Deciphering psilocybin: Cytotoxicity, anti-inflammatory effects, and mechanistic insights.

A decade of clinical research has indicated psilocybin's effectiveness in treating various neuropsychiatric disorders, such as depression and substance abuse. The correlation between increased pro-inflammatory cytokines and the severity of neuropsychiatric symptoms, along with the known anti-inflammatory potential of some psychedelics, suggests an immunomodulatory role for psilocybin. This study aims to understand the mechanism of action of psilocybin by investigating the cytotoxic and immunomodulatory effects of psilocybin and psilocin on both resting and LPS-activated RAW 264.7 murine macrophages. The study evaluated the cytotoxicity of psilocybin and psilocin using an LDH assay across various doses and assessed their impact on cytokine production in RAW 264.7 cells, measuring cytokine expression via ELISA. Different doses, including those above and below the LC50, were used in both pre-treatment and post-treatment approaches. The LDH assay revealed that psilocybin is almost twice as cytotoxic as psilocin, with an LC50 of 12 ng/ml and 28 ng/ml, respectively. In resting macrophages, both psilocybin and psilocin triggered significant release of TNF- α after 4 h, with the lowest doses inducing higher levels of the cytokine than the highest doses. IL-10 expression in resting cells was only triggered by the highest dose of psilocin in the 4-hour incubation group. In LPS-stimulated cells, psilocin reduced TNF- α levels more than psilocybin in pre-treatment and post-treatment, with no significant effects on IL-10 in pre-treatment. Psilocin, but not psilocybin, induced a significant increase of IL-10 in post-treatment, leading to the conclusion that psilocin, but not psilocybin, exerts anti-inflammatory effects on classically activated macrophages.

Short communication: Investigating optimal laboratory growth conditions of Gracilibacillus halotolerans in media supplemented with salt.

Gracilibacillus halotolerans, a new and relatively unstudied extremophile, extracted from the Great Salt Lake USA, survives in an extreme saline environment. Uncovering optimal laboratory growth conditions can be useful to improve treatment strategies against antibiotic resistance and biofilm formation. In the current study, G. halotolerans growth optimization was tested to determine the ideal saline concentration. In addition, a variety of G. halotolerans'-derived survival strategies were reviewed. The major findings of the current study includes the optimal laboratory growth condition for G. halotolerans that requires the supplement of 5% NaCl. In addition, optimal growth was observed up to 72 h in Luria Bertani (LB) broth. Identifying the optimal laboratory growth conditions for G. halotolerans will standardize growth methods, reduce laboratory cost, and can improve future investigations of extremophile bacteria as model organisms to combat antibiotic resistance, biofilm, and other persister cell characteristics that negatively affect research and clinical settings.

Ticks' attraction to electrically charged hosts.

Ticks are blood-feeding parasites with limited locomotion, known for transmitting multiple pathogens to vertebrates. England et al. suggest that ticks can be easily pulled, via electrostatic induction, toward charged hosts with fluffy coats that are prone to accumulate higher electrostatic potentials. Thus, static electricity may influence ticks' ecology and management.

Air-to-land transitions: from wingless animals and plant seeds to shuttlecocks and bio-inspired robots.

Recent observations of wingless animals, including jumping nematodes, springtails, insects, and wingless vertebrates like geckos, snakes, and salamanders, have shown that their adaptations and body morphing are essential for rapid self-righting and controlled landing. These skills can reduce the risk of physical damage during collision, minimize recoil during landing, and allow for a quick escape response to minimize predation risk. The size, mass distribution, and speed of an animal determine its self-righting method, with larger animals depending on the conservation of angular momentum and smaller animals primarily using aerodynamic forces. Many animals falling through the air, from nematodes to salamanders, adopt a skydiving posture while descending. Similarly, plant seeds such as dandelions and samaras are able to turn upright in mid-air using aerodynamic forces and produce high decelerations. These aerial capabilities allow for a wide dispersal range, low-impact collisions, and effective landing and settling. Recently, small robots that can right themselves for controlled landings have been designed based on principles of aerial maneuvering in animals. Further research into the effects of unsteady flows on self-righting and landing in small arthropods, particularly those exhibiting explosive catapulting, could reveal how morphological features, flow dynamics, and physical mechanisms contribute to effective mid-air control. More broadly, studying apterygote (wingless insects) landing could also provide insight into the origin of insect flight. These research efforts have the potential to lead to the bio-inspired design of aerial micro-vehicles, sports projectiles, parachutes, and impulsive robots that can land upright in unsteady flow conditions.

