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Staphylococcus aureus infections and its biofilm removal is an important concern in health care management. Methicillin-resistant S. aureus is responsible for severe morbidity and mortality worldwide. The extensive use of disinfectants against biofilms has led to negative environmental impacts. Developing new and more potent biofilm eradication agents with minimal detrimental effects on human and environmental health is currently on the agenda. The alkyl esters of L-ascorbic acid (ASCn) are antioxidant amphiphiles, which show antimicrobial capacity against methicillin-sensitive and resistant S. aureus strains. ASC12 and ASC14 formulations are able to kill the persister cells of the deepest layers of the biofilm. We tested the hypothesis that the antimicrobial and antibiofilm capacity found for the ASCn emerges from a combined effect of its amphiphilic and their redox capacity. This mechanism appears related to: I) a larger diffusion capacity of the ASC12 micelles than ASC14 and ASC16 microstructures; II) the neutralization of the ASCn acid hydroxyl when the amphiphile reaches the surface of an anionic surface, followed by a rapid insertion; III) the disruption of cell membrane by alteration of membrane tension and structure and IV) ASCn accumulation in the cell membrane or biofilm extracellular matrix surfaces, reducing functional chemical groups and affecting its biological function.
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The impact of lipid diversity on the lateral organization of biological membranes remains a topic of debate. While the existence of domains in lamellar membranes is well-established, the nonlamellar phases occurring in biological systems are less explored due to technical constraints. Here, we present the measurement of the excitation-emission matrices (EEM) of LAURDAN in several lipid structures. LAURDAN is a fluorescence probe widely used for characterizing lipid assemblies. The EEMs were analyzed by multidimensional spectral phasors (MdSP), an approach that seizes information from both the excitation and emission spectra. We developed a computer algorithm to construct EEM data based on a model for LAURDAN's photophysics. The MdSP calculated from the simulated EEMs reveals that all feasible possibilities lie inside a universal triangle in the phasor's plot. We use this triangle to propose a ternary representation for the phasors, allowing a better assessment of LAURDAN's surroundings in terms of hydration, water mobility, and local electronic environment. Building upon this foundation, we constructed a theoretical "phase map" that can assess both lamellar and nonlamellar membranes. We thoroughly validated this theory using well-known lipid mixtures under different phase-state conditions and enzymatically generated systems. Our results confirm that the use of MdSP is a powerful tool for obtaining quantitative information on both lamellar and nonlamellar structures. This study not only advances our understanding of the impact of lipid diversity on membrane organization but also provides a robust and general framework for the assessment of fluorescence properties that can be further extended to other probes.
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Objective: Non-Hispanic Black women have increased rates of preterm birth and low infant birth weight. However, we do not know if these disparities replicate in women veterans, a population that may be at further risk for poor perinatal outcomes. This study sought to examine ethnoracial differences in preterm birth and low infant birth weight in veterans. Methods: A national sample of randomly chosen women veterans (i.e., oversampled for residency in high crime neighborhoods) reported information about all pregnancies they have had in their life, demographic characteristics, and history of childhood trauma exposures. The analytic sample was limited to individuals who identified as Hispanic/Latinx, Black, or White (n = 972). Mixed-effects regression models were used to examine ethnoracial differences in gestational age at delivery and infant birth weight, controlling for age at pregnancy, childhood trauma exposure, pregnancy during military service, income, and education. Results: Both Black and Hispanic/Latinx veterans were significantly more likely to have an infant born at lower gestational age (B = -1.04 and B = -1.11, respectively) and lower infant birth weight (B = -195.83 and B = -144.27, respectively) as compared with White veterans in covariate-adjusted models. Black (odds ratio = 3.24, confidence interval = 1.16, 9.09) veterans were more likely to meet the clinical definition of preterm birth as compared with White veterans. Conclusions: Results align with what is seen in the general population regarding ethnoracial disparities in gestational age at delivery and infant birth weight. Findings highlight the critical need for more research on mechanisms and prevention efforts for ethnoracial disparities in perinatal outcomes.
