Fibrinogen on extracellular vesicles derived from polyhexamethylene guanidine phosphate-exposed mice induces inflammatory effects via integrin ß.

Polyhexamethylene guanidine phosphate (PHMG-p), used as a humidifier disinfectant, causes interstitial lung disease, obliterative bronchiolitis, and lung fibrosis; however, little is known about its effect on intercellular interactions. Extracellular vesicles (EVs), which carry diverse compounds including proteins, RNA, and DNA to mediate cell-to-cell communication through their paracrine effects, have been highlighted as novel factors in lung fibrogenesis. This study aimed to identify the effect of proteins on small EVs (sEVs) from bronchoalveolar lavage fluid (BALF) of the recipient cells after PHMG-p exposure. A week after intratracheal administration of PHMG-p, sEVs were isolated from BALF of tissue showing overexpressed inflammatory and fibrosis markers. To investigate the role of sEVs in inflammation, naïve macrophages were cultured with sEVs, which induced their activation. To identify sEV proteins that are associated with these responses, proteomics analysis was performed. In the gene ontology analysis, coagulation, fibrinolysis, and hemostasis were associated with the upregulated proteins in sEVs. The highest increase was observed in fibrinogen levels, which was also related to those gene ontologies. We validated role of exosomal fibrinogen in inflammation using recombinant fibrinogen and an inhibitor of the integrin, which is the binding receptor for fibrinogen. Overall, we elucidated that increased fibrinogen levels in the early sEVs-PHMG activated inflammatory response during early fibrosis. These results suggest that sEVs from the BALF of PHMG-p-exposed mice could aggravate fibrogenesis by activating naïve macrophages via various proteins in the sEVs, Furthermore, this finding will be broadening the spectrum of communicating mediators.

Comparison of clinical and preimplantation genetic testing for aneuploidy outcomes between in vitro fertilization and intracytoplasmic sperm injection in sibling mature oocytes from high-risk patients: A retrospective study.

AIM: To evaluate the influence of insemination methods on clinical outcomes by assessing preimplantation genetic testing for aneuploidy (PGT-A) outcomes in embryos obtained using in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in sibling mature oocytes from high-risk patients. METHODS: This retrospective study involved 108 couples with nonmale or mild male factor infertility who underwent split insemination cycles from January 2018 to December 2021. PGT-A was performed using trophectoderm biopsy, array comparative genome hybridization, or next-generation sequencing with 24-chromosome screening. RESULTS: Mature oocytes were divided into IVF (n = 660) and ICSI (n = 1028) groups. The normal fertilization incidence was similar between the groups (81.1% vs. 84.6%). The total number of blastocysts biopsied was significantly higher in the IVF group than in the ICSI group (59.3% vs. 52.6%; p = 0.018). However, euploidy (34.4% vs. 31.9%) and aneuploidy (63.4% vs. 66.2%) rates per biopsy and clinical pregnancy rates (60.0% vs. 58.8%) were similar between the groups. Implantation (45.6% vs. 50.8%) and live birth or ongoing pregnancy (52.0% vs 58.8%) rates were slightly higher in the ICSI group than in the IVF group and miscarriage rate per transfer was slightly higher in the IVF group than in the ICSI group (12.0% vs 5.9%); however no significant difference was observed. CONCLUSIONS: IVF and ICSI using sibling mature oocytes had similar clinical outcomes, and euploidy and aneuploidy rates in couples with nonmale and mild male factor infertility. These results suggest that IVF is a useful option, along with ICSI, as an insemination method in PGT-A cycles, especially in high-risk patients.

Polystyrene microplastic particles induce autophagic cell death in BEAS-2B human bronchial epithelial cells.

