Alterations in epididymal sperm maturation caused by ageing.

The epididymis is an organ that performs all the biochemical changes responsible for sperm maturation. During ageing, histological alterations in the epididymis and decreased protein synthesis have been found. This might affect the sperm maturation process. The aim of this study was to determine if the changes in the epididymis during ageing might cause alterations in sperm maturation. Wistar rats of 3-4months old (young) and 18-21months old (old) were used. The testosterone concentration was determined and the epididymides were dissected and divided in three regions: caput, corpus, and cauda. The tissues were used for histological processing and sperm extraction. Testosterone concentration decreased 34% in the old animals compared to the young ones. The distribution of mannose, sialic acid, and N-acetylglucosamine in the glycocalyx of the sperm membrane of old animals was different from that of young animals. The same occurred with phosphatidylserine externalisation and protein phosphorylation at tyrosine residues. Epididymis histology in old animals showed tubular and cellular degeneration. Our results suggest that ageing affects maturational markers, likely due to alterations in the epididymis as a result of the testosterone decrease associated with ageing.

[Bariatric surgery in adolescents with severe obesity: Recommendations of the Nutrition Branch, Chilean Pediatric Society]. / Cirugía bariátrica en adolescentes con obesidad severa: Recomendaciones de la Rama de Nutrición, Sociedad Chilena de Pediatría.

In recent years, severe obesity in adolescents has been rising worldwide, and Chile is no exception to this phenomenon. This condition exponentially increases health risks and it is associated with prema ture mortality. Since 2008, several guidelines on pediatric obesity treatment have included bariatric surgery as a treatment strategy for certain severely obese adolescents. These procedures have proven to be safe and efficient in adults. Recent evidence shows that, when done in specialized centers, the re sults would be similar in adolescents in the short and medium term. Nonetheless, in this group of pa tients, bariatric surgery has risks related to their stage of development, and data on long-term results and complications are still lacking. Therefore, to achieve the expected results, the patient selection, surgery, and follow-up must be carried out by qualified multidisciplinary teams, in hospitals centers that have the appropriate infrastructure, It is essential for the patients a life-long adherence to medi cal and nutritional monitoring. The objective of this document is to present the position statement of the Nutrition Branch of the Chilean Society of Pediatrics on the different issues to be considered for the adequate indication of these procedures in severely obese adolescents.

Abnormal calcium signalling and the caffeine-halothane contracture test.

BACKGROUND: The variable clinical presentation of malignant hyperthermia (MH), a disorder of calcium signalling, hinders its diagnosis and management. Diagnosis relies on the caffeine-halothane contracture test, measuring contraction forces upon exposure of muscle to caffeine or halothane (FC and FH, respectively). Patients with above-threshold FC or FH are diagnosed as MH susceptible. Many patients test positive to halothane only (termed 'HH'). Our objective was to determine the characteristics of these HH patients, including their clinical symptoms and features of cytosolic Ca2+ signalling related to excitation-contraction coupling in myotubes. METHODS: After institutional ethics committee approval, recruited patients undergoing contracture testing at Toronto's MH centre were assigned to three groups: HH, doubly positive (HS), and negative patients (HN). A clinical index was assembled from musculoskeletal symptoms and signs. An analogous calcium index summarised four measures in cultured myotubes: resting [Ca2+]cytosol, frequency of spontaneous cytosolic Ca2+ events, Ca2+ waves, and cell-wide Ca2+ spikes after electrical stimulation. RESULTS: The highest values of both indexes were found in the HH group; the differences in calcium index between HH and the other groups were statistically significant. The principal component analysis confirmed the unique cell-level features of the HH group, and identified elevated resting [Ca2+]cytosol and spontaneous event frequency as the defining HH characteristics. CONCLUSIONS: These findings suggest that HH pathogenesis stems from excess Ca2+ leak through sarcoplasmic reticulum channels. This identifies HH as a separate diagnostic group and opens their condition to treatment based on understanding of pathophysiological mechanisms.

Variational reduced density matrix method in the doubly-occupied configuration interaction space using four-particle N-representability conditions: Application to the XXZ model of quantum magnetism.

This work deals with the variational determination of the two-particle reduced density matrix (2-RDM) and the energy corresponding to the ground state of N-particle systems within the doubly occupied configuration interaction (DOCI) space. Here, we impose for the first time up to four-particle N-representability constraint conditions in the variational determination of the 2-RDM matrix elements using the standard semidefinite programming algorithms. The energies and 2-RDMs obtained from this treatment and the corresponding computational costs are compared with those arisen from previously reported less restrictive variational methods [D. R. Alcoba et al., J. Chem. Phys. 149, 194105 (2018)] as well as with the exact DOCI values. We apply the different approximations to the one-dimensional XXZ model of quantum magnetism, which has a rich phase diagram with one critical phase and constitutes a stringent test for the method. The numerical results show the usefulness of our treatment to achieve a high degree of accuracy.

