Airway wall extracellular matrix changes induced by bronchial thermoplasty in severe asthma.

BACKGROUND: Airway remodeling is a prominent feature of asthma, which involves increased airway smooth muscle mass and altered extracellular matrix composition. Bronchial thermoplasty (BT), a bronchoscopic treatment for severe asthma, targets airway remodeling. OBJECTIVE: We sought to investigate the effect of BT on extracellular matrix composition and its association with clinical outcomes. METHODS: This is a substudy of the TASMA trial. Thirty patients with severe asthma were BT-treated, of whom 13 patients were treated for 6 months with standard therapy (control group) before BT. Demographic data, clinical data including pulmonary function, and bronchial biopsies were collected. Biopsies at BT-treated and nontreated locations were analyzed by histological and immunohistochemical staining. Associations between histology and clinical outcomes were explored. RESULTS: Six months after treatment, it was found that the reticular basement membrane thickness was reduced from 7.28 µm to 5.74 µm (21% relative reduction) and the percentage area of tissue positive for collagen increased from 26.3% to 29.8% (13% relative increase). Collagen structure analysis revealed a reduction in the curvature frequency of fibers. The percentage area positive for fibulin-1 and fibronectin increased by 2.5% and 5.9%, respectively (relative increase of 124% and 15%). No changes were found for elastin. The changes in collagen and fibulin-1 negatively associated with changes in FEV1 reversibility. CONCLUSIONS: Besides reduction of airway smooth muscle mass, BT has an impact on reticular basement membrane thickness and the extracellular matrix arrangement characterized by an increase in tissue area occupied by collagen with a less dense fiber organization. Both collagen and fibulin-1 are negatively associated with the change in FEV1 reversibility.

Hidden in the sand: Phylogenomics unravel an unexpected evolutionary history for the desert-adapted vipers of the genus Cerastes.

The desert vipers of the genus Cerastes are a small clade of medically important venomous snakes within the family Viperidae. According to published morphological and molecular studies, the group is comprised by four species: two morphologically similar and phylogenetically sister taxa, the African horned viper (Cerastes cerastes) and the Arabian horned viper (Cerastes gasperettii); a more distantly related species, the Saharan sand viper (Cerastes vipera), and the enigmatic Böhme's sand viper (Cerastes boehmei), only known from a single specimen in captivity allegedly captured in Central Tunisia. In this study, we sequenced one mitochondrial marker (COI) as well as genome-wide data (ddRAD sequencing) from 28 and 41 samples, respectively, covering the entire distribution range of the genus to explore the population genomics, phylogenomic relationships and introgression patterns within the genus Cerastes. Additionally, and to provide insights into the mode of diversification of the group, we carried out niche overlap analyses considering climatic and habitat variables. Both nuclear phylogenomic reconstructions and population structure analyses have unveiled an unexpected evolutionary history for the genus Cerastes, which sharply contradicts the morphological similarities and previously published mitochondrial approaches. Cerastes cerastes and C. vipera are recovered as sister taxa whilst C. gasperettii is a sister taxon to the clade formed by these two species. We found a relatively high niche overlap (OI > 0.7) in both climatic and habitat variables between C. cerastes and C. vipera, contradicting a potential scenario of sympatric speciation. These results are in line with the introgression found between the northwestern African populations of C. cerastes and C. vipera. Finally, our genomic data confirms the existence of a lineage of C. cerastes in Arabia. All these results highlight the importance of genome-wide data over few genetic markers to study the evolutionary history of species.

Global mercury concentrations in biota: their use as a basis for a global biomonitoring framework.

