Search

Vascular hamartoma is an abnormal development of endothelial tissue that rarely affects horses. Histopathological examination remains the gold standard for definitive diagnosis, yet the presence of abnormal vascular structures must be carefully differentiated from other vascular anomalies and neoplasms. This report describes two cases of vascular proliferation affecting the skin on the lateral side over the left tarsus and the dorsolateral region over the fetlock joint of two fillies. The clinical history, presentation, and radiographic and sonographic findings in both patients suggested a neoplasm of unknown origin. Surgical excision of the mass was successfully performed in both patients. In one patient, a second surgery was performed six months after the first surgery because of the recurrence of the mass. Histopathological examination revealed a disorganized proliferation of well-differentiated, tortuous, and varied-sized blood vessels hemmed in myxoid tissue with abundant fibrocollagenous bands. Immunohistochemical examination of the endothelium markers factor VIII and ERG revealed positive staining of the mass samples in both cases, confirming their vascular origin. The combination of these markers was effective, providing a reliable option for differentiating vascular proliferation in horses. To the best of the author's knowledge, this is the first report applying the ERG endothelial marker to horse vascular malformations., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethical approval The study described in this manuscript involved the use of non-experimental horses. The owners have provided consent for veterinary clinical care for the individual patient at the São Paulo State University —School of Veterinary Medicine and Animal Science (FMVZ/UNESP), Botucatu, Brazil, and for the publication of their pet’s data. Therefore, ethical approval from a committee was not specifically required for publication., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The COVID-19 pandemic has led to the emergence of acute and chronic post-COVID syndromes, which present diverse clinical manifestations. The underlying pathophysiology of these conditions is not yet fully understood, but genetic instability has been proposed as a potential contributing factor. This study aimed to explore the differential impact of physical and psychological health factors on genetic instability in individuals with acute and chronic post-COVID syndromes. In this study, three groups of subjects were analyzed: a control group, an acute post-COVID group, and a chronic post-COVID group, with a total of 231 participants. The participants were assessed using a questionnaire for long-COVID-19COVID, and female participants reported more symptoms than male participants in areas related to fatigue, memory, mental health, and well-being during the chronic phase. Genetic instability was assessed using the comet assay, and participants' physical and psychological profiles were evaluated. The overall results showed no significant differences in DNA damage, as measured by the comet assay, among the three groups, suggesting that genetic instability, as assessed by this method, may not be a primary driver of the distinct clinical presentations observed in post-COVID syndromes. However, when gender was considered, male participants in the acute long COVID group exhibited higher levels of genetic instability compared to females. Multiple linear regression analysis revealed that gender, age, and waist circumference were significant predictors of DNA damage. Among females in the acute group, sexual health, and eye-related symptoms significantly influenced the increase in DNA damage. These findings indicate the need for further investigation on the gender-specific differences in genetic instability and their potential implications for the pathophysiology of post-COVID syndromes. Exploring alternative markers of genetic instability and the interplay between genetic, inflammatory, and cellular processes could provide valuable insights for the management of these debilitating post-viral sequelae., (© The Author(s) 2024. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To compare the effectiveness of inhaled Magnesium Sulfate associated with Salbutamol versus Inhaled Salbutamol alone in patients with moderate and severe asthma exacerbations., Method: Clinical, prospective and randomized study with patients between 3 and 14 years of age divided into two groups: one to receive inhaled salbutamol associated with magnesium sulfate (GSM), the other to receive inhaled salbutamol alone (GS). The sample consisted of 40 patients, 20 patients in each group. Severity was classified using the modified Wood-Downes score, with values between 4 and 7 classified as moderate and 8 or more classified as severe., Results: Post-inhalation scores decreased both in patients who received salbutamol and magnesium and in those who received salbutamol alone, with no statistically significant difference between the groups., Conclusions: Despite the benefits when administered intravenously, inhalation of the drug alone or in combination did not reduce the severity of the exacerbation., Competing Interests: Conflicts of interest The authors declare no conflicts of interest, and they each contributed fully to the preparation of this manuscript., (Copyright © 2024 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

This study aimed to assess the leaf aqueous extract composition of Erythrina crista-galli and the effects of its inclusion on the diet of red-eye tetra (Moenkhausia forestii), concerning enzyme content of digestive, hepatic, and oxidation metabolism and pigmentation. Fish (1.78 ± 0.54 g) were divided into groups: fasting (without feeding), control (commercial feed), and treatment (commercial feed with leaf aqueous extract of E. crista-galli) and feeding apparent satiety for 21 days, in the extracted analysis by mass spectrometry, phenolic compost, and flavonoids. The agitation degree and number of dashes, in all supplemented treatments, were lower than those in the control diet when fed for 7 or 15 days. In the digestive enzymatic activity did not differ (p > 0.05). The hepatoprotective treatment group showed lower alanine aminotransferase (ALT) and higher levels of antioxidant catalase (CAT). The results indicated that the aqueous leaf extract of Erythrina crista-galli assists in function maintenance of the liver; and stimulates CAT in red-eye tetra, suggesting that the identified compounds act on the liver and skin, showing hepatoprotective effects and stimulating tranquility., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To compare the effectiveness of adjunct treatments combined with exercise to exercise alone in people with patellofemoral pain (PFP) and explore the quality of intervention descriptions in randomised controlled trials (RCTs)., Design: Systematic review., Data Sources: Seven databases were searched in November 2023., Eligibility: RCTs that evaluated the effectiveness of any adjunct treatment combined with exercise to exercise alone on self-reported pain and function in people with PFP., Results: We included 45 RCTs (2023 participants), with 25 RCTs (1050 participants) contributing to meta-analyses. Pooled analysis indicated very low-certainty evidence that neuromuscular electrical stimulation or monopolar dielectric diathermy combined with exercise leads to small and large improvements in self-reported pain when compared with exercise alone (standardised mean difference (95% CI)=-0.27 (-0.53 to -0.02) and -2.58 (-4.59 to -0.57), respectively) in the short-term. For self-reported pain and function, very low-certainty evidence indicates that knee taping, whole-body vibration, electromyographic biofeedback and knee brace combined with exercise do not differ from exercise alone. Interventions are poorly described in most RCTs, adjunct treatments scored on average 14/24 and exercise therapy 12/24 in the Template for Intervention Description and Replication checklist., Conclusion: Neuromuscular electrical stimulation and monopolar dielectric diathermy combined with exercise seem to improve self-reported pain in people with PFP compared with exercise alone. Knee taping, whole-body vibration, electromyographic biofeedback and knee brace do not offer additional benefits to exercise alone. Most interventions are poorly described, which is detrimental to translating research knowledge into clinical practice., Prospero Registration Number: CRD42020197081., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Selecting individuals who are the right "fit" for correctional work is not an easy task for prison administrators because of the dangerous nature of correctional work and the centrality of prison employees in the prisoner's rehabilitation process. We analyze fitness for correctional work from the employee's perspective, complementing the scholarship focused on the employer's view. We measure occupational fitness in terms of co-worker expectations, analyzing 104 semi-structured interviews conducted with Federal Canadian Correctional Officer recruits in 2018/2019. Recruits in our sample expected a correctional officer to be accountable, reliable, and confident. Understanding the mind-set of new hires provides insights into the correctional officer role and allows employers to align employer-employee expectations, as well as review training and recruitment, which can improve the employee well-being and reduce turnover rates., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

