Association of COX-2, TNF-α, TLR4, and IKKα With Survival of Patients With Oral Squamous Cell Carcinomas: A Systematic Review.

BACKGROUND: This review investigated the association of COX-2, TNF-α, TLR4, and IKKα with the survival of patients with oral squamous cell carcinoma (SCC). METHODS: A systematic search was conducted in the databases PUBMED, Web of Science, LILACS, EMBASE, Scopus, and Cochrane Library. The studies should assess the expression of those proteins in the tumor and survival outcomes. RESULTS: Twenty-one articles were included. The meta-analysis results leaned towards an association of COX-2 overexpression with a lower overall survival. The estimated hazard ratio was 1.51 (95% CI 0.97, 2.33), but not statistically significant (p=0.07). A low heterogeneity was observed (I2=0%). Regarding TNF-α, TLR4, and IKKα, statistically significant results for the association with survival were presented, but there was not enough data to a meta-analysis. CONCLUSION: COX-2 overexpression may be associated with a poorer prognosis in oral SCC. The insufficiency of studies about TNF-α, TLR4, and IKKα restrained their validation as predictors of prognosis.

Scleromalacia perforans as an early manifestation of late-onset rheumatoid arthritis: a case-based review.

Rheumatoid arthritis is a chronic autoimmune disease that can affect different organs beyond the joints. Ocular involvement includes keratoconjunctivitis sicca, peripheral ulcerative keratitis (PUK), episcleritis, scleritis, anterior uveitis, and corneal impairment. The most severe form of scleritis, scleromalacia perforans, is an aggressive ophthalmic manifestation that can potentially lead to blindness, usually occurring in late stages of disease. We report a case of an elderly woman in which this severe ocular manifestation occurred early on disease onset, differing from most of the previously reported cases of scleromalacia perforans. Ocular symptoms started concomitantly with the polyarthritis and other extra-articular manifestations, including rheumatoid nodules and vasculitic skin lesions. Ocular disease progressed due to patient's loss to follow-up, requiring pulse therapy with methylprednisolone. However, despite treatment, right eye enucleation was required due to melting of the corneal patch with uveal exposition. The patient was then treated with rituximab with improvement of systemic disease. The present case reinforces that, although rare, this complication is severe and must be promptly diagnosed and aggressively treated to improve prognosis of ocular and systemic RA.

Respiratory failure in systemic sclerosis.

Systemic sclerosis (SSc) can lead to dyspnea and respiratory failure through multiple mechanisms, making a precise diagnosis particularly challenging, especially amid the current COVID-19 pandemic. In this report, we present a case involving a 26-year-old female who had previously undiagnosed SSc. She experienced acute respiratory failure necessitating orotracheal intubation. Following an extensive evaluation, the patient exhibited skin thickening, kidney failure, thrombocytopenia, microangiopathic anemia, and an antinuclear antibody with a nuclear fine speckled pattern at a titer of 1:320. A diagnosis of SSc complicated by scleroderma renal crisis (SRC) was established. The patient's condition improved after undergoing hemodialysis, receiving an angiotensin-converting enzyme inhibitor, and undergoing cyclophosphamide treatment. Subsequently, she demonstrated sustained improvement during a follow-up period of 20 months.

Critical digital ischaemia in systemic sclerosis exacerbated by multiple myeloma: A case report.

Introduction: The overlapping of systemic sclerosis with hematologic malignancy has been described previously in the literature. This case report presents a patient with systemic sclerosis and multiple myeloma who had severe digital ischaemia that culminated in the amputation of several fingers. Case report: A 65-year-old White female patient was diagnosed with limited systemic sclerosis in 2002, smouldering multiple myeloma IgG/kappa in 2017 and liver cirrhosis in 2018 due to autoimmune hepatitis. In 2021, she was admitted to the emergency room with dry ischaemia of all fingers and toes despite optimized therapy, associated with visual blurring. The diagnostic hypothesis was hyperviscosity syndrome associated with multiple myeloma reactivation. The patient underwent chemotherapy and despite initial laboratory improvement, 19 digits required amputation. Conclusion: Although the association between systemic sclerosis and multiple myeloma is rare, it should be remembered in cases of significant worsening of Raynaud's phenomenon. Causes unrelated to systemic sclerosis should also be considered in the presence of severe exacerbations in patients with other comorbidities.