An important provision of the Minamata Convention on Mercury is to monitor and evaluate the effectiveness of the adopted measures and its implementation. Here, we describe for the first time currently available biotic mercury (Hg) data on a global scale to improve the understanding of global efforts to reduce the impact of Hg pollution on people and the environment. Data from the peer-reviewed literature were compiled in the Global Biotic Mercury Synthesis (GBMS) database (>550,000 data points). These data provide a foundation for establishing a biomonitoring framework needed to track Hg concentrations in biota globally. We describe Hg exposure in the taxa identified by the Minamata Convention: fish, sea turtles, birds, and marine mammals. Based on the GBMS database, Hg concentrations are presented at relevant geographic scales for continents and oceanic basins. We identify some effective regional templates for monitoring methylmercury (MeHg) availability in the environment, but overall illustrate that there is a general lack of regional biomonitoring initiatives around the world, especially in Africa, Australia, Indo-Pacific, Middle East, and South Atlantic and Pacific Oceans. Temporal trend data for Hg in biota are generally limited. Ecologically sensitive sites (where biota have above average MeHg tissue concentrations) have been identified throughout the world. Efforts to model and quantify ecosystem sensitivity locally, regionally, and globally could help establish effective and efficient biomonitoring programs. We present a framework for a global Hg biomonitoring network that includes a three-step continental and oceanic approach to integrate existing biomonitoring efforts and prioritize filling regional data gaps linked with key Hg sources. We describe a standardized approach that builds on an evidence-based evaluation to assess the Minamata Convention's progress to reduce the impact of global Hg pollution on people and the environment.

Mercury Concentrations in Two Populations of the most Endangered Dolphin (Pontoporia blainvillei) from the Southwestern Atlantic Ocean.

Mercury contamination has been aggravated by emerging environmental issues, such as climate change. Top predators present concerning Hg concentrations once this metal bioaccumulates and biomagnifies. This study evaluated total mercury (THg) concentrations in tissues of 43 franciscanas (Pontoporia blainvillei) from two populations: the Franciscana Management Area (FMA) IIb and FMA IIIa. Animals from FMA IIIa showed mean concentration 5-times and 2.5-times higher in the liver and kidney (4.73 ± 6.84 and 0.52 ± 0.51 µg.g-1, w.w., respectively) than individuals from FMA IIb (0.89 ± 1.04 and 0.22 ± 0.15 µg.g-1, w.w., respectively). This might be due to: (I) individuals sampled from FMA IIIa being larger and older, and/or (II) the area near FMA IIIa presents environmental features leading to higher THg availability. Coastal contamination can affect franciscanas' health and population maintenance at different levels depending on their life history and, therefore, it should be considered to guide specific conservation actions.

Modified Oblique Lobenhoffer (MOL) approach for posterolateral and posteromedial column access in tibial plateau fractures: a detailed cadaveric anatomical study.

BACKGROUND: Tibial plateau fractures involving posteromedial (PM) and posterolateral (PL) columns are complex injuries that require an appropriate approach. The management of the PL column in these cases can be controversial, and limitations using deep posteromedial interval approaches have been referenced. In this paper, a modification of the Lobenhoffer approach, designed to optimize the access to the PL column, is described in detail. The aim of this study was to assess the feasibility of this approach in a cadaveric anatomical study. MATERIALS AND METHODS: In total, five fresh-frozen cadaveric specimens were used for detailed anatomical study surrounding the approach. Relationships with cutaneous and deep neurovascular structures were evaluated. The exposure area of the PL and PM columns using this approach was assessed. RESULTS: The cadaveric study showed safe and adequate exposure. Oblique skin and fascia incision just medial to the posterior midline was safe to protect the medial sural cutaneous nerve and the small saphenous vein. Elevation of the popliteus and tibialis posterior muscles offered safe protection of the anterior tibial artery and popliteal neurovascular bundle during retractor placement. Adequate full proximal exposure of the PM and PL columns, including the posterolateral lateral (PLL) and posterolateral central (PLC) segments, was obtained in all specimens. CONCLUSIONS: The Modified Oblique Lobenhoffer (MOL) approach can be a feasible option to access PL and PM columns in tibial plateau fractures. LEVEL OF EVIDENCE: IV.

The staphylococcal inhibitory protein SPIN binds to human myeloperoxidase with picomolar affinity but only dampens halide oxidation.