The recalcitrance exhibited by many maize ( Zea mays ) genotypes to traditional genetic transformation protocols poses a significant challenge to the large-scale application of genome editing (GE) in this major crop species. Although a few maize genotypes are widely used for genetic transformation, they prove unsuitable for agronomic tests in field trials or commercial applications. This challenge is exacerbated by the predominance of transformable maize lines adapted to temperate geographies, despite a considerable proportion of maize production occurring in the tropics. Ectopic expression of morphogenic regulators (MRs) stands out as a promising approach to overcome low efficiency and genotype dependency, aiming to achieve 'universal' transformation and GE capabilities in maize. Here, we report the successful GE of agronomically relevant tropical maize lines using a MR-based, Agrobacterium -mediated transformation protocol previously optimized for the B104 temperate inbred line. To this end, we used a CRISPR/Cas9-based construct aiming at the knockout of the VIRESCENT YELLOW-LIKE (VYL) gene, which results in an easily recognizable phenotype. Mutations at VYL were verified in protoplasts prepared from B104 and three tropical lines, regardless of the presence of a single nucleotide polymorphism (SNP) at the seed region of the VYL target site in two of the tropical lines. Three out of five tropical lines were amenable to transformation, with efficiencies reaching up to 6.63%. Remarkably, 97% of the recovered events presented indels at the target site, which were inherited by the next generation. We observed off-target activity of the CRISPR/Cas9-based construct towards the VYL paralog VYL-MODIFIER , which could be partly due to the expression of the WUSCHEL (WUS) MR. Our results demonstrate efficient GE of relevant tropical maize lines, expanding the current availability of GE-amenable genotypes of this major crop., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hernandes-Lopes, Pinto, Vieira, Monteiro, Gerasimova, Nonato, Bruno, Vikhorev, Rausch-Fernandes, Gerhardt, Pauwels, Arruda, Dante and Yassitepe.)

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive loss of cognitive functions, and it is the most prevalent type of dementia worldwide, accounting for 60 to 70% of cases. The pathogenesis of AD seems to involve three main factors: deficiency in cholinergic transmission, formation of extracellular deposits of β-amyloid peptide, and accumulation of deposits of a phosphorylated form of the TAU protein. The currently available drugs are prescribed for symptomatic treatment and present adverse effects such as hepatotoxicity, hypertension, and weight loss. There is urgency in finding new drugs capable of preventing the progress of the disease, controlling the symptoms, and increasing the survival of patients with AD. This study aims to present new multipurpose compounds capable of simultaneously inhibiting acetylcholinesterase (AChE), butyrylcholinesterase (BChE)-responsible for recycling acetylcholine in the synaptic cleft-and beta-secretase 1 (BACE-1)-responsible for the generation of amyloid-β plaques. AChE, BChE, and BACE-1 are currently considered the best targets for the treatment of patients with AD. Virtual hierarchical screening based on a pharmacophoric model for BACE-1 inhibitors and a dual pharmacophoric model for AChE and BChE inhibitors were used to filter 214,446 molecules by QFIT BACE > 0 and QFIT DUAL > 56.34. The molecules selected in this first round were subjected to molecular docking studies with the three targets and further evaluated for their physicochemical and toxicological properties. Three structures: ZINC45068352, ZINC03873986, and ZINC71787288 were selected as good fits for the pharmacophore models, with ZINC03873986 being ultimately prioritized for validation through activity testing and synthesis of derivatives for SAR studies.

Exposure to coal mining dust poses a substantial health hazard to individuals due to the complex mixture of components released during the extraction process. This study aimed to assess the oxidative potential of residual coal mining dust on human lymphocyte DNA and telomeres and to perform a chemical characterization of coal dust and urine samples. The study included 150 individuals exposed to coal dust for over ten years, along with 120 control individuals. The results revealed significantly higher levels of DNA damage in the exposed group, as indicated by the standard comet assay, and oxidative damage, as determined by the FPG-modified comet assay. Moreover, the exposed individuals exhibited significantly shorter telomeres compared to the control group, and a significant correlation was found between telomere length and oxidative DNA damage. Using the PIXE method on urine samples, significantly higher concentrations of sodium (Na), phosphorus (P), sulfur (S), chlorine (Cl), potassium (K), iron (Fe), zinc (Zn), and bromine (Br) were observed in the exposed group compared to the control group. Furthermore, men showed shorter telomeres, greater DNA damage, and higher concentrations of nickel (Ni), calcium (Ca), and chromium (Cr) compared to exposed women. Additionally, the study characterized the particles released into the environment through GC-MS analysis, identifying several compounds, including polycyclic aromatic hydrocarbons (PAHs) such as fluoranthene, naphthalene, anthracene, 7H-benzo[c]fluorene, phenanthrene, pyrene, benz[a]anthracene, chrysene, and some alkyl derivatives. These findings underscore the significant health risks associated with exposure to coal mining dust, emphasizing the importance of further research and the implementation of regulatory measures to safeguard the health of individuals in affected populations., (© 2023. The Author(s).)

Glioblastoma (GB) is the most aggressive primary malignant brain tumor and is associated with short survival. O-GlcNAcylation is an intracellular glycosylation that regulates protein function, enzymatic activity, protein stability, and subcellular localization. Aberrant O-GlcNAcylation is related to the tumorigenesis of different tumors, and mounting evidence supports O-GlcNAc transferase (OGT) as a potential therapeutic target. Here, we used two human GB cell lines alongside primary human astrocytes as a non-tumoral control to investigate the role of O-GlcNAcylation in cell proliferation, cell cycle, autophagy, and cell death. We observed that hyper O-GlcNAcylation promoted increased cellular proliferation, independent of alterations in the cell cycle, through the activation of autophagy. On the other hand, hypo O-GlcNAcylation inhibited autophagy, promoted cell death by apoptosis, and reduced cell proliferation. In addition, the decrease in O-GlcNAcylation sensitized GB cells to the chemotherapeutic temozolomide (TMZ) without affecting human astrocytes. Combined, these results indicated a role for O-GlcNAcylation in governing cell proliferation, autophagy, cell death, and TMZ response, thereby indicating possible therapeutic implications for treating GB. These findings pave the way for further research and the development of novel treatment approaches which may contribute to improved outcomes and increased survival rates for patients facing this challenging disease.

Objective: Correctional work involves exposures to correctional-specific potentially psychologically traumatic events (PPTEs); however, the frequency and impact of such PPTEs on the mental health of correctional workers remain unclear. We analyzed the prevalence and frequency of 13 different occupational-specific PPTE exposures among correctional workers ( n = 980; 50.7% female) and estimated associations with mental health symptoms., Method: The survey data used are from the Provincial Ontario Correctional Worker Mental Health Prevalence Study in Canada. Cross-tabulations, Chi-square tests, ANOVAs, and logistic regression are used to examine the following: (a) the distribution of correctional-specific PPTEs across correctional worker occupational categories; (b) the frequencies of correctional-specific PPTE exposures; and (c) the association between correctional-specific PPTEs and mental disorders. Population-attributable fractions (PAFs) are used to estimate the proportion of mental disorders that may be attributable to PPTE exposures., Results: Most correctional workers reported exposures to most types of PPTEs, including being directly threatened or subject to abusive language (94.6%), de-escalating a prison/client in mental health crisis (92.2%), and using force or suit up and resort to "use of force" in a nontraining situation (70.6%). The mean number of lifetime PPTE exposures was 7.79 ( SD = 3.33). There were statistically significant differences in PPTE exposure patterns across correctional worker categories. PPTEs were positively associated with mental disorder symptoms for all participants. PAFs indicated that mental disorders among correctional workers could reduce by 66%-80% with the elimination of all PPTEs among correctional workers., Conclusions: Eliminating PPTE exposures is unlikely in the correctional environment; nevertheless, the results indicate that mitigating PPTEs may drastically improve the mental health of correctional workers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Venous thromboembolism is a complex multifactorial disease considered the most common cause of preventable deaths in hospitalized patients. Recommendations about pharmacological venous thromboembolism prophylaxis in adult hospitalized patients are available in clinical practice guidelines for optimization of healthcare delivery and improvement of patient outcomes. We conducted a systematic review of clinical practice guidelines using ADAPTE to synthesize recommendations for pharmacological prophylaxis of venous thromboembolism in hospitalized medical patients at a medium complexity university hospital. Recommendations for pharmacological prophylaxis were extracted from seven clinical practice guidelines considered of high quality after assessment with the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. These recommendations will support discussion with specialists and implementation of practices in the setting of the hospital studied., Competing Interests: Conflicts of interest: No conflicts of interest declared concerning the publication of this article., (Copyright© 2023 The authors.)