Rendimiento Clínico de las Restauraciones Adhesivas con Resina Compuesta en Casos de Pacientes con Desgaste Severo e Incremento de Dimensión Vertical: Revisión de Literatura Sistematizada / Clínical Performance of Adhesive Restorations with Composite Resin in Cases of Patients with Severe Wear and Increased Vertical Dimension: Systematized Literature Review

El desgaste dental severo se describe como la pérdida sustancial de la estructura dental, con exposición de la dentina y pérdida significativa de igual o más de 1/3 de la corona clínica. El uso de materiales compuestos de resina permite al clínico ser más conservador, debido a su aplicación mínimamente invasiva. Además de ello, son relativamente económicas, proporcionan buena estética general, así como un buen rendimiento y facilidad en la reparación. El objetivo de esta revisión de literatura sistematizada es recopilar información disponible en la literatura referente a cuál es el rendimiento clínico de las restauraciones adhesivas con resina compuesta en casos de pacientes con desgaste severo e incremento de la dimensión vertical como objetivo rehabilitador. Se analizaron artículos entre los años 2000 y 2022, seleccionando cuatro bases de datos (Pubmed, Scopus, Scielo y Web of Science). Para identificar los descriptores se utilizó los Medical subject headings (Mesh): Tooth Wear, Composite Restorations, Resin y Oral Rehabilitation. No se aplicó restricciones de idioma, país de origen, autor o lugar de publicación donde se realizó el estudio. Como resultado de la búsqueda se obtuvieron 71 artículos, de los cuales se seleccionaron 5 que cumplieron con los criterios de elegibilidad para ser considerados en la revisión de literatura sistematizada. Se encontró un promedio de tasa de éxito ente el 89,4 % - 100 % en un promedio total de 5.2 años de seguimiento. Se puede concluir, hasta donde se tiene conocimiento en la literatura científica disponible, que el tratamiento de restauraciones adhesivas con resinas compuestas en pacientes con desgaste severo es recomendable, enfocado en un periodo a corto-mediano plazo (3-5 años), siendo una opción de tratamiento económica y mínimamente invasiva.

Severe tooth wear is described as the substantial loss of tooth structure, with dentin exposure and significant loss of equal to or more than 1/3 of the clinical crown. The use of resin composite materials allows the clinician to be more conservative, due to its minimally invasive application. In addition to this, they are relatively inexpensive, provide good general aesthetics, as well as good performance and ease of repair. The objective of this systematic literature review is to collect information available in the literature regarding the clinical performance of adhesive restorations with composite resin in cases of patients with severe wear and increase in the vertical dimension as a rehabilitation objective. Articles between the years 2000 and 2022 were analyzed, selecting four databases (Pubmed, Scopus, Scielo and Web of Science). To identify the descriptors, the Medical subject headings (Mesh) were used: Tooth Wear, Composite Restorations, Resin and Oral Rehabilitation. No language, country of origin, author or place of publication restrictions where the study was conducted were applied. As a result of the search, 71 articles were obtained, of which 5 were selected that met the eligibility criteria to be considered in the systematic literature review. An average success rate between 89.4 % - 100 % was found in a total average of 5.2 years of follow-up. It can be concluded, to the best of our knowledge in the available scientific literature, that the treatment of adhesive restorations with composite resins in patients with severe wear is recommendable, focused on a short-medium term period (3-5 years), being a Inexpensive and minimally invasive treatment option.

Assessment of Bone Microarchitecture in Patients with Systemic Mastocytosis and its Association with Clinical and Biochemical Parameters of the Disease.

