Revisiting the strain-induced softening behaviour in hydrogels.

The strain-induced softening behaviour observed in the differential modulus K(T,γ) of hydrogels is typically attributed to the breakage of internal network structures, such as the cross-links that bind the polymer chains. In this study, however, we consider a stress-strain relationship derived from a coarse-grained model to demonstrate that rupture of the network is not necessary for rubber-like gels to exhibit such behaviour. In particular, we show that, in some cases, the decrease of K(T,γ) as a function of the strain γ can be associated with the energy-related contribution to the elastic modulus that has been experimentally observed, e.g., for tetra-PEG hydrogels. Our findings suggest that the softening behaviour can be also attributed to the effective interaction between polymer chains and their surrounding solvent molecules, rather than the breakage of structural elements. We compare our theoretical expressions with experimental data determined for several hydrogels to illustrate and validate our approach.

Hybrid modeling of an ultracentrifugation process for separation of full and empty adeno-associated virus particles.

Ultracentrifugation is an attractive method for separating full and empty capsids, exploiting their density difference. Changes of the serotype/capsid, density of loading material, or the genetic information contained in the adeno-associated viruses (AAVs) require the adaptation of the harvesting parameters and the density gradient loaded onto the centrifuge. To streamline these adaptations, a mathematical model could support the design and testing of operating conditions.Here, hybrid models, which combine empirical functions with artificial neural networks, are proposed to describe the separation of full and empty capsids as a function of material and operational parameters, i.e., the harvest model. In addition, critical quality attributes are estimated by a quality model which is operating on top of the harvest model. The performance of these models was evaluated using test data and two additional blind runs. Also, a "what-if" analysis was conducted to investigate whether the models' predictions align with expectations.It is concluded that the models are sufficiently accurate to support the design of operating conditions, though the accuracy and applicability of the models can further be increased by training them on more specific data with higher variability.

Neuronorma Colombia: contributions and methodological characteristics.

INTRODUCTION: Availability of adequate normative data is essential when performing neuropsychological evaluation; good methodological quality of the studies that propose these data ensures that their conclusions are reliable and valid. We present the methodological characteristics of the Neuronorma Colombia Project in order to analyse its contributions and limitations. METHOD: We present the characteristics of the normative sample, inclusion and exclusion criteria, statistical analysis, the procedure for obtaining normative data, and the instruments used. RESULTS: We present graphical profiles of patient performance, based on the Neuronorma Work Unit, to illustrate the interpretation of the results obtained when evaluating patients with the Neuronorma Colombia Battery. DISCUSSION AND CONCLUSIONS: Our study presents several methodological advantages, such as its multicentre, co-normalised design and the availability of the Neuronorma Work Unit, which allows the creation of graphical profiles of patient performance, a fundamental tool for diagnosis and research. We present the findings of subsequent research based on the proposed normative data, which demonstrate the value of the battery. The contribution of this study is discussed in the context of its immediate background.

On the origin of the negative energy-related contribution to the elastic modulus of rubber-like gels.

We consider a coarse-grained polymer model in order to investigate the origin of a recently discovered negative energy-related contribution to the elastic modulus G(T) of rubber-like gels. From this model, we are able to compute an exact expression for the free energy of the system, which allows us to evaluate a stress-strain relationship that displays a non-trivial dependence on the temperature T. We validate our approach through comparisons between the theoretical results and the experimental data obtained for tetra-PEG hydrogels, which indicate that, although simple, the present model works well to describe the experiments. Importantly, our approach unveiled aspects of the experimental analysis which turned out to be different from the conventional entropic and energetic analysis broadly used in the literature. Also, in contrast to the linear dependence predicted by the traditional, i.e., purely entropic, models, our results suggest that the general expression of the elastic modulus should be of the form [Formula: see text], with w(T) being a temperature-dependent correction factor that could be related to the interaction between the chains in the network and the solvent. Accordingly, the correction factor allows the expression found for the elastic modulus to describe both rubber and rubber-like gels.

