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  1. Article ; Online: PIF-pocket as a target for C. albicans Pkh selective inhibitors.

    Pastor-Flores, Daniel / Schulze, Jörg O / Bahí, Anna / Giacometti, Romina / Ferrer-Dalmau, Jofre / Passeron, Susana / Engel, Matthias / Süss, Evelyn / Casamayor, Antonio / Biondi, Ricardo M

    ACS chemical biology

    2013  Volume 8, Issue 10, Page(s) 2283–2292

    Abstract: ... not inhibit the human ortholog. Here, we describe C. albicans Pkh2 biochemically, structurally and ... by using chemical probes in comparison to human PDK1. We found that a regulatory site on the C. albicans ... for C. albicans Pkh2. Together, our results describe novel features of the biology of Pkh and chemical ...

    Abstract The phosphoinositide-dependent protein kinase 1, PDK1, is a master kinase that phosphorylates the activation loop of up to 23 AGC kinases. S. cerevisiae has three PDK1 orthologues, Pkh1-3, which also phosphorylate AGC kinases (e.g., Ypk, Tpk, Pkc1, and Sch9). Pkh1 and 2 are redundant proteins involved in multiple essential cellular functions, including endocytosis and cell wall integrity. Based on similarities with the budding yeast, the Pkh of fungal infectious species was postulated as a novel target for antifungals. Here, we found that depletion of Pkh eventually induces oxidative stress and DNA double-strand breaks, leading to programmed cell death. This finding supports Pkh as an antifungal target since pharmacological inhibition of Pkh would lead to the death of yeast cells, the ultimate goal of antifungals. It was therefore of interest to further investigate the possibility to develop Pkh inhibitors with selectivity for Candida Pkh that would not inhibit the human ortholog. Here, we describe C. albicans Pkh2 biochemically, structurally and by using chemical probes in comparison to human PDK1. We found that a regulatory site on the C. albicans Pkh2 catalytic domain, the PIF-pocket, diverges from human PDK1. Indeed, we identified and characterized PS77, a new small allosteric inhibitor directed to the PIF-pocket, which has increased selectivity for C. albicans Pkh2. Together, our results describe novel features of the biology of Pkh and chemical biology approaches that support the validation of Pkh as a drug target for selective antifungals.
    MeSH term(s) Allosteric Regulation ; Antifungal Agents/chemistry ; Antifungal Agents/pharmacology ; Binding Sites ; Candida albicans/drug effects ; Candida albicans/enzymology ; Chalcones/chemistry ; Chalcones/pharmacology ; Drug Delivery Systems ; Enzyme Activation/drug effects ; Humans ; Models, Molecular ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/pharmacology ; Protein Kinases/chemistry ; Protein Kinases/metabolism ; Reactive Oxygen Species ; Receptors, Neurotransmitter/metabolism ; Thioglycolates/chemistry ; Thioglycolates/pharmacology
    Chemical Substances 2-(3-(4-chlorophenyl)-1-(2-(4-chlorophenylthio)phenyl)-3-oxopropylthio)acetic acid ; Antifungal Agents ; Chalcones ; Protein Kinase Inhibitors ; Reactive Oxygen Species ; Receptors, Neurotransmitter ; Thioglycolates ; prolactin-inhibitory factor receptor ; Protein Kinases (EC 2.7.-)
    Language English
    Publishing date 2013-10-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1554-8937
    ISSN (online) 1554-8937
    DOI 10.1021/cb400452z
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  2. Article: Editorial on the Special Issue Titled "Pathology and Diagnosis of Gynecologic Diseases".

    Giacometti, Cinzia / Ludwig, Kathrin

    Diagnostics (Basel, Switzerland)

    2023  Volume 13, Issue 22

    Abstract: In the medical and diagnostic daily routine, gynecologic diseases present many different scenarios [ ... ]. ...

    Abstract In the medical and diagnostic daily routine, gynecologic diseases present many different scenarios [...].
    Language English
    Publishing date 2023-11-20
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2662336-5
    ISSN 2075-4418
    ISSN 2075-4418
    DOI 10.3390/diagnostics13223480
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  3. Article ; Online: Multiple routes of communication within the amygdala-mPFC network: A comparative approach in humans and macaques.