Patients with systemic mastocytosis (SM) are at high risk of bone deterioration. However, the evaluation of bone microarchitecture in this disease remains unclear. We aimed to assess bone microarchitecture in patients with SM. This was a cross-sectional study of 21 adult patients with SM conducted in a quaternary referral hospital in Sao Paulo, Brazil. A healthy, age-, weight-, and sex-matched cohort of 63 participants was used to provide reference values for bone microarchitecture, assessed by high resolution peripheral quantitative computed tomography (HR-pQCT). Total volumetric bone mineral density (vBMD), cortical vBMD, and cortical thickness at the radius were significantly lower in the control group compared with the SM group (all P < 0.001). Patients with aggressive SM had significantly lower trabecular number (Tb.N) (P = 0.035) and estimated failure load (F.load) (P = 0.032) at the tibia compared with those with indolent SM. Handgrip strength was significantly higher in patients who had more Tb.N at the radius (ρ, 0.46; P = 0.036) and tibia (ρ, 0.49; P = 0.002), and lower who had more trabecular separation at the radius (ρ, -0.46; P = 0.035) and tibia (ρ, -0.52; P = 0.016). Strong and positive associations between F.load (ρ, 0.75; P < 0.001) and stiffness (ρ, 0.70; P < 0.001) at the radius, and between F.load at the tibia (ρ, 0.45; P = 0.038) were observed with handgrip strength. In this cross-sectional study, aggressive SM was more susceptible to bone deterioration compared with indolent SM. In addition, the findings demonstrated that handgrip strength was associated with bone microarchitecture and bone strength.

Strong Dispersal Limitation of Microbial Communities at Shackleton Glacier, Antarctica.

Microbial communities can be structured by both deterministic and stochastic processes, but the relative importance of these processes remains unknown. The ambiguity partly arises from an inability to disentangle soil microbial processes from confounding factors, such as aboveground plant communities or anthropogenic disturbance. In this study, we characterized the relative contributions of determinism and stochasticity to assembly processes of soil bacterial communities across a large environmental gradient of undisturbed Antarctic soils. We hypothesized that harsh soils would impose a strong environmental selection on microbial communities, whereas communities in benign soils would be structured largely by dispersal. Contrary to our expectations, dispersal was the dominant assembly mechanism across the entire soil environmental gradient, including benign environments. The microbial community composition reflects slowly changing soil conditions and dispersal limitation of isolated sites. Thus, stochastic processes, as opposed to deterministic, are primary drivers of soil ecosystem assembly across space at our study site. This is especially surprising given the strong environmental constraints on soil microorganisms in one of the harshest environments on the planet, suggesting that dispersal could be a driving force in microbial community assembly in soils worldwide. IMPORTANCE Because of their diversity and ubiquity, microbes provide an excellent means to tease apart how natural communities are structured. In general, ecologists believe that stochastic assembly processes, like random drift and dispersal, should dominate in benign environments while deterministic processes, like environmental filtering, should be prevalent in harsh environments. To help resolve this debate, we analyzed microbial community composition in pristine Antarctic soils devoid of human influence or plant communities for eons. Our results demonstrate that dispersal limitation is a surprisingly potent force of community limitation throughout all soil conditions. Thus, dispersal appears to be a driving force of microbial community assembly, even in the harshest of conditions.

Social impact of disease parameters and damage accrual in adult Brazilian patients with childhood-onset Systemic Lupus Erythematosus.

OBJECTIVES: To describe the frequency and investigate potential associations of unemployment, need of financial assistance and health-related quality of life in adult patients with childhood-onset Systemic Lupus Erythematosus (cSLE). METHODS: In this multicenter cross-sectional retrospective cohort study including cSLE adult patients, questionnaires were applied evaluating demographic characteristics, medical history, treatment, receipt of government financial assistance, work status, quality of life, economic classification, disease activity, and damage accrual. Disease activity and disease damage were measured at the study visit. RESULTS: Sixty-nine cSLE patients with a median age of 21 years from two Brazilian tertiary centers were included (median disease duration 9 years). Twenty-eight (40.6%) patients were unemployed and 16 (23.2%) were receiving financial assistance or retirement pension. Work unemployment was associated with higher damage scores (OR 1.83, 95% CI 1.08 to 3.09, p = 0.024), and the need of financial assistance was associated with longer disease duration (OR 1.15, 95% CI 1.00 to 1.31, p = 0.045) and worse economic score (OR 0.87, 95% CI 0.77 to 0.99, p = 0.038). Emotional health and body image perception were the most compromised domains of quality of life but showed no association with disease parameters. Disease activity, on the other hand, was inversely associated with symptoms scores (ß = -1.377, p = 0.014) and scores of adverse effects of medications (ß = -1.286, p = 0.020). CONCLUSION: cSLE is a disease with severe outcomes and high social burden that profoundly impacts patients. Damage accrual is a major contributor to unemployment during adulthood and its prevention must be central in the management of cSLE.

Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19.

BACKGROUND: The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown. OBJECTIVES: We aimed to investigate the effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. METHODS: This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in São Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1ß, IL-6, IL-10, TNF-α, and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1ß (MIP-1ß), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes. RESULTS: The study included 200 patients with a mean ± SD age of 55.5 ± 14.3 y and BMI of 32.2 ± 7.1 kg/m2, of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the between-group difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes. CONCLUSIONS: The findings do not support the use of a single dose of 200,000 IU vitamin D3, compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19.This trial was registered at clinicaltrials.gov as NCT04449718.

Response of Antarctic soil fauna to climate-driven changes since the Last Glacial Maximum.

Understanding how terrestrial biotic communities have responded to glacial recession since the Last Glacial Maximum (LGM) can inform present and future responses of biota to climate change. In Antarctica, the Transantarctic Mountains (TAM) have experienced massive environmental changes associated with glacial retreat since the LGM, yet we have few clues as to how its soil invertebrate-dominated animal communities have responded. Here, we surveyed soil invertebrate fauna from above and below proposed LGM elevations along transects located at 12 features across the Shackleton Glacier region. Our transects captured gradients of surface ages possibly up to 4.5 million years and the soils have been free from human disturbance for their entire history. Our data support the hypothesis that soils exposed during the LGM are now less suitable habitats for invertebrates than those that have been exposed by deglaciation following the LGM. Our results show that faunal abundance, community composition, and diversity were all strongly affected by climate-driven changes since the LGM. Soils more recently exposed by the glacial recession (as indicated by distances from present ice surfaces) had higher faunal abundances and species richness than older exposed soils. Higher abundances of the dominant nematode Scottnema were found in older exposed soils, while Eudorylaimus, Plectus, tardigrades, and rotifers preferentially occurred in more recently exposed soils. Approximately 30% of the soils from which invertebrates could be extracted had only Scottnema, and these single-taxon communities occurred more frequently in soils exposed for longer periods of time. Our structural equation modeling of abiotic drivers highlighted soil salinity as a key mediator of Scottnema responses to soil exposure age. These changes in soil habitat suitability and biotic communities since the LGM indicate that Antarctic terrestrial biodiversity throughout the TAM will be highly altered by climate warming.

Precipitation effects on nematode diversity and carbon footprint across grasslands.

Free-living nematodes are one of the most diverse metazoan taxa in terrestrial ecosystems and are critical to the global soil carbon (C) cycling through their role in organic matter decomposition. They are highly dependent on water availability for movement, feeding, and reproduction. Projected changes in precipitation across temporal and spatial scales will affect free-living nematodes and their contribution to C cycling with unforeseen consequences. We experimentally reduced and increased growing season precipitation for 2 years in 120 field plots at arid, semiarid, and mesic grasslands and assessed precipitation controls on nematode genus diversity, community structure, and C footprint. Increasing annual precipitation reduced nematode diversity and evenness over time at all sites, but the mechanism behind these temporal responses differed for dry and moist grasslands. In arid and semiarid sites, there was a loss of drought-adapted rare taxa with increasing precipitation, whereas in mesic conditions increases in the population of predaceous taxa with increasing precipitation may have caused the observed reductions in dominant colonizer taxa and yielded the negative precipitation-diversity relationship. The effects of temporal changes in precipitation on all aspects of the nematode C footprint (respiration, production, and biomass C) were all dependent on the site (significant spatial × temporal precipitation interaction) and consistent with diversity responses at mesic, but not at arid and semiarid, grasslands. These results suggest that free-living nematode biodiversity and their C footprint will respond to climate change-driven shifts in water availability and that more frequent extreme wet years may accelerate decomposition and C turnover in semiarid and arid grasslands.

Influence of vitamin D status on hospital length of stay and prognosis in hospitalized patients with moderate to severe COVID-19: a multicenter prospective cohort study.

