Discovery and structure-activity relationship of Morita-Baylis-Hillman adducts as larvicides against dengue mosquito vector, Aedes aegypti (Diptera: Culicidae).

Neglected tropical diseases (NTDs) have become a significant public health problem worldwide, notably the life-threatening dengue hemorrhagic fever borne by the Aedes aegypti mosquito. Thus, mosquito vector control measures remain essential in public health vector surveillance and control to combat Aedes-borne infections. Therefore, a series of MBH adducts were synthesized and assessed towards the fourth instar mosquito larvae, Aedes aegypti, along with the preliminary structure-activity relationship (SAR). Noteworthy, this compound class might be synthetized by an efficient eco-friendly synthesismethod and a rapid route for the synthesis of commercial larvicide through a single synthetic step. The bioassays showed that this compound class is a promising larvicide to control Aedes aegypti mosquito larvae, mainly 3g, with an LC50 of 41.35 µg/mL, which was higher than evaluated positive controls. Nevertheless, it is a viable larvicidalhit candidate for further hit-to-leadproperties optimization of its biphenyl backbone scaffold with enhanced insecticidalbioactivity. Moreover, scanning electron microscopy analysis suggested a disruption of the osmoregulatory/ionoregulatory functions by the complete deterioration of the terminal exoskeleton hindgut and anal papillae. Therefore, this new study shows the larvicidal efficacy of the tested compounds against the Aedes aegypti larvae.

3D gravity modelling of areas under the aptian lakes in the Jatobá basin and Tucano Norte sub-basin - Negra and Tonã hills.

Due to structural similarities and the possibility of connection between the two Aptian paleolakes in the Jatobá Basin and the Tucano Norte Sub-basin in North-eastern Brazil, the influence of the architecture of the crystalline basement under these lacustrine sedimentary rocks was analysed using gravimetric data near the faulted edges of the basins where the paleolakes are located. The Negra (Jatobá Basin) and Tonã (Tucano Norte Sub-basin) Hills are mainly sedimentary deposits of Aptian age and are linked to the post-rift I tectonic sequence. Aiming at the study of reservoirs analogous to pre-salt reservoirs, the gravimetric data were processed and interpreted to define the structural framework of the basin regions around these hills. Depth maps and density models were generated that could be analysed from various 3D perspectives, and the behaviour of the crystalline basement below these sedimentary sequences was investigated. In addition to the identification of horsts and semi-grabens that influenced the current relief pattern, the modelling showed that the Aptian paleolake sedimentary rocks of the Negra Hill are in the Ibimirim Low, which is approximately 2,900 m deep, while in the Tonã Hill, the sedimentary rocks are in the Salgado do Melão Low, which is approximately 5,100 m deep.

Minimally Invasive Ways to Monitor Changes in Cardiocirculatory Fitness in Running-based Sports: A Systematic Review.

This systematic review provides a synthesis of research investigating submaximal protocols to monitor changes in cardiocirculatory fitness in running-based sports. Following PRISMA guidelines, 2,452 records were identified and 14 studies, representing 515 athletes, satisfied the eligibility criteria. While most studies found large associations between changes in heart rate at standardized, submaximal running speeds and changes in aerobic fitness (r=0.51-0.88), three studies failed to establish a relationship (r=0.19-0.35). The intensity of the submaximal protocols seems to be relevant, with changes in running speeds at 90% of maximal heart rate showing larger relationships with changes in aerobic fitness (r=0.52-0.79) compared to 70% of maximal heart rate (r=0.24-0.52). Conversely, changes in post-exercise heart rate variability were very largely associated with changes in aerobic fitness when the testing protocols were less intense (70% of maximal heart rate) (r=0.76-0.88), but not when the test required participants to achieve 90% of their maximal heart rate (r=-0.02-0.06). Studies on post-exercise heart rate recovery revealed inconclusive results (r=-0.01- -0.55), while rate of heart rate increase may be a promising athlete monitoring metric (r=0.08- -0.84) but requires further research. In summary, when executed, analyzed, and interpreted appropriately, submaximal protocols can provide valuable information regarding changes in athlete cardiocirculatory fitness.

Validity and reproducibility of match-derived ratios of selected external and internal load parameters in soccer players: A simple way to monitor physical fitness?

