Neurodevelopmental outcomes of school-age children conceived after hysterosalpingography with oil-based or water-based iodinated contrast: long-term follow-up of a nationwide randomized controlled trial.

STUDY QUESTION: Does preconceptional exposure to oil-based iodinated contrast media during hysterosalpingography (HSG) impact children's neurodevelopment compared with exposure to water-based alternatives? SUMMARY ANSWER: Our study found no large-sized effects for neurodevelopment in children with preconceptional exposure to oil-based iodinated contrast media during HSG compared with water-based alternatives. WHAT IS KNOWN ALREADY: HSG is widely used as a diagnostic tool in the female fertility work-up. Tubal flushing with oil-based iodinated contrast has been shown to enhance fertility outcomes in couples with unexplained infertility, increasing the chances of pregnancy and live birth compared with water-based alternatives. However, oil-based contrast contains higher doses of iodine and has a longer half-life, and concerns exist that iodinated contrast media can affect women's iodine status and cause temporary (sub)clinical hypothyroidism in mothers and/or foetuses. Considering that thyroid hormones are vital to embryonal and foetal brain development, oil-based contrast media use could increase the risk of impaired neurodevelopment in children conceived shortly after HSG. Here we examine neurodevelopmental outcomes in school-aged children conceived after HSG. STUDY DESIGN, SIZE, DURATION: This is a long-term follow-up of the H2Oil trial in which oil-based or water-based contrast was used during HSG (Netherlands; 2012-2014; NTR3270). Of 369 children born <6 months after HSG in the study, we contacted the mothers of 140 children who gave consent to be contacted for follow-up. The follow-up study took place from January to July 2022 (NCT05168228). PARTICIPANTS/MATERIALS, SETTINGS, METHODS: The study included 69 children aged 6-9 years who were conceived after HSG with oil-based (n = 42) or water-based contrast (n = 27). The assessments targeted intelligence (Wechsler Intelligence Scale for Children), neurocognitive outcomes (computerized neurocognitive tests), behavioural functioning (parent and teacher questionnaires), and academic performance. Linear regression models, adjusted for age, sex, and parental educational attainment were employed to compare groups. MAIN RESULTS AND THE ROLE OF CHANCE: School-aged children born to mothers after oil-based contrast HSG did not significantly differ from children born to mothers after water-based contrast HSG, in regards to intelligence, neurocognitive functioning, behavioural functioning, or academic performance, with the exception of better performance for visuomotor integration functions in children exposed to oil-based contrast preconception. After exploratory correction for multiple comparisons, none of the group differences was statistically significant. LIMITATIONS, REASONS FOR CAUTION: The small sample size of this follow-up study limited statistical power. This study provides evidence for the absence of large-sized differences between preconceptional exposure to the two contrast media types but does not rule out more subtle effects on neurodevelopment compared to naturally conceived children without preconceptional exposure to HSG. WIDER IMPLICATIONS OF THE FINDINGS: This study contributes to our knowledge about the long-term effects of different types of iodinated contrast media used in fertility work-up, indicating that choosing oil-based over water-based iodinated contrast media is unlikely to have major effect on the long-term neurodevelopmental outcomes of children conceived shortly after HSG. However, further research should focus on the overall safety of iodine exposure during HSG, comparing children conceived after HSG to those conceived naturally as both types of contrast contain high amounts of iodine. STUDY FUNDING/COMPETING INTEREST(S): The original H2Oil randomized controlled trial was an investigator-initiated study that was funded by the two academic hospitals now merged into the Amsterdam University Medical Centre. The current follow-up study (Neuro-H2Oil) is funded through a research grant awarded to the authors by the Amsterdam Reproduction & Development (AR&D) research institute. S.K. is funded by a AMC MD/PhD Scholarship from the Amsterdam UMC. S.K. reports holding voluntary roles in the civil society organizations Universities Allied for Essential Medicines and People's Health Movement. V.M. reports receiving travel and speaker fees as well as research grants from Guerbet, Merck and Ferring. K.D. reports receiving travel and speaker fees as well as research grants from Guerbet. BWM is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy, travel support and research funding from Merck, consultancy for Organon and Norgine, and holding stock from ObsEva. The other authors report no conflict of interest. TRIAL REGISTRATION NUMBER: NCT05168228.

The effect of prior hysterosalpingo-foam sonography or hysterosalpingography on tubal patency: a secondary analysis of a randomized controlled trial.

