Relationship of ankyloglossia and obstructive sleep apnea: systematic review and meta-analysis.

PURPOSE: Recent studies have highlighted the potential role of a short lingual frenulum as a risk factor for pediatric obstructive sleep apnea syndrome. A shortened frenulum may contribute to abnormal orofacial development, leading to increased upper airway resistance and susceptibility to upper airway collapsibility during sleep. Recognizing early indicators, such as a short lingual frenulum, is crucial for prompt intervention. This systematic review aims to evaluate the association between a short lingual frenulum and the risk of obstructive sleep apnea syndrome in children. METHODS: This systematic review adheres to PRISMA criteria for a quantitative analysis. A comprehensive search was conducted on five databases until January 2024 to identify relevant studies. The selected articles underwent rigorous analysis, considering study design, sample characteristics, lingual frenulum characterization, sleep assessment methods, and key findings. RESULTS: A total of 239 references were initially identified. Finally, six studies were included in the qualitative synthesis, with four studies eligible for the quantitative synthesis. The Newcastle-Ottawa scale was employed to assess study quality. Meta-analysis, supported by a moderate evidence profile according to the GRADE scale, revealed statistically significant differences, with odds ratios of 3.051 (confidence interval: 1.939 to 4.801) for a short frenulum and 12.304 (confidence interval: 6.141 to 24.653) for a high-arched palate. CONCLUSION: This systematic review and meta-analysis provide evidence supporting the association between ankyloglossia and obstructive sleep apnea in children. Nevertheless, it is crucial to consider additional factors such as tongue mobility and the presence of a high-arched palate in further evaluations.

Strategies of diaspore dispersal investment in Compositae: the case of the Andean highlands.

BACKGROUND AND AIMS: Understanding diaspore morphology and how much a species invests on dispersal appendages is key for improving our knowledge of dispersal in fragmented habitats. We investigate diaspore morphological traits in high-Andean Compositae and their main abiotic and biotic drivers and test whether they play a role in species distribution patterns across the naturally fragmented high-Andean grasslands. METHODS: We collected diaspore trait data for 125 Compositae species across 47 tropical high-Andean summits, focusing on achene length and pappus-to-achene length ratio, with the latter as a proxy of dispersal investment. We analysed the role of abiotic (temperature, elevation and latitude) and biotic factors (phylogenetic signal and differences between tribes) on diaspore traits and whether they are related to distribution patterns across the Andes, using phylogenomics, distribution modelling and community ecology analyses. KEY RESULTS: Seventy-five percent of the studied species show small achenes (length <3.3 mm) and 67% have high dispersal investment (pappus length at least two times the achene length). Dispersal investment increases with elevation, possibly to compensate for lower air density, and achene length increases towards the equator, where non-seasonal climate prevails. Diaspore traits show significant phylogenetic signal, and higher dispersal investment is observed in Gnaphalieae, Astereae and Senecioneae, which together represent 72% of our species. High-Andean-restricted species found across the tropical Andes have, on average, the pappus four times longer than the achene, a significantly higher dispersal investment than species present only in the northern Andes or only in the central Andes. CONCLUSIONS: Small achenes and high diaspore dispersal investment dominate among high-Andean Compositae, traits typical of mostly three tribes of African origin; but traits are also correlated with the environmental gradients within the high-Andean grasslands. Our results also suggest that diaspore dispersal investment is likely to shape species distribution patterns in naturally fragmented habitats.

A unilateral robotic knee exoskeleton to assess the role of natural gait assistance in hemiparetic patients.

