A very-high-energy component deep in the γ-ray burst afterglow.

Gamma-ray bursts (GRBs) are brief flashes of γ-rays and are considered to be the most energetic explosive phenomena in the Universe1. The emission from GRBs comprises a short (typically tens of seconds) and bright prompt emission, followed by a much longer afterglow phase. During the afterglow phase, the shocked outflow-produced by the interaction between the ejected matter and the circumburst medium-slows down, and a gradual decrease in brightness is observed2. GRBs typically emit most of their energy via γ-rays with energies in the kiloelectronvolt-to-megaelectronvolt range, but a few photons with energies of tens of gigaelectronvolts have been detected by space-based instruments3. However, the origins of such high-energy (above one gigaelectronvolt) photons and the presence of very-high-energy (more than 100 gigaelectronvolts) emission have remained elusive4. Here we report observations of very-high-energy emission in the bright GRB 180720B deep in the GRB afterglow-ten hours after the end of the prompt emission phase, when the X-ray flux had already decayed by four orders of magnitude. Two possible explanations exist for the observed radiation: inverse Compton emission and synchrotron emission of ultrarelativistic electrons. Our observations show that the energy fluxes in the X-ray and γ-ray range and their photon indices remain comparable to each other throughout the afterglow. This discovery places distinct constraints on the GRB environment for both emission mechanisms, with the inverse Compton explanation alleviating the particle energy requirements for the emission observed at late times. The late timing of this detection has consequences for the future observations of GRBs at the highest energies.

GABAergic system and chloride cotransporters as potential therapeutic targets to mitigate cell death in ischemia.

Gamma aminobutyric acid (GABA) is a critical inhibitory neurotransmitter in the central nervous system that plays a vital role in modulating neuronal excitability. Dysregulation of GABAergic signaling, particularly involving the cotransporters NKCC1 and KCC2, has been implicated in various pathologies, including epilepsy, schizophrenia, autism spectrum disorder, Down syndrome, and ischemia. NKCC1 facilitates chloride influx, whereas KCC2 mediates chloride efflux via potassium gradient. Altered expression and function of these cotransporters have been associated with excitotoxicity, inflammation, and cellular death in ischemic events characterized by reduced cerebral blood flow, leading to compromised tissue metabolism and subsequent cell death. NKCC1 inhibition has emerged as a potential therapeutic approach to attenuate intracellular chloride accumulation and mitigate neuronal damage during ischemic events. Similarly, targeting KCC2, which regulates chloride efflux, holds promise for improving outcomes and reducing neuronal damage under ischemic conditions. This review emphasizes the critical roles of GABA, NKCC1, and KCC2 in ischemic pathologies and their potential as therapeutic targets. Inhibiting or modulating the activity of these cotransporters represents a promising strategy for reducing neuronal damage, preventing excitotoxicity, and improving neurological outcomes following ischemic events. Furthermore, exploring the interactions between natural compounds and NKCC1/KCC2 provides additional avenues for potential therapeutic interventions for ischemic injury.

Search for Dark Matter Annihilation Signals in the H.E.S.S. Inner Galaxy Survey.

The central region of the Milky Way is one of the foremost locations to look for dark matter (DM) signatures. We report the first results on a search for DM particle annihilation signals using new observations from an unprecedented γ-ray survey of the Galactic Center (GC) region, i.e., the Inner Galaxy Survey, at very high energies (≳100 GeV) performed with the H.E.S.S. array of five ground-based Cherenkov telescopes. No significant γ-ray excess is found in the search region of the 2014-2020 dataset and a profile likelihood ratio analysis is carried out to set exclusion limits on the annihilation cross section ⟨σv⟩. Assuming Einasto and Navarro-Frenk-White (NFW) DM density profiles at the GC, these constraints are the strongest obtained so far in the TeV DM mass range. For the Einasto profile, the constraints reach ⟨σv⟩ values of 3.7×10^{-26} cm^{3} s^{-1} for 1.5 TeV DM mass in the W^{+}W^{-} annihilation channel, and 1.2×10^{-26} cm^{3} s^{-1} for 0.7 TeV DM mass in the τ^{+}τ^{-} annihilation channel. With the H.E.S.S. Inner Galaxy Survey, ground-based γ-ray observations thus probe ⟨σv⟩ values expected from thermal-relic annihilating TeV DM particles.