STUDY QUESTION: Does hysterosalpingo-foam sonography (HyFoSy) prior to hysterosalpingography (HSG) or HSG prior to HyFoSy affect visible tubal patency when compared HSG or HyFoSy alone? SUMMARY ANSWER: Undergoing either HyFoSy or HSG prior to tubal patency testing by the alternative method does not demonstrate a significant difference in visible tubal patency when compared to HyFoSy or HSG alone. WHAT IS KNOWN ALREADY: HyFoSy and HSG are two commonly used visual tubal patency tests with a high and comparable diagnostic accuracy for evaluating tubal patency. These tests may also improve fertility, although the underlying mechanism is still not fully understood. One of the hypotheses points to a dislodgment of mucus plugs that may have disrupted the patency of the Fallopian tubes. STUDY DESIGN, SIZE, DURATION: This is a secondary analysis of the randomized controlled FOAM study, in which women underwent tubal patency testing by HyFoSy and HSG, randomized for order of the procedure. Participants either had HyFoSy first and then HSG, or vice versa. Here, we evaluate the relative effectiveness of tubal patency testing by HyFoSy or HSG prior to the alternative tubal patency testing method on visible tubal patency, compared to each method alone. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertile women aged between 18 and 41 years scheduled for tubal patency testing were eligible for participating in the FOAM study. Women with anovulatory cycles, endometriosis, or with a partner with male infertility were excluded. To evaluate the effect HyFoSy on tubal patency, we relied on HSG results by comparing the proportion of women with bilateral tubal patency visible on HSG in those who underwent and who did not undergo HyFoSy prior to their HSG (HyFoSy prior to HSG versus HSG alone). To evaluate the effect of HSG on tubal patency, we relied on HyFoSy results by comparing the proportion of women with bilateral tubal patency visible on HyFoSy in those who underwent and who did not undergo HSG prior to their HyFoSy (HSG prior to HyFoSy versus HyFoSy alone). MAIN RESULTS AND THE ROLE OF CHANCE: Between May 2015 and January 2019, we randomized 1160 women (576 underwent HyFoSy first followed by HSG, and 584 underwent HSG first followed by HyFoSy). Among the women randomized to HyFoSy prior to HSG, bilateral tubal patency was visible on HSG in 467/537 (87%) women, compared with 472/544 (87%) women who underwent HSG alone (risk difference 0.2%; 95% CI: -3.8% to 4.2%). Among the women randomized to HSG prior to HyFoSy, bilateral tubal patency was visible on HyFoSy in 394/471 (84%) women, compared with 428/486 (88%) women who underwent HyFoSy alone (risk difference -4.4%; 95% CI: -8.8% to 0.0%). LIMITATIONS, REASONS FOR CAUTION: The results of this secondary analysis should be interpreted as exploratory and cannot be regarded as definitive evidence. Furthermore, it has to be noted that pregnancy outcomes were not considered in this analysis. WIDER IMPLICATIONS OF THE FINDINGS: Tubal patency testing by either HyFoSy or HSG, prior to the alternative tubal patency testing method does not significantly affect visible tubal patency, when compared to alternative method alone. This suggests that both methods may have comparable abilities to dislodge mucus plugs in the Fallopian tubes. STUDY FUNDING/COMPETING INTEREST(S): The FOAM study was an investigator-initiated study, funded by ZonMw, a Dutch organization for Health Research and Development (project number 837001504). IQ Medical Ventures provided the ExEm®-FOAM kits free of charge. The funders had no role in study design, collection, analysis, or interpretation of the data. H.R.V. reports consultancy fees from Ferring. M.v.W. received a travel grant from Oxford University Press in the role of Deputy Editor for Human Reproduction and participates in a Data Safety and Monitoring Board as an independent methodologist in obstetrics studies in which she has no other role. M.v.W. is coordinating editor of Cochrane Fertility and Gynaecology. B.W.J.M. received an investigator grant from NHMRC (GNT1176437) and research funding from Merck KGaA. B.W.J.M. reports consultancy for Organon and Merck KGaA, and travel support from Merck KGaA. B.W.J.M. reports holding stocks of ObsEva. V.M. received research grants from Guerbet, Merck and Ferring and travel and speaker fees from Guerbet. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER: International Clinical Trials Registry Platform No. NTR4746.

Niacin-induced flushing: Mechanism, pathophysiology, and future perspectives.

Flushing is a typical physiological reaction to high emotional reactions. It is characterized by cutaneous vasodilation and a feeling of warmth and skin redness, especially in the face areas. Flushing is frequently linked to social anxiety, but it can also be a sign of a number of benign and malignant medical disorders. The study focuses on niacin-induced flushing, a well-researched side effect of the niacin, a drug which increases cholesterol levels. Niacin-induced flushing occurs when the hydroxycarboxylic acid receptor 2 (HCA2 or GPR109A) is activated. This starts a signaling cascade that releases prostaglandins, especially PGD2, which causes cutaneous vasodilation. Furthermore, niacin directly interacts with the transient receptor potential (TRP) channel TRPV1, offering a different, non-prostaglandin-based explanation for flushing brought on by niacin, highlighting the intricate physiological mechanisms behind this widespread occurrence. The review delves deeper into the advantages of niacin treatment for the cardiovascular system, highlighting how it can improve lipid profiles and lower cardiovascular events when used with statins. To sum it up, this study offers a thorough understanding of flushing, including its physiological foundation, many etiologies, diagnostic difficulties, and the subtleties of flushing caused by niacin. The investigation of innovative dose forms and nanomedicine highlights the continuous endeavors to improve patient compliance and reduce side effects, laying the groundwork for further developments in flushing treatment.