Sex Differences in Falls: The Mediating Role of Gait Stability Ratio and Body Balance in Vulnerable Older Adults.

This study, conducted on a large sample of older adults at elevated fall risk (1), aimed to verify statistical differences in gait stability ratio (GSR) and body balance (BB) according to sex, (2) to examine and compare GSR and BB performance between older adult fallers and non-fallers, (3) to determine an association between GSR and BB according to the history of falls, and (4) to explore whether GSR and BB mediate the association between sex and falls. We included 619 individuals (69.8 ± 5.6 years) living in the Autonomous Region of Madeira, Portugal. The frequency of falls was obtained by self-report. BB was determined by the Fullerton Advanced Balance scale, while GSR was established by dividing cadence by gait speed and data collected during the 50-foot walk test. Males indicated a lower prevalence of falls in the last 12 months (23.6%), while females had a higher score (48.7%), as well as a lower balance performance (p < 0.001) and higher GSR scores (p < 0.001). Lower BB control (p < 0.001), as well as higher GSR, were more expressive for fallers (p < 0.001). We found a large, negative and significant correlation between GSR and BB for historical falls (r = −0.560; p < 0.001), and between male and female cohorts (r = −0.507; p < 0.001). The total effect of sex on falls mediated by GSR and BB was 16.4%. Consequently, GSR and BB mediated this association by approximately 74.0% and 22.5%, respectively.

Exploring Mediation Effects of Gait Speed, Body Balance, and Falls in the Relationship between Physical Activity and Health-Related Quality of Life in Vulnerable Older Adults.

The present study aimed to examine whether gait speed (GS), body balance (BB), and falls mediated the relationship between physical activity (PA) and health-related quality of life (HRQoL) in community-dwelling older adults. This is a cross-sectional study that included 305 men and 314 women (69.5 ± 5.6 years), residing in the Autonomous Region of Madeira, Portugal. HRQoL and PA were assessed using the SF-36 and Baecke Questionnaires, respectively. While BB was obtained by the Fullerton Advance Balance (FAB) scale, GS by the 50-foot (15 m) walk test, and the frequency of falls was obtained by self-report. According to the analyses, when GS and BB were placed concomitantly as mediators, the direct effect revealed by the model revealed a non-significant relationship between PA and falls. Thus, in the context of falls, GS and BB partially mediated the association between PA and HRQoL in approximately 29.7%, 56%, and 49.2%, respectively. The total HRQoL model explained a variance of 36.4%. The results can help to understand the role that GS, BB, and falls play in the relationship between PA and HRQoL of the vulnerable older adult population.

Chyloperitoneum due to gastric carcinoma: a case report.

Chyloperitoneum is a rare manifestation of gastric carcinoma, generally occurring late in the course of the disease with a poor prognosis. We report an unusual case of chyloperitoneum in a patient with gastric carcinoma. A 61-year-old male patient presented with postprandial fullness, nausea and weight loss. The upper gastrointestinal endoscopy demonstrated a stenosing lesion of the esophagogastric junction. A biopsy was made and revealed a signet-ring cell gastric adenocarcinoma. The staging CT scan showed multiple abdominal lymphadenopathies and mild ascites. The patient underwent a staging laparoscopy that revealed a large carcinoma of the gastric cardia and a milky-appearing peritoneal fluid. A peritoneal washing and abdominal drainage were performed. The fluid analysis showed a high concentration of triglycerides, compatible with a chyloperitoneum. The patient started medium chain triglycerides-based diet with good response. This case report emphasizes that chyloperitoneum should be considered when assessing patients with gastric carcinoma.

n-3 polyunsaturated fatty acids in the regulation of adipose tissue browning and thermogenesis in obesity: Potential relationship with gut microbiota.

