ALS-associated VRK1 R321C mutation causes proteostatic imbalance and mitochondrial defects in iPSC-derived motor neurons.

Vaccinia-related kinase 1 (VRK1) is a gene which has been implicated in the pathological process of a broad range of neurodevelopmental disorders as well as neuropathies, such as Amyotrophic Lateral Sclerosis (ALS). Here we report a family presenting ALS in an autosomal recessive mode of inheritance, segregating with a homozygous missense mutation located in VRK1 gene (p.R321C; Arg321Cys). Proteomic analyses from iPSC-derived motor neurons identified 720 proteins eligible for subsequent investigation, and our exploration of protein profiles revealed significant enrichments in pathways such as mTOR signaling, E2F, MYC targets, DNA repair response, cell proliferation and energetic metabolism. Functional studies further validated such alterations, showing that affected motor neurons presented decreased levels of global protein output, ER stress and downregulation of mTOR signaling. Mitochondrial alterations also pointed to decreased reserve capacity and increased non-mitochondrial oxygen consumption. Taken together, our results present the main pathological alterations associated with VRK1 mutation in ALS.

The effects of feeding sows at onset of farrowing supplemental energy (blend of carbohydrates and glycerol) on farrowing kinetics and piglet vitality.

Delivering piglets is one of the most energy-demanding activities sows undergo in their lifetime. Sows can have myometrial contractions from 2 to 12 h before the first piglet is expelled as well as a nest-building behavior. Thus, when the first piglet is delivered, the female has already used part of her energy supply. When the sow gets exhausted due to lack of energy, the farrowing process can be interrupted, causing damage to the viability and vitality of the piglets. In the present study, we evaluated the effects of feeding sows an energy supplement at the onset of farrowing on farrowing kinetics and piglet vitality. The energy supplement consisted of a blend of carbohydrates and glycerol which provides 439 kJ of metabolizable energy per kg of metabolic weight. A total of 180 sows were used. At the onset of farrowing, sows were assigned to one of the following treatments: sows that were not supplied energy at the onset of farrowing, serving as controls (CON, n = 85); sows fed the energy supplement at the onset of farrowing (ESP, n = 95). Farrowing kinetics, blood glucose concentration, and piglet vitality were recorded for each sow. Blood glucose concentration was assessed by puncturing the auricular vein and using a portable glucometer at four different time points: after the birth of the 1st piglet (T0), and at 20 (T20), 40 (T40), 80 (T80), and 180 (T180) min after the birth of the 1st piglet. The vitality of the 1st, 6th, 12th, 17th, and 20th piglet born was evaluated using the Apgar score. Piglet birth weight and average colostrum intake were measured. The farrowing duration was 20 min shorter (P < 0.05) for ESP sows in comparison with CON sows. Sows from ESP treatment had higher (P ≤ 0.05) blood glucose concentration at T20 and T40 compared to the CON sows. The inter-piglet birth interval was shortened (P < 0.05) by 14 min between the 1st and 2nd piglet for the ESP treatment. The 17th and 20th piglets born from ESP sows had higher (P < 0.05) Apgar score compared to piglets of the same birth order from CON sows. Colostrum intake was higher (P < 0.01) for piglets born from ESP sows. Litter growth performance did not differ (P > 0.05). In conclusion, feeding a blend of carbohydrates and glycerol as an energy supplement for farrowing sows improved farrowing kinetics and piglet vitality score.

Is tooth loss associated with oral health-related quality of life among young men? Findings from southern Brazil.

OBJECTIVE: To determine the association between tooth loss and oral health-related quality of life (OHRQoL) among young men from southern Brazil. METHODS: Cross-sectional study of 518 young men aged 18-19 years enlisted for mandatory military service in the Brazilian Army in two cities of southern Brazil in 2019-2021. Participants were clinically examined regarding gingivitis, dental caries experience (caries lesions, missing and filled surfaces), and malocclusion. A questionnaire collected socioeconomic information and the Oral Health Impact Profile 14 (OHIP-14). The outcome was OHRQoL, modeled as a discrete variable. The main explanatory variable was tooth loss due to caries (0 or ≥1). Negative binomial regression analysis was used; rate ratios (RR) and 95% confidence intervals (CI) were estimated. RESULTS: Tooth loss prevalence was 22.2%. Associations were detected between tooth loss and OHRQoL in the physical pain and handicap domains. Individuals with at least one missing tooth had 17% higher OHIP-14 scores in the physical pain domain (adjusted RR=1.17; 95%CI=1.01, 1.35) and 49% higher in the handicap domain (adjusted RR=1.49; 95%CI=1.03, 2.15) than those with no tooth loss. CONCLUSIONS: Tooth loss was negatively associated with OHRQoL among 18-19-year-old Brazilian Army conscripts, and this association was related to physical pain and handicap domains.