The heme enzyme myeloperoxidase (MPO) is one of the key players in the neutrophil-mediated killing of invading pathogens as part of the innate immune system. MPO generates antimicrobial oxidants, which indiscriminately and effectively kill phagocytosed pathogens. Staphylococcus aureus, however, is able to escape this fate, in part by secreting a small protein called SPIN (Staphylococcal Peroxidase Inhibitor), which specifically targets and inhibits MPO in a structurally complex manner. Here, we present the first crystal structures of the complex of SPIN-aureus and a truncated version (SPIN-truncated) with mature dimeric leukocyte MPO. We unravel the contributions of the two domains to the kinetics and thermodynamics of SPIN-aureus binding to MPO by using a broad array of complementary biochemical and biophysical methods. The C-terminal "recognition" domain is shown to mediate specific binding to MPO, while interaction of the N-terminal "inhibitory" domain is guided mainly by hydrophobic effects and thus is less sequence dependent. We found that inhibition of MPO is achieved by reducing substrate migration, but SPIN-aureus cannot completely block MPO activity. Its' effectiveness is inversely related to substrate size, with no discernible dependence on other factors. Thus, SPIN-aureus is an extremely high-affinity inhibitor and highly efficient for substrates larger than halogens. As aberrant MPO activity is implicated in a number of chronic inflammatory diseases, SPIN-aureus is the first promising protein inhibitor for specific inhibition of human MPO.

Unraveling phylogenetic relationships and species boundaries in the arid adapted Gerbillus rodents (Muridae: Gerbillinae) by RAD-seq data.

Gerbillus is one of the most speciose genera among rodents, with ca. 51 recognized species. Previous attempts to reconstruct the evolutionary history of Gerbillus mainly relied on the mitochondrial cyt-b marker as a source of phylogenetic information. In this study, we utilize RAD-seq genomic data from 37 specimens representing 11 species to reconstruct the phylogenetic tree for Gerbillus, applying concatenation and coalescence methods. We identified four highly supported clades corresponding to the traditionally recognized subgenera: Dipodillus, Gerbillus, Hendecapleura and Monodia. Only two uncertain branches were detected in the resulting trees, with one leading to diversification of the main lineages in the genus, recognized by quartet sampling analysis as uncertain due to possible introgression. We also examined species boundaries for four pairs of sister taxa, including potentially new species from Morocco, using SNAPP. The results strongly supported a speciation model in which all taxa are treated as separate species. The dating analyses confirmed the Plio-Pleistocene diversification of the genus, with the uncertain branch coinciding with the beginning of aridification of the Sahara at the the Plio-Pleistocene boundary. This study aligns well with the earlier analyses based on the cyt-b marker, reaffirming its suitability as an adequate marker for estimating genetic diversity in Gerbillus.

COVID-19 induces more pronounced extracellular matrix deposition than other causes of ARDS.

BACKGROUND: Lung fibrosis is a major concern in severe COVID-19 patients undergoing mechanical ventilation (MV). Lung fibrosis frequency in post-COVID syndrome is highly variable and even if the risk is proportionally small, many patients could be affected. However, there is still no data on lung extracellular matrix (ECM) composition in severe COVID-19 and whether it is different from other aetiologies of ARDS. METHODS: We have quantified different ECM elements and TGF-ß expression in lung tissue of 28 fatal COVID-19 cases and compared to 27 patients that died of other causes of ARDS, divided according to MV duration (up to six days or seven days or more). In COVID-19 cases, ECM elements were correlated with lung transcriptomics and cytokines profile. RESULTS: We observed that COVID-19 cases presented significant increased deposition of collagen, fibronectin, versican, and TGF-ß, and decreased decorin density when compared to non-COVID-19 cases of similar MV duration. TGF-ß was precociously increased in COVID-19 patients with MV duration up to six days. Lung collagen was higher in women with COVID-19, with a transition of upregulated genes related to fibrillogenesis to collagen production and ECM disassembly along the MV course. CONCLUSIONS: Fatal COVID-19 is associated with an early TGF-ß expression lung environment after the MV onset, followed by a disordered ECM assembly. This uncontrolled process resulted in a prominent collagen deposition when compared to other causes of ARDS. Our data provides pathological substrates to better understand the high prevalence of pulmonary abnormalities in patients surviving COVID-19.