Harlequin syndrome in a patient with probable hemicrania continua and exertional headache - is there a link? a case report.

BACKGROUND: The harlequin syndrome is a rare disorder of the autonomic nervous system characterized by unilateral diminished flushing and sweating of the face following exposure to heat or physical activity. It results from sympathetic dysfunction and most commonly occurs idiopathically. A secondary development due to an underlying pathology (e.g., carotid artery dissection, tumors) must be excluded at first appearance. There is evidence that the cranial autonomic system is involved in the pathophysiology of trigeminal autonomic headaches like hemicrania continua. Therefore, an overlap in the pathophysiology of harlequin syndrome and trigeminal autonomic headache disorders seems plausible. However, the association of a harlequin syndrome with hemicrania continua was never reported. CASE PRESENTATION: This work describes the case of a 42-year-old female patient presenting to our headache unit. The patient reported persisting unilateral headache of the right side of dragging or squeezing character accompanied by trigeminal autonomic symptoms, including lacrimation, nasal congestion, conjunctival injection and Horner's syndrome, and was responsive to treatment with 75mg/d indomethacin. Five months after the initial consultation, the patient noted that the upper right quadrant of her face was pale after jogging. A harlequin syndrome was diagnosed. Further, she developed a short-lasting, bilateral headache of pulsatile character during strenuous exercise consistent with exertional headache. Comprehensive diagnostic evaluations, encompassing cranial and cervical MRI scans, laboratory tests, and biopsies, culminated in the diagnosis of Sjögren's syndrome. This finding suggests that the trigemino-autonomic dysfunction may either be idiopathic or a direct manifestation of Sjögren's syndrome. CONCLUSIONS: This report documents the case of a rare combination of a headache resembling probable hemicrania continua and the harlequin syndrome (and even exertional headache). It illustrates the underlying anatomy of the autonomic nervous system in a clinical context and emphasizes the hypothesis of a pathophysiological link between abnormal sympathetic activity and trigeminal autonomic headaches.

Quantitative Microbial Risk Assessment Framework Incorporating Water Ages with Legionella pneumophila Growth Rates.

Water age in drinking water systems is often used as a proxy for water quality but is rarely used as a direct input in assessing microbial risk. This study directly linked water ages in a premise plumbing system to concentrations of Legionella pneumophila via a growth model. In turn, the L. pneumophila concentrations were used for a quantitative microbial risk assessment to calculate the associated probabilities of infection (Pinf) and clinically severe illness (Pcsi) due to showering. Risk reductions achieved by purging devices, which reduce water age, were also quantified. The median annual Pinf exceeded the commonly used 1 in 10,000 (10-4) risk benchmark in all scenarios, but the median annual Pcsi was always 1-3 orders of magnitude below 10-4. The median annual Pcsi was lower in homes with two occupants (4.7 × 10-7) than with one occupant (7.5 × 10-7) due to more frequent use of water fixtures, which reduced water ages. The median annual Pcsi for homes with one occupant was reduced by 39-43% with scheduled purging 1-2 times per day. Smart purging devices, which purge only after a certain period of nonuse, maintained these lower annual Pcsi values while reducing additional water consumption by 45-62%.

Achieving Carbon Mitigation with Economic Benefits through High-Resolution Analysis of Renewable Resource Integration in Global Coastal Cities.

Coastal regions, home to more than half of the global population and contributing over 50% to the global economy, possess vast renewable resources, such as seawater and solar energy. The effective utilization of these resources, through the seawater-cooled district cooling system (SWDCS), seawater toilet flushing (SWTF), and rooftop solar photovoltaic system (RTPV), has the potential to significantly reduce carbon emissions. However, implementing these technologies in different geographic contexts to achieve the desired carbon and economic outcomes at the city level lacks a clear roadmap. To address this challenge, we comprehensively analyzed 12 coastal megacities worldwide by integrating geospatial building data. Our study evaluated the potential energy savings, carbon mitigation, and levelized carbon abatement costs (LCACs) from a life cycle perspective. The results revealed that using seawater and solar energy within urban boundaries can reduce electricity consumption from 1 to 24% across these cities. The spatial distribution of the LCAC for seawater-based systems exhibited more variation compared to the RTPV. By applying specific LCAC thresholds ranging from 0 to 225 USD/tCO2e, all cities could achieve both carbon reductions and economic benefits. These thresholds resulted in up to 80 million tonnes of carbon emission reductions and 5 billion USD of economic benefits, respectively. Our study provides valuable insights into integrating renewable resource systems, enabling coastal cities to achieve carbon and economic advantages at the city scale simultaneously.