Spatio-temporal analysis of the visceral leishmaniasis in the state of Alagoas, Brazil / Análise espacial-temporal da leishmaniose visceral no estado de Alagoas

Visceral leishmaniosis is a neglected tropical disease. We evaluated the spatial distribution of cases of visceral leishmaniosis in the state of Alagoas, Brazil. All cases of VL, registered by the health department, were analyzed and georeferenced. Results: Between 2008 and 2017, 97.1% of the municipalities presented sporadic classification of transmission. With temporal evolution, the incidence of cases of visceral leishmaniosis was concentrated in most municipalities in the microregion of Santana do Ipanema-AL. Space-time analysis, if considered, may promote the improvement of surveillance and control actions of visceral leishmaniosis.

A leishmaniose visceral é uma doença tropical negligenciada. Foram avaliadas a distribuição espacial dos casos de leishmaniose visceral no estado de Alagoas. Todos os casos de LV, registrados pela secretaria de saúde, foram analisados e georreferenciados. Entre 2008 e 2017, 97,1% dos municípios apresentaram classificação esporádica de transmissão. Com a evolução temporal, a incidência de casos de leishmaniose visceral se concentrou na maioria dos municípios da microrregião de Santana do Ipanema-AL. A análise espaço-tempo, se considerada, pode promover o aprimoramento das ações de vigilância e controle da leishmaniose visceral.

Spatio-temporal analysis of the visceral leishmaniasis in the state of Alagoas, Brazil

Abstract Visceral leishmaniosis is a neglected tropical disease. We evaluated the spatial distribution of cases of visceral leishmaniosis in the state of Alagoas, Brazil. All cases of VL, registered by the health department, were analyzed and georeferenced. Results: Between 2008 and 2017, 97.1% of the municipalities presented sporadic classification of transmission. With temporal evolution, the incidence of cases of visceral leishmaniosis was concentrated in most municipalities in the microregion of Santana do Ipanema-AL. Space-time analysis, if considered, may promote the improvement of surveillance and control actions of visceral leishmaniosis.

Resumo A leishmaniose visceral é uma doença tropical negligenciada. Foram avaliadas a distribuição espacial dos casos de leishmaniose visceral no estado de Alagoas. Todos os casos de LV, registrados pela secretaria de saúde, foram analisados e georreferenciados. Entre 2008 e 2017, 97,1% dos municípios apresentaram classificação esporádica de transmissão. Com a evolução temporal, a incidência de casos de leishmaniose visceral se concentrou na maioria dos municípios da microrregião de Santana do Ipanema-AL. A análise espaço-tempo, se considerada, pode promover o aprimoramento das ações de vigilância e controle da leishmaniose visceral.

High prevalence of pathogenic Eimeria spp. and the main risk factors associated with infection in goats from a semiarid region of Northeastern Brazil.

This study aimed to analyze the epidemiology of infections caused by Eimeria spp. in goats bred in an extensive production system in Northeast Brazil. To this end, an epidemiological survey was performed, wherein 350 fecal samples were collected from goats ranging from 3 months to 8 years old across 30 farms. The number of oocysts per gram of feces (OPG) was counted using the Mini-FLOTAC method. Species were identified based on their morphological and morphometric characteristics. Frequencies between animal categories were assessed using the chi-square test and known risk factors after multivariate analysis. Eimeria oocysts were found in 99.4% (346/348) of samples and 100% (30/30) of the farms. The OPG was influenced by the age of the animals; therefore, young goats (up to 6 months old) eliminated more oocysts (2302.6 + 5454.8) than adult goats (881.7 + 1551.5). Three pathogenic species were identified, with two demonstrating a high prevalence: Eimeria arloingi (88.83%) and Eimeria christenseni (44.7%), in addition to Eimeria caprina (3.72%). In the study, the habit of ground feeding and the use of cisterns as water sources were identified as risk factors, with odds ratios of 4.04 and 9.82, respectively. However, cleaning facilities at shorter intervals was a protective factor (OR = 0.19). We concluded that there was a high prevalence of Eimeria infection in goats bred in extensive production systems, even those in semiarid regions. This high prevalence can be attributed to the congregation of animals in shaded areas and the substantial accumulation of fecal matter at night.