    Giacometti, C / Amiez, C / Hadj-Bouziane, F

    Current research in neurobiology

    2023  Volume 5, Page(s) 100103

    Abstract: The network formed by the amygdala (AMG) and the medial Prefrontal Cortex (mPFC), at the interface between our internal and external environment, has been shown to support some important aspects of behavioral adaptation. Whether and how the anatomo- ... ...

    Abstract The network formed by the amygdala (AMG) and the medial Prefrontal Cortex (mPFC), at the interface between our internal and external environment, has been shown to support some important aspects of behavioral adaptation. Whether and how the anatomo-functional organization of this network evolved across primates remains unclear. Here, we compared AMG nuclei morphological characteristics and their functional connectivity with the mPFC in humans and macaques to identify potential homologies and differences between these species. Based on selected studies, we highlight two subsystems within the AMG-mPFC circuits, likely involved in distinct temporal dynamics of integration during behavioral adaptation. We also show that whereas the mPFC displays a large expansion but a preserved intrinsic anatomo-functional organization, the AMG displays a volume reduction and morphological changes related to specific nuclei. We discuss potential commonalities and differences in the dialogue between AMG nuclei and mPFC in humans and macaques based on available data.
    Language English
    Publishing date 2023-07-28
    Publishing country Netherlands
    Document type Journal Article ; Review
    ISSN 2665-945X
    ISSN (online) 2665-945X
    DOI 10.1016/j.crneur.2023.100103
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Gastro-Esophageal Junction Precancerosis: Histological Diagnostic Approach and Pathogenetic Insights.

    Giacometti, Cinzia / Gusella, Anna / Cassaro, Mauro

    Cancers

    2023  Volume 15, Issue 24

    Abstract: Barrett's esophagus (BE) was initially defined in the 1950s as the visualization of gastric-like mucosa in the esophagus. Over time, the definition has evolved to include the identification of goblet cells, which confirm the presence of intestinal ... ...

    Abstract Barrett's esophagus (BE) was initially defined in the 1950s as the visualization of gastric-like mucosa in the esophagus. Over time, the definition has evolved to include the identification of goblet cells, which confirm the presence of intestinal metaplasia within the esophagus. Chronic gastro-esophageal reflux disease (GERD) is a significant risk factor for adenocarcinoma of the esophagus, as intestinal metaplasia can develop due to GERD. The development of adenocarcinomas related to BE progresses in sequence from inflammation to metaplasia, dysplasia, and ultimately carcinoma. In the presence of GERD, the squamous epithelium changes to columnar epithelium, which initially lacks goblet cells, but later develops goblet cell metaplasia and eventually dysplasia. The accumulation of multiple genetic and epigenetic alterations leads to the development and progression of dysplasia. The diagnosis of BE requires the identification of intestinal metaplasia on histologic examination, which has thus become an essential tool both in the diagnosis and in the assessment of dysplasia's presence and degree. The histologic diagnosis of BE dysplasia can be challenging due to sampling error, pathologists' experience, interobserver variation, and difficulty in histologic interpretation: all these problems complicate patient management. The development and progression of Barrett's esophagus (BE) depend on various molecular events that involve changes in cell-cycle regulatory genes, apoptosis, cell signaling, and adhesion pathways. In advanced stages, there are widespread genomic abnormalities with losses and gains in chromosome function, and DNA instability. This review aims to provide an updated and comprehensible diagnostic approach to BE based on the most recent guidelines available in the literature, and an overview of the pathogenetic and molecular mechanisms of its development.
    Language English
    Publishing date 2023-12-06
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15245725
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Response to raltegravir-based salvage therapy in HIV-infected patients with hepatitis C virus or hepatitis B virus coinfection.

    Weimer, Liliana Elena / Fragola, Vincenzo / Floridia, Marco / Guaraldi, Giovanni / Ladisa, Nicoletta / Francisci, Daniela / Bellagamba, Rita / Degli Antoni, Anna / Parruti, Giustino / Giacometti, Andrea / Manconi, Paolo Emilio / Vivarelli, Angela / D'Ettorre, Gabriella / Mura, Maria Stella / Cicalini, Stefania / Preziosi, Roberta / Sighinolfi, Laura / Verucchi, Gabriella / Libertone, Raffaella /
    Tavio, Marcello / Sarmati, Loredana / Bucciardini, Raffaella

    The Journal of antimicrobial chemotherapy

    2012  Volume 68, Issue 1, Page(s) 193–199

    Abstract: Objectives: To define the impact of coinfection with hepatitis B virus (HBV) or hepatitis C ...