BACKGROUND: Vitamin D acts as a mediator in the immune system regulating antiviral mechanisms and inflammatory processes. Vitamin D insufficiency has been suggested as a potential risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, although its impact on the prognosis of hospitalized patients with coronavirus disease 2019 (COVID-19) remains unclear. OBJECTIVE: This multicenter prospective cohort study was designed to investigate whether serum 25-hydroxyvitamin D [25(OH)D] concentration is associated with hospital length of stay and prognosis in hospitalized patients with COVID-19. METHODS: Patients with moderate to severe COVID-19 (n = 220) were recruited from 2 hospitals in Sao Paulo, Brazil. Serum 25(OH)D concentrations were categorized as follows: <10 ng/mL, 10 to <20 ng/mL, 20 to <30 ng/mL, and ≥30 ng/mL, and <10 ng/mL and ≥10 ng/mL. The primary outcome was hospital length of stay and the secondary outcomes were the rate of patients who required invasive mechanical ventilation and mortality. RESULTS: There were no significant differences in hospital length of stay when the 4 25(OH)D categories were compared (P = 0.120). Patients exhibiting 25(OH)D <10 ng/mL showed a trend (P = 0.057) for longer hospital length of stay compared with those with 25(OH)D ≥10 ng/mL [9.0 d (95% CI: 6.4, 11.6 d) vs. 7.0 d (95% CI: 6.6, 7.4 d)]. The multivariable Cox proportional hazard models showed no significant associations between 25(OH)D and primary or secondary outcomes. CONCLUSIONS: Among hospitalized patients with moderate to severe COVID-19, those with severe 25(OH)D deficiency (<10 ng/mL) exhibited a trend for longer hospital length of stay compared with patients with higher 25(OH)D concentrations. This association was not significant in the multivariable Cox regression model. Prospective studies should test whether correcting severe 25(OH)D deficiency could improve the prognosis of patients with COVID-19.

Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial.

Importance: The efficacy of vitamin D3 supplementation in coronavirus disease 2019 (COVID-19) remains unclear. Objective: To investigate the effect of a single high dose of vitamin D3 on hospital length of stay in patients with COVID-19. Design, Setting, and Participants: This was a multicenter, double-blind, randomized, placebo-controlled trial conducted in 2 sites in Sao Paulo, Brazil. The study included 240 hospitalized patients with COVID-19 who were moderately to severely ill at the time of enrollment from June 2, 2020, to August 27, 2020. The final follow-up was on October 7, 2020. Interventions: Patients were randomly assigned to receive a single oral dose of 200 000 IU of vitamin D3 (n = 120) or placebo (n = 120). Main Outcomes and Measures: The primary outcome was length of stay, defined as the time from the date of randomization to hospital discharge. Prespecified secondary outcomes included mortality during hospitalization; the number of patients admitted to the intensive care unit; the number of patients who required mechanical ventilation and the duration of mechanical ventilation; and serum levels of 25-hydroxyvitamin D, total calcium, creatinine, and C-reactive protein. Results: Of 240 randomized patients, 237 were included in the primary analysis (mean [SD] age, 56.2 [14.4] years; 104 [43.9%] women; mean [SD] baseline 25-hydroxyvitamin D level, 20.9 [9.2] ng/mL). Median (interquartile range) length of stay was not significantly different between the vitamin D3 (7.0 [4.0-10.0] days) and placebo groups (7.0 [5.0-13.0] days) (log-rank P = .59; unadjusted hazard ratio for hospital discharge, 1.07 [95% CI, 0.82-1.39]; P = .62). The difference between the vitamin D3 group and the placebo group was not significant for in-hospital mortality (7.6% vs 5.1%; difference, 2.5% [95% CI, -4.1% to 9.2%]; P = .43), admission to the intensive care unit (16.0% vs 21.2%; difference, -5.2% [95% CI, -15.1% to 4.7%]; P = .30), or need for mechanical ventilation (7.6% vs 14.4%; difference, -6.8% [95% CI, -15.1% to 1.2%]; P = .09). Mean serum levels of 25-hydroxyvitamin D significantly increased after a single dose of vitamin D3 vs placebo (44.4 ng/mL vs 19.8 ng/mL; difference, 24.1 ng/mL [95% CI, 19.5-28.7]; P < .001). There were no adverse events, but an episode of vomiting was associated with the intervention. Conclusions and Relevance: Among hospitalized patients with COVID-19, a single high dose of vitamin D3, compared with placebo, did not significantly reduce hospital length of stay. The findings do not support the use of a high dose of vitamin D3 for treatment of moderate to severe COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04449718.