BACKGROUND: Hemiparetic gait is characterized by strong asymmetries that can severely affect the quality of life of stroke survivors. This type of asymmetry is due to motor deficits in the paretic leg and the resulting compensations in the nonparetic limb. In this study, we aimed to evaluate the effect of actively promoting gait symmetry in hemiparetic patients by assessing the behavior of both paretic and nonparetic lower limbs. This paper introduces the design and validation of the REFLEX prototype, a unilateral active knee-ankle-foot orthosis designed and developed to naturally assist the paretic limbs of hemiparetic patients during gait. METHODS: REFLEX uses an adaptive frequency oscillator to estimate the continuous gait phase of the nonparetic limb. Based on this estimation, the device synchronically assists the paretic leg following two different control strategies: (1) replicating the movement of the nonparetic leg or (2) inducing a healthy gait pattern for the paretic leg. Technical validation of the system was implemented on three healthy subjects, while the effect of the generated assistance was assessed in three stroke patients. The effects of this assistance were evaluated in terms of interlimb symmetry with respect to spatiotemporal gait parameters such as step length or time, as well as the similarity between the joint's motion in both legs. RESULTS: Preliminary results proved the feasibility of the REFLEX prototype to assist gait by reinforcing symmetry. They also pointed out that the assistance of the paretic leg resulted in a decrease in the compensatory strategies developed by the nonparetic limb to achieve a functional gait. Notably, better results were attained when the assistance was provided according to a standard healthy pattern, which initially might suppose a lower symmetry but enabled a healthier evolution of the motion of the nonparetic limb. CONCLUSIONS: This work presents the preliminary validation of the REFLEX prototype, a unilateral knee exoskeleton for gait assistance in hemiparetic patients. The experimental results indicate that assisting the paretic leg of a hemiparetic patient based on the movement of their nonparetic leg is a valuable strategy for reducing the compensatory mechanisms developed by the nonparetic limb.

Validation of Cognitive Rehabilitation as a Balance Rehabilitation Strategy in Patients with Parkinson's Disease: Study Protocol for a Randomized Controlled Trial.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder. This disease is characterized by motor symptoms, such as bradykinesia, tremor, and rigidity. Although balance impairment is characteristic of advanced stages, it can be present with less intensity since the beginning of the disease. Approximately 60% of PD patients fall once a year and 40% recurrently. On the other hand, cognitive symptoms affect up to 20% of patients with PD in early stages and can even precede the onset of motor symptoms. There are cognitive requirements for balance and can be challenged when attention is diverted or reduced, linking a worse balance and a higher probability of falls with a slower cognitive processing speed and attentional problems. Cognitive rehabilitation of attention and processing speed can lead to an improvement in postural stability in patients with Parkinson's. Methods: We present a parallel and controlled randomized clinical trial (RCT) to assess the impact on balance of a protocol based on cognitive rehabilitation focused on sustained attention through the NeuronUP platform (Neuronup SI, La Rioja, Spain) in patients with PD. For 4 weeks, patients in the experimental group will receive cognitive therapy three days a week while the control group will not receive any therapy. The protocol has been registered at trials.gov NCT04730466. Conclusions: Cognitive therapy efficacy on balance improvement may open the possibility of new rehabilitation strategies for prevention of falls in PD, reducing morbidity, and saving costs to the health care system.

Clinical Effects of Immersive Multimodal BCI-VR Training after Bilateral Neuromodulation with rTMS on Upper Limb Motor Recovery after Stroke. A Study Protocol for a Randomized Controlled Trial.

Background and Objectives: The motor sequelae after a stroke are frequently persistent and cause a high degree of disability. Cortical ischemic or hemorrhagic strokes affecting the cortico-spinal pathways are known to cause a reduction of cortical excitability in the lesioned area not only for the local connectivity impairment but also due to a contralateral hemisphere inhibitory action. Non-invasive brain stimulation using high frequency repetitive magnetic transcranial stimulation (rTMS) over the lesioned hemisphere and contralateral cortical inhibition using low-frequency rTMS have been shown to increase the excitability of the lesioned hemisphere. Mental representation techniques, neurofeedback, and virtual reality have also been shown to increase cortical excitability and complement conventional rehabilitation. Materials and Methods: We aim to carry out a single-blind, randomized, controlled trial aiming to study the efficacy of immersive multimodal Brain-Computer Interfacing-Virtual Reality (BCI-VR) training after bilateral neuromodulation with rTMS on upper limb motor recovery after subacute stroke (>3 months) compared to neuromodulation combined with conventional motor imagery tasks. This study will include 42 subjects in a randomized controlled trial design. The main expected outcomes are changes in the Motricity Index of the Arm (MI), dynamometry of the upper limb, score according to Fugl-Meyer for upper limb (FMA-UE), and changes in the Stroke Impact Scale (SIS). The evaluation will be carried out before the intervention, after each intervention and 15 days after the last session. Conclusions: This trial will show the additive value of VR immersive motor imagery as an adjuvant therapy combined with a known effective neuromodulation approach opening new perspectives for clinical rehabilitation protocols.

Woody vegetation dynamics in the tropical and subtropical Andes from 2001 to 2014: Satellite image interpretation and expert validation.