Loss of the laminin subunit alpha-3 induces cell invasion and macrophage infiltration in cutaneous squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a common cancer that invades the dermis through the basement membrane. The role of the basement membrane in poorly differentiated cSCC is not well understood. OBJECTIVES: To study the effect that loss of the laminin subunit alpha-3 (α3) chain from the tumour microenvironment has on tumour invasion and inflammatory cell recruitment. METHODS: We examined the role of the basement membrane proteins laminin subunits α3, ß3 and γ2 in SCC invasion and inflammatory cell recruitment using immunohistochemistry, short hairpin RNA knockdown, RNA-Seq, mouse xenograft models and patient tumour samples. RESULTS: Analysis of SCC tumours and cell lines using antibodies specific to laminin chains α3, ß3 and γ2 identified a link between poorly differentiated SCC and reduced expression of laminin α3 but not the other laminin subunits investigated. Knockdown of laminin α3 increased tumour invasion both in vitro and in vivo. Western blot and immunohistochemical staining identified increased phosphorylated myosin light chain with loss of laminin α3. Inhibition of ROCK (rho-associated protein kinase) but not Rac1 significantly reduced the invasive potential of laminin α3 knockdown cells. Knockdown of laminin subunits α3 and γ2 increased monocyte recruitment to the tumour microenvironment. However, only the loss of laminin α3 correlated with increased tumour-associated macrophages both in xenografted tumours and in patient tumour samples. CONCLUSIONS: These data provide evidence that loss of the laminin α3 chain in cSCC has an effect on both the epithelial and immune components of cSCC, resulting in an aggressive tumour microenvironment.

Forced degradation study and characterization of main impurities of ibuprofen soft gelatin capsules by LC-MS-QTOF.

Ibuprofen soft gelatin capsules were subjected to degradation under acidic, basic, oxidation, photolytic, thermal, humidity, and metal ions conditions. To analyse the degradation products, a reversed-phase liquid chromatography (RP-LC) indicative stability method was successfully developed. Chromatographic separation was achieved using a Poroshell HPH-C18 150 x 4.6 mm, 4 µm, column at 25 °C, with a mobile phase constituted by 0.1% phosphoric acid and acetonitrile in gradient at a flow rate of 1.0 mL• min -1 , using ultraviolet detection at 220 nm and injection volume of 20 µL. In total, eight unknown impurities were found. The peaks RRt 0.49, RRt 0.75, and RRt 0.95 were above 0.17%, corresponding to the identification threshold. Those were identified and characterized by LC-MS-QTOF, with the same chromatographic conditions, except for the exchange of 0.1% phosphoric acid for 0.1% formic acid. The impurities originated from the interaction of ibuprofen with excipients: esterification with PEG, with sorbitol/sorbitan, and with glycerol by-products, which has not yet been reported in the literature. The developed method can be used in several pharmaceutical areas as quality control of impurities, studies of forced degradation, and for the development of future formulations.

Aerosol sources in subway environments.

