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Guilherme Carneiro,1 Elton Luiz Silva,1 Layssa Alves Pacheco,1 Elaine Maria de Souza-Fagundes,2 Natássia Caroline Resende Corrêa,3 Alfredo Miranda de Goes,3 Mônica Cristina de Oliveira,1 Lucas Antônio Miranda Ferreira11Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil; 2Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil; 3Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, BrazilAbstract: This work aims to develop solid lipid nanoparticles (SLNs) loaded with retinoic acid (RA) to evaluate the influence of two lipophilic amines, stearylamine (SA) and benethamine (BA), and one hydrophilic, triethylamine (TA), on drug-encapsulation efficiency (EE) and cytotoxicity in cancer cell lines. The SLNs were characterized for EE, size, and zeta potential. The mean particle size decreased from 155 ± 1 nm (SLNs without amine) to 104 ± 4, 95 ± 1, and 96 ± 1 nm for SLNs prepared with SA, BA, and TA, respectively. SA-RA-loaded SLNs resulted in positively charged particles, whereas those with TA and BA were negatively charged. The EEs were significantly improved with the addition of the amines, and they increased from 36% ± 6% (without amine) to 97% ± 2%, 90% ± 2%, and 100% ± 1% for SA, TA, and BA, respectively. However, stability studies showed higher EE for BA-RA-loaded SLNs than TA-RA-loaded SLNs after 30 days. The formulations containing SA loaded or unloaded (blank SLNs) with RA were cytotoxic in normal and cancer cell lines. In contrast, the blank SLNs containing TA or BA did not show cytotoxicity in human breast adenocarcinoma cells (MCF-7), while RA-loaded SLNs with the respective amines were significantly more cytotoxic than free RA. Furthermore, the cytotoxicity of BA-RA-loaded SLNs was significantly higher than TA-RA-loaded SLNs. These findings are in agreement with the data obtained in the evaluation of subdiploid DNA content and cell-cycle analysis, which showed better anticancer activity for BA-RA-loaded SLNs than TA-RA-loaded SLNs and free RA. Taken together, these findings suggest that the BA-RA-loaded SLN formulation is a promising alternative for the intravenous administration of RA in the treatment of cancer.Keywords: solid lipid nanoparticles, all-trans retinoic acid, cancer, treatment, antitumor activity, ion pairing

Historically, blind intrauterine procedures such as dilation and curettage (D&C) and blind endometrial biopsies have been the primary approach for diagnosing and managing intrauterine pathologies. However, these techniques lack direct visualization, leading to diagnostic limitations, incomplete treatment, and increased complication rates. Despite substantial advances in hysteroscopic technology, including high-definition imaging and minimally invasive instruments, blind procedures remain widely used. This paper examines the limitations of blind intrauterine procedures, underscoring the advantages of hysteroscopy, which provides real-time visualization and allows for more accurate, targeted interventions. With the adoption of the "See and Treat" philosophy, hysteroscopy enables nearly 90% of procedures to be performed in an office setting, enhancing both patient convenience and outcomes. FIGO and GCH advocate for the gradual replacement of blind procedures with hysteroscopic approaches whenever feasible, noting that hysteroscopy improves diagnostic accuracy, reduces risks, and minimizes the need for repeat interventions. Recommendations include expanding access to hysteroscopy through targeted training, especially in low- and middle-income countries, where financial and logistical barriers limit access to advanced gynecological care. Furthermore, this paper emphasizes the importance of patient-centered care, encouraging transparent counseling to support informed decision-making., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

The authors propose a new classification of intrauterine adhesions (IUAs) to facilitate understanding for both the gynecologist and the patient, documenting the location and characteristics of the adhesions in a single image. This tool significantly improves surgical planning and patient outcomes in the treatment of intrauterine adhesions. In addition, having a simple and consistent method of describing IUAs will facilitate longitudinal studies tracking the outcomes of various surgical techniques, adhesion barriers and the impact of hormonal treatment. The proposed new classification system may represent a significant advancement in the field of gynecology. Its adoption may facilitate and simplify the representation of intrauterine adhesion sites, allowing for better communication between doctors and more effective management of intrauterine adhesions., (© 2024 International Federation of Gynecology and Obstetrics.)

Introduction: The diagnostic workflow for endometrial carcinoma in postmenopausal asymptomatic women remains an ongoing dilemma. Whereas an ultrasonographic endometrial thickness greater than 4.0 or 5.0 mm is adequate for warranting further investigations in women with postmenopausal vaginal bleeding, there is still no unanimous consensus on what the ideal endometrial thickness cut-off should be, justifying additional inspection through endometrial sampling when bleeding is absent., Methods: A comprehensive overview of the most recent literature to summarize the clinical pathway necessary for the diagnostic assessment of a postmenopausal asymptomatic woman with increased ultrasonographic endometrial thickness., Results: An endometrial thickness cut-off between 3.0 and 5.9 mm seems to show the lowest specificity while also reducing the chances of missing malignancy. If endometrial thickness can be a valid starting point, a careful evaluation of the other ultrasonographic endometrial features and a thorough scrutiny of patients' risk factors are pivotal to standardizing the diagnostic process while avoiding overtreatment. Although preventing unnecessary procedures is crucial, stratifying the risk and proceeding with further investigations (preferably through outpatient or office hysteroscopically-guided targeted biopsies) should be the goal., Conclusions: Closer collaboration between different fields of medicine (ultrasonography, hysteroscopy, and oncology) is strongly encouraged to facilitate early diagnosis of asymptomatic postmenopausal women at risk of developing endometrial malignancy.