Sociodemographic disparities in oral health-related quality of life of schoolchildren in rural and urban areas.

OBJECTIVE: To assess the association between residence place, socioeconomic conditions and oral health-related quality of life (OHRQoL) among schoolchildren from southern Brazil. METHODS: Participants were 9-14-year-old schoolchildren from rural and urban municipal schools from Rosário do Sul, Brazil. The Child Perceptions Questionnaire (CPQ11-14) was used to assess OHRQoL. A structured questionnaire collected data on sociodemographic condition (family income), residence place (urban or rural), use of dental services, and behavioral variables. Clinical oral examination recorded the presence of missing teeth and the gingival bleeding index. Multilevel Poisson regression analysis with a hierarchical approach assessed the association between predictors and CPQ11-14 scores. Rate ratios (RR) and 95% confidence intervals (CI) were estimated. RESULTS: A total of 373 schoolchildren were included (rural area=122; urban area=251), with a mean CPQ11-14 score of 11.83, ranging from 0 to 42. Low-income schoolchildren living in rural areas had 15% higher CPQ11-14 scores than high-income schoolchildren living in urban areas. In urban areas, family income predicted OHRQoL, with low-income schoolchildren having 9% higher CPQ11-14 scores than high-income children. In rural areas, schoolchildren with low household income had 19% higher CPQ11-14 scores than high-income children. CONCLUSION: Schoolchildren from low-income families had a poorer OHRQoL irrespective of their area of residence (rural or urban). The association between family income and OHRQoL was more pronounced among children living in rural areas.

Probing the Cr3+ luminescence sensitization in ß-Ga2O3 with ion-beam-induced luminescence and thermoluminescence.

Ion-beam-induced luminescence (IBIL) measurements were performed in Cr-doped ß-Ga2O3 using both protons and helium ions, showing a strong enhancement of the Cr3+ luminescence upon ion irradiation. Theoretical modelling of the IBIL intensity curves as a function of the fluence allowed estimating the effective cross-sections associated with the defect-induced IBIL enhancement and quenching processes. The results suggest that sensitizing the Cr3+ luminescence is more efficient for H+ than for He+ irradiation. Thermoluminescence (TL) studies were performed in the pristine sample, with no TL signal being observed in the spectral region corresponding to the Cr3+ emission. In agreement with the IBIL study, upon ion irradiation (with either protons or helium ions), this TL emission is activated. Moreover, it can be quenched by annealing at 923 K for 10 s, thus revealing the role played by the defects induced by the irradiation. These results show that the irradiation-induced defects play a major role in the activation of the Cr3+ luminescence, a fact that can be exploited for radiation sensing and dosimetry.

Pharmacological PI3K inhibition in head and neck squamous cell carcinoma: A systematic review.

BACKGROUND: This systematic review aimed to investigate the in vitro and in vivo effects of phosphatidylinositol-3-kinase (PI3K) inhibitors on head and neck squamous cell carcinoma (HNSCC). Considering the role of PI3K and its downstream effectors in cell proliferation, invasion, and survival, it is reasonable to expect that treatment with PI3K inhibitors could control HNSCC onset and progression. Thus, the research question for our review was whether pharmacological inhibition of PI3K affects HNSCC progression. METHODS: In vitro and in vivo studies were selected from six databases. We collected data regarding cell viability, apoptosis, and the regulation of protein expression levels from in vitro studies. For the in vivo studies, we analyzed the reduction in tumor size or gene and protein expression. RESULTS: The included studies showed reduced cell proliferation and apoptosis after treatment with PI3K inhibitors. PI3K inhibitors in combination with other drugs had an enhanced anticancer effects compared to those of single-drug treatments. CONCLUSIONS: The results support the potential of PI3K inhibitors as candidates for clinical trials in HNSCC.

