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ABSTRACT Relaxation dynamics is universal in science and engineering; its study serves to parameterize a system's response and to help identify a microscopic model of the processes involved. When measured data for a phenomenon cannot be fitted using one exponential, the choice of an alternative function to describe the decay becomes nontrivial. Here, we contrast two different, but fundamentally related approaches to fitting nontrivial decay curves; exponential decomposition and the gamma probability density function. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives/ Hypothesis: The objective was to present the unique case of previously unreported asymptomatic cylindrical tracheal foreign body causing near-total airway obstruction. The asymptomatic nature of the case made diagnosis and management challenging. Study Design: A retrospective case review at an urban health maintenance organization medical center. Methods: A 3.5-year-old asymptomatic boy was incidentally discovered to have a metallic foreign body in his mid trachea on a screening scoliosis roentgenogram. He underwent rigid bronchoscopic retrieval the following day. Results: The foreign body was found to be a corroded, 9 x 6-mm metallic cylinder with a narrowed luminal diameter of 2.0 mm. Intubation was maintained in the pediatric intensive care unit for 48 hours, and extubation was performed in the operating room under direct bronchoscopy. Mitomycin C was applied to a circumferential area of denuded tracheal mucosa. Conclusion: Tracheal foreign bodies are distinctly different clinical entities from bronchial foreign bodies. Asymptomatic bronchial foreign bodies are relatively common, but to the authors' knowledge, an asymptomatic tracheal foreign body had not been reported previously. Discussion focused on pathophysiology with reference to Poiseuille's law, diagnosis, and management of asymptomatic tracheal foreign bodies, including the possibility of elective bronchoscopic retrieval. [ABSTRACT FROM AUTHOR]

Objective: To present a case report and to propose an anatomic explanation for a rare complication of tonsillectomy, severe dysphagia caused by bilateral paralysis of the glossopharyngeal nerve. Study Design: Retrospective case review and prospective cadaveric dissection. Methods: The medical record and radiologic data were reviewed from a patient who had severe dysphagia after tonsillectomy. In addition, 10 formalin-preserved cadaver head and neck specimens were dissected to identify the anatomic course of 20 glossopharyngeal nerves. The distance between the nerve and tonsillar fossa was measured at two sites. Results: The patient was diagnosed with bilateral paralysis of the glossopharyngeal nerve and required use of gastrotomy tube for years postoperatively. The mean distance from the posterosuperior tonsillar fossa and the main trunk of the glossopharyngeal nerve was 10.7 mm, and the mean distance from the posteroinferior tonsillar fossa and the closest lingual branch of the glossopharyngeal nerve was 6.5 mm. Conclusions: Direct nerve injury seems the most plausible explanation for this rare complication of tonsillectomy. The proximity of the glossopharyngeal nerve to the tonsillar fossa emphasizes the importance of maintaining the correct surgical plane during surgery. [ABSTRACT FROM AUTHOR]

Background: Choristoma is a well-defined benign lesion formed by histologically normal tissue in an unusual location. Diagnosis is confirmed after surgical removal of the mass. To our knowledge, to date there has been only one case of thyroid choristoma described in the literature., Patient Findings: A 70-year-old man with a history of non-Hodgkin lymphoma presented with sudden cervical enlargement. Cervical CT scan showed a 47mm hypodense nodule on the right thyroid lobe. Fine-needle aspiration revealed follicular lesion of undetermined significance. During the following weeks there was noticeable thyroid enlargement. Reassessment with thyroid ultrasound showed a 73mm nodule. The patient underwent total thyroidectomy. Histopathological examination revealed a choristoma composed of squamous epithelium lined cysts, smooth muscle, adipose tissue, connective tissue, foci of ossification and extramedullary hematopoiesis. No cytological atypia or tumoral necrosis were found. Thyroid choristomas are an exceedingly rare cause of a thyroid nodule., (© 2024. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

This study aimed to investigate the phytochemistry of lemongrass ( Cymbopogon citratus) inoculated with Azospirillum brasilense and grown in lead (Pb)-contaminated soil to assess its responses to inoculation under different Pb levels. The experimental design was completely randomized in a 2 × 5 factorial scheme: two levels of A. brasilense (absence or presence) and five Pb levels. After four months of treatment, the following were analyzed: total and reducing sugars, total phenolic content, flavonoids, antioxidant activity, antioxidant enzymes, proline, and essential oil (EO) content and composition. Soil Pb levels and A. brasilense inoculation affected phytochemicals in lemongrass plants. Azospirillum inoculation reduced total sugars in the roots at all soil Pb levels, while increasing Pb levels favored a rise in sugar contents. There was an increase in flavonoid content in treatments associated with Pb and inoculated with A. brasilense . Antioxidant capacity was lower at lower Pb levels, regardless of bacterial inoculation. Enzymatic response was mainly affected by Pb concentrations between 50 and 100 mg kg -1 soil. EO content was influenced by soil Pb levels, with higher EO production at 500 mg Pb kg -1 soil and without A. brasilense inoculation. Overall, lemongrass cultivation in Pb-contaminated areas can be an alternative to phytoremediation and EO production for the industry.