BACKGROUND: Obesity is a worldwide public health problem characterized by fat tissue accumulation, favouring adipose tissue and metabolic alterations. Increasing energy expenditure (EE) through brown adipose tissue activation and white adipose tissue (WAT) browning has gained relevance as a therapeutic approach. Different bioactive compounds, such as n-3 polyunsaturated fatty acids (PUFA), have been shown to induce those thermogenic effects. This process is regulated by the gut microbiota as well. Nevertheless, obesity is characterized by gut microbiota dysbiosis, which can be restored by weight loss and n-3 PUFA intake, among other factors. Knowledge gap: However, the role of the gut microbiota on the n-3 PUFA effect in inducing thermogenesis in obesity has not been fully elucidated. OBJECTIVE: This review aims to elucidate the potential implications of this interrelation on WAT browning adiposw sittue (BAT), BAT activity, and EE regulation in obesity models.

Neuronorma Colombia: Contributions and methodological characteristics. / Neuronorma Colombia: aportes y características metodológicas.

INTRODUCTION: Availability of adequate normative data is essential when performing neuropsychological evaluation; good methodological quality of the studies that propose these data ensures that their conclusions are reliable and valid. We present the methodological characteristics of the Neuronorma Colombia Project in order to analyse its contributions and limitations. METHOD: We present the characteristics of the normative sample, inclusion and exclusion criteria, statistical analysis, the procedure for obtaining normative data, and the instruments used. RESULTS: We present graphical profiles of patient performance, based on the Neuronorma Work Unit, to illustrate the interpretation of the results obtained when evaluating patients with the Neuronorma Colombia Battery. DISCUSSION AND CONCLUSIONS: Our study presents several methodological advantages, such as its multicentre, co-normalised design and the availability of the Neuronorma Work Unit, which allows the creation of graphical profiles of patient performance, a fundamental tool for diagnosis and research. We present the findings of subsequent research based on the proposed normative data, which demonstrate the value of the battery. The contribution of this study is discussed in the context of its immediate background.

Microrheology of semiflexible filament solutions based on relaxation simulations.

We present an efficient computational methodology to obtain the viscoelastic response of dilute solutions of semiflexible filaments. By considering an approach based on the fluctuation-dissipation theorem, we were able to evaluate the dynamical properties of probe particles immersed in solutions of semiflexible filaments from relaxation simulations with a relatively low computational cost and higher precision in comparison to those based on stochastic dynamics. We used a microrheological approach to obtain the complex shear modulus and the complex viscosity of the solution through its compliance which was obtained directly from the dynamical properties of a probe particle attached to an effective medium described by a mesoscopic model, i.e., an effective filament model (EFM). The relaxation simulations were applied to assess the effects of the bending energy on the viscoelasticity of the semiflexible filament solutions, and our methodology was validated by comparing the numerical results to the experimental data on DNA and collagen solutions.

Negatively controlled, randomized clinical trial comparing different antimicrobial interventions for treatment of clinical mastitis caused by gram-positive pathogens.