The digestive tract of fish has many morphological adaptations related to habitat and nutrition. Intestinal biometry may reflect these adaptations. Here, we aimed to describe histometric patterns in farmed fish and their relationship with feeding by using a standardized protocol considering cell density by tissue area. Five juvenile specimens of each species (Pseudoplatystoma corruscans, Piaractus mesopotamicus, and Oreochromis niloticus) were used. O. niloticus possessed higher intestinal weight and length besides higher intestinal quotient and intestinal somatic index than the other species. The general histological composition was similar between species. However, P. corruscans showed differences in thickness between the anterior and posterior segments. O. niloticus had thinner serosa and muscularis layers than the other species. The cell density was distinct in both species and segments. Comparing the intestinal segments, O. niloticus displayed the lowest count of granulocytes. Goblet cell density was lower in P. mesopotamicus in all segments. However, the volume of these cells was higher in the anterior and middle anterior segments. Our data demonstrated that intestinal structural plasticity is associated with the difference in feeding habits. Here, we used quantitative standardized histometric criteria to understand the morphophysiological diversity of the fish digestive tract, and this technique can be applied in future studies to evaluate changes in the digestive tracts of vertebrates., (© 2023 Wiley-VCH GmbH.)

Ethnopharmacological Relevance: Hovenia dulcis Thunb. has been used as a medicinal herb for the treatment of hepatic diseases and alcohol intoxication., Aim of the Study: The genotoxic effect and the antigenotoxic potential of ethanolic extract of H. dulcis leaves and its methanolic fraction were evaluated against ethanol-induced damages in SH-SY5Y cells., Materials and Methods: The phytochemical analysis and antioxidant activity of H. dulcis extracts were also assessed. In addition, a systems biology analysis was performed to investigate the molecular pathway of action of the H. dulcis leaves compounds., Results: The ethanolic extract and its methanolic fraction presented genotoxicity through comet assay at 0.5 and 0.25 mg/mL. On the other hand, both extracts showed protective action against ethanol at all concentrations. Additionally, an NBT assay was performed and demonstrated an ability of the extracts to reduce superoxide anion formation when SH-SY5Y cells were challenged with ethanol. HPLC analysis indicated the presence of quercitrin, isoquercitrin, and rutin. Further, system biology assays indicated a molecular action pathway, where the compounds from the leaves of H. dulcis, in addition to performing free radical scavenging activity, activate PP2A, and may inhibit the apoptosis pathway activated by ethanol-induced oxidative stress., Conclusions: This work is important to indicate potential antigenotoxic and antioxidant properties of H. dulcis leaves, and its use can be investigated against DNA damage induced by ethanol., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Although several aspects of lignin metabolism have been extensively characterized, the mechanism(s) by which lignin monomers are transported across the plasma membrane remains largely unknown. Biochemical, proteomic, expression and co-expression analyses from several plant species support the involvement of active transporters, mainly those belonging to the ABC superfamily. Here, we report on the genome-wide characterization of the ABCG gene subfamily in the model C4 grass Setaria viridis and further identification of the members potentially involved in monolignol transport. A total of 48 genes encoding SvABCGs were found in the S. viridis genome, from which 21 SvABCGs were classified as full-size transporters and 27 as half-size transporters. Comprehensive analysis of the ABCG subfamily in S. viridis based on expression and co-expression analyses support a role for SvABCG17 in monolignol transport: (i) SvABCG17 is orthologous to AtABCG29, a monolignol transporter in Arabidopsis thaliana; (ii) SvABCG17 displays a similar expression profile to that of lignin biosynthetic genes in a set of different S. viridis tissues and along the elongating internode; (iii) SvABCG17 is highly co-expressed with lignin-related genes in a public transcriptomic database; (iv) SvABCG17displays particularly high expression in the top of the S. viridis elongating internode, a tissue undergoing active lignification; (v) SvABCG17 mRNA localization coincides with the histochemical pattern of lignin deposition; and (vi) the promoter of SvABCG17 is activated by secondary cell wall-associated transcription factors, especially by lignin-specific activators of the MYB family. Further studies might reveal further aspects of this potential monolignol transporter, including its real substrate specificity and whether it works redundantly with other ABC members during S. viridis lignification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Objectives: To analyze the World Health Organization's (WHO's) contribution to promotion of access to innovative technologies by assessing its initiatives on coronavirus disease 2019 (COVID-19) research, development, and innovation., Methods: A document search was done for previous criteria used by WHO working groups to evaluate innovation and access merits. Two sets of criteria were identified. One set was used to assess the suitability of existing mechanisms to coordinate research, development, and innovation and pool funds globally. The second set was used to measure success in implementing demonstration projects and consider the extent of innovative components being implemented by them. These criteria were applied to the COVID-19 Technology Access Pool (C-TAP) and Access to COVID-19 Tools Accelerator (ACT-A) initiatives. Scores were classified as: meets the criteria (2); partially meets the criteria (1); does not meet the criteria (0)., Results: Both initiatives met all the first set of criteria. C-TAP, an initiative based on a patent pool and other open knowledge approaches, best met the second set of criteria, scoring 7 out of 12 points. ACT-A, based on pooled funds, advanced purchase agreements, and voluntary contributions, met none of the second set of criteria., Conclusions: Equitable access to health technologies has been a recurring problem in recent pandemics and initiatives were proposed to prevent it. However, even though COVID-19 has been the greatest health crisis in the 21st century, market dynamics still prevailed. Income disparities between countries and lack of support for solidarity and a global health approach only aggravated the negative health and economic impacts.

The molecular mechanisms associated with secondary cell wall (SCW) deposition in sorghum remain largely uncharacterized. Here, we employed untargeted metabolomics and large-scale transcriptomics to correlate changes in SCW deposition with variation in global gene expression profiles and metabolite abundance along an elongating internode of sorghum, with a major focus on lignin and phenolic metabolism. To gain deeper insight into the metabolic and transcriptional changes associated with pathway perturbations, a bmr6 mutant [with reduced cinnamyl alcohol dehydrogenase (CAD) activity] was analyzed. In the wild type, internode development was accompanied by an increase in the content of oligolignols, p-hydroxybenzaldehyde, hydroxycinnamate esters, and flavonoid glucosides, including tricin derivatives. We further identified modules of genes whose expression pattern correlated with SCW deposition and the accumulation of these target metabolites. Reduced CAD activity resulted in the accumulation of hexosylated forms of hydroxycinnamates (and their derivatives), hydroxycinnamaldehydes, and benzenoids. The expression of genes belonging to one specific module in our co-expression analysis correlated with the differential accumulation of these compounds and contributed to explaining this metabolic phenotype. Metabolomics and transcriptomics data further suggested that CAD perturbation activates distinct detoxification routes in sorghum internodes. Our systems biology approach provides a landscape of the metabolic and transcriptional changes associated with internode development and with reduced CAD activity in sorghum., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aging is associated with adipose tissue dysfunction and is recognized as a risk factor for shortened life span. Considering that in vitro findings have shown the involvement of microRNA in extracellular vesicles and particles (EVPs) on senescence, we hypothesized that circulating EVPs derived from adipocytes can be involved in the aging process via their microRNA cargo. We aimed to determine the microRNA profiles of circulating EVPs derived from adipocytes (FABP4+) from aged and young adult animals and to perform in silico prediction of their downstream signaling effects. Plasma was obtained from Wistar rats (3 and 21 months old), and adipocyte-derived EVPs were isolated using the commercially available kit. Fatty acid-binding protein 4 (FABP4) was used for adipocyte-derived EVPs isolation; microRNA isolation and microarray expression analysis were performed. The analysis revealed 728 miRNAs, 32 were differentially between groups ( p < 0.05; fold change ≥ |1.1|), of which 15 miRNAs were upregulated and 17 were downregulated in circulating EVPs from aged animals compared to young adults. A conservative filter was applied, and 18 microRNAs had experimentally validated and highly conserved predicted mRNA targets, with a total of 2,228 mRNAs. Canonical pathways, disease and functions, and upstream regulator analyses were performed using IPA-QIAGEN, allowing a global and interconnected evaluation. IPA categories impacted negatively were cell cycle, cellular development, cellular growth and proliferation, and tissue development, while those impacted positively were "digestive system cancer" and "endocrine gland tumor." Interestingly, the upregulated miR-15-5p targets several cyclins, such as CCND1 and CCND2, and miR-24-3p seems to target CDK4 (cyclin-dependent kinase 4); then potentially inhibiting their expression, both miRNAs can induce a negative regulation of cell cycle progression. In contrast, silencing of negative cell cycle checkpoint regulators, such as p21 and p16, can be predicted, which can induce impairment in response to genotoxic stressors. In addition, predicted targets, such as SMAD family members, seem to be involved in the positive control of digestive and endocrine tumors. Taken together, this exploratory study indicates that miRNA signature in circulating adipocyte-derived EVPs may be involved with the double-edged sword of cellular senescence, including irreversible proliferation arrest and tissue-dependent cancer, and seems to be suitable for further validation and confirmatory studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Siqueira, de Souza Rodrigues, Flores, Vieira Cunha, Goldberg, Harmon, Batabyal, Freishtat and Cechinel.)

