Pigmented acuminated condylomas seborrhoeic keratosis-like: a new entity?

BACKGROUND: Condyloma acuminatum is caused by human papillomavirus (HPV), which typically presents as excrescent, pedunculated, papillomatous lesions which may be of a pale colour. On rare occasions, we have observed pigmented genital lesions that are similar to seborrhoeic keratoses, but with histological findings of condyloma acuminatum and positive genotyping for HPV. We have termed these 'seborrhoeic keratosis-like' type condylomas. METHODS: This is an observational retrospective study. The following clinical data were collected: age, sex, time of evolution, location, isolated or multiple lesions, monomorphous or polymorphous/mixed lesions. HPV genotyping was performed in all cases, and excision for histological study in eight cases. RESULTS: A total of 31 patients were diagnosed with this type of pigmented condylomata acuminata. Of these, 16 had isolated lesions (less than five lesions) and 15 had multiple lesions. 67% of the lesions exhibited slow growth, with an evolution period of greater than 1 year. The most frequent location was the base of the penis and pubis. HPV genotyping of the lesions was positive in all cases, with the HPV-6 genotype predominating (28 cases, 90.3%). The lesions exhibited dermoscopic differences from other pigmented lesions and histological findings attributable to HPV infection (pseudoparakeratosis, koilocytosis, etc) and others similar to those observed in seborrhoeic keratoses. CONCLUSIONS: A total of 31 patients were diagnosed with pigmented verrucous lesions, excrescents, isolated or multiple, in the genital region. These lesions exhibited clinical characteristics similar to seborrhoeic keratoses, with positive genotyping for HPV. In the majority of cases, the genotype was HPV-6. These lesions have been named 'pigmented condylomata acuminata seborrhoeic keratosis-like'. Only 10 cases of these lesions have been described in the literature.

Liquid crystal wave plate operating close to 18†THz.

Controlling the properties of mid- and far-infrared radiation can provide a means to transiently alter the properties of materials for novel applications. However, a limited number of optical elements are available to control its polarization state. Here we show that a 15-µm thick liquid crystal cell containing 8CB (4-octyl-4'-cyanobiphenyl) in the ordered, smectic A phase can be used as a phase retarder or wave plate. This was tested using the bright, short-pulsed (∼1 ps) radiation centered at 16.5 µm (18.15 THz) that is emitted by a free electron laser at high repetition rate (13 MHz). These results demonstrate a possible tool for the exploration of the mid- and far-infrared range and could be used to develop novel metamaterials or extend multidimensional spectroscopy to this portion of the electromagnetic spectrum.

Plantar keratoderma-like crusted scabies in an immunocompetent infant after topical steroids.

A healthy 6-month-old girl presented with plantar keratoderma-like lesions unresponsive to topical corticosteroids. Nocturnal pruritus in 13 relatives, presence of burrows on clinical exam, and the positive scabies preparation led to the diagnosis of crusted scabies. She was successfully treated with topical and oral scabicides. Crusted scabies is a severe form of Sarcoptes scabiei infection uncommon in immunocompetent subjects, in whom previous corticosteroid use may favor its occurrence.

Rescue in vitro maturation using ovarian support cells of human oocytes from conventional stimulation cycles yields oocytes with improved nuclear maturation and transcriptomic resemblance to in vivo matured oocytes.

PURPOSE: Determine if the gene expression profiles of ovarian support cells (OSCs) and cumulus-free oocytes are bidirectionally influenced by co-culture during in vitro maturation (IVM). METHODS: Fertility patients aged 25 to 45 years old undergoing conventional ovarian stimulation donated denuded immature oocytes for research. Oocytes were randomly allocated to either OSC-IVM culture (intervention) or Media-IVM culture (control) for 24-28 h. The OSC-IVM culture condition was composed of 100,000 OSCs in suspension culture with human chorionic gonadotropin (hCG), recombinant follicle stimulating hormone (rFSH), androstenedione, and doxycycline supplementation. The Media-IVM control lacked OSCs and contained the same supplementation. A limited set of in vivo matured MII oocytes were donated for comparative evaluation. Endpoints consisted of MII formation rate, morphological and spindle quality assessment, and gene expression analysis compared to in vitro and in vivo controls. RESULTS: OSC-IVM resulted in a statistically significant improvement in MII formation rate compared to the Media-IVM control, with no apparent effect on morphology or spindle assembly. OSC-IVM MII oocytes displayed a closer transcriptomic maturity signature to IVF-MII controls than Media-IVM control MII oocytes. The gene expression profile of OSCs was modulated in the presence of oocytes, displaying culture- and time-dependent differential gene expression during IVM. CONCLUSION: The OSC-IVM platform is a novel tool for rescue maturation of human oocytes, yielding oocytes with improved nuclear maturation and a closer transcriptomic resemblance to in vivo matured oocytes, indicating a potential enhancement in oocyte cytoplasmic maturation. These improvements on oocyte quality after OSC-IVM are possibly occurring through bidirectional crosstalk of cumulus-free oocytes and ovarian support cells.

