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Background: Treatment of some blood cancers with T cells that express a chimeric antigen receptor (CAR) against CD19 have shown remarkable results. In contrast, CAR-T cell efficacy against solid tumors has been difficult to achieve., Methods: To examine the potential of CAR-T cell treatments against ovarian cancers, we used the mouse ovarian cancer cell line ID8 in an intraperitoneal model that exhibits disseminated solid tumors in female C57BL/6J mice. The CAR contained a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the transferase-dependent chaperone Cosmc . The efficacy of four Tn-dependent CARs with varying affinity to Tn antigen, and each containing CD28/CD3ζ cytoplasmic domains, were compared in vitro and in vivo in this study., Results: In line with many observations about the impact of aberrant O-linked glycosylation, the ID8 Cosmc knock-out (ID8 Cosmc -KO) exhibited more rapid tumor progression compared with wild-type ID8. Despite the enhanced tumor growth in vivo, 237 CAR and a mutant with 30-fold higher affinity, but not CARs with lower affinity, controlled advanced ID8 Cosmc -KO tumors. Tumor regression could be achieved with a single intravenous dose of the CARs, but intraperitoneal administration was even more effective. The CAR-T cells persisted over a period of months, allowing CAR-treated mice to delay tumor growth in a re-challenge setting. The most effective CARs exhibited the highest affinity for antigen. Antitumor effects observed in vivo were associated with increased numbers of T cells and macrophages, and higher levels of cleaved caspase-3, in the tumor microenvironment. Notably, the least therapeutically effective CAR mediated tonic signaling leading to antigen-independent cytokine expression and it had higher levels of the immunosuppressive cytokine interleukin10., Conclusion: The findings support the development of affinity-optimized CAR-T cells as a potential treatment for established ovarian cancer, with the most effective CARs mediating a distinct pattern of inflammatory cytokine release in vitro. Importantly, the most potent Tn-dependent CAR-T cells showed no evidence of toxicity in tumor-bearing mice in a syngeneic, immunocompetent system., Competing Interests: Competing interests: DMK is a member of the scientific advisory board of Affini-T Therapeutics and a consultant for Tempus. PS, HS, KS, and DMK are co-inventors on a patent application related to these chimeric antigen receptors. No potential conflicts of interest were disclosed by the other authors., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Tuberculosis (TB) remains a major health problem worldwide, and the emergence of multi-resistant strains to first-line drugs has become the biggest obstacle to its treatment. On the other hand, the incidence of non-tuberculous mycobacteria (NTM) in humans has increased remarkably in recent years. The search for new and better treatments against mycobacterial infections is a constant at the global level. Hence, in this study, we propose to investigate the antimycobacterial effect of the extracts and major compounds of Hedeoma drummondii against clinical isolates of Mycobacterium tuberculosis and non-tuberculous mycobacteria: M. abscessus , M. fortuitum , M. intracellulare , and M. gordonae . To determine the antimycobacterial activity, a microdilution assay was used to establish the minimum inhibitory concentration (MIC) of the different strains of Mycobacterium . The methanolic extract presented the best activity against M. tuberculosis , inhibiting ten of the twelve strains analyzed at a concentration < 2500 µg/mL; meanwhile, the hexanic extract presented the best activity against non-tuberculous mycobacteria (NTM) by inhibiting eight of the ten strains studied at ≤625 µg/mL. Moreover, there is a strong positive correlation between the antimycobacterial activity of pulegone and the hexanic extract against non-tuberculous strains, so this compound could serve as a predictability marker against these types of microorganisms.

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.

Triple negative breast cancer (TNBC) is an aggressive type of cancer that accounts for ~23% of breast tumors in Mexico. In an attempt to understand in an improved way the behavior of TNBC, throughout the years, gene expression in these tumors has been studied. Lehman et al identified 6 subtypes of gene expression in TNBC with distinct characteristics. In the present study, it was aimed to assess clinical, pathological and prognostic characteristics of TNBC in a Mexican-based cohort. A total of 55 patients diagnosed with TNBC at Mexico's National Institute of Cancer (INCan) were included. Tumor needle biopsy samples were obtained and subjected to microarray analysis. Patients were thus classified into one of the 6 TNBC molecular subtypes. The prognostic, clinical and pathological information of patients was obtained, and differences across molecular subtypes were sought. Out of the 55 included patients, the following subtypes were identified: 9 basal-like-1, 11 basal-like-2 (BSL2), 16 immunomodulatory (IM), 12 mesenchymal, 6 androgen receptor-like and 1 mesenchymal stem-like. Mean follow-up time was 47.1 months. The IM molecular subtype had the best overall survival (OS) (median OS was not reached). BSL2 had the worst OS (15 months). A complete pathologic response to neoadjuvant chemotherapy was obtained more often in the IM subtype (P=0.032). No significant associations were found between any of the clinical or pathological characteristics and the TNBC molecular subtypes. The results obtained from the present study should be considered when seeking to implement a clinical-molecular model for TNBC patient care, particularly in Hispanic-based populations, as they have been frequently underrepresented in clinical studies assessing TNBC molecular subtypes., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Ortiz Valdez et al.)

Ungurahui, or Patawa, fruits are a popular fruit and medicinal food used in the Amazon. Here, we have studied nine natural populations of ungurahui from the Peruvian Amazon regarding their nutritional and biological activities, including metal composition, proximal analyses, cytotoxic, antioxidant and cholinesterase inhibition activities. Twenty-four compounds have been detected in these Peruvian natural populations by UHPLC-MS, including nine phenolic acids (peaks 1-6, 8, 9 and 11), four C-glycosyl flavonoids (peaks 12, 16, 17 and 18), two flavonols (peaks 7 and 10), one flavanol (peak 15), three anthocyanins (peaks 13, 14 and 22) and five resveratrol derivatives (peaks 19-21, 23 and 24). Sample 9, Tunaants, showed the highest DPPH clearing capacity regarding the content of Trolox equivalents (2208.79 μmol Trolox/g), but an ORAC test of the sample collected in San Lorenzo showed the highest clearing activity (1222.28 μmol Trolox/g) and the sample collected in Allpahuayo Mishana showed the most powerful ABTS (1803.72 μmol Trolox/g). The sample from Jenaro Herrera was the most powerful in AChe inhibition (IC 50 2.05 ± 0.03 μg/mL), followed by the sample from Contamana (IC 50 2.43 ± 0.12 μg/mL). In BChE inhibition, the sample from Palestina was the most active (4.42 ± 0.06 μg/mL), followed by samples from Tunaants and San Lorenzo. The differences among bioactivities can be related to the different growing conditions of the populations of ungurahui. The palm tree fruit proved to be a good source of natural antioxidants and dietary fatty acids, and their consumption represents an alternative for the prevention of neurodegenerative or related non-chronic transmittable diseases.

Objective: To examine the perceptions of labor and delivery (L&D) nurses and childbearing women in the postpartum period regarding a restricted visitor policy during the COVID-19 pandemic., Design: Descriptive mixed-methods survey and open-ended questions., Setting/local Problem: One hospital in the southwestern United States. There is limited evidence regarding recently imposed visitor restrictions related to COVID-19., Participants: Individuals who were pregnant and self-identified as women who gave birth during October 2020 through March 2021 (n = 674) and L&D nurses (n = 47)., Intervention/measurements: Participants who had given birth with visitor restrictions completed an online survey, and L&D nurses completed a paper survey., Results: Childbearing women had positive and negative views; they valued a more intimate familial bonding and recovery without visitors and appreciated decreased pressure to accommodate family/friends. They were also disappointed with sibling restrictions and were sad and frustrated with visitor limitations, especially in special circumstances (e.g., NICU admission or extended stays). Nurses expressed that visitor restrictions allowed more time for higher-quality nursing care/patient teaching and decreased distractions in emergencies, leading to safer care. Women and nurses reported that visitor restrictions allowed women more rest and relaxation as well as less worry and strain from juggling family and friends who wanted to visit, but they also identified that there was decreased family support when it was needed., Conclusion: Women's responses were mixed, with some preferring support from many visitors, while others appreciated the intimate focus of just their partner. Most nurses preferred fewer visitors but could empathize with women., (Copyright © 2022 AWHONN. Published by Elsevier Inc. All rights reserved.)