Erythromelalgia. Part II: Differential diagnoses and management.

The management of erythromelalgia is challenging and requires multidisciplinary effort. Patient education is crucial as unsafe self-administered cooling techniques can lead to significant morbidity, including acral necrosis, infection, and amputation. The goal of management is pain control, reduction of flare frequency, and prevention of complications. This text is focused on the management of erythromelalgia and several other incompletely understood and under-recognized neurovascular disorders such as red scrotum syndrome, red ear syndrome, facial flushing, and complex regional pain syndrome.

Residual chemotherapy drugs after flushing infusion lines.

INTRODUCTION: During administration of chemotherapies, disconnection presents risks for nurses. Thus, it is recommended to flush the infusion line with solvent to reduce this risk and ensure that the entire dose is administered. Objectives of this study were to evaluate flushing practices and to investigate the efficiency of flushing, according to the type of hospitalization, in hospitalization (HU) or day-care unit (DCU), for three drugs. METHODS: Twenty secondary infusion lines were collected in five HU and 20 in two DCU. Flushing volumes were estimated by weighing solvent bags. The amount of residual drug was measured for secondary lines by mass spectrometry coupled with high-performance liquid chromatography. RESULTS: Chemotherapies were administered by 26 nurses. All of infusion lines contained chemotherapy after flushing. Flushing volumes, residual concentrations and flushing efficiencies were significantly different between these two types of units. In contrast, flushing volumes administrated did not differ between chemotherapy drugs. CONCLUSIONS: Local recommendations are fully implemented in HU and partially in DCU. The use of small volumes in DCU is related to the patient length of stay, it may, also, be due to omitting the average tubing volume. All infusion lines still contained chemotherapy, including those with a flush volume much higher than recommended, showing that the risk of exposure persists. To achieve a rinse volume greater than 50 mL, it is necessary to use at least 100 mL. It is also important to insist on personal protective equipment and to consider closed safety system for administration.

Congenital Insensitivity to Pain With Anhidrosis Is Associated With Harlequin Color Change: A Survey Study.

Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy (HSAN) type IV, is an extremely rare autosomal recessive congenital condition characterized by the loss of sensation to pain and absence of sweating with one case report linking this with harlequin color change. To explore the relationship further, we developed a survey using the Research Electronic Data Capture software and distributed it to families and others with close relationships and knowledge of patients with CIPA. Our results indicate that harlequin color change, characterized by unilateral flushing of the face and/or body, was significant and noted by all respondents as being present early in the condition appearing around the same time as first symptoms and around or before diagnosis of CIPA. Future clinicians should be aware of this dermatological phenomenon and its potential association with CIPA patients, especially during early disease manifestation where diagnosis can be difficult.

Phenological trends and associated climate drivers of a tree community in lowland dipterocarp forest, Western Ghats, India.

Understanding phenological responses of tropical forest plant communities is crucial for identifying climate-induced changes in ecosystem dynamics. Monitoring phenology across diverse species in natural habitats provides cost-effective insights for conserving both species and forests. We studied tree phenology in a lowland evergreen dipterocarp forest in the Western Ghats, India. About 719 tree individuals representing 95 species were monitored for their vegetative and reproductive phenology from April 2021 to September 2023. Circular statistics detected seasonality in phenological events and Generalized Linear Mixed Modelling (GLMM) identified influence of climate variables on the phenological responses of the tree community. We also assessed how the activity and intensity of phenophases vary over the study period. Our results showed that leaf flushing and flowering peaked during the dry season, with mass flowering observed in two dominant dipterocarps. Fruit production peaked before the monsoon. We also observed diversity in vegetative and reproductive phenodynamics across species groups (forest strata, sexual system, and seed size). Leaf flushing was positively correlated with maximum relative humidity and negatively correlated with maximum temperature and the number of rainy days. Flowering had negative correlations with maximum relative humidity, rainfall days, and maximum temperature but showed a positive correlation with minimum temperature. Fruiting was positively correlated with maximum temperature and negatively correlated with rainy days. This detailed phenological information provides critical knowledge on resource availability and insights into how climate and seasonal changes affect plant growth cycles thereby aiding reforestation and biodiversity conservation strategies in vulnerable forest areas.

Ultrasound-guided Lipiodol® hysterosalpingography: A prospective study on pregnancy and complication rates.