The interactions between climate and land-use change are dictating the distribution of flora and fauna and reshuffling biotic community composition around the world. Tropical mountains are particularly sensitive because they often have a high human population density, a long history of agriculture, range-restricted species, and high-beta diversity due to a steep elevation gradient. Here we evaluated the change in distribution of woody vegetation in the tropical Andes of South America for the period 2001-2014. For the analyses we created annual land-cover/land-use maps using MODIS satellite data at 250 m pixel resolution, calculated the cover of woody vegetation (trees and shrubs) in 9,274 hexagons of 115.47 km2 , and then determined if there was a statistically significant (p < 0.05) 14 year linear trend (positive-forest gain, negative-forest loss) within each hexagon. Of the 1,308 hexagons with significant trends, 36.6% (n = 479) lost forests and 63.4% (n = 829) gained forests. We estimated an overall net gain of ~500,000 ha in woody vegetation. Forest loss dominated the 1,000-1,499 m elevation zone and forest gain dominated above 1,500 m. The most important transitions were forest loss at lower elevations for pastures and croplands, forest gain in abandoned pastures and cropland in mid-elevation areas, and shrub encroachment into highland grasslands. Expert validation confirmed the observed trends, but some areas of apparent forest gain were associated with new shade coffee, pine, or eucalypt plantations. In addition, after controlling for elevation and country, forest gain was associated with a decline in the rural population. Although we document an overall gain in forest cover, the recent reversal of forest gains in Colombia demonstrates that these coupled natural-human systems are highly dynamic and there is an urgent need of a regional real-time land-use, biodiversity, and ecosystem services monitoring network.

Tree mortality and recruitment in secondary Andean tropical mountain forests along a 3000 m elevation gradient.

This study addresses the understudied dynamics of mortality and recruitment in Tropical Mountain forests, critical determinants of forest structural processes and biomass turnover. We examine how these demographic processes change with elevation and varying degrees of forest recovery by utilizing two forest censuses (2015 and 2019) from 16 plots (0.36 ha) across a 600-3500 m asl elevation gradient in the Ecuadorian Andes. Employing multivariate PCA analyses, we characterize successional forest dynamics and explore relationships between demographic rates, elevation, and indicators of forest recovery using standard linear regression and generalized additive models (GAMs). Contrary to our hypothesis, mortality exhibits a unimodal response, peaking at mid-elevations, with no significant relationship to above-ground biomass productivity (AGBp). In our successional forests, dominance by fast-growing species alters expected patterns, leading to increased mortality rates and AGBp, particularly at low-mid elevations. Forest recovery emerges as a significant driver of mortality and the sole predictor of recruitment, especially across different recovery statuses. Although forest recovery doesn't impact mortality rates, it elucidates the identity of declining species in forests with varying recovery degrees. Our findings underscore that while forest recovery does not alter mortality rates, it provides critical insights into understanding which species are affected under varying recovery conditions. Recruitment, primarily driven by successional dynamics, exhibits higher rates in sites with less recovery. Furthermore, we demonstrate the utility of forest structure indicators, such as above-ground biomass, in inferring successional dynamics when the time since the last disturbance is unknown. The study emphasizes the importance of considering disturbances in comprehending the intricate interplay between the environment and forest dynamics in secondary forests.

Effects of motor imagery-based neurofeedback training after bilateral repetitive transcranial magnetic stimulation on post-stroke upper limb motor function: an exploratory crossover clinical trial.

OBJECTIVE: To examine the clinical effects of combining motor imagery-based neurofeedback training with bilateral repetitive transcranial magnetic stimulation for upper limb motor function in subacute and chronic stroke. DESIGN: Clinical trial following an AB/BA crossover design with counterbalanced assignment. SUBJECTS: Twenty individuals with subacute (n = 4) or chronic stroke (n = 16). METHODS: Ten consecutive sessions of bilateral repetitive transcranial magnetic stimulation alone (therapy A) were compared vs a combination of10 consecutive sessions of bilateral repetitive transcranial magnetic stimulation with 12 non-consecutive sessions of motor imagery-based neurofeedback training (therapy B). Patients received both therapies (1-month washout period), in sequence AB or BA. Participants were assessed before and after each therapy and at 15-days follow-up, using the Fugl-Meyer Assessment-upper limb, hand-grip strength, and the Nottingham Sensory Assessment as primary outcome measures. RESULTS: Both therapies resulted in improved functionality and sensory function. Therapy B consistently exhibited superior effects compared with therapy A, according to Fugl-Meyer Assessment and tactile and kinaesthetic sensory function across multiple time-points, irrespective of treatment sequence. No statistically significant differences between therapies were found for hand-grip strength. CONCLUSION: Following subacute and chronic stroke, integrating bilateral repetitive transcranial magnetic stimulation and motor imagery-based neurofeedback training has the potential to enhance functional performance compared with using bilateral repetitive transcranial magnetic stimulation alone in upper limb recovery.