Objective: To examine whether musculoskeletal injury history is a factor that influences countermovement jump (CMJ) performance in rugby players and to compare CMJ performance between player's position (forwards or backs)., Methods: Thirty rugby players (15 with an injury history and 15 without an injury history) performed the CMJ using an inertial sensor (Baiobit®) to evaluate kinematic (Jump Height, Velocity and Phase duration) and kinetic data (rate of force development [RFD], impact peak [IP], take-off force and Stiffness]. The group comparison was performed with an independent t-test, and the association between CMJ performance, sociodemographic variables and injury history was investigated with Pearson's correlation test., Results: Rugby players with and without history of musculoskeletal injury differed in age and playing experience, but there was no difference in CMJ performance between groups. Jump height of uninjured players was positively correlated with take-off force and RFD and negatively correlated with concentric phase duration and RFD. Injured players demonstrated a negative correlation between take-off force and IP. Compared to backs, forwards were heavier and taller, showed greater IPs and were more likely to have an injury history., Conclusions: There were no differences in CMJ performance between rugby players with and without an injury history. Forwards showed greater IPs and were more likelier to have an injury history than backs., Competing Interests: Declaration of competing interest We state that all authors (Luiz Alexandre Pacheco, Matheus Correa Morais, Jose Davi Oltramari and William Dhein) have made substantial contributions to the article, either in its conception and design or in the acquisition of data and analysis and interpretation of it. Also, all authors participated in the drafting of the article and in its reviews until was considered for submitting. We hereby state that each of the authors has read and concurs with the content in the manuscript. Also, we declare that this paper has not been published elsewhere and the authors declare that was no conflict of interest in this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hysteroscopy has truly revolutionized the field of diagnostic and operative gynecology. It is presently regarded as the gold standard method for both the diagnosis and treatment of intrauterine diseases and it has fundamentally altered the way gynecologists treat patients with such conditions. These pathologies can now be diagnosed and treated in an outpatient setting, thanks to technological advancements and instrument downsizing. Two hundred years of development and notable innovation are now reflected in the present hysteroscopic practice. This review attempts to trace the boundaries-pushing history of hysteroscopy by highlighting the advancements in technology and the therapeutic and diagnostic benefits offered by this groundbreaking approach., (© 2024. The Author(s).)

The growing use of Unmanned Aerial Vehicles (UAVs) raises the need to improve their autonomous navigation capabilities. Visual odometry allows for dispensing positioning systems, such as GPS, especially on indoor flights. This paper reports an effort toward UAV autonomous navigation by proposing a translational velocity observer based on inertial and visual measurements for a quadrotor. The proposed observer complementarily fuses available measurements from different domains and is synthesized following the Immersion and Invariance observer design technique. A formal Lyapunov-based observer error convergence to zero is provided. The proposed observer algorithm is evaluated using numerical simulations in the Parrot Mambo Minidrone App from Simulink-Matlab.

The purpose of this State-of-the-Art Review was to provide a strategic analysis, in terms of strengths, weaknesses, opportunities and threats (SWOT analysis), of the current evidence regarding the management of uterine isthmocele (Cesarean scar defect). Strengths include the fact that isthmocele can be diagnosed on two-dimensional transvaginal ultrasound, and that surgical repair may restore natural fertility potential and prevent secondary infertility, as well as reduce the risk of miscarriage and other obstetric complications. However, there is a lack of high-quality evidence regarding the best diagnostic method and criteria, as well as the potential benefits of surgical repair with respect to fertility. There is a need for experienced surgeons skilled in the various isthmocele repair techniques. Isthmocele repair does not prevent the need for Cesarean delivery in subsequent pregnancies. There is increasing awareness regarding the accuracy of transvaginal ultrasound in diagnosing isthmocele. This may lead to surgical correction and prevention of obstetric and perinatal complications in subsequent pregnancies, including Cesarean scar pregnancy. Regarding threats, the existence of different surgical techniques means that there is a risk of selecting an inadequate approach if the type of isthmocele and the patient's characteristics are not considered. There is a risk of overtreatment when asymptomatic defects are repaired surgically. Finally, there is an absence of cost-effectiveness analyses to justify routine repair. Thus, while there are many data suggesting that isthmocele has an adverse effect on both natural fertility and the outcome of assisted reproduction techniques, high-quality evidence to support surgical isthmocele repair in all asymptomatic patients desiring future fertility are lacking. There is increasing agreement to recommend hysteroscopic repair of isthmocele as a first-line approach as long as the residual myometrial thickness is at least 2.5-3.0 mm. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