The detection of high levels of microplastics in indoor and outdoor air has increased concerns regarding its toxic effects on the respiratory system. They are not easily degradable and can be deposited deep in the lungs. Although several studies have reported inhalation toxicities of microplastics, they are still controversial due to a lack of evidence. Herein, we evaluated the inhalation toxicities of three differently charged polystyrene microplastics (PS-MPs), the most abundant microplastics in the air. Cytotoxicity and ROS generation were evaluated using WST-1 and DCF-DA assays, respectively. To evaluate the toxic effects on the lung, inflammatory responses were analyzed after repeated exposure to the PS-MPs through intratracheal instillation. To explore the mechanism of toxicity, autophagy and ER stress-associated proteins were analyzed. Only the positively charged PS-MPs (NH2 -PS-MPs) showed cytotoxicity and increased ROS generation in BEAS-2B cells. Similarly, only NH2 -PS-MPs significantly increased the expression and secretion of the pro-inflammatory cytokine IL-ß in the animal experiments. The expression of ER stress proteins indicated that NH2 -PS-MPs increased ER stress via PERK-EIF2α and ATF4-CHOP pathways. Moreover, accumulation of NH2 -PS-MPs in lysosomes and deformity of the nucleus were observed in BEAS-2B cells with autophagy induction. Taken together, our results demonstrated that NH2 -PS-MPs induced autophagic cell death in bronchial epithelial cells, leading to inflammatory responses in the lungs. These results suggest that repeated inhalation of microplastics can result in inflammatory responses in the lung through cellular damage of lung epithelial cells, and that inhalation microplastics should be monitored to reduce inhalation health risks.

Guillain-Barre Syndrome After Two COVID-19 Vaccinations: Two Case Reports With Follow-up Electrodiagnostic Study.

Guillain-Barre syndrome (GBS) is an immune-mediated acute polyradiculoneuropathy and commonly occurs after a preceding infection or immunization sequalae. Following the severe acute respiratory syndrome-coronavirus-2 virus pandemic with co-introduction of massive vaccinations, several GBS cases associated with coronavirus disease 2019 (COVID-19) infection per se or after vaccination for COVID-19 were reported internationally. Herein, we report two cases of Korean GBS presenting with tetraplegia after two different COVID-19 vaccinations (42-year old man by AstraZeneca and 48-year woman by Pfizer vaccines) within four weeks after vaccination. The patients were diagnosed with clinical examination, serial electromyography, and compatible laboratory results and improved after comprehensive rehabilitative treatment and intravenous immunoglobulin therapy. Furthermore, we performed an electrodiagnostic follow-up study of each case to examine their unique characteristics.

Poziotinib suppresses ovarian cancer stem cell growth via inhibition of HER4-mediated STAT5 pathway.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, with an overall 5-year survival rate of only 30%. EOC is associated with drug resistance, frequent recurrence, and poor prognosis. A major contributor toward drug resistance might be cancer stem cells (CSCs), which may remain after chemotherapy. Here, we aimed to find therapeutic agents that target ovarian CSCs. We performed a high-throughput screening using the Clinical Compound Library with a sphere culture of A2780 EOCs. Poziotinib, a pan-human epidermal growth factor receptor (HER) inhibitor, decreased sphere formation, viability, and proliferation, and induced G1 cell cycle arrest and apoptosis in ovarian CSCs. In addition, poziotinib suppressed stemness and disrupted downstream signaling of Wnt/ß-catenin, Notch, and Hedgehog pathways, which contribute to many characteristics of CSCs. Interestingly, HER4 was overexpressed in ovarian CSCs and Poziotinib reduced the phosphorylation of STAT5, AKT, and ERK, which are regulated by HER4. Our results suggest that HER4 may be a promising therapeutic target for ovarian CSCs, and that poziotinib may be an effective therapeutic option for the prevention of ovarian cancer recurrence.