Evaluation of the efficacy of a 2-step etch-and-rinse, 2-step self-etch and 1-step self-etch adhesive systems, in class II primary molars restorations. An one year prospective, randomized clinical trial.

PURPOSE: To evaluate the clinical efficacy at 6 months (6 M) and 12 months (12 M) of 3 adhesive strategies (two-step etch-and-rinse; two-step self-etch; one step self-etch) used in composite resin restorations in primary molars. METHODS: This randomized clinical study involved 101 class II restorations in primary molars of 34 children (4-8 years old), distributed by 3 groups according to the 3 tested adhesive systems: GI- ClearfilTMS3Bond Plus (CSB); GII- ClearfilTMSE Protect Bond (CSEPB); GIII- Prime&Bond®XP (PBXP). Restorations were evaluated according to FDI criteria, immediately after execution, at 6 M and 12 M. All ethical and legal requirements were met. Statistical analysis was performed using IBM®SPSS®v26 and MS Excel® (5% significance level). RESULTS: The aesthetic, biological and most of the functional parameters evaluated remained without significant changes over time. Statistically significant differences were only found regarding the "marginal adaptation" parameter at 12 M, with worsening of scores for the three groups (p < 0.001). Comparing the groups, no significant differences were detected between any of the evaluated parameters (aesthetics properties: p = 0.721; functional properties: p = 0.122). CONCLUSIONS: After a one-year period, the self-etch adhesives tested presented a clinical efficacy similar to the etch-and-rinse adhesive in restoring class II cavities in primary molars. TRIAL REGISTRATION NUMBER: ISRCTN11458186.

The COVID-19 and TB syndemic: the way forward.

Together, SARS-CoV-2 and M. tuberculosis have killed approximately 5.7 million people worldwide over the past 2 years. The COVID-19 pandemic, and the non-pharmaceutical interventions to mitigate COVID-19 transmission (including social distancing regulations, partial lockdowns and quarantines), have disrupted healthcare services and led to a reallocation of resources to COVID-19 care. There has also been a tragic loss of healthcare workers who succumbed to the disease. This has had consequences for TB services, and the fear of contracting COVID-19 may also have contributed to reduced access to TB services. Altogether, this is projected to have resulted in a 5-year setback in terms of mortality from TB and a 9-year setback in terms of TB detection. In addition, past and present TB disease has been reported to increase both COVID-19 fatality and incidence. Similarly, COVID-19 may adversely affect TB outcomes. From a more positive perspective, the pandemic has also created opportunities to improve TB care. In this review, we highlight similarities and differences between these two infectious diseases, describe gaps in our knowledge and discuss solutions and priorities for future research.

Exploring Ductility in Dental Ceramics.

Two damage regimes-"brittle" and "ductile"-have been identified in the literature on ceramic grinding, machining, grit blasting, and wear. In the brittle regime, the damage mechanism is essentially crack formation, while in the ductile region, it is quasiplasticity. Onset of the brittle mode poses the greater threat to strength, so it becomes important to understand the mechanics of ductile-brittle thresholds in these materials. Controlled microcontact tests with a sharp indenter are employed to establish such thresholds for a suite of contemporary computer-aided design/computer-aided manufacturing dental ceramics. Plots of flexural strength S versus indentation load P show a steep decline beyond the threshold, consistent with well-established contact mechanics relations. Threshold dimensions occur on a scale of order 1 µm and contact load of order 1 N, values pertinent to practical grit finishing protocols. The ductile side of ceramic shaping is accessed by reducing grit sizes, applied loads, and depths of cut below critical levels. It is advocated that critical conditions for ductile shaping may be most readily quantified on analogous S(P) plots, but with appropriate machining variable (grit size, depths of cut, infeed rate) replacing load P. Working in the ductile region offers the promise of compelling time and cost economies in prosthesis fabrication and preparation.

The Influence of Cement Removal Techniques on In Situ Bacterial Adhesion and Biodegradation at the Marginal Interface of Ceramic Laminates.