Fish chorus variation in a tropical estuarine environmenta).

Fish choruses are still understudied in the Southwestern Atlantic Ocean. Temporal and spatial variation of fish choruses at two sites inside Guanabara Bay were investigated between 2021 and 2022; one sampling site was in a Marine Protected Area (MPA), and the other was in a rocky environment closer to vessel trafficking areas. Acoustic recordings were performed on 17 sampling occasions of 24 h, coupled to a temperature data logger. Long-term spectral averages were employed to determine choruses' start, end, and peak times, and third-octave levels were used to characterize spectral characteristics. Fish sounds were also analyzed and investigated with a principal components analysis. Choruses in the MPA lasted, on average, 4.5 h and had a peak frequency of 547.2 ± 226.6 kHz with a peak level of 104.6 ± 8.7 dB re 1 µPa. In contrast, the rocky site choruses lasted 5.5 h on average and had a peak frequency of 371.7 ± 131.0 Hz with a peak level of 113.4 ± 4.0 dB re 1 µPa. Chorus peak frequency was positively correlated to temperature (r = 0.4). Different types of fish sounds were identified, with some acoustics parameters varying between sites. Results indicate more than one chorusing species that may react to different factors.

Simultaneous Estimation of Azimuth and Elevation Angles Using a Decision Tree-Based Method.

This study addresses the problem of accurately predicting azimuth and elevation angles of signals impinging on an antenna array employing Machine Learning (ML). Using the information obtained at a receiving system when a transmitter's signal hits it, a Decision Tree (DT) model is trained to estimate azimuth and elevation angles simultaneously. Simulation results demonstrate the robustness of the proposed DT-based method, showcasing its ability to predict the Direction of Arrival (DOA) in diverse conditions beyond the ones present in the training dataset, i.e., the results display the model's generalization capability. Additionally, the comparative analysis reveals that DT-based DOA estimation outperforms the state-of-the-art MUltiple SIgnal Classification (MUSIC) algorithm. Our results demonstrate an average reduction of over 90% in the prediction error and 50% in the prediction time achieved by our proposal when compared to the MUSIC algorithm. These results establish DTs as competitive alternatives for DOA estimation in signal reception systems.

Densified biochar capsules as an alternative to conventional seedings.

The application of biochar in soil provides various benefits that can vary in intensity as the pyrolysis temperature increases. However, its low density makes this material easily transportable and prone to being removed from the system. The objective of this study was to investigate the pyrolysis temperatures and compression pressure of densified biochar carrier capsules on the physiological quality of Schizolobium parahyba var. amazonicum seeds. Produced at three final pyrolysis temperatures (300, 600, and 900 °C), the biochar was characterized through bulk and true density analyses, immediate composition, pH, electrical conductivity, cation exchange capacity, water-soluble carbon, characterization of organic structures by FTIR, and PAH analysis. Subsequently, the biochar was compacted by briquetting at two compression pressures (50 and 200 psi) with one seed per capsule, and germination, emergence, and quality of generated seedlings were evaluated. After verifying residue normality and variance homogeneity, analysis of variance was conducted following a completely randomized design in a 3 × 2 factorial arrangement, with four replications per treatment and two additional control treatments. Upon identifying significant differences, regression model adjustments were performed. Cluster-based multivariate analysis was used to identify similarities among the studied treatments, both for capsules and controls. Pyrolysis temperature and compression pressure influenced seed germination, emergence, and initial seedling growth. Lower pressure favored shoot development, while higher pressure favored root development and generated seedlings of higher quality. The benefits of biochar to soil, combined with the implementation of seeds, make the production of densified biochar capsules an alternative to conventional seedings, potentially reducing high energy and financial costs and enabling the recovery of degraded areas, even in difficult-to-access regions.

