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1.
Nat Commun ; 15(1): 4427, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38789427

ABSTRACT

Atoms and their different arrangements into molecules are nature's building blocks. In a regime of strong coupling, matter hybridizes with light to modify physical and chemical properties, hence creating new building blocks that can be used for avant-garde technologies. However, this regime relies on the strong confinement of the optical field, which is technically challenging to achieve, especially at terahertz frequencies in the far-infrared region. Here we demonstrate several schemes of electromagnetic field confinement aimed at facilitating the collective coupling of a localized terahertz photonic mode to molecular vibrations. We observe an enhanced vacuum Rabi splitting of 200 GHz from a hybrid cavity architecture consisting of a plasmonic metasurface, coupled to glucose, and interfaced with a planar mirror. This enhanced light-matter interaction is found to emerge from the modified intracavity field of the cavity, leading to an enhanced zero-point electric field amplitude. Our study provides key insight into the design of polaritonic platforms with organic molecules to harvest the unique properties of hybrid light-matter states.

2.
BMC Womens Health ; 24(1): 264, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38678204

ABSTRACT

BACKGROUND: Domestic and sexual violence have been linked to adverse gynecological and obstetric outcomes. Survivors often find it difficult to verbalize such violence due to feelings of shame and guilt. Vulnerable or socially excluded women are frequently excluded from research, particularly qualitative studies on violence. This study aimed to characterize the perceived impact of domestic or sexual violence on the gynecological health and follow-up among women with complex social situations. METHODS: We analyzed the data following inductive thematic analysis methods. RESULTS: Between April 2022 and January 2023, we conducted 25 semi-structured interviews, lasting on average 90 min (range: 45-180), with women aged between 19 and 52, recruited in an emergency shelter in the Paris area. The women described physical and psychological violence mainly in the domestic sphere, their altered gynecological and mental health and their perception of gynecological care. The levels of uptake of gynecological care were related to the characteristics of the violence and their consequences. The description of gynecological examination was close to the description of coerced marital sexuality which was not considered to be sexual violence. Gynecological examination, likely to trigger embarrassment and discomfort, was always perceived to be necessary and justified, and consent was implied. CONCLUSION: This study can help question the appropriateness of professional practices related to the prevention of violence against women and gynecological examination practices. Any gynecological examination should be carried out within the framework of an equal relationship between caregiver and patient, for the general population and for women with a history of violence. It participates in preventing violence in the context of care, and more widely, in preventing violence against women.


Subject(s)
Qualitative Research , Sex Offenses , Humans , Female , Adult , Middle Aged , Sex Offenses/psychology , Sex Offenses/statistics & numerical data , Young Adult , Domestic Violence/psychology , Domestic Violence/statistics & numerical data , Gynecological Examination/psychology , Gynecological Examination/statistics & numerical data , Gynecological Examination/methods , Paris , Gynecology , Patient Acceptance of Health Care/psychology , Patient Acceptance of Health Care/statistics & numerical data
3.
Eur J Obstet Gynecol Reprod Biol ; 296: 215-220, 2024 May.
Article in English | MEDLINE | ID: mdl-38471336

ABSTRACT

OBJECTIVE: The aim of this study was to examine the association between exposure to domestic and sexual violence and low uptake of gynecological consultation. STUDY DESIGN: Between October 2021 and October 2022, a case-control studywas conducted in mother andchild centers and sexual health centers in the Paris, France area. The case group included pregnant women who did not have a scheduled gynecological consultation in the past two years. The control group included pregnant women who had a scheduled gynecological consultation in the past two years. Pregnant women were interviewed using a standardized questionnaire about a history of domestic and sexual violence, the date of their last gynecological consultation and the gynecological health. RESULTS: A total of 405 pregnant women were included in the case group (n = 129) or in the control group (n = 276). After adjustment for age, couple, social security, supplementary health insurance, dyspareunia, abnormal vaginal discharge, dysmenorrhea, regular pelvic pain, mastodynia, vulvodynia and history of difficult delivery, a history of intimate partner violence was associated with the absence of a gynecological consultation in the past two years (OR 2.13; CI95% 1.21-3.73, p = 0.008). A history of sexual violence, regardless of age, was associated with the absence a gynecological consultation in the past two years (OR 1.92; CI95% 1.05-3.49, p = 0.03). The absence of a gynecological consultation was associated with dyspareunia and domestic or sexual violence (p < 0.0001 and p < 0.0001, respectively). CONCLUSIONS: This study highlighted the association between domestic and sexual violence and the absence of gynecological consultations in the past two years. It underlines the importance of screening for domestic and sexual violence during gynecological consultations and its impacts on mental health, in particular psychotraumatic symptoms, and on gynecological health, in particular dyspareunia.


