Insulin-sensitizing agents for infertility treatment in woman with polycystic ovary syndrome: a narrative review of current clinical practice.

PURPOSE: Polycystic ovary syndrome (PCOS) is an endocrine, metabolic, and reproductive disorder which, according to the Rotterdam criteria, affects up to 24% of women of childbearing age. Although the prevalence of infertility in this subpopulation of women is high, the optimal treatment has not been fully established yet. Insulin resistance is considered to be an important mechanism involved in the development of PCOS; hence, the aim of this narrative review is to present an overview of the current pharmacological insulin-sensitizing treatment modalities for infertile women with PCOS. METHODS: A MEDLINE and PubMed search for the years 1990-2023 was performed using a combination of keywords. Clinical trials with insulin sensitizers used for infertility treatment as well as analyses of systematic reviews and meta-analyses were evaluated. When deemed necessary, additional articles referenced in the retrieved papers were included in this narrative review. RESULTS: Several insulin-sensitizing compounds and various therapeutical protocols are available for infertility treatment of women with PCOS. Metformin is the most common adjuvant medication to induce ovulation in infertile women with PCOS and is more frequently administered in combination with clomiphene citrate than on its own. Recently, inositol and glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as possible options for infertility treatment in PCOS. CONCLUSION: The future of medical treatment of PCOS women with infertility lies in a personalized pharmacological approach, which involves various compounds with different mechanisms of action that could modify ovarian function and endometrial receptivity, ultimately leading to better overall reproductive outcomes in these women.

Imaging elastic waves in solids: how to use laser feedback interferometry to visualize them.

The use of ultrasonic elastic waves is a well established technique for non-destructive testing of materials and structures, in particular to exploit the interaction of waves with structural features to detect and characterize defects. Optical methods offer the advantage of visualising the distribution of elastic waves in a non-contact manner without disturbing the elastic wave. In this work we propose a laser feedback interferometry (LFI) based system as a cost effective, non-contact, alternative to a well established laser Doppler vibrometer technique. We demonstrate the visualization of the elastic waves, using an example of an elastic wave propagating through a prismatic acrylic rod. We show that the ultra-compact and simple implementation of LFI enables accurate visualization of the elastic waves in solids, and opens the pathway to a range of new opportunities in ultrasonic non-destructive testing and evaluation.

Coherent terahertz laser feedback interferometry for hydration sensing in leaves.

The response of terahertz to the presence of water content makes it an ideal analytical tool for hydration monitoring in agricultural applications. This study reports on the feasibility of terahertz sensing for monitoring the hydration level of freshly harvested leaves of Celtis sinensis by employing a imaging platform based on quantum cascade lasers and laser feedback interferometry. The imaging platform produces wide angle high resolution terahertz amplitude and phase images of the leaves at high frame rates allowing monitoring of dynamic water transport and other changes across the whole leaf. The complementary information in the resulting images was fed to a machine learning model aiming to predict relative water content from a single frame. The model was used to predict the change in hydration level over time. Results of the study suggest that the technique could have substantial potential in agricultural applications.

Integrated Bioinformatics Investigation of Novel Biomarkers of Uterine Leiomyosarcoma Diagnosis and Outcome.

Uterine leiomyosarcomas (uLMS) have a poor prognosis and a high percentage of recurrent disease. Bioinformatics has become an integral element in rare cancer studies by overcoming the inability to collect a large enough study population. This study aimed to investigate and highlight crucial genes, pathways, miRNAs, and transcriptional factors (TF) on uLMS samples from five Gene Expression Omnibus datasets and The Cancer Genome Atlas Sarcoma study. Forty-one common differentially expressed genes (DEGs) were enriched and annotated by the DAVID software. With protein-protein interaction (PPI) network analysis, we selected ten hub genes that were validated with the TNMplotter web tool. We used the USCS Xena browser for survival analysis. We also predicted TF-gene and miRNA-gene regulatory networks along with potential drug molecules. TYMS and TK1 correlated with overall survival in uLMS patients. Finally, our results propose further validation of hub genes (TYMS and TK1), miR-26b-5p, and Sp1 as biomarkers of pathogenesis, prognosis, and differentiation of uLMS. Regarding the aggressive behavior and poor prognosis of uLMS, with the lack of standard therapeutic regimens, in our opinion, the results of our study provide enough evidence for further investigation of the molecular basis of uLMS occurrence and its implication in the diagnosis and therapy of this rare gynecological malignancy.

