Trans-abdominal fetal reduction in higher order multiple pregnancies: a pioneer cohort retrospective study in Nepal.

Objective: To share the initial experience of trans-abdominal multifetal pregnancy reduction (MFPR) in Nepal. Method: The procedure was performed in 108 patients in a private hospital over a period of 3 years. Under ultrasound guidance, intracardiac injection of 0.2-3.0 ml of 15% w/v (2 mEq/ml) potassium chloride (KCl) was administered via trans-abdominal route. Results: A total of 108 fetal reduction procedures were carried out at the seventh to fifteenth weeks of gestation, a maximum of 44 (40.7%) of which were done at the ninth to tenth weeks of gestation. A total of 123 fetuses were reduced. Out of total 108 multifetal pregnancies, 96 (88.8%) were due to in-vitro fertilization (IVF). Eighty-five pregnancies (78.7%) underwent reduction from triplet to twin. The second-time reduction was needed in five cases. Two attempts (in the same sitting) were required in three cases. The inadvertent demise of the second fetus was noted in three cases of dichorionic tri-amniotic triplet pregnancy. Conclusion: Ultrasound-guided trans-abdominal fetal reduction performed between the seventh and twelfth weeks of gestation is safe and effective.

Tissue explants as tools for studying the epigenetic modulation of the GH-IGF-I axis in farmed fish.

Somatic growth in vertebrates is mainly controlled by the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. The role of epigenetic mechanisms in regulating this axis in fish is far from being understood. This work aimed to optimize and evaluate the use of short-term culture of pituitary and liver explants from a farmed fish, the gilthead seabream Sparus aurata, for studying epigenetic mechanisms involved in GH/IGF-I axis regulation. Our results on viability, structure, proliferation, and functionality of explants support their use in short-term assays. Pituitary explants showed no variation in gh expression after exposure to the DNA methylation inhibitor decitabine (5-Aza-2'-deoxycytidine; DAC), despite responding to DAC by changing dnmt3bb and tet1 expression, and TET activity, producing an increase in overall DNA hydroxymethylation. Conversely, in liver explants, DAC had no effects on dnmt s and tet s expression or activity, but modified the expression of genes from the GH-IGF-I axis. In particular, the expression of igfbp2a was increased and that of igfbp4, ghri and ghrii was decreased by DAC as well as by genistein, which is suggestive of impaired growth. While incubation of liver explants with S-adenosylmethionine (SAM) produced no clear effects, it is proposed that nutrients must ensure the methylation milieu within the liver in the fish to sustain proper growth, which need further in vivo verification. Pituitary and liver explants from S. aurata can be further used as described herein for the screening of inhibitors or activators of epigenetic regulators, as well as for assessing epigenetic mechanisms behind GH-IGF-I variation in farmed fish.

Structural analysis of type 3 resistant starch from Canna edulis during in vitro simulated digestion and its post-digested residue impact on human gut microbiota.

Introduction: Resistant starch (RS) has garnered attention for its health benefits, including modulating the gut microbiota and promoting the production of short-chain fatty acids (SCFAs). Methods: This study investigates structural changes of type 3 resistant starch from Canna edulis (CE) during in vitro simulated digestion and explores its health-relevant properties using healthy individuals' fecal microbiota. Results: CE, prepared with a RS content of 59.38%, underwent a comprehensive analysis employing X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). During simulated digestion, XRD analysis demonstrated a significant rise in CE's relative crystallinity from 38.92 to 49.34%. SEM illustrated the transition of CE from a smooth to a rough surface, a notable morphological shift. Post-digestion, CE was introduced into microbial fermentation. Notably, propionic acid and valeric acid levels significantly increased compared to the control group. Furthere more, beneficial Bifidobacterium proliferated while pathogenic Escherichia-Shigella was suppressed. When comparing CE to the well-known functional food fructo-oligosaccharide (FOS), CE showed a specific ability to support the growth of Bifidobacterium and stimulate the production of short-chain fatty acids (SCFAs) without causing lactic acid accumulation. Discussion: CE demonstrates potential as a functional health food, with implications for gut health enhancement and SCFAs production.