Background: Corpus callosal abnormalities (CCA) are midline developmental brain malformations and are usually associated with a wide spectrum of other neurological and non-neurological abnormalities. The study aims to highlight the diagnostic role of fetal MRI to characterize heterogeneous corpus callosal abnormalities using the latest classification system. It also helps to identify associated anomalies, which have prognostic implications for the postnatal outcome., Methods: In this study, retrospective data from antenatal women who underwent fetal MRI between January 2014 and July 2023 at Rush University Medical Center were evaluated for CCA and classified based on structural morphology. Patients were further assessed for associated neurological and non-neurological anomalies., Results: The most frequent class of CCA was complete agenesis (79.1%), followed by hypoplasia (12.5%), dysplasia (4.2%), and hypoplasia with dysplasia (4.2%). Among them, 17% had isolated CCA, while the majority (83%) had complex forms of CCA associated with other CNS and non-CNS anomalies. Out of the complex CCA cases, 58% were associated with other CNS anomalies, while 8% were associated with non-CNS anomalies. 17% of cases had both., Conclusion: The use of fetal MRI is valuable in the classification of abnormalities of the corpus callosum after the confirmation of a suspected diagnosis on prenatal ultrasound. This technique is an invaluable method for distinguishing between isolated and complex forms of CCA, especially in cases of apparent isolated CCA. The use of diffusion-weighted imaging or diffusion tensor imaging in fetal neuroimaging is expected to provide further insights into white matter abnormalities in fetuses diagnosed with CCA in the future.

Objective: To evaluate the results obtained with an artificial intelligence-based software for predicting the risk of malignancy in breast masses from ultrasound images., Materials and Methods: This was a retrospective, single-center study evaluating 555 breast masses submitted to percutaneous biopsy at a cancer referral center. Ultrasonographic findings were classified in accordance with the BI-RADS lexicon. The images were analyzed by using Koios DS Breast software and classified as benign, probably benign, low to intermediate suspicion, high suspicion, or probably malignant. The histological classification was considered the reference standard., Results: The mean age of the patients was 51 years, and the mean mass size was 16 mm. The radiologist evaluation had a sensitivity and specificity of 99.1% and 34.0%, respectively, compared with 98.2% and 39.0%, respectively, for the software evaluation. The positive predictive value for malignancy for the BI-RADS categories was similar between the radiologist and software evaluations. Two false-negative results were identified in the radiologist evaluation, the masses in question being classified as suspicious by the software, whereas four false-negative results were identified in the software evaluation, the masses in question being classified as suspicious by the radiologist., Conclusion: In our sample, the performance of artificial intelligence-based software was comparable to that of a radiologist.

Spermatogenesis is a very complex process with an intricate transcriptional regulation. The transition from the diploid to the haploid state requires the involvement of specialized genes in meiosis, among other specific functions for the formation of the spermatozoon. The transcription factor cAMP-response element modulator (CREM) is a key modulator that triggers the differentiation of the germ cell into the spermatozoon through the modification of gene expression. CREM has multiple repressor and activator isoforms whose expression is tissue-cell-type specific and tightly regulated by various factors at the transcriptional, post-transcriptional and post-translational level. The activator isoform CREMτ controls the expression of several relevant genes in post-meiotic stages of spermatogenesis. In addition, exposure to xenobiotics negatively affects CREMτ expression, which is linked to male infertility. On the other hand, antioxidants could have a positive effect on CREMτ expression and improve sperm parameters in idiopathically infertile men. Therefore, CREM expression could be used as a biomarker to detect and even counteract male infertility. This review examines the importance of CREM as a transcription factor for sperm production and its relevance in male fertility, infertility and the response to environmental xenobiotics that may affect CREMτ expression and the downstream regulation that alters male fertility. Also, some health disorders in which CREM expression is altered are discussed.

Beetroot juice (BJ) is commonly used as an ergogenic aid in endurance and team sports, however, the effect of this supplement on climbing performance is barely studied. The purpose of the current study was to investigate the effect of acute BJ ingestion on neuromuscular and biochemical variables in amateur male sport climbers. Ten physically active sport climbers (28.8 ± 3.7 years) underwent a battery of neuromuscular tests consisting of the half crimp test, the pull-up to failure test, the isometric handgrip strength test, the countermovement jump (CMJ) and the squat jump (SJ). Participants performed the neuromuscular test battery twice in a cross-over design separated by 10 days, 150 min after having consumed either 70-mL of BJ (6.4 mmol NO 3- ) or a 70-mL placebo (0.0034 mmol NO 3- ). In addition, nitrate (NO 3- ) and nitrite (NO 2- ) saliva concentrations were analysed, and a side effect questionnaire related to ingestion was administrated. No differences were reported in particular neuromuscular variables measured such as the CMJ (p = 0.960; ES = 0.03), the SJ (p = 0.581; ES = -0.25), isometric handgrip strength (dominant/non dominant) (p = 0.459-0.447; ES = 0.34-0.35), the pull-up failure test (p = 0.272; ES = 0.51) or the maximal isometric half crimp test (p = 0.521-0.824; ES = 0.10-0.28). Salivary NO 3- and NO 2- increased significantly post BJ supplementation compared to the placebo (p < 0.001), while no side effects associated to ingestion were reported (p = 0.330-1.000) between conditions (BJ/placebo ingestion). Acute dietary nitrate supplementation (70-mL) did not produce any statistically significant improvement in neuromuscular performance or side effects in amateur sport climbers., Competing Interests: The authors declare no conflict of interest., (Copyright: © Academy of Physical Education in Katowice.)