BACKGROUND: Fluoroscopic hysterosalpingography (HSG) with Lipiodol® is safe and has a therapeutic effect on fertility: transient in endometriosis-related infertility and sustained in unexplained infertility. Ultrasound is replacing fluoroscopy as the preferred imaging modality for HSG due to comfort and radiation safety (no ionising radiation). The safety of ultrasound-guided Lipiodol® HSG is uncertain. AIMS: Prospectively observe pregnancy and complication rates after ultrasound-guided Lipiodol® HSG. MATERIALS AND METHODS: A single-centre prospective study of women with unexplained infertility undergoing ultrasound-guided Lipiodol® uterine bathing and tubal flushing after tubal patency confirmed with ExEm® Foam HyFoSy (hysterosalpingo-foam-sonography). Pregnancy outcomes at six months and serum and urinary thyroid function at one, three and eight weeks were recorded. Pain scores were recorded during and immediately after HSG. Descriptive statistics are reported. RESULTS: Fifty-two participants were enrolled between July 2019 and April 2021, median age 33 years (range 21-45). Only 45 (87%, 45/52) completed the Lipiodol® HSG; 5/7 experienced intravasation during initial HyFoSy. Of 30 women at follow-up, 57% had biochemical (17/30, 95% CI 37%-75%), 53% clinical (16/30 95% CI 34%-72%) and 35% ongoing pregnancies (11/30, 95% CI 20%-56%). The rate of subclinical hypothyroidism (SCH) at two months was 41% (7/17). One intravasation event occurred during Lipiodol® HSG (2%, 1/45). Median pain score was 5/10 (range 0-9, interquartile range 2.5-7). No anaphylaxis, infection or oil embolism was observed. CONCLUSION: Outpatient ultrasound-guided Lipiodol® HSG was safe, with pregnancy rates comparable to previous studies of fluoroscopic guidance. Rates of intravasation and SCH were also similar, confirming the need to monitor thyroid function.

The potential to manage releases of Bacillus anthracis using bioretention and a high flow media filter: Results of simulated runoff testing with tracer spores Bacillus globigii.

The threat of bioterrorism has spurred research on the decontamination and containment of different agents. Anthrax [causative agent Bacillus anthracis (Ba)] is a disease that can lead to severe infections within human and animals, particularly when inhaled. This research investigated the use of spore-contaminated simulated runoff events into stormwater control measures (SCMs), which are designed to retain and improve the quality of runoff and may have the potential to filter and contain the spores. In this study, the effectiveness of a bioretention cell (BRC) and high flow media filter (HFMF) in Huron, Ohio, were evaluated for removal of Bacillus globigii (Bg) spores (a harmless cognate of Ba). Three 4-8 mm simulated runoff events were created for each SCM using a fire hydrant and Bg spores were injected into the runoff upstream of the SCM inlets. The BRC significantly (p < 0.001) outperformed the HFMF in reducing Bg concentrations and loads, with an average load reduction of 1.9 log (∼99% reduction) compared to 0.4 (∼60% reduction), respectively. A probable critical design factor leading to these differences was the infiltration rate of the media and subsequent retention time within the filters, which was supported by similar disparities in suspended solids reductions. Differences in spore removal may also have been due to particle size distribution of the HFMF, which was more gravelly than the bioretention cell. At 3 and 6 months after the-simulated runoff tests, soil samples taken from both SCMs, yielding detectable Bg spores within the top 15 cm of media, with increased spore concentrations where ponding occurred for longer durations during the tests. This suggests that forebays and areas near inlets may be hotspots for spore cleanup in a real-world bioterrorism incident.

Rumen-protected l-carnitine supplementation during mating period altered metabolic status and reproductive performance of ewes.

Current study hypothesized that dietary l-carnitine (LC) inclusion during the mating period ameliorates both metabolic status and reproductive performance of ewes. Seventy Baluchi ewes (52 ± 4.2 kg of bodyweight and 18 ± 6 months old of age) were enrolled in this study. Animals were randomly allocated into two dietary treatments, control (only basal diet) or basal diet plus supplementation with a rumen-protected LC (Carneon 20 Rumin-pro; 20% LC; Kaesler Nutrition GmbH) at the rate of 10 g/head/day from 21 days before until 35 days after introducing rams to the ewes (MP). Feed intake was monitored by subtracting the ort from feed offered. Blood sample collection was conducted on Days -10, +10 and +20 relative to MP. Pregnancy was confirmed on Day 30 post-MP. Feed intake of the ewes in the LC group was higher than the control (p < 0.05). LC supplementation increased the cholesterol concentration in the ewes (p < 0.05). Blood urea concentration of animals in the LC group was significantly lower than the control (p < 0.05). The mRNA expression of toll-like receptor 4 was evidently lower in animals supplemented with LC than the control (p < 0.05). Both lambing and fecundity rates in the LC group tended to be higher compared with the control. LC supplementation showed potential to alter certain metabolites in the ewes. A tendency for higher lambing rate may partly be driven by dams efficient energy partitioning to support foetal growth and maintaining pregnancy.