Objective: This systematic review investigated whether people with patellofemoral osteoarthritis (PFOA) have muscle strength, volume, and activation around the hip and knee that is different from asymptomatic controls., Methods: Searches were carried out in five electronic databases, with terms related to PFOA, including muscle strength, volume and activation. Only studies with at least one group with symptomatic PFOA and one asymptomatic group were included. The methodological quality of the studies was assessed using the Downs and Black checklist. Certainty of evidence was assessed using the GRADE methodology. Using the random effects model, a meta-analysis was performed when there were at least two studies reporting the same domain., Results: Eight studies (250 participants) met the inclusion criteria. Subjects with PFOA had weaker hip abduction (SMD -0.96; 95%CI = -1.34 to -0.57), hip external rotation (-0.55;-1.07 to -0.03), hip extension (-0.72;-1.16 to -0.28), and knee extension (-0.97;-1.41 to -0.53) when compared to asymptomatic controls. People with PFOA also presented with smaller volumes of the gluteus medius, gluteus minimus, tensor fascia lata, vastus medialis (VM), vastus lateralis (VL) and rectus femoris when compared to asymptomatic controls. Also, people with PFOA presented with changes in muscle activation for the VL, VM and gluteus maximus (GMax) when compared to asymptomatic controls., Conclusion: People with PFOA present with lower strength and volume of the hip and quadriceps muscles and altered muscle activation of the VM, VL and GMax during ascending and descending stairs when compared to asymptomatic controls. However, the certainty of these findings are very low., Trial Registration Number: PROSPERO systematic review protocol (ID = CRD42020197776)., (Copyright © 2022. Published by Elsevier Ltd.)

Abstract: The aim of this study was to determine the prevalence of sleep disorders and associated factors in people living with HIV (PLWH). This was a cross-sectional study with a sample of 385 participants followed-up on an outpatient basis in Fortaleza, Ceará, Brazil. Interviews were conducted using the Sociodemographic, Epidemiological and Clinical Form for PLWH and the Pittsburgh Sleep Quality Index. Descriptive statistics and univariate and multivariate logistic regression analysis were performed, and the odds ratio (OR) and 95% confidence interval (95% CI) were calculated, considering p < .05 as statistically significant. The prevalence of sleep disorders was 43.38%. Having children ( p = .0054; OR = 1.91; 95% CI = 1.21-3.01), less than 8 years of education ( p = .0013; OR = 2.11; 95% CI = 1.34-3.34), and not engaging in regular physical exercise ( p = .0001; OR = 2.61; 95% CI = 1.61-4.23) were factors associated with the occurrence of sleep disorders. It was concluded that almost half of the sample had sleep disorders, especially those with children, low level education, and sedentary habits. These data point to the need for increased guidance on sleep hygiene, in addition to the practice of regular physical exercise for this population., (Copyright © 2022 Association of Nurses in AIDS Care.)

Introduction: Drug scheduling in older adults can be a challenge, especially considering polypharmacy, physical dependency, and possible drug interactions. Properly testing alternative treatment regimens could therefore help to overcome treatment barriers. Hypothyroidism is a prevalent condition in older adults, however, studies evaluating L-thyroxine treatment effectiveness in this specific age group are still lacking. Most studies testing an evening administration of levothyroxine were mainly composed of younger adults. Therefore, this trial is aimed to assess if evening levothyroxine (LT4) administration can effectively control hypothyroidism in older patients., Materials and Methods: A randomized crossover clinical trial was conducted between June 2018 and March 2020 at the Hospital de Clínicas de Porto Alegre, a teaching hospital in Brazil, to compare the efficacy of morning and evening administration of LT4 for hypothyroidism control in older patients. The study protocol is published elsewhere. A total of 201 participants, ≥60 years old, with primary hypothyroidism treated with LT4 for at least 6 months and on stable doses for at least 3 months were included. Participants were randomly assigned to a starting group of morning LT4 intake (60 min before breakfast) or bedtime LT4 intake (60 min after the last meal). After ≥12 weeks of follow-up, a crossover between strategies was performed. The primary outcome was the change in serum thyrotropin (Thyroid-Stimulating Hormone; TSH) levels after 12 weeks of each LT4 administration regimen., Results: A total of 201 participants with mean age of 72.4 ± 7.2 years were included, out of which 84.1% were women; baseline characteristics and frequency of controlled hypothyroidism were similar between groups. Mean baseline TSH was 3.43 ± 0.25 mUI/L. In total, 118 participants attended three meetings, allowing 135 comparisons by crossover analytic strategy. Mean TSH levels after follow-up were 2.95 ± 2.86 in the morning group and 3.64 ± 2.86 in the bedtime group, p = 0.107., Discussion: Thyroid-Stimulating Hormone levels and frequency of controlled hypothyroidism were similar during the follow-up period regardless of the treatment regimen (morning or bedtime)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 de Mello, Giassi, Stahl, Machado Assis, Flores, de Lima, Piccoli and da Costa Rodrigues.)