[Bariatric surgery in adolescents]. / Cirugía bariátrica en adolescentes.

The obesity epidemic affects transversally the entire life cycle. Particularly in recent decades, an in crease in severe obesity has been observed in adolescents. At this stage of life, characterized by deep physical and emotional changes, and great vulnerability, severe obesity has few effective treatment options. In adolescents, the treatment results focused on lifestyle modifications are poor and the pharmacological options are very limited and ineffective. Bariatric Surgery (BS) has emerged as a via ble therapeutic option for a selected group of adolescents. The objective of this review is to update the current view regarding indications, contraindications, complications, and results of these procedures in the adolescent population.

Further contributions to the understanding of nitrogen removal in waste stabilization ponds.

A set of experiments were conducted in Brazil in a pilot-scale waste stabilization pond (WSP) system (a four-maturation-pond series) treating an upflow anaerobic sludge blanket (UASB) reactor effluent. Over a year and a half the pond series was monitored under two flow rate conditions, hence also different hydraulic retention times and surface loading rates. On-site and laboratory trials were carried out to assess: (i) ammonia losses by volatilization using acrylic capture chambers placed at the surface of the ponds; (ii) organic nitrogen sedimentation rates using metal buckets placed at the bottom of the ponds for collecting settled particulate matter; (iii) nitrogen removal by algal uptake based on the nitrogen content of the suspended particulate matter in samples from the ponds' water column. In addition, nitrification and denitrification rates were measured in laboratory-based experiments using pond water and sediment samples. The pond system achieved high nitrogen removal (69% total nitrogen and 92% ammonia removal). The average total nitrogen removal rates varied from 10,098 to 3,849 g N/ha·d in the first and the last ponds, respectively, with the following fractions associated with the various removal pathways: (i) 23.5-45.6% sedimentation of organic nitrogen; (ii) 13.1-27.8% algal uptake; (iii) 1.2-3.1% ammonia volatilization; and (iv) 0.15-0.34% nitrification-denitrification.

Factorization and Criticality in Finite XXZ Systems of Arbitrary Spin.

We analyze ground state (GS) factorization in general arrays of spins s_{i} with XXZ couplings immersed in nonuniform fields. It is shown that an exceptionally degenerate set of completely separable symmetry-breaking GSs can arise for a wide range of field configurations, at a quantum critical point where all GS magnetization plateaus merge. Such configurations include alternating fields as well as zero-bulk field solutions with edge fields only and intermediate solutions with zero field at specific sites, valid for d-dimensional arrays. The definite magnetization-projected GSs at factorization can be analytically determined and depend only on the exchange anisotropies, exhibiting critical entanglement properties. We also show that some factorization-compatible field configurations may result in field-induced frustration and nontrivial behavior at strong fields.

[Cost of family planning care in 10-19 years old teenagers]. / Costo de atención por servicios de planificación familiar a adolescentes de 10-19 años.

Objetives: To identify the costs of family planning care in adolescents. Material and methods: Longitudinal study of the cost of care for family planning carried out in 2015 in a group of individuals with age limits of 10 and 19 years in a unit first level of health care in the state of Queretaro, Mexico. The profile of use of family planning (FP) was created for the teen was performed services through counseling, provision of contraception and review of intrauterine device (IUD) in a year; cost projections for the population of adolescents and different coverage scenarios between 5 and 100% were made. Results: The average annual cost was 228.84 Mexican pesos. Ideally the identified cost was 2,708.94 pesos. The projection with 20 % coverage was 207,251,330 pesos. The average annual family planning consultations was 0.9. The most commonly used method was with medroxyprogesterone-estradiol at doses of 25 and 5 mg. Conclusion: The cost of planning in adolescents is low, taking into account the costs that the care of high-risk pregnancies and associated comorbidities.

Recurrent pneumococcal invasive disease in the region of Madrid during a five-year period.