The study aim was to assess whether match-derived external-to-internal load ratios are a valid and reliable tool to measure physical fitness. Sixteen elite youth soccer players (17 ± 1 years) performed two maximal fitness tests. Subsequently, players participated in three intra-squad soccer matches in three consecutive weeks. Three GPS-based parameters of external load (total distance, PlayerLoad, high-intensity distance) were divided by three heart rate-based parameters of internal load (iTRIMP, Banister TRIMP, average percentage heart rate reserve) for the ratio calculations. Validity was established by comparing the ratios with results of the fitness tests, while between-athlete and within-athlete reliability were quantified. Most integrated load ratios were moderately-to-largely correlated with the various fitness parameters. Overall, a ratio consisting of PlayerLoad and average percentage heart rate reserve demonstrated the most consistent correlations with maximum treadmill speed (r = 0.69, P = 0.003) and the speeds associated with 4 mmol/L of blood lactate (r = 0.56, P = 0.024) and 80% of heart rate reserve (r = 0.54, P = 0.031). Most of the ratios displayed acceptable levels of reproducibility (intraclass correlation coefficient > 0.8 and coefficient of variation < 10%), with the minimal detectable change of all ratios ranging between 7.1 and 37.8%. Given their associations with physical fitness and non-invasive nature, certain external-to-internal load ratios may be used to monitor physical fitness in soccer players. However, the ratios may not be sensitive enough to detect small yet practically relevant alterations in player fitness.

Synthesis of Esters Containing Cinnamoyl Motif with Potential Larvicide Action: A Computational, Ecotoxicity and in Vitro Cytotoxicity Assessments.

An increasing morbidity and mortality rate has been related to arboviruses transmitted by Aedes aegypti. Compounds with cinnamoyl moiety represent an alternative against mosquitos, considering their larvicidal activity. This study aimed to assess the larvicidal activity of cinnamic ester derivates against Aedes aegypti larvae, along with evaluating their toxicity effect to assess its safety as a larvicide. Ethyl cinnamate demonstrated larvicidal activity (LC50 =48.59 µg/mL). Morphological changes in larvae were detected, as a degenerative response in the thorax. Through molecular docking, the molecular binding mode between 3b, 3c, and acetylcholinesterase showed strong hydrogen bond interactions. Preliminary in vitro cell viability revealed the non-cytotoxicity of 3c. Ecotoxicity results indicated a sensitivity of Artemia salina to cinnamic esters. The phytotoxicity bioassays show potential for cinnamic compounds to enhance germination and root development. These findings suggest that compound 3c is more suitable as a larvicide since it demonstrated low toxicity.

A New Portable Device to Reliably Measure Maximal Strength and Rate of Force Development of Hip Adduction and Abduction.

ABSTRACT: Gonçalves, BM, Mesquita, RNO, Tavares, F, Brito, J, Correia, P, Santos, P, and Mil-Homens, P. A new portable device to reliably measure maximal strength and rate of force development of hip adduction and abduction. J Strength Cond Res 36(9): 2465-2471, 2022-Groin injuries are a major issue in sports involving kicking or quick changes of direction. Decreased hip adduction and abduction strength have been indicated as one of the main risk factors for groin injury. The methods currently available to measure hip adduction and abduction strength are reliable but highly dependent on the evaluator skills. Furthermore, several studies have reported the reliability of maximal strength (MVIC), but very few studies investigated the reliability of explosive strength (RFD), a parameter that has been previously shown to have a higher functional value. The aim of the current investigation was to assess the reliability of a user-independent portable dynamometer that concurrently measures MVIC and RFD. Twenty-five healthy young subjects performed maximal isometric hip adduction and abduction in both sitting and supine positions. Measurements occurred in 2 different days separated by 48-72 hours. Test-retest reliability was calculated for both MVIC and RFD. Both MVIC and RFD showed good relative reliability (intraclass correlation coefficient = 0.77-0.98) with no differences between positions or muscle actions. Measurement error was similar between positions for MVIC in both hip adduction and abduction. Measurements of RFD showed higher reliability using a time window of at least 0-100 milliseconds, and lower measurement error was observed in sitting for adduction and in supine for abduction. This study shows that portable dynamometry can be used to concurrently measure hip adduction and abduction maximal and explosive strength, with levels of reliability that are similar to previously described methods.