The coliphage mEp021 belongs to a phage group with a unique immunity repressor, and its life cycle requires the host factor Nus. mEp021 has been classified as non-lambdoid based on its specific characteristics. The mEp021 genome carries a gene encoding an N λ -like antiterminator protein, termed Gp17, and three nut sites (nutL, nutR1, and nutR2). Analysis of plasmid constructs containing these nut sites, a transcription terminator, and a GFP reporter gene showed high levels of fluorescence when Gp17 was expressed, but not in its absence. Like lambdoid N proteins, Gp17 has an arginine-rich motif (ARM), and mutations in its arginine codons inhibit its function. In infection assays using the mutant phage mEp021ΔGp17::Kan (where gp17 has been deleted), gene transcripts located downstream of transcription terminators were obtained only when Gp17 was expressed. In contrast to phage lambda, mEp021 virus particle production was partially restored (>1/3 relative to wild type) when nus mutants (nusA1, nusB5, nusC60, and nusE71) were infected with mEp021 and Gp17 was overexpressed. Our results suggest that RNA polymerase reads through the third nut site (nutR2), which is more than 7.9 kbp downstream of nutR1., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Compared to other animals, the spontaneous occurrence of tumors in wild amphibians is relatively rare, generally limited to specific populations or species. The number of reports of spontaneous tumors in amphibians known up to 1986 was 491 cases in anurans and about 253 cases in urodeles. Similarly, there have been many, unsuccessful attempts to chemically or biologically induce tumors in amphibians. With these considerations, it is inevitable to wonder: do urodeles and anurans have an inherent resistance to cancer? Here, we review the spontaneous and induced occurrence of tumors in amphibians in a timeline, as well as failed attempts to induce tumors in these amphibians. Indeed, recent studies seem to indicate that there is a relationship between regeneration and cancer because regenerating tissues seem to resist tumorigenesis, as opposed to nonregenerative tissues of the same amphibian models. Although the mechanisms that allow regenerating tissues to resist tumorigenesis have not been elucidated, it is worth to note that, in addition to the apparent relationship between regeneration and cancer, amphibians possess characteristics that could contribute to their ability to resist the development of neoplastic events. The implications of these features in cancer susceptibility are discussed., (© 2022 International Federation for Cell Biology.)

In the past decades, the ability of Giardia duodenalis to perform homologous recombination has been suggested, supported by the observations of genomic integration of foreign plasmids and the disruption of genes using CRISPR technology. Unfortunately, the direct study of a HR mechanism has not been addressed, which would be pertinent in a minimalist organism lacking fundamental DNA-repair elements and even complete pathways. In addition, the constant ploidy changes through the life cycle of this parasite highlight the conservation and relevance of homologous recombination in maintaining genomic stability. In this research, we analyzed different recombinable plasmid systems and their outcomes after G. duodenalis transfection, using this approach we determined genomic, intra-plasmid and inter-plasmid recombination, moreover, we examined the presence of the non-conservative single-strand annealing pathway. With the intention of corroborating that the observed processes were done by homologous recombination, we used a chemical inhibitor named Mirin, which specifically inhibits Mre11 3'- 5' exonuclease activity, one of the first steps involved in homologous recombination and fundamental to success in repairing. Overall, these results describe the multiple recombinational substrates used by G. duodenalis to achieve HR and demonstrate the presence and use of single-strand annealing recombination., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Enolase, a multifunctional protein expressed by multiple pathogens activates plasminogen to promote proteolysis on components of the extracellular matrix, an important event in early host-pathogen interactions. A secreted form of enolase that is released upon the interaction of trophozoites with epithelial cells has been detected in the secretome of G. duodenalis . However, the role of enolase in the host-pathogen interactions remains largely unknown. In this work, the effects of G. duodenalis enolase (Gd-eno) on the epithelial cell model (IEC-6) were analyzed. Firstly, the coding sequence of Giardia enolase was cloned and the recombinant protein used to raise antibodies that were then used to define the localization and role of enolase in epithelial cell-trophozoite interactions. Gd-eno was detected in small cytoplasmic vesicles as well as at the surface and is enriched in the region of the ventral disk of Giardia trophozoites. Moreover, the blocking of the soluble monomeric form of the enzyme, which is secreted upon interaction with IEC-6 cells by the anti-rGd-eno antibodies, significantly inhibited trophozoite attachment to intestinal IEC-6 cell monolayers. Further, rGd-eno was able to bind human plasminogen (HsPlg) and enhanced plasmin activity in vitro when the trophozoites were incubated with the intrinsic plasminogen activators of epithelial cells. In IEC-6 cells, rGd-eno treatment induced a profuse cell damage characterized by copious vacuolization, intercellular separation and detachment from the substrate; this effect was inhibited by either anti-Gd-eno Abs or the plasmin inhibitor ϵ- aminocaproic acid. Lastly, we established that in epithelial cells rGd-eno treatment induced a necroptotic-like process mediated by tumor necrosis factor α (TNF-α) and the apoptosis inducing factor (AIF), but independent of caspase-3. All together, these results suggest that Giardia enolase is a secreted moonlighting protein that stimulates a necroptotic-like process in IEC-6 epithelial cells via plasminogen activation along to TNFα and AIF activities and must be considered as a virulence factor., 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 Barroeta-Echegaray, Fonseca-Liñán, Argüello-García, Rodríguez-Muñoz, Bermúdez-Cruz, Nava and Ortega-Pierres.)