Subject(s)
Domestic Violence , Dyspareunia , Intimate Partner Violence , Sex Offenses , Female , Humans , Pregnancy , Case-Control Studies , Follow-Up Studies , Prevalence
4.
Opt Lett ; 49(6): 1556-1559, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38489449

ABSTRACT

We combine parametric frequency upconversion with the single-photon counting technology to achieve terahertz (THz) detection sensitivity down to the zeptojoule (zJ) pulse energy level. Our detection scheme employs a near-infrared ultrafast source, a GaP nonlinear crystal, optical filters, and a single-photon avalanche diode. This configuration is able to resolve 1.4 zJ (1.4 × 10-21 J) THz pulse energy, corresponding to 1.5 photons per pulse, when the signal is averaged within only 1 s (or 50,000 pulses). A single THz pulse can also be detected when its energy is above 1185 zJ. These numbers correspond to the noise-equivalent power and THz-to-NIR photon detection efficiency of 1.3 × 10-16 W/Hz1/2 and 5.8 × 10-2%, respectively. To test our scheme, we perform spectroscopy of the water vapor between 1 and 3.7 THz and obtain results that are in agreement with those acquired with a standard electro-optic sampling (EOS) method. Our technique provides a 0.2 THz spectral resolution offering a fast alternative to EOS THz detection for monitoring specific spectral components in spectroscopy, imaging, and communication applications.

5.
Opt Express ; 31(20): 32468-32477, 2023 Sep 25.
Article in English | MEDLINE | ID: mdl-37859049

ABSTRACT

We demonstrate a table-top high-field terahertz (THz) source based on optical rectification of a collimated near-infrared pulse in gallium phosphide (GaP) to produce peak fields above 300 kV/cm with a spectrum centered at 2.6 THz. The experimental configuration, based on tilted-pulse-front phase matching, is implemented with a phase grating etched directly onto the front surface of the GaP crystal. Although the THz generation efficiency starts showing a saturation onset as the near-infrared pulse energy reaches 0.57 mJ, we can expect our configuration to yield THz peak fields up to 866 kV/cm when a 5 mJ generation NIR pulse is used. This work paves the way towards broadband, high-field THz sources able to access a new class of THz coherent control and nonlinear phenomena driven at frequencies above 2 THz.

6.
Appl Opt ; 62(15): 4097-4101, 2023 May 20.
Article in English | MEDLINE | ID: mdl-37706722

ABSTRACT

Terahertz time-domain spectroscopy (THz-TDS) is a powerful technique that enables the characterization of a large range of bulk materials, devices, and products. Although this technique has been increasingly used in research and industry, the standard THz-TDS configuration relying on the use of a near-infrared (NIR) laser source remains experimentally complex and relatively costly, impeding its availability to those without the expertise to build a high-performance setup based on nonlinear optics or without the financial means to acquire a commercial unit. Broadband THz-TDS systems require an even larger financial investment, primarily because the generation and detection of spectral components exceeding 3 THz typically need an ultrafast NIR source delivering sub-100-fs pulses. Such an ultrafast source can be bulky and cost upwards of $100,000. Here, we present a broadband, compact, and portable THz-TDS system comprising three modules that allow for the implementation of a single low-cost ultrafast laser, hence significantly decreasing the overall cost of the system. In the first module, the output laser pulses are spectrally broadened through nonlinear propagation in a polarization-maintaining optical fiber and then temporally compressed to achieve a higher peak power. The other two modules utilize thick nonlinear crystals with periodically patterned surfaces that diffract NIR pulses and optimize the efficiency of THz generation and detection processes by enabling a noncollinear beam geometry. Phase-matching conditions in the nonlinear crystals are controlled by the period of the gratings to gain access to a large spectral THz bandwidth. The whole system, combining these three modules, provides access to a THz spectrum peaking at 3.5 THz and extending beyond 6 THz with a maximum dynamic range of 50 dB for time-resolved spectroscopy applications. We demonstrate the functionality of this configuration by performing THz spectroscopy measurements of water vapor contained within a closed cell. Our compact system design paves the way towards a high-performance, yet cost-effective, THz-TDS system that can be readily used in academia and industry.