Safety and Immunogenicity of an Investigational Respiratory Syncytial Virus Vaccine (RSVPreF3) in Mothers and Their Infants: A Phase 2 Randomized Trial.

BACKGROUND: In a phase 1/2 study, a maternal respiratory syncytial virus vaccine candidate (RSVPreF3) demonstrated an acceptable safety profile and efficiently increased RSV-specific humoral immune responses in non-pregnant women. METHODS: In this phase 2 observer-blind, placebo-controlled, randomized clinical trial (NCT04126213), the safety of RSVPreF3 (60 or 120 µg), administered during late second or third trimester, was evaluated in 213 18- to 40-year-old healthy pregnant women through 6 months postdelivery and their offspring through infancy; immunogenicity was evaluated through day 43 postdelivery and day 181 postbirth, respectively. RESULTS: RSVPreF3 was well tolerated. No pregnancy-related or neonatal adverse events of special interest were considered vaccine/placebo related. In the 60 and 120 µg RSVPreF3 groups: (1) neutralizing antibody (nAb) titers in mothers increased 12.7- and 14.9-fold against RSV-A and 10.6- and 13.2-fold against RSV-B, respectively, 1 month postvaccination and remained 8.9-10.0-fold over prevaccination at day 43 postdelivery; (2) nAb titers were consistently higher compared to placebo recipients; (3) placental transfer ratios for anti-RSVPreF3 antibodies at birth were 1.62 and 1.90, respectively, and (4) nAb levels in infants were highest at birth and declined through day 181 postbirth. CONCLUSIONS: RSVPreF3 maternal vaccination had an acceptable safety risk profile and induced robust RSV-specific immune responses with successful antibody transfer to their newborns. CLINICAL TRIALS REGISTRATION: NCT04126213.

WHAT IS THE CONTEXT?: Infants, especially those less than 6 months of age, are at increased risk of lung infection caused by respiratory syncytial virus (RSV). However, this risk could be reduced with maternal vaccination against RSV during pregnancy. A previous clinical trial found that a vaccine candidate (named RSVPreF3) was well tolerated when given to non-pregnant women. WHAT IS NEW?: In pregnant women, RSVPreF3 was also well tolerated. Occurrence of unsolicited adverse events was similar between vaccine and placebo recipients. None of the serious adverse events or events of interest for pregnant women or newborns were considered related to the study intervention. One month after vaccination, mothers who received RSVPreF3 had 11­15 times higher levels of antibodies against RSV than before vaccination. These antibody levels remained similar until 43 days after delivery. In the infants born to mothers vaccinated during pregnancy with RSVPreF3, antibody levels were highest at birth, when levels were higher than in their mothers, and declined through day 181 postbirth. WHAT IS THE IMPACT?: RSVPreF3 had an acceptable safety risk profile in pregnant women and their babies. This vaccine induced potent immune responses against RSV, with maternal antibodies transferred to infants of the vaccinated mothers.

Beneficial effect of ursodeoxycholic acid in patients with acyl-CoA oxidase 2 (ACOX2) deficiency-associated hypertransaminasemia.