This practice guideline provides updated evidence for the gynecologist who performs endometrial biopsy (EB) in gynecologic clinical practice. An international committee of gynecology experts developed the recommendations according to AGREE Reporting Guideline. An adequate tissue sampling is mandatory when performing an EB. Blind methods should not be first choice in patients with suspected endometrial malignancy. Hysteroscopy is the targeted-biopsy method with highest diagnostic accuracy and cost-effectiveness. Blind suction techniques are not reliable for the diagnosis of endometrial polyps. In low resources settings, and in absence of the capacity to perform office hysteroscopy, blind techniques could be used for EB. Hysteroscopic punch biopsy allows to collect only limited amount of endometrial tissue. grasp biopsy technique should be considered first choice in reproductive aged women, bipolar electrode chip biopsy should be preferred with hypotrophic or atrophic endometrium. EB is required for the final diagnosis of chronic endometritis. There is no consensus regarding which endometrial thickness cut-off should be used for recommending EB in asymptomatic postmenopausal women. EB should be offered to young women with abnormal uterine bleeding and risk factors for endometrial carcinoma. Endometrial pathology should be excluded with EB in nonobese women with unopposed hyperestrogenism. Hysteroscopy with EB is useful in patients with abnormal bleeding even without sonographic evidence of pathology. EB has high sensitivity for detecting intrauterine pathologies. In postmenopausal women with uterine bleeding, EB is recommended. Women with sonographic endometrial thickness > 4 mm using tamoxifen should undergo hysteroscopic EB., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background and Objectives : Hysteroscopic endometrial resection (ER) or global endometrial ablation (GEA) are feasible methods to treat heavy menstrual bleeding (HMB). The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to assess patient's quality of life (QoL) in women treated with ER/GEA compared to hysterectomy. Materials and Methods : Electronic searches in MEDLINE Scopus, ClinicalTrials.gov, EMBASE, PROSPERO and Cochrane CENTRAL were conducted from their inception to July 2022. Inclusion criteria were RCTs of premenopausal women with HMB randomized to conservative surgical treatment (ER/GEA) or hysterectomy. The primary outcome was the evaluation of QoL using the SF-36 score. Results : Twelve RCTs (2773 women) were included in the analysis. Women treated with hysteroscopic ER/GEA showed significantly lower scores for the SF-36 general health perception (mean difference (MD) -8.56 [95% CI -11.75 to -5.36]; I 2 = 0%), social function (MD -12.90 [95% CI -23.90 to -1.68]; I 2 = 91%), emotional role limitation (MD -4.64 [95% CI -8.43 to -0.85]; I 2 = 0%) and vitality (MD -8.01 [95% CI -14.73 to -1.30]; I 2 = 74%) domains relative to hysterectomy. Anxiety, depression scores and complication rates were similar between treatments. Relative to uterine balloon therapy, amenorrhea was more common with EA/GER (relative risk 1.51 [95% CI 1.03 to 1.20] I 2 = 28 %), but posttreatment satisfaction was similar. Conclusions : Women's perception of QoL might be seen to be less improved after hysteroscopic ER/GEA rather than hysterectomy. However, such findings need to be confirmed by additional trials due to the high number of outdated studies and recent improvements in hysteroscopic instrumentation and techniques.

Introducción. Desde el primer reporte en la provincia de Wuhan (China) en el año 2019, el SARS-CoV-2 se ha diseminado por todo el mundo, provocando un enorme impacto en la salud pública. Para su diagnóstico, la Organización Mundial de la Salud ha incentivado el desarrollo de pruebas rápidas, de simple ejecución, sensibles y específicas, que complementan la RT-qPCR como prueba de referencia. La prueba RT-LAMP ha mostrado ser una excelente alternativa para la detección del SARS-CoV-2 en diferentes biofluidos., Objetivo: Validar la técnica RT-LAMP colorimétrica en muestras de hisopado nasofaríngeo previamente confirmadas por RT-qPCR, usando el protocolo Charité, Berlín, Alemania. Materiales y métodos. Un total de 153 muestras de hisopado nasofaríngeo de individuos con sospecha de COVID-19 se sometieron a RT-qPCR y RT-LAMP, usando un estuche comercial colorimétrico (NEB, Germany). La RT-LAMP se practicó con las muestras de ARN extraídas del hisopado nasofaríngeo y con muestras crudas sin previa extracción de ARN. El resultado fue evaluado por un simple cambio de color en la reacción., Resultados: La sensibilidad y especificidad de la técnica RT-LAMP para detectar el gen N del SARS-CoV-2 mediante un set de cebadores previamente reportados (set de Broughton), arrojó valores de 0,97 (0,85-1,00) y 0,81 (0,65-0,92), respectivamente, con un intervalo de confianza del 95%. Otro set de cebadores dirigidos contra otra región del mismo gen (set de Lalli) arrojó valores de sensibilidad y especificidad de 0,96 (0,78-1,00) y 0,77 (0,55-0,92), respectivamente. Sin previa extracción de ARN, se encontró que la sensibilidad fue del 0,95 (0,74-1,00) y la especificidad del 0,88 (0,64-0,99)., Conclusiones: Estos resultados evidencian que la técnica RT-LAMP podría considerarse una prueba diagnóstica rápida, de fácil ejecución, libre de equipos sofisticados, sensible y específica, para el diagnóstico del SARS-CoV-2 en muestras de hisopados nasofaríngeos.

Objective: we performed a systematic review/meta-analysis to evaluate the impact of septate uterus and hysteroscopic metroplasty on pregnancy rate-(PR), live birth rate-(LBR), spontaneous abortion-(SA) and preterm labor (PL) in infertile/recurrent miscarriage-(RM) patients. Data sources: a literature search of relevant papers was conducted using electronic bibliographic databases (Medline, Scopus, Embase, Science direct). Study eligibility criteria: we included in this meta-analysis all types of observational studies that evaluated the clinical impact of the uterine septum and its resection (hysteroscopic metroplasty) on reproductive and obstetrics outcomes. The population included were patients with a diagnosis of infertility or recurrent pregnancy loss. Study appraisal and synthesis methods: outcomes were evaluated according to three subgroups: (i) Women with untreated uterine septum versus women without septum (controls); (ii) Women with treated uterine septum versus women with untreated septum (controls); (iii) Women before and after septum removal. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for the outcome measures. A p-value < 0.05 was considered statistically significant. Subgroup analysis was performed according to the depth of the septum. Sources of heterogeneity were explored by meta-regression analysis according to specific features: assisted reproductive technology/spontaneous conception, study design and quality of papers included Results: data from 38 studies were extracted. (i) septum versus no septum: a lower PR and LBR were associated with septate uterus vs. controls (OR 0.45, 95% CI 0.27−0.76; p < 0.0001; and OR 0.21, 95% CI 0.12−0.39; p < 0.0001); a higher proportion of SA and PL was associated with septate uterus vs. controls (OR 4.29, 95% CI 2.90−6.36; p < 0.0001; OR 2.56, 95% CI 1.52−4.31; p = 0.0004). (ii) treated versus untreated septum: PR and PL were not different in removed vs. unremoved septum(OR 1.10, 95% CI 0.49−2.49; p = 0.82 and OR 0.81, 95% CI 0.35−1.86; p = 0.62); a lower proportion of SA was associated with removed vs. unremoved septum (OR 0.47, 95% CI 0.21−1.04; p = 0.001); (iii) before-after septum removal: the proportion of LBR was higher after the removal of septum (OR 49.58, 95% CI 29.93−82.13; p < 0.0001) and the proportion of SA and PL was lower after the removal of the septum (OR 0.02, 95% CI 0.02−0.04; p < 0.000 and OR 0.05, 95% CI 0.03−0.08; p < 0.0001) Conclusions: the results show the detrimental effect of the uterine septum on PR, LBR, SA and PL. Its treatment reduces the rate of SA.