Near-Field Localization of the Boson Peak on Tantalum Films for Superconducting Quantum Devices.

Superconducting circuits are among the most advanced quantum computing technologies; however, their performance is limited by losses found in surface oxides and disordered materials. In this work, we demonstrate the identification and spatial localization of a near-field signature of loss centers on tantalum films using terahertz scattering-type scanning near-field optical microscopy. By utilizing terahertz nanospectroscopy, we observe a localized excess vibrational mode around 0.5 THz and identify this resonance as the boson peak, a signature of amorphous materials. Grazing-incidence wide-angle X-ray scattering reveals that oxides on freshly solvent-cleaned samples are amorphous, whereas crystalline phases emerge after aging in air. Through nanoscale localization of defect centers, our findings provide valuable insights for the optimization of fabrication procedures for new low-loss superconducting circuits.

Terahertz imaging of human skin pathologies using laser feedback interferometry with quantum cascade lasers.

Early detection of skin pathologies with current clinical diagnostic tools is challenging, particularly when there are no visible colour changes or morphological cues present on the skin. In this study, we present a terahertz (THz) imaging technology based on a narrow band quantum cascade laser (QCL) at 2.8 THz for human skin pathology detection with diffraction limited spatial resolution. THz imaging was conducted for three different groups of unstained human skin samples (benign naevus, dysplastic naevus, and melanoma) and compared to the corresponding traditional histopathologic stained images. The minimum thickness of dehydrated human skin that can provide THz contrast was determined to be 50 µm, which is approximately one half-wavelength of the THz wave used. The THz images from different types of 50 µm-thick skin samples were well correlated with the histological findings. The per-sample locations of pathology vs healthy skin can be separated from the density distribution of the corresponding pixels in the THz amplitude-phase map. The possible THz contrast mechanisms relating to the origin of image contrast in addition to water content were analyzed from these dehydrated samples. Our findings suggest that THz imaging could provide a feasible imaging modality for skin cancer detection that is beyond the visible.

Comparison of Physical and System Factors Impacting Hydration Sensing in Leaves Using Terahertz Time-Domain and Quantum Cascade Laser Feedback Interferometry Imaging.

To reduce the water footprint in agriculture, the recent push toward precision irrigation management has initiated a sharp rise in photonics-based hydration sensing in plants in a non-contact, non-invasive manner. Here, this aspect of sensing was employed in the terahertz (THz) range for mapping liquid water in the plucked leaves of Bambusa vulgaris and Celtis sinensis. Two complementary techniques, broadband THz time-domain spectroscopic imaging and THz quantum cascade laser-based imaging, were utilized. The resulting hydration maps capture the spatial variations within the leaves as well as the hydration dynamics in various time scales. Although both techniques employed raster scanning to acquire the THz image, the results provide very distinct and different information. Terahertz time-domain spectroscopy provides rich spectral and phase information detailing the dehydration effects on the leaf structure, while THz quantum cascade laser-based laser feedback interferometry gives insight into the fast dynamic variation in dehydration patterns.

Feedback Regimes of LFI Sensors: Experimental Investigations.

In this article, we revisit the concept of optical feedback regimes in diode lasers and explore each regime experimentally from a somewhat unconventional point of view by relating the feedback regimes to the laser bias current and its optical feedback level. The results enable setting the operating conditions of the diode laser in different applications requiring operation in different feedback regimes. We experimentally explored and theoretically supported this relationship from the standard Lang and Kobayashi rate equation model for a laser diode under optical feedback. All five regimes were explored for two major types of laser diodes: inplane lasers and vertical-cavity surface emitting lasers. For both lasers, we mapped the self-mixing strength vs. drive current and feedback level, observed the differences in the shape of the self-mixing fringes between the two laser architectures and a general simulation, and monitored other parameters of the lasers with changing optical feedback.