BACKGROUND AND AIMS: A variant (p.Arg225Trp) of peroxisomal acyl-CoA oxidase 2 (ACOX2), involved in bile acid (BA) side-chain shortening, has been associated with unexplained persistent hypertransaminasemia and accumulation of C27-BAs, mainly 3α,7α,12α-trihydroxy-5ß-cholestanoic acid (THCA). We aimed to investigate the prevalence of ACOX2 deficiency-associated hypertransaminasemia (ADAH), its response to ursodeoxycholic acid (UDCA), elucidate its pathophysiological mechanism and identify other inborn errors that could cause this alteration. METHODS AND RESULTS: Among 33 patients with unexplained hypertransaminasemia from 11 hospitals and 13 of their relatives, seven individuals with abnormally high C27-BA levels (>50% of total BAs) were identified by high-performance liquid chromatography-mass spectrometry. The p.Arg225Trp variant was found in homozygosity (exon amplification/sequencing) in two patients and three family members. Two additional nonrelated patients were heterozygous carriers of different alleles: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). In patients with ADAH, impaired liver expression of ACOX2, but not ACOX3, was found (immunohistochemistry). Treatment with UDCA normalized aminotransferase levels. Incubation of HuH-7 hepatoma cells with THCA, which was efficiently taken up, but not through BA transporters, increased reactive oxygen species production (flow cytometry), endoplasmic reticulum stress biomarkers (GRP78, CHOP, and XBP1-S/XBP1-U ratio), and BAXα expression (reverse transcription followed by quantitative polymerase chain reaction and immunoblot), whereas cell viability was decreased (tetrazolium salt-based cell viability test). THCA-induced cell toxicity was higher than that of major C24-BAs and was not prevented by UDCA. Fourteen predicted ACOX2 variants were generated (site-directed mutagenesis) and expressed in HuH-7 cells. Functional tests to determine their ability to metabolize THCA identified six with the potential to cause ADAH. CONCLUSIONS: Dysfunctional ACOX2 has been found in several patients with unexplained hypertransaminasemia. This condition can be accurately identified by a noninvasive diagnostic strategy based on plasma BA profiling and ACOX2 sequencing. Moreover, UDCA treatment can efficiently attenuate liver damage in these patients.

Human-induced pluripotent stem cell-derived ovarian support cell co-culture improves oocyte maturation in vitro after abbreviated gonadotropin stimulation.