Bronchial eosinophils, neutrophils, and CD8 + T cells influence asthma control and lung function in schoolchildren and adolescents with severe treatment-resistant asthma.

BACKGROUND: Studies in adult severe treatment-resistant asthma (STRA) have demonstrated heterogeneous pathophysiology. Studies in the pediatric age group are still scarce, and few include bronchial tissue analysis. OBJECTIVE: We investigated 6-18-year-old patients diagnosed with STRA in Sao Paulo, Brazil, by characterizing the different lung compartments and their correlations with asthma control and lung function. METHODS: Inflammatory profiles of 13 patients with a confirmed diagnosis of STRA were analyzed using blood, induced sputum, bronchoalveolar lavage, viral and bacterial screens and endobronchial biopsy. Inflammatory cells, cytokines, and basement membrane thickening were tested for correlations with the asthma control test (ACT) and spirometry and plethysmography parameters. RESULTS: Endobronchial biopsy specimens from 11 patients were viable for analysis. All biopsies showed eosinophilic infiltration. Submucosal (SM) eosinophils and neutrophils were correlated with worse lung function (pre-BD FEV1), and SM neutrophils were correlated with fixed obstruction (post-BD FEV1). Intraepithelial (IE) neutrophils were positively correlated with lung function (pre-BD sGaw). CD8 + T cells had the highest density in the IE and SM layers and were positively correlated with ACT and negatively correlated with the cytokines IL1ß, IL2, IL5, IL7, IL10, IL12, IL17, GCSF, MCP-1, INF-δ, and TNFα in sputum supernatant. The ASM chymase + mast cell density correlated positively with quality-of-life score (pAQLQ) and ACT. CONCLUSION: Eosinophils and SM neutrophils correlated with worse lung function, while IE neutrophils correlated with better lung function. Most importantly, CD8 + T cells were abundant in bronchial biopsies of STRA patients and showed protective associations, as did chymase + mast cells.

Predictors of Pornography Use: Difficulties in Emotion Regulation and Loneliness.

BACKGROUND: Pleasure-seeking reasons are the main drivers of pornography use (PU), but the regulation of unpleasant states, namely distraction from or suppression of negative emotions and stress relief, are other potential predictors of this behavior. AIM: Our main objective is to develop an explanatory model of problematic PU, assessing difficulties in emotion regulation, loneliness, perceived stress, as well as age and gender as predictors. METHODS: A cross-sectional study was conducted that included a total of 340 participants (M = 28.50 years, SD = 10.32). Self-report inventories were administered that measured problematic PU (PPCS), difficulties in emotion regulation (DERS-SF), loneliness (UCLALS-3), and perceived stress (PSS-10). RESULTS: The findings were indicative of recreational PU, with only a small number of participants (4.6%) reporting a possible problematic PU. There were statistically significant gender differences (F(1,337) = 33.306, P ≤ .001), namely that men were more likely to report problematic PU (M = 36.03, SD = 21.30) than women (M = 25.32, SD = 9.24). Problematic PU was significantly and positively correlated either with difficulties in emotion regulation, loneliness, perceived stress and age. Stepwise multiple linear regression analysis showed that difficulties in emotion regulation (ß = 0.259, P ≤ .001), loneliness (ß = 0.209, P = .001), and gender (ß = -0.377, P ≤ .001) define the best subset of predictors of problematic PU. Age and perceived stress were not selected as predictors in this subset. CLINICAL TRANSLATION: The promotion of better emotion regulation abilities and strategies for adaptive coping with loneliness must be taken into consideration, namely in cases of problematic PU or compulsive sexual behavior disorder. STRENGTHS & LIMITATIONS: Being a cross-sectional study with a convenience sample and the fact that these variables explain only a part of the explained variance of the problematic PU are the main limitations. Despite the limitations, the principal contribution of this study is the understanding that gender, difficulties in emotion regulation, and loneliness remain as main predictors of problematic PU, even when combined in the explanatory model. CONCLUSION: The current study provides a better understanding of the predictors of problematic PU related with the reduction or avoidance of unpleasant states. Emotion regulation, loneliness, and perceived stress, studied simultaneously, provide a better understanding of the complex relationships between these factors and problematic PU. Difficulties in emotion regulation and loneliness are predictors of higher problematic PU, as well as the expected gender effect. Cardoso J, Ramos C, Brito J, et al. Predictors of Pornography Use: Difficulties in Emotion Regulation and Loneliness. J Sex Med 2022;19:620-628.