Introduction: Patellofemoral pain (PFP) is a chronic condition that affects up to 25% of the general population and has a negative impact on functionality and quality of life due to the high levels of pain experienced by these patients. In order to improve pain and function, rehabilitation programmes that combine adjunctive treatments with exercise therapy are often used in research and clinical settings. However, despite the variety of adjunctive treatments available, their effectiveness when compared with exercise therapy has yet to be elucidated. Thus, the aim of this study is to evaluate the effectiveness of adjunctive treatments plus exercise therapy versus exercise therapy, and determine the relative efficacy of different types of adjunctive treatments plus exercise therapy for individuals with PFP., Methods and Analysis: A systematic review and network meta-analysis will be conducted based on the Cochrane Collaboration recommendations and reported in line with Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We will search Embase, PubMed (MEDLINE), CENTRAL, CINAHL, PEDro, SPORTDiscus, Web of Science and OpenGrey. It will be included randomised controlled trials that compared adjunctive treatment plus exercise therapy to placebo adjunctive treatment plus exercise therapy or exercise therapy. The outcomes of interest will be pain and function, with no restrictions on language, setting or year of publication. Study selection will be performed by two independent reviewers, based on the eligibility criteria. Risk of bias will be assessed using the Physiotherapy Evidence Database scale and the evidence summarised via the Grading of Recommendation, Assessment, Development and Evaluation approach. A Bayesian network meta-analysis will be performed to compare the efficacy of different adjunctive treatments plus exercise therapy. Consistency between direct and indirect comparisons will be assessed., Ethics and Dissemination: No ethical statement will be required for this systematic review and meta-analysis. The findings will be published in a relevant international peer-reviewed journal and presented at conferences., Prospero Registration Number: CRD42020197081., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The leaves of the wild tomato Solanum galapagense harbor type-IV glandular trichomes (GT) that produce high levels of acylsugars (AS), conferring insect resistance. Conversely, domesticated tomatoes ( S. lycopersicum ) lack type-IV trichomes on the leaves of mature plants, preventing high AS production, thus rendering the plants more vulnerable to insect predation. We hypothesized that cultivated tomatoes engineered to harbor type-IV trichomes on the leaves of adult plants could be insect-resistant. We introgressed the genetic determinants controlling type-IV trichome development from S. galapagense into cv. Micro-Tom (MT) and created a line named " Galapagos-enhanced trichomes " (MT- Get ). Mapping-by-sequencing revealed that five chromosomal regions of S. galapagense were present in MT- Get . Further genetic mapping showed that S. galapagense alleles in chromosomes 1, 2, and 3 were sufficient for the presence of type-IV trichomes on adult organs but at lower densities. Metabolic and gene expression analyses demonstrated that type-IV trichome density was not accompanied by the AS production and exudation in MT- Get . Although the plants produce a significant amount of acylsugars, those are still not enough to make them resistant to whiteflies. We demonstrate that type-IV glandular trichome development is insufficient for high AS accumulation. The results from our study provided additional insights into the steps necessary for breeding an insect-resistant tomato.

Low concentrations of biomarkers as well as the complexity of biological samples make the clinical diagnoses of several diseases a challenging task. Sample preparation protocols remain a fundamental piece in the puzzle of analytical processes, and smart sorbents including molecularly imprinted polymers (MIPs) have been successfully used in this case. In this review, we depict the state of art for the rational design of MIPs to be used in solid phase extraction of disease biomarkers from biological samples. The topics are divided into (1) strategies for MIP syntheses, (2) setups for sample preparation protocols with MIPs, (3) the applications of these combined principles in the analyses of different classes of disease biomarkers, and (4) remaining challenges and future trends for the application of Molecular Imprinting Technology in sample preparation for clinical diagnosis.

Melipona quadrifasciata anthidioides is a species of stingless bee popularly known in Brazil as "mandaçaia". Products derived from bees for food and therapeutic uses, have stimulated the evaluation of the chemical composition of geopropolis. Concentrations of 24 essential and potentially toxic elements were determined in geopropolis samples, using a sequential optical emission spectrometer with inductively coupled plasma (ICP OES) after microwave-assisted acid digestion. Principal component analysis (PCA) and Hierarchical cluster analysis (HCA) were used to carry out an exploratory analysis of the samples. The following elements were quantified (in mg Kg -1 ): Al (320,414.40-36,911.1), As (

Hematological parameters can provide key information to an animal health status. However, this information is usually hard to obtain. Here, we described the hematological parameters of Leptodactylus podicipinus in the Brazilian Pantanal. We measured red blood cell morphometrics, erythrogram, and leukogram. We also tested for phylogenetic signal in the erythrogram and leukogram of 48 frog species from 15 families, testing if body size explains their variation. Lymphocytes were the most abundant leukocytes (>60%) in L. podicipinus , followed by neutrophils (∼10%). Given that L. podicipinus is an abundant and widely distributed species in central Brazil, knowing its hematological pattern can help establish a baseline and improve its use as a bioindicator of environmental degradation. Mean corpuscular hemoglobin and value contributed more to the phylomorphospace of erythrogram, in which Leptodactylus spp. and Hypsiboas raniceps had lower values of these variables, whereas Bufotes viridis and Hyla arborea had high values. The phylogenetic signal was spread throughout the dimensions of the leukogram phylomorphospace. The variables that most contributed to it were total leukocytes counts, lymphocytes, and neutrophils. We also found a moderate phylogenetic signal for both the erythrogram and leukogram. Accordingly, body size accounted for a low proportion of variation in both the leukogram (4.7%) and erythrogram (0.57%). By applying phylogenetic comparative methods to hematological parameters, our results add a new perspective on the evolution of blood cell physiology in frogs., (© The Author(s) (2021). Published by Oxford University Press on behalf of Editorial Office, Current Zoology.)

The aging process is associated with many brain structural alterations. These changes are not associated with neuronal loss but can be due to cortical structural changes that may be related to white matter (WM) structural alterations. In this study, we evaluated age-related changes in WM and gray matter (GM) parameters and how they correlate for specific brain tracts in a cohort of 158 healthy individuals, aged between 18 and 83 years old. In the tract-cortical analysis, cortical regions connected by tracts demonstrated similar thinning patterns for the majority of tracts. Additionally, a significant relationship was found between mean cortical thinning rate with fractional anisotropy (FA) and mean diffusivity (MD) alteration rates. For all tracts, age was the main effect controlling diffusion parameter alterations. We found no direct correlations between cortical thickness and FA or MD, except for in the fornix, for which the subcallosal gyrus thickness was significantly correlated to FA and MD (p < 0.05 FDR corrected). Our findings lead to the conclusion that alterations in the WM diffusion parameters are explained by the aging process, also associated with cortical thickness changes. Also, the alteration rates of the structural parameters are correlated to the different brain tracts in the aging process.

Diflubenzuron (DFB) is a widely used insecticide to control ectoparasites in fish farming. Although therapeutic concentrations (i.e., 50 to 100 mg/L) are safe as they fail to induce mortality, they can promote tissue changes. In Brazil, Pacu (Piaractus mesopotamicus) is a native species used for commercial production, and it remains crucial to determine underlying mechanisms to mitigate the potential effects of pathogens on productivity. The aim of this study was to analyze the transaminase profile and histopathological changes in the liver of P. mesopotamicus exposed to a DFB bath. Hence, the fish were exposed to an immersion bath containing a 70 mg/L nominal concentration of Difluchem 240 SC® (24% (m/m) DFB) for 30 (n = 10), 60 (n = 10), and 120 min (n = 10), every 24 h for 3 days. Following exposure, plasma transaminases and liver histology were analyzed. In DFB-exposed fish, levels of aspartate transaminase (AST) and alanine transaminase (ALT) were elevated when compared with the control at 30 and 60 min. Furthermore, liver morphology was altered based on exposure times. Compared with controls, the degree of reversible damage (degree of tissue change (DTC)) demonstrated high scores for all exposure times, with no difference between individual groups. Irreversible changes were increased in the 60 and 120-min baths. These findings highlight the impact of the therapeutic DFB concentration (i.e., 70 mg/L), revealing that 60-min and 120-min bathing induces irreversible and progressive hepatic changes.

The size and shape of red blood cells (RBCs) provide key information on life-history strategies in vertebrates. However, little is known about how RBC shape evolved in response to environmental factors, body size and the role of evolutionary rate. Here, we analysed RBC morphometrics in a set of Teleostei (bony fishes) and Elasmobranchii (sharks and rays) species testing the hypothesis that phylogenetic relationship explains species occupation of morphospace. We collected data on cell and nucleus area and volume, nucleus:cytoplasm ratio and shape factor for 65 species belonging to 28 orders. Then, we built phylomorphospaces separately for bony fish and sharks and rays. To test whether phylogenetic relationships predicted phenotypic similarity, we calculated multivariate phylogenetic signal. We also estimated the evolutionary rate of RBC shape for each node and tip using ridge regression. Finally, we tested whether habitat and body size influenced RBC shape using a PGLS. We found a significant phylogenetic signal in RBC shape for bony fish, but not sharks and rays. Saltwater teleost species were more clustered than freshwater ones in the phylomorphospace, suggesting clade disparity. Accordingly, the rate of evolution was highly heterogeneous, with significant decrease in Acanthopterygii. Neither habitat nor body size influenced RBC shape. In conclusion, RBC shape seems to have evolved in fishes in response to multiple selective pressures independent of life-history characters., (© 2021 European Society for Evolutionary Biology. Journal of Evolutionary Biology © 2021 European Society for Evolutionary Biology.)

