Surface electrical stimulation of the auditory cortex preserves efferent medial olivocochlear neurons and reduces cochlear traits of age-related hearing loss.

The auditory cortex is the source of descending connections providing contextual feedback for auditory signal processing at almost all levels of the lemniscal auditory pathway. Such feedback is essential for cognitive processing. It is likely that corticofugal pathways are degraded with aging, becoming important players in age-related hearing loss and, by extension, in cognitive decline. We are testing the hypothesis that surface, epidural stimulation of the auditory cortex during aging may regulate the activity of corticofugal pathways, resulting in modulation of central and peripheral traits of auditory aging. Increased auditory thresholds during ongoing age-related hearing loss in the rat are attenuated after two weeks of epidural stimulation with direct current applied to the surface of the auditory cortex for two weeks in alternate days (Fernández del Campo et al., 2024). Here we report that the same cortical electrical stimulation protocol induces structural and cytochemical changes in the aging cochlea and auditory brainstem, which may underlie recovery of age-degraded auditory sensitivity. Specifically, we found that in 18 month-old rats after two weeks of cortical electrical stimulation there is, relative to age-matched non-stimulated rats: a) a larger number of choline acetyltransferase immunoreactive neuronal cell body profiles in the ventral nucleus of the trapezoid body, originating the medial olivocochlear system.; b) a reduction of age-related dystrophic changes in the stria vascularis; c) diminished immunoreactivity for the pro-inflammatory cytokine TNFα in the stria vascularis and spiral ligament. d) diminished immunoreactivity for Iba1 and changes in the morphology of Iba1 immunoreactive cells in the lateral wall, suggesting reduced activation of macrophage/microglia; d) Increased immunoreactivity levels for calretinin in spiral ganglion neurons, suggesting excitability modulation by corticofugal stimulation. Altogether, these findings support that non-invasive neuromodulation of the auditory cortex during aging preserves the cochlear efferent system and ameliorates cochlear aging traits, including stria vascularis dystrophy, dysregulated inflammation and altered excitability in primary auditory neurons.

[Laparoscopic excision versus open excision for the treatment of choledochal cysts: a systematic review and meta-analysis]. / Laparoskopicheskoe i otkrytoe khirurgicheskoe lechenie kist kholedokha: sistematicheskii obzor i metaanaliz.

OBJECTIVE: To determine if laparoscopic excision is more effective than open excision in the treatment of choledochal cysts. MATERIAL AND METHODS: A systematic review of randomized clinical trials in 3 databases measuring the efficacy of laparoscopic and open excision of choledochal cysts was performed. The authors considered international and national reports, whose results were analyzed in detail. RESULTS: Mean duration of laparoscopic excision was 51 min, open excision - 35.4 min. Length of hospital-stay after laparoscopic excision ranged between 5 and 74 days, after open excision - between 7 and 146 days. Bile leakage rate was 1-2% and 4%, respectively. Laparoscopic excision was followed by lower complication rate. Morbidity and mortality in laparoscopic excision was 20% and 0%, in open excision - 60% and 3.3%, respectively. CONCLUSION: Laparoscopic excision is more effective than open excision in the treatment of choledochal cysts.

Multisession anodal epidural direct current stimulation of the auditory cortex delays the progression of presbycusis in the Wistar rat.

Presbycusis or age-related hearing loss (ARHL) is one of the most prevalent chronic health problems facing aging populations. Along the auditory pathway, the stations involved in transmission and processing, function as a system of interconnected feedback loops. Regulating hierarchically auditory processing, auditory cortex (AC) neuromodulation can, accordingly, activate both peripheral and central plasticity after hearing loss. However, previous ARHL-prevention interventions have mainly focused on preserving the structural and functional integrity of the inner ear, overlooking the central auditory system. In this study, using an animal model of spontaneous ARHL, we aim at assessing the effects of multisession epidural direct current stimulation of the AC through stereotaxic implantation of a 1-mm silver ball anode in Wistar rats. Consisting of 7 sessions (0.1 mA/10 min), on alternate days, in awake animals, our stimulation protocol was applied at the onset of hearing loss (threshold shift detection at 16 months). Click- and pure-tone auditory brainstem responses (ABRs) were analyzed in two animal groups, namely electrically stimulated (ES) and non-stimulated (NES) sham controls, comparing recordings at 18 months of age. At 18 months, NES animals showed significantly increased threshold shifts, decreased wave amplitudes, and increased wave latencies after click and tonal ABRs, reflecting a significant, spontaneous ARHL evolution. Conversely, in ES animals, no significant differences were detected in any of these parameters when comparing 16 and 18 months ABRs, indicating a delay in ARHL progression. Electrode placement in the auditory cortex was accurate, and the stimulation did not cause significant damage, as shown by the limited presence of superficial reactive microglial cells after IBA1 immunostaining. In conclusion, multisession DC stimulation of the AC has a protective effect on auditory function, delaying the progression of presbycusis.