Allergic sensitization and exposure to ambient air pollution beginning early in life lead to a COPD-like phenotype in young adult mice.

The perinatal period and early infancy are considered critical periods for lung development. During this period, adversities such as environmental exposures, allergic sensitization, and asthma are believed to impact lung health in adulthood. Therefore, we hypothesized that concomitant exposure to allergic sensitization and urban-derived fine particulate matter (PM2.5) in the early postnatal period of mice would cause more profound alterations in lung alveolarization and growth and differently modulate lung inflammation and gene expression than either insult alone in adult life. BALB/c mice were sensitized with ovalbumin (OVA) and exposed to PM2.5 from the fifth day of life. Then, we assessed lung responsiveness, inflammation in BALF, lung tissue, and alveolarization by stereology. In addition, we performed a transcriptomic analysis of lung tissue on the 40th day of life. Our results showed that young adult mice submitted to allergic sensitization and exposure to ambient PM2.5 since early life presented decreased lung growth with impaired alveolarization, a mixed neutrophilic-eosinophilic pattern of lung inflammation, increased airway responsiveness, and increased expression of genes linked to neutrophil recruitment when compared to animals that were OVA-sensitized or PM2.5 exposed only. Both, early life allergic sensitization and PM2.5 exposure, induced inflammation and impaired lung growth, but concomitant exposure was associated with worsened inflammation parameters and caused alveolar enlargement. Our experimental data provide pathological support for the hypothesis that allergic or environmental insults in early life have permanent adverse consequences for lung growth. In addition, combined insults were associated with the development of a COPD-like phenotype in young adult mice. Together with our data, current evidence points to the urgent need for healthier environments with fewer childhood disadvantage factors during the critical windows of lung development and growth.

Systematics, biogeography and evolution of the Saharo-Arabian naked-toed geckos genus Tropiocolotes.

Plate tectonics constitute one of the main mechanisms of biological diversification on Earth, often being associated with cladogenetic events at different phylogenetic levels, as well as with exchange of faunas and floras across previously isolated biogeographic regions. North Africa and Arabia share a complex geological history that dates back to the break-up of the Arabian plate from the African plate ~30-25 Mya, followed by various geological events, such as the formation of the Red Sea or the connection between the African, Arabian and Eurasian plates. Species with Saharo-Arabian distributions have shown a close association between their evolutionary history and these geological events. In this study, we investigate the systematics, biogeography and evolution of the genus Tropiocolotes, a group of small ground-dwelling geckos, comprised by 12 species distributed from the Atlantic coast of North Africa to southwestern Iran. Species delimitation analyses uncovered the existence of high levels of undescribed diversity, with forms here considered at the species level including Tropiocolotes tripolitanus (Mauritania and southern Morocco), T. nattereri (southern Israel) and T. scorteccii (Yemen and Oman). Phylogenetic and biogeographic analyses recovered two main clades, an exclusively African clade and a Saharo-Arabian clade, that split ~25 Mya following the vicariant event mediated by the separation of the Arabian and African plates. The complex geological activity around the Red Sea is associated with the diversification within the Saharo-Arabian clade, including the colonization of North Africa from a second Tropiocolotes group. Results also provide new insights into the geographic distribution of Tropiocolotes nubicus, previously considered as exclusively associated to the Nile River valley, extending its known distribution further west, up to the Central Mountains of the Sahara. Accordingly, the Nile River seems to act as a major biogeographic barrier, separating Tropiocolotes nubicus and T. steudneri in their western and eastern margins, respectively.

Tracking the time course of pathological patterns of lung injury in severe COVID-19.