Background: Endometrial cancer is the most common gynaecological neoplasia in western countries. Diagnosis of endometrial cancer requires an endometrial biopsy. A good quality endometrial biopsy allows not only the identification of the pathology, but also preoperative histologic subtype classification. Endometrial biopsy can be performed under direct hysteroscopic visualisation, but also using blind sampling techniques., Objectives: To compare endometrial biopsy performed under direct hysteroscopic visualisation versus blind sampling for the diagnosis of endometrial hyperplasia and cancer., Materials and Methods: Systematic review and meta-analysis. Electronic databases were searched from their inception until March 2022.We included all studies comparing endometrial biopsy performed under direct hysteroscopic visualisation versus blind endometrial sampling., Main Outcome Measures: Sample adequacy, failure rate to detect endometrial cancer or endometrial hyperplasia, and rate of detection of endometrial cancer. The summary measures were reported as relative risk (RR) with 95% of confidence interval (CI)., Results: Four studies with a total of 1,295 patients were included. Endometrial biopsy under direct hysteroscopic visualisation was associated with a significantly higher rate of sample adequacy (RR 1.13, 95% CI 1.10 to 1.17), and significantly lower risk of failure to detect endometrial cancer or endometrial hyperplasia (RR 0.16, 95% CI 0.03 to 0.92) compared to blind endometrial sampling. However, there was no significant difference between endometrial biopsies taken under direct hysteroscopic visualisation or blindly, with or without a preceding diagnostic hysteroscopy, in the rate of detection of endometrial cancer (RR 0.18, 95% CI 0.03 to 1.06)., Conclusion: Hysteroscopic endometrial biopsy under direct visualisation is associated with significantly higher rate of sample adequacy and is comparable to blind endometrial sampling for the diagnosis of endometrial cancer and precancer., What Is New?: Hysteroscopic endometrial biopsy under direct visualisation would be expected to reduce diagnostic failure for endometrial cancer compared to blind endometrial sampling.

The COVID-19 pandemic highlighted health systems vulnerabilities, as well as thoughtlessness by governments and society. Due to the nature of this contingency, the use of geographic information systems (GIS) is essential to understand the SARS-CoV-2 distribution dynamics within a defined geographic area. This work was performed in Tepic, a medium-sized city in Mexico. The residence of 834 COVID-19 infected individuals was georeferenced and categorized by viral load (Ct). The analysis took place during the maximum contagion of the first four waves of COVID-19 in Mexico, analyzing 158, 254, 143, and 279 cases in each wave respectively. Then heatmaps were built and categorized into five areas ranging from very low to very high risk of contagion, finding that the second wave exhibited a greater number of cases with a high viral load. Additionally, a spatial analysis was performed to measure urban areas with a higher risk of contagion, during this wave this area had 19,203.08 km 2 (36.11% of the city). Therefore, a kernel density spatial model integrated by meaningful variables such as the number of infected subjects, viral load, and place of residence in cities, to establish geographic zones with different degrees of infection risk, could be useful for decision-making in future epidemic events.

Introduction: Endometriosis is a gynecologic disease affecting approximately 10% of reproductive age women, around 21-47% of women presenting subfertility and 71-87% of women with chronic pelvic pain. Main symptoms are chronic pelvic pain, dysmenorrhea, dyspareunia and infertility that seem to be well controlled by oral contraceptive pill, progestogens, GnRh antagonists. The aim of this review was to illustrate the modern diagnosis of endometriosis during pregnancy, to evaluate the evolution of endometriotic lesions during pregnancy and the incidence of adverse outcomes., Evidence Acquisition: Published literature was retrieved through searches of the database PubMed (National Center for Biotechnology Information, US National Library of Medicine, Bethesda, MD, USA). We searched for all original articles published in English through April 2020 and decided to extract every notable information for potential inclusion in this review. The search included the following MeSH search terms, alone or in combination: "endometriosis" combined with "endometrioma," "biomarkers," "complications," "bowel," "urinary tract," "uterine rupture," "spontaneous hemoperitoneum in pregnancy" and more "adverse pregnancy outcome," "preterm birth," "miscarriage," "abruption placentae," "placenta previa," "hypertensive disorder," "preeclampsia," "fetal grow restriction," "small for gestation age," "cesarean delivery.", Evidence Synthesis: Pregnancy in women with endometriosis does not always lead to disappearance of symptoms and decrease in the size of endometriotic lesions, but it may be possible to observe a malignant transformation of ovarian endometriotic lesions. Onset of complications may be caused by many factors: chronic inflammation, adhesions, progesterone resistance and a dysregulation of genes involved in the embryo implantation. As results, the pregnancy can be more difficult because of endometriosis related complications (spontaneous hemoperitoneum [SH], bowel complications, etc.) or adverse outcomes like preterm birth, FGR, hypertensive disorders, obstetrics hemorrhages (placenta previa, abruptio placenta), miscarriage or cesarean section. Due to insufficient knowledge about its pathogenesis, currently literature data are contradictory and do not show a strong correlation between endometriosis and these complications except for miscarriage and cesarean delivery., Conclusions: Future research should focus on the potential biological pathways underlying these relationships in order to inform patients planning a birth about possible complications during pregnancy.