OBJECTIVES: This in situ study aimed to analyze the influence of different resin cement removal techniques on bacterial adhesion and biodegradation at the marginal interface of ceramic laminates. METHODS AND MATERIALS: Eighty feldspathic ceramic (F) blocks were prepared and cemented onto bovine enamel slabs (7×2.5×2 mm). Excess cement was removed using a microbrush (MBR), a scalpel blade (SCP), or a Teflon spatula (TSP). For the biodegradation analysis, 40 disc-shaped resin cement specimens were prepared (7×1.5 mm) using a Teflon mold. The specimens were randomly allocated into two groups: (1) No finishing procedure (only Mylar strip), and (2) with finishing and polishing procedures using the Jiffy system (Ultradent, South Jordan, UT, USA) (n=20). The in situ phase consisted of using an intraoral palatal device by 20 volunteers for 7 days. Each device contained five cylindrical wells (8×3 mm), where three dental blocks and two cement specimens were included in the wells. Surface roughness (Ra) was measured using a contact profilometer. A micromorphological analysis was performed under a stereomicroscope and a scanning electron microscope. Bacterial adhesion was quantitated based on the number of colony-forming units (CFU/mL) and their biofilm development potential. RESULTS: The cement removal techniques directly affected surface roughness at the marginal interface (p<0.001), and the SCP technique produced higher mean roughness, regardless of the surface area analyzed. Surface polishing protected cement specimens from further biodegradation (p=0.148). There were no differences in CFU counts between the groups after the in situ phase (p=0.96). All specimens showed CFU with a strong ability to develop a biofilm. CONCLUSIONS: The techniques used for cement removal increased the surface roughness of ceramic laminates, particularly SCP, but they did not affect bacterial adhesion at the marginal interface. Surface polishing of the resin cement is recommended to mitigate biodegradation.

A sustainable ultra-high strength Fe18Mn3Ti maraging steel through controlled solute segregation and α-Mn nanoprecipitation.

The enormous magnitude of 2 billion tons of alloys produced per year demands a change in design philosophy to make materials environmentally, economically, and socially more sustainable. This disqualifies the use of critical elements that are rare or have questionable origin. Amongst the major alloy strengthening mechanisms, a high-dispersion of second-phase precipitates with sizes in the nanometre range is particularly effective for achieving ultra-high strength. Here, we propose an alternative segregation-based strategy for sustainable steels, free of critical elements, which are rendered ultrastrong by second-phase nano-precipitation. We increase the Mn-content in a supersaturated, metastable Fe-Mn solid solution to trigger compositional fluctuations and nano-segregation in the bulk. These fluctuations act as precursors for the nucleation of an unexpected α-Mn phase, which impedes dislocation motion, thus enabling precipitation strengthening. Our steel outperforms most common commercial alloys, yet it is free of critical elements, making it a new platform for sustainable alloy design.

Spatio-temporal analysis of the visceral leishmaniasis in the state of Alagoas, Brazil.

Visceral leishmaniosis is a neglected tropical disease. We evaluated the spatial distribution of cases of visceral leishmaniosis in the state of Alagoas, Brazil. All cases of VL, registered by the health department, were analyzed and georeferenced. Results: Between 2008 and 2017, 97.1% of the municipalities presented sporadic classification of transmission. With temporal evolution, the incidence of cases of visceral leishmaniosis was concentrated in most municipalities in the microregion of Santana do Ipanema-AL. Space-time analysis, if considered, may promote the improvement of surveillance and control actions of visceral leishmaniosis.