Objective: Studies confirm the benefit of surgical treatment for fixation of displaced midshaft clavicle fractures. Plate fixation and intramedullary nail are the two most used techniques. Our study seeks to compare these two surgical techniques., Methods: This is a retrospective study, conducted by the evaluation of patients treated for displaced midshaft clavicle fracture with intramedullary nail, and plate and screws. Socioeconomic variables were collected, a visual pain scale questionnaire was applied, the shoulder function was measured using CONSTANT and UCLA scores, and radiography was performed to verify the consolidation and evaluation of the final clavicle shortening., Results: Sixty-five patients were evaluated, 36 (55.4%) of which were subjected to clavicle fixation with plate and screws and 29 (44.6%) with intramedullary nail. The median shortening was 0.1mm for plate and 5.8mm for nail (p = 0.001). The UCLA score shows an average of 35 in the plate group and 35 in the intramedullary group. The median CONSTANT scores were 96.5 for plate and 95 for nail, without significance. In all groups, 13 (20%) complications were registered, 9 fixed with plate and 4 fixed with intramedullary nail. The most common complication was skin erosion with exposure of the synthetic material. Conclusion: The two techniques present satisfactory results for the treatment of displaced midshaft clavicle fractures. Level of Evidence III, Therapeutic Studies Investigating the Results of Treatment., Competing Interests: All authors declare no potential conflict of interest related to this article.

Plant lignocellulosic biomass, mostly composed of polysaccharide-rich secondary cell walls (SCWs), provides fermentable sugars that may be used to produce biofuels and biomaterials. However, the complex chemical composition and physical structure of SCWs hinder efficient processing of plant biomass. Understanding the molecular mechanisms underlying SCW deposition is, thus, essential to optimize bioenergy feedstocks. Here, we establish a xylogenic culture as a model system to study SCW deposition in sugarcane; the first of its kind in a C4 grass species. We used auxin and brassinolide to differentiate sugarcane suspension cells into tracheary elements, which showed metaxylem-like reticulate or pitted SCW patterning. The differentiation led to increased lignin levels, mainly caused by S-lignin units, and a rise in p -coumarate, leading to increased p -coumarate:ferulate ratios. RNAseq analysis revealed massive transcriptional reprogramming during differentiation, with upregulation of genes associated with cell wall biogenesis and phenylpropanoid metabolism and downregulation of genes related to cell division and primary metabolism. To better understand the differentiation process, we constructed regulatory networks of transcription factors and SCW-related genes based on co-expression analyses. Accordingly, we found multiple regulatory modules that may underpin SCW deposition in sugarcane. Our results provide important insights and resources to identify biotechnological strategies for sugarcane biomass optimization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Simões, Ferreira, Grandis, Rencoret, Persson, Floh, Ferraz, del Río, Buckeridge and Cesarino.)

Contagious agalactia is a disease caused by Mycoplasma agalactiae that leads to a reduction or complete stop of milk production. Caprine arthritis encephalitis (CAE) is an infectious disease caused by a lentivirus of the Retroviridae family, member of the small ruminant lentivirus (SRLV) group. Although these diseases are caused by distinct pathogens, the clinical presentation is similar. Hence, this study aimed to perform a serological investigation, as well as to assess correlation between both diseases and risk factors associated in two mesoregions of Rio Grande do Norte, Brazil. Enzyme-linked immunosorbent assay (ELISA) was used for contagious agalactia and western blot for CAE. A total of 538 serum samples were used in this study that were collected from goats and sorted from a blood bank of the Brazilian Agricultural Research Corporation. Seroprevalence of M. agalactiae in flocks from Rio Grande do Norte was 7.8% (42/538). In both regions that were investigated, 25.9% (14/54) of farms had positive animals. CAE results revealed that 3.9% (21/538) of animals and 42.6% (23/54) of farms had this disease. Concerning risk factors, only sex and animal category presented significant relevance (P < 0.05) for contagious agalactia, in which females presented higher frequency of seropositive individuals (10.1%; 39/387). In the animal category, 4.3% (14/326) and 11.1% (36/323) of female breeders were positive for CAE and contagious agalactia, respectively, and significance was identified only in the latter (P < 0.05). In conclusion, there was no correlation between the investigated diseases, considering that no animal demonstrated antibodies for both pathogens.

The biotrophic fungus Phakopsora pachyrhizi is currently the major pathogen affecting soybean production worldwide. It has already been suggested for the non-host interaction between P. pachyrhizi and Arabidopsis thaliana that the fungus in early infection induces jasmonic acid (JA) pathway to the detriment of the salicylic acid (SA) pathway as a mechanism to the establishment of infection. In this study, we verified that this mechanism might also be occurring during the compatible interaction in soybean (Glycine max L. Merril). It was demonstrated that P. pachyrhizi triggers a JA pathway during the early and late stages of infection in a susceptible soybean cultivar. The expression of the GmbZIP89 was induced in a biphasic profile, similarly to other JA responsive genes, which indicates a new marker gene for this signaling pathway. Additionally, plants silenced for GmbZIP89 (iGmZIP89) by the virus-induced gene silencing (VIGS) approach present lower severity of infection and higher expression of pathogenesis related protein 1 (PR1). The lower disease severity showed that the iGmbZIP89 plants became more resistant to infection. These data corroborate the hypothesis that the GmbZIP89 may be a resistance negative regulator. In conclusion, we demonstrated that P. pachyrhizi mimics a necrotrophic fungus and activates the JA/ET pathway in soybean. It is possible to suppose that its direct penetration on epidermal cells or fungal effectors may modulate the expression of target genes aiming the activation of the JA pathway and inhibition of SA defense., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

MRI diffusion data suffers from significant inter- and intra-site variability, which hinders multi-site and/or longitudinal diffusion studies. This variability may arise from a range of factors, such as hardware, reconstruction algorithms and acquisition settings. To allow a reliable comparison and joint analysis of diffusion data across sites and over time, there is a clear need for robust data harmonization methods. This review article provides a comprehensive overview of diffusion data harmonization concepts and methods, and their limitations. Overall, the methods for the harmonization of multi-site diffusion images can be categorized in two main groups: diffusion parametric map harmonization (DPMH) and diffusion weighted image harmonization (DWIH). Whereas DPMH harmonizes the diffusion parametric maps (e.g., FA, MD, and MK), DWIH harmonizes the diffusion-weighted images. Defining a gold standard harmonization technique for dMRI data is still an ongoing challenge. Nevertheless, in this paper we provide two classification tools, namely a feature table and a flowchart, which aim to guide the readers in selecting an appropriate harmonization method for their study., (Copyright © 2020 Pinto, Paolella, Billiet, Van Dyck, Guns, Jeurissen, Ribbens, den Dekker and Sijbers.)