The general objective of this study was to evaluate the effect of 3 intramammary antibiotic interventions using 2 commercially available antibiotics with narrow- or broad-spectrum activity on cure rates of clinical mastitis (CM) caused by gram-positive bacteria. We also compared the efficacy of treatment protocols, including a negative control, on outcomes at the cow and mammary quarter level. Before the onset of the study, 5,987 animals more than 12 mo old were randomly preassigned to 1 of 4 protocols in the event of gram-positive CM (except for Staphylococcus aureus and Trueperella pyogenes) during lactation: 3 infusions with 62.5 mg of amoxicillin performed 12 h apart (AMOX-L); 5 infusions once a day with 62.5 mg of amoxicillin (AMOX-EL); 5 infusions once a day with 125 mg of ceftiofur hydrochloride (CEFT-L); or negative control, no treatment performed until 5 d after diagnosis (NEG-CTR). Randomization was performed to preassign 90% of cows to one of the antibiotic protocols (30% in each group) and 10% to the negative control. A total of 696 quarter cases of CM met the inclusion criteria and were evaluated in the study. Quarter-level outcomes were assessed based on 5 milk samples collected up to 14 ± 3 d following enrollment (i.e., first day of treatment), whereas variables at the cow level [composite somatic cell count (SCC), milk production, and survival in the herd] were assessed up to 90 d after CM diagnosis. Streptococcus uberis, followed by Streptococcus dysgalactiae, were the main causes of gram-positive CM. Overall, clinical cure was higher for CEFT-L than for AMOX-EL, and no difference was observed between CEFT-L and AMOX-L. Likewise, no significant differences were detected on overall bacteriological cure, although some treatment effects were observed at the species level. Compared with antibiotic-treated groups, quarters assigned to NEG-CTR had higher counts of colony-forming units (cfu), 16S rRNA gene copy numbers, and Streptococcus relative abundance (RA) until d 5 after enrollment. Quarters treated with AMOX-L had higher cfu counts on d 5, 8, and 14 after enrollment compared with the other antibiotic protocols. In addition, the RA of Streptococcus spp. was higher on d 14 after enrollment for AMOX-treated quarters compared with the CEFT-L group. Linear score of SCC was higher for AMOX-treated cows than for CEFT-L in the first test day after CM. However, cows assigned to AMOX-L had higher milk production than those submitted to the AMOX-EL and CEFT-L protocols. In conclusion, the 2-d protocol with 3 intramammary infusions of amoxicillin (narrow-spectrum antimicrobial) had similar overall clinical and bacteriological cures as 5 administrations (once a day) with ceftiofur hydrochloride (wide spectrum). No significant difference was observed on CM recurrence and cow survival. However, quarters treated with 5-d protocols were more effective at reducing milk cfu counts than quarters in the AMOX-L protocol. In addition, lower Streptococcus spp. RA was observed in ceftiofur-treated quarters compared with the amoxicillin protocols at d 14 after CM diagnosis. Based on results of microbiome and bacterial load (quantitative PCR and cfu count) up to 5 d after CM diagnosis, antibiotic use remains an indispensable strategy for treatment of CM caused by gram-positive bacteria.

Flavonoid glycosides and their putative human metabolites as potential inhibitors of the SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp).

BACKGROUND: Since the World Health Organization (WHO) declared Coronavirus disease 2019 (COVID-19) to be a pandemic infection, important severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural proteins (nsp) have been analysed as promising targets in virtual screening approaches. Among these proteins, 3-chymotrypsin-like cysteine protease (3CLpro), also named main protease, and the RNA-dependent RNA polymerase (RdRp), have been identified as fundamental targets due to its importance in the viral replication stages. OBJECTIVES: To investigate, in silico, two of the most abundant flavonoid glycosides from Dysphania ambrosioides; a medicinal plant found in many regions of the world, along with some of the putative derivatives of these flavonoid glycosides in the human organism as potential inhibitors of the SARS-CoV-2 3CLpro and RdRp. METHODS: Using a molecular docking approach, the interactions and the binding affinity with SARS-CoV-2 3CLpro and RdRp were predicted for quercetin-3-O-rutinoside (rutin), kaempferol-3-O-rutinoside (nicotiflorin) and some of their glucuronide and sulfate derivatives. FINDINGS: Docking analysis, based on the crystal structure of 3CLpro and RdRp, indicated rutin, nicotiflorin, and their glucuronide and sulfate derivatives as potential inhibitors for both proteins. Also, the importance of the hydrogen bond and π-based interactions was evidenced for the presumed active sites. MAIN CONCLUSIONS: Overall, these results suggest that both flavonoid glycosides and their putative human metabolites can play a key role as inhibitors of the SARS-CoV-2 3CLpro and RdRp. Obviously, further researches, mainly in vitro and in vivo experiments, are necessary to certify the docking results reported here, as well as the adequate application of these substances. Furthermore, it is necessary to investigate the risks of D. ambrosioides as a phytomedicine for use against COVID-19.

Serological Evidence of Rickettsia Exposure among Patients with Unknown Fever Origin in Angola, 2016-2017.