Millions of people use rail subway public transport around the world, despite the relatively high particulate matter (PM) concentrations in these underground environments, requiring the identification and quantification of the aerosol source contributions to improve the air quality. An extensive aerosol monitoring campaign was carried out in eleven subway stations in the Barcelona metro system, belonging to seven subway lines. PM2.5 samples were collected during the metro operating hours and chemically analysed to determine major and trace elements, inorganic ions, and total carbon. The chemical compositions of subway components such as brake pads, rail tracks and pantographs were also determined. The mean PM2.5 concentrations varied widely among stations, ranging from 26 µg m-3 to 86 µg m-3. Subway PM2.5 was mainly constituted by Fe2O3 (30-66%), followed by carbonaceous matter (18-37%) for the old stations, while for new stations equipped with Platform Screen Doors (PSD) these percentages go down to 21-44% and 15-30%, respectively. Both the absolute concentrations and the relative abundance of key species differed for each subway station, although with common patterns within a given subway line. This is a result of the different emission chemical profiles in different subway lines (using diverse types of brakes and/or pantographs). The co-emission of different sources poses a problem for their separation by receptor models. Nevertheless, receptor modelling (Positive Matrix Factorization) was applied resulting in ten sources, five of them subway-specific: RailWheel, RailWheel+Brake, Brake_A, Brake_B, Pb. The sum of their contributions accounted for 43-91% of bulk PM2.5 for the old stations and 21-52% for the stations with PSD. The decrease of the activity during the weekends resulted in a decrease (up to 56%) in the subway-specific sources contribution to the -already lower- bulk PM2.5 concentrations compared to weekdays. The health-related elements are mainly apportioned (> 60%) by subway sources.

Level of circulating concentrations of progesterone during ovulatory follicle development affects timing of pregnancy loss in lactating dairy cows.

The objective of this experiment was to determine the effect of high versus low progesterone (P4) during the pre-dominance or dominance phase (or both) of ovulatory follicle development on follicular dynamics and fertility of lactating dairy cows. Progesterone (P4) was manipulated to reach high (H) or low (L) serum concentrations during the pre-dominance phase (d 0 to 4 of the wave) and dominance phase (d 5 to 7 of the wave) of a second follicular wave ovulatory follicle, creating 4 treatments: H/H, H/L, L/H, and L/L. Luteolysis was induced with PGF2α on d 7 of the wave and ovulation was induced with GnRH 56 h after PGF2α. Cows (n = 558) received artificial insemination (AI) 16 h following GnRH. Pregnancy was determined at 6 intervals during gestation and at calving to quantify pregnancy loss beginning at d 23 post-AI utilizing pregnancy-specific protein B (PSPB) in novel within-cow comparisons. Cows with single ovulations assigned to the L/L treatment had greater pre-ovulatory follicle diameter compared with cows assigned to the L/H or H/L treatments. Cows with single ovulations had greater pre-ovulatory follicle diameter compared with cows with double ovulations. Low P4 in H/L, L/H, and L/L increased double ovulation rate compared with H/H. Cows with double ovulations had greater pregnancies per AI (P/AI) on d 23 post-AI compared with cows with single ovulations but had greater losses if ovulations were unilateral. Cows with low P4 during the entire period of the ovulatory follicle development also had greater P/AI on d 23 post-AI compared with cows with high P4 during both phases. However, full-term P/AI was not different between treatments. This was a result of the greater incidence of pregnancy losses between d 35 and 56 of gestation for cows with unilateral double ovulations compared with bilateral double ovulations and single ovulatory cows. Cows with single ovulation and low circulating P4 during the dominance period of follicle development had increased pregnancy losses between d 35 and 56 of gestation compared with cows with single ovulations and high P4. The PSPB measurements on d 16 and 23 post-AI were highly accurate in the prediction of pregnancy at d 28. The PSPB differed on d 23 and 28 between cows that had versus cows that did not have pregnancy losses between d 28 and 35 of gestation. In summary, circulating concentrations of P4 during ovulatory follicle development affected numbers of follicles ovulated and timing of subsequent pregnancy losses.

One or two ligatures inducing periodontitis are sufficient to cause fatty liver.