Harnessing Artificial Intelligence to Predict Ovarian Stimulation Outcomes in In Vitro Fertilization: Scoping Review.

BACKGROUND: In the realm of in vitro fertilization (IVF), artificial intelligence (AI) models serve as invaluable tools for clinicians, offering predictive insights into ovarian stimulation outcomes. Predicting and understanding a patient's response to ovarian stimulation can help in personalizing doses of drugs, preventing adverse outcomes (eg, hyperstimulation), and improving the likelihood of successful fertilization and pregnancy. Given the pivotal role of accurate predictions in IVF procedures, it becomes important to investigate the landscape of AI models that are being used to predict the outcomes of ovarian stimulation. OBJECTIVE: The objective of this review is to comprehensively examine the literature to explore the characteristics of AI models used for predicting ovarian stimulation outcomes in the context of IVF. METHODS: A total of 6 electronic databases were searched for peer-reviewed literature published before August 2023, using the concepts of IVF and AI, along with their related terms. Records were independently screened by 2 reviewers against the eligibility criteria. The extracted data were then consolidated and presented through narrative synthesis. RESULTS: Upon reviewing 1348 articles, 30 met the predetermined inclusion criteria. The literature primarily focused on the number of oocytes retrieved as the main predicted outcome. Microscopy images stood out as the primary ground truth reference. The reviewed studies also highlighted that the most frequently adopted stimulation protocol was the gonadotropin-releasing hormone (GnRH) antagonist. In terms of using trigger medication, human chorionic gonadotropin (hCG) was the most commonly selected option. Among the machine learning techniques, the favored choice was the support vector machine. As for the validation of AI algorithms, the hold-out cross-validation method was the most prevalent. The area under the curve was highlighted as the primary evaluation metric. The literature exhibited a wide variation in the number of features used for AI algorithm development, ranging from 2 to 28,054 features. Data were mostly sourced from patient demographics, followed by laboratory data, specifically hormonal levels. Notably, the vast majority of studies were restricted to a single infertility clinic and exclusively relied on nonpublic data sets. CONCLUSIONS: These insights highlight an urgent need to diversify data sources and explore varied AI techniques for improved prediction accuracy and generalizability of AI models for the prediction of ovarian stimulation outcomes. Future research should prioritize multiclinic collaborations and consider leveraging public data sets, aiming for more precise AI-driven predictions that ultimately boost patient care and IVF success rates.

METAPHOR: Metabolic evaluation through phasor-based hyperspectral imaging and organelle recognition for mouse blastocysts and oocytes.

Only 30% of embryos from in vitro fertilized oocytes successfully implant and develop to term, leading to repeated transfer cycles. To reduce time-to-pregnancy and stress for patients, there is a need for a diagnostic tool to better select embryos and oocytes based on their physiology. The current standard employs brightfield imaging, which provides limited physiological information. Here, we introduce METAPHOR: Metabolic Evaluation through Phasor-based Hyperspectral Imaging and Organelle Recognition. This non-invasive, label-free imaging method combines two-photon illumination and AI to deliver the metabolic profile of embryos and oocytes based on intrinsic autofluorescence signals. We used it to classify i) mouse blastocysts cultured under standard conditions or with depletion of selected metabolites (glucose, pyruvate, lactate); and ii) oocytes from young and old mouse females, or in vitro-aged oocytes. The imaging process was safe for blastocysts and oocytes. The METAPHOR classification of control vs. metabolites-depleted embryos reached an area under the ROC curve (AUC) of 93.7%, compared to 51% achieved for human grading using brightfield imaging. The binary classification of young vs. old/in vitro-aged oocytes and their blastulation prediction using METAPHOR reached an AUC of 96.2% and 82.2%, respectively. Finally, organelle recognition and segmentation based on the flavin adenine dinucleotide signal revealed that quantification of mitochondria size and distribution can be used as a biomarker to classify oocytes and embryos. The performance and safety of the method highlight the accuracy of noninvasive metabolic imaging as a complementary approach to evaluate oocytes and embryos based on their physiology.