Spotted fever group Rickettsia (SFGR) is one among the aetiologies that cause fever of unknown origin in Angola. Despite their occurrence, there is little information about its magnitude in this country either because it is misdiagnosed or due to the lack of diagnostic resources. For this purpose, eighty-seven selected malaria- and yellow fever-negative serum specimens collected between February 2016 and March 2017 as part of the National Laboratory of Febrile Syndromes, from patients with fever (≥37.5°C) for at least 4 days and of unknown origin, were screened for Rickettsia antibodies through an immunofluorescence assay (IFA). Serological results were interpreted according to the 2017 guidelines for the detection of Rickettsia spp. Three seroreactive patients had detectable IgM antibodies to Rickettsia with an endpoint titre of 32 and IgG antibodies with endpoint titres of 128 and 256. These findings supported a diagnosis of Rickettsia exposure amongst these patients and highlight that rickettsioses may be among the cause of unknown febrile syndromes in Angola. Therefore, physicians must be aware of this reality and must include this vector-borne disease as part of aetiologies that should be considered and systematically tested in order to delineate appropriate strategies of diagnostic and control of Rickettsia in Angola.

Photophysical and Theoretical Interpretation of the Insensitive Emission to Temperature of a Metallopolymer Containing Europium Ions.

The luminescence and thermochromic properties of a europium-containing metallopolymer were investigated in experimental and theoretical aspects using the same polymer backbone complexed with two different contents of europium ions (25 and 65% molar). The polymer presented an emission insensitive to temperature variation which was attributed to a balance between two factors: the first is the "stiffening effect" on the polymer backbone brought about by ion complexation, and the second is the interconnection of the alkyl chains because of the rotation of the bipyridine sites required for the complexation.

Genetic and environmental influences on human height from infancy through adulthood at different levels of parental education.

Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregate-level data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis.

Warm afterglow from the Toarcian Oceanic Anoxic Event drives the success of deep-adapted brachiopods.

Many aspects of the supposed hyperthermal Toarcian Oceanic Anoxic Event (T-OAE, Early Jurassic, c. 182 Ma) are well understood but a lack of robust palaeotemperature data severely limits reconstruction of the processes that drove the T-OAE and associated environmental and biotic changes. New oxygen isotope data from calcite shells of the benthic fauna suggest that bottom water temperatures in the western Tethys were elevated by c. 3.5 °C through the entire T-OAE. Modelling supports the idea that widespread marine anoxia was induced by a greenhouse-driven weathering pulse, and is compatible with the OAE duration being extended by limitation of the global silicate weathering flux. In the western Tethys Ocean, the later part of the T-OAE is characterized by abundant occurrences of the brachiopod Soaresirhynchia, which exhibits characteristics of slow-growing, deep sea brachiopods. The unlikely success of Soaresirhynchia in a hyperthermal event is attributed here to low metabolic rate, which put it at an advantage over other species from shallow epicontinental environments with higher metabolic demand.

Truly continuous low pH viral inactivation for biopharmaceutical process integration.

Continuous virus inactivation (VI) has received little attention in the efforts to realize fully continuous biomanufacturing in the future. Implementation of continuous VI must assure a specific minimum incubation time, typically 60 min. To guarantee the minimum incubation time, we implemented a packed bed continuous viral inactivation reactor (CVIR) with narrow residence time distribution (RTD) for low pH incubation. We show that the RTD does not broaden significantly over a wide range of linear flow velocities-which highlights the flexibility and robustness of the design. Prolonged exposure to acidic pH has no impact on bed stability, assuring constant RTD throughout long term operation. The suitability of the packed bed CVIR for low pH inactivation is shown with two industry-standard model viruses, that is xenotropic murine leukemia virus and pseudorabies virus. Controls at neutral pH showed no system-induced VI. At low pH, significant VI is observed, even after only 15 min. Based on the low pH inactivation kinetics, the continuous process is equivalent to traditional batch operation. This study establishes a concept for continuous low pH inactivation and, together with previous reports, highlights the versatility of the packed bed reactor for continuous VI, regardless of the inactivation method.

Muscle Mass and Muscle Strength Relationships to Balance: The Role of Age and Physical Activity.