7.
JAMA Pediatr ; 177(9): 894-902, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37459059

ABSTRACT

Importance: Bacterial vaginosis (BV) is a well-known risk factor for preterm birth. Molecular diagnosis of BV is now available. Its impact in the screening and treatment of BV during pregnancy on preterm births has not been evaluated to date. Objective: To evaluate the clinical and economic effects of point-of-care quantitative real-time polymerase chain reaction screen and treat for BV in low-risk pregnant women on preterm birth. Design, Setting, and Participants: The AuTop trial was a prospective, multicenter, parallel, individually randomized, open-label, superiority trial conducted in 19 French perinatal centers between March 9, 2015, and December 18, 2017. Low-risk pregnant women before 20 weeks' gestation without previous preterm births or late miscarriages were enrolled. Data were analyzed from October 2021 to November 2022. Interventions: Participants were randomized 1:1 to BV screen and treat using self-collected vaginal swabs (n = 3333) or usual care (n = 3338). BV was defined as Atopobium vaginae (Fannyhessea vaginae) load of 108 copies/mL or greater and/or Gardnerella vaginalis load of 109 copies/mL or greater, using point-of-care quantitative real-time polymerase chain reaction assays. The control group received usual care with no screening of BV. Main Outcomes and Measures: Overall rate of preterm birth before 37 weeks' gestation and total costs were calculated in both groups. Secondary outcomes were related to treatment success as well as maternal and neonate health. Post hoc subgroup analyses were conducted. Results: Among 6671 randomized women (mean [SD] age, 30.6 [5.0] years; mean [SD] gestational age, 15.5 [2.8] weeks), the intention-to-treat analysis of the primary clinical and economic outcomes showed no evidence of a reduction in the rate of preterm birth and total costs with the screen and treat strategy compared with usual care. The rate of preterm birth was 3.8% (127 of 3333) in the screen and treat group and 4.6% (153 of 3338) in the control group (risk ratio [RR], 0.83; 95% CI, 0.66-1.05; P = .12). On average, the cost of the intervention was €203.6 (US $218.0) per participant, and the total average cost was €3344.3 (US $3580.5) in the screen and treat group vs €3272.9 (US $3504.1) in the control group, with no significant differences being observed. In the subgroup of nulliparous women (n = 3438), screen and treat was significantly more effective than usual care (RR, 0.62; 95% CI, 0.45-0.84; P for interaction = .003), whereas no statistical difference was found in multiparous (RR, 1.30; 95% CI, 0.90-1.87). Conclusion and Relevance: In this clinical trial of pregnant women at low risk of preterm birth, molecular screening and treatment for BV based on A vaginae (F vaginae) and/or G vaginalis quantification did not significantly reduce preterm birth rates. Post hoc analysis suggests a benefit of screen and treat in low-risk nulliparous women, warranting further evaluation in this group. Trial Registration: ClinicalTrials.gov Identifier: NCT02288832.