    Abstract Objectives: To define the impact of coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) on viroimmunological response to raltegravir-based salvage regimens that also include new HIV inhibitors such as maraviroc, darunavir and etravirine.
    Methods: We used data from a national observational study of patients starting raltegravir-based regimens to compare virological suppression and CD4 cell change from baseline in patients with and without concomitant HBV or HCV infection.
    Results: Overall, 275 patients (107 coinfected and 168 non-coinfected) were evaluated. Coinfected patients were more commonly former intravenous drug users and had a longer history of HIV infection and higher baseline aminotransferase levels. Both HIV-RNA and CD4 response were similar in the two groups. Mean time to first HIV-RNA copy number <50 copies/mL was 4.1 months (95% CI 3.5-4.6) in non-coinfected patients and 3.9 months (95% CI 3.3-4.5) in coinfected patients (hazard ratio 1.039, 95% CI 0.761-1.418, P = 0.766, log-rank test). The risk of developing new grade 3-4 hepatic adverse events was significantly higher in coinfected patients (hazard ratio 1.779, 95% CI 1.123-2.817, P = 0.009). The two groups of coinfected and non-coinfected patients had similar rates of interruption of any baseline drug (hazard ratio 1.075, 95% CI 0.649-1.781, P = 0.776) and of raltegravir (hazard ratio 1.520, 95% CI 0.671-3.447, P = 0.311). Few AIDS-defining events and deaths occurred.
    Conclusions: Viroimmunological response to regimens based on raltegravir and other recent anti-HIV inhibitors is not negatively affected by coinfection with HBV or HCV. Liver toxicity, either pre-existing or new, is more common in coinfected patients, but with no increased risk of treatment interruption.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Coinfection/drug therapy ; Coinfection/epidemiology ; Female ; Follow-Up Studies ; HIV Infections/drug therapy ; HIV Infections/epidemiology ; Hepacivirus/drug effects ; Hepatitis B/drug therapy ; Hepatitis B/epidemiology ; Hepatitis B virus/drug effects ; Hepatitis C/drug therapy ; Hepatitis C/epidemiology ; Humans ; Male ; Middle Aged ; Salvage Therapy/methods ; Treatment Outcome ; Young Adult
    Language English
    Publishing date 2012-09-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 191709-2
    ISSN 1460-2091 ; 0305-7453
    ISSN (online) 1460-2091
    ISSN 0305-7453
    DOI 10.1093/jac/dks341
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The association of high-sensitivity c-reactive protein and other biomarkers with cardiovascular disease in patients treated for HIV: a nested case-control study.

    De Luca, Andrea / de Gaetano Donati, Katleen / Colafigli, Manuela / Cozzi-Lepri, Alessandro / De Curtis, Amalia / Gori, Andrea / Sighinolfi, Laura / Giacometti, Andrea / Capobianchi, Maria Rosaria / D'Avino, Alessandro / Iacoviello, Licia / Cauda, Roberto / D'Arminio Monforte, Antonella

    BMC infectious diseases

    2013  Volume 13, Page(s) 414

    Abstract: Background: Elevated high-sensitivity C-reactive protein (hsCRP) increases the risk ...