BACKGROUND: Periodontitis is a chronic disease that due to an intense inflammatory response triggers systemic changes such as hepatic alterations. This study aimed to compare hepatic damage in rats that received experimental periodontitis at one or two periodontal sites with ligatures. MATERIAL AND METHODS: Eighteen rats were separated into three groups: control, without ligature; periodontitis 1, with one ligature; and periodontitis 2, with two ligatures. The following parameters were assessed: gingival bleeding index, probing pocket depth, tooth mobility, alveolar bone loss, malondialdehyde (MDA) and myeloperoxidase (MPO) activity in periodontal tissue; histopathological evaluation of hepatic tissue (steatosis score); glutathione levels (GSH), MDA, MPO, cholesterol and triglycerides in the liver; and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). RESULTS: Periodontal evaluation data showed that the periodontitis model worked well. The groups with periodontitis did not differ significantly in relation to MPO activity and MDA levels in the gingival samples, but they were significantly different when compared with the control group. Steatosis was observed in the histological analysis of the groups with periodontitis, but between the periodontitis groups, two ligatures did not cause increase in steatosis score. The levels of GSH, MDA, total cholesterol and triglycerides in the hepatic tissue were not altered between groups with periodontitis, but they showed significant differences in comparison with the control group. The activity of MPO in hepatic tissue and serum levels of AST and ALT did not present significant difference among the three groups. CONCLUSION: In conclusion, our results demonstrated that one or two ligatures inducing periodontitis were both sufficient to cause fatty liver. Steatosis caused by two ligatures did not present larger extension and severity than steatosis caused by one ligature.

A recombinant chimeric protein composed of human and mice-specific CD4+ and CD8+ T-cell epitopes protects against visceral leishmaniasis.

In this study, a recombinant chimeric protein (RCP), which was composed of specific CD4+ and CD8+ T-cell epitopes to murine and human haplotypes, was evaluated as an immunogen against Leishmania infantum infection in a murine model. BALB/c mice received saline were immunized with saponin or with RCP with or without an adjuvant. The results showed that RCP/saponin-vaccinated mice presented significantly higher levels of antileishmanial IFN-γ, IL-12 and GM-CSF before and after challenge, which were associated with the reduction of IL-4 and IL-10 mediated responses. These animals showed significant reductions in the parasite burden in all evaluated organs, when both limiting dilution and quantitative real-time PCR techniques were used. In addition, the protected animals presented higher levels of parasite-specific nitrite, as well as the presence of anti-Leishmania IgG2a isotype antibodies. In conclusion, the RCP/saponin vaccine could be considered as a prophylactic alternative to prevent against VL.

The characterization of Bordetella pertussis strains isolated in the Central-Western region of Brazil suggests the selection of a specific genetic profile during 2012-2014 outbreaks.

Pertussis is a worldwide acute respiratory disease caused by the bacterium Bordetella pertussis. Despite high vaccine coverage, the bacterium continues to circulate in populations and is still one of the most common vaccine-preventable diseases. In Brazil, pertussis incidence has presented a significant decrease since 1990 but since 2011 a sudden increase in incidence has been observed. Thus, the aim of this study was to perform a molecular epidemiological characterization of B. pertussis strains isolated in the Central-Western region (specifically in Distrito Federal) of Brazil from August 2012 to August 2014. During this period, 92 B. pertussis strains were isolated from the outbreaks. All strains were characterized by serotyping and XbaI pulsed-field gel electrophoresis profiles. From August to December 2012, the most prevalent serotype observed was 1,3 (13/17). During 2013 the prevalence of serotype 1,3 decreased (13/30) and from January 2014 to August 2014 the most prevalent serotype was 1,2 (33/45). Fourteen PFGE profiles were identified. Of these, BP-XbaI0039 prevalence increased from 3/17 in 2012 to 10/30 in 2013, and 35/45 in 2014. These results evidence the selection of a specific genetic profile during this period, suggesting the occurrence of a bacterial genomic profile with high circulation potential.

Bioaerosols in the Barcelona subway system.