Combined Poziotinib with Manidipine Treatment Suppresses Ovarian Cancer Stem-Cell Proliferation and Stemness.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy in women worldwide, with an overall 5 year survival rate below 30%. The low survival rate is associated with the persistence of cancer stem cells (CSCs) after chemotherapy. Therefore, CSC-targeting strategies are required for successful EOC treatment. Pan-human epidermal growth factor receptor 4 (HER4) and L-type calcium channels are highly expressed in ovarian CSCs, and treatment with the pan-HER inhibitor poziotinib or calcium channel blockers (CCBs) selectively inhibits the growth of ovarian CSCs via distinct molecular mechanisms. In this study, we tested the hypothesis that combination treatment with poziotinib and CCBs can synergistically inhibit the growth of ovarian CSCs. Combined treatment with poziotinib and manidipine (an L-type CCB) synergistically suppressed ovarian CSC sphere formation and viability compared with either drug alone. Moreover, combination treatment synergistically reduced the expression of stemness markers, including CD133, KLF4, and NANOG, and stemness-related signaling molecules, such as phospho-STAT5, phospho-AKT, phospho-ERK, and Wnt/ß-catenin. Moreover, poziotinib with manidipine dramatically induced apoptosis in ovarian CSCs. Our results suggest that the combinatorial use of poziotinib with a CCB can effectively inhibit ovarian CSC survival and function.

Calcium Channels as Novel Therapeutic Targets for Ovarian Cancer Stem Cells.

Drug resistance in epithelial ovarian cancer (EOC) is reportedly attributed to the existence of cancer stem cells (CSC), because in most cancers, CSCs still remain after chemotherapy. To overcome this limitation, novel therapeutic strategies are required to prevent cancer recurrence and chemotherapy-resistant cancers by targeting cancer stem cells (CSCs). We screened an FDA-approved compound library and found four voltage-gated calcium channel blockers (manidipine, lacidipine, benidipine, and lomerizine) that target ovarian CSCs. Four calcium channel blockers (CCBs) decreased sphere formation, viability, and proliferation, and induced apoptosis in ovarian CSCs. CCBs destroyed stemness and inhibited the AKT and ERK signaling pathway in ovarian CSCs. Among calcium channel subunit genes, three L- and T-type calcium channel genes were overexpressed in ovarian CSCs, and downregulation of calcium channel genes reduced the stem-cell-like properties of ovarian CSCs. Expressions of these three genes are negatively correlated with the survival rate of patient groups. In combination therapy with cisplatin, synergistic effect was shown in inhibiting the viability and proliferation of ovarian CSCs. Moreover, combinatorial usage of manidipine and paclitaxel showed enhanced effect in ovarian CSCs xenograft mouse models. Our results suggested that four CCBs may be potential therapeutic drugs for preventing ovarian cancer recurrence.

Assessment of water samples with complex compositions using microalgal bioassay based on the community level physiological profiling (CLPP).

The ability to effectively characterize the response of microalgal communities to changes in water quality is limited. Earlier, a microalgal bioassay was developed based on community level physiological profiling (CLPP). The efficacy of this assay was evaluated using three wetland water samples, a surface water sample, and two wastewater samples (i.e. primary and secondary), all collected from southwestern Ontario, Canada. In addition, the assay was applied to untreated and activated carbon treated oil sand process water (OSPW). YT (Yeast Identification Test Panel) and Biolog plates were successfully utilized for defined microalgal community under both heterotrophic and mixotrophic growth conditions to characterize the changes in the defined microalgal community due to the changes in water type. It was found that, although the degrees of changes in the algal community varied, all tested water samples were distinguished under both growth regimes using principal component analysis (PCA). The variations in the algal community were caused by the differences of the water samples. The response of the assay due to changes in the algal community caused by different waters was found to be very sensitive and could be used to differentiate different water bodies. It further can be used to monitor temporal changes of water quality of the same water body.

Prolonged stimulation with low-intensity ultrasound induces delayed increases in spontaneous hippocampal culture spiking activity.