To examine the uterine cavity and/or to perform hysteroscopic surgery, one has to access the uterine cavity through the cervix, distend the cavity with a fluid (liquid or gas) to visualize it with a telescope and/or a camera system and use energy (mechanical or thermal) to affect and/or remove tissue. Distension of the uterine cavity then is an important component of hysteroscopy, and during the last century, numerous attempts have been made to achieve an undistorted and unobstructed panoramic view of the uterine cavity. In order to achieve this goal, the uterine cavity has been distended with fluids using a variety of techniques, including gravity-assisted systems, pressure cuffed systems, and electronic pumps. Excessive fluid intravasation during hysteroscopy can lead to significant complications, and hence, automated fluid delivery systems have been developed recently to provide a safe and more efficient method of fluid delivery. This review aims to describe the evolution of distension media delivery systems chronologically from the 1900s to the present day.

Objective: To evaluate sleep characteristics of children and adolescents with type 1 diabetes mellitus (T1DM) and their relationship with glycemic control., Methods: A cross-sectional study was conducted at a public hospital in São Paulo, Brazil. It included 86 patients with T1DM, aged between 10 and 18 years old, who were on insulin therapy, had performed at least three measurements of capillary blood glucose throughout the day, and had normal thyroid function. The clinical, anthropometric, and laboratory data of each patient were evaluated. The Pediatric Daytime Sleepiness Scale (PDSS) and the Munich Chronotype Questionnaire (MCTQ) were used to assess the sleep characteristics., Results: The mean level of glycated hemoglobin (HbA1c) was 9.2±2.1%, and it was higher in adolescents than in children. The mean score of PDSS was 13.9±4.7. Patients with HbA1c<7.5% had lower PDSS scores and longer sleep duration on weekdays than patients with HbA1c≥7.5%. HbA1c levels were negatively correlated with chronotype values and sleep duration on weekdays and positively correlated with social jet lag. Patients who had had T1DM for less than three years had a higher prevalence of daytime sleepiness. The regression analysis showed that higher HbA1c (≥7.5%) and shorter time since the diagnosis of T1DM increased the chance of daytime sleepiness, regardless of age and sex., Conclusions: Patients with higher HbA1c had more daytime sleepiness, a morning chronotype, shorter sleep duration on weekdays and a more significant social jet lag. The shorter diagnosis time for T1DM and greater levels of HbA1c increased the chance of daytime sleepiness.

Introduction: This study aimed to assess the feasibility and efficacy of office hysteroscopy to diagnose and treat the specific uterine pathologies frequently diagnosed and thought to be associated with female infertility., Material and Methods: Using office hysteroscopy, we examined the uterine cavity in women with primary or secondary infertility and evaluated the reproductive outcomes of those affected by one or more pathologies, including cervico-isthmic adhesions, intrauterine polyps and intrauterine adhesions. Additional patient characteristics considered were age and parity, uterine pathology, pain during hysteroscopy, and outcomes including spontaneous pregnancies achieved and time between treatment and pregnancy., Results: Reproductive outcomes of 200 patients affected by one or more uterine pathologies were evaluated. Cervico-isthmic adhesions were the most frequent findings in older women, with nearly 80% of them achieving pregnancy sooner than the others in our study. Spontaneous pregnancy rates following office hysteroscopy were 76%, 53% and 22% in women with cervico-isthmic adhesions, polyps (< 5 mm) and intrauterine adhesions, respectively., Conclusions: Office hysteroscopy is a feasible and highly effective diagnostic and therapeutic procedure for cervico-isthmic and intrauterine adhesions, as well as for small polyps, allowing the resolution of female infertility related to these pathologies, without trauma and with only minimal discomfort.

The present study aimed to investigate the cytotoxic effect of 38 new thiosemicarbazone derivatives on hematological neoplastic cells lines and to select the most effective compounds to investigate the main molecular mechanisms involved in cell death. Cytotoxicity screening on Daudi and Jurkat cells revealed that only compound 1b met the selection criteria; therefore, it was chosen for further investigation. Cell viability of Daudi, Jurkat, Molt-4, Namalwa, K562, and MM.1S cell lines decreased in a concentration- and time-dependent manner after compound1b incubation; nevertheless the compound neither caused significant hemolysis nor reduction in peripheral blood mononuclear cell viability. Although no changes were observed on cell cycle or Ki-67 expression, compound1b induced apoptotic-like cell death with mitochondrial involvement, Bax/Bcl-2 inversion, AIF release, survivin inhibition, and caspase-3 activation in both Daudi and Jurkat cells. Furthermore, the compound reduced NFκB expression in Jurkat cells. In Daudi cells, compound1b also decreased CHOP, Akt, pAkt, and MAPK/ERK2 expression, thereby suggesting modulation of UPR, PI3K/Akt/mTOR, and MAPK/ERK signaling pathways. Finally, the compound was able to reduce the cell viability of samples collected from patients with different lymphoid neoplasms subtypes, showing that thiosemicarbazones derivatives could be used in the development of new drugs with anticancer activity., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest regarding the publication of the present article., (Copyright © 2020 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