Subject(s)
Premature Birth , Vaginosis, Bacterial , Pregnancy , Female , Infant, Newborn , Humans , Adult , Adolescent , Premature Birth/prevention & control , Vaginosis, Bacterial/diagnosis , Vaginosis, Bacterial/drug therapy , Prospective Studies , Gestational Age , Treatment Outcome
8.
Nat Commun ; 14(1): 2595, 2023 May 05.
Article in English | MEDLINE | ID: mdl-37147407

ABSTRACT

Slow motion movies allow us to see intricate details of the mechanical dynamics of complex phenomena. If the images in each frame are replaced by terahertz (THz) waves, such movies can monitor low-energy resonances and reveal fast structural or chemical transitions. Here, we combine THz spectroscopy as a non-invasive optical probe with a real-time monitoring technique to demonstrate the ability to resolve non-reproducible phenomena at 50k frames per second, extracting each of the generated THz waveforms every 20 µs. The concept, based on a photonic time-stretch technique to achieve unprecedented data acquisition speeds, is demonstrated by monitoring sub-millisecond dynamics of hot carriers injected in silicon by successive resonant pulses as a saturation density is established. Our experimental configuration will play a crucial role in revealing fast irreversible physical and chemical processes at THz frequencies with microsecond resolution to enable new applications in fundamental research as well as in industry.

9.
J Med Internet Res ; 25: e45002, 2023 04 13.
Article in English | MEDLINE | ID: mdl-37052967

ABSTRACT

BACKGROUND: Secondary use of health data has reached unequaled potential to improve health systems governance, knowledge, and clinical care. Transparency regarding this secondary use is frequently cited as necessary to address deficits in trust and conditional support and to increase patient awareness. OBJECTIVE: We aimed to review the current published literature to identify different stakeholders' perspectives and recommendations on what information patients and members of the public want to learn about the secondary use of health data for research purposes and how and in which situations. METHODS: Using PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines, we conducted a scoping review using Medline, CINAHL, PsycINFO, Scopus, Cochrane Library, and PubMed databases to locate a broad range of studies published in English or French until November 2022. We included articles reporting a stakeholder's perspective or recommendations of what information patients and members of the public want to learn about the secondary use of health data for research purposes and how or in which situations. Data were collected and analyzed with an iterative thematic approach using NVivo. RESULTS: Overall, 178 articles were included in this scoping review. The type of information can be divided into generic and specific content. Generic content includes information on governance and regulatory frameworks, technical aspects, and scientific aims. Specific content includes updates on the use of one's data, return of results from individual tests, information on global results, information on data sharing, and how to access one's data. Recommendations on how to communicate the information focused on frequency, use of various supports, formats, and wording. Methods for communication generally favored broad approaches such as nationwide publicity campaigns, mainstream and social media for generic content, and mixed approaches for specific content including websites, patient portals, and face-to-face encounters. Content should be tailored to the individual as much as possible with regard to length, avoidance of technical terms, cultural competence, and level of detail. Finally, the review outlined 4 major situations where communication was deemed necessary: before a new use of data, when new test results became available, when global research results were released, and in the advent of a breach in confidentiality. CONCLUSIONS: This review highlights how different types of information and approaches to communication efforts may serve as the basis for achieving greater transparency. Governing bodies could use the results: to elaborate or evaluate strategies to educate on the potential benefits; to provide some knowledge and control over data use as a form of reciprocity; and as a condition to engage citizens and build and maintain trust. Future work is needed to assess which strategies achieve the greatest outreach while striking a balance between meeting information needs and use of resources.


Subject(s)
Health Records, Personal , Patient Participation , Humans , Communication , Forecasting , Learning , Patients , Trust
10.
Death Stud ; 47(2): 204-210, 2023.
Article in English | MEDLINE | ID: mdl-35244527

ABSTRACT

In this study, 20 medical assistance in dying (MAiD) providers were interviewed about their experience when assessing patients with unmet needs, including medical, financial or social needs. Collectively they had experience with over 3700 MAiD assessments and found that unmet needs were rare. In the cases where patients had unmet needs, these were usually related to loneliness and poverty. This led to the ethical dilemma of providers deciding to honor their wishes for MAiD, knowing that some of their suffering was due to society's failure to provide for them.