Ultrasound is a promising neural stimulation modality, but an incomplete understanding of its range and mechanism of effect limits its therapeutic application. We investigated the modulation of spontaneous hippocampal spike activity by ultrasound at a lower acoustic intensity and longer time scale than has been previously attempted, hypothesizing that spiking would change conditionally upon the availability of glutamate receptors. Using a 60-channel multielectrode array (MEA), we measured spontaneous spiking across organotypic rat hippocampal slice cultures (N = 28) for 3 min each before, during, and after stimulation with low-intensity unfocused pulsed or sham ultrasound (spatial-peak pulse average intensity 780 µW/cm2 ) preperfused with artificial cerebrospinal fluid, 300 µM kynurenic acid (KA), or 0.5 µM tetrodotoxin (TTX) at 3 ml/min. Spike rates were normalized and compared across stimulation type and period, subregion, threshold level, and/or perfusion condition using repeated-measures ANOVA and generalized linear mixed models. Normalized 3-min spike counts for large but not midsized, small, or total spikes increased after but not during ultrasound relative to sham stimulation. This result was recapitulated in subregions CA1 and dentate gyrus and replicated in a separate experiment for all spike size groups in slices pretreated with aCSF but not KA or TTX. Increases in normalized 18-sec total, midsized, and large spike counts peaked predominantly 1.5 min following ultrasound stimulation. Our low-intensity ultrasound setup exerted delayed glutamate receptor-dependent, amplitude- and possibly region-specific influences on spontaneous spike rates across the hippocampus, expanding the range of known parameters at which ultrasound may be used for neural activity modulation. © 2016 Wiley Periodicals, Inc.

The influence of light on copper-limited growth of an oceanic diatom, Thalassiosira oceanica (Coscinodiscophyceae).

Thalassiosira oceanica (CCMP 1005) was grown over a range of copper concentrations at saturating and subsaturating irradiance to test the hypothesis that Cu and light were interacting essential resources. Growth was a hyperbolic function of irradiance in Cu-replete medium (263 fmol Cu' · L-1 ) with maximum rates achieved at 200 µmol photons · m-2  · s-1 . Lowering the Cu concentration at this irradiance to 30.8 fmol Cu' · L-1 decreased cellular Cu quota by 7-fold and reduced growth rate by 50%. Copper-deficient cells had significantly slower (P < 0.0001) rates of maximum, relative photosynthetic electron transport (rETRmax ) than Cu-sufficient cells, consistent with the role of Cu in photosynthesis in this diatom. In low-Cu medium (30.8 fmol Cu' · L-1 ), growth rate was best described as a positive, linear function of irradiance and reached the maximum value measured in Cu-replete cells when irradiance increased to 400 µmol photons · m-2  · s-1 . Thus, at high light, low-Cu concentration was no longer limiting to growth: Cu concentration and light interacted strongly to affect growth rate of T. oceanica (P < 0.0001). Relative ETRmax and Cu quota of cells grown at low Cu also increased at 400 µmol photons · m-2  · s-1 to levels measured in Cu-replete cells. Steady-state uptake rates of Cu-deficient and sufficient cells were light-dependent, suggesting that faster growth of T. oceanica under high light and low Cu was a result of light-stimulated Cu uptake.

Nanoporous silver cathode surface treated by atomic layer deposition of CeO(x) for low-temperature solid oxide fuel cells.

We evaluated the performance of solid oxide fuel cells (SOFCs) with a 50 nm thin silver (Ag) cathode surface treated with cerium oxide (CeO(x)) by atomic layer deposition (ALD). The performances of bare and ALD-treated Ag cathodes were evaluated on gadolinia-doped ceria (GDC) electrolyte supporting cells with a platinum (Pt) anode over 300 °C-450 °C. Our work confirms that ALD CeO(x) treatment enhances cathodic performance and thermal stability of the Ag cathode. The performance difference between cells using a Ag cathode optimally treated with an ALD CeO(x) surface and a reference Pt cathode is about 50% at 450 °C in terms of fuel cell power output in our experiment. The bare Ag cathode completely agglomerated into islands during fuel cell operation at 450 °C, while the ALD CeO(x) treatment effectively protects the porosity of the cathode. We also discuss the long-term stability of ALD CeO(x)-treated Ag cathodes related to the microstructure of the layers.