Enhanced accumulation of biologically active compounds in lichens with potential functional food applications.

Lichens have great potential as food, functional food additives or flavourings. The presence of specific substances with multiple biological activities is one of the characteristics of lichens. However, research on lichens as a food source or functional food additive is limited. The present study simulated, for the first time, the potential bioaccessibility of active compounds from 6 lichen species in simulated gastric and intestinal conditions. An in vitro digestion showed that the lichen substances had different bioaccessibility and stability during digestion. It was found that the application of some metabolic modulators significantly altered the accumulation of metabolites in most species. In addition, the study demonstrated the antimicrobial activity of the tested extracts as well as of 14 isolated lichen metabolites. These multi-directional studies demonstrate the potential of lichens in terms of their use as antimicrobial functional food additives.

Bioaccessibility and Caco-2 Cell Uptake of Iron Chlorophyllin Using A Biologically Relevant Digestion Model.

Iron deficiency remains a top nutrient deficiency worldwide. Iron chlorophyllin (IC), a compound structurally analogous to heme, utilizes the protoporphyrin ring of chlorophyll to bind iron. IC has previously been shown to deliver more iron to Caco-2 cells than FeSO4, the most common form prescribed for supplementation. However, previous test conditions used digestive conditions outside of those observed in humans. This study sought to assess IC bioaccessibility and Caco-2 cell uptake using physiologically relevant digestive solutions, pH, and incubation time, as compared to other iron sources (i.e. FeSO4, and hemoglobin (Hb)). Co-digestion with ascorbic acid (AA) and albumin was also investigated. Following gastric, duodenal, and jejunal digestion, IC-bound iron was less bioaccessible than iron delivered as FeSO4, and IC-bound iron was less bioaccessible than Hb-bound iron. IC-bound iron bioaccessibility was not affected by AA and was enhanced 2x with co-digested with a low dose of albumin. However, Caco-2 cell incubation with IC-containing digesta increased cell ferritin 2.5x more than FeSO4 alone, and less than Hb. IC with AA or with 400 mg albumin also increased cell ferritin more than IC alone, with the greatest increases observed following incubation of digesta containing IC + AA + 400 mg albumin. These results suggest IC can serve as an improved source of iron for supplementation as compared to FeSO4. These results also support further in vivo investigations of IC-based iron delivery in populations at risk of iron deficiency.

Factors infl uencing delivery in women with multiple fetus pregnancy.

OBJECTIVE: This paper aims to analyze the factors that can influence the method of childbirth in women with multiple pregnancies. MATERIALS AND METHODS: Retrospective analysis of selected parameters in women with multiple pregnancies who gave birth at the 2nd Clinic of Gynecology and Obstetrics of the Faculty of Medicine (FM), Comenius University (CU) and University Hospital (UH) Bratislava in the years 2010-2022. RESULTS: Between 2010 and 2022, at the 2nd Clinic of Gynecology and Obstetrics of the FM CU and UH in Bratislava, 1.13% of births were multiple pregnancies. After statistical data processing, primiparity appeared statistically significant as a risk of acute caesarean section (C-section); multiparous women had a higher probability to give birth vaginally. Since 2017, the clinic has had a decreasing trend in the number of caesarean sections. Women with an acute caesarean section, in turn had on average a lower pH of both fetuses compared to vaginal delivery. However, the incidence of asphyxia in fetuses was not statistically significantly different. We found no risk factor increasing the likelihood of acute caesarean section for fetus B in twins. CONCLUSION: Multiple pregnancy has a higher morbidity not only for the woman but also for the fetuses. The incidence of multiple pregnancies is influenced by assisted reproduction. Delivery method depends on various factors such as chorionicity, fetal presentation, and history of a previous caesarean section.

