase ABC (ChABC) to digest PNNs at different time points of the learning process to ascertain whether their removal can affect drug-induced memory. Our results show that PNN digestion using ChABC in the posterior vermis (Lobule VIII) did not affect the acquisition of cocaine-induced conditioned preference. However, the removal of PNNs in Lobule VIII -but not in the DCN- disrupted short-term memory of conditioned preference. Moreover, although PNN digestion facilitated the formation of extinction, reinstatement of cocaine-induced conditioned preference was encouraged under PNN digestion. The present findings suggests that PNNs around Golgi interneurons are needed to maintain cocaine-induced Pavlovian memory but also to stabilize extinction memory. Conversely, PNN degradation within the DCN did not affect stability of cocaine-induced memories. Therefore, degradation of PNNs in the vermis might be used as a promising tool to manipulate drug-induced memory.
    MeSH term(s) Cerebellar Cortex ; Cerebellum/metabolism ; Chondroitin ABC Lyase/metabolism ; Chondroitin ABC Lyase/pharmacology ; Cocaine/metabolism ; Cocaine/pharmacology ; Extracellular Matrix/metabolism ; Neurons/metabolism
    Chemical Substances Chondroitin ABC Lyase (EC 4.2.2.20) ; Cocaine (I5Y540LHVR)
    Language English
    Publishing date 2022-08-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218272-5
    ISSN 1873-7064 ; 0028-3908
    ISSN (online) 1873-7064
    ISSN 0028-3908
    DOI 10.1016/j.neuropharm.2022.109210
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Clinical impact of delays in the management of lung cancer patients in the last decade: systematic review.

    Guirado, María / Fernández Martín, Elena / Fernández Villar, Alberto / Navarro Martín, Arturo / Sánchez-Hernández, Alfredo

    Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico

    2022  Volume 24, Issue 8, Page(s) 1549–1568

    Abstract: Introduction: Due to the importance of lung cancer early treatment because of its severity and extent worldwide a systematic literature review was conducted about the impact of delays in waiting times on the disease prognosis.: Materials and methods: ...

    Abstract Introduction: Due to the importance of lung cancer early treatment because of its severity and extent worldwide a systematic literature review was conducted about the impact of delays in waiting times on the disease prognosis.
    Materials and methods: We conducted a systematic search of observational studies (2010-2020) including adult patients diagnosed with lung cancer and reporting healthcare timelines and their clinical consequences.
    Results: We included 38 articles containing data on waiting times and prognosis; only 31 articles linked this forecast to a specific waiting time. We identified 41 healthcare time intervals and found medians of 6-121 days from diagnosis to treatment and 4-19.5 days from primary care to specialist visit: 37.5% of the intervals indicated better prognosis with longer waiting times.
    Conclusions: All articles emphasized that waiting times must be reduced to achieve good management and prognosis of lung cancer. Further prospective studies are needed on the relationship between waiting times and prognosis of lung cancer.
    MeSH term(s) Adult ; Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/therapy ; Prognosis ; Prospective Studies ; Time-to-Treatment
    Language English
    Publishing date 2022-03-07
    Publishing country Italy
    Document type Journal Article ; Review ; Systematic Review
    ZDB-ID 2397359-6
    ISSN 1699-3055 ; 1699-048X
    ISSN (online) 1699-3055
    ISSN 1699-048X
    DOI 10.1007/s12094-022-02796-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Putting forward a model for the role of the cerebellum in cocaine-induced pavlovian memory.

    Melchor-Eixea, Ignasi / Guarque-Chabrera, Julian / Sanchez-Hernandez, Aitor / Ibáñez-Marín, Patricia / Pastor, Raúl / Miquel, Marta

    Frontiers in systems neuroscience

    2023  Volume 17, Page(s) 1154014

    Abstract: Substance Use Disorder (SUD) involves emotional, cognitive, and motivational dysfunction. Long-lasting molecular and structural changes in brain regions functionally and anatomically linked to the cerebellum, such as the prefrontal cortex, amygdala, ... ...

    Abstract Substance Use Disorder (SUD) involves emotional, cognitive, and motivational dysfunction. Long-lasting molecular and structural changes in brain regions functionally and anatomically linked to the cerebellum, such as the prefrontal cortex, amygdala, hippocampus, basal ganglia, and ventral tegmental area, are characteristic of SUD. Direct and indirect reciprocal connectivity between the cerebellum and these brain regions can explain cerebellar roles in Pavlovian and reinforcement learning, fear memory, and executive functions. It is increasingly clear that the cerebellum modulates brain functions altered in SUD and other neuropsychiatric disorders that exhibit comorbidity with SUD. In the present manuscript, we review and discuss this evidence and present new research exploring the role of the cerebellum in cocaine-induced conditioned memory using chemogenetic tools (designer receptor exclusively activated by designer drug, DREADDs). Our preliminary data showed that inactivation of a region that includes the interposed and lateral deep cerebellar nuclei reduces the facilitating effect of a posterior vermis lesion on cocaine-induced preference conditioning. These findings support our previous research and suggest that posterior vermis damage may increase drug impact on the addiction circuitry by regulating activity in the DCN. However, they raise further questions that will also be discussed.
    Language English
    Publishing date 2023-06-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2453005-0
    ISSN 1662-5137
    ISSN 1662-5137
    DOI 10.3389/fnsys.2023.1154014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Von Recklinghausen disease associated with colon cancer: Dangerous friendships.

    Sánchez Hernández, A / López-Caleya, J F / Viñuela Díaz-Moro, I

    Revista clinica espanola

    2018  Volume 219, Issue 1, Page(s) 55–56

    Title translation Enfermedad de von Recklinghausen asociada a cáncer de colon: amistades peligrosas.
    Language Spanish
    Publishing date 2018-06-11
    Publishing country Spain
    Document type Journal Article
    ISSN 2254-8874
    ISSN (online) 2254-8874
    DOI 10.1016/j.rce.2018.04.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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