Electrical characterization of benzenedithiolate molecular electronic devices with graphene electrodes on rigid and flexible substrates.

We investigated the electrical characteristics of molecular electronic devices consisting of benzenedithiolate self-assembled monolayers and a graphene electrode. We used the multilayer graphene electrode as a protective interlayer to prevent filamentary path formation during the evaporation of the top electrode in the vertical metal-molecule-metal junction structure. The devices were fabricated both on a rigid SiO2/Si substrate and on a flexible poly(ethylene terephthalate) substrate. Using these devices, we investigated the basic charge transport characteristics of benzenedithiolate molecular junctions in length- and temperature-dependent analyses. Additionally, the reliability of the electrical characteristics of the flexible benzenedithiolate molecular devices was investigated under various mechanical bending conditions, such as different bending radii, repeated bending cycles, and a retention test under bending. We also observed the inelastic electron tunneling spectra of our fabricated graphene-electrode molecular devices. Based on the results, we verified that benzenedithiolate molecules participate in charge transport, serving as an active tunneling barrier in solid-state graphene-electrode molecular junctions.

Gate-dependent asymmetric transport characteristics in pentacene barristors with graphene electrodes.

We investigated the electrical characteristics and the charge transport mechanism of pentacene vertical hetero-structures with graphene electrodes. The devices are composed of vertical stacks of silicon, silicon dioxide, graphene, pentacene, and gold. These vertical heterojunctions exhibited distinct transport characteristics depending on the applied bias direction, which originates from different electrode contacts (graphene and gold contacts) to the pentacene layer. These asymmetric contacts cause a current rectification and current modulation induced by the gate field-dependent bias direction. We observed a change in the charge injection barrier during variable-temperature current-voltage characterization, and we also observed that two distinct charge transport channels (thermionic emission and Poole-Frenkel effect) worked in the junctions, which was dependent on the bias magnitude.

Minimal systems analysis of mitochondria-dependent apoptosis induced by cisplatin.

Recently, it was reported that the role of mitochondria-reactive oxygen species (ROS) generating pathway in cisplatin-induced apoptosis is remarkable. Since a variety of molecules are involved in the pathway, a comprehensive approach to delineate the biological interactions of the molecules is required. However, quantitative modeling of the mitochondria-ROS generating pathway based on experiment and systemic analysis using the model have not been attempted so far. Thus, we conducted experiments to measure the concentration changes of critical molecules associated with mitochondrial apoptosis in both human mesothelioma H2052 and their ρ(0) cells lacking mitochondrial DNA (mtDNA). Based on the experiments, a novel mathematical model that can represent the essential dynamics of the mitochondrial apoptotic pathway induced by cisplatin was developed. The kinetic parameter values of the mathematical model were estimated from the experimental data. Then, we have investigated the dynamical properties of this model and predicted the apoptosis levels for various concentrations of cisplatin beyond the range of experiments. From parametric perturbation analysis, we further found that apoptosis will reach its saturation level beyond a certain critical cisplatin concentration.

Successful pregnancy and delivery after ICSI with artificial oocyte activation by calcium ionophore in in-vitro matured oocytes: a case report.