Evaluation of contrast sensitivity in non-high-risk proliferative diabetic retinopathy treated with panretinal photocoagulation with and without intravitreal injections of ranibizumab / Avaliação da sensibilidade ao contraste em retinopatia diabética proliferativa de não alto risco tratada com panfotocoagulação retiniana com ou sem injeções intravítrea de ranibizumabe

ABSTRACT Purpose: To evaluate contrast sensitivity in non-high-risk, treatment-naïve proliferative diabetic retinopathy patients treated with panretinal photocoagulation and intravitreal injections of ranibizumab) versus panretinal photocoagulation alone. Methods: Sixty eyes of 30 patients with bilateral proliferative diabetic retinopathy were randomized into two groups: one received panretinal photocoagulation and ranibizumab injections (study group), while the other received panretinal photocoagulation alone (control group). All eyes were treated with panretinal photocoagulation in three sessions according to the Early Treatment Diabetic Retinopathy Study guidelines. Contrast sensitivity measurements were performed under photopic conditions (85 cd/m2) with the Visual Contrast Test Sensitivity 6500 chart, allowing for the evaluation of five spatial frequencies with sine wave grating charts: 1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree (cpd). Outcomes were measured in contrast sensitivity threshold scores among and within groups, from baseline to 1, 3, and 6 months. Results: Fifty-eight eyes (28 in the study group and 30 in the control group) reached the study endpoint. A comparative analysis of changes in contrast sensitivity between the groups showed significant differences mainly in low frequencies as follows: at month 1 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.04); at month 3 in 1.5 cpd (p=0.016), and at month 6 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.026) in favor of the study group. Conclusions: In eyes of patients with non-high-risk proliferative diabetic retinopathy, panretinal photocoagulation treatment with ranibizumab appears to cause less damage to contrast sensitivity compared with panretinal photocoagulation treatment alone. Thus, our evaluation of contrast sensitivity may support the use of ranabizumab as an adjuvant to panretinal photocoagulation for the treatment of proliferative diabetic retinopathy.

RESUMO Objetivos: Avaliar a sensibilidade ao contraste em pacientes virgens de tratamento com retinopatia diabética proliferativa de não alto risco, submetidos a panfotocoagulação retiniana com injeções intravítreas de ranibizumabe versus pan­fotocoagulação isolada. Métodos: Sessenta olhos de 30 pa­cientes foram randomizados em dois grupos: um submetido a panfotocoagulação com injeções de ranibizumabe (grupo estudo), e o outro submetimedo a panfotocoagulação isolada (grupo controle). Todos olhos foram tratados em 3 sessões de laser, seguindo recomendação do Early Treatment Diabetic Retinopathy Study (ETDRS). Avaliação da sensibilidade ao contraste foi realizada sob condições fotópicas (85 cd/m2) com tabela Visual Contrast Test Sensitivity 6500, permitindo avaliação de cinco frequências espaciais medidas com redes senoidais: 1.5, 3.0, 6.0, 12.0 e 18.0 ciclos por grau de ângulo visual (cpd). Foram realizadas medidas dos limiares de sensibilidade ao contraste intra e entre grupos na visita inicial, no 1º, 3º, e 6º mês de seguimento. Resultados: Cinquenta e oito olhos, 28 do grupo estudo e 30 do grupo controle, atingiram o término do estudo. Análise comparativa da SC entre os grupos mostrou diferença estatisticamente significante, nas baixas frequências espaciais, no 1º mês em 1.5 cpd (p=0,001) e 3.0 cpd (p=0,04), no 3º mês em 1.5 cpd (p=0,016) e no 6º mês em 3.0 cpd (p=0,026) a favor do grupo estudo. Conclusão: O tratamento com panfotocoagulação associada a injeção de ranibizumabe parece causar menos danos a sensibilidade ao contraste quando comparada com panfotocoagulação isolada em olhos com retinopatia diabética proliferativa de não alto risco. Dessa forma, os resultados apresentados podem justificar a associação do ranibizumabe à panfotocoagulação nestes pacientes.

The temporal stability of premorbid intelligence: A non-clinical 10-year follow-up study using the Irregular Word Reading Test (TeLPI).