Ni-P-PTFE cathode with low surface energy for enhancing electrochemical water softening performance.

Efficient cathode regeneration is a significant challenge in the electrochemical water softening process. This work explores the use of an electroless plating Ni-P-PTFE electrode with low surface energy for this purpose. The Ni-P-PTFE electrode demonstrates improved self-cleaning performance at high current densities. By combining the low surface energy of the electrode with fluid flushing shear force, the precipitation rate on the Ni-P-PTFE electrode remains stable at approximately 18 g/m2·h over extended periods of operation. Additionally, the cleaning efficiency of the Ni-P-PTFE electrode surpasses that of stainless steel by 66.34%. The Ni-P-PTFE electrode can maintain a larger active area and a longer operational lifespan is attributed to its self-cleaning performance derived from low surface energy. Furthermore, the loose scale layers on the electrode surface are easily removed during electrochemical water softening processes, presenting a novel approach to cathode surface design.

Transdermal Delivery of Niacin Through Polysaccharide Films Ameliorates Cutaneous Flushing in Experimental Wistar Rats.

BACKGROUND: Niacin, an established therapeutic for dyslipidemia, is hindered by its propensity to induce significant cutaneous flushing when administered orally in its unmodified state, thereby constraining its clinical utility. OBJECTIVE: This study aimed to fabricate, characterize, and assess the in-vitro and in-vivo effectiveness of niacin-loaded polymeric films (NLPFs) comprised of carboxymethyl tamarind seed polysaccharide. The primary objective was to mitigate the flushing-related side effects associated with oral niacin administration. METHODS: NLPFs were synthesized using the solvent casting method and subsequently subjected to characterization, including assessments of tensile strength, moisture uptake, thickness, and folding endurance. Surface characteristics were analyzed using a surface profiler and scanning electron microscopy (SEM). Potential interactions between niacin and the polysaccharide core were investigated through X-ray diffraction experiments (XRD) and Fourier transform infrared spectroscopy (FTIR). The viscoelastic properties of the films were explored using a Rheometer. In-vitro assessments included drug release studies, swelling behavior assays, and antioxidant assays. In-vivo efficacy was evaluated through skin permeation assays, skin irritation assays, and histopathological analyses. RESULTS: NLPFs exhibited a smooth texture with favorable tensile strength and moisture absorption capabilities. Niacin demonstrated interaction with the polysaccharide core, rendering the films amorphous. The films displayed slow and sustained drug release, exceptional antioxidant properties, optimal swelling behavior, and viscoelastic characteristics. Furthermore, the films exhibited biocompatibility and non-toxicity towards skin cells. CONCLUSION: NLPFs emerged as promising carrier systems for the therapeutic transdermal delivery of niacin, effectively mitigating its flushing-associated adverse effects.

The benefits of flushing with Lemuru fish oil as a source of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on the performance of reproductive parameters in Garut ewes.

This study aimed to evaluate and analyze the effects of a flushing diet containing Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) from Lemuru (Sardinella sp) fish oil on the reproductive performance parameters of Garut ewes. Forty (n = 40) primiparous Garut ewes aged 12-14 months with an average body weight of 28.92 ± 4.94 kg were assigned into four experimental treatment groups. The experimental diets contained roughage: concentrate (30:70%) designated as control concentrate (CNT), flushing concentrate with 6% palm oil (PO), flushing concentrate with 3% palm oil mixed with 3% lemuru oil as DHA and EPA sources (PFO), and flushing concentrate with the addition of 6% lemuru oil (FO). Treatment animals were fed two weeks before and after conception and parturition (8 weeks of total flushing treatment). The addition of fish oil at either 3% (PFO) or 6% (FO) resulted in significantly higher reproductive performance of ewes by increasing the litter size, as reflected by the birth of multiple kids (P < 0.05) compared to CNT and PO. Adding fish oil (PFO and FO) also maintains gestation, resulting in increased lamb yield, especially in the FO treatment, which yields the highest lamb yield (0% single lamb birth). The lamb male ratio was also higher with fish oil supplementation (PFO and PO) (P < 0.05). This research revealed a positive effect of 6% Lemuru oil on decreasing embryo loss and increasing the proportion of twin births. These findings thus support the hypothesis that ration flushing with double the required DHA and EPA from 6% Lemuru fish oil (FO) resulted in significantly higher reproductive performance in Garut sheep.

Genetic influences on alcohol flushing in East Asian populations.