Combined non-invasive neuromodulation using transcranial direct current stimulation, motor imagery and action observation for motor, cognitive and functional recovery in cortico-basal degeneration: a single case study.

This case report presents a comprehensive assessment and therapeutic intervention using non-invasive motor cortex neuromodulation for a 70-year-old female patient diagnosed with corticobasal degeneration (CBD). The study followed the CARE guidelines. The patient meets the criteria for probable CBD, with neuroimaging evidence of exclusively cortical impairment. The patient underwent a non-invasive neuromodulation protocol involving transcranial direct current stimulation (tDCS) and action observation plus motor imagery (AO+MI). The neuromodulation protocol comprised 20 sessions involving tDCS over the primary motor cortex and combined AO+MI. Anodal tDCS was delivered a 2 mA excitatory current for 20 minutes. AO+MI focused on lower limb movements, progressing over four weeks with video observation and gradual execution, both weekly and monthly. The neuromodulation techniques were delivered online (i.e. applied simultaneously in each session). Outcome measures were obtained at baseline, post-intervention and follow-up (1 month later), and included motor (lower limb), cognitive/neuropsychological and functional assessments. Walking speed improvements were not observed, but balance (Berg Balance Scale) and functional strength (Five Times Sit-to-Stand Test) improved post-treatment. Long-term enhancements in attentional set-shifting, inhibitory control, verbal attentional span, and working memory were found. There was neurophysiological evidence of diminished intracortical inhibition. Functional changes included worsening in Cortico Basal Ganglia Functional Scale score. Emotional well-being and general health (SF-36) increased immediately after treatment but were not sustained, while Falls Efficacy Scale International showed only long-term improvement. The findings suggest potential benefits of the presented neuromodulation protocol for CBD patients, highlighting multifaceted outcomes in motor, cognitive, and functional domains.

TDCS for parkinson's disease disease-related pain: A randomized trial.

OBJECTIVE: To evaluate the effects of transcranial direct current stimulation (tDCS) on Parkinson's disease (PD)-related pain. METHODS: This triple-blind randomized controlled trial included twenty-two patients (age range 38-85, 10 male) with PD-related pain. Eleven subjects received ten sessions of 20 minutes tDCS over the primary motor cortex contralateral to pain at 2 mA intensity. Eleven subjects received sham stimulation. Outcome measures included changes in the Kinǵs Parkinsons Pain Scale (KPPS), Brief Pain Inventory (BPI), widespread mechanical hyperalgesia (WMH), temporal summation of pain (TS), and conditioned pain modulation (CPM). RESULTS: Significant differences were found in KPPS between groups favoring the active-tDCS group compared to the sham-tDCS group at 15-days follow-up (p = 0.014) but not at 2 days post-intervention (p = 0.059). The active-group showed significant improvements over the sham-group after 15 days (p = 0.017). Significant changes were found in CPM between groups in favor of active-tDCS group at 2 days post-intervention (p = 0.002) and at 15 days (p = 0.017). No meaningful differences were observed in BPI or TS. CONCLUSIONS: tDCS of the primary motor cortex alleviates perceived PD-related pain, reduces pain sensitization, and enhances descending pain inhibition. SIGNIFICANCE: This is the first study to test and demonstrate the use of tDCS for improving PD-related pain.

Robotic exoskeleton embodiment in post-stroke hemiparetic patients: an experimental study about the integration of the assistance provided by the REFLEX knee exoskeleton.

Hemiparetic gait is the most common motor-disorder after stroke and, in spite of rehabilitation efforts, it is persistent in 50% of community dwelling stroke-survivors. Robotic exoskeletons have been proposed as assistive devices to support impaired joints. An example of these devices is the REFLEX knee exoskeleton, which assists the gait of hemiparetic subjects and whose action seems to be properly embodied by stroke survivors, who were able to adapt the motion of their non-assisted limbs and, therefore, reduce their compensation mechanisms. This paper presents an experimental validation carried out to deepen into the effects of REFLEX's assistance in hemiparetic subjects. Special attention was paid to the effect produced in the muscular activity as a metric to evaluate the embodiment of this technology. Significant differences were obtained at the subject level due to the assistance; however, the high dispersion of the measured outcomes avoided extracting global effects at the group level. These results highlight the need of individually tailoring the action of the robot to the individual needs of each patient to maximize the beneficial outcomes. Extra research effort should be done to elucidate the neural mechanisms involved in the embodiment of external devices by stroke survivors.