Subject(s)
Black or African American , Hispanic or Latino , Infant, Low Birth Weight , Pregnancy Outcome , Premature Birth , Veterans , White People , Humans , Female , Veterans/statistics & numerical data , Pregnancy , Adult , Premature Birth/ethnology , Hispanic or Latino/statistics & numerical data , White People/statistics & numerical data , Pregnancy Outcome/ethnology , Pregnancy Outcome/epidemiology , Black or African American/statistics & numerical data , Infant, Newborn , Gestational Age , United States/epidemiology , Health Status Disparities , Birth Weight , Socioeconomic FactorsABSTRACT
ISG15 is a type I interferon-induced ubiquitin-like modifier that functions in innate immune responses. The major human ISG15 ligase is hHERC5, a ribosome-associated HECT E3 that broadly ISGylates proteins cotranslationally. Here, we characterized the hHERC5-dependent ISGylome and identified over 2,000 modified lysines in over 1,100 proteins in IFN-ß-stimulated cells. In parallel, we compared the substrate selectivity hHERC5 to the major mouse ISG15 ligase, mHERC6, and analysis of sequences surrounding ISGylation sites revealed that hHERC5 and mHERC6 have distinct preferences for amino acid sequence context. Several features of the datasets were consistent with ISGylation of ribosome-tethered nascent chains, and mHERC6, like hHERC5, cotranslationally modified nascent polypeptides. The ISGylome datasets presented here represent the largest numbers of protein targets and modification sites attributable to a single Ub/Ubl ligase and the lysine selectivities of the hHERC5 and mHERC6 enzymes may have implications for the activities of HECT domain ligases, generally.
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This study investigated the prevalence of pigmentary keratitis (PK) in Pug-breed dogs and described the ocular surface characteristics associated with this disease. A total of 219 eyes from 110 dogs were examined, with 94.5% of them affected by PK. Age, previous ocular diseases, corneal vascularization, and corneal sensitivity were significantly associated with the presence of PF and the severity of corneal pigmentation. The study also found that low tear production and blinks incomplete with tear signs, as well as reduced corneal sensitivity, were linked to more severe forms of corneal pigmentation. The Tear Ferning Test (TFT) was identified as a valuable tool for evaluating tear quality in dogs, with worse test results indicating a higher risk of severe PK. A lower mean Tear Break-Up Time (TBUT) test was observed in dogs with PK. Additionally, the study observed a statistically significant difference in corneal thickness between the nasal and temporal zones, with the nasal zone being thicker. It was also suggested that sex and fertility status may influence the incidence of PK and the severity of corneal pigmentation. Overall, these findings provide insight into the underlying causes of PK in Pugs and can inform future treatment strategies for this breed.
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BACKGROUND AND OBJECTIVES: The development of severe COVID-19 is related to the preexistence of comorbidities and an inadequate nutritional status. The latter is a critical factor for the development of infection and the progression of the disease. Notably, optimal nutrition impacts immune system function, as malnutrition is related to high cytokine levels in the late phase of the disease, correlating with a poor prognosis. In this sense, omega-3 fatty acids (O3FAs) have anti-inflammatory properties that may reduce morbidity and mortality from COVID-19 infection. O3FAs are linked to a better prognosis in COVID-19 patients. MATERIALS AND METHODS: In this randomized, double-blind clinical trial, we evaluate the administration of O3FAs to unvaccinated Mexican patients for two weeks starting after the first two hours of hospitalization. RESULTS: The findings support the notion that O3FAs (in a dose high enough to satisfy human physiological requirements in a short time, one capsule of 1.4 g O3FAs daily) exert a comprehensive multi-systemic modulatory influence, affecting inflammatory and metabolic pathways. Significant perturbations in biomarkers, including absolute neutrophil count, hematocrit, and platelet indices, underscore the compound's anti-inflammatory effect. Concurrently, the intervention modulates pivotal metabolic and hepatic parameters, attenuating cardiovascular risk profiles and expediting patient convalescence. These multifarious effects are likely orchestrated through intricate biochemical mechanisms and are subject to individual variations predicated on metabolic factors. CONCLUSIONS: The results of this trial support the notion that O3FA supplementation has beneficial effects on COVID-19 patients with moderate presentation by regulating metabolism and limiting inflammation.