Updating 'Data on the determination of human epidermis integrity in skin permeation experiments by electrical resistance' with Data on pig ear skin.

The data presented in this article are an update of the dataset provided by Musazzi et al. [1] and are related to the research article entitled "Equivalence assessment of creams with quali-quantitative differences in light of the EMA and FDA regulatory framework" [2]. In vitro permeation study (IVPT) is typically conducted using the method of Franz's diffusion cell for assessing the biopharmaceutical performance of topically applied products. While the human epidermis is considered the benchmark, various animal models (for instance, pig ear) have been accepted as a permeation membrane. Nonetheless, it is crucial to evaluate the integrity of the membrane to ensure the quality of the experiments. The methods employed for this assessment vary, and the outcomes are heavily reliant on the operational conditions, and the model membrane. The article contributes to the existing dataset by providing data on the electrical resistance values of pig ear skin samples and their correlation with the in vitro permeability fluxes of caffeine and benzoic acid. This data is utilized to determine a suitable cut-off for verifying the skin integrity of such an animal model. This information could be beneficial for facilitating critical or comprehensive analyses, contributing to the creation of a standard method.

Gonadotropin-Releasing Hormone (GnRH) Agonist Protocol Improves Pregnancy Outcomes During In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) Treatment in Young Infertile Women: A Retrospective Study.

Objective The objective of this study was to determine if gonadotropin-releasing hormone agonist (GnRH-a) or gonadotropin-releasing hormone antagonist (GnRH-ant) protocols during in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment in young infertile women improve their pregnancy outcomes. Methodology We retrospectively reviewed the records of 876 young infertile women aged 20-35 years who underwent fresh embryo transfer in IVF/ICSI cycles. The data were collected from their initial visits to the reproductive medicine center of the Second Affiliated Hospital of Zhengzhou University between January 2019 and December 2022. We divided them into two groups according to the controlled ovarian hyperstimulation (COH) protocols: GnRH-a (n = 580) and GnRH-ant (n = 296). The primary outcome assessed in this study was the live birth rate. The secondary observation indicators included the total dose and duration of gonadotropin (Gn), total embryo transfer, day three (D3) embryo transfer, total two pro-nuclei (2PN) cleavage count, number of fertilizations, and implantation rate. Results The live birth rate had no clinical significance (P > 0.05). The total dose and duration of Gn stimulation in the GnRH-ant group were lower than in the GnRH-a group (P  < 0.05). The total embryo transfer, D3 embryo transfer, total cleavage count, total 2PN cleavage count, number of fertilizations, transfer, and mature oocytes in metaphase II (MII) of D3 embryos in the GnRH-a group were higher than those in the GnRH-ant group (P  < 0.05). The clinical pregnancy rate and implantation rate of the GnRH-a group were higher than those of the control group. Conclusions The total embryo transfer, D3 embryo transfer, total cleavage count, total 2PN cleavage count, number of fertilizations, transfer and MII of D3 embryos, clinical pregnancy, and implantation rates were significantly higher in the GnRH-a protocol group. The total dosage of Gn and duration of Gn stimulation were lower in the GnRH-ant group than in the GnRH-a group. These findings provide the basis for the selection of the COH protocol in normal Chinese ovarian response patients undergoing IVF/ICSI.

How D-amino acids embedded in the protein sequence modify its digestibility: Behaviour of digestive enzymes tested on a model peptide used as target.

D-amino acids can affect the action of digestive enzymes, hence the protein digestion. In this work the behaviour of the main stomach and gut digestive enzymes (pepsin, trypsin, and chymotrypsin) in the presence of D-amino acids in the protein chain was monitored over time using a model peptide, Ac-LDAQSAPLRVYVE-NH2 (belonging to ß-lactoglobulin, position 48-60), where L-amino acids were systematically substituted by D-amino acids. The results showed several changes in the behaviour of digestive enzymes, not only when the D-amino acids are inserted at the specific cleavage sites (after Val-57), but in some cases also when in distant positions. The effect seemed more pronounced in the case of pepsin rather than the gut enzymes, possibly indicating a better resilience of the upper gut phase of digestion to racemization. These results demonstrated that racemization could impair nutritional value by slowing down digestibility and has different effects according to the enzyme/amino acids involved.