Self-Pulsations in Terahertz Quantum Cascade Lasers under Strong Optical Feedback: The Effect of Multiple Reflections in the External Cavity.

We have recently reported the self-pulsation phenomenon under strong optical feedback in terahertz (THz) quantum cascade lasers (QCLs). One important issue, however, we left open: the effect of multiple round trips in the external cavity on the laser response to feedback. Our current analysis also casts additional light on the phenomenon of self-pulsations. Using only one external cavity round trip (ECRT) in the model has been the common approach following the seminal paper by Lang-Kobayashi in 1980. However, the conditions under which the Lang-Kobayashi model, in its original single-ECRT formulation, is applicable has been rarely explored. In this work, we investigate the self-pulsation phenomenon under multiple ECRTs. We found that the self-pulsation waveform changes when considering more than one ECRT. This we attribute to the combined effect of the extended external cavity length and the frequency modulation of the pulsation frequency by the optical feedback. Our findings add to the understanding of the optical feedback dynamics under multiple ECRTs and provide a pathway for selecting the appropriate numerical model to study the optical feedback dynamics in THz QCLs and semiconductor lasers in general.

Melimine-Modified 3D-Printed Polycaprolactone Scaffolds for the Prevention of Biofilm-Related Biomaterial Infections.

Biomaterial-associated infections are one of the major causes of implant failure. These infections result from persistent bacteria that have adhered to the biomaterial surface before, during, or after surgery and have formed a biofilm on the implant's surface. It is estimated that 4 to 10% of implant surfaces are contaminated with bacteria; however, the infection rate can be as high as 30% in intensive care units in developed countries and as high as 45% in developing countries. To date, there is no clinical solution to prevent implant infection without relying on the use of high doses of antibiotics supplied systemically and/or removal of the infected device. In this study, melimine, a chimeric cationic peptide that has been tested in Phase I and II human clinical trials, was immobilized onto the surface of 3D-printed medical-grade polycaprolactone (mPCL) scaffolds via covalent binding and adsorption. X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) spectra of melimine-treated surfaces confirmed immobilization of the peptide, as well as its homogeneous distribution throughout the scaffold surface. Amino acid analysis showed that melimine covalent and noncovalent immobilization resulted in a peptide density of ∼156 and ∼533 ng/cm2, respectively. Furthermore, we demonstrated that the immobilization of melimine on mPCL scaffolds by 1-ethyl-3-[3-(dimethylamino)propyl] carbodiimide hydrochloride (EDC) coupling and noncovalent interactions resulted in a reduction of Staphylococcus aureus colonization by 78.7% and 76.0%, respectively, in comparison with the nonmodified control specimens. Particularly, the modified surfaces maintained their antibacterial properties for 3 days, which resulted in the inhibition of biofilm formation in vitro. This system offers a biomaterial strategy to effectively prevent biofilm-related infections on implant surfaces without relying on the use of prophylactic antibiotic treatment.

Spatial tomography of light resolved in time, spectrum, and polarisation.

Measuring polarisation, spectrum, temporal dynamics, and spatial complex amplitude of optical beams is essential to studying phenomena in laser dynamics, telecommunications and nonlinear optics. Current characterisation techniques apply in limited contexts. Non-interferometric methods struggle to distinguish spatial phase, while phase-sensitive approaches necessitate either an auxiliary reference source or a self-reference, neither of which is universally available. Deciphering complex wavefronts of multiple co-propagating incoherent fields remains particularly challenging. We harness principles of spatial state tomography to circumvent these limitations and measure a complete description of an unknown beam as a set of spectrally, temporally, and polarisation resolved spatial state density matrices. Each density matrix slice resolves the spatial complex amplitude of multiple mutually incoherent fields, which over several slices reveals the spectral or temporal evolution of these fields even when fields spectrally or temporally overlap. We demonstrate these features by characterising the spatiotemporal and spatiospectral output of a vertical-cavity surface-emitting laser.

Comparison of Post-Cesarean Pain Perception of General Versus Regional Anesthesia, a Single-Center Study.