Purpose: Head and neck squamous cell carcinoma (HNSCC) incidence is high in South America, where recent data on survival are sparse. We investigated the main predictors of HNSCC survival in Brazil, Argentina, Uruguay, and Colombia., Methods: Sociodemographic and lifestyle information was obtained from standardized interviews, and clinicopathologic data were extracted from medical records and pathologic reports. The Kaplan-Meier method and Cox regression were used for statistical analyses., Results: Of 1,463 patients, 378 had a larynx cancer (LC), 78 hypopharynx cancer (HC), 599 oral cavity cancer (OC), and 408 oropharynx cancer (OPC). Most patients (55.5%) were diagnosed with stage IV disease, ranging from 47.6% for LC to 70.8% for OPC. Three-year survival rates were 56.0% for LC, 54.7% for OC, 48.0% for OPC, and 37.8% for HC. In multivariable models, patients with stage IV disease had approximately 7.6 (LC/HC), 11.7 (OC), and 3.5 (OPC) times higher mortality than patients with stage I disease. Current and former drinkers with LC or HC had approximately 2 times higher mortality than never-drinkers. In addition, older age at diagnosis was independently associated with worse survival for all sites. In a subset analysis of 198 patients with OPC with available human papillomavirus (HPV) type 16 data, those with HPV-unrelated OPC had a significantly worse 3-year survival compared with those with HPV-related OPC (44.6% v 75.6%, respectively), corresponding to a 3.4 times higher mortality., Conclusion: Late stage at diagnosis was the strongest predictor of lower HNSCC survival. Early cancer detection and reduction of harmful alcohol use are fundamental to decrease the high burden of HNSCC in South America.

Plants have developed mechanisms to avoid harmful effects of Na + accumulation, such as the signaling pathway of carrier proteins Na + /H + (NHX) and salt overly sensitive (SOS). Besides, endoplasmic reticulum (ER) could integrate plant cell response. Thus, we aimed to understand the effects of ER homeostasis impairment, and its relationship to salt stress during early stages of the Sorghum bicolor CSF 20 a salt-tolerant variety. Three days old seedlings were challenged with NaCl (0, 50, 75 and 100 mM), dithiothreitol (DTT) at 0, 2.5, 5.0 10.0 mM, and the combined NaCl and DTT treatments. Tunicamycin (TUN) was also used as a second inducer of ER stress in a quantitative PCR, to corroborate with DTT's results. There was no significant change in growth parameters under NaCl treatments. Nevertheless, seedling length, mass and Na + content were decreased as DTT concentration was increased. Under combined NaCl and DTT treatments, shoot length and fresh and dry masses were maintained at control levels. On the other hand, the levels of Na + were decreased, in comparison to NaCl treatment. Genes analyzed by qPCR revealed that NaCl was able to induce all of them, except for SbbZIP60, however it was induced under combined stresses. In conclusion, the results indicated that S. bicolor seedlings of CSF 20 variety were tolerant to salt and sensible to ER stress. The combination of both stresses restored the ER homeostasis promoting a decrease of Na + content via the membrane transporters SbNHX1, SbSOS1, and SbPDI ER-chaperone and the ER sensor SbbZIP60., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Main Conclusion: Five laccase genes are potentially involved in developmental lignification in the model C4 grass Setaria viridis and their different tissue specificities suggest subfunctionalization events. Plant laccases are copper-containing glycoproteins involved in monolignol oxidation and, therefore, their activity is essential for lignin polymerization. Although these enzymes belong to large multigene families with highly redundant members, not all of them are thought to be involved in lignin metabolism. Here, we report on the genome-wide characterization of the laccase gene family in the model C4 grass Setaria viridis and further identification of the members potentially involved in monolignol oxidation. A total of 52 genes encoding laccases (SvLAC1 to SvLAC52) were found in the genome of S. viridis, and phylogenetic analyses showed that these genes were heterogeneously distributed among the characteristic six subclades of the family and are under relaxed selective constraints. The observed expansion in the total number of genes in this species was mainly caused by tandem duplications within subclade V, which accounts for 68% of the whole family. Comparative phylogenetic analyses showed that the expansion of subclade V is specifically observed for the Paniceae tribe within the Panicoideae subfamily in grasses. Five SvLAC genes (SvLAC9, SvLAC13, SvLAC15, SvLAC50, and SvLAC52) fulfilled the criteria established to identify lignin-related candidates: (1) phylogenetic proximity to previously characterized lignin-related laccases from other species, (2) similar expression pattern to that observed for lignin biosynthetic genes in the S. viridis elongating internode, and (3) high expression in S. viridis tissues undergoing active lignification. In addition, in situ hybridization experiments not only confirmed that these selected SvLAC genes were expressed in lignifying cells, but also that their expression showed different tissue specificities, suggesting subfunctionalization events within the family. These five laccase genes are strong candidates to be involved in lignin polymerization in S. viridis and might be good targets for lignin bioengineering strategies.

Trypanosoma cruzi causes Chagas disease, a neglected illness that affects millions of people worldwide, especially in Latin America. The balance between biochemical pathways triggered by the parasite and host cells response will ultimately define the progression of a life-threatening disease, justifying the efforts to understand cellular mechanisms for infection restrain. In this interaction, parasite and host cells are affected by different physiological responses as autophagy modulation, which could be under intense cellular stress, such as nutrient deprivation, hormone depletion, or infection. Autophagy is a constitutive pathway that leads to degradation of macromolecules and cellular structures and may induce cell death. In Trypanosoma cruzi infection, the relevance of host autophagy is controversial regarding in vitro parasite intracellular life cycle. In the present study, we evaluated host cell autophagy during T. cruzi infection in phagocytic and non-professional phagocytic cells. We described that the presence of the parasite increased the number of LC3 puncta, a marker for autophagy, in cardiac cells and peritoneal macrophages in vitro. The induction of host autophagy decreased infection in macrophages in early and late time-periods. We suggest that starved phagocytic cells reduced internalization, also confirmed by inert particles and dead trypomastigotes. Whereas, in cardiac cells, starvation-induced autophagy decreased lipid droplets and infection in later time-point, by reducing parasite differentiation/proliferation. In ATG5 knockout MEF cells, we confirmed our hypothesis of autophagy machinery activation during parasite internalization, increasing infection. Our data suggest that host autophagy downregulates T. cruzi infection through impairing parasite intracellular life cycle, reducing the infection in primary culture cells., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

NAC proteins are one of the largest families of plant-specific transcription factors (TFs). They regulate diverse complex biological processes, including secondary xylem differentiation and wood formation. Recent genomic and transcriptomic studies of Tectona grandis L.f. (teak), one of the most valuable hardwood trees in the world, have allowed identification and analysis of developmental genes. In the present work, T. grandis NAC genes were identified and analyzed regarding to their evolution and expression profile during wood formation. We analyzed the recently published T. grandis genome, and identified 130 NAC proteins that are coded by 107 gene loci. These proteins were classified into 23 clades of the NAC family, together with Populus , Eucalyptus, and Arabidopsis. Data on transcript expression revealed specific temporal and spatial expression patterns for the majority of teak NAC genes. RT-PCR indicated expression of VND genes ( Tg11g04450-VND2 and Tg15g08390-VND4 ) related to secondary cell wall formation in xylem vessels of 16-year-old juvenile trees. Our findings open a way to further understanding of NAC transcription factor genes in T. grandis wood biosynthesis, while they are potentially useful for future studies aiming to improve biomass and wood quality using biotechnological approaches., Competing Interests: The authors declare no conflicts of interest.

Key Message: The core set of biosynthetic genes potentially involved in developmental lignification was identified in the model C4 grass Setaria viridis. Lignin has been recognized as a major recalcitrant factor negatively affecting the processing of plant biomass into bioproducts. However, the efficient manipulation of lignin deposition in order to generate optimized crops for the biorefinery requires a fundamental knowledge of several aspects of lignin metabolism, including regulation, biosynthesis and polymerization. The current availability of an annotated genome for the model grass Setaria viridis allows the genome-wide characterization of genes involved in the metabolic pathway leading to the production of monolignols, the main building blocks of lignin. Here we performed a comprehensive study of monolignol biosynthetic genes as an initial step into the characterization of lignin metabolism in S. viridis. A total of 56 genes encoding bona fide enzymes catalyzing the consecutive ten steps of the monolignol biosynthetic pathway were identified in the S. viridis genome. A combination of comparative phylogenetic studies, high-throughput expression analysis and quantitative RT-PCR analysis was further employed to identify the family members potentially involved in developmental lignification. Accordingly, 14 genes clustered with genes from closely related species with a known function in lignification and showed an expression pattern that correlates with lignin deposition. These genes were considered the "core lignin toolbox" responsible for the constitutive, developmental lignification in S. viridis. These results provide the basis for further understanding lignin deposition in C4 grasses and will ultimately allow the validation of biotechnological strategies to produce crops with enhanced processing properties.