The essential oil (EO) composition of leaves of Campomanesia aurea was analyzed by GC-MS. The plant was collected in April (EOA) and October (EOO) in São Francisco de Assis/RS. The essential oils were obtained by hydrodistillation in a modified Clevenger apparatus. The yields were 4.44% in April, and 6.15%, in October. Thirty-one compounds were identified in EOA, accounting for 96.87% of the total, and twenty-eight compounds were identified in EOO, accounting for 99.46% of the total. For EOA, the major identified monoterpene was p-cymene (8.33%) and the major identified sesquiterpene was α-cadinol (10.72%), while regarding EOO the major identified monoterpene was repeatedly Terpinolene (3.43%), whereas the major identified sesquiterpene was α-cadinol (12.79%). The antibacterial activity of the essential oil was evaluated against the three Listeria monocytogenes from the American Type Culture Collection (strains ATCC 7644, 19114 and 13932). The essential oil showed a MIC of 10 mg/mL against the strains ATCC 7644 and 19114, with bacteriostatic effect of 20 mg/mL and a MIC of 20 mg/mL for ATCC 13932. Regarding the antibiofilm activity, o EOO showed the best results with an inhibition of 90% in the sessile growth with an applied concentration of 4.0 mg/mL.

Glatiramer acetate (GA), a linear random copolypeptide, is a first-line treatment for multiple sclerosis (MS). A major concern, however, is that GA treatment is associated with adverse effects and poor patient adherence due to the need for frequent injections. Here we describe improved performance of the polymeric drug, even at low doses with less-frequent injections, through the modification of its architecture into a star-shaped GA (sGA). In a sGA, multiple GAs are covalently linked onto a core, which greatly changes their properties such as molecular weight, size, and shape. The spherical sGA is retained longer in the body after intraperitoneal injection, and is more readily internalized by RAW 264.7 macrophage cells and bone marrow-derived dendritic cells than GA. In C57BL/6 mice induced with experimental autoimmune encephalitis, a mouse model for MS, sGA treatment exerts disease amelioration effect that is significantly better than that of GA despite a lower dose and less frequent injection. Moreover, spinal cord pathologies of demyelination and leukocyte infiltration are dramatically less pronounced in the sGA treatment condition compared to the GA treatment condition. Thus, we propose that sGA with a higher-ordered architecture offers an attractive and potentially viable treatment option for MS patients.

Acute leukemias are a heterogeneous group of aggressive malignant neoplasms associated with severe morbidities due to the nonselectivity of current chemotherapeutic drugs to nonmalignant cells. The investigation of novel natural and synthetic structures that might be used for the development of new drugs with greater efficiency and selectivity to leukemic cells is mandatory. In this context, thiosemicarbazones have been well described in the literature by their several biological properties and their reaction is known as versatile, low-cost, and highly chemoselective. With this perspective, this study aimed to investigate the cytotoxic effect and the main death mechanisms of a novel thiosemicarbazone (LAP17) on acute leukemia cell lines K562 and Jurkat. The results show that the strong cytotoxic effect of LAP17 to leukemic cells is due to apoptosis induction, which resulted in caspase-3 activation and DNA fragmentation. Intrinsic apoptosis seems to be related to the inversion of Bax/Bcl-2 expression, ΔΨm loss, and AIF release, whereas extrinsic apoptosis was initiated by FasR. Gene-expression profiling of HL-60 cells treated with LAP17 by the microarray technique revealed a significant enrichment of gene sets related to cell cycle arrest at G2/M. Accordingly, K562 and Jurkat cells treated with LAP17 revealed a clear arrest at G2/M phase. Taking into consideration that LAP17 was not cytotoxic to nonhematological cells (peripheral blood mononuclear cell and erythrocytes), these results suggest that LAP17 is a promising new compound that might be used as a prototype for the development of new antileukemic agents.

Ribozymes synthesize proteins in a highly regulated local environment to minimize side reactions caused by various competing species. In contrast, it is challenging to prepare synthetic polypeptides from the polymerization of N -carboxyanhydrides (NCAs) in the presence of water and impurities, which induce monomer degradations and chain terminations, respectively. Inspired by natural protein synthesis, we herein report the preparation of well-defined polypeptides in the presence of competing species, by using a water/dichloromethane biphasic system with macroinitiators anchored at the interface. The impurities are extracted into the aqueous phase in situ, and the localized macroinitiators allow for NCA polymerization at a rate which outpaces water-induced side reactions. Our polymerization strategy streamlines the process from amino acids toward high molecular weight polypeptides with low dispersity by circumventing the tedious NCA purification and the demands for air-free conditions, enabling low-cost, large-scale production of polypeptides that has potential to change the paradigm of polypeptide-based biomaterials., Competing Interests: The authors declare no conflict of interest.

Cutaneous injury can ignite excessive fibroproliferative growth that results in keloid formation. Keloids are associated with significant morbidity related to disfigurement and/or symptoms (e.g., pain and pruritus). First-line treatment of formed keloids involves topical or intralesional steroids. Recurrent or resistant keloids are managed by surgical excision or cryotherapy, followed by steroidal application or adjuvant irradiation. Although adjuvant irradiation appears to be most efficacious, alternative therapeutic options are needed for patients without access to radiation centers. Botulinum Toxin A (BTA) appears to have similar inhibitory effects to irradiation on the cell cycle via downregulation of pathogenic cytokines. Herein, we conducted a study to compare the efficacy of intralesional triamcinolone used alone, or in combination with BTA, in the treatment of formed keloid scars. Twenty patients with a cumulative of 40 keloids completed the study. There was no significant difference between treatment arms with respect to height vascularization, pliability, and pigmentation scores. The addition of BTA resulted in significant symptomatic improvement of pain and pruritus as compared to intralesional triamcinolone alone (p < 0.001). Irradiation is only effective when administered in the adjuvant setting where inhibitory effects on cell cycle and migration are optimized. Future studies with intralesional triamcinolone and BTA should be performed adjuvantly., (© 2018 Wiley Periodicals, Inc.)