Primary adenoid cystic carcinoma (ACC) of the trachea is a rare entity, with a 5-year survival between 50% and 80% for resectable cases and 30% in case of unresectable disease. We report a case of a primary ACC on a woman in her 70s that presented with a drawn-out history of dyspnoea. She was diagnosed with an unresectable obstructive tumour of the trachea, which required the placement of a Y-shaped stent. The patient underwent concomitant chemoradiotherapy, with partial response, and is still in follow-up, without evidence of disease progression., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Giardia duodenalis, is a binuclear and microaerophilic protozoan that causes giardiasis. Up to date, several molecular approaches have been taken to understand the molecular mechanisms of diverse cellular processes in this parasitic protozoan. However, the role of many genes involved in these processes needs further analysis. The CRISPR interference (CRISPRi) system has been widely used, as a constitutive expression system for gene silencing purposes in several parasites, including Giardia. The aim of this work was to implement a tunable t-CRISPRi system in Giardia to silence abundant, moderately and low expressed genes, by constructing an optimized and inducible plasmid for the expression of both gRNA and dCas9. A doxycycline inducible pRan promoter was used to express dCas9 and each gRNA, consistently dCas9 expression and nuclear localization were confirmed by Western-blot and immunofluorescence in transfected trophozoites. The transcriptional repression was performed on α-tubulin (high expression), giardipain-1 (moderate expression) and Sir2 and Sir4 (low expression) genes. The α-tubulin gene knock-down caused by dCas9 doxycycline-induction was confirmed by a decrease in its protein expression which was of 50% and 60% at 24 and 48 h, respectively. This induced morphological alterations in flagella. The giardipain-1 knock down, showed a decrease in protein expression of 40 and 50% at 12 and 24 h, respectively, without affecting trophozoites viability, consistent with this a zymogram analysis on giardipain-1 knock down revealed a decrease in giardipain-1 protease activity. When repressing sirtuins expression, a total repression was obtained but trophozoites viability was compromised. This approach provides a molecular tool for a tailored repression to produce specific gene knockdowns., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Limb regeneration in the axolotl is achieved by epimorphosis, thus depending on the blastema formation, a mass of progenitor cells capable of proliferating and differentiating to recover all lost structures functionally. During regeneration, the blastema cells accelerate the cell cycle and duplicate its genome, which is inherently difficult to replicate because of its length and composition, thus being prone to suffer double-strand breaks., Results: We identified and characterized two remarkable components of the homologous recombination repair pathway (Amex.RAD51 and Amex.MRE11), which were heterologously expressed, biochemically characterized, and inhibited by specific chemicals. These same inhibitors were applied at different time points after amputation to study their effects during limb regeneration. We observed an increase in cellular senescent accompanied by a slight delay in regeneration at 28 days postamputation regenerated tissues; moreover, inhibitors caused a rise in the double-strand break signaling as a response to the inhibition of the repair mechanisms., Conclusions: We confirmed the participation and importance of homologous recombination during limb regeneration. The chemical inhibition induces double-strand breaks that lead to DNA damage associated senescence, or in an alternatively way, this damage could be possibly repaired by a different DNA repair pathway, permitting proper regeneration and avoiding senescence., (© 2022 American Association for Anatomy.)

Background: It has been reported that the oncoprotein E7 from human papillomavirus type 16 (HPV16-E7) can induce the excessive synthesis of centrosomes through the increase in the expression of PLK4, which is a transcriptional target of E2F1. On the other hand, it has been reported that increasing MPS1 protein stability can also generate an excessive synthesis of centrosomes. In this work, we analyzed the possible role of MPS1 in the amplification of centrosomes mediated by HPV16-E7., Results: Employing qRT-PCR, Western Blot, and Immunofluorescence techniques, we found that E7 induces an increase in the MPS1 transcript and protein levels in the U2OS cell line, as well as protein stabilization. Besides, we observed that inhibiting the expression of MPS1 in E7 protein-expressing cells leads to a significant reduction in the number of centrosomes., Conclusions: These results indicate that the presence of the MPS1 protein is necessary for E7 protein to increase the number of centrosomes, and possible implications are discussed., (© 2021. The Author(s).)