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BACKGROUND: Sexually transmitted infections (STIs) associated with genital ulcer disease due to herpes simplex virus-2 (HSV-2) are a prominent cause of morbidity and mortality. Serologic screening for HSV-2 is recommended only for individuals with genital herpes symptom history. However, no validated symptom screening tool currently exists. METHODS: Currently asymptomatic adults presenting for routine care at STI clinics in Lima, Peru completed a survey of prior genital herpes symptoms and received HSV-2 serological testing with the Euroimmun Anti-HSV-2 (gG2) ELISA IgG (Lubeck, Germany). A sub-sample of indeterminate results were sent for Western blot confirmatory testing. We assessed associations between past symptoms and anti-HSV-2 positivity and corrected the HSV-2 prevalence by re-classifying indeterminates per Western Blot results. RESULTS: We enrolled 131 participants between July and October 2022. HSV-2 antibody test results found 21.4% positive, 41.2% indeterminate, and 37.4% negative. Excluding indeterminate results, 36.4% were positive. Of participants with no prior symptoms 31.2% tested positive, compared to 35.7% with one prior symptom, 50.0% with 2, and 50.0% with 3+ prior symptoms. Among the sub-sample of indeterminates, 92.6% were confirmed positive by Western Blot, bringing the total estimated proportion of participants with HSV-2 antibodies to 59.5%. Either based on the original classification of HSV-2 antibody status or after incorporation of confirmatory testing results, there was no significant association between symptom history and HSV-2 antibody positivity. CONCLUSIONS: With currently available tests, recommendations to screen individuals based on genital herpes symptom history may not be useful. More discriminatory symptom screening tools or HSV-2 antibody tests with better performance are needed.
Subject(s)
Herpes Genitalis , Herpesvirus 2, Human , Adult , Humans , Herpes Genitalis/diagnosis , Antibodies, Viral , Enzyme-Linked Immunosorbent Assay , GermanyABSTRACT
OBJECTIVE: Seasonal patterns are often undetectable in population-based depression studies, calling into question the existence of winter seasonal affective disorder (SAD). If SAD has construct validity, individuals with SAD should show spontaneous depression remission in the summer. Data are sparse on prospectively assessed summer mood status in confirmed SAD patients. METHOD: We conducted prospective summer followup of community adults who, the winter before, were diagnosed with Major Depression, Recurrent with Seasonal Pattern on the Structured Clinical Interview for DSM-IV Axis I Disorders, developed a current SAD episode on the Structured Interview Guide for the Hamilton Rating Scale for Depression-Seasonal Affective Disorder Version (SIGH-SAD), and enrolled in a clinical trial comparing group cognitive-behavioral therapy for SAD and light therapy. In July/August after treatment, 143/153 (93.5 %) participants provided data on the SIGH-SAD, the Beck Depression Inventory-Second Edition, and the Longitudinal Interval Followup Evaluation (LIFE). RESULTS: Summer mean depression scores were in the normal range, with the substantial majority in remission across different measures. On the LIFE, 113/143 (79.0 %) experienced complete summer remission, 19/143 (13.3 %) experienced partial summer remission, and 11/143 (7.7 %) had major depression in the summer. Depression scores were significantly lower at summer than post-treatment in both treatments, indicating incomplete treatment response. LIMITATIONS: This was a single-site study with a relatively homogeneous sample. CONCLUSIONS: Supporting construct validity for SAD, the substantial majority experienced complete summer remission, with a minority in partial remission and a very small minority in episode. Both treatments left residual symptoms at treatment endpoint compared to summer.
Subject(s)
Depressive Disorder, Major , Seasonal Affective Disorder , Humans , Adult , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/therapy , Seasons , Depression , Prospective Studies , Seasonal Affective Disorder/diagnosis , Seasonal Affective Disorder/therapy , Seasonal Affective Disorder/psychology , PhototherapyABSTRACT
Plant pathogens and pests can cause significant losses in crop yields, affecting food security and the global economy. Many traditional chemical pesticides are used to combat these organisms. This can lead to the development of pesticide-resistant strains of pathogens/insects and negatively impact the environment. The development of new bioprotectants, which are less harmful to the environment and less likely to lead to pesticide-resistance, appears as a sustainable strategy to increase plant immunity. Natural Rhamnolipids (RL-Nat) are a class of biosurfactants with bioprotectant properties that are produced by an opportunistic human pathogen bacterium. RL-Nat can act as plant resistance inducers against a wide variety of pathogens. Recently, a series of bioinspired synthetic mono-RLs produced by green chemistry were also reported as phytoprotectants. Here, we explored their capacity to generate novel colloidal systems that might be used to encapsulate bioactive hydrophobic compounds to enhance their performance as plant bioprotectants. The synthetic mono-RLs showed good surfactant properties and emulsification power providing stable nanoemulsions capable of acting as bio-carriers with good wettability. Synthetic RLs-stabilized nanoemulsions were more effective than RLs suspensions at inducing plant immunity, without causing deleterious effects. These nanoemulsions were innocuous to native substrate microbiota and beneficial soil-borne microbes, making them promising safe bio-carriers for crop protection.