STUDY QUESTION: Can in vitro maturation (IVM) and developmental competence of human oocytes be improved by co-culture with ovarian support cells (OSCs) derived from human-induced pluripotent stem cells (hiPSCs)? SUMMARY ANSWER: OSC-IVM significantly improves the rates of metaphase II (MII) formation and euploid Day 5 or 6 blastocyst formation, when compared to a commercially available IVM system. WHAT IS KNOWN ALREADY: IVM has historically shown highly variable performance in maturing oocytes and generating oocytes with strong developmental capacity, while limited studies have shown a positive benefit of primary granulosa cell co-culture for IVM. We recently reported the development of OSCs generated from hiPSCs that recapitulate dynamic ovarian function in vitro. STUDY DESIGN, SIZE, DURATION: The study was designed as a basic science study, using randomized sibling oocyte specimen allocation. Using pilot study data, a prospective sample size of 20 donors or at least 65 oocytes per condition were used for subsequent experiments. A total of 67 oocyte donors were recruited to undergo abbreviated gonadotropin stimulation with or without hCG triggers and retrieved cumulus-oocyte complexes (COCs) were allocated between the OSC-IVM or control conditions (fetal-like OSC (FOSC)-IVM or media-only IVM) in three independent experimental design formats. The total study duration was 1 April 2022 to 1 July 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: Oocyte donors between the ages of 19 and 37 years were recruited for retrieval after informed consent, with assessment of anti-Mullerian hormone, antral follicle count, age, BMI and ovarian pathology used for inclusion and exclusion criteria. In experiment 1, 27 oocyte donors were recruited, in experiment 2, 23 oocyte donors were recruited, and in experiment 3, 17 oocyte donors and 3 sperm donors were recruited. The OSC-IVM culture condition was composed of 100 000 OSCs in suspension culture with hCG, recombinant FSH, androstenedione, and doxycycline supplementation. IVM controls lacked OSCs and contained either the same supplementation, FSH and hCG only (a commercial IVM control), or FOSCs with the same supplementation (Media control). Experiment 1 compared OSC-IVM, FOSC-IVM, and a Media control, while experiments 2 and 3 compared OSC-IVM and a commercial IVM control. Primary endpoints in the first two experiments were the MII formation (i.e. maturation) rate and morphological quality assessment. In the third experiment, the fertilization and embryo formation rates were assessed with genetic testing for aneuploidy and epigenetic quality in blastocysts. MAIN RESULTS AND THE ROLE OF CHANCE: We observed a statistically significant improvement (∼1.5×) in maturation outcomes for oocytes that underwent IVM with OSCs compared to control Media-IVM and FOSC-IVM in experiment 1. More specifically, the OSC-IVM group yielded a MII formation rate of 68% ± 6.83% SEM versus 46% ± 8.51% SEM in the Media control (P = 0.02592, unpaired t-test). FOSC-IVM yielded a 51% ± 9.23% SEM MII formation rate which did not significantly differ from the media control (P = 0.77 unpaired t-test). Additionally, OSC-IVM yielded a statistically significant ∼1.6× higher average MII formation rate at 68% ± 6.74% when compared to 43% ± 7.90% in the commercially available IVM control condition (P = 0.0349, paired t-test) in experiment 2. Oocyte morphological quality between OSC-IVM and the controls did not significantly differ. In experiment 3, OSC-IVM oocytes demonstrated a statistically significant improvement in Day 5 or 6 euploid blastocyst formation per COC compared to the commercial IVM control (25% ± 7.47% vs 11% ± 3.82%, P = 0.0349 logistic regression). Also in experiment 3, the OSC-treated oocytes generated blastocysts with similar global and germline differentially methylated region epigenetic profiles compared commercial IVM controls or blastocysts after either conventional ovarian stimulation. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: While the findings of this study are compelling, the cohort size remains limited and was powered on preliminary pilot studies, and the basic research nature of the study limits generalizability compared to randomized control trials. Additionally, use of hCG-triggered cycles results in a heterogenous oocyte cohort, and potential differences in the underlying maturation state of oocytes pre-IVM may limit or bias findings. Further research is needed to clarify and characterize the precise mechanism of action of the OSC-IVM system. Further research is also needed to establish whether these embryos are capable of implantation and further development, a key indication of their clinical utility. WIDER IMPLICATIONS OF THE FINDINGS: Together, these findings demonstrate a novel approach to IVM with broad applicability to modern ART practice. The controls used in this study are in line with and have produced similar to findings to those in the literature, and the outcome of this study supports findings from previous co-culture studies that found benefits of primary granulosa cells on IVM outcomes. The OSC-IVM system shows promise as a highly flexible IVM approach that can complement a broad range of stimulation styles and patient populations. Particularly for patients who cannot or prefer not to undergo conventional gonadotropin stimulation, OSC-IVM may present a viable path for obtaining developmentally competent, mature oocytes. STUDY FUNDING/COMPETING INTEREST(S): A.D.N., A.B.F., A.G., B.P., C.A., C.C.K., F.B., G.R., K.S.P., K.W., M.M., P.C., S.P., and M.-J.F.-G. are shareholders in the for-profit biotechnology company Gameto Inc. P.R.J.F. declares paid consultancy for Gameto Inc. P.C. also declares paid consultancy for the Scientific Advisory Board for Gameto Inc. D.H.M. has received consulting services from Granata Bio, Sanford Fertility and Reproductive Medicine, Gameto, and Buffalo IVF, and travel support from the Upper Egypt Assisted Reproduction Society. C.C.K., S.P., M.M., A.G., B.P., K.S.P., G.R., and A.D.N. are listed on a patent covering the use of OSCs for IVM: U.S. Provisional Patent Application No. 63/492,210. Additionally, C.C.K. and K.W. are listed on three patents covering the use of OSCs for IVM: U.S. Patent Application No. 17/846,725, U.S Patent Application No. 17/846,845, and International Patent Application No.: PCT/US2023/026012. C.C.K., M.P.S., and P.C. additionally are listed on three patents for the transcription factor-directed production of granulosa-like cells from stem cells: International Patent Application No.: PCT/US2023/065140, U.S. Provisional Application No. 63/326,640, and U.S. Provisional Application No. 63/444,108. The remaining authors have no conflicts of interest to declare.

Lifestyle behaviors clusters in a nationwide sample of Spanish children and adolescents: PASOS study.