Seven medicinal plants from Chiapas, Mexico, used by Native Americans were analyzed, aiming to improve the understanding of their medicinal properties through the evaluation of various biological activities, i.e., bactericidal, antioxidant, α-glucosidase inhibition, and toxicity, to provide a scientific basis for the management of infectious and hyperglycemic diseases in the Mexican southeast. Plant extracts were obtained from Cordia dodecandra, Gaultheria odorata, Heliotropium angiospermum, Justicia spicigera, Leucaena collinsii spp. collinsii, Tagetes nelsonii, and Talisia oliviformis through maceration techniques using methanol and chloroform (1:1). Minimum Inhibitory Concentration (MIC) was employed to determine the antibacterial activity against Staphylococcus aureus, Enterobacter faecalis, Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeuroginosa. The antiradical/antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays and antihemolytic activity using the 2,2’-Azobis(2-amidinopropane) dihydrochloride radical (APPH). The anti-α-glucosidase activity was evaluated in vitro through the chromogenic PNPG assay. The toxicity was assessed using the brine shrimp lethality assay. The highest antimicrobial activity was displayed by T. nelsonii, mainly against E. faecalis and P. aeuroginosa. The extracts of L. collinsii, J. spicigera, and T. nelsonii possess antioxidant properties with EC50 < 50 μg/mL. J. spicigera and T. nelsonii extracts showed the highest antihemolytic activity with IC50 < 14 μg/mL. T. nelsonii exhibited a remarkable inhibitor effect on the α-glucosidase enzyme and the greatest toxic effect on Artemia salina with IC50 = 193 ± 20 μg/mL and LD50 = 14 ± 1 μg/mL, respectively. According to our results, G. odorata, J. spicigera, T. nelsonii, and T. oliviformis extracts contained active antimicrobial compounds. At the same time, T. nelsonii stands to be a possible source of effective antineoplastic and antihyperglycemic compounds.

Cirrhosis is a liver disease that could impair the functionality of the neural system, limiting cognitive processes and reduce mobility, possibly because alterations on dynamics of neural communications. In this study the dynamics of band power fluctuations on ß and γ bands were studied on three groups: control, patients with cirrhosis and patients diagnosed with minimal hepatic encephalopathy. EEG signals were recorded on an oddball paradigm and analyzed to obtain the latency and amplitude of the P300 wave and Detrended Fluctuation Analysis (DFA) exponent values over ß and γ band power time series for each channel. As expected, the latency of the P300 wave was significantly different for control subjects ( ). Amplitudes were not as different, but they tend to decrease for cirrhosis and minimal hepatic encephalopathy groups. DFA exponent values also tends to describe a more regular process and seems to be related with presence of symptoms of hepatic encephalopathy. These subtle changes could be produced by the mechanisms of a mild neurological impairment and be used, if it is confirmed, as an index to evaluate such deterioration.

Background: Intermittent fasting (IF), consisting of either a one-day (IF1) or two consecutive days (IF2) per week, is commonly used for optimal body weight loss. Our laboratory has previously shown an IF1 diet combined with 6d/week of protein pacing (P; 4-5 meals/day evenly spaced, ~ 30% protein/day) significantly enhances weight loss, body composition, and cardiometabolic health in obese men and women. Whether an IF1-P or IF2-P, matched for weekly energy intake (EI) and expenditure (EE), is superior for weight loss, body composition, and cardiometabolic health is unknown., Methods: This randomized control study directly compared an IF1-P (n = 10) versus an IF2-P (n = 10) diet on weight loss and body composition, cardiovascular (blood pressure and lipids), hormone, and hunger responses in 20 overweight men and women during a 4-week weight loss period. Participants received weekly dietary counseling and monitoring of compliance from a registered dietitian. All outcome variables were assessed pre (week 0) and post (week 5)., Results: Both groups significantly reduced body weight, waist circumference, percent body fat, fat mass, hunger, blood pressure, lipids, glucose, and increased percent fat-free mass (p < 0.05). However, IF2-P resulted in significantly greater reductions in body weight (-29%) and waist circumference (-38%) compared to IF1-P (p < 0.05), and showed a strong tendency for greater reductions in fat mass, glucose, and hunger levels (p < 0.10) despite similar weekly total EI (IF1-P, 9058 ± 692 vs. IF2-P, 8389 ± 438 kcals/week; p = 0.90), EE (~ 300 kcals/day; p = 0.79), and hormone responses (p > 0.10)., Conclusions: These findings support short-term IF1-P and IF2-P to optimize weight loss and improve body composition, cardiometabolic health, and hunger management, with IF2-P providing enhanced benefits in overweight women and men., Trial Registration: This trial was registered March 03, 2020 at www., Clinicaltrials: gov as NCT04327141 ., (© 2022. The Author(s).)

Objective: To explore birth and at-home postpartum experiences of individuals with lower extremity nerve injury (LENI) related to childbirth., Design: Mixed-methods, descriptive, cross-sectional survey with open-ended questions., Setting: Closed Facebook support group., Participants: Two hundred-thirty individuals who experienced LENI during childbirth., Measurements: Two research team members developed the online LENI survey that incorporated suggestions from LENI support group leaders. We used descriptive statistics, linear regression, and Kaplan-Meier survival curves to summarize the quantitative data and used content analysis for open-ended items., Results: We described labor, birth, and postpartum characteristics in our sample, including immediate and long-term LENI symptoms. Falls resulting from LENI were common in the hospital (55.6%) and at home (75.6%). At discharge home, respondents reported low confidence in their ability to care for themselves and their infants as well as high levels of dependence on others. There was an 89.6% prevalence of depression in the first month at home. Approximately 80% of participants rated their degree of healing at 5 years as 80% to 100% healed. Content analysis yielded six themes: (a) Grieving Loss of Current and Future Life; (b) Caregiver Responses That Helped or Hindered; (c) Being in Danger; (d) Experiencing Emotional Turmoil; (e) Dealing With Family, Marital, and Financial Difficulties; and (f) Finding Strength, Overcoming Obstacles, and Experiencing Personal Growth., Conclusion: Participants in our sample reported a very high rate of falls, anxiety, and depression at home. Nurses should recognize LENI symptoms, take action to prevent falls, and offer accurate information and referrals., Competing Interests: Author Disclosures The authors report no conflicts of interest or relevant financial relationships., (Copyright © 2022 AWHONN. Published by Elsevier Inc. All rights reserved.)

Introduction: Twenty percent of patients with Guillain-Barré syndrome (GBS) have poor outcomes despite proper management. The aim of the study was to characterize electrophysiological factors related to poor outcome in patients with GBS., Methods: We conducted an observational study from a prospective cohort of 91 patients with GBS in a tertiary healthcare center in Mexico, from 2017 to 2019. Demographics and nerve conduction studies were performed on admission, and a 3-month follow-up for GBS disability score was ensued, allocating patients in good (GBS disability score ≤ 2) and poor outcome (GBS disability score ≥ 3) groups. A logistic regression analysis for independent walk at 3 months was performed. Kaplan-Meier estimator curves for independent walk in very low (< 20% LLN) and low-normal ( ≥20% LLN) peroneal nerve CMAPs are presented., Results: From the 91 GBS patients included, 37 (40.6%) did not regain independent walk at 3 months. Axonal variants were more common in the poor outcome group (31.4% vs 59.4%, p = 0.01) as well as AIDP variants with motor conduction block (6.6% vs 42.4%, p = 0.018). Univariable analysis was statistically significant for very low median, ulnar, tibial, and peroneal CMAP amplitudes in poor outcome patients; however, multivariable analysis was only significant for very low peroneal nerve CMAP amplitude (OR 3.6 [1.1-11.5, p = 0.024]). Conversely, a greater proportion of GBS patients with low-normal CMAPs recovered independent walk at 90 days (75% vs 30%, p < 0.001)., Conclusion: Severe axonal injury of the peroneal nerve, axonal, and AIDP with motor conduction block variants predicts worse functional outcome regarding independent walk at 3 months., (© 2021. Fondazione Società Italiana di Neurologia.)