Background and Objectives: Pain during and after the procedure remains the leading concern among women undergoing cesarean section. Numerous studies have concluded that the type of anesthesia used during a cesarean section undoubtedly affects the intensity and experience of pain after the operation. Materials and Methods: This prospective cohort study was conducted at the Clinic for Gynecology and Obstetrics, Clinical Center "Dragisa Misovic-Dedinje", Belgrade, Serbia. Patients at term pregnancy (37-42 weeks of gestation) with an ASA I score who delivered under general (GEA) or regional anesthesia (RA) by cesarean section were included in the study. Following the procedure, we assessed pain using the Serbian McGill questionnaire (SF-MPQ), Visual Analogue Scale (VAS) and the pain attributes questionnaire at pre-established time intervals of 2, 12, and 24 h after the procedure. Additionally, time to patient's functional recovery was noted. We also recorded the time to the first independent mobilization, first oral intake, and lactation establishment. Results: GEA was performed for 284 deliveries while RA was performed for 249. GEA had significantly higher postoperative sensory and affective pain levels within intervals of 2, 12, and 24 h after cesarean section. GEA had significantly higher postoperative VAS pain levels. On pain attribute scale intensity, GEA had significantly higher postoperative pain levels within all intervals. Patients who received RA had a shorter time to first oral food intake, first independent mobilization, and faster lactation onset in contrast to GEA. Conclusions: The application of RA presented superior postoperative pain relief, resulting in earlier mobilization, shorter time to first oral food intake, and faster lactation onset in contrast to GEA.

Terahertz quantum cascade laser under optical feedback: effects of laser self-pulsations on self-mixing signals.

In this article, we explore the interplay between the self-pulsations (SPs) and self-mixing (SM) signals generated in terahertz (THz) quantum cascade lasers (QCLs) under optical feedback. We find that optical feedback dynamics in a THz QCL, namely, SPs, modulate the conventional SM interference fringes in a laser feedback interferometry system. The phenomenon of fringe loss in the SM signal - well known in interband diode lasers - was also observed along with pronounced SPs. With an increasing optical feedback strength, SM interference fringes transition from regular fringes at weak feedback (C ≤ 1) to fringes modulated by SPs under moderate feedback (1 < C ≤ 4.6), and then [under strong feedback (C > 4.6)] to a SM waveform with reduced number of fringes modulated by SP, until eventually (under even greater feedback) all the fringes are lost and only SPs are left visible. The transition route described above was identified in simulation when the SM fringes are created either by a moving target or a current modulation of the THz QCL. This SM signal transition route was successfully validated experimentally in a pulsed mode THz QCL with SM fringes created by current modulation during the pulse. The effects of SP dynamics in laser feedback interferometric system investigated in this work not only provides a further understanding of nonlinear dynamics in a THz QCL but also helps to understand the SM waveforms generated in a THz QCLs when they are used for various sensing and imaging applications.

Probing peptide nanowire conductivity by THz nanoscopy.

Significant efforts have recently been invested in assessing the physical and chemical properties of microbial nanowires for their promising role in developing alternative renewable sources of electricity, bioelectronic materials and implantable sensors. One of their outstanding properties, the ever-desirable conductivity has been the focus of numerous studies. However, the lack of a straightforward and reliable method for measuring it seems to be responsible for the broad variability of the reported data. Routinely employed methods tend to underestimate or overestimate conductivity by several orders of magnitude. In this work, synthetic peptide nanowires conductivity is interrogated employing a non-destructive measurement technique developed on a terahertz scanning near-field microscope to test if peptide aromaticity leads to higher electrical conductivity. Our novel peptide conductivity measurement technique, based on triple standards calibration method, shows that in the case of two biopolymer mimicking peptides, the sample incorporating aromatic residues (W6) is about six times more conductive than the negative control (L6). To the best of our knowledge, this is the first report of a quantitative nano-scale terahertz s-SNOM investigation of peptides. These results prove the suitability of the terahertz radiation-based non-destructive approach in tandem with the designer peptides choice as model test subjects. This approach requires only simple sample preparation, avoids many of the pitfalls of typical contact-based conductivity measurement techniques and could help understanding fundamental aspects of nature's design of electron transfer in biopolymers.