Giardia duodenalis is a flagellated protozoan that is responsible for many cases of diarrheal disease worldwide and is characterized by its great divergence from the model organisms commonly used in studies of basic cellular processes. The life cycle of Giardia involves an infectious cyst form and a proliferative and mobile trophozoite form. Each Giardia trophozoite has two nuclei and a complex microtubule cytoskeleton that consists of eight flagellar axonemes, basal bodies, the adhesive disc, the funis and the median body. Since the success of Giardia infecting other organisms depends on its ability to divide and proliferate efficiently, Giardia must coordinate its cell division to ensure the duplication and partitioning of both nuclei and the multiple cytoskeletal structures. The purpose of this review is to summarize current knowledge about cell division and its regulation in this protist., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Cardiac echinococcosis is a rare manifestation of Echinococcus infection, affecting 0.5-2% of the patients. Since it may be a life-threatening condition, surgical treatment should be always considered. Herein, here we present a case of a 66-year-old male with chest pain. Subsequent exams confirmed the diagnosis of multiple cardiac hydatic cysts. The patient initiated treatment with albendazole and was submitted to a surgical resection with cardiopulmonary bypass. A complete surgical resection was achieved, and patient remains asymptomatic without disease signs of recurrence on imaging exams. We highlight the necessity of cardiac screening in echinococcosis cases and the surgical management in this case.

The remarkable regenerative capabilities of the salamander Ambystoma mexicanum have turned it into one of the principal models to study limb regeneration. During this process, a mass of low differentiated and highly proliferative cells, called blastema, propagates to reestablish the lost tissue in an accelerated way. Such a process implies the replication of a huge genome, 10 times larger than humans, with about 65.6% of repetitive sequences. These features make the axolotl genome inherently difficult to replicate and prone to bear mutations. In this context, the role of DNA repair mechanisms acquires great relevance to maintain genomic stability, especially if we consider the necessity of ensuring the correct replication and integrity of such a large genome in the blastema cells, which are key for tissue regeneration. On the contrary, DNA damage accumulation in these cells may result in senescence, apoptosis and premature differentiation, all of them are mechanisms employed to avoid DNA damage perpetuation but with the potential to affect the limb regeneration process. Here we review and discuss the current knowledge on the implications of DNA damage responses during salamander regeneration., (© 2020 American Association of Anatomists.)

Giardiavirus is the only virus that infects Giardia duodenalis, a highly prevalent parasite worldwide, especially in low-income and developing countries. This virus belongs to the Totiviridae family, being a relative of other viruses that infect fungi and protozoa. It has a simple structure with only two proteins encoded in its genome and it appears that it can leave the cell without lysis. All these characteristics make it an interesting study model; however, its research has unfortunately made little progress in recent years. Thus, in this review, we summarize the currently available data on Giardiavirus, from their structure, genome and main proteins, to the uses that have been given to them and the possible health applications for the future.

Giardia duodenalis is a parasite of great medical interest due to the number of infections it causes worldwide each year. Although research on epigenetic mechanisms in this protist has only begun recently, epigenetic regulation has already been shown to have important roles in encystation, antigenic variation, and resistance to antibiotics in Giardia. In this work, we show that a Giardia ortholog of Sir2, GdSir2.4, is involved in the silencing of rRNA expression. Our results demonstrate that GdSir2.4 localizes to the nucleolus, and its binding to the intergenic spacer region of the rDNA is associated with the deacetylation of the chromatin in this region. Given the importance of the regulation of rRNA expression to maintain adequate levels of ribosomes and genomic stability within the cells, GdSir2.4 can be considered a target to create new therapeutic agents against this parasite., (© 2021 John Wiley & Sons Ltd.)

Giardia duodenalis is a parasite that causes a large number of diarrheal diseases around the world. It is noteworthy that in a large number of processes, Giardia requires fewer components than other eukaryotes, even without some organelles such as mitochondria and peroxisomes. Despite this, core histones are known to exist in Giardia and epigenetic marks have been found on them, suggesting that they somehow control the expression of certain genes. The regulation of the expression of ribosomal DNA (rDNA) is essential, since it is required to maintain adequate levels of ribosomes and, given the nature of tandem repeat, it is a feasible area to create genomic instability. In Giardia, it is not known how this process occurs, but as in other eukaryotes, it is suggested through various epigenetic mechanisms. Thus, in the present work we seek to identify how chromatin is distributed through the Giardia rDNA and if there were histone marks that could control its expression., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Resistance to current cancer treatments is an important problem that arises through various mechanisms, but one that stands out involves an overexpression of several factors associated with DNA repair. To counteract this type of resistance, different drugs have been developed to affect one or more DNA repair pathways, therefore, to test different compounds of natural origin that have been shown to induce cell death in cancer cells is paramount. Since natural compounds target components of the DNA repair pathways, they have been shown to promote cancer cells to be resensitized to current treatments. For this and other reasons, natural compounds have aroused great curiosity and several research projects are being developed around the world to establish combined treatments between them and radio or chemotherapy. In this work, we summarize the effects of different natural compounds on the DNA repair mechanisms of cancer cells and emphasize their possible application to re-sensitize these cells., (Copyright © 2020 Lagunas-Rangel and Bermúdez-Cruz.)