The achievement of a successful pregnancy and delivery after oocyte activation with calcium ionophore is reported in a couple having low fertilization rates after intracytoplasmic sperm injection (ICSI) of in-vitro matured oocytes. A couple, in which the wife had polycystic ovary syndrome and the husband had moderate oligoteratozoospermia, showed a low fertilization rate in a previous in-vitro maturation cycle (2/11 [18.2%]). The most likely cause of complete fertilization failure or low fertilization rates is failure of oocyte activation. Therefore, artificial oocyte activation by calcium ionophore was combined with ICSI to achieve viable fertilized oocytes. Oocytes were stimulated with calcium ionophore for 30 min after ICSI. The fertilization rate of oocytes activated with calcium ionophore (13/15 [86.7%] and 7/9 [77.8%]) was higher than that of the non-activated oocytes. In the latest cycle, three embryos derived from the activated oocytes were transferred into the uterus on day 3. Subsequently, two gestational sacs were identified on ultrasound. The patient delivered dizygotic twins (girl 2260 g and boy 2760 g) at 35 weeks and 6 days gestation by caesarean section. This result suggests that calcium ionophore could be useful for oocyte fertilization in couples with low fertilization rates after ICSI of in-vitro matured oocytes.

Atomic layer deposition of ruthenium on plasma-treated vertically aligned carbon nanotubes for high-performance ultracapacitors.

It is challenging to realize a conformal metal coating by atomic layer deposition (ALD) because of the high surface energy of metals. In this study, ALD of ruthenium (Ru) on vertically aligned carbon nanotubes (CNTs) was carried out. To activate the surface of CNTs that lack surface functional groups essential for ALD, oxygen plasma was applied ex situ before ALD. X-ray photoelectron spectroscopy and Raman spectroscopy confirmed surface activation of CNTs by the plasma pretreatment. Transmission electron microscopy analysis with energy-dispersive x-ray spectroscopy composition mapping showed that ALD Ru grew conformally along CNTs walls. ALD Ru/CNTs were electrochemically oxidized to ruthenium oxide (RuOx) that can be a potentially useful candidate for use in the electrodes of ultracapacitors. Electrode performance of RuOx/CNTs was evaluated using cyclic voltammetry and galvanostatic charge-discharge measurements.

Primary cutaneous mucinous carcinoma in a periorbital lesion: two case reports and literature review.

Primary cutaneous mucinous carcinoma (PCMC) is a rare malignancy of the sweat glands that most commonly affects the periorbital area. It is characterized by slow growth over a prolonged period, and its morphology can be easily confused with a benign tumor, such as an epidermal cyst. Consequently, many patients experience recurrence after undergoing multiple resections. However, there are few reports concerning the surgical management of PCMC. We present two cases of PCMC originating in the periorbital area. The first case involved a 76-year-old man with a mass measuring 3.0× 1.5 cm that had been increasing in size. The second case was a 61-year-old man with two masses, each measuring 1.0× 1.0 cm, that were also growing. Both patients underwent wide excision with a 5-mm safety margin, which was determined based on the widest view of the cross-section of the mass on the magnetic resonance imaging. Subsequently, based on the intraoperative frozen biopsy results, both patients underwent additional excision with a 5-mm safety margin in only one direction. This report shows that, when determining the surgical margin of PCMC in periorbital area, employing imaging modalities and intraoperative frozen biopsies can be helpful for narrowing the surgical margin.

Python-Based Algorithm for Estimating the Parameters of Physical Property Models for Substances Not Available in Database.

An in-house Python-based algorithm was developed using simplified molecular-input line-entry specification (SMILES) strings and a dipole moment for estimating the normal boiling point, critical properties, standard enthalpy, vapor pressure, liquid molar volume, enthalpy of vaporization, heat capacity, viscosity, thermal conductivity, and surface tension of molecules. Normal boiling point, critical properties, and standard enthalpy were estimated by using the Joback group contribution method. Vapor pressure, liquid molar volume, enthalpy of vaporization, heat capacity, and surface tension were estimated by using the Riedel model, Gunn-Yamada model, Clausius-Clapeyron equation, Joback group contribution method, and Brock-Bird model, respectively. Viscosities of liquid and gas were estimated by using the Letsou-Stiel model and the Chapman-Enskog-Brokaw model, respectively. Thermal conductivities of liquid and gas were estimated by using the Sato-Riedel model and Stiel-Thodos model, respectively. Dipole moment was calculated through molecular dynamics simulation using the MMFF94 force field, performed with Avogadro software. A case study was conducted with dihydro-2-methyl-3-furanone (DHMF), 2-furaldehyde diethyl acetal (FDA), 1,1-diethoxy-3-methyl butane (DEMB), glutathione (GSH), vitamin B5 (VITB5), homocysteine (HCYS), and O-acetyl-l-homoserine (AH), which are not present in the existing property database. Cross-validation indicated that the developed Python-based algorithm provided pure component model parameters nearly identical with those obtained with the Aspen Property Constant Estimation System (PCES) method, except for the enthalpy of vaporization. The parameters for estimating the enthalpy of vaporization using the current Python-based algorithm accurately represented the behavior of the actual substances, as determined using the Clausius-Claperyon equation. This Python-based algorithm provides a detailed and clear reference for estimating pure property parameters.