Management of Cervical Ectopic Pregnancy with Small-Caliber Hysteroscopy.

BACKGROUND AND OBJECTIVES: Cervical ectopic pregnancy is one of the rarest forms of ectopic pregnancy. We present a single center case series of 10 cases of cervical ectopic pregnancy, where 3 patients underwent small-caliber hysteroscopy as a single treatment method. METHODS: This was a retrospective study of women treated at our medical center with the diagnosis of cervical ectopic pregnancy from January 1, 2018 to December 31, 2020. Patient characteristics, medical history, obstetric history, diagnostic methods were collected. Small-caliber hysteroscopy treatment was performed in 3 patients and 7 patients underwent dilation and curettage (D&C). RESULTS: We identified 10 patients diagnosed with cervical ectopic pregnancy who were treated at our center. Ultrasonography was used to diagnose all cervical ectopic pregnancies Three patients underwent small-caliber hysteroscopy as a single treatment option, while D&C was performed in 7 patients. Patients who underwent small-caliber hysteroscopy had a median gestational age at diagnosis of 7 weeks and initial ßHCG < 10,000 mIU/mL. These patients had shorter hospital stay and a lower estimated blood loss than patients who underwent D&C. CONCLUSIONS: In our experience, small-caliber hysteroscopy is a safe and effective single treatment option for cervical ectopic pregnancy, but requires a skilled and experienced gynecologist.

A Rare Case of Epithelioid Trophoblastic Tumor Presenting as Hematoma of a Caesarean Scar in the Lower Uterine Segment.

Epitheliod trophoblastic tumor (ETT) account for only 1-2% of all the cases of gestational trophoblastic neoplasia (GTN), with a reported mortality rate of 10-24%. ETT is derived from chorionic type intermediate trophoblastic cells, which appears to be the reason for the only slightly elevated ßhCG levels in these patients. We present a case of a 42-year-old patient who was admitted to the clinic eight months after Caesarean delivery, for irregular vaginal bleed with normal values of beta-human chorionic gonadotropin (ßhCG). A 6 × 5 cm hematoma was evacuated from the isthmic uterine segment during the operation, and the histopathological exam of the tissue surrounding the hematoma revealed ETT. There were no metastatic lesions on the thoracal, abdominal, and pelvic CT. The second ultrasonographic exam revealed tumefaction of 5 cm at the site from the previous surgical procedure. Color Doppler imaging revealed no central nor peripheral blood flow. The patient underwent a total abdominal hysterectomy with bilateral adnexectomy without adjuvant chemotherapy. This appears to be one of the shortest intervals from the anteceded gestational event until the diagnosis of this tumor, along with the absence of the significant ultrasonographic feature of the ETT-peripheral Doppler signal pattern. We underline that, even with normal values of ßhCG, irregular vaginal bleeding following the antecedent gestational event should always arouse suspicion of GTN.

Trace elements in different tissues in aging rats.

BACKGROUND: Trace elements (TE) in the human body provide a connecting link between the environment, lifestyle and biochemical modulation of homeodynamics. On the other hand, many non-essential (toxic) elements are linked to numerous diseases. Our study tried to identify differences in TE levels between healthy old and young Wistar rats in blood and the tissues of kidney, liver, heart, and testicles. Furthermore, we wanted to see if there were age-related differences in correlations between essential and/or non-essential (toxic) TE within and between mentioned tissues. METHODS: We used 28 healthy male Wistar rats which were divided into two age groups: young, aged 10 weeks (n = 15) and old, aged 36 months (n = 13). The animals were sacrificed under general anesthesia and the blood samples, and samples from the tissues of the heart, kidneys, testicles, and liver were used for the determination of TE content in them. Analysis of the 16 elements was performed by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Toxic elements in old rats (As, Hg, and Cd) were significantly higher in all of the tissues where the difference in levels of these elements was found. Tissues of the kidney and liver had the most correlations between TE in old and young rats, respectively. In both old and young rats, arsenic was the toxic element that had most of the correlations with other essential or non-essential elements. In old rats, most of the TE correlations were detected between the tissues of the kidney and heart (11 correlations), while in young rats most of the correlations were observed between the tissues of kidney and liver, and kidney and testicles (with 9 correlations both). CONCLUSIONS: Our study has found significant changes in levels of trace elements in all of the mentioned tissues, with kidney and testicles being the tissues with the most TE differences between the two aged groups. This and other similar studies should encourage other investigators to evaluate the mutual connections between TE and physiological, or the "unhealthy" aging. More studies with more tissues included, more biomarkers of the systemic function, and even molecular methods are needed to provide the answers to numerous questions relating to TE and aging.