Subway systems worldwide transport more than 100 million people daily; therefore, air quality on station platforms and inside trains is an important urban air pollution issue. We examined the microbiological composition and abundance in space and time of bioaerosols collected in the Barcelona subway system during a cold period. Quantitative PCR was used to quantify total bacteria, Aspergillus fumigatus, influenza A and B, and rhinoviruses. Multitag 454 pyrosequencing of the 16S rRNA gene was used to assess bacterial community composition and biodiversity. The results showed low bioaerosol concentrations regarding the targeted microorganisms, although the bacterial bioburden was rather high (104 bacteria/m3 ). Airborne bacterial communities presented a high degree of overlap among the different subway environments sampled (inside trains, platforms, and lobbies) and were dominated by a few widespread taxa, with Methylobacterium being the most abundant genus. Human-related microbiota in sequence dataset and ascribed to potentially pathogenic bacteria were found in low proportion (maximum values below 2% of sequence readings) and evenly detected. Hence, no important biological exposure marker was detected in any of the sampled environments. Overall, we found that commuters are not the main source of bioaerosols in the Barcelona subway system.

Cross-protective efficacy from a immunogen firstly identified in Leishmania infantum against tegumentary leishmaniasis.

Experimental vaccine candidates have been evaluated to prevent leishmaniasis, but no commercial vaccine has been proved to be effective against more than one parasite species. LiHyT is a Leishmania-specific protein that was firstly identified as protective against Leishmania infantum. In this study, LiHyT was evaluated as a vaccine to against two Leishmania species causing tegumentary leishmaniasis (TL): Leishmania major and Leishmania braziliensis. BALB/c mice were immunized with rLiHyT plus saponin and lately challenged with promastigotes of the two parasite species. The immune response generated was evaluated before and 10 weeks after infection, as well as the parasite burden at this time after infection. The vaccination induced a Th1 response, which was characterized by the production of IFN-γ, IL-12 and GM-CSF, as well as by high levels of IgG2a antibodies, after in vitro stimulation using both the protein and parasite extracts. After challenge, vaccinated mice showed significant reductions in their infected footpads, as well as in the parasite burden in the tissue and organs evaluated, when compared to the control groups. The anti-Leishmania Th1 response was maintained after infection, being the IFN-γ production based mainly on CD4(+) T cells. We described one conserved Leishmania-specific protein that could compose a pan-Leishmania vaccine.

Prophylactic properties of a Leishmania-specific hypothetical protein in a murine model of visceral leishmaniasis.

In this work, the effect of vaccination of a newly described Leishmania infantum antigenic protein has been studied in BALB/c mice infected with this parasite species. The LiHyD protein was characterized after a proteomic screening performed with the sera from dogs suffering visceral leishmaniasis (VL). Its recombinant version was expressed, purified and administered to BALB/c mice in combination with saponin. As a result of vaccination and 10 weeks after challenge using an infective dose of L. infantum stationary promastigotes, vaccinated mice showed lower parasite burdens in different organs (liver, spleen, bone marrow and footpads' draining lymph nodes) than mice inoculated with the adjuvant alone or the vaccine diluent. Protected mice showed anti-Leishmania IgG2a antibodies and a predominant IL-12-driven IFN-γ production (mainly produced by CD4(+) T cells) against parasite proteins, whereas unprotected controls showed anti-Leishmania IgG1 antibodies and parasite-mediated IL-4 and IL-10 responses. Vaccinated mice showed an anti-LiHyD IgG2a humoral response, and their spleen cells were able to secrete LiHyD-specific IFN-γ, IL-12 and GM-CSF cytokines before and after infection. The protection was correlated with the Leishmania-specific production on nitric oxide. Altogether, the results indicate that the new LiHyD protein could be considered in vaccine formulations against VL.

A multivalent chimeric vaccine composed of Schistosoma mansoni SmTSP-2 and Sm29 was able to induce protection against infection in mice.