End of Life in Patients With Advanced Non-curable Cancer: Patient Considerations Around the Moment of Death.

There is limited knowledge regarding Colombian patients with advanced cancer preferences regarding their final moments, place of death, and post-death wishes. To better understand these preferences, we conducted 23 in-depth interviews with patients between the ages of 28 and 78 receiving treatment at two academic hospitals and the National Cancer Institute. While many participants desired a peaceful death, few were comfortable discussing the topic of death directly. Some younger participants expressed an interest in euthanasia but had not received any guidance or support. While several participants preferred a home death, some expressed a desire to die in a hospital due to better symptom control. Additionally, when discussing post-death wishes, some participants expressed frustration about being unable to have these conversations with their loved ones and their preferences for funeral arrangements. Socioeconomic and geographical factors significantly impacted the wishes and preferences expressed, with many individuals hesitant to initiate difficult conversations.

Characterisation of acylated anthocyanins from red cabbage, purple sweet potato, and Tradescantia pallida leaves as natural food colourants by HPLC-DAD-ESI(+)-QTOF-MS/MS and ESI(+)-MSn analysis.

Anthocyanins in red cabbage, sweet potato, and Tradescantia pallida leaves were characterised. A total of 18 non-, mono-, and diacylated cyanidins was identified in red cabbage by high performance liquid chromatography-diode array detection coupled to high-resolution and multi-stage mass spectrometry. Sweet potato leaves contained 16 different cyanidin- and peonidin glycosides being predominantly mono- and diacylated. In T. pallida leaves, the tetra-acylated anthocyanin tradescantin prevailed. The large proportion of acylated anthocyanins resulted in a superior thermal stability during heating of aqueous model solutions (pH 3.0) coloured with red cabbage and purple sweet potato extracts as compared to that of a commercial Hibiscus-based food dye. However, their stability was still outperformed by that of the most stable Tradescantia extract. Comparing vis spectra from pH 1-10, the latter had an additional, uncommon absorption maximum at approx. 585 nm at slightly acidic to neutral pH values, yielding intensely red to purple colours.

Directional takeoff, aerial righting, and adhesion landing of semiaquatic springtails.

Springtails (Collembola) have been traditionally portrayed as explosive jumpers with incipient directional takeoff and uncontrolled landing. However, for these collembolans that live near the water, such skills are crucial for evading a host of voracious aquatic and terrestrial predators. We discover that semiaquatic springtails, Isotomurus retardatus, can perform directional jumps, rapid aerial righting, and near-perfect landing on the water surface. They achieve these locomotive controls by adjusting their body attitude and impulse during takeoff, deforming their body in midair, and exploiting the hydrophilicity of their ventral tube, known as the collophore. Experiments and mathematical modeling indicate that directional-impulse control during takeoff is driven by the collophore's adhesion force, the body angle, and the stroke duration produced by their jumping organ, the furcula. In midair, springtails curve their bodies to form a U-shape pose, which leverages aerodynamic forces to right themselves in less than ~20 ms, the fastest ever measured in animals. A stable equilibrium is facilitated by the water adhered to the collophore. Aerial righting was confirmed by placing springtails in a vertical wind tunnel and through physical models. Due to these aerial responses, springtails land on their ventral side ~85% of the time while anchoring via the collophore on the water surface to avoid bouncing. We validated the springtail biophysical principles in a bioinspired jumping robot that reduces in-flight rotation and lands upright ~75% of the time. Thus, contrary to common belief, these wingless hexapods can jump, skydive, and land with outstanding control that can be fundamental for survival.

Somatic embryogenesis and plant regeneration from transverse thin cell layers of adult peach palm (Bactris gasipaes) lateral offshoots.