Ehretia tinifolia Linnaeus (Boraginacea) and Sideroxylon lanuginosum Michaux (Sapotaceae) are wild fruits consumed in North America and are appreciated for their pleasant flavor and sweet taste. However, details regarding their composition and biological properties in the available literature are scarce. This study reports the phenolic composition, antioxidant, antiproliferative activities, and digestive enzymatic inhibition of amberlite-retained methanolic extracts from both fruits. Results revealed that these wild fruit extracts are rich in antioxidants. S. lanuginosum had lower phenolic but higher flavonoid contents (21.4 ± 1.5 mg GAE/100 g FW and 6.42 ± 0.9 mg CE/100 g FW) than E. tinifolia (64.7 ± 2.6 mg GAE/100 g FW and 5.1 ± 0.4 mg CE/100 g FW). HPLC-DAD-MS/MS analysis showed rosmarinic acid as a major polyphenol in E. tinifolia and quercetin glucoside in S. lanuginosum . Polyphenols content in E. tinifolia was related to a significant free radical scavenging ability: DPPH (EC 50 = 0.32 ± 0.03 mg/mL), TEAC (4134 ± 9.7 μM TE/g dry extract), and hemolysis inhibition (IC 50 = 58.55 ± 2.4 μg/mL). Both extracts were capable of inhibiting α -glucosidase, partially inhibiting α -amylase, and showed no inhibition against lipase, while showing antiproliferative activity against HeLa, HT-29 and MCF-7 cancer cell lines. Our study revealed that these wild fruit extracts are rich in health-beneficial phytochemicals and hold significant potential for elaborating functional foods.

Introduction: To describe clinical characteristics and electrophysiological variants of GBS cases during the pandemic, we carried out a comparative analysis between SARS-CoV2 related GBS and non-SARS-CoV2 patients and then compared to the 2019 cases., Patients and Methods: We carried out a cross-sectional study of GBS patients diagnosed according to Asbury and Cornblath criteria. We collected information on clinical and paraclinical variables. We defined a SARS-CoV-2 related GBS case according to the description of Ellul et al. We used Hadden criteria to classify the electrophysiological variants. We performed a comparative analysis between groups., Results: Fourty-two patients were diagnosed with GBS in 2020, men 64.2%, age 46 ± 17.4 years, patients with obesity/overweight 42.8%, previous diarrhea 31%, history of respiratory tract infection 14.2%. Guillain Barre Disability Scale = 3 points 71.4% and, cranial nerve involvement 69%. The most frequent electrophysiological variant was acute inflammatory demyelinating polyradiculoneuropathy (AIDP) 53.5%. Seven (16.6%) cases were SARS-CoV2 related, four men, age 43.4 ± 13.4 years. When comparing patients with GBS in 2020 vs patients in 2019, we observed a decrease in the previous infection history during 2020 (45.2% vs 73.3%, p-value = 0.005) and a decrease in previous respiratory infection (14.2% vs 33.3%, p = 0.045), as well as a higher frequency of cranial nerve involvement, and albuminocytologic dissociation., Conclusions: SARS-CoV2 virus infection preventive measures may be impacting the presentation of post-infectious diseases such as GBS. We did not observe an increase in GBS cases during 2020. Also, the AIDP variant were more frequent in our population in the COVID-19 pandemic.

Parkinson's disease (PD) is a neuropathy characterized by motor disorders, but it has also been associated with the presence of autonomic alterations as a result of degradation of the dopaminergic system. Studying the relation between Band Power time series (BPts) and Heart Rate Variability (HRV), has been proposed as a tool to explore the bidirectional communication pathways between cortex and autonomic control. This work presents a primer analysis on study brain ↔ heart interaction on a databse of PD patients under two conditions: without and after levadopa (L-dopa) intake. Additionally a healthy control population was also analyzed, and used as comparison level between both conditions. Results show PD affects pathways by reducing the number of connections, specially association of beta and power and the second faster component of HRV seems to be more sensitive to L-dopa administration.

An important challenge when designing Brain Computer Interfaces (BCI) is to create a pipeline (signal conditioning, feature extraction and classification) requiring minimal parameter adjustments for each subject and each run. On the other hand, Convolutional Neural Networks (CNN) have shown outstanding to automatically extract features from images, which may help when distribution of input data is unknown and irregular. To obtain full benefits of a CNN, we propose two meaningful image representations built from multichannel EEG signals. Images are built from spectrograms and scalograms. We evaluated two kinds of classifiers: one based on a CNN-2D and the other built using a CNN-2D combined with a LSTM. Our experiments showed that this pipeline allows to use the same channels and architectures for all subjects, getting competitive accuracy using different datasets: 71.3 ± 11.9% for BCI IV-2a (four classes); 80.7 ± 11.8 % for BCI IV-2a (two classes); 73.8 ± 12.1% for BCI IV-2b; 83.6 ± 1.0% for BCI II-III and 82.10% ± 6.9% for a private database based on mental calculation.

Parkinson's Disease is a neuropathy that produces changes in several biomarkers, these changes could be used to evaluate even sub-clinical conditions. This paper presents an evaluation of indices extracted from electroencephalography and Heart Rate Variability (HRV), when used to classify a sample of subjects from three groups: control (healthy), medicated and non medicated subjects diagnosed with Parkinson's disease. Classification performance was measured using accuracy over these classes and a cross validation scheme was used to assess repeatability for the classification process. Results tend to prove that inclusion of an autonomic index derived from HRV analysis enhances classification, suggesting that Parkinson's disease could be related with unperceptible to mild alterations of the Autonomic Nervous System.

Objective: Dynamics of humoral immune responses to SARS-CoV-2 antigens following infection suggest an initial decay of antibody followed by subsequent stabilisation. We aim to understand the longitudinal humoral responses to SARS-CoV-2 nucleocapsid (N) protein and spike (S) protein and to evaluate their correlation to clinical symptoms among healthcare workers (HCWs)., Design: A prospective longitudinal study., Setting: This study was conducted in a New York City public hospital in the South Bronx, New York., Participants: HCWs participated in phase 1 (N=500) and were followed up 4 months later in phase 2 (N=178) of the study. They underwent SARS-CoV-2 PCR and serology testing for N and S protein antibodies, in addition to completion of an online survey in both phases. Analysis was performed on the 178 participants who participated in both phases of the study., Primary Outcome Measure: Evaluate longitudinal humoral responses to viral N (qualitative serology testing) and S protein (quantitative Mount Sinai Health System ELISA to detect receptor-binding domain and full-length S reactive antibodies) by measuring rate of decay., Results: Anti-N antibody positivity was 27% and anti-S positivity was 28% in phase 1. In phase 1, anti-S titres were higher in symptomatic (6754 (5177-8812)) than in asymptomatic positive subjects (5803 (2825-11 920)). Marginally higher titres (2382 (1494-3797)) were seen in asymptomatic compared with the symptomatic positive subgroup (2198 (1753-2755)) in phase 2. A positive correlation was noted between age (R=0.269, p<0.01), number (R=0.310, p<0.01) and duration of symptoms (R=0.434, p<0.01), and phase 1 anti-S antibody titre. A strong correlation (R=0.898, p<0.001) was observed between phase 1 titres and decay of anti-S antibody titres between the two phases. Significant correlation with rate of decay was also noted with fever (R=0.428, p<0.001), gastrointestinal symptoms (R=0.340, p<0.05), and total number (R=0.357, p<0.01) and duration of COVID-19 symptoms (R=0.469, p<0.001)., Conclusions: Higher initial anti-S antibody titres were associated with larger number and longer duration of symptoms as well as a faster decay between the two time points., Competing Interests: Competing interests: FK is listed as a co-inventor on a patent application filed by the Icahn School of Medicine at Mount Sinai relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. FK has consulted for Merck and Pfizer (before 2020), and is currently consulting for Seqirus and Avimex. FK’s Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The shrimp gut is a long digestive structure that includes the Foregut (stomach), Midgut (hepatopancreas) and Hindgut (intestine). Each component has different structural, immunity and digestion roles. Given these three gut digestive tract components' significance, we examined the bacterial compositions of the Foregut, Hindgut, and Midgut digestive fractions. Those bacterial communities' structures were evaluated by sequencing the V3 hypervariable region of the 16S rRNA gene, while the functions were predicted by PICRUSt2 bioinformatics workflow. Also, to avoid contamination with environmental bacteria, shrimp were maintained under strictly controlled conditions. The pairwise differential abundance analysis revealed differences among digestive tract fractions. The families Rhodobacteraceae and Rubritalaceae registered higher abundances in the Foregut fraction, while in the Midgut, the families with a higher proportion were Aeromonadaceae, Beijerinckiaceae and Propionibacteriaceae. Finally, the Cellulomonadaceae family resulted in a higher proportion in the Hindgut. Regarding the predicted functions, amino acid and carbohydrate metabolism pathways were the primary functions registered for Foregut microbiota; conversely, pathways associated with the metabolism of lipids, terpenoids and polyketides, were detected in the Midgut fraction. In the Hindgut, pathways like the metabolism of cofactors and vitamins along with energy metabolism were enriched. Structural changes were followed by significant alterations in functional capabilities, suggesting that each fraction's bacteria communities may carry out specific metabolic functions. Results indicate that white shrimp's gut microbiota is widely related to the fraction analyzed across the digestive tract. Overall, our results suggest a role for the dominant bacteria in each digestive tract fraction, contributing with a novel insight into the bacterial community., Competing Interests: The authors declare that they have no competing interests., (© 2021 Garibay-Valdez et al.)