Repetitive transcranial magnetic stimulation of primary motor cortex for stroke upper limb motor sequelae rehabilitation: A systematic review.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) over the primary motor cortex (M1) has been used to treat stroke motor sequelae regulating cortical excitability. Early interventions are widely recommended, but there is also evidence showing interventions in subacute or chronic phases are still useful. OBJECTIVE: To synthetize the evidence of rTMS protocols to improve upper limb motor function in people with subacute and/or chronic stroke. METHODS: Four databases were searched in July 2022. Clinical trials investigating the effectiveness of different rTMS protocols on upper limb motor function in subacute or chronic phases post-stroke were included. PRISMA guidelines and PEDro scale were used. RESULTS: Thirty-two studies representing 1137 participants were included. Positive effects of all types of rTMS protocols on upper limb motor function were found. These effects were heterogeneous and not always clinically relevant or related to neurophysiological changes but produced evident changes if evaluated with functional tests. CONCLUSION: rTMS interventions over M1 are effective for improving upper limb motor function in people with subacute and chronic stroke. When rTMS protocols were priming physical rehabilitation better effects were achieved. Studies considering minimal clinical differences and different dosing will help to generalize the use of these protocols in clinical practice.

Historical Assembly of Andean Tree Communities.

Patterns of species diversity have been associated with changes in climate across latitude and elevation. However, the ecological and evolutionary mechanisms underlying these relationships are still actively debated. Here, we present a complementary view of the well-known tropical niche conservatism (TNC) hypothesis, termed the multiple zones of origin (MZO) hypothesis, to explore mechanisms underlying latitudinal and elevational gradients of phylogenetic diversity in tree communities. The TNC hypothesis posits that most lineages originate in warmer, wetter, and less seasonal environments in the tropics and rarely colonize colder, drier, and more seasonal environments outside of the tropical lowlands, leading to higher phylogenetic diversity at lower latitudes and elevations. In contrast, the MZO hypothesis posits that lineages also originate in temperate environments and readily colonize similar environments in the tropical highlands, leading to lower phylogenetic diversity at lower latitudes and elevations. We tested these phylogenetic predictions using a combination of computer simulations and empirical analyses of tree communities in 245 forest plots located in six countries across the tropical and subtropical Andes. We estimated the phylogenetic diversity for each plot and regressed it against elevation and latitude. Our simulated and empirical results provide strong support for the MZO hypothesis. Phylogenetic diversity among co-occurring tree species increased with both latitude and elevation, suggesting an important influence on the historical dispersal of lineages with temperate origins into the tropical highlands. The mixing of different floras was likely favored by the formation of climatically suitable corridors for plant migration due to the Andean uplift. Accounting for the evolutionary history of plant communities helps to advance our knowledge of the drivers of tree community assembly along complex climatic gradients, and thus their likely responses to modern anthropogenic climate change.

Enhanced T cell responses against hepatitis C virus by ex vivo targeting of adenoviral particles to dendritic cells.

UNLABELLED: Injection of dendritic cells (DCs) presenting viral proteins constitutes a promising approach to stimulate T cell immunity against hepatitis C virus (HCV). Here we describe a strategy to enhance antigen loading and immunostimulatory functions of DCs useful in the preparation of therapeutic vaccines. Incubation of murine DCs with CFm40L, an adapter molecule containing the coxsackie-adenovirus receptor fused to the ecto-domain of murine CD40L-induced DC maturation, produced high amounts of interleukin-12 and up-regulation of molecules associated with T helper 1 responses. Accordingly, targeting of an adenovirus encoding HCV NS3 protein (AdNS3) to DCs with CFm40L strongly enhanced NS3 presentation in vitro, activating interferon-γ-producing T cells. Moreover, immunization of mice with these DCs promoted strong CD4 and CD8 T cell responses against HCV NS3. CFh40L, a similar adapter molecule containing human CD40L, enhanced transduction and maturation of human monocyte-derived DCs. Comparison of DCs transduced with AdNS3 and CFh40L from patients with chronic HCV infection and healthy donors revealed similar maturation levels. More importantly, DCs from the patients induced NS3-specific responses when transduced with AdNS3 and CFh40L but not with AdNS3 alone. CONCLUSION: DCs transduced with AdNS3 and the adapter molecule CFm/h40L exhibit enhanced immunostimulatory functions, induce robust anti-HCV NS3 immunity in animals, and can induce antiviral immune responses in subjects with chronic HCV infection. This strategy may serve as therapeutic vaccination for patients with chronic hepatitis C.