BACKGROUND: Although it is known that variation in the aldehyde dehydrogenase 2 (ALDH2) gene family influences the East Asian alcohol flushing response, knowledge about other genetic variants that affect flushing symptoms is limited. METHODS: We performed a genome-wide association study meta-analysis and heritability analysis of alcohol flushing in 15,105 males of East Asian ancestry (Koreans and Chinese) to identify genetic associations with alcohol flushing. We also evaluated whether self-reported flushing can be used as an instrumental variable for alcohol intake. RESULTS: We identified variants in the region of ALDH2 strongly associated with alcohol flushing, replicating previous studies conducted in East Asian populations. Additionally, we identified variants in the alcohol dehydrogenase 1B (ADH1B) gene region associated with alcohol flushing. Several novel variants were identified after adjustment for the lead variants (ALDH2-rs671 and ADH1B-rs1229984), which need to be confirmed in larger studies. The estimated SNP-heritability on the liability scale was 13% (S.E. = 4%) for flushing, but the heritability estimate decreased to 6% (S.E. = 4%) when the effects of the lead variants were controlled for. Genetic instrumentation of higher alcohol intake using these variants recapitulated known associations of alcohol intake with hypertension. Using self-reported alcohol flushing as an instrument gave a similar association pattern of higher alcohol intake and cardiovascular disease-related traits (e.g. stroke). CONCLUSION: This study confirms that ALDH2-rs671 and ADH1B-rs1229984 are associated with alcohol flushing in East Asian populations. Our findings also suggest that self-reported alcohol flushing can be used as an instrumental variable in future studies of alcohol consumption.

Follicular flushing increases the number of oocytes retrieved: a randomized controlled trial.

STUDY QUESTION: Does follicular flushing increase the number of cumulus-oocyte complexes (COCs) retrieved compared to single aspiration? SUMMARY ANSWER: Follicular flushing significantly increases the number of COCs retrieved compared to single aspiration. WHAT IS KNOWN ALREADY: On the basis of published meta-analyses, follicular flushing does not seem to increase the number of oocytes retrieved, the probability of clinical pregnancy, or that of live birth and has been associated with an increase in the duration of oocyte retrieval. It should be noted, however, that all the eligible randomized controlled trials (RCTs) in these meta-analyses have randomized patients into either single aspiration or follicular flushing. This study design might not allow the detection of the true effect of follicular flushing. Despite randomization, this might still be obscured, to an extent, by heterogeneity in patients, stimulation characteristics, and differences in the oocyte retrieval procedure. STUDY DESIGN, SIZE, DURATION: A prospective, single centre, RCT, including 105 patients was performed between July and December 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible patients were those undergoing oocyte retrieval for ICSI, aged <43 years, with BMI 18-35 kg/m2. Patients with all types of ovarian response (low-normal-high), as assessed on the day of triggering final oocyte maturation, were included. Random allocation of the ovaries of each patient to either single aspiration or follicular flushing was performed on the day of oocyte retrieval, using a computer-generated randomization list. Patients could enter the study only once. All follicles from ovaries allocated to either follicular flushing or single aspiration, were aspirated by the same 16G double lumen needle, with a constant aspiration pressure of 190 mmHg, resulting in flow rate of 0.42 ml/s. In the ovaries allocated to the follicular flushing group, if a COC was not recovered in the initial aspirate of each follicle, follicular flushing was performed until a COC was retrieved, up to a maximum of five times. The primary outcome measure was the number of COCs retrieved. Secondary outcomes were oocyte recovery rate, oocyte maturation rate, fertilization rate, and rate of good quality embryos on Day 2. Values are expressed as a median (inter-quartile range). MAIN RESULTS AND THE ROLE OF CHANCE: Significantly more COCs were retrieved in the follicular flushing as compared to the single aspiration group in all patients [5 (7) vs 2 (3), P < 0.001, respectively], as well as in patients with high [9 (3) vs 5 (4), P < 0.001, respectively], normal [5 (2) vs 2 (3), P < 0.001, respectively] and low [1 (1) vs 1 (1), P < 0.001, respectively] ovarian response. In patients with low ovarian response, no COCs were retrieved in 5.7% of the ovaries in the flushing group vs 42.8% of the ovaries in the single aspiration group (P < 0.001). The oocyte retrieval rate was significantly higher in the follicular flushing vs the single aspiration group, in all patients [88.9% (25.0) vs 45.5% (37.5), P < 0.001, respectively], as well as in patients with high [81.8% (15.9) vs 45.5% (22.2), P < 0.001, respectively], normal [85.7% (28.6) vs 40.0% (30.0), P < 0.001, respectively], and low [100% (0) vs 50.0% (100), P < 0.001, respectively] ovarian response. No significant difference was observed regarding maturation rate [85.2% (30.8) vs 100% (33.3), P = 0.78], fertilization rate [76.4% (50) vs 83.3% (50) P = 0.42], and the proportion of good quality embryos on Day 2 [83.3% (40) vs 100% (50), P = 0.62]. Similarly, no differences in the above variables were observed in patients with different types of ovarian response. Follicular flushing as compared to single aspiration was associated with a significant increase in the duration of oocyte retrieval in all patients [248 s (332) vs 135 s (164), respectively], as well as in patients with high [464 s (225) vs 237 s (89), P < 0.001, respectively], normal [248 s (108) vs 141 s (95), P < 0.001, respectively], and low [64 s (59) vs 48 s (10), P < 0.001, respectively] ovarian response. LIMITATIONS, REASONS FOR CAUTION: Although the current study design allows for a more accurate evaluation of the true effect of follicular flushing on the number of COCs retrieved, it does not permit the evaluation of its role on the probability of pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: This is the first RCT to suggest that follicular flushing increases the number of COCs retrieved compared to single aspiration, independently of ovarian response. This implies that follicular flushing plays an important role in the optimization of oocyte retrieval. These results, however, need to be confirmed in future studies, in which an equal flow rate should be used during oocyte retrieval. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NCT05473455. TRIAL REGISTRATION DATE: 15 July 2022. DATE OF FIRST PATIENT'S ENROLMENT: 27 July 2022.