Prolonged-release pirfenidone in patients with pulmonary fibrosis as a phenotype of post-acute sequelae of COVID-19 pneumonia. Safety and efficacy.

INTRODUCTION: One of the major concerns with post-acute sequelae of COVID-19 (PASC) is the development of pulmonary fibrosis, for which no approved pharmacological treatment exists. Therefore, the primary aim of this open-label study was to evaluate the safety and the potential clinical efficacy of a prolonged-release pirfenidone formulation (PR-PFD) in patients having PASC-pulmonary fibrosis. METHODS: Patients with PASC-pulmonary fibrosis received PR-PFD 1800 mg/day (1200 mg in the morning after breakfast and 600 mg in the evening after dinner) for three months. Blood samples were taken to confirm the pharmacokinetics of PR-PFD, and adverse events (AEs) were evaluated monthly using a short questionnaire. Symptoms, dyspnea, and pulmonary function tests (spirometry, diffusing capacity for carbon monoxide, plethysmography, and 6-min walk test [6MWT]) were evaluated at baseline, and one and three months after having started the PR-PFD treatment. RESULTS: Seventy subjects with mild to moderate lung restriction were included. The most common AEs were diarrhea (23%), heartburn (23%), and headache (16%), for which no modifications in the drug study were needed. Two patients died within the first 30 days of enrolment, and three opted not to continue the study, events which were not associate with PR-PFD. Pulmonary function testing, 6MWT, dyspnea, symptoms, and CT scan significantly improved after three months of treatment with PR-PFD. CONCLUSION: In patients with PASC pulmonary fibrosis, three months' treatment with PR-PFD was safe and showed therapeutic efficacy. Still, it remains to be seen whether the pulmonary fibrotic process remains stable, becomes progressive or will improve.

VEGF-A related SNPs: a cardiovascular context.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Currently, cardiovascular disease risk algorithms play a role in primary prevention. However, this is complicated by a lack of powerfully predictive biomarkers that could be observed in individuals before the onset of overt symptoms. A key potential biomarker for heart disease is the vascular endothelial growth factor (VEGF-A), a molecule that plays a pivotal role in blood vessel formation. This molecule has a complex biological role in the cardiovascular system due to the processes it influences, and its production is impacted by various CVD risk factors. Research in different populations has shown single nucleotide polymorphisms (SNPs) may affect circulating VEGF-A plasma levels, with some variants associated with the development of CVDs, as well as CVD risk factors. This minireview aims to give an overview of the VEGF family, and of the SNPs reported to influence VEGF-A levels, cardiovascular disease, and other risk factors used in CVD risk assessments.

IGF-1 deficiency causes atrophic changes associated with upregulation of VGluT1 and downregulation of MEF2 transcription factors in the mouse cochlear nuclei.

Insulin-like growth factor 1 (IGF-1) is a neurotrophic protein that plays a crucial role in modulating neuronal function and synaptic plasticity in the adult brain. Mice lacking the Igf1 gene exhibit profound deafness and multiple anomalies in the inner ear and spiral ganglion. An issue that remains unknown is whether, in addition to these peripheral abnormalities, IGF-1 deficiency also results in structural changes along the central auditory pathway that may contribute to an imbalance between excitation and inhibition, which might be reflected in abnormal auditory brainstem responses (ABR). To assess such a possibility, we evaluated the morphological and physiological alterations in the cochlear nucleus complex of the adult mouse. The expression and distribution of the vesicular glutamate transporter 1 (VGluT1) and the vesicular inhibitory transporter (VGAT), which were used as specific markers for labeling excitatory and inhibitory terminals, and the involvement of the activity-dependent myocyte enhancer factor 2 (MEF2) transcription factors in regulating excitatory synapses were assessed in a 4-month-old mouse model of IGF-1 deficiency and neurosensorial deafness (Igf1 (-/-) homozygous null mice). The results demonstrate decreases in the cochlear nucleus area and cell size along with cell loss in the cochlear nuclei of the deficient mouse. Additionally, our results demonstrate that there is upregulation of VGluT1, but not VGAT, immunostaining and downregulation of MEF2 transcription factors together with increased wave II amplitude in the ABR recording. Our observations provide evidence of an abnormal neuronal cytoarchitecture in the cochlear nuclei of Igf1 (-/-) null mice and suggest that the increased efficacy of glutamatergic synapses might be mediated by MEF2 transcription factors.

Six mode selective fiber optic spatial multiplexer.

Low-loss all-fiber photonic lantern (PL) mode multiplexers (MUXs) capable of selectively exciting the first six fiber modes of a multimode fiber (LP01, LP11a, LP11b, LP21a, LP21b, and LP02) are demonstrated. Fabrication of the spatial mode multiplexers was successfully achieved employing a combination of either six step or six graded index fibers of four different core sizes. Insertion losses of 0.2-0.3 dB and mode purities above 9 dB are achieved. Moreover, it is demonstrated that the use of graded index fibers in a PL eases the length requirements of the adiabatic tapered transition and could enable scaling to large numbers.