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BACKGROUND: Government responses and restrictions due to the COVID-19 pandemic (e.g., limits to non-urgent health care services, including non-urgent outpatient appointments) led to the suspension of center-based (in-person) cardiac rehabilitation (CR), with many programs switching to virtual delivery. This study aimed to understand the characteristics and correlates of disease-related knowledge and exercise self-efficacy in a group of patients attending a virtual CR program during the first COVID-19 lockdown in Peru. METHODS: In this prospective observational study, 240 patients receiving virtual CR care (exercise instructions and patient education) between August/2020 and December/2021 completed questionnaires pre- and post-CR assessing disease-related knowledge (CADE-Q SV questionnaire) and self-efficacy (SE; Bandura's Exercise SE scale). Paired t tests were used to investigate changes pre/post-CR and Pearson correlation coefficients were used to determine the association between knowledge/SE and patients' characteristics. RESULTS: Participants were mainly comprised of men, with a cardiac diagnosis of stable coronary artery disease, who underwent percutaneous coronary intervention or had a known diagnosis of hypertension and with at least one cardiovascular risk factor (95.8%). Mean total knowledge scores improved significantly at post-CR (12.9 ± 2.4 to 15.6 ± 2.0/20; p<0.001), as well as in 4/5 knowledge areas (cardiovascular risk factors, exercise, nutrition, and psychosocial risk; p<0.001). Mean SE scores improved significantly at post-CR (1.9 ± 0.9 to 3.0 ± 0.9/5; p = 0.01). Post-CR knowledge and SE were significantly correlated with cardiac diagnosis and surgical procedures (r = 0.17, p = 0.02 and r = 0.27, p = 0.02, respectively). CONCLUSIONS: The virtual CR program improved disease-related knowledge and SE of cardiac patients during the first months of the COVID-19 pandemic. Post-CR outcomes were correlated with cardiac diagnosis and surgical procedures and more research with other characteristics is warrantied.
Subject(s)
COVID-19 , Cardiac Rehabilitation , Male , Humans , Peru , Self Efficacy , Pandemics , Communicable Disease ControlABSTRACT
Objective: Cardiac Rehabilitation (CR) programs based on telehealth are an alternative in the context of a pandemic and represent an opportunity to continue in the intervention of cardiovascular diseases (CVD). The present study aims to evaluate the effect of a Cardiac Tele-Rehabilitation (CTR) program on quality of life, anxiety/depression index, exercise safety and Level Of disease awareness in patients discharged from a national referral institute in times of pandemic. Methods: A pre-experimental study in cardiac patients who entered the cardiac rehabilitation program at INCOR from August to December 2020. The study included low-risk patients who were administered a questionnaire (on cardiovascular disease, exercise safety, anxiety/depression, and quality of life) at the beginning and end of the program, which was applied through a virtual platform. Descriptive and comparative before-after analysis was used through hypothesis testing. Results: Sixty-four patients were included (71.9% male). The mean age was 63.6 ±11.1 years. Regarding exercise safety, an increase in the mean score was found after the application of the program (3.06 ± 0.8 to 3.18 ± 0.7, p=0.324). Concerning anxiety, the mean score was reduced from 8.61 to 4.75, while for depression, the reduction was from 7.27 to 2.92. Regarding the quality-of-life score, the global component improved from 111.48 to 127.92. Conclusions: The CTR program implemented through a virtual platform during the COVID-19 pandemic enhanced quality of life and decreased stress and depression in cardiac patients discharged from a national cardiovascular referral center.