Increased association between Epstein-Barr virus EBNA2 from type 2 strains and the transcriptional repressor BS69 restricts EBNA2 activity.

Natural variation separates Epstein-Barr virus (EBV) into type 1 and type 2 strains. Type 2 EBV is less transforming in vitro due to sequence differences in the EBV transcription factor EBNA2. This correlates with reduced activation of the EBV oncogene LMP1 and some cell genes. Transcriptional activation by type 1 EBNA2 can be suppressed through the binding of two PXLXP motifs in its transactivation domain (TAD) to the dimeric coiled-coil MYND domain (CC-MYND) of the BS69 repressor protein (ZMYND11). We identified a third conserved PXLXP motif in type 2 EBNA2. We found that type 2 EBNA2 peptides containing this motif bound BS69CC-MYND efficiently and that the type 2 EBNA2TAD bound an additional BS69CC-MYND molecule. Full-length type 2 EBNA2 also bound BS69 more efficiently in pull-down assays. Molecular weight analysis and low-resolution structures obtained using small-angle X-ray scattering showed that three BS69CC-MYND dimers bound two molecules of type 2 EBNA2TAD, in line with the dimeric state of full-length EBNA2 in vivo. Importantly, mutation of the third BS69 binding motif in type 2 EBNA2 improved B-cell growth maintenance and the transcriptional activation of the LMP1 and CXCR7 genes. Our data indicate that increased association with BS69 restricts the function of type 2 EBNA2 as a transcriptional activator and driver of B cell growth and may contribute to reduced B-cell transformation by type 2 EBV.

A Spatiotemporal Deep Learning Approach for Automatic Pathological Gait Classification.

Human motion analysis provides useful information for the diagnosis and recovery assessment of people suffering from pathologies, such as those affecting the way of walking, i.e., gait. With recent developments in deep learning, state-of-the-art performance can now be achieved using a single 2D-RGB-camera-based gait analysis system, offering an objective assessment of gait-related pathologies. Such systems provide a valuable complement/alternative to the current standard practice of subjective assessment. Most 2D-RGB-camera-based gait analysis approaches rely on compact gait representations, such as the gait energy image, which summarize the characteristics of a walking sequence into one single image. However, such compact representations do not fully capture the temporal information and dependencies between successive gait movements. This limitation is addressed by proposing a spatiotemporal deep learning approach that uses a selection of key frames to represent a gait cycle. Convolutional and recurrent deep neural networks were combined, processing each gait cycle as a collection of silhouette key frames, allowing the system to learn temporal patterns among the spatial features extracted at individual time instants. Trained with gait sequences from the GAIT-IT dataset, the proposed system is able to improve gait pathology classification accuracy, outperforming state-of-the-art solutions and achieving improved generalization on cross-dataset tests.

Intermuscular Coordination in the Power Clean Exercise: Comparison between Olympic Weightlifters and Untrained Individuals-A Preliminary Study.

Muscle coordination in human movement has been assessed through muscle synergy analysis. In sports science, this procedure has been mainly applied to the comparison between highly trained and unexperienced participants. However, the lack of knowledge regarding strength training exercises led us to study the differences in neural strategies to perform the power clean between weightlifters and untrained individuals. Synergies were extracted from electromyograms of 16 muscles of ten unexperienced participants and seven weightlifters. To evaluate differences, we determined the pairwise correlations for the synergy components and electromyographic profiles. While the shape of activation patterns presented strong correlations across participants of each group, the weightings of each muscle were more variable. The three extracted synergies were shifted in time with the unexperienced group anticipating synergy #1 (-2.46 ± 18.7%; p < 0.001) and #2 (-4.60 ± 5.71%; p < 0.001) and delaying synergy #3 (1.86 ± 17.39%; p = 0.01). Moreover, muscle vectors presented more inter-group variability, changing the composition of synergy #1 and #3. These results may indicate an adaptation in intermuscular coordination with training, and athletes in an initial phase of training should attempt to delay the hip extension (synergy #1), as well as the upper-limb flexion (synergy #2).

Predictors of emotional distress in pregnant women: the mediating role of relationship intimacy.