In this work, we report a successful protocol to obtain in vitro peach palm (Bactris gasipaes Kunth) "Diamantes 10" plants through somatic embryogenesis from transverse thin cell layer (TCL) explants, dissected from three sections (basal, medial, and apical) of lateral offshoots of adult plants cultured on different concentrations of 4-amino-3,5,6-trichloropicolonic acid (picloram). After swelling and development of primary callus in all treatments, without any strong effect of explant origin or picloram concentration, it was possible to observe the formation of embryogenic structures and the exact point from where they developed. Browning was also observed and correlated to the induction treatments, although it was not an impairment for the production of embryogenic structures. Subsequent maturation and conversion of somatic embryos into plantlets allowed their acclimatization 17 months after culture initiation (ACI), which was quicker than previous reports with juvenile tissues (from embryos or seed-germinated plantlets). To the best of our knowledge, this is the first report on peach palm regeneration through somatic embryogenesis from TCL explants from adult plants and could constitute, after fine-tuning the acclimatization stage, a tool for mass clonal propagation of elite genotypes of this open-pollinated crop, as well as for the establishment of conservation strategies of in situ gene bank plant accessions endangered due to aging and other threats.

Occurrence of mycotoxins in pulses.

Pulses, dry grains of the Fabaceae family used for food and feed, are particularly important agricultural products with increasing commercial and nutritional relevance. Similar to other plant commodities, pulses can be affected by fungi in the field and during postharvest. Some of these fungi produce mycotoxins, which can seriously threaten human and animal health by causing acute poisoning and chronic effects. In this review, information referring to the analysis and occurrence of these compounds in pulses is summarized. An overview of the aims pursued, and of the methodologies employed for mycotoxin analysis in the different reports is presented, followed by a comprehensive review of relevant articles on mycotoxins in pulses, categorized according to the geographical region, among other considerations. Moreover, special attention was given to the effect of climatic conditions on microorganism infestation and mycotoxin accumulation. Furthermore, the limited literature available was considered to look for possible correlations between the degree of fungal infection and the mycotoxin incidence in pulses. In addition, the potential effect of certain phenolic compounds on reducing fungi infestation and mycotoxin accumulation was reviewed with examples on beans. Emphasis was also given to a specific group of mycotoxins, the phomopsins, that mainly impact lupin. Finally, the negative consequences of mycotoxin accumulation on the physiology and development of contaminated seeds and seedlings are presented, focusing on the few reports available on pulses. Given the agricultural and nutritional potential that pulses offer for human well-being, their promotion should be accompanied by attention to food safety issues, and mycotoxins might be among the most serious threats. Practical Application: According to the manuscript template available in the website, this section is for "JFS original research manuscripts ONLY; optional". Since we are publishing in CRFSFS this requirement will not be done.

SunUp and Sunset genomes revealed impact of particle bombardment mediated transformation and domestication history in papaya.

Transgenic papaya is widely publicized for controlling papaya ringspot virus. However, the impact of particle bombardment on the genome remains unknown. The transgenic SunUp and its progenitor Sunset genomes were assembled into 351.5 and 350.3 Mb in nine chromosomes, respectively. We identified a 1.64 Mb insertion containing three transgenic insertions in SunUp chromosome 5, consisting of 52 nuclear-plastid, 21 nuclear-mitochondrial and 1 nuclear genomic fragments. A 591.9 kb fragment in chromosome 5 was translocated into the 1.64 Mb insertion. We assembled a gapless 9.8 Mb hermaphrodite-specific region of the Yh chromosome and its 6.0 Mb X counterpart. Resequencing 86 genomes revealed three distinct groups, validating their geographic origin and breeding history. We identified 147 selective sweeps and defined the essential role of zeta-carotene desaturase in carotenoid accumulation during domestication. Our findings elucidated the impact of particle bombardment and improved our understanding of sex chromosomes and domestication to expedite papaya improvement.

Vitamin E and carotenoid profiles in leaves, stems, petioles and flowers of stinging nettle (Urtica leptophylla Kunth) from Costa Rica.