INTRODUCTION: The Cognitive Reserve (CR) describes the brain's ability to actively cope with neurological damage, enabling the maintenance of premorbid cognitive functioning through compensatory processes. The most common way to estimate CR is through formal education, the intelligence quotient (IQ) and participation in cognitive stimulating activities. In the absence of IQ data, the Irregular Word Reading Test (TeLPI) allows you to estimate the premorbid intelligence. OBJECTIVE: The comparison of the TeLPI results between two times of assessment (baseline and re-assessment) with an interval time (IT) of 9 years. To analyze of the stability of their results as a valid dimension for the CR estimation. RESULTS: The TeLPI presented temporal stability of its results between the two evaluation times (IT = 9.07 ± 1.02). The sample, composed by 63 cognitively healthy participants, showed no differences for the estimated Full Scale IQ (t(62) = 0.49, p = .63), for the Estimated Verbal IQ (t(62) = 0.71, p = .48) and for the estimated Performance IQ (t(62) = 0.64, p = .52). Likewise, no differences were found in the number of TeLPI errors at the two assessment times (t(62) = -0.61, p = .54). CONCLUSIONS: Considering that CR is characterized as being relatively stable, the TeLPI should be included in its assessment, as an indicator with proved stability over a long period of time, on the physiological aging spectrum.

Boat noise impacts early life stages in the Lusitanian toadfish: A field experiment.

Marine traffic is the most common and chronic source of ocean noise pollution. Despite the evidence of detrimental effects of noise exposure on fish, knowledge about the effects on the critical early life stages - embryos and larvae - is still scarce. Here, we take a natural habitat-based approach to examine potential impacts of boat noise exposure in early life stages in a wild fish population of the Lusitanian toadfish (Halobatrachus didactylus). In-situ experiments were carried out in the Tagus estuary, an estuary with significant commercial and recreational boat traffic. Nests with eggs were exposed to either ambient (control) or boat noise (treatment), for 1 fortnight. Eggs were photographed before being assigned to each treatment, and after exposure, to count number of eggs and/or larvae to assess survival, and sampled to study development and oxidative stress and energy metabolism-related biomarkers. Data concerns 4 sampling periods (fortnights) from 2 years. Results indicate that offspring survival did not differ between treatments, but boat noise induced a detrimental effect on embryos and larvae stress response, and on larvae development. Embryos showed reduced levels of electron transport system (ETS), an energy metabolism-related biomarker, while larvae showed higher overall stress responses, with increased levels of superoxide dismutase (SOD) and DNA damage (oxidative stress related responses), ETS, and reduced growth. With this study, we provided the first evidence of detrimental effects of boat noise exposure on fish development in the field and on stress biomarker responses. If these critical early stages are not able to compensate and/or acclimate to the noise stress later in the ontogeny, then anthropogenic noise has the potential to severely affect this and likely other marine fishes, with further consequences for populations resilience and dynamics.

Evaluation of contrast sensitivity in non-high-risk proliferative diabetic retinopathy treated with panretinal photocoagulation with and without intravitreal injections of ranibizumab.

PURPOSE: To evaluate contrast sensitivity in non-high-risk, treatment-naïve proliferative diabetic retinopathy patients treated with panretinal photocoagulation and intravitreal injections of ranibizumab) versus panretinal photocoagulation alone. METHODS: Sixty eyes of 30 patients with bilateral proliferative diabetic retinopathy were randomized into two groups: one received panretinal photocoagulation and ranibizumab injections (study group), while the other received panretinal photocoagulation alone (control group). All eyes were treated with panretinal photocoagulation in three sessions according to the Early Treatment Diabetic Retinopathy Study guidelines. Contrast sensitivity measurements were performed under photopic conditions (85 cd/m2) with the Visual Contrast Test Sensitivity 6500 chart, allowing for the evaluation of five spatial frequencies with sine wave grating charts: 1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree (cpd). Outcomes were measured in contrast sensitivity threshold scores among and within groups, from baseline to 1, 3, and 6 months. RESULTS: Fifty-eight eyes (28 in the study group and 30 in the control group) reached the study endpoint. A comparative analysis of changes in contrast sensitivity between the groups showed significant differences mainly in low frequencies as follows: at month 1 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.04); at month 3 in 1.5 cpd (p=0.016), and at month 6 in 1.5 cpd (p=0.001) and 3.0 cpd (p=0.026) in favor of the study group. CONCLUSIONS: In eyes of patients with non-high-risk proliferative diabetic retinopathy, panretinal photocoagulation treatment with ranibizumab appears to cause less damage to contrast sensitivity compared with panretinal photocoagulation treatment alone. Thus, our evaluation of contrast sensitivity may support the use of ranabizumab as an adjuvant to panretinal photocoagulation for the treatment of proliferative diabetic retinopathy.