Subject(s)
Suicide, Assisted , Humans , Canada , Qualitative Research
11.
ACS Omega ; 7(14): 11973-11979, 2022 Apr 12.
Article in English | MEDLINE | ID: mdl-35449940

ABSTRACT

We present a comparative investigation between thin films of graphene oxide (GO) and chemically reduced graphene oxide (rGO) deposited onto glass substrates via spray pyrolysis. Two reduction techniques are investigated: (1) the exposition of a sprayed layer of GO to vapors of hydrazine hydrate to produce rGOV and (2) the addition of liquid hydrazine hydrate to a suspended GO solution, which is then sprayed onto a substrate to produce rGOL. Three different spectroscopy techniques, Raman, Fourier transform infrared, and UV-Vis-NIR, show that the two reduced samples have less lattice disorder in comparison to GO, with rGOL having the highest degree of reduction. Interestingly, topography characterization by atomic force microscopy reveals a morphological change occurring during the exposure to hydrazine hydrate vapors, resulting in a thickness of 110 nm for the rGOV film, which is a factor of 16 larger than rGOL and GO. Finally, I-V measurements show a significant decrease of the GO's resistivity after the reduction process, where rGOL features a resistivity 90 times lower than rGOV, confirming that rGOL has the highest degree of reduction. Our results indicate that the reduction process for rGOV is susceptible to introducing intercalated water molecules in the material while the fabrication technique for rGOL is a suitable route to obtain a material with minimal lattice disorder and properties approaching those of graphene.

12.
Sensors (Basel) ; 22(6)2022 Mar 19.
Article in English | MEDLINE | ID: mdl-35336554

ABSTRACT

We present the design, fabrication, and testing of a drone-mountable gas sensing platform for environmental monitoring applications. An array of graphene-based field-effect transistors in combination with commercial humidity and temperature sensors are used to relay information by wireless communication about the presence of airborne chemicals. We show that the design, based on an ESP32 microcontroller combined with a 32-bit analog-to-digital converter, can be used to achieve an electronic response similar, within a factor of two, to state-of-the-art laboratory monitoring equipment. The sensing platform is then mounted on a drone to conduct field tests, on the ground and in flight. During these tests, we demonstrate a one order of magnitude reduction in environmental noise by reducing contributions from humidity and temperature fluctuations, which are monitored in real-time with a commercial sensor integrated to the sensing platform. The sensing device is controlled by a mobile application and uses LoRaWAN, a low-power, wide-area networking protocol, for real-time data transmission to the cloud, compatible with Internet of Things (IoT) applications.


Subject(s)
Graphite , Mobile Applications , Humidity , Monitoring, Physiologic/methods , Unmanned Aerial Devices
13.
ACS Appl Mater Interfaces ; 13(51): 61751-61757, 2021 Dec 29.
Article in English | MEDLINE | ID: mdl-34910450

ABSTRACT

Real time, rapid, and accurate detection of chemical warfare agents (CWA) is an ongoing security challenge. Typical detection methods for CWA are adapted from traditional chemistry techniques such as chromatography and mass spectrometry, which lack portability. Here, we address this challenge by evaluating graphene field effect transistors (GFETs) as a sensing platform for sarin gas using both experiment and theory. Experimentally, we measure the sensing response of GFETs when exposed to dimethyl methylphosphonate (DMMP), a less toxic compound used as simulant due to its chemical similarities to sarin. We find low detection limits of 800 ppb, the highest sensitivity reported up to date for this type of sensing platform. In addition to changes in resistance, we implement an in-operando monitor of the GFETs characteristics during and after exposure to the analyte, which gives insights into the graphene-DMMP interactions. Moreover, using theoretical calculations, we show that DMMP and sarin interact similarly with graphene, implying that GFETs should be highly sensitive to detecting sarin. GFETs offer a versatile platform for the development of compact and miniaturized devices that can provide real-time detection of dangerous chemicals in the local environment.

14.
ACS Sens ; 6(12): 4417-4424, 2021 12 24.
Article in English | MEDLINE | ID: mdl-34788995

ABSTRACT

The ability to detect and recognize airborne chemical species is essential to enable applications in security, health, and environmental monitoring. Here, we report a sensing platform based on graphene field-effect transistor (GFET) devices combined with optical illumination for the detection of volatile compounds. We compare the change in resistance of GFET sensors upon exposure to analytes such as ethanol, dimethyl methylphosphonate (DMMP), and water vapors with and without the presence of a local illuminating ultraviolet (UV) light-emitting diode (LED). Our results show that UV illumination acts as a control knob for the electronic transport properties of graphene, increasing the device's response to ethanol, water, and DMMP, up to a factor of 54, and enabling ppb-level detection of DMMP at 800 ppb without chemical functionalization of the graphene layer. The sensing response can be optimized to reveal an analyte-specific interplay between the induced changes in carrier concentration and mobility of the GFET. These findings provide a pathway to enhancing the sensitivity of GFET sensors and a differentiation channel to improve their selectivity.


Subject(s)
Graphite , Lighting , Transistors, Electronic
15.
Sci Rep ; 11(1): 8729, 2021 Apr 22.
Article in English | MEDLINE | ID: mdl-33888755

ABSTRACT

We explore the substrate-dependent charge carrier dynamics of large area graphene films using contact-free non-invasive terahertz spectroscopy. The graphene samples are deposited on seven distinct substrates relevant to semiconductor technologies and flexible/photodetection devices. Using a Drude model for Dirac fermions in graphene and a fitting method based on statistical signal analysis, we extract transport properties such as the charge carrier density and carrier mobility. We find that graphene films supported by substrates with minimal charged impurities exhibit an enhanced carrier mobility, while substrates with a high surface roughness generally lead to a lower transport performance. The smallest amount of doping is observed for graphene placed on the polymer Zeonor, which also has the highest carrier mobility. This work provides valuable guidance in choosing an optimal substrate for graphene to enable applications where high mobility is required.

16.
Nat Commun ; 12(1): 974, 2021 Feb 12.
Article in English | MEDLINE | ID: mdl-33579934

ABSTRACT

Plasmonic nanostructures hold promise for the realization of ultra-thin sub-wavelength devices, reducing power operating thresholds and enabling nonlinear optical functionality in metasurfaces. However, this promise is substantially undercut by absorption introduced by resistive losses, causing the metasurface community to turn away from plasmonics in favour of alternative material platforms (e.g., dielectrics) that provide weaker field enhancement, but more tolerable losses. Here, we report a plasmonic metasurface with a quality-factor (Q-factor) of 2340 in the telecommunication C band by exploiting surface lattice resonances (SLRs), exceeding the record by an order of magnitude. Additionally, we show that SLRs retain many of the same benefits as localized plasmonic resonances, such as field enhancement and strong confinement of light along the metal surface. Our results demonstrate that SLRs provide an exciting and unexplored method to tailor incident light fields, and could pave the way to flexible wavelength-scale devices for any optical resonating application.

17.
Opt Express ; 28(14): 20296-20304, 2020 Jul 06.
Article in English | MEDLINE | ID: mdl-32680092

ABSTRACT

We demonstrate ultrafast tuning of a plasmonic spectral filter at terahertz (THz) frequencies. The device is made of periodically spaced gold crosses deposited on the surface of an undoped silicon wafer in which transient free carriers can be optically injected with a femtosecond resonant pulse. We demonstrate the concept by measuring the transmission spectrum of a notch filter using time-domain THz spectroscopy. Proper synchronization of the THz probe and visible excitation pulses leads to an enhanced transmission at the resonance by more than two orders of magnitude. Finite-difference time-domain simulations, which are in agreement with the experimental results, show that the underlying mechanisms responsible for the resonance blueshift and linewidth broadening can be attributed to the photoinduced change in dielectric properties of the substrate. This is supported by the numerically simulated field distribution and reflection/transmission coefficients. The device can be used in future pulse shaping and ultrafast switching experiments.