BACKGROUND: Youth is a vulnerable period. To classify lifestyle behaviors and its relationship with health-related outcomes of Spanish children and adolescents. METHODS: Cross-sectional study including 3261 children aged 7.5-17.5 y (52.8% females). Physical activity (PA), screen-time, sleep time, adherence to Mediterranean diet (MD), weight status (WS) by validated methods. Cluster analysis was run considering chronological age. RESULTS: Six clusters were identified: C1: high screen time, low adherence to MD and sleep time (n = 431,13.20%); C2: high WS, medium adherence to MD,high sleep time, and low screen time (n = 466,14.30%); C3: young group with low screen time and high PA, adherence to MD and sleep (n = 537,16.40%); C4: worst profile regarding adherence to MD, PA, WS and sleep time (n = 609,18.70%); C5: low screen time and PA, high sleep time (n = 804,24.70%); C6: high PA and screen time, low WS (n = 414,12.70%). Mean absolute values were statistically different among PA levels, screen and sleep time, adherence to MD, age, and WS (all p < 0.001). CONCLUSIONS: The most prevalent pattern was low levels of PA, MD, and screen time, and high sleep time. The second most prevalent was characterized by very low levels of PA, sleep time, and adherence to MD, and high screen time, and WS in adolescents. IMPACT STATEMENT: The main identified lifestyle behavior was poor physical activity, low adherence to Mediterranean Diet and high screen and sleep time. Children should increase physical activity levels, adherence to Mediterranean diet, decrease screen and sleep the appropriate hours per day. Families, schools, and medical communities must work together to gloss over present and future diseases. Sleep time had not been previously included in cluster analysis with physical activity, sedentary behaviors, obesity, and nutritional status, thus the present data open a new perspective in Spanish population. Health policies should focus on promoting physical activity, Mediterranean diet, adequate sleep and reducing screen time.

Stark control of multiphoton ionization through Freeman resonances in alkyl iodides.

Multiphoton ionization (MPI) of alkyl iodides (RI, R = CnH2n+1, n = 1-4) has been investigated with femtosecond laser pulses centered at 800 and 400 nm along with photoelectron imaging detection. In addition, the ultraviolet (UV)-vacuum ultraviolet (VUV) absorption spectra of gas-phase RIs have been measured in the photon energy range of 5-11 eV using the VUV Fourier transform spectrometer at the VUV DESIRS beamline of the synchrotron SOLEIL facility. The use of high-laser-field strengths in matter-radiation interaction generates highly non-linear phenomena, such as the Stark shift effect, which distorts the potential energy surfaces of molecules by varying both the energy of electronic and rovibrational states and their ionization energies. The Stark shift can then generate resonances between intermediate states and an integer number of laser photons of a given wavelength, which are commonly known as Freeman resonances. Here, we study how the molecular structure of linear and branched alkyl iodides affects the UV-VUV absorption spectrum, the MPI process, and the generation of Freeman resonances. The obtained results reveal a dominant resonance in the experiments at 800 nm, which counter-intuitively appears at the same photoelectron kinetic energy in the whole alkyl iodide series. The ionization pathways of this resonance strongly involve the 6p(2E3/2) Rydberg state with different degrees of vibrational excitation, revealing an energy compensation effect as the R-chain complexity increases.

Long-Term Effects of Inspiratory Muscle Training in Institutionalized Elderly Women: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Inspiratory muscle training (IMT) has been applied to different populations, but evidence in elderly women and maintenance of improvements achieved during training is scarce. The objective of the study was to evaluate the effectiveness of IMT 6 months after finishing the training period in elderly women. METHODS: A controlled, randomized, double-blind trial was conducted, with allocation concealment performed on 26 institutionalized elderly women distributed into 2 groups: high loads and low loads. Over an 8-week period, an IMT protocol was followed; later, elderly women continued for 6 months with their daily normal activities. Inspiratory strength, expiratory strength, and functional capacity were measured pre-IMT, post-IMT, and 6 months after intervention. RESULTS: After an 8-week training, respiratory strength and functional capacity increased in both groups. Six months after finishing the intervention, these benefits were lost. Inspiratory strength decreased in the high-loads group but was 32% higher than initial values (p = 0.007); in the low-loads group, patients lost 41% (p = 0.015). Improvements were higher in the high-loads group after training (p = 0.000) and follow-up (p = 0.002). Functional capacity was similar to initial values in both groups. CONCLUSION: The improvements achieved with IMT in elderly women disappeared 6 months after the end of training. High loads were more effective to keep inspiratory strength than low loads.

Cross education is modulated by set configuration in knee extension exercise.