Background: Assessment and treatment of emotional distress during pregnancy show that worries during pregnancy and interpersonal relationships with partners are the important factors determining psychological health.Aims: The present study aimed to investigate the impact of worries during pregnancy, relationship intimacy, and marital satisfaction on anxiety, depression, and stress symptoms in pregnant women, as well as to analyse the mediating effect of relationship intimacy between marital satisfaction and emotional distress.Method: During their second and third trimester of pregnancy, 200 Portuguese women were recruited during childbirth preparation consultations and completed the Cambridge Worry Scale (CWS), the Personal Assessment of Intimacy in Relationships Scale (PAIR), the Marital Life Areas Satisfaction Evaluation Scale (MLASES), and the Depression, Anxiety, and Stress Scale (DASS-21).Results: Hierarchical multiple regression analyses showed that being unemployed or on sick leave, being younger, having a history of miscarriage, having more worries during pregnancy, and declaring low-relationship intimacy were the main predictors of emotional distress. Relationship intimacy mediated the relation of marital satisfaction to anxiety and depression symptoms.Conclusions: This study highlights the importance of the worries during pregnancy and relationship intimacy in shaping pregnant women's emotional distress, and identifies both as targets of intervention.

Light Fields for Face Analysis.

The term "plenoptic" comes from the Latin words plenus ("full") + optic. The plenoptic function is the 7-dimensional function representing the intensity of the light observed from every position and direction in 3-dimensional space. Thanks to the plenoptic function it is thus possible to define the direction of every ray in the light-field vector function. Imaging systems are rapidly evolving with the emergence of light-field-capturing devices. Consequently, existing image-processing techniques need to be revisited to match the richer information provided. This article explores the use of light fields for face analysis. This field of research is very recent but already includes several works reporting promising results. Such works deal with the main steps of face analysis and include but are not limited to: face recognition; face presentation attack detection; facial soft-biometrics classification; and facial landmark detection. This article aims to review the state of the art on light fields for face analysis, identifying future challenges and possible applications.

Automatic Classification of Gait Impairments Using a Markerless 2D Video-Based System.

Systemic disorders affecting an individual can cause gait impairments. Successful acquisition and evaluation of features representing such impairments make it possible to estimate the severity of those disorders, which is important information for monitoring patients' health evolution. However, current state-of-the-art systems perform the acquisition and evaluation of these features in specially equipped laboratories, typically limiting the periodicity of evaluations. With the objective of making health monitoring easier and more accessible, this paper presents a system that performs automatic detection and classification of gait impairments, based on the acquisition and evaluation of biomechanical gait features using a single 2D video camera. The system relies on two different types of features to perform classification: (i) feet-related features, such as step length, step length symmetry, fraction of foot flat during stance phase, normalized step count, speed; and (ii) body-related features, such as the amount of movement while walking, center of gravity shifts and torso orientation. The proposed system uses a support vector machine to decide whether the observed gait is normal or if it belongs to one of three different impaired gait groups. Results show that the proposed system outperforms existing markerless 2D video-based systems, with a classification accuracy of 98.8%.

A single amino acid in EBNA-2 determines superior B lymphoblastoid cell line growth maintenance by Epstein-Barr virus type 1 EBNA-2.

UNLABELLED: Sequence differences in the EBNA-2 protein mediate the superior ability of type 1 Epstein-Barr virus (EBV) to transform human B cells into lymphoblastoid cell lines compared to that of type 2 EBV. Here we show that changing a single amino acid (S442D) from serine in type 2 EBNA-2 to the aspartate found in type 1 EBNA-2 confers a type 1 growth phenotype in a lymphoblastoid cell line growth maintenance assay. This amino acid lies in the transactivation domain of EBNA-2, and the S442D change increases activity in a transactivation domain assay. The superior growth properties of type 1 EBNA-2 correlate with the greater induction of EBV LMP-1 and about 10 cell genes, including CXCR7. In chromatin immunoprecipitation assays, type 1 EBNA-2 is shown to associate more strongly with EBNA-2 binding sites near the LMP-1 and CXCR7 genes. Unbiased motif searching of the EBNA-2 binding regions of the differentially regulated cell genes identified an ETS-interferon regulatory factor composite element motif that closely corresponds to the sequences known to mediate EBNA-2 regulation of the LMP-1 promoter. It appears that the superior induction by type 1 EBNA-2 of the cell genes contributing to cell growth is due to their being regulated in a manner different from that for most EBNA-2-responsive genes and in a way similar to that for the LMP-1 gene. IMPORTANCE: The EBNA-2 transcription factor plays a key role in B cell transformation by EBV and defines the two EBV types. Here we identify a single amino acid (Ser in type 1 EBV, Asp in type 2 EBV) of EBNA-2 that determines the superior ability of type 1 EBNA-2 to induce a key group of cell genes and the EBV LMP-1 gene, which mediate the growth advantage of B cells infected with type 1 EBV. The EBNA-2 binding sites in these cell genes have a sequence motif similar to the sequence known to mediate regulation of the EBV LMP-1 promoter. Further detailed analysis of transactivation and promoter binding provides new insight into the physiological regulation of cell genes by EBNA-2.