Improved dendritic cell-based immunization against hepatitis C virus using peptide inhibitors of interleukin 10.

UNLABELLED: The high levels of interleukin 10 (IL-10) present in chronic hepatitis C virus (HCV) infection have been suggested as responsible for the poor antiviral cellular immune responses found in these patients. To overcome the immunosuppressive effect of IL-10 on antigen-presenting cells such as dendritic cells (DCs), we developed peptide inhibitors of IL-10 to restore DC functions and concomitantly induce efficient antiviral immune responses. Two IL-10-binding peptides (p9 and p13) were selected using a phage-displayed library and their capacity to inhibit IL-10 was assessed in a bioassay and in STAT-3 (signal transducer and activator of transcription 3) phosphorylation experiments in vitro. In cultures of human leukocytes where HCV core protein induces the production of IL-10, p13 restored the ability of plasmacytoid DC to produce interferon alpha (IFN-α) after Toll-like receptor 9 (TLR9) stimulation. Similarly, when myeloid DCs were stimulated with CD40L in the presence of HCV core, p9 enhanced IL-12 production by inhibiting HCV core-induced as well as CD40L-induced IL-10. Moreover, in vitro, p13 potentiated the effect of maturation stimuli on human and murine DC, increasing their IL-12 production and stimulatory activity, which resulted in enhanced proliferation and IFN-γ production by responding T-cells. Finally, immunization with p13-treated murine DC induced stronger anti-HCV T-cell responses not only in wildtype mice but also in HCV transgenic mice and in mice transiently expressing HCV core in the liver. CONCLUSION: These results suggest that IL-10 inhibiting peptides may have important applications to enhance anti-HCV immune responses by restoring the immunostimulatory capabilities of DC.

A peptide inhibitor of FOXP3 impairs regulatory T cell activity and improves vaccine efficacy in mice.

Immunosuppressive activity of regulatory T cells (Treg) may contribute to the progression of cancer or infectious diseases by preventing the induction of specific immune responses. Using a phage-displayed random peptide library, we identified a 15-mer synthetic peptide, P60, able to bind to forkhead/winged helix transcription factor 3 (FOXP3), a factor required for development and function of Treg. P60 enters the cells, inhibits FOXP3 nuclear translocation, and reduces its ability to suppress the transcription factors NF-κB and NFAT. In vitro, P60 inhibited murine and human-derived Treg and improved effector T cell stimulation. P60 administration to newborn mice induced a lymphoproliferative autoimmune syndrome resembling the reported pathology in scurfy mice lacking functional Foxp3. However, P60 did not cause toxic effects in adult mice and, when given to BALB/c mice immunized with the cytotoxic T cell epitope AH1 from CT26 tumor cells, it induced protection against tumor implantation. Similarly, P60 improved the antiviral efficacy of a recombinant adenovirus expressing NS3 protein from hepatitis C virus. Functional inhibition of Treg by the FOXP3-inhibitory peptide P60 constitutes a strategy to enhance antitumor and antiviral immunotherapies.

Blocking TGF-ß1 protects the peritoneal membrane from dialysate-induced damage.