BACKGROUND: Local leafy vegetables are gaining attention as affordable sources of micronutrients, including vitamins, pro-vitamin carotenoids and other bioactive compounds. Stinging nettles (Urtica spp.) are used as source of fibers, herbal medicine and food. However, despite the relatively wide geographical spread of Urtica leptophylla on the American continent, little is known about its content of vitamin E congeners and carotenoids. We therefore investigated the particular nutritional potential of different plant structures of wild Costa Rican U. leptophylla by focusing on their vitamin E and carotenoid profiles. RESULTS: Young, mature and herbivore-damaged leaves, flowers, stems and petioles were collected and freeze-dried. Vitamin E and carotenoids were determined by high-performance liquid chromatography after liquid/liquid extraction with hexane. α-Tocopherol was the major vitamin E congener in all structures. Flowers had a high content of γ-tocopherol. Herbivore-damaged leaves had higher contents of vitamin E than undamaged leaves. Lutein was the major and ß-carotene the second most abundant carotenoid in U. leptophylla. No differences in carotenoid profiles were observed between damaged and undamaged leaves. CONCLUSION: The leaves of U. leptophylla had the highest nutritional value of all analyzed structures; therefore, they might represent a potential source of α-tocopherol, lutein and ß-carotene. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Design of a Biologically Inspired Water-Walking Robot Powered by Artificial Muscle.

The agile and power-efficient locomotion of a water strider has inspired many water-walking devices. These bioinspired water strider robots generally adopt a DC motor to create a sculling trajectory of the driving leg. These robots are, thus, inevitably heavy with many supporting legs decreasing the velocity of the robots. There have only been a few attempts to employ smart materials despite their advantages of being lightweight and having high power densities. This paper proposes an artificial muscle-based water-walking robot capable of moving forward and turning with four degrees of freedom. A compliant amplified shape memory alloy actuator (CASA) used to amplify the strain of a shape memory alloy wire enables a wide sculling motion of the actuation leg with only four supporting legs to support the entire weight of the robot. Design parameters to increase the actuation strain of the actuator and to achieve a desired swing angle (80°) are analyzed. Finally, experiments to measure the forward speed and angular velocities of the robot are carried out to compare with other robots. The robot weighs only 0.236 g and has a maximum and average speed of 1.56, 0.31 body length per second and a maximum and average angular velocity of 145.05°/s and 14.72°/s.

Knifefish turning control and hydrodynamics during forward swimming.

Rapid turning and swimming contribute to ecologically important behaviors in fishes such as predator avoidance, prey capture, mating and the navigation of complex environments. For riverine species, such as knifefishes, turning behaviors may also be important for navigating locomotive perturbations caused by turbulent flows. Most research on fish maneuvering focuses on fish with traditional fin and body morphologies, which primarily use body bending and the pectoral fins during turning. However, it is uncertain how fishes with uncommon morphologies are able to achieve sudden and controllable turns. Here, we studied the turning performance and the turning hydrodynamics of the black ghost knifefish (Apteronotus albifrons, N=6) which has an atypical elongated ribbon fin. Fish were filmed while swimming forward at ∼2 body lengths s-1 and feeding from a fixed feeder (control) and an oscillating feeder (75 Hz) at two different amplitudes. 3D kinematic analysis of the body revealed the highest pitch angles and lowest body bending coefficients during steady swimming. Low pitch angle, high maximum yaw angles and large body bending coefficients were characteristic of small and large turns. Asynchrony in pectoral fin use was low during turning; however, ribbon fin wavelength, frequency and wave speed were greatest during large turns. Digital particle image velocimetry (DPIV) showed larger counter-rotating vortex pairs produced during turning by the ribbon fin in comparison to vortices rotating in the same direction during steady swimming. Our results highlight the ribbon fin's role in controlled rapid turning through modulation of wavelength, frequency and wave speed.