OBJECTIVES: The main aim of this study was to determine the effects of set configuration during five weeks of unilateral knee extension resistance training on untrained knee extensors performance. METHODS: Thirty-five subjects were randomly assigned to traditional training (TTG; n=14), rest-redistribution (RRG; n=10) and control group (CON; n=11). TTG and RRG groups trained the dominant knee extensors twice a week with the 10-repetition maximum (RM) load. TTG performed four sets of eight repetitions with three min-rest between sets and RRG 32 repetitions with 17.4 seconds of rest between each one. Before and after interventions, anthropometry, muscle thickness (MT), pennation angle (PA), 1RM, number of repetitions with 10RM pretest load (N10RM), maximum propulsive power (MPP) and maximum voluntary isometric contraction (MVIC) were measured. RESULTS: 1RM of the untrained leg increased only in the TTG group (p<0.001, 10.3% compared with Pre-test). 1RM, MPP and N10RM increased in the trained leg in both TTG (p<0.001) and RRG (p<0.001). No changes occurred in MT or PA. CONCLUSIONS: These results suggest that, when it is not possible to perform bilateral exercises (e.g., leg injury), traditional set configurations should be recommended to improve maximal voluntary force in the untrained leg.

The effect of vitrification on blastocyst mitochondrial DNA dynamics and gene expression profiles.

PURPOSE: Does vitrification/warming affect the mitochondrial DNA (mtDNA) content and the gene expression profile of blastocysts? METHODS: Prospective cohort study in which 89 blastocysts were obtained from 50 patients between July 2017 and August 2018. mtDNA was measured in a total of 71 aneuploid blastocysts by means of real-time polymerase chain reaction (RT-PCR). Transcriptomic analysis was performed by RNA sequencing (RNA-seq) in an additional 8 aneuploid blastocysts cultured for 0 h after warming, and 10 aneuploid blastocysts cultured for 4-5 h after warming. RESULTS: A significant decrease in mtDNA content just during the first hour after the warming process in blastocysts was found (P < 0.05). However, mtDNA content experimented a significantly increased along the later culture hours achieving the original mtDNA levels before vitrification after 4-5 h of culture (P < 0.05). Gene expression analysis and functional enrichment analysis revealed that such recovery was accompanied by upregulation of pathways associated with embryo developmental capacity and uterine embryo development. Interestingly, the significant increase in mtDNA content observed in blastocysts just after warming also coincided with the differential expression of several cellular stress response-related pathways, such as apoptosis, DNA damage, humoral immune responses, and cancer. CONCLUSION: To our knowledge, this is the first study demonstrating in humans, a modulation in blastocysts mtDNA content in response to vitrification and warming. These results will be useful in understanding which pathways and mechanisms may be activated in human blastocysts following vitrification and warming before a transfer.

Natural Products as Modulators of Nrf2 Signaling Pathway in Neuroprotection.

Neurodegenerative diseases (NDs) affect the West due to the increase in life expectancy. Nervous cells accumulate oxidative damage, which is one of the factors that triggers and accelerates neurodegeneration. However, cells have mechanisms that scavenge reactive oxygen species (ROS) and alleviate oxidative stress (OS). Many of these endogenous antioxidant systems are regulated at the gene expression level by the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2). In the presence of prooxidant conditions, Nrf2 translocates to the nucleus and induces the transcription of genes containing ARE (antioxidant response element). In recent years, there has been an increase in the study of the Nrf2 pathway and the natural products that positively regulate it to reduce oxidative damage to the nervous system, both in in vitro models with neurons and microglia subjected to stress factors and in vivo models using mainly murine models. Quercetin, curcumin, anthocyanins, tea polyphenols, and other less studied phenolic compounds such as kaempferol, hesperetin, and icariin can also modulate Nrf2 by regulating several Nrf2 upstream activators. Another group of phytochemical compounds that upregulate this pathway are terpenoids, including monoterpenes (aucubin, catapol), diterpenes (ginkgolides), triterpenes (ginsenosides), and carotenoids (astaxanthin, lycopene). This review aims to update the knowledge on the influence of secondary metabolites of health interest on the activation of the Nrf2 pathway and their potential as treatments for NDs.

Plasma miR-486-5p Expression Is Upregulated in Atrial Fibrillation Patients with Broader Low-Voltage Areas.