Case report of persistent elevation of ßhCG in a nonpregnant woman: A diagnostic puzzle.

Detectable serum levels of beta subunit of human chorionic gonadotropin (ßhCG) in nonpregnant, perimenopausal women bring confusion in both clinician and patient and could lead to unnecessary diagnostic and therapeutic procedures. A 45-year-old woman with the continuous elevation of ßhCG underwent hysteroscopy, two laparoscopic surgeries, two explorative uterine cavity curettages and three cycles of cytostatic therapy. No ultrasonographic, macroscopic or histological signs of pregnancy, both uterine and ectopic or gestational trophoblastic disease were found. Both radiographic and computed tomography reports ruled out the presence of a nongynecological neoplasm. All recommended steps were taken for confirmation or ruling out the possibility of heterophile antibodies interference, but the results were not absolute. Finally, the referent laboratory confirmed the presence of the antibodies, but their exact type remains unknown. This case underlines the importance of the universally accepted protocol in the cases of persistent ßhCG elevation in nonpregnant, perimenopausal women.

Laser feedback interferometry in multi-mode terahertz quantum cascade lasers.

The typical modal characteristics arising during laser feedback interferometry (LFI) in multi-mode terahertz (THz) quantum cascade lasers (QCLs) are investigated in this work. To this end, a set of multi-mode reduced rate equations with gain saturation for a general Fabry-Pérot multi-mode THz QCL under optical feedback is developed. Depending on gain bandwidth of the laser and optical feedback level, three different operating regimes are identified, namely a single-mode regime, a multi-mode regime, and a tuneable-mode regime. When the laser operates in the single-mode and multi-mode regimes, the self-mixing signal amplitude (peak to peak value of the self-mixing fringes) is proportional to the feedback coupling rate at each mode frequency. However, this rule no longer holds when the laser enters into the tuneable-mode regime, in which the feedback level becomes sufficiently strong (the boundary value of the feedback level depends on the gain bandwidth). The mapping of the identified feedback regimes of the multi-mode THz QCL in the space of the gain bandwidth and feedback level is investigated. In addition, the dependence of the aforementioned mapping of these three regimes on the linewidth enhancement factor of the laser is also explored, which provides a systematic picture of the potential of LFI in multi-mode THz QCLs for spectroscopic sensing applications.

Colorectal cancer and trace elements alteration.

BACKGROUND: Trace elements have important influence on body function primarily because of the vital role they have in many physiological processes. Their alterations have been found in many disorders, including cancer. It has been well known for decades that disturbances in elemental concentration may lead to cell damaging, DNA injuries and imbalance in oxidative burden. Our study tried to determine the difference of trace elements concentrations between colorectal adenocarcinoma and adjacent healthy intestinal tissue. METHODS: 59 subjects participated in this study. Healthy colon mucosa samples and colon tumor tissue samples were obtained from patients previously diagnosed with colon carcinoma by standard diagnostic procedures. Analysis of the elements was performed by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: The results showed that Na, K, Mg, Ca, Cu, Zn, Se, Mn, Cd, Cr and Hg significantly differ between malignant tissue of colorectal cancer (CRC) and adjacent healthy bowel tissue. We have, also, found that Cu/Zn tissue ratio was significantly higher in CRC compared to a healthy tissue and that patients with higher CRC stages had also significantly higher ratio. CONCLUSIONS: Since this is the first such study in Balkan region, we assume that results of our study could be a good indicator of elemental alterations in colorectal cancer of Balkan population, due to similarity in lifestyle, dietary intake, pollution and exposure to toxic elements.