Some hypotheses relate oscillations of EEG band power with autonomic processes derived from homeostatic control modulated by structures like the Central Autonomic Network and the Autonomic Nervous System. This research project studies the causal relationships between fluctuations of an autonomic process marker like the Heart Rate Variability (HRV) and the proposed EEG band power time series (BPts). To verify the existence of directional causal relationships, using Granger Causality (GC) test between HRV and BPts. Analyses were performed using two databases, of 9 and 14 subjects respectively. Experiments consisted of spontaneous breathing and a controlled breathing task (CBT). GC was tested over Intrinsinc Mode Functions of HRV derived from Empirical Mode Decomposition and BPts computed over α, β and γ bands. Positive GC tests were observed through each experimental task, channels, IMFs, EEG band, and direction. The largest number of positive GC relationships were found from BPts to HRV when testing, higher EEG band and IMF with lower spectral content. Opposite direction achieves lower total counts, but more related with IMFs of higher spectral content. Its presence also suggests that some homeostatic condition alters the BPts course given its increment under the CBT. It is important to notice that in both cases γ band achieves larger values for almost all of the studied conditions. Suggesting that such band has an important influence over HRV, but alterations on breathing condition also produce changes on BPts evolution, suggesting that the closed loop for homeostatic control alters neural dynamics at cortical level., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Reproduction is the biological process that sustains life. It is regulated by a neuro-hormonal mechanism that is synchronized by the interaction among the hypothalamus, hypophysis, and ovaries. Ovulation is regulated by the secretion of the gonadotropin-releasing hormone (GnRH), which stimulates the release of the luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In addition to these neuroendocrine signals, other signals originating from the central nervous system, hypophysis, thyroid, adrenal glands, and the ovary itself are also involved. One of the neurotransmission systems involved in the regulation of ovulation is the cholinergic system, which not only participates in the regulation of reproductive functions but also modulates motor coordination, thermoregulation, and cognitive function. In mammals, the vagus nerve is one of the pathways through which acetylcholine reaches the ovary, and this pathway also participates in the regulation of ovulation. However, this regulation depends on the age of the animal (prepubertal or adult) and its endocrine status. The present review analyzes evidence of the roles of the central and peripheral cholinergic system and vagal innervation in the regulation of GnRH secretion and ovulation as well as their roles in the development and persistence of polycystic ovary syndrome (PCOS)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Multidrug-resistant infections due to Mycobacterium abscessus often require complex and prolonged regimens for treatment. Here, we report the evaluation of a new ex vivo antimicrobial susceptibility testing model using organotypic cultures of murine precision-cut lung slices, an experimental model in which metabolic activity, and all the usual cell types of the organ are found while the tissue architecture and the interactions between the different cells are maintained., Methods: Precision cut lung slices (PCLS) were prepared from the lungs of wild type BALB/c mice using the Krumdieck ® tissue slicer. Lung tissue slices were ex vivo infected with the virulent M. abscessus strain L948. Then, we tested the antimicrobial activity of two drugs: imipenem (4, 16 and 64 μg/mL) and tigecycline (0.25, 1 and 4 μg/mL), at 12, 24 and 48 h. Afterwards, CFUs were determined plating on blood agar to measure the surviving intracellular bacteria. The viability of PCLS was assessed by Alamar Blue assay and corroborated using histopathological analysis., Results: PCLS were successfully infected with a virulent strain of M. abscessus as demonstrated by CFUs and detailed histopathological analysis. The time-course infection, including tissue damage, parallels in vivo findings reported in genetically modified murine models for M. abscessus infection. Tigecycline showed a bactericidal effect at 48 h that achieved a reduction of > 4log 10 CFU/mL against the intracellular mycobacteria, while imipenem showed a bacteriostatic effect., Conclusions: The use of this new organotypic ex vivo model provides the opportunity to test new drugs against M. abscessus, decreasing the use of costly and tedious animal models.

Objective: To describe the incidence, health effects, risk factors, and practice implications of lower extremity nerve injury (LENI) related to vaginal births., Data Sources: We searched MEDLINE, CINAHL, and PubMed from 2000 to 2020 for peer-reviewed published case reports and research studies of LENI related to vaginal births., Study Selection: We identified 188 potential records, and 20 met inclusion criteria (six research studies and 14 case studies)., Data Extraction: Three independent reviewers extracted details of injuries and births into an Excel spreadsheet and analyzed data using SPSS., Data Synthesis: Using birth data from each case study and from four of the six research articles, we found the incidence of LENI in vaginal births was 0.3% to 1.8%. The description of health effects includes affected nerves and the location, description, and duration of symptoms. Analyses of risk factors were limited by missing birth data (length of second stage, birth weight, etc). Vaginal births with LENI were 76% spontaneous, 77% with neuraxial anesthesia, and 64% first vaginal birth. Practice implications focused on prevention through specific positioning strategies. Despite nurses being the primary caregivers during labor, LENI was reported most often in anesthesia journals with virtually no reports in nursing journals., Conclusion: LENI is a potential complication of vaginal birth, and little published research is available on prevention and prognosis. While obstetric and anesthesia factors can cause or contribute to nerve injury, LENI is usually caused by positioning and is considered preventable. Care recommendations include the following: avoid prolonged hyperflexion of women's thighs and knees; minimize time in lithotomy, squatting, or kneeling positions; prevent hand or other deep pressure on lateral knee and posterior thigh areas; avoid motor-blocking neuraxial (epidural) anesthesia; and implement frequent repositioning. The paucity of literature contributes to the lack of awareness of LENI among clinicians., (Copyright © 2020 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

A new library of twenty triazole-lapachol and nor-lapachol derivatives was synthesized. The compounds were evaluated against the epimastigotes form of Trypanosoma cruzi and promastigotes of Leishmania braziliensis and L. infantum. The cytotoxicity of the compounds was determined on murine fibroblasts and used to assess the selectivity index. The introduction of triazole rings in the naphthoquinone derivatives improved activity against the parasitic protozoa T. cruzi and Leishmania species. Some of the derivatives were three to six times more potent than benznidazole against T. cruzi, with similar or slightly better selectivity indexes. The results against L. braziliensis showed that the derivatives 5b and 5e were the most selective compounds. However, they were less selective than the reference compound, miltefosine. Among all products, the derivative 3a was the most selective compound against L. infantum. Nevertheless, it was less potent and less selective than miltefosine. Also, the minimum inhibitory concentration values of the derivatives against nine different bacteria were determined. Moderate antibacterial activity was observed for compound 5c against Staphylococcus aureus., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Most methods for sudden cardiac death (SCD) prediction require long-term (24 h) electrocardiogram recordings to measure heart rate variability (HRV) indices or premature ventricular complex indices (with the heartprint method). This work aimed to identify the best combinations of HRV and heartprint indices for predicting SCD based on short-term recordings (1000 heartbeats) through a support vector machine (SVM). Eleven HRV indices and five heartprint indices were measured in 135 pairs of recordings (one before an SCD episode and another without SCD as control). SVMs (defined with a radial basis function kernel with hyperparameter optimization) were trained with this dataset to identify the 13 best combinations of indices systematically. Through 10-fold cross-validation, the best area under the curve (AUC) value as a function of γ (gamma) and cost was identified. The predictive value of the identified combinations had AUCs between 0.80 and 0.86 and accuracies between 80 and 86%. Further SVM performance tests on a different dataset of 68 recordings (33 before SCD and 35 as control) showed AUC = 0.68 and accuracy = 67% for the best combination. The developed SVM may be useful for preventing imminent SCD through early warning based on electrocardiogram (ECG) or heart rate monitoring.