Schistosoma mansoni is a blood fluke parasite responsible for schistosomiasis. The best long-term strategy to control schistosomiasis is through immunization combined with drug treatment. In this study, we cloned, expressed and purified SmTSP-2 fused to the N- and C-terminal halves of Sm29 and tested these chimeras as vaccine candidates using an adjuvant approved to be used in humans. The results demonstrated that vaccination with SmTSP-2 fused to N- or C-terminus of Sm29-induced reduction in worm burden and liver pathology when compared to control animals. Additionally, we detected high levels of mouse-specific IgG, IgG1 and IgG2a against both chimeras and significant amounts of IFN-γ and TNF-α and no IL-4. Finally, studies with sera from patients resistant to infection and living in schistosomiasis endemic areas revealed high levels of specific IgG to both chimeras when compared to healthy individuals. In conclusion, SmTSP-2/Sm29 chimeras tested here induced partial protection against infection and might be a potential vaccine candidate.

The cytokinesis-blocked micronucleus assay: dose estimation and inter-individual differences in the response to γ-radiation.

Biological dosimetry plays an important role in case of a radiation accident or incident, either when it is the only way to estimate the dose or when it is used to complement physical dosimetry. A cytogenetic study was conducted in a group of 16 Portuguese individuals by use of the cytokinesis-blocked micronucleus (CBMN) assay. A dose-response curve for micronuclei yield was established with a linear-quadratic model: Y=(0.0122±0.0010)+(0.0241±0.0023)D+(0.0193±0.0007)D(2). Also, baseline values for the micronucleus formation in the 16 donors were analyzed, with results in close agreement with those from other laboratories. A validation experiment was carried out with three individuals. The real and the estimated doses obtained with the dose-response curve were in very good agreement, allowing the use of the micronucleus dose-response calibration curve in biological dosimetry for estimation of radiation dose in case of overexposure. The results obtained for the cytogenetic endpoints, studied in the same group of 16 individuals, were also analyzed as a function of age and gender. A higher inter-variability was observed for the higher dose points and differences in response were identified between genders, above 2Gy, for all endpoints.

Acceleration and transport of relativistic electrons in the jets of the microquasar SS 433.

SS 433 is a microquasar, a stellar binary system that launches collimated relativistic jets. We observed SS 433 in gamma rays using the High Energy Stereoscopic System (H.E.S.S.) and found an energy-dependent shift in the apparent position of the gamma-ray emission from the parsec-scale jets. These observations trace the energetic electron population and indicate that inverse Compton scattering is the emission mechanism of the gamma rays. Our modeling of the energy-dependent gamma-ray morphology constrains the location of particle acceleration and requires an abrupt deceleration of the jet flow. We infer the presence of shocks on either side of the binary system, at distances of 25 to 30 parsecs, and that self-collimation of the precessing jets forms the shocks, which then efficiently accelerate electrons.

Implementation of a dose-response curve for γ-radiation in the Portuguese population by use of the chromosomal aberration assay.

An in vitro dose-response curve following exposure to γ-radiation was determined at the IST/ITN, by use of the chromosomal aberration assay. This is the first study of this kind carried out among the Portuguese population. Un-irradiated and γ-irradiated peripheral blood lymphocytes from 16 healthy donors were cultured. A total of 22,395 metaphases were analyzed for frequency and distribution of dicentrics and centric rings, as a function of the radiation dose. The dose-response data for dicentrics and dicentrics plus centric rings were fitted by use of a linear-quadratic model: Y(dic)=(0.0011±0.0006)+(0.0105±0.0035)D+(0.0480±0.0019)D(2) and Y(dic+rings)=(0.0011±0.0006)+(0.0095±0.0036)D+(0.0536±0.0020)D(2). Also, calibration curves related to age and gender were determined, but no significant differences were found. Following the establishment of the dose-response curves, a validation experiment was carried out with three individuals. Real and estimated doses, obtained with the dose-response curves, were in agreement. These results give us confidence to apply both dose-response calibration curves in future biological dosimetry requirements.

Antimicrobial resistance profile of Aeromonas spp. isolated from asymptomatic Colossoma macropomum cultured in the Amazonas State, Brazil.