    Abstract Background: Elevated high-sensitivity C-reactive protein (hsCRP) increases the risk of cardiovascular disease (CVD) in the general population, but its role as a predictive marker in HIV-positive patients remains unclear. Aim of the study was to evaluate whether hsCRP or other biomarkers are independent predictors of CVD risk in HIV-infected patients.
    Methods: Retrospective, nested case-control study. HIV-positive men and women (35-69 years of age) receiving combination antiretroviral therapy (cART) were included. Cases (n = 35) had a major CVD event. Controls (n = 74) free from CVD events for at least 5 years from starting ART were matched on diabetes and smoking. HsCRP, D-dimer, P-selectin, interleukin-6 (IL-6), tissue plasminogen activator, plasminogen activator inhibitor-1 levels were measured.
    Results: High hsCRP was associated with CVD risk, independently of traditional cardiovascular risk factors, HIV replication and the type of ART received at the time of sampling (adjusted odds ratio 8.00 [1.23-51.94] comparing >3.3 mg/L with <0.9 mg/L; P = 0.03). Higher IL-6 and P-selectin levels were also independently associated with increased CVD risk, although the association was weaker than for hsCRP. Higher total cholesterol and lower HDL cholesterol increased CVD risk, independent of hsCRP.
    Conclusion: hsCRP may be a useful additional biomarker to predict CVD risk in HIV-infected patients receiving cART.
    MeSH term(s) Adult ; Aged ; Anti-HIV Agents/therapeutic use ; Biomarkers/blood ; C-Reactive Protein/analysis ; Cardiovascular Diseases/blood ; Cardiovascular Diseases/diagnosis ; Cardiovascular Diseases/etiology ; Case-Control Studies ; Female ; HIV Infections/blood ; HIV Infections/complications ; HIV Infections/drug therapy ; Humans ; Interleukin-6/blood ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors
    Chemical Substances Anti-HIV Agents ; Biomarkers ; Interleukin-6 ; C-Reactive Protein (9007-41-4)
    Language English
    Publishing date 2013-09-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1471-2334
    ISSN (online) 1471-2334
    DOI 10.1186/1471-2334-13-414
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  7. Article ; Online: How seasonality influences the thermal biology of lizards with different thermoregulatory strategies: a meta-analysis.

    Giacometti, Danilo / Palaoro, Alexandre V / Leal, Laura C / de Barros, Fábio C

    Biological reviews of the Cambridge Philosophical Society

    2023  Volume 99, Issue 2, Page(s) 409–429

    Abstract: Ectotherms that maintain thermal balance in the face of varying climates should be able to colonise a wide range of habitats. In lizards, thermoregulation usually appears as a variety of behaviours that buffer external influences over physiology. Basking ...

    Abstract Ectotherms that maintain thermal balance in the face of varying climates should be able to colonise a wide range of habitats. In lizards, thermoregulation usually appears as a variety of behaviours that buffer external influences over physiology. Basking species rely on solar radiation to raise body temperatures and usually show high thermoregulatory precision. By contrast, species that do not bask are often constrained by climatic conditions in their habitats, thus having lower thermoregulatory precision. While much focus has been given to the effects of mean habitat temperatures, relatively less is known about how seasonality affects the thermal biology of lizards on a macroecological scale. Considering the current climate crisis, assessing how lizards cope with temporal variations in environmental temperature is essential to understand better how these organisms will fare under climate change. Activity body temperatures (T
    MeSH term(s) Humans ; Animals ; Lizards/physiology ; Phylogeny ; Body Temperature Regulation ; Temperature ; Biology ; Body Temperature
    Language English
    Publishing date 2023-10-23
    Publishing country England
    Document type Meta-Analysis ; Journal Article
    ZDB-ID 1423558-4
    ISSN 1469-185X ; 0006-3231 ; 1464-7931
    ISSN (online) 1469-185X
    ISSN 0006-3231 ; 1464-7931
    DOI 10.1111/brv.13028
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  8. Article ; Online: Performances of two rapid LAMP-based techniques for the intrapartum detection of Group B Streptococcus vaginal colonization.

    Charfi, Rym / Guyonnet, Cécile / Untrau, Meiggie / Giacometti, Gaëlle / Paper, Thierry / Poyart, Claire / Plainvert, Céline / Tazi, Asmaa

    Annals of clinical microbiology and antimicrobials

    2024  Volume 23, Issue 1, Page(s) 37

    Abstract: Purpose: Group B Streptococcus (GBS) is the leading cause of invasive infections in newborns. The prevention of GBS neonatal disease relies on the administration of an intrapartum antibiotic prophylaxis to GBS-colonized women. In recent years, rapid ... ...