During peritoneal dialysis (PD), mesothelial cells undergo mesothelial-to-mesenchymal transition (MMT), a process associated with peritoneal-membrane dysfunction. Because TGF-ß1 can induce MMT, we evaluated the efficacy of TGF-ß1-blocking peptides in modulating MMT and ameliorating peritoneal damage in a mouse model of PD. Exposure of the peritoneum to PD fluid induced fibrosis, angiogenesis, functional impairment, and the accumulation of fibroblasts. In addition to expressing fibroblast-specific protein-1 (FSP-1), some fibroblasts co-expressed cytokeratin, indicating their mesothelial origin. These intermediate-phenotype (Cyto(+)/FSP-1(+)) fibroblasts had features of myofibroblasts with fibrogenic capacity. PD fluid treatment triggered the appearance of CD31(+)/FSP-1(+) and CD45(+)/FSP-1(+) cells, suggesting that fibroblasts also originate from endothelial cells and from cells recruited from bone marrow. Administration of blocking peptides significantly ameliorated fibrosis and angiogenesis, improved peritoneal function, and reduced the number of FSP-1(+) cells, especially in the Cyto(+)/FSP-1(+) subpopulation. Conversely, overexpression of TGF-ß1 in the peritoneum by adenovirus-mediated gene transfer led to a marked accumulation of fibroblasts, most of which derived from the mesothelium. Taken together, these results demonstrate that TGF-ß1 drives the peritoneal deterioration induced by dialysis fluid and highlights a role of TGF-ß1-mediated MMT in the pathophysiology of peritoneal-membrane dysfunction.

Elevational biodiversity gradients in the Neotropics: Perspectives from freshwater caddisflies (Insecta: Trichoptera).

Aquatic insects in the order Trichoptera are extremely diverse in number of species and their trophic roles. However, their distribution and diversity patterns are poorly known in the Neotropics, including the species restricted to tropical mountain ecosystems. Recent studies in tropical mountains have shown high levels of endemism of aquatic insects and changes in the composition of communities over short distances. Still, the incidence of environmental filters that explain such patterns has not been addressed quantitatively. Given the relevance of understanding Trichoptera spatial diversity patterns to prioritize conservation areas for freshwaters, as well as to obtain baseline information to predict changes in aquatic communities facing global environmental changes, we assessed the species distribution and assemblages of caddisflies along an elevational gradient from 600 to 3,600 m a.s.l. on the equatorial Andes. In this area, we had long-term continuous climate data with hourly resolution. We collected adult caddisflies in seven localities along this gradient using light traps. We sampled each locality for two hours after sunset for three consecutive days. All specimens collected were identified to species or morphospecies. Our results showed an increase in species and genera numbers with decreasing altitude, albeit no significant. Minimum air temperature is the main environmental variable explaining Trichoptera community assemblages. ß-diversity (taxon turnover among sites), as opposed to species richness, increased with altitude and showed a bimodal distribution along the elevation gradient for both genera and species assemblages, which resulted in a significant shift in community composition of species and genera at 2,000 m a.s.l. Our null-models confirm the observed patterns of B-diversity are non-random and suggest a strong environmental filtering of tropical caddisflies community assemblies and turnover. Geographic distance coupled with changes in environmental conditions along the elevation gradient explained a high percentage of community variance, as documented for other taxa (e.g., vascular plants), suggesting the importance of securing habitat connectivity along the altitudinal gradient to protect aquatic insect diversity effectively.

Comparison of the phenotypic characteristics between responders and non-responders to obstructive sleep apnea treatment using mandibular advancement devices in adult patients: Systematic review and meta-analysis.

Mandibular advancement device (MAD) therapy is the most commonly used second-line treatment for obstructive sleep apnea (OSA), but MAD may be ineffective in a subgroup of patients. The aim of this systematic review is to identify predictors of the efficacy of oral appliance (OA) therapy for OSA in adult patients. This review focuses on performing the quantitative analysis by subgroups based on the response criteria used in the literature and based on the type of device. PubMed, EMBASE, Scopus, Web of Science and Cochrane databases was conducted to identify potentially relevant studies published until Dec 2021. The search identified 1343 preliminary references. A total of 99 studies met the eligibility criteria and were included in the review, and 60 in the meta-analysis. The quality of studies was assessed using the Newcastle-Ottawa scale and the Cochrane scale. Based on meta-analysis, and considering a low to moderate evidence profile according to the GRADE scale, responders are younger patients, with smaller neck circumference, lower body mass index. Responders have shorter maxillary length, lower anterior and posterior facial height, a shorter distance from the hyoid bone to the third cervical vertebra, a shorter airway length, a smaller minimum airway cross-sectional area and a higher minimum oxygen saturation during sleep. Responders needed a lower optimal continuous positive airway pressure than non-responders. The type of device has not affected the results of the meta-analysis. The criterion "AHI <10 and reduction AHI >50%" is the one that provides the "weight" of significance for several variables. This criterion should be taken into consideration for future studies to predict OSA treatment by OA.

International Consensus Document on Obstructive Sleep Apnea. / Documento internacional de consenso sobre apnea obstructiva del sueño.

The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents).