Evaluation of the antifungal effect of plant extracts on oral Candida spp. - a critical methodological analysis of the last decade.

INTRODUCTION: In 2022, the World Health Organization published a report encouraging researchers to focus on Candida spp. to strengthen the global response to fungal oral infections and antifungal resistance. In the context of innovative research, it seems pertinent to investigate the antifungal potential of natural extracts of plants and the methodology involved in the recent reports. The aim of this systematic review is to identify the current state of in vitro research on the evaluation of the ability of plant extracts to inhibit Candida spp. MATERIAL AND METHODS: A bibliographic search has been developed to on a 10-year period to identify which plant extracts have an antifungal effect on the Candida spp. found in the oral cavity. RESULTS: A total of 20 papers were reviewed and fulfilled all the selection criteria and were included in the full data analysis. DISCUSSION: Plants have been tested in a wide range of states - whole extracts, extraction of particular components such as flavonoids or polyphenols, or even using the plant to synthesize nanoparticles. Of forty-five plants tested, five of them did not show any effect against Candida spp., which weren't part of the same family. There is a wide range of plant that exhibit antifungal proprieties. CONCLUSION: Many plants have been tested in a wide range of states - whole extracts, extraction of components such as flavonoids or polyphenols, or even using the plant to synthetize nanoparticles. The combination of plants, the addition of plants to a traditional antifungal and the interference with adhesion provided by some plants seem to be promising strategies. Nonetheless, on contrary to drugs, there is a critical lack of standardization on methodologies and protocols, which makes it difficult to compare data and, consequently, to conclude, beyond doubts, about the most promising plants to fight Candida spp. oral infections.

Spatial accumulation of flood-driven riverside litter in two Northern Atlantic Rivers.

The escalation of litter accumulation in aquatic environments is recognized as an emerging global concern. Although rivers represent the main conduits for land-based waste into the oceans, the spatial dynamics of litter accumulation in these systems remain poorly investigated, especially after hydro-climatic extreme events. Floods have been identified as major drivers of litter mobilization, including macroplastics, within rivers. However, predicting flood-induced litter accumulation along riverbanks is complex due to the cumulative interplay of multiple environmental (geomorphological and riparian) and anthropogenic factors. Using empirical data collected from 14 stream reaches in two Northern Atlantic rivers in Portugal, our study evaluates which factors, among geomorphological, riparian, and anthropogenic descriptors, best drive riverside litter accumulation after floods. Taking into account the longitudinal gradient and the spatial heterogeneity of the studied reaches, our study enhances how the accumulation and characteristics (type, size) of riverside litter vary across a rural-urban continuum. Our model reveals that the combination of the human population density and the stream slope at river reach showed the highest explanatory power for the accumulation of riverside litter. Our findings indicate that litter tends to be retained close to the source, even under flood conditions. We also found that the structure of riparian vegetation showed low explanatory power for litter accumulation. However, riparian trapping could be influenced by litter input (density and type) which varies with anthropogenic activities. This work highlights the importance of gathering field data to identify critical areas of riverside litter accumulation within river basins. Our findings can further support environmental managers in designing and implementing effective cleanup campaigns and implementing plastic recovery strategies at specific areas. Nevertheless, it is crucial to enhance coordinated efforts across the entire value chain to reduce plastic pollution, promote innovative approaches for plastic litter valorization, and establish effective prevention pathways.

CETP gene polymorphisms and haplotypes are explanatory variables for HDL cholesterol level in sickle cell disease.

Variations in lipid profile have been observed in sickle cell disease (SCD) and understanding their relationship with disease severity is crucial. This study aimed to investigate the association of polymorphisms of the CETP gene and laboratory markers of disease severity with lipid profile in a pediatric population with SCD. Biochemical and anthropometric analyses and CETP and alpha-thalassemia genotyping were performed. The study included 133 children and adolescents with sickle cell anemia (SCA) or hemoglobin SC disease (SCC), in steady-state. The SCA and no hydroxyurea (no HU) groups had higher values of ApoB, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) compared to the SCC and HU groups. However, there were no significant differences in ApoA1 and HDL-C levels between the groups based on genotype. Furthermore, the groups with altered levels of ApoA1, HDL-C, and the triglyceride/HDL ratio exhibited lower hemoglobin (Hb) levels and higher white blood cell counts. Hb level was associated to HDL-C levels. Analysis of CETP gene variants showed that the minor alleles of rs3764261 (C>A), rs247616 (C>T), and rs183130 (C>T), as well as the TTA haplotype, are explanatory variables for HDL-C levels. These findings suggested that dyslipidemia in SCD, specifically related to HDL-C levels, may be influenced by individual genetic background. Additionally, further investigation is needed to determine if clinical manifestations are impacted by CETP gene variants.

Sustained PGC-1α2 or PGC-1α3 expression induces astrocyte dysfunction and degeneration.

Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) transcriptional coactivators are key regulators of energy metabolism-related genes and are expressed in energy-demanding tissues. There are several PGC-1α variants with different biological functions in different tissues. The brain is one of the tissues where the role of PGC-1α isoforms remains less explored. Here, we used a toxin-based mouse model of Parkinson's disease (PD) and observed that the expression levels of variants PGC-1α2 and PGC-1α3 in the nigrostriatal pathway increases at the onset of dopaminergic cell degeneration. This increase occurs concomitant with an increase in glial fibrillary acidic protein levels. Since PGC-1α coactivators regulate cellular adaptive responses, we hypothesized that they could be involved in the modulation of astrogliosis induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Therefore, we analysed the transcriptome of astrocytes transduced with expression vectors encoding PGC-1α1 to 1α4 by massively parallel sequencing (RNA-seq) and identified the main cellular pathways controlled by these isoforms. Interestingly, in reactive astrocytes the inflammatory and antioxidant responses, adhesion, migration, and viability were altered by PGC-1α2 and PGC-1α3, showing that sustained expression of these isoforms induces astrocyte dysfunction and degeneration. This work highlights PGC-1α isoforms as modulators of astrocyte reactivity and as potential therapeutic targets for the treatment of PD and other neurodegenerative disorders.

CETP gene polymorphisms and haplotypes are explanatory variables for HDL cholesterol level in sickle cell disease

Variations in lipid profile have been observed in sickle cell disease (SCD) and understanding their relationship with disease severity is crucial. This study aimed to investigate the association of polymorphisms of the CETP gene and laboratory markers of disease severity with lipid profile in a pediatric population with SCD. Biochemical and anthropometric analyses and CETP and alpha-thalassemia genotyping were performed. The study included 133 children and adolescents with sickle cell anemia (SCA) or hemoglobin SC disease (SCC), in steady-state. The SCA and no hydroxyurea (no HU) groups had higher values of ApoB, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) compared to the SCC and HU groups. However, there were no significant differences in ApoA1 and HDL-C levels between the groups based on genotype. Furthermore, the groups with altered levels of ApoA1, HDL-C, and the triglyceride/HDL ratio exhibited lower hemoglobin (Hb) levels and higher white blood cell counts. Hb level was associated to HDL-C levels. Analysis of CETP gene variants showed that the minor alleles of rs3764261 (C>A), rs247616 (C>T), and rs183130 (C>T), as well as the TTA haplotype, are explanatory variables for HDL-C levels. These findings suggested that dyslipidemia in SCD, specifically related to HDL-C levels, may be influenced by individual genetic background. Additionally, further investigation is needed to determine if clinical manifestations are impacted by CETP gene variants.

Long-term memory in Staphylococcus aureus α-hemolysin ion channel kinetics.

The kinetics of an ion channel are classically understood as a random process. However, studies have shown that in complex ion channels, formed by multiple subunits, this process can be deterministic, presenting long-term memory. Staphylococcus aureus α-hemolysin (α-HL) is a toxin that acts as the major factor in Staphylococcus aureus virulence. α-HL is a water-soluble protein capable of forming ion channels into lipid bilayers, by insertion of an amphipathic  ß-barrel. Here, the α-HL was used as an experimental model to study memory in ion channel kinetics. We applied the approximate entropy (ApEn) approach to analyze randomness and the Detrended Fluctuation Analysis (DFA) to investigate the existence of long memory in α-HL channel kinetics. Single-channel currents were measured through experiments with α-HL channels incorporated in planar lipid bilayers. All experiments were carried out under the following conditions: 1 M NaCl solution, pH 4.5; transmembrane potential of + 40 mV and temperature 25 ± 1 °C. Single-channel currents were recorded in real-time in the memory of a microcomputer coupled to an A/D converter and a patch-clamp amplifier. The conductance value of the α-HL channels was 0.82 ± 0.0025 nS (n = 128). The DFA analysis showed that the kinetics of α-HL channels presents long-term memory ([Formula: see text] = 0.63 ± 0.04). The ApEn outcomes showed low complexity to dwell times when open (ApEno = 0.5514 ± 0.28) and closed (ApEnc = 0.1145 ± 0.08), corroborating the results of the DFA method.

Ikaros expression is associated with an increased risk of chronic graft-versus-host disease.

Immune reconstitution after hematopoietic stem cell transplantation (HSCT) is a complex and extremely variable process. The Ikaros transcription factor plays an important role in hematopoiesis in several cell lines, especially in the lymphoid lineage. We hypothesized that Ikaros might influence immune reconstitution, and consequently, the risk of opportunistic infections, relapse, and graft versus host disease (GVHD). Samples were collected from the graft and from the peripheral blood (PB) of the recipients 3 weeks after neutrophil recovery. Real-time polymerase chain reaction (RT-PCR) was performed to analyze the absolute and relative Ikaros expression. Patients were divided into two groups, according to Ikaros expression in the graft and in the recipients' PB based on the ROC curves for moderate/severe cGVHD. A cutoff of 1.48 was used for Ikaros expression in the graft, and a cutoff of 0.79 was used for Ikaros expression in the recipients' PB. Sixty-six patients were included in this study. Median age of patients was 52 years (range 16-80 years), 55% of them were male, and 58% of them had acute leukemia. Median follow-up period was 18 months (range 10-43 months). There was no association between Ikaros expression and the risk of acute GVHD, relapse, or mortality. However, a significant association was observed with the risk of chronic GVHD. Higher Ikaros expression in the graft was associated with a significantly higher cumulative incidence (CI) of moderate/severe chronic GVHD according to the National Institute of Health (NIH) classification at two years (54% vs. 15% for patients with lower expression, P = 0.03). A higher Ikaros expression in the recipients' PB 3 weeks after engraftment was also associated with a significantly higher risk of moderate/severe chronic GVHD (65% vs. 11%, respectively, P = 0.005). In conclusion, Ikaros expression in the graft and in the recipients' PB after transplantation was associated with a higher risk of moderate/severe chronic GVHD. Ikaros expression should be evaluated in larger prospective trials as a potential biomarker for chronic GVHD.

Exploiting Real-Time Genomic Surveillance Data To Assess 4CMenB Meningococcal Vaccine Performance in Scotland, 2015 to 2022.

The United Kingdom implemented the first national infant immunization schedule for the meningococcal vaccine 4CMenB (Bexsero) in September 2015, targeting serogroup B invasive meningococcal disease (IMD). Bexsero contains four variable subcapsular proteins, and postimplementation IMD surveillance was necessary, as nonhomologous protein variants can evade Bexsero-elicited protection. We investigated postimplementation IMD cases reported in Scotland from 1 September 2015 to 30 June 2022. Patient demographics and vaccination status were combined with genotypic data from the causative meningococci, which were used to assess vaccine coverage with the meningococcal deduced vaccine antigen reactivity (MenDeVAR) index. Eighty-two serogroup B IMD cases occurred in children >5 years of age, 48 (58.5%) of which were in unvaccinated children and 34 (41%) of which were in children who had received ≥1 Bexsero dose. Fifteen of the 34 vaccinated children had received one dose, 17 had received two doses, and two had received three doses. For 39 cases, meningococcal sequence data were available, enabling MenDeVAR index deductions of vaccine-preventable (M-VP) and non-vaccine-preventable (M-NVP) meningococci. Notably, none of the 19 of the children immunized ≥2 times had IMD caused by M-VP meningococci, with 2 cases of NVP meningococci, and no deduction possible for 17. Among the 15 children partially vaccinated according to schedule (1 dose), 7 were infected by M-VP meningococci and 2 with M-NVP meningococci, with 6 for which deductions were not possible. Of the unvaccinated children with IMD, 40/48 were ineligible for vaccination and 20/48 had IMD caused by M-VP meningococci, with deductions not being possible for 14 meningococci. IMPORTANCE This study demonstrates the value of postimplementation genomic surveillance of vaccine-preventable pathogens in providing information on real-world vaccine performance. The data are consistent with 2 and 3 doses of Bexsero, delivered according to schedule, providing good protection against invasive disease caused by meningococci deduced from genomic data to be vaccine preventable. Single doses provide poorer protection to infants. In practical terms, these data can provide public health reassurance when vaccinated individuals develop IMD with non-vaccine-preventable variants. They further indicate that additional testing is needed on variants for which no immunological data exist to improve estimates of protection, although these data suggest that the uncharacterized variants are unlikely to be covered by Bexsero. Finally, the confirmation that incomplete or absent doses in infancy lead to reduced protection supports public health and general practitioners in promoting vaccination according to schedule.

Effect of Multiple Firings on the Microshear Bond Strength Between a Translucent Zirconia and a Resin Cement.

PURPOSE: This study investigated the microshear bond strength between a resin cement and a translucent zirconia subjected to multiple characterization firings. METHODS AND MATERIALS: 5Y-PSZ zirconia blocks (Katana UTML) were sliced, sintered (1550°C, 2 h), and randomly divided into six groups (n=10) according to the number of characterization firings (0, 1, 2, 3, 5, or 10) and aging (baseline or after thermocycling). Each characterization firing was performed at 750°C for 1 minute. The ceramic surfaces were all sandblasted with 50 µm Al2O3 and silanized. Then, cylinders of resin cement (0.96 mm diameter × 2 mm height) were bonded onto their surfaces. The baseline samples were immersed in distilled water for 24 hours before the microshear bond strength (µSBS) tests. The aged samples were tested after 5000 thermocycles in water (5°C-55°C). The failure modes were classified as adhesive, predominantly adhesive, or cohesive. Scanning electron microscope images of the failure modes and the ceramic surfaces after the firings were taken. The µSBS data were analyzed by two-way ANOVA and Tukey's test. RESULTS: The number of characterization firings and aging affected the bond strength. The highest bond strength values were observed from the 2-firing group at baseline. The µSBS results after 1, 2, or 3 characterization firings were similar at baseline and after aging. On the other hand, 0, 5, and 10 firings revealed the lowest bond strengths. The most frequent failures were adhesive and predominantly adhesive. Zirconia grains were not affected by the multiple firings. CONCLUSION: One to three characterization firings after sintering improve the bond strength of 5Y-PSZ to the resin cement when compared to none or several (five or ten) firing cycles.

Phylogeography of Eriotheca species complex: insights into the origin and range expansion of apomictic and polyploid trees in Neotropical Savannas.

Polyploidy and whole genome duplication are major evolutionary drivers in plants. Climate variations during the Pleistocene have influenced distribution and range expansion worldwide. Similar trends have been reported for Cerrado plants, but no attempt has been made to link phylogeography with ploidy and breeding changes. Thus, we aimed to (i) assess ploidy and genome size of Eriotheca estevesiae Carv.-Sobr., and compare it with E. pubescens (Mart.) Schott & Endl. (Both included into the Eriotheca Stellate Trichome Species Complex - ESTSC). (ii) Subsequently, we investigated their phylogeography to see whether genetic structure and range expansion trends were similar to those previously described for the Cerrado biome. Finally (iii), we discuss whether ESTSC phylogeographic patterns could be associated with geographic parthenogenesis processes. Common cytogenetic techniques and flow cytometry were used to confirm chromosome number and genome size of E. estevesiae. We used three cpDNA regions to analyse 14 ESTSC Cerrado populations, for which we also obtained ploidy level and breeding information. We investigated haplotype diversity, population structure and tested neutrality, aiming to reconstruct phylogeographic scenarios. We found three ploidy levels and eight cpDNA haplotypes in ESTSC, one shared by most populations. Haplotype and ploidy distribution corroborated that E. pubescens, the widely distributed polyploid and apomictic species, may have originated from northern diploid and probably sexual E. estevesiae. Matrilinear cpDNA links support the idea that apomixis and polyploidy in ESTSC may have allowed range expansion during the Pleistocene, in a process analogous to the geographic parthenogenesis described elsewhere.