Effects of captan, mancozeb and azoxystrobin fungicides on motility, oxidative stress and fatty acid profiles in rainbow trout (Oncorhynchus mykiss) spermatozoa.

An in vitro study using rainbow trout spermatozoa was designed to evaluate the toxic effects of different concentrations of captan (CPT), mancozeb (MCZ), and azoxystrobin (AZX) fungicides on motility parameters, lipid peroxidation, SOD activity, total antioxidant capacity (TAC), and DPPH inhibition. Moreover, changes in fatty acids profiles caused by the fungicides were determined for the first time. The results revealed that motility parameters, SOD activities, TAC values, and DPPH inhibitions decreased significantly while lipid peroxidation increased after ≥2 µg/L of CPT, ≥1 µg/L of MCZ, and ≥5 µg/L of AZX incubations for 2 h at 4 °C. Additionally, 10 µg/L CPT, 5 µg/L MCZ, and 200 µg/L AZX reduced motility to the 50 % level. Our results clearly demonstrated significant changes in the fatty acids profiles of spermatozoa exposed to these concentrations of the fungicides. The highest lipid peroxidation and the lowest monounsaturated and polyunsaturated saturated fatty acids (MUFA and PUFA, respectively) were detected in AZX. Even though the susceptibility of spermatozoa to oxidative damage is generally attributed to PUFA contents, the results of this study have represented that MUFA content could play a part in this tendency. Moreover, the lower concentration of MCZ reduced motility to the % 50 level while it deteriorated the fatty acids profile less than did AZX. Overall, the present study demonstrated that the detrimental effects of the fungicides on mitochondrial respiration and related enzymes have more priority than oxidative stress in terms of their toxicities on spermatozoa. It has also been suggested that fish spermatozoa are a good model for determining changes in the fatty acid profiles by fungicides, probably, by other pesticides and environmental contaminants as well.

Identifying assessment criteria for in vitro studies: a method and item bank.

To support the development of appraisal tools for assessing the quality of in vitro studies, we developed a method for literature-based discovery of study assessment criteria, used the method to create an item bank of assessment criteria of potential relevance to in vitro studies, and analyzed the item bank to discern and critique current approaches for appraisal of in vitro studies. We searched four research indexes and included any document that identified itself as an appraisal tool for in vitro studies, was a systematic review that included a critical appraisal step, or was a reporting checklist for in vitro studies. We abstracted, normalized, and categorized all criteria applied by the included appraisal tools to create an "item bank" database of issues relevant to the assessment of in vitro studies. The resulting item bank consists of 676 unique appraisal concepts from 67 appraisal tools. We believe this item bank is the single most comprehensive resource of its type to date, should be of high utility for future tool development exercises, and provides a robust methodology for grounding tool development in the existing literature. While we set out to develop an item bank specifically targeting in vitro studies, we found that many of the assessment concepts we discovered are readily applicable to other study designs. Item banks can be of significant value as a resource; however, there are important challenges in developing, maintaining, and extending them of which researchers should be aware.

Vitamin D levels in couples undergoing In vitro Fertilization: Lack of Association with Embryo Quality or Pregnancy Rates.