Brainwaves amplitude obtained from electroencephalography (EEG) has been well-recognized as a basis for cognitive capacity, memory, and learning on animals and humans. Adult neurogenesis mechanism is also linked to memory and learning improvement. Traditionally, researchers used to assess learning and memory parameters in rodent models by behavioral tasks. Therefore, the simultaneous monitoring of behavioral changes and EEG is particularly interesting in correlating data between brain activity and task-related behaviors. However, most of the equipment required to perform both studies are either complex, expensive, or uses a wired setup network that hinders the natural animals' movement. In this study, EEG was recorded with a wireless electrophysiology device along with the execution of a novel object recognition task (NORT). The animal's behavior was monitored simultaneously by a video tracking system. Both recordings were analyzed offline by their timestamps which were synched to link EEG signals with the animal's actions. Subjects consist of adult Wistar rats after medium-term environmental enrichment treatment. Six skull screw electrodes were fixed in pairs on both hemispheres over frontal, central, and parietal regions and were referenced to an electrode located posterior of the nasal bone. NORT protocol consists of exposing the animal to two identical objects for 10 min. After 2 h and 24 h, one of the objects was replaced with a novel one. Exploration time for each object was monitored by a behavioral tracking software (BTS) and EEG data recording. The analysis of the EEG synced with behavioral data consists of estimations of alpha and beta relative band power and comparisons between novel object recognition versus familiar object exploration, between three experimental stages. In this manuscript, we have discussed electrodes manufacturing process, epidural electrodes implantation surgery, environmental enrichment protocol, NORT protocol, BTS setup, EEG - BTS coupling for simultaneous monitoring in real-time, and EEG data analysis based on automatic events detection.

This work aimed to evaluate the link between the occurrence/abundance of Vibrio populations and bacterial composition in shrimp's intestine (Litopenaeus vannamei) during post-larval ontogenetic development and in its culture water, and the correlation of these with environmental parameters. The total and metabolically active populations of Vibrio in the digestive tract of shrimp during its post-larval development were analysed using quantitative PCR (qPCR) and reverse transcription qPCR targeting the 16S rRNA gene sequence. A lab-scale shrimp bioassay was performed for 80 days in a recirculating aquarium under strictly controlled conditions. The results indicate that the Vibrio population from shrimp's gut is associated with its developmental stage and the environment. Multivariate analyses revealed that the presence of Vibrio spp. drove the studied system, but their metabolically active performance was related to earlier developmental stages in an aqueous environment. Also, the samples taken from water of culture units to compare the influence of the aquatic environment on the intestinal microbial community during shrimp's ontogenetic development showed significant differences. Finally, our results revealed that Vibrio is an important member of shrimp's gut microbiota; however, its metabolic activity seems to be highly regulated, possibly by the host and by the rest of the microbiota.

Purpose: Little is known about the role of the superior ovarian nerve (SON) in follicular development during the estrus cycle. The aim of the present study was to analyze the role of neural signals arriving through the SON at the ovaries in the regulation of follicular development and ovarian steroid secretion in diestrus 1 of cyclic rats., Methods: Cyclic rats were subjected to left, right, or bilateral SON sectioning or to unilateral or bilateral laparotomy at diestrus 1 at 11:00 h. Animals were sacrificed 24 h after surgery., Results: Compared to laparotomized animals, unilateral SON sectioning decreased the number of preovulatory follicles, while bilateral SON sectioning resulted in a decreased number of atretic preantral follicles. An important observation was the presence of invaginations in the follicular wall of large antral and preovulatory follicles in animals with denervation. Furthermore, left SON sectioning increased progesterone levels but decreased testosterone levels, which are effects that were not observed in animals that were subjected to right denervation., Conclusions: At 11:00 h of diestrus 1, the SON was found to stimulate follicle development, possibly via neural signals, such as noradrenaline and/or vasoactive intestinal peptide, and this stimulation induced the formation of follicle-stimulating hormone receptors. The role of the SON in the regulation of ovarian steroid secretion is asymmetric: the left SON inhibits the regulation of progesterone and stimulates testosterone secretion, and the right nerve does not participate in these processes.

Marine environments represent a great opportunity for the discovery of compounds with a wide spectrum of bioactive properties. Due to their large variety and functions derived from natural selection, marine natural products may allow the identification of novel drugs based not only on newly discovered bioactive metabolites but also on already known compounds not yet thoroughly investigated. Since drug resistance has caused an increase in infections by Mycobacterium tuberculosis and nontuberculous mycobacteria, the re-evaluation of known bioactive metabolites has been suggested as a good approach to addressing this problem. In this sense, this study presents an evaluation of the in vitro effect of laurinterol and aplysin, two brominated sesquiterpenes isolated from Laurencia johnstonii , against nine M. tuberculosis strains and six nontuberculous mycobacteria (NTM). Laurinterol exhibited good antimycobacterial activity, especially against nontuberculous mycobacteria, being remarkable its effect against Mycobacterium abscessus , with minimum inhibitory concentration (MIC) values lower than those of the reference drug imipenem. This study provides further evidence for the antimycobacterial activity of some sesquiterpenes from L. johnstonii , which can be considered interesting lead compounds for the discovery of novel molecules to treat NTM infections.

Aedes aegypti is the main vector of arboviral diseases such as dengue, chikungunya and Zika. A key feature for disease transmission modeling and vector control planning is adult mosquito dispersal. We studied Ae aegypti adult dispersal by conducting a mark-capture study of naturally occurring Ae. aegypti from discarded containers found along a canal that divided two residential communities in Donna, Texas, USA. Stable isotopes were used to enrich containers with either 13 C or 15 N. Adult mosquitoes were collected outdoors in the yards of households throughout the communities with BG Sentinel 2 traps during a 12-week period. Marked mosquito pools with stable isotopes were used to estimate the mean distance travelled using three different approaches (Net, Strip or Circular) and the probability of detecting an isotopically marked adult at different distances from the larval habitat of origin. We consistently observed, using the three approaches that male (Net: 220 m, Strip: 255 m, Circular: 250 m) Ae. aegypti dispersed further in comparison to gravid (Net: 135 m, Strip: 176 m, Circular: 189 m) and unfed females (Net: 192 m, Strip: 213 m, Circular: 198 m). We also observed that marked male capture probability slightly increased with distance, while, for both unfed and gravid females, such probability decreased with distance. Using a unique study design documenting adult dispersal from natural larval habitat, our results suggest that Ae. aegypti adults disperse longer distances than previously reported. These results may help guide local vector control authorities in their fight against Ae. aegypti and the diseases it transmits, suggesting coverage of 200 m for the use of insecticides and innovative vector control tools.

Objective: To examine whether frailty in older men is associated with poorer oral health and lower levels of dental service utilisation., Background: Poor oral health has been associated with some frailty components. Less is known about the link between frailty and oral health outcomes., Methods: A cross-sectional analysis. Data were collected from 601 older men with both frailty status and oral health information. Frailty was defined as meeting three or more of the Cardiovascular Health Study criteria: weight loss, weakness, exhaustion, slowness and low activity. Dental service utilisation (DSU) behaviour was collected from self-response questionnaires and face-to-face interviews. Oral status (number of remaining and functional teeth, periodontal disease, active coronal decayed surface [ACDS] and self-rated oral health [SROH]) was recorded by two oral health therapists. The association between frailty and oral health behaviour and risk markers was modelled using logistic regression., Results: Nineteen per cent of the participants were identified as frail. There were significant associations between frailty and dentition status (odds ratio [OR]: 2.49, 95% confidence interval [CI]: (1.17-5.30), and frailty and ACDS (OR: 3.01, CI: 1.50-6.08) but only ACDS remained significant after adjusting for confounders (adjusted OR: 2.46, CI: 1.17-5.18). There was no association between frailty and DSU and frailty and SROH., Conclusion: Frailty was independently associated with the presence of dental caries. However, DSU, SROH and other oral health markers were not significantly associated with frailty after adjusting for confounders. The prevalence of periodontal disease was high regardless of their frailty status., (© 2019 Gerodontology Association and John Wiley & Sons Ltd.)