Ingeniería genética contra estrés abiótico en cultivos neotropicales: osmolitos, factores de transcripción y CRISPR/Cas9 / Genetic engineering against abiotic stress in Neotropical crop plants: osmolites, transcription factors and CRISPR/Cas9

RESUMEN El neotrópico es sitio de origen de gran variedad de plantas que actualmente son cultivadas con éxito en diferentes regiones del mundo. Sin embargo, condiciones climáticas adversas, que se pueden ver acrecentadas por efectos del cambio climático antropogénico, pueden afectar su rendimiento y productividad debido a las situaciones de estrés abiótico que se pueden generar. Como alternativa para contrarrestar estos efectos, se ha experimentado con modificaciones genéticas, particularmente en genes relacionados con la producción de osmolitos y factores de transcripción que han llevado a que estas plantas, a nivel experimental, tengan mayor tolerancia a estrés oxidativo, altas y bajas temperaturas y fotoinhibición, sequía y salinidad, mediante la acumulación de osmoprotectores, la regulación en la expresión de genes y cambios en el fenotipo. En este trabajo se presentan y describen las estrategias metodológicas planteadas con estos fines y se complementan con ejemplos de trabajos realizados en cultivos de origen neotropical de importancia económica, como maíz, algodón, papa y tomate. Además, y debido a la novedad y potencial que ofrece la edición génica por medio del sistema CRISPR/Cas9, también se mencionan trabajos realizados en plantas con origen neotropical, enfocados en comprender e implementar mecanismos de tolerancia a sequía. Las metodologías aquí descritas podrían constituirse en opciones prácticas para mejorar la seguridad alimentaria con miras a contrarrestar las consecuencias negativas del cambio climático antropogénico.

ABSTRACT The neotropics are the site of origin of a large variety of plants that are currently successfully cultivated in different regions of the world. However, adverse climatic conditions, which can be exacerbated by the effects of anthropogenic climate change, can affect their yield and productivity due to the abiotic stresses that can be generated. As an alternative to counteract these effects, genetic modifications have been experimentally implemented, particularly in genes related to osmolyte production and transcription factors, which have ultimately led to increased tolerance of these plants to oxidative stress, high and low temperatures and photoinhibition, drought and salinity, through the accumulation of osmoprotectants, regulation of gene expression and changes in phenotype. In this work, the methodological strategies proposed to these aims are presented and described, and they are complemented with examples of studies carried out in economically important crops of neotropical origin, such as corn, cotton, potato and tomato. In addition, and due to the novelty and potential that gene editing offers through the CRISPR/Cas9 system, works conducted in plants with neotropical origin, focused on understanding and implementing drought tolerance mechanisms, are also mentioned. The methodologies described here could become practical options to achieve food security in the frame of the adverse effects caused by anthropogenic climate change.

Beyond the Kármán gait: knifefish swimming in periodic and irregular vortex streets.

Neotropical freshwater fishes such as knifefishes are commonly faced with navigating intense and highly unsteady streams. However, our knowledge on locomotion in apteronotids comes from laminar flows, where the ribbon fin dominates over the pectoral fins or body bending. Here, we studied the 3D kinematics and swimming control of seven black ghost knifefish (Apteronotus albifrons) moving in laminar flows (flow speed U∞≈1-5 BL s-1) and in periodic vortex streets (U∞≈2-4 BL s-1). Two different cylinders (∼2 and ∼3 cm diameter) were used to generate the latter. Additionally, fish were exposed to an irregular wake produced by a free oscillating cylinder (∼2 cm diameter; U∞≈2 BL s-1). In laminar flows, knifefish mainly used their ribbon fin, with wave frequency, speed and acceleration increasing with U∞. In contrast, knifefish swimming behind a fixed cylinder increased the use of pectoral fins, which resulted in changes in body orientation that mimicked steady backward swimming. Meanwhile, individuals behind the oscillating cylinder presented a combination of body bending and ribbon and pectoral fin movements that counteract the out-of-phase yaw oscillations induced by the irregular shedding of vortices. We corroborated passive out-of-phase oscillations by placing a printed knifefish model just downstream of the moving cylinder, but when placed one cylinder diameter downstream, the model oscillated in phase. Thus, the wake left behind an oscillating body is more challenging than a periodic vortex shedding for an animal located downstream, which may have consequences on inter- and intra-specific interactions.