Bacterial diseases are important factors that limit productivity in aquaculture. To reduce negative economic impacts, fish farmers use antimicrobials, often indiscriminately, and this action has led to bacterial resistance to drugs. The objectives of this study were to isolate and identify the main putative pathogenic bacterial species in tambaqui (Colossoma macropomum), establish the profile of resistance to antimicrobials by the methods of disc diffusion, and determine the minimum inhibitory concentration (MIC) values. Two hundred and ninety asymptomatic fish were collected between March and November 2015 from ten fish farms in the Amazonas state (Brazil). Of the total strains recovered from tambaqui, seven were identified as Aeromonas spp. by sequencing the 16S rRNA gene. These seven isolates showed resistance to ampicillin, 28% to erythromycin, and 28% to sulfonamide. Additionally, the seven isolates showed a MIC higher than the range evaluated for amoxicillin, penicillin, novobiocin, tylosin tartrate, and clindamycin, and 85% showed resistance to erythromycin. The results of this study indicate the need to increase the awareness of fish farmers and, most importantly, the government, about the lack of drug regulations for use in aquaculture, and good management practices, so the indiscriminate prophylactic and systemic use of antimicrobials be inhibited.

Reliability and validity of the Chester step test in patients with interstitial lung disease.

BACKGROUND: The Chester Step Test (CST) is a simple and inexpensive field test, which requires minimal physical space to assess exercise capacity. Such characteristics make the CST suitable to be used in different settings, however, its measurement properties in patients with interstitial lung diseases (ILD) are unknown. METHODS: A cross-sectional study was conducted in patients with ILD. First, a CST-1 and a 6-minute walk test (6MWT) were performed. After 48-72 hours, a CST-2 was repeated. A 2nd rater was present in one of the sessions. Relative reliability was measured using intraclass correlation coefficient (ICC1,1 and ICC2,1). Absolute reliability was determined using standard error of measurement (SEM), minimal detectable change at 95% confidence interval (MDC95) and the Bland-Altman method. The values of SEM and MDC95 were also expressed as a percentage of the mean. Construct validity was explored using Spearman correlation coefficient (rs) between the number of steps taken in the best CST and the distance performed in the 6MWT. RESULTS: Sixty-six patients with ILD (65.5±12.9 years; 48.5%men; FVC 79.4±18.8pp; DLCO 49.0±18.3pp) participated in the study. Relative (ICC 0.95-1.0) and absolute reliability were excellent without evidence of systematic bias. The SEM and MDC95 were 11.8 (14.7%) and 32.6 steps (40.7%), respectively. The correlation between CST and 6MWT was significant, positive, and high (rs=0.85, p=0.001). CONCLUSION: The CST is a reliable and valid test and might be especially useful to assess exercise capacity in patients with ILD in limited space environments.

Does the addition of chlorhexidine to glass ionomer cements influence its antimicrobial effect and survival rate? A systematic review.

PURPOSE: To evaluate the influence of the addition of chlorhexidine on the antimicrobial effect and on the survival of restorations performed with glass ionomer cement. METHODS: Nine databases were used to search for randomized clinical trials that compared the survival rate and the antimicrobial effect of glass ionomer cement (GIC) restorations with and without the incorporation of chlorhexidine (CHX), without restrictions on year or language. Cochrane Collaboration's Risk of Bias 2 was used to assess the risk of bias. The GRADE approach was used to assess the certainty of evidence. RESULTS: From 593 studies found, seven met the inclusion criteria. The concentration of CHX varied between 0.5 and 2%. In general, the addition of CHX to GIC promoted reductions in Streptococcus mutans and Lactobacillus acidophilus burdens when compared to those without CHX. No study showed a difference in the survival of restorations between GIC with CHX and conventional GIC. Individual risk of bias varied from low to high and the certainty of evidence was classified as very low. CONCLUSIONS: Based on a very low level of certainty, the evidence suggests that the incorporation of CHX in GIC might improve the antimicrobial effects for a short time, in addition to having little influence on the survival of the restoration.