PURPOSE: The aim of this study was to describe the clinical and microbiological characteristics of recurrent invasive pneumococcal disease (RIPD) cases identified in the Region of Madrid between January 2007 and December 2011. METHODS: Streptococcus pneumoniae serotyping was performed by Pneumotest-Latex and Quellung reaction. Molecular typing was carried out by pulsed-field gel electrophoresis (PFGE). A relapse was defined as any case of RIPD caused by strains with similar PFGE profile. Re-infections were defined by detection of recurrent episodes caused by strains with different PFGE patterns. RESULTS: During the study period, 2,929 S. pneumoniae strains isolated from 2,858 patients with invasive pneumococcal disease (IPD) were studied. In 61 patients (2.1 %), 132 episodes of RIPD were detected (two episodes in 52 patients, three in 8 and four in 1). Twelve patients had relapses, 47 had re-infections and two had re-infections followed by relapses. Common risk factors to developing RIPD were HIV (42.6 %) and haematological malignancies (16.4 %). The most frequent serotypes were 8 (16 episodes) and 19A (15 episodes). Fourteen strains that were resistant to levofloxacin were also resistant to erythromycin. The proportion of strains co-resistant to erythromycin and levofloxacin was significantly higher in relapses (11/29) than in re-infections (3/103). CONCLUSIONS: The occurrence of repeated episodes of IPD in the same patient over the time is not an exceptional issue. Some underlying conditions that may favour these recurrences, mainly immunosuppression, need to be considered in patients having an episode of IPD.

Further contributions to nitrogen removal modelling in waste stabilization ponds.

A large database from an experimental maturation pond system in Brazil was used to verify the agreement of field results with values predicted by some of the most widely accepted models to describe ammonium and total nitrogen (TN) removal in facultative and maturation ponds. The same database was used to derive a pH-independent linear model to predict ammonium removal in ponds, which was proved to be, essentially, a function of ammonium surface loading rate. In general, all these models made reasonable predictions of ammonium or TN removal but tended to overestimate low ammonium effluent concentrations while underestimating higher values of field data.

Methods to obtain protein concentrates from jumbo squid (Dosidicus gigas) and evaluation of their functionality.

Jumbo squid is an important fishery resource in Mexico, and its muscle is lean and white and it has a very low price in the market. It is abundant, but with little or nothing added value, therefore is necessary to search alternatives of processing. Due to muscle characteristics, the aim of this study was to obtain protein concentrates using different methods. They were obtained by means of acidic (acid protein concentrates) and alkaline (alkaline protein concentrates) dissolution. Moreover, a protein concentrate was obtained by direct isoelectric precipitation and by the traditional method (neutral protein concentrates). The yield with better results was alkaline protein concentrates (63.58 ± 1.8%). The gel hardness was significantly different (p < 0.05), especially for the alkaline protein concentrates. The acid protein concentrates, isoelectric precipitation and alkaline protein concentrates were better with regard to the neutral protein concentrates, concerning the emulsifying and foaming properties. The protein concentrates by means of alkaline dissolution gave a better gelling property, but all the processes had the potential to obtain protein with emulsifying and foaming properties.

Efficacy of delafloxacin alone and in combination with cefotaxime against cefotaxime non-susceptible invasive isolates of Streptococcus pneumoniae.

OBJECTIVE: We assessed the in vitro activity of delafloxacin and the synergy between cefotaxime and delafloxacin among cefotaxime non-susceptible invasive isolates of Streptococcus pneumoniae (CNSSP). METHODS: A total of 30 CNSSP (cefotaxime MIC > 0.5 mg/L) were studied. Serotyping was performed by the Pneumotest-Latex and Quellung reaction. Minimum inhibitory concentrations (MICs) of delafloxacin, levofloxacin, penicillin, cefotaxime, erythromycin and vancomycin were determined by gradient diffusion strips (GDS). Synergistic activity of delafloxacin plus cefotaxime against clinical S. pneumoniae isolates was evaluated by the GDS cross method. RESULTS: Delafloxacin showed a higher pneumococcal activity than its comparator levofloxacin (MIC50, 0.004 versus 0.75 mg/L and MIC90, 0.047 versus >32 mg/L). Resistance to delafloxacin was identified in 7/30 (23.3%) isolates, belonging to serotypes 14 and 9V. Synergy between delafloxacin and cefotaxime was detected in 2 strains (serotypes 19A and 9V). Antagonism was not observed. Addition of delafloxacin increased the activity of cefotaxime in all isolates. Delafloxacin susceptibility was restored in 5/7 (71.4%) strains. CONCLUSIONS: CNSSP showed a susceptibility to delafloxacin of 76.7%. Synergistic interactions between delafloxacin and cefotaxime were observed in vitro among CNSSP by GDS cross method.

Synthesis of novel fatty acid 3,4-dihydropyrimidin-2-(1H)-one and antitumoral activity against breast and gastric cancer cells.