Mycobacterium tuberculosis secretes two protein tyrosine phosphatases as virulence factors, PtpA and PtpB. Inhibition studies of these enzymes have shown significant attenuation of the M. tuberculosis growth in vivo. As PtpA mediates many effects on the regulation of host signaling ensuring the intracellular survival of the bacterium we report, for the first time, thiosemicarbazones as potential novel class of PtpA inhibitors. Several compounds were synthesized and biologically evaluated, revealing interesting results. Enzyme kinetic assays showed that compounds 5, 9 and 18 are non-competitive inhibitors of PtpA, with K i values ranging from 1.2 to 5.6 µM. Modeling studies clarified the structure-activity relationships observed in vitro and indicated a possible allosteric binding site in PtpA structure. To the best of our knowledge, this is the first disclosure of potent non-competitive inhibitors of PtpA with great potential for future studies and development of analogues., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Synthetic polypeptides derived from the ring-opening polymerization of N-carboxyanhydrides can spontaneously fold into stable secondary structures under specific environmental conditions. These secondary structures and their dynamic transitions play an important role in regulating the properties of polypeptides in self-assembly, catalysis, polymerization, and biomedical applications. Here, we review the current strategies to modulate the secondary structures, and highlight the conformation-specific dynamic properties of synthetic polypeptides and the corresponding materials. A number of mechanistic studies elucidating the role of secondary structures are discussed, aiming to provide insights into the new designs and applications of synthetic polypeptides. We aim for this article to bring to people's attention synthetic polymers with ordered conformations, which may exhibit association behaviors and material properties that are otherwise not found in polymers without stable secondary structures.

The use of Internet of Things (IoT) is rapidly growing and a huge amount of data is being generated by IoT devices. Cloud computing is a natural candidate to handle this data since it has enough power and capacity to process, store and control data access. Moreover, this approach brings several benefits to the IoT, such as the aggregation of all IoT data in a common place and the use of cloud services to consume this data and provide useful applications. However, enforcing user privacy when sending sensitive information to the cloud is a challenge. This work presents and evaluates an architecture to provide privacy in the integration of IoT and cloud computing. The proposed architecture, called PROTeCt - P rivacy a R quitecture for integrati O n of internet of T hings and C loud computing, improves user privacy by implementing privacy enforcement at the IoT devices instead of at the gateway, as is usually done. Consequently, the proposed approach improves both system security and fault tolerance, since it removes the single point of failure (gateway). The proposed architecture is evaluated through an analytical analysis and simulations with severely constrained devices, where delay and energy consumption are evaluated and compared to other architectures. The obtained results show the practical feasibility of the proposed solutions and demonstrate that the overheads introduced in the IoT devices are worthwhile considering the increased level of privacy and security.

Purpose: Infection by Human Herpes Viruses (HHV) types 1-3, are prevalent throughout the world. It is known that radiotherapy can reactivate HHVs, but it is unclear how and to what extent reactivations can interact with or affect radiotherapeutic efficacy, patient outcomes and mortality risk. Herein, we aim to summarize what is known about Herpes Simplex Virus (HSV)-1,2 and Varicella Zoster Virus (VZV) pathophysiology as it relates to tumor biology, radiotherapy, chemo-radiotherapy, diagnosis and management so as to optimize cancer treatment in the setting of active HHV infection. Our secondary aim is to emphasize the need for further research to elucidate the potential adverse effects of active HHV infection in irradiated tumor tissue and to design optimal management strategies to incorporate into cancer management guidelines., Materials and Methods: The literature regarding herpetic infection, herpetic reactivation, and recurrence occurring during radiotherapy and that regarding treatment guidelines for herpetic infections are reviewed. We aim to provide the oncologist with a reference for the infectious dangers of herpetic reactivation in patients under their care and well established methods for prevention, diagnosis, and treatment of such infections. Pain management is also considered., Conclusions: In the radiotherapeutic setting, serologic assays for HSV-1 and HSV-2 are feasible and can alert the clinician to patients at risk for viral reactivation. RT-PCR is specific in identifying the exact viral culprit and is the preferred diagnostic method to measure interventional efficacy. It can also differentiate between herpetic infection and radionecrosis. The MicroTrak ® HSV1/HSV2/VZV staining kit has high sensitivity and specificity in acute lesions, is also the most rapid means to confirm diagnosis. Herpetic reactivation and recurrences during radiotherapy can cause interruptions, cessations, or prolongations of the radiotherapeutic course, thus decreasing the biologically effective dose, to sub-therapeutic levels. Active HHV infection within the treatment volume results in increased tumor radio-resistance and potentially sub-therapeutic care if left untreated. Visceral reactivations may result in fatality and therefore, a high index of suspicion is important to identify these active infections. The fact that such infections may be mistaken for acute and/or late radiation effects, leading to less than optimal treatment decisions, makes knowledge of this problem even more relevant. To minimize the risk of these sequelae, prompt anti-viral therapy is recommended, lasting the course of radiotherapy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Neurofibromatosis type 1 (NF1) is a monogenic disorder affecting cognitive function. About one third of children with NF1 have attentional disorders, and the cognitive phenotype is characterized by impairment in prefrontally-mediated functions. Mouse models of NF1 show irregularities in GABA release and striatal dopamine metabolism. We hypothesized that youth with NF1 would show abnormal behavior and neural activity on a task of risk-taking reliant on prefrontal-striatal circuits., Methods: Youth with NF1 (N=29) and demographically comparable healthy controls (N=22), ages 8-19, were administered a developmentally sensitive gambling task, in which they chose between low-risk gambles with a high probability of obtaining a small reward, and high-risk gambles with a low probability of obtaining a large reward. We used functional magnetic resonance imaging (fMRI) to investigate neural activity associated with risky decision making, as well as age-associated changes in these behavioral and neural processes., Results: Behaviorally, youth with NF1 tended to make fewer risky decisions than controls. Neuroimaging analyses revealed significantly reduced neural activity across multiple brain regions involved in higher-order semantic processing and motivation (i.e., anterior cingulate, paracingulate, supramarginal, and angular gyri) in patients with NF1 relative to controls during the task. We also observed atypical age-associated changes in neural activity in patients with NF1, such that during risk taking, neural activity tended to decrease with age in controls, whereas it tended to increase with age in patients with NF1., Conclusions: Findings suggest that developmental trajectories of neural activity during risky decision-making may be disrupted in youth with NF1.