Laser Speckle Contrast Imaging-based diagnosis of severe mesenteric traction syndrome: Hemodynamics and prostacyclin - A prospective cohort study.

BRIEF ABSTRACT: Today, the diagnosis and grading of mesenteric traction syndrome relies on a subjective assessment of facial flushing. However, this method has several limitations. In this study, Laser Speckle Contrast Imaging and a predefined cut-off value are assessed and validated for the objective identification of severe mesenteric traction syndrome. BACKGROUND: Severe mesenteric traction syndrome (MTS) is associated with increased postoperative morbidity. The diagnosis is based on an assessment of the developed facial flushing. Today this is performed subjectively, as no objective method exists. One possible objective method is Laser Speckle Contrast Imaging (LSCI), which has been used to show significantly higher facial skin blood flow in patients developing severe MTS. Using these data, a cut-off value has been identified. This study aimed to validate our predefined LSCI cut-off value for identifying severe MTS. METHODS: A prospective cohort study was performed on patients planned for open esophagectomy or pancreatic surgery from March 2021 to April 2022. All patients underwent continuous measurement of forehead skin blood flow using LSCI during the first hour of surgery. Using the predefined cut-off value, the severity of MTS was graded. In addition, blood samples for prostacyclin (PGI2) analysis and hemodynamics were collected at predefined time points to validate the cut-off value. MAIN RESULTS: Sixty patients were included in the study. Using our predefined LSCI cut-off value, 21 (35 %) patients were identified as developing severe MTS. These patients were found to have higher concentrations of 6-Keto-PGFaα (p = 0.002), lower SVR (p < 0.001), lower MAP (p = 0.004), and higher CO (p < 0.001) 15 min into surgery, as compared with patients not developing severe MTS. CONCLUSION: This study validated our LSCI cut-off value for the objective identification of severe MTS patients as this group developed increased concentrations of PGI2 and more pronounced hemodynamic alterations compared with patients not developing severe MTS.

Does follicular flushing increase oocyte number in poor responders? An update of a systematic review.

RESEARCH QUESTION: Does flushing of the follicles at ovum retrieval increase the number of retrieved oocytes in poor-response IVF patients? DESIGN: An update of an electronic literature search was performed to identify randomized controlled trials (RCT) investigating follicular flushing versus no flushing in women with a poor response to IVF treatment. No exclusion criteria for type of needle, stimulation or protocol were applied. A meta-analysis was conducted using the software RevMan 5.4. RESULTS: Six RCT were identified that had the primary objective of testing for an increase in mean number of cumulus-oocyte complexes or/and metaphase II oocytes between flushing and no flushing. A double-lumen needle was used in five trials, one study investigated a pseudo-double-lumen needle, and a conventional single-lumen needle was used in all the control groups. The main risk of bias in all the included studies is a lack of blinding of the physicians performing the puncture and incomplete data in four trials. A heterogeneity of direction and size of effect of follicular flushing on mean oocyte number retrieved was detected (I2 = 80, P = 0.0001), which precludes a synthesis of the data. Two studies showed a decrease or tendency towards a decrease in oocyte numbers, one study showed similar oocyte numbers, and one study showed a strong tendency towards increased oocyte numbers with flushing. A similar picture was seen for metaphase II oocytes (I2 = 73, P = 0.002). CONCLUSIONS: It is uncertain whether follicular flushing in poor-response IVF patients affects the number of retrieved oocytes. Larger pragmatic trials are warranted to clarify the effect of flushing on oocyte numbers and clinical outcomes in poor responders and monofollicular patients.