Impact of parity and delivery mode on pelvic floor function in young women: a 3D ultrasound evaluation.

INTRODUCTION AND HYPOTHESIS: The objectives were to evaluate clinical and anatomical parameters assessed by three-dimensional pelvic floor ultrasound (3D ultrasound) in parous and nulliparous women of childbearing age and to assess underreported symptoms of sexual dysfunction (SD), urinary incontinence (UI) and flatus incontinence (FI). METHODS: Women without complaints of pelvic floor dysfunction, aged 20-50 years, were eligible for this prospective cross-sectional study. They completed the King's Health Questionnaire, Female Sexual Function Index and St Mark's Incontinence Score adapted for this study. Next, a physical examination and 3D ultrasound were performed. The scores obtained in the questionnaires were compared with the 3D ultrasound data. RESULTS: In total, 326 women were invited to participate. Of these, 203 women met the inclusion criteria, and their cases were classified as nulliparity (NU, 59), vaginal delivery (VD, 80), forceps delivery (FD, 18) and caesarean section (CS, 48). These groups were homogeneous regarding age (p=0.096), parity (p=0.051) and body mass index (p=0.06). The hiatal dimension (HD; p=0.003) and transverse diameter (TD) (p=0.001) were significantly different among the groups. Compared with the NU and CS groups, the VD and FD groups had an increased HD and TD. The frequencies of underreported symptoms identified by questionnaires were as follows: SD (46.3%), UI (35%) and FI (28%). After VD and FD, women were more likely to present UI (p<0.001), FI (p<0.001) and SD (p=0.002) than the women with NU and those who had undergone a CS. UI was related to a greater HD (p=0.002) and anteroposterior diameter (p=0.022), FI was associated with a thinner left pubovisceral muscle (p=0.013), and SD was related to a greater HD (p=0.026). CONCLUSIONS: Three-dimensional ultrasound can identify mild morphological changes in young women with apparently normal physical examinations, mainly after VD and FD. In such individuals, these findings are associated with higher incidences of underreported sexual, urinary and anal symptoms.

A Critical Review of Dental Lithia-Based Glass-Ceramics.

The purpose of this article is to review current understanding of lithia-based glass-ceramics and to identify future research needs for this class of dental materials in relation to novel compositions and fabrication methods. With rapid advances in material development and digital technology, time efficiency of dental workflow and fit accuracy of ceramic restorations are ever improving. Lithia-based glass-ceramics are at the forefront of this advance-new variants with more efficient fabrication routes are continually being introduced into the marketplace. Base glass composition, crystallization heat treatment, nucleant and coloration additives, and property gradation are some pertinent variables. The trend in fabrication is to move from CAD/CAM grinding of partially crystallized glass-ceramics to fully crystallized materials, thereby circumventing the need for postmachining firing altogether. In these endeavors, a better understanding of mechanical properties and evolving shaping technologies, such as ductile grinding, is paramount. Additive manufacturing and 3-dimensional printing methodologies offer a promising alternative to current CAD/CAM subtractive manufacturing routes. Challenges to the implementation of new technologies in efficient development and production of high-quality dental glass-ceramic prostheses are addressed.

Prevalence of canalis sinuosus and accessory canals of canalis sinuosus on cone beam computed tomography: a systematic review and meta-analysis.

The aim of this systematic review was to determine the prevalence of the canalis sinuosus (CS) and accessory canals of the canalis sinuosus (ACCS) as identified on cone beam computed tomography (CBCT). Online searches were conducted in the MEDLINE (via PubMed), Scopus, LILACS, Cochrane CENTRAL, Web of Science, and SIGLE (via OpenGrey) databases. Primary studies that determined the prevalence of canalis sinuosus and/or its anatomical variations using CBCT were included. The risk of bias assessment was performed using the AQUA tool. The quality effects model using double arcsine transformation was used for the meta-analysis of prevalence. Heterogeneity, publication bias, and sensitivity analyses were performed. Of 3237 initial results, 17 papers were included for systematic review. The meta-analysis comprising 1994 patients showed a pooled prevalence of CS of 0.80 (95% confidence interval (CI) 0.51-0.99; P = 0.001; I2 = 99%). Publication bias analysis revealed minor asymmetry (LFK index 1.84). The meta-analysis of 4605 patients showed a pooled prevalence of ACCS of 0.54 (95% CI 0.38-0.69; P = 0.001; I2 = 99%). The sensitivity analysis showed a pooled prevalence of ACCS of 0.53 (95% CI 0.32-0.74; P = 0.001; I2 = 99%) for studies with ≥ 1000 patients and 0.55 (95% CI 0.33-0.76; P = 0.001; I2 = 98%) for studies with< 1000 patients. Canalis sinuosus showed a pooled prevalence of 0.80 and ACCS showed a pooled prevalence of 0.54; hence both should be considered as anatomical structures, which means that they are present in most people. Surgeons must be aware of the CS and ACCS on CBCT analysis during pre-surgical planning. PROSPERO REGISTRATION NUMBER: CRD42020154195.

Chronic obstructive pulmonary disease exacerbations' management in Portuguese hospitals - EvaluateCOPDpt, a multicentre, observational, prospective study.

INTRODUCTION AND OBJECTIVES: In order to improve the quality of chronic obstructive pulmonary disease (COPD) patients' care, better knowledge of clinical practice and the factors associated with patient outcomes are needed. This study aimed to evaluate the relation between clinical practice and the outcomes of patients admitted for COPD exacerbations in Portuguese hospitals. MATERIALS AND METHODS: Observational, multicentre, prospective study with a 60-days follow-up period, in 11 hospitals, including patients aged ≥ 30 years, admitted to hospital for at least 24 hours due to an acute exacerbation of COPD. Demographic and clinical data were collected, including sex, age, smoking habits, hospitalisations, pulmonary function, comorbidities, COPD symptoms, and treatment. Sixty days after discharge, COPD exacerbations management, outcome measures, and readmission data were evaluated through a structured phone follow-up interview. RESULTS: 196 patients were included (85.7% male, mean age 71.2 years), the majority admitted through the emergency service. Ex-smokers and current smokers accounted for 51% and 36%, respectively. On admission, 72.4% were on LAMA, 54.6% on LABA, and 45.5% were on LABA/LAMA. Inhaled corticosteroids (ICS) were used in 37.3% and systemic steroids (SCS) in 10.3%. 35.7 % had had at least one exacerbation, with hospitalisation, in the previous year. There was no spirometry data for 23.2%. On hospitalisation, 98.5% of patients were treated with oxygen and 38.3% with non-invasive ventilation. Additionally, 93.4% used SCS and 60.2% ICS. Antibiotics were administered to 85.2%. 95.4% of patients were discharged; 9 died, 5 of whom had a COPD-related death. The median length of stay was 12 days for discharged patients and 33 days for patients who died. At discharge, 79.1% were prescribed with LAMA, 63.6% SCS, 61.5% LABA and 55.6% LAMA+LABA. 26,2% were prescribed with ICS+LABA+LAMA. At follow-up, 44.4% had a scheduled medical appointment within the 60 days after being discharged, and 28.3% were later readmitted due to exacerbation, of whom 52.8% were hospitalised. CONCLUSIONS: The severity of COPD, particularly in exacerbations, is directly related to impaired lung function and quality of life, mortality, and significant health system costs. Knowledge about COPD exacerbations' management in acute hospital admissions in Portugal may help stimulate a national discussion and review of existing data to engage clinicians, policymakers, managers, and patients, raising awareness and promoting action on COPD.

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.

COPD phenotypes by computed tomography and ventilatory response to exercise.