Introduction: The purpose of this study is to use Youth Participatory Action Research (YPAR) methods and Photovoice to identify the perceived environmental factors that influence substance use among adolescents living at the U.S.-Mexico border., Methods: One academic and a local youth health coalition engaged in Youth Participatory Action Research (YPAR) using Photovoice and qualitative methods to examine the perceived factors influencing adolescent substance use in their border community., Results: Identified novel risk factors for adolescent substance use on the border included the normalization of drug trafficking, normalization of substance use, and cross-border access to substances. Novel protective factors included living in a close-knit binational community and having strong binational family and social support systems. The findings also illustrate a nexus of 'factors' wherein risk and protective elements overlap., Conclusion: This study contributes to the broader literature on international border health and how living in a border space influences adolescent substance use. The examination of influential border-bound factors provides a more complete understanding of the experiences of youth living on the U.S.-Mexico border, and informs the field of the importance of considering the border experience for future prevention and risk reduction efforts with border adolescents., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: To describe the associations between chewing function with oral health and certain general health characteristics, in a population of community-dwelling older Australian men., Methods: Analysis of data obtained from a cross-sectional analysis of the 4th wave of the Concord Health and Ageing in Men Project cohort of 614 participants, 524 whom were dentate, aged 78 years and over. Their chewing capacity was assessed using three main indicators: capacity to chew eleven food items ranging from boiled eggs through to fresh carrots and nuts; discomfort when eating; and interruption of meals. Associations with chewing were tested for dentate vs edentate participants, numbers of teeth present, active dental disease and key general health conditions such as disabilities, comorbidities and cognitive status. Log binomial regression models adjusted for age, country of birth, income, education and marital status. Prevalence ratios and 95% confidence intervals were estimated., Results: Twenty-one per cent of participants could not eat hard foods, while 23.1% reported discomfort when eating, and 8.8% reported interrupted meals when eating. There was a threefold difference in the capacity of dentate men to chew firm meat over that of edentulous men (95% CI, 2.0-4.9); a 2.5 times greater likelihood of edentate men reporting discomfort when eating (95% CI: 1.5-4.3); and 1.9 times greater likelihood of edentate participants reporting having meals interrupted (95% CI: 1.4-2.6). Chewing/eating difficulties were associated with both dental status (number of teeth, active dental caries) and self-rated dental health. Fewer than 20 teeth and the presence of active coronal or root decay were associated with more discomfort when eating. General health conditions associated with chewing function included disability, physical activity, comorbidities, cognitive status and depression. Older men's self-rated oral health and general health perceptions were also associated with aspects of chewing function. Poorer self-reported oral health was associated with inability to eat hard foods (95% CI: 1.3-2.7) and with discomfort when eating (95% CI: 2.6-5.1), while poorer self-reported general health was associated with discomfort when eating (95% CI: 1.2-2.2)., Conclusions: Falling rates of edentulism may lead to improved chewing and eating function in older men. Maintaining 20 or more natural teeth, and preventing active coronal and root caries should enhance chewing function and promote self-reported health and oral health. Lower capacity to chew hard foods and a higher reporting of discomfort when eating is associated with co-morbidity in older Australian men., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The yellow fever mosquito, Aedes aegypti, has facilitated the re-emergence of dengue virus (DENV) and emergence of chikungunya virus (CHIKV) and Zika virus (ZIKV) in the Americas and the Caribbean. The recent transmission of these arboviruses in the continental United States has been limited, to date, to South Florida and South Texas despite Ae. aegypti occurring over a much larger geographical region within the country. The main goal of our study was to provide the first long term longitudinal study of Ae. aegypti and enhance the knowledge about the indoor and outdoor relative abundance of Ae. aegypti as a proxy for mosquito-human contact in South Texas, a region of the United States that is at high risk for mosquito-borne virus transmission. Here, the relative abundance of indoors and outdoors mosquitoes of households in eight different communities was described. Surveillance was done weekly from September 2016 to April 2018 using the CDC Autocidal Gravid Ovitraps in low- and middle-income communities. A total of 69 houses were included in this survey among which 36 were in the low-income communities (n = 11 for Donna, n = 15 for Progresso, n = 5 for Mesquite, n = 5 for Chapa) and 33 in middle-income communities (n = 9 for La Feria, n = 8 for Weslaco, n = 11 for McAllen, and n = 5 for Rio Rico). Overall, Ae. aegypti was the dominant species (59.2% of collections, n = 7255) followed by Culex spp. mosquitoes (27.3% of collections, n = 3350). Furthermore, we demonstrated for Ae. aegypti that 1) outdoor relative abundance was higher compared to indoor relative abundance, 2) low-income communities were associated with an increase in mosquito relative abundance indoors when compared to middle-income communities, 3) no difference was observed in the number of mosquitoes collected outdoors between low-income and middle-income communities, and 4) warmer months were positively correlated with outdoor relative abundance whereas no seasonality was observed in the relative abundance of mosquitoes indoors. Additionally, Ae. aegypti mosquitoes collected in South Texas were tested using a specific ZIKV/CHIKV multiplex real-time PCR assay, however, none of the mosquitoes tested positive. Our data highlights the occurrence of mosquitoes indoors in the continental United States and that adults are collected nearly every week of the calendar year. These mosquito data, obtained concurrently with local ZIKV transmission of 10 locally acquired cases in nearby communities, represent a baseline for future studies in the Lower Rio Grande Valley (LRGV) including vector control interventions relying on the oviposition behavior to reduce mosquito populations and pathogen transmission., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Precision-cut tissue slices are considered an organotypic 3D model widely used in biomedical research. The comet assay is an important screening test for early genotoxicity risk assessment that is mainly applied on in vitro models. The aim of the present study was to provide a 3D organ system for determination of genotoxicity using a modified method of the comet assay since the stromal components from the original tissue make this technique complicated., Materials and Methods: A modified comet assay technique was validated using precision-cut hamster kidney slices to analyze the antigenotoxic effect of the phenolic compounds caffeic acid, chlorogenic acid, and rosmarinic acid in tissue slices incubated with 15 µM HgCl 2 . Cytotoxicity of the phenolic compounds was studied in Vero cells, and by morphologic analysis in tissue slices co-incubated with HgCl 2 and phenolic compounds., Results: A modification of the comet assay allows obtaining better and clear comet profiles for analysis. Non-cytotoxic concentrations of phenolic acids protected kidney tissue slices against mercury-induced DNA damage, and at the same time, were not nephrotoxic. The highest protection was provided by 3 µg/ml caffeic acid, although 6 µg/ml rosmarinic and 9 µg/ml chlorogenic acids also exhibited protective effects., Conclusion: This is the first time that a modification of the comet assay technique is reported as a tool to visualize the comets from kidney tissue slices in a clear and simple way. The phenolic compounds tested in this study provided protection against mercury-induced genotoxic damage in precision-cut kidney slices., Competing Interests: All authors declared no conflict of interest in present manuscript.

Macroalgae represent an important source of bioactive compounds with a wide range of biotechnological applications. Overall, the discovery of effective cytotoxic compounds with pharmaceutical potential is a significant challenge, mostly because they are scarce in nature or their total synthesis is not efficient, while the bioprospecting models currently used do not predict clinical responses. Given this context, we used three-dimensional (3D) cultures of human breast cancer explants to evaluate the antitumoral effect of laurinterol, the major compound of an ethanolic extract of Laurencia johnstonii . To this end, we evaluated the metabolic and histopathological effects of the crude extract of L. johnstonii and laurinterol on Vero and MCF-7 cells, in addition to breast cancer explants. We observed a dose-dependent inhibition of the metabolic activity, as well as morphologic and nuclear changes characteristic of apoptosis. On the other hand, a reduced metabolic viability and marked necrosis areas were observed in breast cancer explants incubated with the crude extract, while explants treated with laurinterol exhibited a heterogeneous response which was associated with the individual response of each human tumor sample. This study supports the cytotoxic and antitumoral effects of laurinterol in in vitro cell cultures and in ex vivo organotypic cultures of human breast cancer explants.

Focused on our interest to develop novel antiparasistic agents, the present study was aimed to evaluate the biological activity of an extract of Laurencia johnstonii collected in Baja California Sur, Mexico, against an Acantamoeba castellanii Neff strain. Bioassay-guided fractionation allowed us to identify the amoebicidal diastereoisomers α-bromocuparane ( 4 ) and α-isobromocuparane ( 5 ). Furthermore, bromination of the inactive laurinterol ( 1 ) and isolaurinterol ( 2 ) yielded four halogenated derivatives, ( 6 )⁻( 9 ), which improved the activity of the natural sesquiterpenes. Among them, the most active compound was 3α-bromojohnstane ( 7 ), a sesquiterpene derivative which possesses a novel carbon skeleton johnstane.

Chronic kidney disease impacts the cognitive abilities of patients, and yet few works have analyzed functional electroencephalographic changes on event-related potentials before and after an hemodialysis session. This work shows that, as a consequence of hemodialysis, cognitive potential waveforms suffer changes, occurring with reduced latency $( \sim 50$ ms) and with larger amplitude $( \sim 0.128\mathrm {a}$.u.) after the treatment session. While only a limited sample of five patients is reported herein, the observed changes immediately after hemodialysis could be a sign of central nervous system alterations that are not clinically evaluated. Signs like these could entail an early indicator of possible evolution into some neuropathology.