Atrial fibrillation (AF) is the most common arrhythmia worldwide, affecting 1% of the population over 60 years old. The incidence and prevalence of AF are increasing globally, representing a relevant health problem, suggesting that more advanced strategies for predicting risk stage are highly needed. miRNAs mediate several processes involved in AF. Our aim was to identify miRNAs with a prognostic value as biomarkers in patients referred for AF ablation and its association with LVA extent, based on low-voltage area (LVA) maps. In this study, we recruited 44 AF patients referred for catheter ablation. We measured the expression of 84 miRNAs in plasma from peripheral blood in 3 different groups based on LVA extent. Expression analysis showed that miR-486-5p was significantly increased in patients with broader LVA (4-fold, p = 0.0002; 5-fold, p = 0.0001). Receiver operating characteristic curve analysis showed that miR-486-5p expression could predict atrium LVA (AUC, 0.8958; p = 0.0015). Also, miR-486-5p plasma levels were associated with AF-type (AUC, 0.7137; p = 0.0453). In addition, miR-486-5p expression was positively correlated with LVA percentage, left atrial (LA) area, and LA volume (r = 0.322, p = 0.037; r = 0.372, p = 0.015; r = 0.319, p = 0.045, respectively). These findings suggest that miR-486-5p expression might have prognostic significance in LVA extent in patients with AF.

Identification of potential invasive alien species in Spain through horizon scanning.

Invasive alien species have widespread impacts on native biodiversity and ecosystem services. Since the number of introductions worldwide is continuously rising, it is essential to prevent the entry, establishment and spread of new alien species through a systematic examination of future potential threats. Applying a three-step horizon scanning consensus method, we evaluated non-established alien species that could potentially arrive, establish and cause major ecological impact in Spain within the next 10 years. Overall, we identified 47 species with a very high risk (e.g. Oreochromis niloticus, Popillia japonica, Hemidactylus frenatus, Crassula helmsii or Halophila stipulacea), 61 with high risk, 93 with moderate risk, and 732 species with low risk. Many of the species categorized as very high or high risk to Spanish biodiversity are either already present in Europe and neighbouring countries or have a long invasive history elsewhere. This study provides an updated list of potential invasive alien species useful for prioritizing efforts and resources against their introduction. Compared to previous horizon scanning exercises in Spain, the current study screens potential invaders from a wider range of terrestrial, freshwater, and marine organisms, and can serve as a basis for more comprehensive risk analyses to improve management and increase the efficiency of the early warning and rapid response framework for invasive alien species. We also stress the usefulness of measuring agreement and consistency as two different properties of the reliability of expert scores, in order to more easily elaborate consensus ranked lists of potential invasive alien species.

Neuropharmacological Effects in Animal Models and HPLC-Phytochemical Profiling of Byrsonima crassifolia (L.) Kunth Bark Extracts.

B. crassifolia is a species that grows in various areas of Latin America. It was known to be useful for the treatment of different human ailments. The present work evaluated the neuropharmacological and analgesic effects of hydroalcoholic and dichloromethane extracts of B. crassifolia. The effect on the central nervous system (CNS) of both extracts obtained from bark, administered by the intraperitoneal route in mice, was evaluated by different tests: spontaneous motor activity, hole-board, motor coordination, pentobarbital induced hypnosis, and rectal temperature. Analgesic activity was evaluated using a hot plate test. Phytochemical analysis was performed by high-performance liquid chromatography (HPLC) using reversed-phase and gradient of elution. The hydroalcoholic extract (dose 0.5 g dry plant/kg weigh) administration caused an important reduction of the head-dipping response in the hole board test. A decrease in spontaneous motor activity test and a disturbance of motor coordination in the rotarod test was observed. The hydroalcoholic extract produced a significant prolongation of pentobarbital induced sleeping time. This extract prevented hot plate test induced nociception. The phytochemical analysis revealed the presence of catechin, epicatechin, and procyanidin B12. Therefore, this study revealed that the hydroalcoholic extract of B. crassifolia possesses analgesic and sedative CNS activity.

Immunomodulatory, Anti-Inflammatory, and Anti-Cancer Properties of Ginseng: A Pharmacological Update.