INTRODUCTION: Computed tomographic (CT) phenotypic patterns of chronic obstructive pulmonary disease (COPD) identify different clinical features of disease. The impact of these variables on the physiological response to exercise has been the focus of a great deal of research as it allows more individualized clinical approaches. The aim of our study was to evaluate the relationships between CT phenotyping of subjects with COPD and the ventilatory response during cardiopulmonary exercise testing (CPET). METHODS: Subjects with COPD were classified into four phenotypes based on CT metrics of emphysema (low attenuation area less than a threshold of -950 Hounsfield [%LAA-950]) and airwall thickness (bronchial wall area percentage [%WA]). RESULTS: Eighty COPD patients (78.8% males, median age 65±11.3 years) were enrolled in the study. Based on CT phenotype, 25 (31.3%) patients were classified as normal, 27 (33.8%) air dominant, 17 (21.3%) emphysema dominant and 11 (13.8%) mixed type. The emphysema and mixed phenotypes showed the highest ventilatory equivalent for carbon dioxide (VE/VCO2) and VE/VCO2 slope (p<0,05). In all phenotypes, %LAA was positive correlated with VE/VCO2 and VE/VCO2 slope (r = 0.437, p = 0.006 and r = 0.503, p<0.001, respectively). %WA also showed a positive correlation with VE/VCO2 and VE/VCO2 slope (r = 0.541, p<0.001 and r = 0.299, p = 0.033, respectively). In multivariate regression models, after adjustment for age, BMI, sex and FEV1, %LAA was the only independent predictor of VE/VCO2 and VE/VCO2 slope (ß 0.343, SE 0.147, 95% CI 0.009/0.610, p = 0.044 and ß 0.496, SE 0.081, 95% CI 0.130/0.455, p = 0.001, respectively). CONCLUSION: Emphysema (%LAA) and airways metrics (%WA) had strong relationships with the different characteristics of ventilatory response to exercise in subjects with mild to moderate COPD. In particular, %LAA seemed to play an important role as an independent predictor of VE/VCO2 and VE/VCO2 slope. These results suggested that CT phenotyping may help predicting ventilatory response to exercise in subjects with COPD.

The need for European harmonization of Nutrivigilance in a public health perspective: a comprehensive review.

According to the European Union regulation, some countries have established a pre-market notification system for food supplements while others have not. As this regulation is unfulfilled, a notified and marketed food supplement ingredient in one country may be forbidden in another. Even though food supplements shall not be placed on the market if unsafe, some products may still expose the consumers to risks. The risk is increased by easier access due to worldwide dissemination fostered by the internet and free movement of goods in the European Union. The Rapid Alert System for Food and Feed and the Emerging Risks Exchange Network are described. To date, the European Union legislation does not include a provision to establish a dedicated vigilance system for food supplements (Nutrivigilance). Six European Union countries have nevertheless set up national systems, which are presented. The present lack of European Union data collection harmonization, does not allow easy cooperation between countries. This article advocates for creating a coordinated European Nutrivigilance System to detect and scrutinize adverse effects of food supplements. This, to help in directing science-based risk assessments and reinforce the science-based decision of policy makers to improve public health safety.

Structure-activity relationship, molecular docking, and molecular dynamic studies of diterpenes from marine natural products with anti-HIV activity.

HIV-1 infection is a global epidemic whose treatment is limited majorly by viral resistance and adverse effects. Natural products from algae have been studied for many years, including antiviral, being an alternative to anti-HIV drug design. Since the isolation of natural products can be a hurdle, molecular modeling is an important tool to study these compounds. Herein, structure-activity relationship, molecular docking, and molecular dynamic studies were performed to direct the studies of ten marine natural products with anti-HIV activity. In the structure-activity relationship, descriptors were identified associating the anti-HIV activity of five diterpenes with possible action on the reverse transcriptase allosteric site. These diterpenes were evaluated by molecular docking, and it was identified that only dolabelladienetriol interacted in the allosteric site. Molecular dynamics suggested that the dolabelladienetriol might interfere with the viral RNA binding to HIV-1 RT by inducing a conformational change of the enzyme. Also, in silico ADMET simulations predicts that the dolabelladienetriol present a high potential to be successfully developed as a drug. Thus, applying in silico approaches was possible to suggest potential anti-HIV compounds derived from marine natural products.Communicated by Ramaswamy H. Sarma.