    Abstract Purpose: Group B Streptococcus (GBS) is the leading cause of invasive infections in newborns. The prevention of GBS neonatal disease relies on the administration of an intrapartum antibiotic prophylaxis to GBS-colonized women. In recent years, rapid intrapartum detection of GBS vaginal colonization using real-time nucleic acid amplification tests (NAATs) emerged as an alternative to antenatal culture screening methods.
    Methods: We compared the performances of two loop-mediated isothermal amplification (LAMP) tests, the Ampliflash® GBS and the PlusLife® GBS tests, to standard culture for GBS detection in vaginal specimens from pregnant women. The study was conducted from April to July 2023 in a French hospital of the Paris area.
    Results: A total of 303 samples were analyzed, including 85 culture-positive samples (28.1%). The Ampliflash® GBS test and the PlusLife® GBS tests gave a result for 100% and 96.3% tests, respectively. The performances of the tests were as follows: sensitivity 87.1% (95% confidence interval (CI) 78.3-92.6) and 98.7% (95% CI 93.0-99.8), specificity 99.1% (95% CI 96.7-99.8), and 91.9% (95% CI 87.3-95.0), respectively. False negative results of the Ampliflash® GBS test correlated with low-density GBS cultures. Time-to-results correlated with GBS culture density only for the PlusLife® GBS test (p < 0.001).
    Conclusion: Both techniques provide excellent analytical performances with high sensitivity and specificity together with a short turnaround time and results available in 10 to 35 min. Their potential to further reduce the burden of GBS neonatal disease compared with antenatal culture screening needs to be assessed in future clinical studies.
    MeSH term(s) Humans ; Female ; Nucleic Acid Amplification Techniques/methods ; Streptococcus agalactiae/genetics ; Streptococcus agalactiae/isolation & purification ; Pregnancy ; Streptococcal Infections/diagnosis ; Streptococcal Infections/microbiology ; Vagina/microbiology ; Pregnancy Complications, Infectious/diagnosis ; Pregnancy Complications, Infectious/microbiology ; Sensitivity and Specificity ; Molecular Diagnostic Techniques/methods ; Infant, Newborn ; Adult
    Language English
    Publishing date 2024-04-25
    Publishing country England
    Document type Journal Article ; Comparative Study
    ZDB-ID 2097873-X
    ISSN 1476-0711 ; 1476-0711
    ISSN (online) 1476-0711
    ISSN 1476-0711
    DOI 10.1186/s12941-024-00695-2
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  9. Article: Characterisation of Monovarietal Olive Oils Obtained from Croatian

    Giacometti, Jasminka / Milin, Čedomila / Giacometti, Fabio / Ciganj, Zlatko

    Foods (Basel, Switzerland)

    2018  Volume 7, Issue 11

    Abstract: The aim of this study was the monitoring of the chemical composition of olive oil at different ripening stages to determine the appropriate harvesting time during any given crop season in the northern Adriatic region. For this purpose, from September to ... ...

    Abstract The aim of this study was the monitoring of the chemical composition of olive oil at different ripening stages to determine the appropriate harvesting time during any given crop season in the northern Adriatic region. For this purpose, from September to November, two Croatian olive cultivars (Drobnica and Buza) were taken from two different olive orchards and for the respective olive oils, prepared on a laboratory scale, the major saponifiable, unsaponifiable and phenolic compounds were determined. Based on the chemical analyses performed, the optimal harvesting time has been set in October for both cultivars. Buza had a higher oleic acid, but lower total sterols, squalene and total alkanols. Compared to the local cultivars, the studied cultivars had a high total phenolic content and antioxidant activity. The antioxidant activity and concentrations of total phenols correlated with α-tocopherol in oil samples taken during the ripening progress. Finally, trace minerals detected in Buza and Drobnica oil differed, which can be an indicator of oxidative stability and authenticity of oils.
    Language English
    Publishing date 2018-11-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704223-6
    ISSN 2304-8158
    ISSN 2304-8158
    DOI 10.3390/foods7110188
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  10. Article: Kaposi Sarcoma in People Living with HIV: Is it Water under the Bridge?

    Papalini, Chiara / Brescini, Lucia / Curci, Laura / Bastianelli, Sabrina / Barchiesi, Francesco / Giacometti, Andrea / Francisci, Daniela

    Mediterranean journal of hematology and infectious diseases

    2023  Volume 15, Issue 1, Page(s) e2023027

    Language English
    Publishing date 2023-05-01
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2674750-9
    ISSN 2035-3006
    ISSN 2035-3006
    DOI 10.4084/MJHID.2023.027
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