OBJECTIVE: To investigate the potential impact of vitamin D serum levels of couples going through in vitro fertilization in terms of embryo quality and pregnancy rates. DESIGN: Retrospective cohort study SETTING: Fertipraxis, private human reproduction center on Rio de Janeiro, Brazil. SUBJECTS: 267 couples who underwent intracytoplasmic sperm injection between January 2017 and March 2019. EXPOSURE: The couples were categorized into four groups based on 25OH vitamin D levels measured at the beginning of the stimulation protocol: Group 1 with levels ≥ 30 ng/mL for both women and men; Group 2 with levels < 30 ng/mL for both; Group 3 with women < 30 ng/mL and men ≥ 30 ng/mL; and Group 4 with women ≥ 30 ng/mL and men < 30 ng/mL. MAIN OUTCOME MEASURES: We consider quantity and quality of embryos during the cleavage and blastocyst stages as primary outcomes. Correspondingly, clinical pregnancy rate was regarded as a secondary outcome. RESULTS: Our findings revealed no significant correlations between the studied VD groups and the evaluated outcomes. This includes quantity and quality of embryos during the cleavage and blastocyst stages, as well as clinical pregnancy rate. Primary analysis revealed a small but statistically significant difference in the duration of controlled ovarian stimulation between group 1 and group 2 (p=0.035; CI=0.07 - 3.04) and between group 1 and group 3 (p=0.040; CI=0.05 - 3.23). CONCLUSION: The present study found no correlation between the studied VD levels and quantity and quality of cleavage or blastocyst stage embryos, nor did it show any impact on clinical pregnancy rates. Further well designed, prospective studies are warranted to determine whether and how vitamin D affects reproductive outcomes.

Characterization, in vitro elderly digestion, and organoids cell uptake of curcumin-loaded nanoparticles.

Curcumin, a bioactive compound, showed versatile in anti-inflammatory and anti-cancer ability, while their biological fate in elderly is unclear. In this study, curcumin-loaded nanoparticles based on octyl succinate hydrate (OSA) starch and sodium caseinate were prepared and the in vitro elderly digestion and absorption fate was investigated. The loading capacity of curcumin-loaded nanoparticles prepared from OSA starch (HI), sodium caseinate (SC) and OSA starch­sodium caseinate (HS) were all higher than 15%. Curcumin release behavior of the three nanoparticles during in vitro digestion conformed to first-order kinetics. Meanwhile, the transport efficiency of curcumin for HI, SC, and HS increased significantly than the free curcumin (near 1-fold), and the permeability were 1.9, 2.0, and 2.0 times, respectively. The gene expressions of TNF-α, SREBP2 and NPC1L1 in the organoids were enhanced than control group. This study provided scientific reference and guidance for encapsulation of curcumin and digestion and absorption properties in elderly.

A Novel 3D Printed Model of Infected Human Hair Follicles to Demonstrate Targeted Delivery of Nanoantibiotics.

Hair follicle-penetrating nanoparticles offer a promising avenue for targeted antibiotic delivery, especially in challenging infections like acne inversa or folliculitis decalvans. However, demonstrating their efficacy with existing preclinical models remains difficult. This study presents an innovative approach using a 3D in vitro organ culture system with human hair follicles to investigate the hypothesis that antibiotic nanocarriers may reach bacteria within the follicular cleft more effectively than free drugs. Living human hair follicles were transplanted into a collagen matrix within a 3D printed polymer scaffold to replicate the follicle's microenvironment. Hair growth kinetics over 7 days resembled those of simple floating cultures. In the 3D model, fluorescent nanoparticles exhibited some penetration into the follicle, not observed in floating cultures. Staphylococcus aureus bacteria displayed similar distribution profiles postinfection of follicles. While rifampicin-loaded lipid nanocapsules were as effective as free rifampicin in floating cultures, only nanoencapsulated rifampicin achieved the same reduction of CFU/mL in the 3D model. This underscores the hair follicle microenvironment's critical role in limiting conventional antibiotic treatment efficacy. By mimicking this microenvironment, the 3D model demonstrates the advantage of topically administered nanocarriers for targeted antibiotic therapy against follicular infections.

Synthesis of Novel Acrylamide Graft Copolymer of Acacia nilotica Gum for the Stabilization of Melatonin Nanoparticles for Improved Therapeutic Effect: Optimization Using (3)2 Factorial Design.