BACKGROUND: Pulmonary involvement in COVID-19 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis, leading to the clinical picture of Acute Respiratory Distress Syndrome. The direct action of SARS-CoV-2 in lung cells and the dysregulated immuno-coagulative pathways activated in ARDS influence pulmonary involvement in severe COVID, that might be modulated by disease duration and individual factors. In this study we assessed the proportions of different lung pathology patterns in severe COVID-19 patients along the disease evolution and individual characteristics. METHODS: We analysed lung tissue from 41 COVID-19 patients that died in the period March-June 2020 and were submitted to a minimally invasive autopsy. Eight pulmonary regions were sampled. Pulmonary pathologists analysed the H&E stained slides, performing semiquantitative scores on the following parameters: exudative, intermediate or advanced DAD, bronchopneumonia, alveolar haemorrhage, infarct (%), arteriolar (number) or capillary thrombosis (yes/no). Histopathological data were correlated with demographic-clinical variables and periods of symptoms-hospital stay. RESULTS: Patient´s age varied from 22 to 88 years (18f/23 m), with hospital admission varying from 0 to 40 days. All patients had different proportions of DAD in their biopsies. Ninety percent of the patients presented pulmonary microthrombosis. The proportion of exudative DAD was higher in the period 0-8 days of hospital admission till death, whereas advanced DAD was higher after 17 days of hospital admission. In the group of patients that died within eight days of hospital admission, elderly patients had less proportion of the exudative pattern and increased proportions of the intermediate patterns. Obese patients had lower proportion of advanced DAD pattern in their biopsies, and lower than patients with overweight. Clustering analysis showed that patterns of vascular lesions (microthrombosis, infarction) clustered together, but not the other patterns. The vascular pattern was not influenced by demographic or clinical parameters, including time of disease progression. CONCLUSION: Patients with severe COVID-19 present different proportions of DAD patterns over time, with advanced DAD being more prevalent after 17 days, which seems to be influenced by age and weight. Vascular involvement is present in a large proportion of patients, occurs early in disease progression, and does not change over time.

Long-Term Consequences of High Polychlorinated Biphenyl Exposure: Projected Decline of Delphinid Populations in a Hotspot for Chemical Pollution.

Rough-toothed dolphins, Steno bredanensis, are closely associated with coastal waters in the Southwestern Atlantic Ocean, increasing the exposure to multiple stressors, such as chemical pollution. Persistent organic pollutants (POPs) are known to affect the health of cetacean species. To comprehend the potential impacts of POPs on populations' viability, it is necessary to distinguish populations and predict their risk of long-term exposure. Blubbers of rough-toothed dolphins (n = 28) collected along the southeastern (SE) and southern (S) Brazilian coast were screened for polychlorinated biphenyls (PCBs) and pesticides in a gas chromatograph coupled to a mass spectrometer. Based on the contamination profile, a discriminant function analysis separated the rough-toothed dolphins into three ecological populations: two coastal and one offshore. POP concentrations were the highest reported for the species worldwide and highest among the delphinids in Brazilian waters, reaching 647.9 µg g-1 lw for PCBs. The SE population presented 212.9 ± 163.0, S population presented 101.0 ± 96.7, and OCS/S population presented 183.3 ± 85.3 µg g-1 lw (mean ± SD) of PCBs. The potential risk of effects triggered by elevated PCB concentrations was assessed in an individual-based model. A risk of severe decline in population size is projected for the three populations in the next 100 years, especially in SE Brazil, varying between 67 and 99%.

A scalable insect cell-based production process of the human recombinant BMX for in-vitro covalent ligand high-throughput screening.