Dormancy-Associated gene 1/Auxin Repressed protein (DRM1/ARP) genes are responsive to hormones involved in defense response to biotic stress, such as salicylic acid (SA) and methyl jasmonate (MeJA), as well as to hormones that regulate plant growth and development, including auxins. These characteristics suggest that this gene family may be an important link between the response to pathogens and plant growth and development. In this investigation, the DRM1/ARP genes were identified in the genome of four legume species. The deduced proteins were separated into three distinct groups, according to their sequence conservation. The expression profile of soybean genes from each group was measured in different organs, after treatment with auxin and MeJA and in response to the nematode Meloidogyne javanica. The results demonstrated that this soybean gene family is predominantly expressed in root. The time auxin takes to alter DRM1/ARP expression suggests that these genes can be classified as a late response to auxin. Nevertheless, only the groups 1 and 3 are induced in roots infected by M. javanica and only group 3 is induced by MeJA, which indicates a high level of complexity in expression control mechanisms of DRM1/ARP family in soybean., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Obesity is an important nutritional disorder worldwide. Its association with environmental pollution may trigger an increase in oxidative stress and inflammatory parameters. Coal is a resource used throughout the world as an important fuel source for generating electricity. The ashes released by the coal combustion cause serious problems for human health due to their high toxicity and their capacity to bioaccumulate. The aim of this work was to investigate the effects of coal dust inhalation in the organs of obese and non-obese Wistar rats. Pro-inflammatory cytokines, oxidative stress, oxidative damage, histological analysis, comet assay, and micronuclei were investigated. Both obesity and coal dust inhalation increased the pro-inflammatory cytokines IL-1β and TNF-α and decreased HSP70 levels in serum, however, in obese animals that inhaled coal dust these changes were more pronounced. Liver histological analysis showed severe microvesicular steatosis in obese animals that inhaled coal dust. Lung histologic investigation showed abnormalities in lung structure of animals exposed to coal dust and showed severe lung distensibility in obese animals exposed to coal dust. The comet assay showed DNA damage in animals subjected to coal. In addition, there were modulations in enzymatic activities and damage to protein and lipids. Based on our results, the coal dust inhalation can potentiate the pro-inflammatory profile present in obese rats. We also observed an increase in the protein oxidative damage in obese rats that inhaled coal dust. Taken together, our results suggest that the combination of obesity and coal inhalation increased the risks of the development of diseases related to oxidative stress and inflammation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Peak sound levels during sleep can compromise the development of hospitalized infants. Quiet time is a strategy implemented in neonatal units to promote the sleeping of neonates by reducing noise levels, luminosity, and handling during particular periods of the day., Purpose: To determine the impact of quiet time on reducing sound levels and increasing total sleep time., Methods: This longitudinal study was conducted at a neonatal intermediate care unit with a convenience sample of 12 premature infants. Four times per day, 60-minute quiet times were provided in the neonatal unit. Sleep-awake states and sound levels were evaluated during quiet times as well as 60 minutes before and afterward. Polysomnography was used for sleep-awake state assessment, and a noise dosimeter was used to check sound levels every 24 hours., Results: The preterm infants had a corrected gestational age of 35.0 ± 1.5 weeks and weighed 1606.0 ± 317.8 g. Total sleep time was highest during quiet time (P = .005). Premature infants remained awake for longer following quiet times (P = .005). There was also a reduction in sound level during quiet times compared with the other time frames (P = .006). No statistically significant relationship was found between total sleep time and sound levels more than 24 hours., Implications for Practice: Quiet time is a nursing intervention that should be implemented in all neonatal units., Implications for Research: Future research should use a greater sample size and other factors that influence sleep should be further investigated.

Aim: Dexamethasone (Dex) has been used for the treatment of ocular diseases, presenting concentrations up to 150 ng/ml in the biological matrix. Drug sampling has been performed from aqueous humor (AH), which the volume varies from 50 to 200 μl, becoming a challenge for analytical analyses., Results: We developed and validated a direct and sensitive method by LC-MS/MS for Dex measurement in human AH, using water as surrogate matrix to reduce the sample volume applied in some validation assays. With accuracies of 99.6% and precision within 15% in the range of 0.1-150 ng/ml, Dex had an 87-day stability., Conclusion: Our method is robust and sensitive enough to be applied in bioequivalence studies with human AH using only 20 μl of biological sample.

Despite substantial improvement in prognosis and quality of life among people living with HIV/AIDS (PLWHA) in Brazil, inequalities in access to treatment remain. We assessed the impact of these inequalities on survival in Rio de Janeiro over a 12-year period (2000/11). Data were merged from four databases that comprise the national AIDS monitoring system: SINAN-AIDS (Brazilian Information System for Notificable Diseases; AIDS cases), SISCEL (laboratory tests), SICLOM (electronic dispensing system), and SIM (Brazilian Mortality Information System), using probabilistic linkage. Cox regressions were fitted to assess the impact of HAART (highly active antiretroviral therapy) on AIDS-related mortality among men who have sex with men (MSM), people who inject drugs (PWID), and heterosexuals diagnosed with AIDS, between 2000 and 2011, in the city of Rio de Janeiro, RJ, Brazil. Among 15,420 cases, 60.7% were heterosexuals, 36.1% MSM and 3.2% PWID. There were 2,807 (18.2%) deaths and the median survival time was 6.29. HAART and CD4+ > 200 at baseline were associated with important protective effects. Non-whites had a 33% higher risk of dying in consequence of AIDS than whites. PWID had a 56% higher risk and MSM a 11% lower risk of dying of AIDS than heterosexuals. Non-white individuals, those with less than eight years of formal education, and PWID, were more likely to die of AIDS and less likely to receive HAART. Important inequalities persist in access to treatment, resulting in disparate impacts on mortality among exposure categories. Despite these persistent disparities, mortality decreased significantly during the period for all categories under analysis, and the overall positive impact of HAART on survival has been dramatic.

Different sampling strategies, analytic alternatives, and estimators have been proposed to better assess the characteristics of different hard-to-reach populations and their respective infection rates (as well as their sociodemographic characteristics, associated harms, and needs) in the context of studies based on respondent-driven sampling (RDS). Despite several methodological advances and hundreds of empirical studies implemented worldwide, some inchoate findings and methodological challenges remain. The in-depth assessment of the local structure of networks and the performance of the available estimators are particularly relevant when the target populations are sparse and highly stigmatized. In such populations, bottlenecks as well as other sources of biases (for instance, due to homophily and/or too sparse or fragmented groups of individuals) may be frequent, affecting the estimates.In the present study, data were derived from a cross-sectional, multicity RDS study, carried out in 12 Brazilian cities with transgender women (TGW). Overall, infection rates for HIV and syphilis were very high, with some variation between different cities. Notwithstanding, findings are of great concern, considering the fact that female TGW are not only very hard-to-reach but also face deeply-entrenched prejudice and have been out of the reach of most therapeutic and preventive programs and projects.We cross-compared findings adjusted using 2 estimators (the classic estimator usually known as estimator II, originally proposed by Volz and Heckathorn) and a brand new strategy to adjust data generated by RDS, partially based on Bayesian statistics, called for the sake of this paper, the RDS-B estimator. Adjusted prevalence was cross-compared with estimates generated by non-weighted analyses, using what has been called by us a naïve estimator or rough estimates.