The objective of the present study was to optimize the microwave-assisted synthesis of the acrylamide graft copolymer of Acacia nilotica gum (AM-co-ANG). Furthermore, graft copolymer was used for the formulation of a nanoparticulate system using a novel top to bottom solvent antisolvent technique for the delivery of melatonin. Grafting of ANG was optimized by using 32 factorial design, where concentrations of polymer and monomer (acrylamide) were used as independent variables and swelling index in acidic (0.1 N HCl) and basic (1 N NaOH) pH. Grafted polymers were further used to develop and optimize nanoparticulate system using concentration of the graft copolymer and concentration of drug as independent variables. The size of the nanoformulation and entrapment efficiency were selected as dependent variables. Difference in infrared spectrum and absorbance maxima in the ultraviolet region confirm that grafting has taken place. Porous structure and a higher contact angle confirmed hydrophobic nature of AM-co-ANG as compared with the native polymer. Acrylamide graft copolymers show more swelling in 1 N NaOH as compared with 0.1 N HCl. In vitro toxicity studies in hepatic (HepG2 cell line), brain (SHSY5Y cell line), and skin (HaCaT cell line) cells easily predict that synthesized polymer have no cytotoxicity. The entrapment efficiency ranged from 55.24 ± 1.35% to 73.21 ± 1.83%. A nonlinear correlation was observed between independent and dependent variables, as confirmed by multivariate analysis of variance, surface regression, and the correlation report. The prepared formulations were able to release drug up to 12 h. The regression coefficient easily predicted that most of the formulations followed Baker-Lonsdale drug release kinetics.

Recent Australian Legislative Developments in the Regulation of Assisted Reproductive Technology.

This section considers the recent resurgence of regulatory interest in the field of assisted reproductive technology (ART) practices focusing on the new legislative framework in the Australian Capital Territory (ACT). It provides an overview of the Australian regulatory framework in this field and considers how the new legislation in the ACT sits alongside this framework. A detailed overview of the key provisions of the ACT legislation is provided, before considering whether the legislation goes far enough in addressing some of the more controversial issues in the field of ART.

Monitoring of controlled ovarian stimulation in IVF.

Since the inception of in vitro fertilization (IVF), monitoring of controlled ovarian stimulation (COS) has traditionally involved numerous appointments for ultrasound and laboratory testing to guide medication use and dosing, determine trigger timing, and allow for measures to reduce the risk of ovarian hyperstimulation syndrome (OHSS). Recent advances in the field of assisted reproductive technology (ART) have called into question the timing and frequency of COS monitoring appointments, as discussed in this commentary.

Tackling neurodegeneration in vitro with omics: a path towards new targets and drugs.

Drug discovery is a generally inefficient and capital-intensive process. For neurodegenerative diseases (NDDs), the development of novel therapeutics is particularly urgent considering the long list of late-stage drug candidate failures. Although our knowledge on the pathogenic mechanisms driving neurodegeneration is growing, additional efforts are required to achieve a better and ultimately complete understanding of the pathophysiological underpinnings of NDDs. Beyond the etiology of NDDs being heterogeneous and multifactorial, this process is further complicated by the fact that current experimental models only partially recapitulate the major phenotypes observed in humans. In such a scenario, multi-omic approaches have the potential to accelerate the identification of new or repurposed drugs against a multitude of the underlying mechanisms driving NDDs. One major advantage for the implementation of multi-omic approaches in the drug discovery process is that these overarching tools are able to disentangle disease states and model perturbations through the comprehensive characterization of distinct molecular layers (i.e., genome, transcriptome, proteome) up to a single-cell resolution. Because of recent advances increasing their affordability and scalability, the use of omics technologies to drive drug discovery is nascent, but rapidly expanding in the neuroscience field. Combined with increasingly advanced in vitro models, which particularly benefited from the introduction of human iPSCs, multi-omics are shaping a new paradigm in drug discovery for NDDs, from disease characterization to therapeutics prediction and experimental screening. In this review, we discuss examples, main advantages and open challenges in the use of multi-omic approaches for the in vitro discovery of targets and therapies against NDDs.