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In treating an acute episode of winter depression, cognitive-behavioral therapy for seasonal affective disorder (CBT-SAD) and light therapy are comparably efficacious, with improvement in depression symptoms during CBT-SAD mediated by reduced seasonal beliefs (i.e., maladaptive thoughts about the seasons, light availability, and weather). Here, we tested whether the enduring benefit of CBT-SAD over light therapy following treatment is associated with offsetting seasonal beliefs during CBT-SAD. Currently depressed adults with Major Depression, Recurrent with Seasonal Pattern (Nâ¯=â¯177) were randomized to 6 weeks of light therapy or group CBT-SAD and followedup one and two winters after treatment. Outcomes measured during treatment and at each follow-up included depression symptoms on the Structured Clinical Interview for the Hamilton Rating Scale for Depression-SAD Version and Beck Depression Inventory-Second Edition. Candidate mediators measured at pre-, mid-, and posttreatment were SAD-specific negative cognitions (Seasonal Beliefs Questionnaire; SBQ); general depressogenic cognitions (Dysfunctional Attitudes Scale; DAS); brooding rumination (Ruminative Response Scale-Brooding subscale; RRS-B); and chronotype (Morningness-Eveningness Questionnaire; MEQ). Latent growth curve mediation models found a significant positive path from treatment group to the slope of SBQ during treatment, with CBT-SAD showing larger improvements in seasonal beliefs with overall change in seasonal beliefs in the medium-effect range, and significant positive paths from SBQ slope to depression scores at the first and second winter follow-ups, indicating greater change towards more flexible seasonal beliefs during active treatment was associated with less severe depression symptoms following treatment. Estimated indirect effects (treatment groupâ¯ââ¯SBQ changeâ¯*â¯SBQ changeâ¯ââ¯outcome) were also significant at each follow-up for each outcome with ßindirect ranging from .091 to .162. Models also found significant positive paths from treatment group to the slope of MEQ and RRS-B during treatment, with light therapy showing a greater increase in "morningness" and CBT-SAD showing a greater decrease in brooding during active treatment; however, neither construct emerged as a mediator of follow-up depression scores. Change in seasonal beliefs during treatment mediates both the acute antidepressant and long-term effects of CBT-SAD and explains lower depression severity following CBT-SAD relative to light therapy.
Subject(s)
Cognitive Behavioral Therapy , Depressive Disorder, Major , Seasonal Affective Disorder , Adult , Humans , Seasonal Affective Disorder/therapy , Seasonal Affective Disorder/diagnosis , Seasonal Affective Disorder/psychology , Seasons , Phototherapy , Depressive Disorder, Major/therapy , Treatment OutcomeABSTRACT
Accurately modeling healthy and disease conditions in vitro is vital for the development of new treatment strategies and therapeutics. For cardiac and skeletal muscle diseases, contractile force and kinetics constitute key metrics for assessing muscle function. New and improved methods for generating engineered muscle tissues (EMTs) from induced pluripotent stem cells have made in vitro disease modeling more reliable for contractile tissues; however, reproducibly fabricating tissues from suspended cell cultures and measuring their contractility is challenging. Such techniques are often plagued with high failure rates and require complex instrumentation and customized data analysis routines. A new platform and device that utilizes 3D EMTs in conjunction with a label-free, highly-parallel, and automation-friendly contractility assay circumvent many of these obstacles. The platform enables facile and reproducible fabrication of 3D EMTs using virtually any cell source. Tissue contractility is then measured via an instrument that simultaneously measures 24 tissues without the need for complex software analysis routines. The instrument can reliably measure micronewton changes in force, allowing for dose-dependent compound screening to measure the effect of a drug or therapeutic on contractile output. Engineered tissues made with this device are fully functional, generating twitch and tetanic contractions upon electrical stimulation, and can be analyzed longitudinally in culture over weeks or months. Here, we show data from cardiac muscle EMTs under acute and chronic dosing with known toxicants, including a drug (BMS-986094) that was pulled from clinical trials after patient fatalities due to unanticipated cardiotoxicity. Altered skeletal muscle function in engineered tissues in response to treatment with a myosin inhibitor is also presented. This platform enables the researcher to integrate complex, information-rich bioengineered model systems into their drug discovery workflow with minimal additional training or skills required.