This study evaluated the ability of Brassica napus for extracting gold (Au), silver (Ag) and copper (Cu) from a mine tailings, with the inoculation of two Aspergillus niger strains, and the application of ammonium thiocyanate (NH 4 SCN) or ammonium thiosulfate [(NH 4 ) 2 S 2 O 3 ]. After seven weeks of growth inoculated or non-inoculated plants were applied with 1 or 2 g kg -1 of either NH 4 SCN or (NH 4 ) 2 S 2 O 3 , respectively. Eight days after the application of the chemical compounds, plants were harvested for determining the total dry biomass, and the content of Au, Ag, and Cu in plant organs. Application of (NH 4 ) 2 S 2 O 3 or NH 4 SCN resulted in enhanced Au-accumulation in stems (447% and 507%, respectively), while either (NH 4 ) 2 S 2 O 3 +Aspergillus, or NH 4 SCN increased the Au-accumulation in roots (198.5% and 404%, respectively) when compared to the control. Treatments with (NH 4 ) 2 S 2 O 3 or (NH 4 ) 2 S 2 O 3 +Aspergillus significantly increased (P ≤ 0.001) the accumulation of Ag in leaves (677% and 1376%, respectively), while NH 4 SCN + Aspergillus, and (NH 4 ) 2 S 2 O 3 enhanced the accumulation in stems (7153% and 6717.5%). The Ag-accumulation in roots was stimulated by NH 4 SCN+ Aspergillus, and (NH 4 ) 2 S 2 O 3 + Aspergillus (132.5% and 178%, respectively), when compared to the control. The combination of NH 4 SCN+Aspergillus significantly enhanced the Cu-accumulation in leaves (228%); whereas NH 4 SCN+ Aspergillus, or (NH 4 ) 2 S 2 O 3 + Aspergillus resulted in greater accumulation of Cu in stems (1233.5% and 1580%, respectively) than the control. Results suggest that either NH 4 SCN or (NH 4 ) 2 S 2 O 3 (with or without Aspergillus) improved the accumulation of Au and Ag by B. napus. Accumulation of Au and Ag in plant organs overpassed the hyperaccumulation criterion (> 1 mg kg -1 of plant biomass); whereas Cu-accumulation in stems and roots also overpassed such criterion (> 1000 mg kg -1 ) by applying either NH 4 SCN or (NH 4 ) 2 S 2 O 3 + A. niger., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Breast cancer is the most common cancer type diagnosed in women, it represents a critical public health problem worldwide, with 1,671,149 estimated new cases and nearly 571,000 related deaths. Research on breast cancer has mainly been conducted using two-dimensional (2D) cell cultures and animal models. The usefulness of these models is reflected in the vast knowledge accumulated over the past decades. However, considering that animal models are three-dimensional (3D) in nature, the validity of the studies using 2D cell cultures has recently been questioned. Although animal models are important in cancer research, ethical questions arise about their use and usefulness as there is no clear predictivity of human disease outcome and they are very expensive and take too much time to obtain results. The poor performance or failure of most cancer drugs suggests that preclinical research on cancer has been based on an over-dependence on inadequate animal models. For these reasons, in the last few years development of alternative models has been prioritized to study human breast cancer behavior, while maintaining a 3D microenvironment, and to reduce the number of experiments conducted in animals. One way to achieve this is using organotypic cultures, which are being more frequently explored in cancer research because they mimic tissue architecture in vivo. These characteristics make organotypic cultures a valuable tool in cancer research as an alternative to replace animal models and for predicting risk assessment in humans. This chapter describes the cultures of multicellular spheroids, organoids, 3D bioreactors, and tumor slices, which are the most widely used organotypic models in breast cancer research.

Polyunsaturated fatty acids (PUFA) contained in fish oil (FO) are ligands for peroxisome proliferator-activated receptors (PPAR) that may induce changes in cardiometabolic markers. Variation in PPAR genes may influence the beneficial responses linked to FO supplementation in young adults. The study aimed to analyze the effect of FO supplementation on glucose metabolism, circulating lipids and inflammation according to PPARα L162V and PPARγ2 P12A genotypes in young Mexican adults. 191 young, non-smoking subjects between 18 and 40 years were included in a one-arm study. Participants were supplemented with 2.7 g/day of EPA+DHA, during six weeks. Dietary analysis, body composition measurements and indicators for glucose metabolism, circulating lipids, and markers for inflammation were analyzed before and after intervention. An overall decrease in triglycerides (TG) and an increase in HS-ω3 index were observed in all subjects [-4.1 mg/dL, (SD:±51.7), P=.02 and 2.6%, (SD:±1.2), P<.001 respectively]. Mean fasting insulin and glycated hemoglobin (HbA1c%) were significantly decreased in all subjects [-0.547mlU/L, (SD:±10.29), P=.034 and-0.07%, (SD:±0.3), P<.001 respectively], whereas there was no change in body composition, fasting glucose, adiponectin and inflammatory markers. Subjects carrying the minor alleles of PPARα L162V and PPARγ2 P12A had higher responses in reduction of TG and fasting insulin respectively. Interestingly, doses below 2.7 g/day (1.8 g/day) were sufficient to induce a significant reduction in fasting insulin and HbA1c% from baseline (P=.019 and P<.001). The observed responses in triglycerides and fasting insulin in the Mexican population give further evidence of the importance of FO supplementation in young people as an early step towards the prevention of cardiometabolic disease., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The goal of insulin therapy in type 1 diabetes (T1D) is to reduce hemoglobin A1C (A1C) to ≤7.0% (53 mmol/mol) with minimal hypoglycemia. We investigated the possibility that "insulin timing" would improve A1C without incurring severe hypoglycemia in volunteers with T1D over a 6-month observation period., Methods: Forty healthy adult volunteers with T1D were randomly assigned for 6 months to either a control group or an insulin timing group. The primary endpoint was the difference in A1C between the two groups. As a secondary endpoint, both groups were further divided to assess the importance of the baseline A1C in determining the response to timing. The insulin timing algorithm altered the time when the meal dose of insulin was injected or infused from 30 minutes before the meal to 15 minutes after the meal, depending upon the premeal blood glucose concentration., Results: An improvement in mean A1C was observed in the timing group compared with no change in the control group, but this improvement did not reach statistical significance (P>.05). In contrast, when the two groups were analyzed according to baseline A1C, the timing volunteers with baseline A1C values in the upper half (separated by the A1C median of 7.45% [57.9 mmol/mol]) of the timing group had a more robust response to timing (decline in A1C) than the upper half of the control group (P<.05)., Conclusion: Insulin timing is a patient-centered translational approach that is safe and effective in improving A1C in individuals with T1D with an elevated A1C., Abbreviations: A1C = hemoglobin A1C ANOVA = analysis of variance CGM = continuous glucose monitoring CSII = continuous subcutaneous insulin infusion MDI = multiple daily injection T1D = type 1 diabetes.

This study describes the total phenolic and flavonoid content as well as cytotoxic, alpha-glucosidase inhibition and antiradical/antioxidant potential of extracts obtained from the edible fruits of Cordia boissieri, which is widely distributed throughout northeastern Mexico. Phenolic and flavonoid content were evaluated by means of the Folin-Ciocalteu method and aluminum chloride colorimetric assay respectively. The antiradical/antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and Trolox Equivalent Antioxidant Capacity (TEAC) assays. Cytotoxic activity was assessed by means of human cancer cell lines (MCF-7 and HeLa), alpha-glucosidase inhibition was determined by colorimetric assay using p-Nitrophenyl a-D-glucopyranoside (PNPG) as a substrate. Results indicate that extract of C. boissieri fruit has a good antioxidant potential to show a EC₅₀: 137.76 ± 35 ptg/mL and 65 ±2 ltM/g in the DPPH and TEAC assays respectively, inhibitor of the enzyme alpha-glu- cosidase involved in sugar uptake (ICSO: 215.20 ± 35 μg/ mL), cytotoxic activities against MCF-7 (IC50: 310 ± 42 μg/mL) and HeLa (IC₅₀0: 450.4 ±21μgg/mL) cancer cell lines as well as an important phenolic content with 230 t 23 mg/1OOg and 54±11 mg100g g of phenols and flavonoids totals respectively. These results point towards an interesting potential for the fruits of C. boissieri as chemopreventive properties and expand the possibilities.