Sensitivity of Minimally Invasive Protocols to Monitor Changes in Endurance Performance in Elite Junior Football (Soccer) Players.

PURPOSE: Adequate physical fitness is a key requirement for elite footballers. Maximal fitness tests are the standard for evaluating fitness but are often fatiguing and time consuming. This study investigated the ability of various minimally invasive protocols to reflect changes in standard parameters of football players' physical fitness. METHODS: Twenty-one elite junior footballers performed 2 standard fitness tests (stepwise incremental treadmill test with blood-lactate and heart-rate [HR] measurements and Yo-Yo Intermittent Recovery 1 test) and various proxy fitness evaluations (submaximal runs with measurement of exercise HR and HR recovery and external-to-internal load ratios with data collected during match play) 3 times over the course of 19 weeks. Changes in the standard parameters were compared with changes in proxy parameters. RESULTS: Changes in maximal endurance performance showed small to moderate associations with HR-based proxy parameters (r = -.1 to -.46; P = .004-.56), whereas changes in the running velocity at anaerobic threshold had trivial to moderate associations (r = -.07 to -.39; P = .01-.67). Alterations in HR recovery following 2 short, submaximal runs were very largely correlated with changes in the running velocity corresponding to an HR of 170 beats·min-1 (r = -.74 and r = -.75; P < .001). Changes in external-to-internal load ratios derived from match play were not significantly correlated with changes in any of the standard parameters (r = -.03 to .31; P > .05). CONCLUSIONS: Parameters of maximal running performance and parameters describing physiological thresholds do not seem to be adequately captured by different minimally invasive protocols. In contrast, HR recovery following short, submaximal runs may be a valid tool to monitor changes in aerobic endurance adaptations.

Phosphoenolpyruvate phosphotransferase system regulates detection and processing of the quorum sensing signal autoinducer-2.

Autoinducer-2 (AI-2) a signal produced by a range of phylogenetically distant microorganisms, enables inter-species cell-cell communication and regulates many bacterial phenotypes. Certain bacteria can interfere with AI-2-regulated behaviours of neighbouring species by internalizing AI-2 using the Lsr transport system (encoded by the lsr operon). AI-2 imported by the Lsr is phosphorylated by the LsrK kinase and AI-2-phosphate is the inducer of the lsr operon. Here we show that in Escherichia coli the phosphoenolpyruvate phosphotransferase system (PTS) is required for Lsr activation and is essential for AI-2 internalization. Although the phosphorylation state of Enzyme I of PTS is important for this regulation, LsrK is necessary for the phosphorylation of AI-2, indicating that AI-2 is not phosphorylated by PTS. Our results suggest that AI-2 internalization is initiated by a PTS-dependent mechanism, which provides sufficient intracellular AI-2 to relieve repression of the lsr operon and, thus induce depletion of AI-2 from the extracellular environment. The fact that AI-2 internalization is not only controlled by the community-dependent accumulation of AI-2, but also depends on the phosphorylation state of PTS suggests that E. coli can integrate information on the availability of substrates with external communal information to control quorum sensing and its interference.

Urethrocystography: a guide for urological surgery?