Methocinnamox Reverses and Prevents Fentanyl-Induced Ventilatory Depression in Rats.

Opioid use disorder affects over 2 million Americans with an increasing number of deaths due to overdose from the synthetic opioid fentanyl and its analogs. The Food and Drug Administration-approved opioid receptor antagonist naloxone (e.g., Narcan) is used currently to treat overdose; however, a short duration of action limits its clinical utility. Methocinnamox (MCAM) is a long-lasting opioid receptor antagonist that may reverse and prevent the ventilatory-depressant effects of fentanyl. This study compared the ability of naloxone (0.0001-10 mg/kg) and MCAM (0.0001-10 mg/kg) to reverse and prevent ventilatory depression by fentanyl and compared the duration of action of MCAM intravenously and subcutaneously in two procedures: ventilation and warm-water tail withdrawal. In male Sprague-Dawley rats (N = 8), fentanyl (0.0032-0.178 mg/kg, i.v.) decreased minute volume in a dose- and time-dependent manner with a dose of 0.178 mg/kg decreasing VE to less than 40% of control. MCAM and naloxone reversed the ventilatory-depressant effects of 0.178 mg/kg fentanyl in a dose-related manner. The day after antagonist administration, MCAM but not naloxone attenuated the ventilatory-depressant effects of fentanyl. The duration of action of MCAM lasted up to 3 days and at least 2 weeks after intravenous and subcutaneous administration, respectively. MCAM attenuated the antinociceptive effects of fentanyl, with antagonism lasting up to 5 days and more than 2 weeks after intravenous and subcutaneous administration, respectively. Reversal and prolonged antagonism by MCAM might provide an effective treatment option for the opioid crisis, particularly toxicity from fentanyl and related highly potent analogs. SIGNIFICANCE STATEMENT: This study demonstrates that like naloxone, methocinnamox (MCAM) reverses the ventilatory-depressant effects of fentanyl in a time- and dose-related manner. However, unlike naloxone, the duration of action of MCAM was greater than 2 weeks when administered subcutaneously and up to 5 days when administered intravenously. These data suggest that MCAM might be particularly useful for rescuing individuals from opioid overdose, including fentanyl overdose, as well as protecting against the reemergence of ventilatory depression (renarconization).

Knifefish's suction makes water boil.

We discovered that knifefish (Apteronotus albifrons) during suction feeding can produce millimeter-sized cavitation bubbles and flow accelerations up to ~ 450 times the acceleration of gravity. Knifefish may use this powerful suction-induced cavitation to cause physical damage on prey hiding in narrow refuges, therefore facilitating capture.

Natural barriers: waterfall transit by small flying animals.

Waterfalls are conspicuous geomorphological features with heterogeneous structure, complex dynamics and multiphase flows. Swifts, dippers and starlings are well-known to nest behind waterfalls, and have been reported to fly through them. For smaller fliers, by contrast, waterfalls seem to represent impenetrable barriers, but associated physical constraints and the kinematic responses of volant animals during transit are unknown. Here, we describe the flight behaviour of hummingbirds (the sister group to the swifts) and of various insect taxa as they fly through an artificial sheet waterfall. We additionally launched plastic balls at different speeds at the waterfall so as to assess the inertial dependence of sheet penetration. Hummingbirds were able to penetrate the waterfall with reductions in both their translational speed, and stroke amplitude. The body tilted more vertically and exhibited greater rotations in roll, pitch and yaw, along with increases in tail spread and pitch. The much smaller plastic balls and some flies moving at speeds greater than 2.3 m s-1 and 1.6 m s-1, respectively, also overcame effects of surface tension and water momentum and passed through the waterfall; objects with lower momentum, by contrast, entered the sheet but then fell along with the moving water. Waterfalls can thus represent impenetrable physical barriers for small and slow animal fliers, and may also serve to exclude both predators and parasites from nests of some avian taxa.

Hearing Aid Use and Auditory Verbal Therapy Improve Voice Quality of Deaf Children.