Next generation risk assessment of biocides (PHMG-p and CMIT/MIT)-induced pulmonary fibrosis using adverse outcome pathway-based transcriptome analysis.

Next-generation risk assessment (NGRA) has emerged as a promising alternative to non-animal studies owing to the increasing demand for the risk assessment of inhaled toxicants. In this study, NGRA was used to assess the inhalation risks of two biocides commonly used as humidifier disinfectants: polyhexamethylene guanidine phosphate (PHMG-p) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT). Human bronchial epithelial cell transcriptomic data were processed based on adverse outcome pathways and used to establish transcriptome-based points of departure (tPODs) for each biocide. tPOD values were 0.00500-0.0510 µg/cm2 and 0.0342-0.0544 µg/cm2 for PHMG-p and CMIT/MIT, respectively. tPODs may provide predictive power comparable to that of traditional animal-based PODs (aPODs). The tPOD-based NGRA determined that both PHMG-p and CMIT/MIT present a high inhalation risk. Moreover, the identified PHMG-p posed a higher risk than CMIT/MIT, and children were identified as more susceptible population compared to adults. This finding is consistent with observations from actual exposure events. Our findings suggest that NGRA with transcriptomics offers a reliable approach for risk assessment of specific humidifier disinfectant biocides, while acknowledging the limitations of current models and in vitro systems, particularly regarding uncertainties in pharmacokinetics (PK) and pharmacodynamics (PD).

Clinical outcomes of preimplantation genetic testing for aneuploidy in high-risk patients: a retrospective cohort study.

OBJECTIVE: The purpose of this study was to evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on clinical outcomes among high-risk patients. METHODS: This retrospective study involved 1,368 patients and the same number of cycles, including 520 cycles with PGT-A and 848 cycles without PGT-A. The study participants comprised women of advanced maternal age (AMA) and those affected by recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or severe male factor infertility (SMF). RESULTS: PGT-A was associated with significant improvements in the implantation rate (IR) and the ongoing pregnancy rate/live birth rate (OPR/LBR) per embryo transfer cycle in the AMA (39.3% vs. 16.2% [p<0.001] and 42.0% vs. 21.8% [p<0.001], respectively), RIF (41.7% vs. 22.0% [p<0.001] and 47.0% vs. 28.6% [p<0.001], respectively), and RPL (45.6% vs. 19.5% [p<0.001] and 49.1% vs. 24.2% [p<0.001], respectively) groups, as well as the IR in the SMF group (43.3% vs. 26.5%, p=0.011). Additionally, PGT-A was associated with lower overall incidence rates of early pregnancy loss in the AMA (16.7% vs. 34.3%, p=0.001) and RPL (16.7% vs. 50.0%, p<0.001) groups. However, the OPR/LBR per total cycle across all PGT-A groups did not significantly exceed that for the non-PGT-A groups. CONCLUSION: PGT-A demonstrated beneficial effects in high-risk patients. However, our findings indicate that these benefits are more pronounced in carefully selected candidates than in the entire high-risk patient population.