Visceral adipose tissue in granulomatosis with polyangiitis: association with disease activity parameters.

OBJECTIVE: To assess the body composition (BC) of patients with granulomatosis with polyangiitis (GPA) compared to healthy controls, emphasizing visceral adipose tissue (VAT) and associated BC parameters with disease activity, the damage index, and inflammatory parameters in patients with GPA. METHODS: This study was conducted in 43 patients with GPA and 43 healthy controls matched by sex, age, and body mass index (BMI). BC was analyzed using dual-energy X-ray absorptiometry (DXA). The fat mass parameters evaluated were total fat mass (FM), adiposity (%), the fat mass index (FMI: fat mass/ht2), and VAT (g, cm2, cm3). Disease activity was assessed by the Birmingham Vasculitis Activity Score (BVAS). Damage was assessed by the Vasculitis Damage Index (VDI). C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were measured. RESULTS: Comparing patients with GPA with healthy controls, patients had a significantly greater VAT (VAT in g: 685.81 ± 306.10 vs. 581.21 ± 235.57, p = 0.04; VAT in cm2: 142.23 ± 63.48 vs. 119.84 ± 49.54, p = 0.03; VAT in cm3: 741.33 ± 330.97 vs. 628.44 ± 254.66, p = 0.04). Patients with higher VAT (≥ 768 g) had an increased value of ESR (22.77 ± 26.79 vs. 11.57 ± 11.30 mm/1st hour, p = 0.04) and an increased value of BVAS (3.18 ± 4.15 vs. 0.90 ± 1.70, p = 0.01) when compared to patients with less VAT (< 768 g). CONCLUSION: Patients with GPA have altered BC compared to healthy controls. Moreover, higher VAT was associated with disease activity and higher inflammatory markers, suggesting a relationship between GPA activity and adiposity parameters. Key points • Granulomatosis with polyangiitis patients have increased visceral adipose tissue when compared to health controls; • Granulomatosis with polyangiitis patients with higher values of visceral adipose tissue have worse disease activity and higher inflammatory markers; • This paper represents important contribution to the well-studied association between vasculitis and inflammatory markers, adding the role of adipose visceral tissue in the disease physiopathology.

Ecto- and endoparasitic nematodes respond differently across sites to changes in precipitation.

Plant parasitic nematodes are among the greatest consumers of primary production in terrestrial ecosystems. Their feeding strategies can be divided into endoparasites and ectoparasites that differ substantially, not only in their damage potential to host tissue and primary production, but also in their susceptibility to environmental changes. Climate change is predicted to increase variability of precipitation in many systems, yet the effects on belowground biodiversity and associated impacts on primary productivity remain poorly understood. To examine the impact of altered precipitation on endo- and ectoparasitic soil nematodes, we conducted a 2-year precipitation manipulation study across an arid, a semiarid, and a mesic grassland. Plant parasite feeding type abundance, functional guilds, and herbivory index in response to precipitation were evaluated. Responses of endo- and ectoparasites to increased precipitation varied by grassland type. There was little response of ectoparasites to increased precipitation although their population declined at the mesic site with increased precipitation. The abundance of endoparasites remained unchanged with increasing precipitation at the arid site, increased at the semiarid, and decreased at the mesic site. The herbivory index followed closely the trends seen in the endoparasites response by stagnating at the arid site, increasing at the semiarid, and decreasing at the mesic site. Our findings suggest that altered precipitation has differing effects on plant parasite feeding strategies as well as functional guilds. This may have important implications for grassland productivity, as plant parasite pressure may exacerbate the effects of climate change on host plants.

KLOTHO polymorphisms and age-related outcomes in community-dwelling older subjects: The São Paulo Ageing & Health (SPAH) Study.