Harmful Trichodesmium blooms have been reported on the continental slope of the southwestern South Atlantic Ocean; we sampled six such blooms. The highest saxitoxin concentration was observed where the number of colonies was proportionally greater relative to the total density of trichomes. Trichodesmium blooms are harmful to shrimp larvae and may lead to plankton community mortality. This study is the first record of neurotoxic blooms in the open waters of the South Atlantic., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The effects of mineral-supplement delivery system on patterns of supplement use by grazing beef cows were measured in 2 studies. Study 1 was conducted on 4 pastures grazed by pregnant, mature beef cows (BW = 562 ± 38 kg) from February to May. Study 2 was conducted on 4 pastures grazed by lactating beef cows (BW = 579 ± 54 kg) and their calves from May to September. Treatments were mineral delivered in salt-based, granular form (salty) or mineral provided in a low-protein, cooked, molasses-based block (sweet); both were fed ad libitum. The salty supplement was supplied to cattle via a covered mineral feeder; the sweet supplement was supplied via an open-topped barrel. Both salty and sweet supplements were deployed in each pasture. No additional salt was supplied to cattle. Forage use in the vicinity of each supplement-deployment site and the frequency and duration of herd visits to each supplement-deployment site were measured during four 14-d periods during study 1 and seven 14-d periods during study 2. Supplements were moved to new locations within pastures at the beginning of each period. Consumption of the sweet supplement was greater than salty during each data-collection period in study 1; however, relative differences in consumption diminished over time (treatment × time, P = 0.03). In study 2, sweet consumption was greater than salty in periods 1, 6, and 7 but was not different from salty during periods 2, 3, 4, and 5 (treatment × time, P < 0.01). Increased consumption of the sweet supplement in study 1 translated to greater frequency of herd visits to supplement-deployment sites compared with the salty sites (2.82 vs. 2.47 herd visits/d; P = 0.02) and longer herd visits to supplement-deployment sites compared with the salty sites (125.7 vs. 54.9 min/herd visit; P < 0.01). The frequency of herd visits to mineral feeding sites in study 2 was similar (P > 0.10) between treatments for periods 1 through 6; however, herds visited the sweet sites more often than salty during period 7 (P < 0.01). Herd visits to the sweet sites were longer than those to the salty sites in study 2 (83.8 vs. 51.4 min/herd visit; P < 0.01). Forage disappearance within 100 m of supplement-deployment sites was not influenced (P ≥ 0.54) by treatment in either study. Results were interpreted to suggest that the sweet supplement influenced the location of grazing cattle more strongly than the salty supplement and may be more effective for luring cattle into specific areas of pasture during the winter, spring, and early fall but not during summer.

Extensive research, intervention equipment, money, and media coverage have been directed at controlling Escherichia coli O157:H7 in beef cattle. However, much of the focus has been on controlling this pathogen postcolonization. This study was conducted to examine the performance, health, and shedding characteristics of beef calves that were vaccinated with an E. coli O157:H7 SRP bacterial extract. These calves had been born to cows vaccinated prepartum with the same vaccine. Cows and calves were assigned randomly to one of four treatments: (i) neither cows nor calves vaccinated with E. coli O157:H7 SRP (CON), (ii) cows vaccinated with E. coli O157:H7 SRP prepartum but calves not vaccinated (COWVAC), (iii) calves vaccinated with E. coli O157:H7 SRP but born to cows not vaccinated (CALFVAC), (iv) cows vaccinated with E. coli O157:H7 SRP prepartum and calves also vaccinated (BOTH). Calves born to vaccinated cows had significantly higher titers of anti-E. coli O157:H7 SRP antibodies (SRPAb) in circulation at branding time (P < 0.001). Upon entry to the feedlot, overall fecal E. coli O157:H7 prevalence was 23 % among calves, with 25 % in the CON treatment group, 19 % in the CALFVAC group, 32 % in the COWVAC group, and 15 % in the BOTH group (P > 0.05). Fecal shedding of E. coli O157 on arrival to the feedlot was not correlated with fecal shedding at slaughter (Spearman's rho = -0.02; P = 0.91). No significant effects of cow or calf E. coli O157:H7 SRP vaccination treatment were found on feedlot calf health or performance (P > 0.05), prevalence of lung lesions or liver abscess (P > 0.05), or morbidity, retreatment, or mortality numbers (P > 0.05). The findings of this study indicate that the timing of vaccination of calves against E. coli O157:H7 may be an important consideration for maximizing the field efficacy of this vaccine.