Bone Marrow Tyrosine kinase in the chromosome X (BMX) is a TEC family kinase associated with numerous pathological pathways in cancer cells. Covalent inhibition of BMX activity holds promise as a therapeutic approach against cancer. To screen for potent and selective covalent BMX inhibitors, large quantities of highly pure BMX are normally required which is challenging with the currently available production and purification processes. Here, we developed a scalable production process for the human recombinant BMX (hrBMX) using the insect cell-baculovirus expression vector system. Comparable expression levels were obtained in small-scale shake flasks (13 mL) and in stirred-tank bioreactors (STB, 5 L). A two-step chromatographic-based process was implemented, reducing purification times by 75% when compared to traditional processes, while maintaining hrBMX stability. The final production yield was 24 mg of purified hrBMX per litter of cell culture, with a purity of > 99%. Product quality was assessed and confirmed through a series of biochemical and biophysical assays, including circular dichroism and dynamic light scattering. Overall, the platform herein developed was capable of generating 100 mg purified hrBMX from 5 L STB in just 34 days, thus having the potential to assist in-vitro covalent ligand high-throughput screening for BMX activity inhibition.

Periprosthetic Hip Fractures With a Loose Stem: Open Reduction and Internal Fixation Versus Stem Revision.

BACKGROUND: It is recommended revision for periprosthetic hip fractures (PPHF) with a loose stem. However, several authors have argued that under certain conditions, this fracture could be treated using osteosynthesis. The aim is to compare stem revision versus internal fixation in the treatment of PPHF with a loose stem. METHODS: All patients with PPHF with a loose stem treated by osteosynthesis and stem revision between January 2009 and January 2019 were included. We assessed hospital stay, American Society of Anesthesiologists, Charlson comorbidity index, surgery time, blood transfusion, complications, reoperation rate, first-year mortality, radiological, and functional results. RESULTS: A total of 57 patients were included (40 osteosyntheses and 17 stem revision), with an average follow-up time of 3.1 years. Their mean age was 78.47 years (R 45-92). In the osteosynthesis group, fewer patients required blood transfusion (32.5% vs. 70.6%), surgical times were shorter (108 minutes vs. 169 minutes), and the cost was lower, both in terms of total cost (€14,239.07 vs. €21,498.45 and operating room cost (€5014.63 vs. €8203.34). No significant differences were found between the groups in terms of complications, reoperation rate, or functional outcomes. CONCLUSION: Compared with stem revision, osteosynthesis requires less surgery time, has a lower need for blood transfusions, and a reduced hospital cost. Stem revision remains the treatment of choice in PPHF with a loose stem, but in V-B2 fractures in elderly patients with low functional demand, high anesthetic risk (American Society of Anesthesiologists ≥3), and many comorbidities (Charlson comorbidity index ≥5) in whom anatomic reconstruction is possible, osteosynthesis can be a viable option. EVIDENCE LEVEL: Historical cohorts. Level III.

"Safe incision" in calcaneal sliding osteotomies reduces the incidence of sural nerve injury.

PURPOSE: The purpose of this study was to demonstrate whether application of the so-called safe incision when performing calcaneal sliding osteotomies reduces the risk of sural nerve injury. METHODS: Patients who underwent either medial or lateral sliding calcaneal osteotomies between 2010 and 2018 were analysed retrospectively. A thorough neurological examination was performed, and the location of the surgical wound and the type of wound closure were recorded. The European Foot and Ankle Surgery (EFAS) score and 12-item Short Form Survey (SF-12) were also documented. RESULTS: A total of 57 patients were included, of which 20 (35.1%) had a sural nerve injury. Five patients had a neurapraxia (8.8%), while 15 patients had a permanent injury (26.3%). Respecting the "safe incision" decreased sural nerve injury (p = 0.02). The type of osteotomy and closure was not significant. No significant differences were found in the functional tests between the different techniques, or between patients who presented sural nerve injury and those who did not. CONCLUSION: Sural nerve injury after calcaneal sliding osteotomies is higher than previously reported in the scientific literature, with an incidence of 35.1% (20/57 patients). Respecting the so-called safe zone (oblique incision that runs through the point that is > 1/3 of the distance from the tip of the lateral malleolus to the posteroinferior margin of the calcaneus) clearly decreases the incidence of sural nerve injury. Finally, the majority of patients remained asymptomatic despite the neurological injury.