Defective KLOTHO gene expression in mice led to a syndrome resembling human ageing. This study evaluated three KLOTHO polymorphisms, namely G395A, C1818T, and C370S, in an elderly population (mean age of 73 years) and their associations with ageing-related outcomes (cardiovascular events, kidney function, osteoporosis, sarcopenia) and mortality. Estimated glomerular filtration rates (eGFR) was lower in subjects with 1818TT (P = 0.047) and 370SS (P = 0.046) genotypes. The 1818TT genotype (P = 0.006) and 1818T allele were associated with higher frequency of myocardial infarction (MI) (CC:1.7% vs. CT + TT:7.0%; P = 0.002). The 370SS genotype was associated with lower stroke frequency (P = 0.001). MI (OR 3.35 [95% CI: 1.29-8.74]) and stroke (OR 3.64 [95% CI: 1.48-8.97]) were associated with mortality. Regarding MI, logistic regression showed 1818T allele was a risk factor for death-related MI (OR 4.29 [95% CI: 1.60-11.52]; P = 0.003), while 370C was protective (OR 0.03 [95% CI: 0.01-0.08]; P < 0.001). Regarding stroke, the 395A and 370C alleles were protective factors (respectively: OR 0.28 [95% CI: 0.20-0.80]; P = 0.018; OR 0.10 [95% CI: 0.05-0.18]; P < 0.001). This is the first study to determine potential associations between common ageing-related outcomes/mortality and KLOTHO polymorphisms. The 1818T allele was a risk factor for MI-related death. The 395A and 370C alleles were protective factors for stroke-related death in elderly from community.

Drought suppresses soil predators and promotes root herbivores in mesic, but not in xeric grasslands.

Precipitation changes among years and locations along gradients of mean annual precipitation (MAP). The way those changes interact and affect populations of soil organisms from arid to moist environments remains unknown. Temporal and spatial changes in precipitation could lead to shifts in functional composition of soil communities that are involved in key aspects of ecosystem functioning such as ecosystem primary production and carbon cycling. We experimentally reduced and increased growing-season precipitation for 2 y in field plots at arid, semiarid, and mesic grasslands to investigate temporal and spatial precipitation controls on the abundance and community functional composition of soil nematodes, a hyper-abundant and functionally diverse metazoan in terrestrial ecosystems. We found that total nematode abundance decreased with greater growing-season precipitation following increases in the abundance of predaceous nematodes that consumed and limited the abundance of nematodes lower in the trophic structure, including root feeders. The magnitude of these nematode responses to temporal changes in precipitation increased along the spatial gradient of long-term MAP, and significant effects only occurred at the mesic site. Contrary to the temporal pattern, nematode abundance increased with greater long-term MAP along the spatial gradient from arid to mesic grasslands. The projected increase in the frequency of extreme dry years in mesic grasslands will therefore weaken predation pressure belowground and increase populations of root-feeding nematodes, potentially leading to higher levels of plant infestation and plant damage that would exacerbate the negative effect of drought on ecosystem primary production and C cycling.

Amazonian deforestation and soil biodiversity.

Clearance and perturbation of Amazonian forests are one of the greatest threats to tropical biodiversity conservation of our times. A better understanding of how soil communities respond to Amazonian deforestation is crucially needed to inform policy interventions that effectively protect biodiversity and the essential ecosystem services it provides. We assessed the impact of deforestation and ecosystem conversion to arable land on Amazonian soil biodiversity through a meta-analysis. We analyzed 274 pairwise comparisons of soil biodiversity in Amazonian primary forests and sites under different stages of deforestation and land-use conversion: disturbed (wildfire and selective logging) and slash-and-burnt forests, pastures, and cropping systems. Overall, 60% and 51% of responses of soil macrofauna and microbial community attributes (i.e., abundance, biomass, richness, and diversity indexes) to deforestation were negative, respectively. We found few studies on mesofauna (e.g., microarthropods) and microfauna (e.g., protozoa and nematodes), so those groups could not be analyzed. Macrofauna abundance and biomass were more vulnerable to the displacement of forests by pastures than by agricultural fields, whereas microbes showed the opposite pattern. Effects of Amazonian deforestation on macrofauna were more detrimental at sites with mean annual precipitation >1900 mm, and higher losses of microbes occurred in highly acidic soils (pH < 4.5). Limited geographic coverage, omission of meso- and microfauna, and low taxonomic resolution were main factors impairing generalizations from the data set. Few studies assessed the impacts of within-forest disturbance (wildfires and selective logging) on soil species in Amazonia, where logging operations rapidly expand across public lands and more frequent severe dry seasons are increasing the prevalence of wildfires.