18.
ACS Appl Mater Interfaces ; 12(35): 39764-39771, 2020 Sep 02.
Article in English | MEDLINE | ID: mdl-32658444

ABSTRACT

Graphene has demonstrated great promise for technological use, yet control over material growth and understanding of how material imperfections affect the performance of devices are challenges that hamper the development of applications. In this work, we reveal new insight into the connections between the performance of the graphene devices as environmental sensors and the microscopic details of the interactions at the sensing surface. We monitor changes in the resistance of the chemical-vapor deposition grown graphene devices as exposed to different concentrations of ethanol. We perform thermal surface treatments after the devices are fabricated, use scanning probe microscopy to visualize their effects down to nanometer scale and correlate them with the measured performance of the device as an ethanol sensor. Our observations are compared to theoretical calculations of charge transfers between molecules and the graphene surface. We find that, although often overlooked, the surface cleanliness after device fabrication is responsible for the device performance and reliability. These results further our understanding of the mechanisms of sensing in graphene-based environmental sensors and pave the way to optimizing such devices, especially for their miniaturization, as with decreasing size of the active zone the potential role of contaminants will rise.

19.
Nat Commun ; 11(1): 2673, 2020 05 29.
Article in English | MEDLINE | ID: mdl-32471973

ABSTRACT

Aldosterone, produced by the adrenals and under the control of plasma angiotensin and potassium levels, regulates hydromineral homeostasis and blood pressure. Here we report that the neuropeptide substance P (SP) released by intraadrenal nerve fibres, stimulates aldosterone secretion via binding to neurokinin type 1 receptors (NK1R) expressed by aldosterone-producing adrenocortical cells. The action of SP is mediated by the extracellular signal-regulated kinase pathway and involves upregulation of steroidogenic enzymes. We also conducted a prospective proof-of-concept, double blind, placebo-controlled clinical trial aimed to investigate the impact of the NK1R antagonist aprepitant on aldosterone secretion in healthy male volunteers (EudraCT: 2008-003367-40, ClinicalTrial.gov: NCT00977223). Participants received during two 7-day treatment periods aprepitant (125 mg on the 1st day and 80 mg during the following days) or placebo in a random order at a 2-week interval. The primary endpoint was plasma aldosterone levels during posture test. Secondary endpoints included basal aldosterone alterations, plasma aldosterone variation during metoclopramide and hypoglycaemia tests, and basal and stimulated alterations of renin, cortisol and ACTH during the three different stimulatory tests. The safety of the treatment was assessed on the basis of serum transaminase measurements on days 4 and 7. All pre-specified endpoints were achieved. Aprepitant decreases aldosterone production by around 30% but does not influence the aldosterone response to upright posture. These results indicate that the autonomic nervous system exerts a direct stimulatory tone on mineralocorticoid synthesis through SP, and thus plays a role in the maintenance of hydromineral homeostasis. This regulatory mechanism may be involved in aldosterone excess syndromes.


Subject(s)
Aldosterone/blood , Aprepitant/pharmacology , Neurokinin-1 Receptor Antagonists/pharmacology , Receptors, Neurokinin-1/metabolism , Substance P/metabolism , Adolescent , Adrenal Cortex/metabolism , Adrenal Glands/metabolism , Adult , Aldosterone/metabolism , Cells, Cultured , Humans , Hypoglycemia/blood , Male , Metoclopramide , Mineralocorticoids/biosynthesis , Placebos/administration & dosage , Proof of Concept Study , Prospective Studies , Transaminases/blood , Young Adult
20.
Opt Express ; 28(3): 3237-3248, 2020 Feb 03.
Article in English | MEDLINE | ID: mdl-32121996

ABSTRACT

We theoretically investigate the propagation of broadband single-cycle terahertz (THz) pulses through a medium with a nonlinear optical response. Our model takes into account non-paraxial effects, self-focusing and diffraction, as well as dispersion, in both the linear and nonlinear optical regimes. We investigate the contribution of non-instantaneous Kerr-type nonlinearity to the overall instantaneous and delayed Kerr effect at the THz frequencies. We show how increasing the nonlinear relaxation time and its dispersion modifies the THz pulse after the propagation through a transparent medium. We also discuss the effect of linear dispersion on self-action during the pulse propagation.

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