Giardia duodenalis is a flagellated unicellular eukaryotic microorganism that commonly causes diarrheal disease throughout the world. Treatment of giardiasis is limited to nitroheterocyclic compounds as metronidazole and benzimidazoles as albendazole, where remarkably treatment failure is relatively common. Consequently, the need for new options to treat this disease is underscored. We predicted by a bioinformatic approach that nicotinamide inhibits Giardia sirtuins by the nicotinamide exchange pathway, and since sirtuins are involved in cell cycle control, they could be related with arrest and decrease of viability. When trophozoites were treated with nicotinamide (NAM), a strong arrest of Giardia trophozoites in G2 phase was observed and at the same time changes in transcriptional expression of sirtuins were produced. Interestingly, the G2 arrest is not related to double-strand breaks, which strengthens the role of sirtuins in the control of the Giardia cell cycle. Results with NAM-treated trophozoites as predicted demonstrate antigiardial effects and thus open new options for the treatment of giardiasis, either with the combination of nicotinamide with another antigiardial drug, or with the design of specific inhibitors for Giardia sirtuins., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: This study aims to analyze the construct and content validity of the Iconographical Falls Efficacy Scale (Icon-FES) in order to measure the fear of falling in community-dwelling older adults., Methods: The Icon-FES was applied to 333 older adults. An exploratory factor analysis was performed to assess internal consistency. Item response theory (IRT) and confirmatory factor analysis (CFA) were used to evaluate the consistency of the questionnaire and whether it corresponded satisfactorily to the construct "concern about falling." Concurrent validity with the Falls Efficacy Scale-International (FES-I) and convergent validity with the Senior Fitness Test (SFT) were also assessed. Receiving operator characteristic (ROC) curves were used to determine the sensitivity and specificity., Results: The structural model of the 30-item and 10-item Icon-FES showed some theoretical fragility. The final model of the new short version of the Icon-FES consisted of 13 items, yielding a theoretically satisfactory structural model. Validity analyses indicated that the 13-item Icon-FES had a moderate relationship with the SFT, a strong relationship with the FES-I, and good sensitivity and specificity for a history of falls., Conclusion: The 13-item Icon-FES has excellent psychometric properties for measuring fear of falling in community-dwelling older adults. It can be recommended as a screening tool for fear of falling for both research and clinical purposes.

Obesity is a serious medical condition worldwide, which needs new approaches and recognized international consensus in treating diseases leading to morbidity. The aim of this review was to examine heterogeneous links among the various phenotypes of obesity in adults. Proteins and associated genes in each group were analysed to differentiate between biomarkers. A variety of terms for classification and characterization within this pathology are currently in use; however, there is no clear consensus in terminology. The most significant groups reviewed include metabolically healthy obese, metabolically abnormal obese, metabolically abnormal, normal weight and sarcopenic obese. These phenotypes do not define particular genotypes or epigenetic gene regulation, or proteins related to inflammation. There are many other genes linked to obesity, though the value of screening all of those for diagnosis has low predictive results, as there are no significant biomarkers. It is important to establish a consensus in the terminology used and the characteristics attributed to obesity subtypes. The identification of specific molecular biomarkers is also required for better diagnosis in subtypes of obesity., Competing Interests: None

Breastfeeding is one of the oldest and most useful practices for human race. It is crucial for optimal newborn development and yet the stigma built around it has proven to be devastating for its implementation over the years. For the past few decades, numerous studies have been conducted to shed light on the countless benefits of breastfeeding and to cast off the taboo around it. In 1991 the World Health Organization, together with the United Nations International Children's Emergency Fund, created the Baby-Friendly Hospital Initiative (BFHI) with the aim of protecting, promoting and strengthening breastfeeding in hospitals and health centers, through the implementation of 10 steps to successful breastfeeding . There are a number of requirements that must be fulfilled in order to implement this initiative. However, due to local and regional characteristics of each health care unit, a certain degree of adequacy of these steps is required for its implementation. Therefore, at the Instituto Mexicano del Seguro Social (Mexican Institute for Social Security), seven steps and three annexes have been adapted for their implementation in the first level health care units of this institution.