Ginseng, a medicinal plant of the genus Panax, boasts a rich historical record of usage that dates back to the Paleolithic period. This botanical is extensively acknowledged and consumed in Eastern countries for its therapeutic properties, and, in Western countries, it is becoming increasingly popular as a remedy for fatigue and asthenia. This review provides an update on current research pertaining to ginseng and its isolated compounds, namely, ginsenosides and polysaccharides. The primary focus is on three crucial pharmacological activities, namely, immunomodulation, anti-inflammatory, and anti-cancer effects. The review encompasses studies on both isolated compounds and various ginseng extracts obtained from the root, leaves, and berries.

Can artificial intelligence increase the efficiency of referrals from primary to specialized care?

The overload of the current healthcare model makes the search for strategies to improve process efficiency essential. An artificial intelligence (AI) program based on Natural Language Processing pipelines (1-5) was used. It analyzed the referrals from primary care to Gastroenterology in the health area corresponding to our hospital in order to identify the most frequent reasons for consultation and to assign them a protocol for the performance of complementary tests before being seen for the first time in specialized care. We compared all referrals received in the first half of 2018, prior to the implementation of the AI pathway July 2018, with those received in the first half of 2019. Our aim was to evaluate the efficiency of this program in terms of discharges, need for additional tests and the number of follow-up visits required (number of follow-up visits/number of first visits in a given time period, FU/F index). In 2018, 1799 referrals were received, 1309 within our health area and 490 from outside the area. In 2019, 2261 referrals were received, 1392 from our area and 869 out-of-area. The AI pathway was applied to 31.4% of the area-referred patients. Overall, in 2019, the number of blood tests and CT scans requested at the first visit decreased (55.3 vs 61.4% and 4.4 vs 7.4% respectively, p<0.05 for both comparisons). The FU/F index in 2019 was 1.9 ± 0.04 vs 2.26 ± 0.07 in 2018 (p<0.05). When analysing patients from our health area, a higher number of discharges at the first consultation was observed during 2019 The number of requested supplementary exams among patients referred using the AI pathway was reduced compared to 2018. The FU/F index in patients referred using the AI pathway was 1.72 ± 0.08 vs 2.25 ± 0.08 in 2018 (p<0.05) and 1.93 ± 0.07 in those referred through the standard pathway in 2019 (p=0.07). Among patients referred from outside our health area, the number of endoscopies requested in 2019 was higher. The FU/F index improved in 2019 (1.95 ± 0.06 vs 2.29 ± 0.13, p<0.05). The number of patients referred using the AI pathway remains low, which could explain the lack of differences observed in the number of discharges or tests requested compared to patients referred via the standard pathway. However, the number of endoscopies and follow up visits requested for these patients did decrease.

Lack of SARS-CoV-2 RNA evidence in the lungs from wild European polecats (Mustela putorius) from Spain.

Data on SARS-CoV-2 infection in wildlife species is limited. The high prevalences found in mustelid species such as free-ranging American minks (Neovison vison) and domestic ferrets (Mustela putorius furo) justify the study of this virus in the closely related autochthonous free-ranging European polecat (Mustela putorius). We analysed lung samples from 48 roadkilled polecats collected when the human infection reached its highest levels in Spain (2020-2021). We did not detect infections by SARS-CoV-2; however, surveillance in wild carnivores and particularly in mustelids is still warranted, due to their susceptibility to this virus.

Transcriptional organization and regulation of the Pseudomonas putida flagellar system.

A single region of the Pseudomonas putida genome, designated the flagellar cluster, includes 59 genes potentially involved in the biogenesis and function of the flagellar system. Here, we combine bioinformatics and in vivo gene expression analyses to clarify the transcriptional organization and regulation of the flagellar genes in the cluster. We have identified 11 flagellar operons and characterized 22 primary and internal promoter regions. Our results indicate that synthesis of the flagellar apparatus and core chemotaxis machinery is regulated by a three-tier cascade in which fleQ is a Class I gene, standing at the top of the transcriptional hierarchy. FleQ- and σ54 -dependent Class II genes encode most components of the flagellar structure, part of the chemotaxis machinery and multiple regulatory elements, including the flagellar σ factor FliA. FliA activation of Class III genes enables synthesis of the filament, one stator complex and completion of the chemotaxis apparatus. Accessory regulatory proteins and an intricate operon architecture add complexity to the regulation by providing feedback and feed-forward loops to the main circuit. Because of the high conservation of the gene arrangement and promoter motifs, we believe that the regulatory circuit presented here may also apply to other environmental pseudomonads.