BACKGROUND: Adequate phonation is self-regulated by auditory feedback. Children with bilateral profound hearing loss (PHL) lack this feedback resulting in abnormal voice. Adequate hearing aid use and auditory-verbal therapy (AVT) may improve voice quality in deaf children. OBJECTIVE: To study whether hearing aid use and AVT approach improve acoustic parameters of voice of children with bilateral PHL. MATERIALS AND METHODS: Nineteen children with bilateral PHL were studied. Age range 2-5 years (X = 53.04 months; SD = 9.54). All children were fitted with hearing aids according to auditory testing and they underwent a 1-year auditory habilitation period using the AVT approach. Acoustic analysis of voice including F0, shimmer, and jitter was performed at the onset and at the end of the auditory habilitation period. Final acoustic data were compared to a matched control group of 19 children, age range 2-5 years (X = 52.85; SD = 9.74) with normal hearing. RESULTS: Mean fundamental frequency (F0) was significantly increased after AVT intervention. Shimmer and jitter significantly (P < 0.05) improved after the intervention period. However, despite the improvements, mean F0 at the end of the intervention period was still significantly (P < 0.05) decreased as compared to controls. Also, mean shimmer and jitter at the end of the habilitation period were still significantly (P < 0.05) higher as compared to controls. CONCLUSIONS: The results of this preliminary study suggest that hearing aid use and auditory habilitation with AVT approach improved acoustic voice parameters of children with PHL. However, acoustic parameters persisted abnormal as compared to matched normal hearing controls. AVT approach and regular hearing aid use seem to be safe and reliable clinical tools for improving voice quality of children with PFL.

Persistence of Burkholderia thailandensis E264 in lung tissue after a single binge alcohol episode.

BACKGROUND: Binge drinking, an increasingly common form of alcohol use disorder, is associated with substantial morbidity and mortality; yet, its effects on the immune system's ability to defend against infectious agents are poorly understood. Burkholderia pseudomallei, the causative agent of melioidosis can occur in healthy humans, yet binge alcohol intoxication is increasingly being recognized as a major risk factor. Although our previous studies demonstrated that binge alcohol exposure increased B. pseudomallei near-neighbor virulence in vivo and increased paracellular diffusion and intracellular invasion, no experimental studies have examined the extent to which bacterial and alcohol dosage play a role in disease progression. In addition, the temporal effects of a single binge alcohol dose prior to infection has not been examined in vivo. PRINCIPAL FINDINGS: In this study, we used B. thailandensis E264 a close genetic relative of B. pseudomallei, as useful BSL-2 model system. Eight-week-old female C57BL/6 mice were utilized in three distinct animal models to address the effects of 1) bacterial dosage, 2) alcohol dosage, and 3) the temporal effects, of a single binge alcohol episode. Alcohol was administered comparable to human binge drinking (≤ 4.4 g/kg) or PBS intraperitoneally before a non-lethal intranasal infection. Bacterial colonization of lung and spleen was increased in mice administered alcohol even after bacterial dose was decreased 10-fold. Lung and not spleen tissue were colonized even after alcohol dosage was decreased 20 times below the U.S legal limit. Temporally, a single binge alcohol episode affected lung bacterial colonization for more than 24 h after alcohol was no longer detected in the blood. Pulmonary and splenic cytokine expression (TNF-α, GM-CSF) remained suppressed, while IL-12/p40 increased in mice administered alcohol 6 or 24 h prior to infection. Increased lung and not intestinal bacterial invasion was observed in human and murine non-phagocytic epithelial cells exposed to 0.2% v/v alcohol in vitro. CONCLUSIONS: Our results indicate that the effects of a single binge alcohol episode are tissue specific. A single binge alcohol intoxication event increases bacterial colonization in mouse lung tissue even after very low BACs and decreases the dose required to colonize the lungs with less virulent B. thailandensis. Additionally, the temporal effects of binge alcohol alters lung and spleen cytokine expression for at least 24 h after alcohol is detected in the blood. Delayed recovery in lung and not spleen tissue may provide a means for B. pseudomallei and near-neighbors to successfully colonize lung tissue through increased intracellular invasion of non-phagocytic cells in patients with hazardous alcohol intake.