Subject(s)
Muscle Contraction , Myocardium , Humans , Heart , Muscle, Skeletal/physiology , Tissue Engineering/methodsABSTRACT
Relationship identities are established through romantic interactions and informed by sociohistorical context. The associations between lesbian, gay, and bisexual (LGB) identities and identities in other domains, including relationship identities, have yet to receive sufficient attention from researchers. In this exploratory study, through a qualitative analysis of life-history interviews from the Generations Study, we identified participants who described their identity in terms of a romantic relationship (e.g., partner, husband/wife). In describing their relationship identities, two themes emerged: (a) negotiation of a relationship identity with other identities, such as gender or race/ethnicity and (b) navigating being visible or invisible within the LGB community and/or at the societal level. Together these themes suggest that relationships may be salient components of personal identity when sexual minority individuals in a couple either individually or jointly feel that they stand out (or that they become invisible).
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Chronic obstructive pulmonary disease (COPD) patients frequently suffer from multiple comorbidities, resulting in poor outcomes for these patients. Diabetes is observed at a higher frequency in COPD patients than in the general population. Both type 1 and 2 diabetes mellitus are associated with pulmonary complications, and similar therapeutic strategies are proposed to treat these conditions. Epidemiological studies and disease models have increased our knowledge of these clinical associations. Several recent genome-wide association studies have identified positive genetic correlations between lung function and obesity, possibly due to alterations in genes linked to cell proliferation; embryo, skeletal, and tissue development; and regulation of gene expression. These studies suggest that genetic predisposition, in addition to weight gain, can influence lung function. Cigarette smoke exposure can also influence the differential methylation of CpG sites in genes linked to diabetes and COPD, and smoke-related single nucleotide polymorphisms are associated with resting heart rate and coronary artery disease. Despite the vast literature on clinical disease association, little direct mechanistic evidence is currently available demonstrating that either disease influences the progression of the other, but common pharmacological approaches could slow the progression of these diseases. Here, we review the clinical and scientific literature to discuss whether mechanisms beyond preexisting conditions, lifestyle, and weight gain contribute to the development of COPD associated with diabetes. Specifically, we outline environmental and genetic confounders linked with these diseases.
Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Pulmonary Disease, Chronic Obstructive , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Genome-Wide Association Study , Humans , Lung , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/epidemiology , Weight GainABSTRACT
Shoulder antepulsion, altered scapular kinematics and imbalance of muscle activity are commonly associated with shoulder pain. This study aimed to observe if there is an association between the forward shoulder angle (FSA) and the pectoralis minor length index (PMI) in volleyball players with and without shoulder pain. Furthermore, this study observed if there is an association between shoulder posture and upper limb mechanical hyperalgesia in volleyball players with and without shoulder pain. Methods: a cross-sectional study was conducted in the Physiotherapy and Pain Research Center in Alcalá de Henares (Spain). A total of 56 volleyball players met the inclusion criteria and agreed to enter the study. Subjects were divided into two groups: shoulder pain group (SPG) and control group (without pain). The following measurements of the dominant sides of the players were collected: FSA, PMI, and pressure pain threshold (PPT) in serratus anterior, lower trapezius, infraspinatus, teres minor, upper trapezius, levator scapulae, pectoralis major, radial nerve, cubital nerve, and median nerve. Results: The Spearman's Rho revealed no significant correlations were found between FSA and PMI. Moreover, Spearman's Rho test revealed in the SPG a negative moderate correlation between FSA and Infraspinatus-PPT (Rho = −0.43; p = 0.02); FSA and levator scapulae-PPT (Rho = −0.55; p < 0.01); FSA and pectoralis major-PPT (Rho = −0.41; p = 0.02); PMI and cubital nerve-PPT (Rho = −0.44; p = 0.01). Conclusions: No association was found between the forward shoulder angle and the pectoralis minor index in volleyball players with and without shoulder pain. There is a moderate negative association between shoulder forward angle and muscle mechanical hyperalgesia in volleyball players with shoulder pain, but no such associations were found in volleyball players without shoulder pain. Treatment of the infraspinatus, levator scapulae, pectoralis major, and pectoralis minor muscles could improve shoulder pain and ulnar nerve mechanosensitivity.