Deforestación en el Amazonas y Biodiversidad del Suelo Resumen Actualmente, el despeje y la perturbación de los bosques del Amazonas son las principales amenazas para la conservación de la biodiversidad tropical. Se requiere urgentemente de un mejor entendimiento sobre cómo las comunidades del suelo responden a la deforestación amazónica para informar a las intervenciones políticas que protegen efectivamente a la biodiversidad y a los servicios ambientales esenciales que proporciona. Evaluamos el impacto de la deforestación y la conversión del ecosistema a suelo arable sobre la biodiversidad del suelo amazónico por medio de un meta-análisis. Analizamos 274 comparaciones por pares de la biodiversidad del suelo amazónico en bosques primarios y sitios bajo diferentes etapas de deforestación y conversión de uso de suelo: bosques perturbados (incendios forestales y tala selectiva) y de corte-y-quema, pasturas, y sistemas agrícolas. En general, el 60% y el 51% de las respuestas de los atributos (es decir, abundancia, biomasa, riqueza, e índices de biodiversidad) de la macrofauna del suelo y de las comunidades microbianas ante la deforestación fueron negativas, respectivamente. Encontramos pocos estudios sobre la mesofauna (p. ej.: microartrópodos) y la microfauna (p. ej.: protozoarios y nematodos), así que estos grupos no pudieron ser analizados. La abundancia de la macrofauna y la biomasa fueron más vulnerables al desplazamiento de bosques por las pasturas que por los campos agrícolas, mientras que los microbios mostraron el patrón opuesto. Los efectos de la deforestación amazónica sobre la macrofauna fueron más dañinos en sitios con una precipitación anual media mayor a los 1,900 mm, y ocurrieron pérdidas más elevadas de microbios en suelos con una acidez alta (pH < 4.5). La cobertura geográfica limitada, la omisión de la mesofauna y la microfauna, y la baja resolución taxonómica fueron los factores principales que obstaculizaron las generalizaciones del conjunto de datos. Pocos estudios evaluaron los impactos de las perturbaciones internas del bosque (incendios forestales y tala selectiva) sobre las especies del suelo amazónico, a la vez que las operaciones de tala se expanden rápidamente en los terrenos públicos y la ocurrencia con mayor frecuencia de temporadas con sequía grave aumentan la prevalencia de los incendios forestales.

Improvement of bone microarchitecture parameters after 12 months of treatment with asfotase alfa in adult patient with hypophosphatasia: Case report.

RATIONALE: Hypophosphatasia is an inborn error of metabolism that can appear any time in life, mainly with bone manifestations due to low alkaline phosphatase activity. Asfotase alfa is a specific enzyme reposition treatment that has shown promising results in children; however, there are few reports about the outcomes in adult patients. PATIENT CONCERNS: A 36-year-old male presented with an early history of craniosynostosis, short stature, and multiple fractures since the age of 13 years-which needed numerous surgical corrections. He was admitted with a previous diagnosis of osteogenesis imperfecta, taking alendronate, calcium carbonate, cholecalciferol, and calcitriol. Bone mineral density was low (lumbar spine Z-score = -3.0 SD), with impairment of all parameters of high-resolution peripheral quantitative computed tomography (HR-pQCT). Kidney impairment was also observed with reduced creatinine clearance, nephrolithiasis, and nephrocalcinosis. DIAGNOSIS: Alkaline phosphatase was unexpectedly low (6 U/L, reference value: 30-120 U/L), with high serum vitamin B6 (260 mcg/L, reference value: 5.2-34.1). Genetic testing showed a homozygous missense mutation in ALPL gene c.443 C>T: p.Thr148Ile. INTERVENTION: Asfotase alfa was requested due to important bone deterioration, ambulatory disability, and kidney impairment. It was given subcutaneously 2 mg/kg per dose, 3 times a week, for 12 months before reassessment. OUTCOMES: Bone mineral densities of the lumbar spine and whole body, besides almost all HR-pQCT microstructural parameters of the distal tibia, showed improvements and the patient was able to walk without assistant device. Kidney function did not further deteriorate. LESSONS: Hypophosphatasia should be considered as a differential diagnosis in young patients with multiple fractures and kidney impairment, since the use of antiresorptive drugs, calcium and vitamin D, commonly used to treat fractures, worsen its symptoms and prognosis. A 12-month asfotase alfa treatment improved bone density and structural parameters even in an adult patient with late diagnosis.