Aim: We aimed to assess the influence of fasting insulin resistance on metabolically healthy obesity (MHO) prevalence in adolescents and to identify associated factors., Methods: This retrospective, registry-based, cross-sectional study included 418 (51.9% girls) 10- to 18-year-old adolescents with obesity from a tertiary outpatient clinic in Sao Paulo, Brazil, between 2009 and 2013. The prevalence of MHO was estimated according to two definitions: (i) no cardiometabolic risk factors (CMRF) by the International Diabetes Federation parameters and (ii) no CMRF and homeostatic model assessment for insulin resistance <3.16. Adjusted prevalence ratios and 95% confidence intervals (CI) evaluated the association of gender, age, pubertal stages, skin colour and degree of obesity with MHO., Results: Metabolically healthy obesity prevalence was lower in definition II than definition I (12.7%; 95% CI 9.1-16.3% versus 43.1%; 95% CI 38.0-48.2%, respectively). Adjusted results showed negative association between severe obesity and MHO by both definitions (p ≤ 0.01). Male and later pubertal stages were also less likely to have MHO, but neither remained significant in definition II., Conclusion: Metabolically healthy obesity prevalence decreased when insulin resistance was part of the definition. Detecting pre-clinical insulin resistance may improve the management of treatment-seeking adolescents, especially when they present no CMRF., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Orthodontic traction of impacted canines stands as a major challenge for Orthodontics. It is a relatively frequent clinical complaint which management, more often than not, requires a multidisciplinary approach. Surgical exposure of the impacted canine, and the complex orthodontic mechanics applied to align the tooth back into the arch, may frequently lead to complications involving supporting tissues, not to mention the long treatment time and high costs imposed to patients. In face of that, it is worth highlighting the relevance of early diagnosis as to intervene efficiently and as soon as possible. This paper presents a review of the main concepts involving prevalence, etiology and classification of impacted canines, and describes the different clinical management options that would help solve the problem. It illustrates the topic by presenting a treatment delivered to a 13 year 7 months old male patient, suffering from a Class II, division 2, left subdivision, malocclusion, associated to a deep bite and a prolonged retention of a primary upper canine caused by the impaction of the permanent tooth. Corrective orthodontic therapy was associated to a rapid maxillary expansion and to the use of a high pull headgear. Impacted canine was submitted to orthodontic traction and correctly positioned back into the arch. This approach proved to be efficient in meeting both functional and aesthetic goals.

Giardia duodenalis is a flagellated unicellular eukaryotic microorganism that usually parasitizes the small intestine of humans and many other vertebrates causing diarrheal disease throughout the world. Notably, Giardia despite minimization of most cellular systems shows different strategies to adapt to environmental conditions, evade the immune system and resist exposure to antimicrobial agents. Over the past years, epigenetic regulation of gene expression has been shown to have a relevant role in the parasite's biology. Interestingly, analysis of the Giardia genome revealed the presence of enzymes responsible for post-translational modification in histones, therefore suggesting that epigenetic mechanisms may regulate gene expression in this parasite. Thus, the purpose of this review is to summarize how epigenetic mechanisms play relevant roles in the pathogenicity of Giardia, with a particular emphasis on the molecular mechanisms associated with parasite differentiation, antigenic variation and antimicrobial resistance., (Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

The mechanisms underlying metronidazole (MTZ) resistance in Giardia duodenalis have been associated with decreased activity of the enzymes implicated in its activation including nitroductase-1, thioredoxin reductase and pyruvate-ferredoxin oxidoreductase (PFOR). MTZ activation generates radicals that can form adducts with proteins such as thioredoxin reductase and α- and -β giardins as well as DNA damage resulting in trophozoite's death. The damage induced in DNA requires a straight forward response that may allow parasite survival. Here, we studied changes in histone H2A phosphorylation to evaluate the DNA repair response pathway after induction of double strand break (DSB) by MTZ in Giardia DNA. Our results showed that the DNA repair mechanisms after exposure of Giardia trophozoites to MTZ, involved a homologous recombination pathway. We observed a significant increase in the expression level of proteins GdDMC1B, which carries out Rad51 role in G. duodenalis, and GdMre11, after 12 h of exposure to 3.2 μM MTZ. This increase was concomitant with the generation of DSB in the DNA of trophozoites treated MTZ. Altogether, these results suggest that MTZ-induced DNA damage in Giardia triggers the DNA homologous recombination repair (DHRR) pathway, which may contribute to the parasite survival in the presence of MTZ., (Copyright © 2018. Published by Elsevier Inc.)

The chronic indeterminate phase of Chagas' disease is asymptomatic despite positive test results for antibodies specific to Trypanosoma cruzi. CD62P-APC (P-selectin) and PAC-1 FITC (GpIIb/IIIa) may improve diagnosis as biomarkers of platelet activity. Nine asymptomatic seropositive subjects, previously untreated, were selected from a blood bank within a year of Chagas' disease detection, in addition to a control group of four. All subjects were evaluated by flow cytometry for CD62P, PAC-1 and CD41, and in a complementary study, by Tissue Doppler Echocardiography for isovolumic relaxation times (IVRT) and E/A ratios. The subjects were classified as positive or negative for CD62P and PAC-1 by a cut off obtained from their mean±2SD. For IVRT and E/A ratios, cut offs were obtained from the American Society of Echocardiography and the European Association of Cardiovascular Imaging recommendations. Fisher's exact test was used for associated findings. Pre-test and post-test probability, sensitivity, specificity, positive and negative predictive values and likelihood ratios were calculated. Abnormalities were expressed as platelet hyperactivity and ventricular dysfunction in CD62P, PAC-1, IVRT and E/A ratios. CD62P appears to have greater sensitivity (0.75) and PAC-1, more accurate specificity (0.75), which may explain thrombotic events in Chagas' disease. We recommend the use of CD62P and PAC-1 as biomarkers of platelet hyperactivity in patients in the chronic indeterminate phase of Chagas' disease.