Urethrocystography remains the gold-standard technique for urethral pathology diagnosis. Nowadays, of the various indications for performing urethrocystography, the most common is due to a clinical suspicion of urethral stricture. Due to the high prevalence of strictures and their substantial impact on a patient's quality of life, the examination must allow the location, exclusion of multifocality, and assessment of the extent of the stricture to influence surgical planning. This article intends to demonstrate that the radiologist's role, by performing and interpreting the modality of urethrocystography, influences and is crucial for the urologic therapeutic decision and that the patients who were submitted to reconstruction by urethroplasty had a better success rate. The authors aim to review the radiological anatomy of the male urethra, discuss the modalities of choice for imaging the urethra (retrograde urethrography and voiding cystourethrography), provide an overview of the different indications for performing the study, examine the different etiologies for urethral strictures, understand the relevance of the different appearances of urethral pathology, and identify the surgical options, especially in the treatment of urethral strictures. Simultaneously, the study exposes cases of urethral trauma, fistulas, diverticulum, and congenital abnormalities.

Abdominal splenosis mimicking peritoneal carcinomatosis of ovarian cancer.

We present the clinical case of a 53-year-old woman referred for suspicion of recurrence of a mesonephric-like adenocarcinoma of the ovary. Abdominal and pelvic CT revealed multiple round/oval solid nodules with similar density scattered throughout the abdomen and pelvis, the biggest ones appearing in the left hypochondrium; no normal-appearing spleen or ascites were observed. These radiological findings and the absence of significant elevation of CA 125 levels made the radiologists hypothesize that these aspects were related to abdominal splenosis. They asked the patient about previous medical history of splenic injury, which she confirmed, referring it was a consequence of a remote major trauma. A 99mTc-labeled heat-denatured erythrocytes (99mTc-DRBC) scintigraphy/ hybrid SPECT/CT was then performed for definitive diagnosis; it showed spleen remnants as foci of increased radiopharmaceutical uptake in the same locations as the nodules appearing in the CT. This diagnostic work-up was consistent with abdominal splenosis, mimicking peritoneal carcinomatosis of ovarian cancer.

Molecular Docking, ADMET Analysis and Molecular Dynamics (MD) Simulation to Identify Synthetic Isoquinolines as Potential Inhibitors of SARS-CoV-2 MPRO.

BACKGROUND: The rapidly widespread SARS-CoV-2 infection has affected millions worldwide, thus becoming a global health emergency. Although vaccines are already available, there are still new COVID-19 cases daily worldwide, mainly due to low immunization coverage and the advent of new strains. Therefore, there is an utmost need for the discovery of lead compounds to treat COVID-19. OBJECTIVE: Considering the relevance of the SARS-CoV-2 MPRO in viral replication and the role of the isoquinoline moiety as a core part of several biologically relevant compounds, this study aimed to identify isoquinoline-based molecules as new drug-like compounds, aiming to develop an effective coronavirus inhibitor. METHODS: 274 isoquinoline derivatives were submitted to molecular docking interactions with SARS-CoV-2 MPRO (PDB ID: 7L0D) and drug-likeness analysis. The five best-docked isoquinoline derivatives that did not violate any of Lipinski's or Veber's parameters were submitted to ADMET analysis and molecular dynamics (MD) simulations. RESULTS: The selected compounds exhibited docking scores similar to or better than chloroquine and other isoquinolines previously reported. The fact that the compounds interact with residues that are pivotal for the enzyme's catalytic activity, and show the potential to be orally administered makes them promising drugs for treating COVID-19. CONCLUSION: Ultimately, MD simulation was performed to verify ligand-protein complex stability during the simulation period.

Malignant peripheral nerve sheath tumor mimicking an adnexal mass: a radio-pathologic correlation.

We report the case of a pelvic malignant peripheral nerve sheath tumor mimicking an adnexal mass. A 59-year-old postmenopausal woman presented with a 3-month history of diffuse abdominal bloating and urinary frequency. Laboratory tests revealed an increased CA 125. Radiologic evaluation depicted a large, heterogeneous solid mass located right to the uterus, pushing it to the left. After a multidisciplinary board discussion, the diagnosis of a right adnexal lesion was assumed, and the patient was referred to surgery. The final diagnosis was only achieved after pathology examination, which prove to be a malignant peripheral nerve sheath tumor. This paper highlights some clinical, radiologic and pathological features of malignant peripheral nerve sheath tumors, a rare entity that should be considered as a differential in patients presenting with pelvic tumors of uncertain origin.