**9. Periapical exposure**

Periapical exposure must be achievedafter full thickness flap elevation by using a sterile round surgical burr. Mostly the cortical bone overlying the apex has been resorbed due to underlying apical pathosis, exposing a soft tissue lesion. If the opening is small, it is enlarged, until approximately half the root and the lesion are visible. With a limited bony opening, radio‐ graphs are used in conjunction with root and bone topography to locate the apex. Regardless of the handpiece used, there should be copious irrigation with a syringe or through the handpiece with sterile saline solution. Enough overlying bone should be removed to expose the area around the apex and at least half the length of the root. Good access and visibility are important; the bony window must be adequate. The clinician should not be concerned about the bone removal because once the infection resolves, the bone will reform. The exposure of the root is done before resecting the root to avoid the potential of blending the root in with the bone and losing surgical orientation. This is especially critical in the mandible where the bone is dense. Lower incisor roots are carefully exposed because the proximity with adjacent teeth could lead to treatment of the wrong apex. Fig:4

**Figure 4.** Periapical exposure

### **10. Curettage**

Granulomatous, inflamed tissue around the periradicular area should be removed to gain access and visibility of the apex, to obtain a biopsy for histologic examination (when indicated), and to minimize hemorrhage. If possible, the tissue should be enucleated with a suitably sized sharp curette. Fig:5


**5. Conclusions**

diffraction patterns to be obtained on time scales shorter than the onset of radiation damage of samples. This approach has been successfully demonstrated in studies of biological samples with the use of X‐ray free electron lasers (XFEL) producing femtosecond pulses of high

There has been remarkable progress in the development of XFELs that hold the great promise for user experiments ranging from atomic physics to biological structure determination. Despite the fact that these lasers are powerful tools in studies of matter structure and physics of light‐matter interaction, they have limited accessibility because of their high cost and large‐ scale. This makes the current search for alternative X‐ray sources of laboratory scale to be of

Presently, there are two main approaches to the development of compact ultrashort‐pulsed sources of coherent soft X‐ray: above considered HHG by gas and solid targets, as well as the generation of coherent X‐ray radiation in the laser plasma. The first one is characterized by low‐intensity soft X‐ray radiation, insufficient for the realization of holographic imaging methods. The laser plasma enables generation of lasing in the soft X‐ray region with beam

Actually, only collisional and recombination schemes of active media excitation to produce soft X‐ray in a laser plasma are of practical interest. The first of them was realized in a laser plasma with high electron temperature, providing a population inversion on transitions between excited states of ions, which typically lie in the range 10–50 nm [72]. The most promising way to extend the spectral range of the X‐ray lasers deeper into the X‐ray region, including the "water window," lies in the further developing recombination scheme of

The first observation of the amplification on the transition to the ground state dates back to 1983 [73] when hydrogen‐like lithium ions were excited in the laser plasma produced due to optical field ionization (OFI) by the UV radiation from a subpicosecond KrF laser. Later that year, this observation was confirmed in different experimental conditions [74–76]. The OFI approach to excitation of recombination soft X‐ray lasers is particularly attractive since it produces fully stripped ions on a time scale of one period of the incident laser electric field and enables formation of cold electrons with low residual energy (for a linearly polarized laser pulse) providing favorable conditions for high‐rate three‐body recombination. Residual energy is proportional to the square of a pump laser wavelength and can be reduced by using

An electron removed from an atom due to OFI interacts with the plane polarized laser field and acquires quiver energy of the coherent electron oscillation in the field and energy of electron drift along the laser field direction [77, 78]. For ultrashort pulses, the quiver energy is returned to the wave, and it does not contribute to residual energy. Most of the electrons are ionized within a narrow interval near the crest of the oscillating electric field because of the exponential dependence of the ionization rate on the electric field amplitude. Classically, the average drift energy, ε, of an electron depends on the phase mismatch, Δϕ, between the phase

at which the electron is freed and the crest of the electromagnetic wave:

excitation of transitions to the ground state of recombining fully stripped ions.

intensity (For example, see [71]).

15020 High Energy and Short Pulse Lasers

performances close to those of XFELs [72].

a short‐wavelength driver pulse.

great importance.

Development of the photochemical method for exciting active media has resulted in the emerging of the new class of gas lasers in the spectral range extending from the NIR to UV regions. The most remarkable achievements of these studies belong to the visible range where no alternatives are available so far for the excitation of broadband gaseous active me‐ dia (XeF(C‐A), Xe2Cl, and Kr2F) that would not be strongly modified by transient absorp‐ tion. This pave the way for the development of hybrid (solid/gas) laser systems towards petawatt peak power in the blue‐green spectral region due to their broad amplification bandwidths, able to support as short as 10 fs pulses, and their relatively high saturation flu‐ ences (0.05–0.2 J cm-2), promising as high as 10 TW peak power to be obtained from square cm of an output aperture.

To demonstrate the high potential of the hybrid approach relying on the optically driven broadband active media in the visible, two femtosecond hybrid systems are now under development with the aim of conducting proof‐of‐principle experiments: THL‐30 at LPI, designed for about 5 TW of output peak power, and THL‐100 at IHCE, designed to be ten times more powerful. Behind these systems is the amplification of the second harmonic of Ti:sap‐ phire front ends in the power‐boosting XeF(C‐A) amplifiers driven by the e‐beam‐to‐VUV flash converters. In the pilot experiments performed in the THL‐100 system, peak power of 14 TW has been attained in the 50 fs pulse at the output energy of 0.7 J. After upgrading pumping source, an energy output has been enhanced up to 2.5 J in the 2.4 ps pulse before its recom‐ pression promising a peak power of 50 TW to be obtained. Besides spectral matching between a solid‐state frond‐end and gas XeF(C‐A) amplifier, the nonlinear frequency upconversion results in efficient temporal cleaning of the ultrashort optical pulse, thereby providing a high contrast ratio for the output blue‐green pulses produced by a hybrid laser chain. This was confirmed by the results of ASE measurements in the XeF(C‐A) amplifier of the THL‐100 system, which argue that a contrast ratio of 1012–1013 is feasible in the blue‐green hybrid femtosecond systems with a peak power of about 100 TW.