OBJECTIVE: To investigate the relations of balance to muscle mass (MM) and muscle strength (MS), depending on age and physical activity, which is of particular importance to functional independence in older people. METHODS: This cross-sectional study included 802 volunteers (69.82 ± 5.60 years). The Fullerton Advanced Balance scale was used to assess balance and a composite score, including arm curl and chair stand tests for assessing MS. MM was estimated by dual-energy X-ray absorptiometry and physical activity by questionnaire. RESULTS: Greater MM (r = .26, p < .001) and MS (r = .53, p < .001) were positively correlated to balance. The old-old adults and less active individuals attained lower balance. Notably, moderation and subsequent simple slope analyses revealed that the relations of balance, MM, and MS were larger in less active and the old-old adults. CONCLUSIONS: The old-old and less active adults were more prone to muscle weakness and balance impairments. Tailored interventions should particularly consider these vulnerable groups.

A narrow residence time incubation reactor for continuous virus inactivation based on packed beds.

A narrow residence time distribution (RTD) is highly desirable for continuous processes where a strict incubation time must be ensured, such as continuous virus inactivation. A narrow RTD also results in faster startup and shut down phases and limits the broadening of potential disturbances in continuous processes. A packed bed reactor with non-porous inert beads was developed to achieve narrow RTDs. The performance was defined as the ratio between the onset of the cumulative RTD and the median residence time (tx%/t50%). Laboratory-scale packed columns were used to study the influence of the column parameters on the RTD. A larger column with a void volume of 0.65 L and a length of 89 cm, packed with beads in a size range of 125 to 250 µm, achieved t0.5%/t50% >0.93 across flow rates from 0.1 to 9.8 mL/min. The RTD was significantly narrower than the RTDs of other reactor designs, such as the Coiled Flow Inverter and Jig in a Box. The pressure drop remained under 3 kPa for all tested flow rates. Fluorescent nanoparticles (30 and 200 nm) were used to mimic viruses. These two sizes showed less than 2% difference in terms of t1%/t50% and t0.01%/t50% scores. These results indicated that viruses travelled through the column at rates independent of size. This proposal of packed beds as incubation chambers for continuous virus inactivation is simple, scalable, and can be realized as single-use devices. Due to the low pressure drop, the system can be easily integrated into a fully continuous process.

Flavonoid glycosides and their putative human metabolites as potential inhibitors of the SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp)

BACKGROUND Since the World Health Organization (WHO) declared Coronavirus disease 2019 (COVID-19) to be a pandemic infection, important severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural proteins (nsp) have been analysed as promising targets in virtual screening approaches. Among these proteins, 3-chymotrypsin-like cysteine protease (3CLpro), also named main protease, and the RNA-dependent RNA polymerase (RdRp), have been identified as fundamental targets due to its importance in the viral replication stages. OBJECTIVES To investigate, in silico, two of the most abundant flavonoid glycosides from Dysphania ambrosioides; a medicinal plant found in many regions of the world, along with some of the putative derivatives of these flavonoid glycosides in the human organism as potential inhibitors of the SARS-CoV-2 3CLpro and RdRp. METHODS Using a molecular docking approach, the interactions and the binding affinity with SARS-CoV-2 3CLpro and RdRp were predicted for quercetin-3-O-rutinoside (rutin), kaempferol-3-O-rutinoside (nicotiflorin) and some of their glucuronide and sulfate derivatives. FINDINGS Docking analysis, based on the crystal structure of 3CLpro and RdRp, indicated rutin, nicotiflorin, and their glucuronide and sulfate derivatives as potential inhibitors for both proteins. Also, the importance of the hydrogen bond and π-based interactions was evidenced for the presumed active sites. MAIN CONCLUSIONS Overall, these results suggest that both flavonoid glycosides and their putative human metabolites can play a key role as inhibitors of the SARS-CoV-2 3CLpro and RdRp. Obviously, further researches, mainly in vitro and in vivo experiments, are necessary to certify the docking results reported here, as well as the adequate application of these substances. Furthermore, it is necessary to investigate the risks of D. ambrosioides as a phytomedicine for use against COVID-19.