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A genomically recoded Escherichia coli strain that lacks all amber codons and release factor 1 (C321.∆A) enables efficient genetic encoding of chemically diverse non-canonical amino acids (ncAAs) into proteins. While C321.∆A has opened new opportunities in chemical and synthetic biology, this strain has not been optimized for protein production, limiting its utility in widespread industrial and academic applications. To address this limitation, the construction of a series of genomically recoded organisms that are optimized for cellular protein production is described. It is demonstrated that the functional deactivation of nucleases (e.g., rne, endA) and proteases (e.g., lon) increases production of wild-type superfolder green fluorescent protein (sfGFP) and sfGFP containing two ncAAs up to ≈5-fold. Additionally, a genomic IPTG-inducible T7 RNA polymerase (T7RNAP) cassette into these strains is introduced. Using an optimized platform, the ability to introduce two identical N6 -(propargyloxycarbonyl)-L -Lysine residues site specifically into sfGFP with a 17-fold improvement in production relative to the parent strain is demonstrated. The authors envision that their library of organisms will provide the community with multiple options for increased expression of proteins with new and diverse chemistries.
Subject(s)
Amino Acids , Escherichia coli , Amino Acids/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Synthetic BiologyABSTRACT
Resumen Un desafío en Colombia, a partir de la firma del Acuerdo de Paz con las FARC-EP, es retejer los vínculos rotos entre excombatientes y sociedad, aspiración presente en propuestas de desarme, desmovilización y reincorporación; reconciliación y salud mental. Desde una investigación cualitativa con excombatientes, familiares y vecinos, se presentan aspectos relacionados con el ingreso, permanencia y reincorporación y las contradicciones del retorno a la vida civil. Incumplimientos, incertidumbre, ausencia de un relato de corresponsabilidad, estigma y reaprendizaje de los códigos de la vida social, entre otros, son examinados desde los encuentros cotidianos con comunidades receptoras en contextos rurales.
Abstract A challenge in Colombia, since the signing of the Peace Agreement with the FARCEP, is to reweave the broken links between ex-combatants and society, an aspiration present in proposals for disarmament, demobilization, and reincorporation; reconciliation and mental health. From qualitative research with ex-combatants, family members, and neighbors, aspects related to the entry, permanence, and reincorporation, and the contradictions of the return to civilian life are presented. Non-compliance, uncertainty, absence of a narrative of co-responsibility, stigma, and re-learning of the codes of social life, among others, are examined from daily encounters with receiving communities in rural contexts.
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Bifidobacterial proteins have been widely studied to elucidate the metabolic mechanisms of diet adaptation and survival of Bifidobacteria, among others. The use of heterologous expression systems to obtain proteins in sufficient quantities to be characterized has been essential in these studies. L. lactis and the same Bifidobacterium as expression systems highlight ways to corroborate some of the functions attributed to these proteins. The most studied proteins are enzymes related to carbohydrate metabolism, particularly glycosidases, due to their potential application in the synthesis of neoglycoconjugates, prebiotic neooligosaccharides, and active metabolites as well as their high specificity and efficiency in processing glycoconjugates. In this review, we classified the recombinant bifidobacterial proteins reported to date whose characterization has demonstrated their usefulness or their ability to produce a product of commercial interest for the food industry, biomedicine, process innovation and glycobiology. Future directions for their study are also discussed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00957-1.
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BACKGROUND: During the COVID-19 pandemic, the need for judicious use of diagnostic tests and to limit personnel exposure has led to increased use and dependence on point-of-care ultrasound (POCUS) examinations. We reviewed POCUS findings in patients admitted to the intensive care unit (ICU) for acute respiratory failure with COVID-19 and correlated the findings to severity of illness and 30-day outcomes. METHODS: Patients admitted to the ICU in March and April 2020 were reviewed for inclusion (acute hypoxemic respiratory failure secondary to COVID-19 pneumonia; documentation of POCUS findings). RESULTS: Forty-three patients met inclusion criteria. B lines and pleural thickening were associated with a lower PaO2/FiO2 by 71 (P = .005; adjusted R 2 = 0.24). Right ventricle (RV) dilation was more common in patients with 30-day mortality (P = .02) and was a predictor of mortality when adjusted for hypertension, diabetes mellitus, and age (odds ratio, 12.0; P = .048). All patients with RV dilation had bilateral B lines with pleural irregularities. CONCLUSIONS: Although lung ultrasound abnormalities are prevalent in patients with severe disease, RV involvement seems to be predictive of outcomes. Further studies are needed to discern the etiology and pathophysiology of RV dilation in COVID-19.