Cervical ectopic pregnancy is a rare and danger clinical presentation because it has high risk of massive bleeding. The incidence is reported in 1:2500 pregnancies and has high relation with a history of cervical dilatation and curettage and assisted reproductive techniques. Advances in ultrasound resolution and use of beta fraction of human chorionic gonadotropin allow early diagnosis and provide conservative treatment with decreased morbidity, mortality and fertility preservation. Various techniques have been reported associated with cervical curettage, to reduce bleeding at the implantation site. In this report three cases of cervical ectopic pregnancy managed with cervical curettage, prior vaginal impingement of uterine arteries (Zea Technique) at the Instituto Nacional de Perinatología Isidro Espinosa de los Reyes are described. The Zea technique represents an effective option in the control of obstetric hemorrhage, including patients diagnosed with cervical ectopic pregnancy in who the bleeding volume decrease after its placement. The Zea Technique is easy to apply and preserves fertility. The success of combining this technique with endocervical curettage for the management of cervical ectopic pregnancy is demonstrated. Training for performing this technique does not require highly specialized or highly complex resources since the required material is the usual every area of obstetric care.

This paper presents an evaluation of the continuous detection of mental calculation episodes, which may be useful for users who strive to operate current BCI paradigms or even for augmenting degrees of freedom. The experimentation consisted in the alternated realization of basic arithmetic mental calculations and resting periods. EEG data were analyzed using sliding windows of 2s length. The experimental population was comprised of fifteen healthy subjects who participated in three sessions on different days. The features used for the classification process were the power spectral density over the beta band ([14-35] Hz) and the scaling exponent obtained via detrended fluctuation analysis. Both indices were estimated over four channels, specifically selected for each subject. The performance was evaluated using the Area Under the ROC Curve (AUC) by measuring the overall classification performance of each experimental session with a cross-validation procedure, and by transferring the model obtained from one session to the others called inter Session Validation (iSV). The best AUC values computed in each cross-validation session were: 0.87±0.067, 0.89±0.056 and 0.88±0.040 respectively; and the iSV provided a value of 0.67±0.122. These high values indicate that a mental calculation paradigm and a combination of features can efficiently control a BCI system. Notwithstanding that several days passed between sessions, the AUC mean value estimated for the iSV is similar to the performance of a motor imagery-BCI calibrated on the same day., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The aims of this research were to examine the antibacterial, cytotoxic and antiradical/antioxidant activities of the organic extracts obtained from the leaves of the medicinal plant Morus celtidifolia (Family: Moraceae). To evaluate its antimicrobial properties, M. celtidifolia was tested against the bacteria of medical importance: Bacillus subtilis, Staphyloccocus aureus, Enterococcus faecalis, Escherichia coli, Enterobacter cloacae and Enterobacter aerogenes. Cytotoxic activity was assessed by using the brine shrimp (Artemia salina) lethality assay and also by toxicity screening against human cancer cell lines: MCF-7 (human breast adenocarcinoma) and HeLa (cervix adenocarcinoma). The free radical-scavenging activity was determined by the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay. Results revealed that the hexanic extract has antibacterial activity only against Gram positive strains, while the methanolic extract showed better cytotoxic and antioxidant activities than the non- polar extract with a median lethal dose (LD₅₀) of 125μg/ml, 90μg/ml and 75μg/ml against A. salina, MCF-7 and HeLa cells respectively, and median effective concentration (EC₅₀) of 152μg/ml on radical scavenging assay. This is the first study reporting the biological activities of leaves of Morus celtidifolia.

Titanium (Ti) and its alloys are amongst the most commonly-used biomaterials in orthopedic and dental applications. The Ti-aluminum-vanadium alloy (Ti6Al4V) is widely used as a biomaterial for these applications by virtue of its favorable properties, such as high tensile strength, good biocompatibility and excellent corrosion resistance. TiO₂ nanotube (NTs) layers formed by anodization on Ti6Al4V alloy have been shown to improve osteoblast adhesion and function when compared to non-anodized material. In his study, NTs were grown on a Ti6Al4V alloy by anodic oxidation for 5 min using a super-oxidative aqueous solution, and their in vitro biocompatibility was investigated in pig periosteal osteoblasts and cartilage chondrocytes. Scanning electron microscopy (SEM), energy dispersion X-ray analysis (EDX) and atomic force microscopy (AFM) were used to characterize the materials. Cell morphology was analyzed by SEM and AFM. Cell viability was examined by fluorescence microscopy. Cell adhesion was evaluated by nuclei staining and cell number quantification by fluorescence microscopy. The average diameter of the NTs was 80 nm. The results demonstrate improved cell adhesion and viability at Day 1 and Day 3 of cell growth on the nanostructured material as compared to the non-anodized alloy. In conclusion, this study evidences the suitability of NTs grown on Ti6Al4V alloy using a super-oxidative water and a short anodization process to enhance the adhesion and viability of osteoblasts and chondrocytes. The results warrant further investigation for its use as medical implant materials.

Breast cancer is the leading cause of death in women worldwide. The search for novel compounds with antitumor activity, with less adverse effects and higher efficacy, and the development of methods to evaluate their toxicity is an area of intense research. In this study we implemented the preparation and culture of breast tumor explants, which were obtained from precision-cut breast tumor slices. In order to validate the model we are proposing to screen antineoplastic effect of natural compounds, we selected caffeic acid, ursolic acid, and rosmarinic acid. Using the Krumdieck tissue slicer, precision-cut tissue slices were prepared from breast cancer samples; from these slices, 4 mm explants were obtained and incubated with the selected compounds. Viability was assessed by Alamar Blue assay, LDH release, and histopathological criteria. Results showed that the viability of the explants cultured in the presence of paclitaxel (positive control) decreased significantly (P < 0.05); however, tumor samples responded differently to each compound. When the explants were coincubated with paclitaxel and compounds, a synergic effect was observed. This study shows that ex vivo culture of breast cancer explants offers a suitable alternative model for evaluating natural or synthetic compounds with antitumor properties within the complex microenvironment of the tumor.

Objective: Continuous subcutaneous insulin infusion (CSII) programming for an early morning increase in insulin delivery is frequently recommended to counteract the rise in glucose prior to breakfast (dawn phenomenon). However, both the effectiveness and safety of this approach have not been tested in the ambulatory setting. Using continuous glucose monitoring, we investigated the safety and effectiveness of early morning CSII programming for management of the dawn phenomenon in subjects with type 1 diabetes., Methods: We conducted a controlled, observational eight-month longitudinal study of type 1 diabetic patients (n=40). Reproducibility of the dawn phenomenon was determined in subjects treated with multiple daily injections of insulin (MDI, n=12) and those on CSII who did not program an early morning increase in insulin delivery (CSII non-programmers, n=8). The effects of early morning CSII programming were determined by comparing rates of the dawn phenomenon and hypoglycemia in CSII non-programmers versus CSII-users who programmed an early morning increase in insulin delivery (CSII programmers, n=20)., Results: The dawn phenomenon occurred in all tested subjects to a variable extent (median rate 56% of nights). CSII programming was not associated with a reduction in the occurrence of the dawn phenomenon (42%) compared to non-programmers (48%) (P=0.47) nor in the magnitude of the dawn phenomenon. Hypoglycemia occurred more frequently in the CSII programmers (37%) compared to non-programmers (18%) (P=0.001)., Conclusion: The dawn phenomenon occurs unpredictably; therefore, early morning CSII programming for a fixed increase in early morning insulin delivery is ineffective and may be hazardous to the patient.

Background: The masked continuous glucose monitoring system (Masked-CGMS) differs from standard CGMSs in three ways: (1) there is no feedback to the user so that no immediate regimen changes can be made; (2) it can only be worn for up to 5 days; and (3) there are no alarms to warn of hyperglycemia or hypoglycemia. Since 2008 masked-CGMS has become popular for identifying reasons that a patient's hemoglobin A1C does not correlate closely with his or her capillary blood glucose measurements. To date only one study addressing the clinical utility of Masked-CGMS for improving A1C in diabetes has been published. No studies are available specifically examining the variability and correlation of Masked-CGMS and A1C., Subjects and Methods: We performed 156 Masked-CGMS studies (40 patients studied sequentially a maximum of four times each) in type 1 diabetes patients. We then analyzed the resulting interstitial glucose levels obtained from the Masked-CGMS compared with an A1C measurement performed within 1 week of the Masked-CGMS study., Results: There was a very low correlation between the A1C and the Masked-CGMS-derived mean interstitial glucose level. This statistic did not provide sufficiently predictive information to be clinically useful for changing an individual patient's intensive insulin therapy regimen., Conclusions: Our data demonstrate that a very weak correlation exists between 5 days of masked CGMS and a concurrently measured A1C level. For the individual type 1 diabetes patient, this relationship would unlikely to be clinically useful in altering the individual's treatment regimen.