By the example of LWFA, HHG, and recombination soft X‐ray lasers, it was shown that, in some cases, application of shorter wavelength lasers (as compared to Ti:sapphire lasers operating in the NIR) for laser‐matter interaction may be advantageous and extends the frontiers of experimental ability to provide deeper insight into the physical mechanisms of the laser‐matter interaction. One of the greatest challenges is the development of recombination‐ pumped soft X‐ray lasers that have potential to extend SXRL spectral range towards "water window" and beyond.

Actually, the above‐discussed blue‐green hybrid concept can be considered as an alternative to the direct nonlinear upconversion of intense NIR laser radiation to the visible with the use of second harmonic generation (SHG) technique. However, to the best of our knowledge, the highest peak power reached so far in the visible with SHG does not exceed 4 TW, producing the peak intensity in a focal spot diameter of about 3 μm as low as 3 × 1018 W/cm2 because of poor beam quality [83]. Achieving higher parameters in Ti:sapphire laser systems with SHG meets serious technical problems arising from a variety of nonlinear effects in crystals at high intensities leading to a significant spatiotemporal degradation of beam quality [84]. Moreover, a broad spectrum of femtosecond pulses and strong nonlinear wave front distortion require application of very thin (0.5–1 mm) nonlinear crystals of large diameter (>10 cm). The tech‐ nology of such crystals manufacture is not yet available. Nevertheless, a large ongoing effort is presently devoted to overcome these difficulties in SHG and to reach hundreds of TW at wavelength of the second harmonic [85, 86]. The hybrid (solid/gas) laser technology is free of these problems because peak powers of 0.1–1 TW are required for a seed pulse generated by the solid‐state front end in order to extract most of the energy stored in the final gaseous amplifier.

At the same time, it is necessary to say that the hybrid systems relying on the photochemically driven boosting amplifiers are inferior to the all‐solid‐state systems from the view point of a pulse‐repetition rate reaching 1 kHz at moderate output peak powers. The hybrid systems operating in the visible could be of interest for the use in low repetition rate experiments, which require an output peak power of tens and hundreds of TW. In the case of the Xe2Cl active medium, repetition rates up to 10 Hz seems to be attainable with proper engineering.


*6.3. Endocannabinoid Receptors*

The first biologically active component of cannabis was identified in the 1960s as delta-9-tetrahydrocannabinol (THC), a potent drug classified as a sedative-hypnotic. This was followed by the discovery of two cannabinoid receptors, cannabinoid receptor 1 (CB1R) and cannabinoid receptor 2 (CB2R), in the early 1990s. Both are G-protein-coupled receptors and serve as the primary sites of action for THC. Together, they are involved in the major neuromodulatory endocannabinoid system (ECS), whose primary goal is to promote homeostasis [68]. The ECS is widespread, and CB1Rs are found throughout the central nervous system and some peripheral tissues, while CB2Rs are primarily found in peripheral tissues and immune cells [69]. Cannabinoids act on receptors other than CB1R and CB1R. They modulate transient receptor potential (TRP) channels, including TRP vanilloid (TRPV) channels, which are involved in neuropathic pain signals in EM [70].

There is a broad range of mechanisms by which cannabinoids modulate pain, and given the high impact of EM on women's quality of life such as the high prevalence of EM, cannabinoid-mediated effects on EM-related pain have become a subject of inquiry [68,69].

Different categories of EM pain may be modulated by cannabinoids [71,72]. There is evidence that a disruption of the normal ECS potentiates pain in EM patients. In women with EM, decreased CB1R expression compared to controls and increased anandamide (AEA) and 2-arachidonoylglycerol (2-AG) expression, both endogenous ligands of the CB1R and CB2R, are consistent with a negative feedback loop that is permissive of inflammation [68].

In vitro studies have shown that exogenous cannabinoids could correct these dysregulations. When endometrial cells were treated with cannabinoid agonist WIN 5512-2, the result was decreased cell proliferation, decreased reactive oxygen species production, and reduction in alpha-smooth muscle actin expression, lending supporting evidence to the anti-inflammatory effects of cannabinoids [73]. Bilgic et al. [74] also found that CB1R and CB2R expressions are decreased in EM tissue compared to control, with concurrently decreased apoptosis indexes. The same study found that exposure of EM tissue to CB1R and CB2 agonists resulted in pro-apoptotic effects. However, animal model studies have shown divergent results. A nude mouse model of transplanted human deep infiltrating EM confirmed the antiproliferative effects of cannabinoids on the growth of deep infiltrating lesions [64]. In contrast, in a mouse analogue of early-stage EM, the activation resulted in an increased disease burden [75]. The complexity of the ECS superimposed on the two different mouse models used may account for the different results [76].

Endocannabinoids have also been shown to trigger endometrial cell migration [77]. Moreover, CB1Rs have been found on the sensory and sympathetic neurons innervating EM lesions [78]. Given the above role of the ECS in the EM modulation, cannabinoids have been proposed as a putative therapy. In fact, an Australian cross-sectional survey showed that self-management strategies were very common in EM patients and that cannabis and cannabis products were among the most effective at pain reduction [79].