Allometric relationships predicting foliar biomass and leaf area:sapwood area ratio from tree height in five Costa Rican rain forest species.

We developed allometric equations to predict whole-tree leaf area (A(l)), leaf biomass (M(l)) and leaf area to sapwood area ratio (A(l):A(s)) in five rain forest tree species of Costa Rica: Pentaclethra macroloba (Willd.) Kuntze (Fabaceae/Mim), Carapa guianensis Aubl. (Meliaceae), Vochysia ferru-gi-nea Mart. (Vochysiaceae), Virola koshnii Warb. (Myristicaceae) and Tetragastris panamensis (Engl.) Kuntze (Burseraceae). By destructive analyses (n = 11-14 trees per species), we observed strong nonlinear allometric relationships (r(2) > or = 0.9) for predicting A(l) or M(l) from stem diameters or A(s) measured at breast height. Linear relationships were less accurate. In general, A(l):A(s) at breast height increased linearly with tree height except for Penta-clethra, which showed a negative trend. All species, however, showed increased total A(l) with height. The observation that four of the five species increased in A(l):A(s) with height is consistent with hypotheses about trade--offs between morphological and anatomical adaptations that favor efficient water flow through variation in the amount of leaf area supported by sapwood and those imposed by the need to respond quickly to light gaps in the canopy.

Baseline assessment for environmental services payments from satellite imagery: a case study from Costa Rica and Mexico.

In this study we evaluate the accuracy of four global and regional forest cover assessments (MODIS, IGBP, GLC2000, PROARCA) as tools for baseline estimation. We conduct this research at the national scale for Costa Rica and for two tropical dry forest study sites in Costa Rica (Santa Rosa) and Mexico (Chamela-Cuixmala). We found that at the national level, the total forest cover accuracy of the four land cover maps was inflated due to an overestimation of forest in areas with an evergreen canopy. However, the four maps greatly underestimated the extent of the deciduous forest (dry forest); an ecosystem that faces high deforestation pressure and poses complications to the mapping of its extent from remotely sensed data. For the tropical dry forest sites, all maps have low forest cover accuracies (mean for Santa Rosa: 27%; mean for Chamela-Cuixmala: 56%). This has implications for policy implementation.

Unilateral cochlear ablation in adult ferrets results in upregulation in calretinin immunostaining in the central nucleus of the inferior colliculus.

In the present study, unilateral cochlear ablations were performed in adult ferrets in order to determine whether an upregulation of the calretinin immunostained plexus in the central nucleus of the inferior colliculus occurs and if so, what the time course of this upregulation is. Accordingly, the mean gray level and the calretinin-immunostained area of the axonal plexus in the central nucleus of the inferior colliculus were evaluated at 1, 20 and 90 days after cochlear ablation. In unoperated animals, the calretinin-immunostained plexus was bilaterally symmetric. In ablated animals, both the mean gray level and the immunostained area of the plexus increased in the central nucleus of the inferior colliculus contralateral to the lesion compared with both the ipsilateral side and unoperated animals. This upregulation was present 24 h after the ablation and did not change at the two subsequent time points. In a previous study in young ferrets, the immunostained area of the plexus in the central nucleus of the inferior colliculus contralateral to the lesion increased 200% compared with control ferrets [J Comp Neurol 460 (2003) 585], whereas it increased only 33% in adult ferrets. These findings suggest that 1) calretinin upregulation in the contralateral central nucleus of the inferior colliculus following cochlear ablation occurs by 24 h after cochlear ablation and 2) there is an age-related decline in the magnitude of this upregulation after cochlear ablation.

Calibration and assessment of seasonal changes in leaf area index of a tropical dry forest in different stages of succession.

A simple measure of the amount of foliage present in a forest is leaf area index (LAI; the amount of foliage per unit ground surface area), which can be determined by optical estimation (gap fraction method) with an instrument such as the Li-Cor LAI-2000 Plant Canopy Analyzer. However, optical instruments such as the LAI-2000 cannot directly differentiate between foliage and woody components of the canopy. Studies investigating LAI and its calibration (extracting foliar LAI from optical estimates) in tropical forests are rare. We calibrated optical estimates of LAI from the LAI-2000 with leaf litter data for a tropical dry forest. We also developed a robust method for determining LAI from leaf litter data in a tropical dry forest environment. We found that, depending on the successional stage of the canopy and the season, the LAI-2000 may underestimate LAI by 17% to over 40%. In the dry season, the instrument overestimated LAI by the contribution of the woody area index. Examination of the seasonal variation in LAI for three successional stages in a tropical dry forest indicated differences in timing of leaf fall according to successional stage and functional group (i.e., lianas and trees). We conclude that when calculating LAI from optical estimates, it is necessary to account for the differences between values obtained from optical and semi-direct techniques. In addition, to calculate LAI from litter collected in traps, specific leaf area must be calculated for each species rather than from a mean value for multiple species.