The adhesion of Giardia duodenalis trophozoites to intestinal epithelial cells allows the onset and maintenance of giardiasis. During these interactions, epithelial cells can be committed to apoptosis by enzymes secreted by the parasites, including cysteine proteases that are increasingly identified as virulence factors in parasitic protozoa. In this work, a monoclonal antibody (mAb1G3) raised against G. duodenalis surface components was found to react with a 25 kDa protein expressed in the cell surface and flagella of G. duodenalis trophozoites. When trophozoites expressing this protein were cultured with IEC-6 intestinal epithelial cell monolayers, a dynamic release of this protein was observed with mAbIG3. Proteomic analysis identified the protein as a mature cathepsin B-like (gCatB) enzyme, whose proteolytic activity, detected in zymograms, was eliminated by CatB inhibitor E-64. This protein was named giardipain-1 due to its functional papain-like features and was purified by affinity chromatography using mAbIG3. Upon exposure to the purified, mature and secreted forms of giardipain-1, IEC-6 epithelial cell monolayers displayed membrane blebbing and phosphatidylserine exposure on the outer cell surface, indicating an apoptotic process. In Madin Darby Canine Kidney (MDCK) cell monolayers, giardipain-1 leads to the appearance of pore-like regions and of gaps along cell-cell junctions, to decreased transepithelial electrical resistance (TER), caspase-3 activation and poly-ADP-ribose polymerase (PARP) fragmentation. At early times during exposure, giardipain-1 co-localized at cell-cell junctions, associated with occludin and induced the delocalization and degradation of tight junction proteins occludin and claudin-1. The damage caused to epithelial monolayers by giardipain-1 was blocked by pre-incubation with the CatB B Inhibitor E-64. Furthermore, silencing the giardipain-1 gene in trophozoites lowered the proteolytic activity of giardipain-1 and reduced the damage in IEC-6 monolayers. The damage observed appears to be specific to giardipain activity since almost no damage was observed when IEC-6 monolayers were incubated with papain, a non-related cysteine protease. Hence this study suggests that giardipain-1 triggers, in epithelial cells, degradation of cell-cell junctional components and apoptotic damage, supporting the notion of giardiapain-1 as a virulence factor of Giardia., (Copyright © 2018 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.)

Giardia duodenalis is a flagellated binucleated protozoan that colonizes the small intestine in mammals, causing giardiasis, acute or chronic diarrhea. DNA double strand break either endogenously or exogenously generated is a major insult to DNA and its repair by homologous recombination (HR) is crucial for genomic stability. During HR, Rad52 plays key roles in the loading of the Rad51 recombinase, and the annealing of the second double-strand break end to the displaced strand of the D-loop structure. Among the functions found in vitro in yeast and human Rad52 protein are: ssDNA or dsDNA binding activity, ability to anneal bare or RPA coated-ssDNA, as well as multimeric ring formation. In this work, we searched for conserved domains in a putative Rad52 protein from G. duodenalis (GdRad52). Its coding sequence was cloned, expressed and purified to study its biochemical properties. rGdRad52 binds to dsDNA and ssDNA, with greater affinity for the latter. Likewise, rGdRad52 promotes annealing of DNA uncoated and coated with GdRPA1. rGdRad52 interacts with GdDMC1B and with GdRPA1 protein as shown in far western blotting assay. Additionally, rGdRad52 formed multimeric rings as observed by electronic microscopy. Finally, GdRad52 is over expressed in response upon DNA damage inflicted on trophozoites., (© The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)

Giardia duodenalis is the protozoan parasite responsible for most cases of parasitic diarrhea worldwide. The pathogenic mechanisms of giardiasis have not yet been fully characterized. In this context parasite's excretory/secretory products have been related to the damage induced by the parasite on enterocytes. Among these is the Variable Surface Proteins (VSPs) family involved in antigenic variation and in the induction of protective response. In proteomic analyses carried out to identify the proteases with high molecular weight secreted by Giardia trophozoites during the initial phase of interaction with IEC-6 cell monolayers we identified the VSP9B10A protein. In silico bioinformatics analyses predicted a central region in residues 324-684 displaying the catalytic triad and the substrate binding pocket of cysteine proteases. The analysis of the effect of the VSP9B10A protein on epithelial cell monolayers using trophozoites that were transfected with a plasmid carrying the vsp9b10a gene sequence under the control of a constitutive promoter showed that transfected trophozoites expressing the VSP9B10A protein caused cytotoxic damages on IEC-6 and MDCK cell monolayers. This was characterized by loss of cell-cell contacts and cell detachment from the substrate while no damage was observed with trophozoites that did not express the VSP9B10A protein. The same cytotoxic effect was detected when IEC-6 cell monolayers were incubated only with supernatants from co-cultures of IEC-6 cell monolayers with VSP9B10A transfected trophozoites and this effect was not observed when transfected trophozoites were incubated with a monospecific polyclonal antibody anti-VSP9B10A previous to interaction with IEC-6 monolayers. These results demonstrate that the VSP9B10A protein secreted upon interaction with epithelial cells caused damage in these cells. Thus this protein might be considered as a conditional virulence factor candidate. To our knowledge this is the first report on the proteolytic activity from a Giardia VSP opening new research lines on these proteins., (Copyright © 2017 Elsevier Inc. All rights reserved.)