Monastrol is the best-known small compound from the dihydropyrimidinones/thiones (DHPMs) heterocycle family, a cell-permeable molecule recognized as an inhibitor of mitotic kinesin Eg5, that is over-expressed in tumor cells and is a very promising target for the development of new drugs for cancer. The lipophilic properties of the DHPMs have been demonstrated to be of pivotal importance in the design of new molecules. This work describes the synthesis and antitumoral activity of novel C5-substituted fatty-DHPMs against breast and gastric cancer cell lines. The compounds were synthesized via Biginelli multicomponent reaction from oleyl ß-ketoester in good yields (40-72%) using a simple approach catalyzed by nontoxic and free-metal sulfamic acid. Among the compounds tested, the compound 10c, derived from 3-hydroxybenzaldehyde and urea, exhibited 77% cellular viability to normal cells (C2C12) and was selected to be evaluated against tumoral breast (MCF-7) and gastric (AGS) cell lines. The results obtained afforded an IC50 of breast cancer cells of 2.3 µM, qualifying the molecule as the most potent, and making it a promising compound for future experiments in vivo.

Definitive radiation therapy for treatment of laryngeal carcinoma: impact of local relapse on outcome and implications for treatment strategies.

PURPOSE: The purpose of this work was to evaluate outcome after radiotherapy (RT) for laryngeal carcinoma and investigate effects of local relapse on ultimate disease control, including surgical salvage procedures. METHODS AND MATERIALS: In all, 435 patients with laryngeal carcinoma (cT1-cT4a) treated with primary RT were retrospectively analyzed. Uni- and multivariate analyses were performed to identify prognostic factors for local relapse-free survival and overall survival. RESULTS: Median follow-up was 38 months (range 1-144 months). The cumulative frequency of local recurrence was dependent on T stage: cT1 tumors 10%, cT2 18%, cT3 23%, and cT4 36% (p<0.001). Salvage surgery for local persistent/recurrent disease was performed in 59 of 78 patients (76%). The ultimate local control rates at 5 years (including salvage therapy) were 98, 98, 87, and 68% for cT1, cT2, cT3, and cT4 tumors (p<0.001), respectively. For the patients who developed local recurrence, the 5-year ultimate local control rates were 80, 88, 55, and 26% (p<0.001), respectively. Overall survival at 5 years was 68% for patients without local relapse and 50% for patients experiencing local failure (p<0.001). In univariate analysis, cT stage, cN stage, and tumor volume were statistically significant associated with local relapse-free survival. In multivariate analysis for the cT3-4 tumors, only tumor volume remained statistically significant (HR 1.017, p=0.001) for local relapse-free survival. CONCLUSION: Local control rates for cT1-2 laryngeal carcinomas are favorable and in concordance with previous reports and most recurrences are salvaged. For cT3-4 tumors treated with RT alone, initial local control rates are moderate, and in 60% of recurring cases salvage surgery is attempted, with ultimate local control being achieved in only a subset. For voluminous, locally advanced laryngeal tumors, more aggressive treatment modalities should be considered, including upfront laryngectomy or radiochemotherapy.

Extending Brain-Computer Interface Access with a Multilingual Language Model in the P300 Speller.

Brain-computer interfaces (BCI) such as the P300 speller have the potential to restore communication to advanced-stage neuromuscular disease patients. Research has improved typing speed and accuracy through innovations including the use of language models. While significant advances have been made, implementations have largely been restricted to a single language, primarily English. It is unclear whether these improvements would extend to other languages that present potential technical hurdles due to different alphabets and grammatical structures. Here, we adapt a language model-based classifier designed for English to two other languages, Spanish and Greek, to demonstrate the generalizability of these methods. Online experimental trials with 30 healthy native English, Spanish, and Greek speakers showed no significant difference between performances using the different versions of the system (66.20 vs. 61.97 vs. 60.89 bits/minute). Extending these methods across languages allows for expanding access to BCI systems to other populations, particularly in the developing world.

Impact of the implementation of a Sepsis Code Program in medical patient management: a cohort study in an Internal Medicine ward.

OBJECTIVE: Sepsis is the main cause of death in hospitals and the implementation of diagnosis and treatment bundles has shown to improve its evolution. However, there is a lack of evidence about patients attended in conventional units. METHODS: A 3-year retrospective cohort study was conducted. Patients hospitalized in Internal Medicine units with sepsis were included and assigned to two cohorts according to Sepsis Code (SC) activation (group A) or not (B). Baseline and evolution variables were collected. RESULTS: A total of 653 patients were included. In 296 cases SC was activated. Mean age was 81.43 years, median Charlson comorbidity index (CCI) was 2 and 63.25% showed some functional disability. More bundles were completed in group A: blood cultures 95.2% vs 72.5% (p <0.001), extended spectrum antibiotics 59.1% vs 41.4% (p < 0.001), fluid resuscitation 96.62% vs 80.95% (p < 0.001). Infection control at 72 hours was quite higher in group A (81.42% vs 55.18%, odds ratio 3.55 [2.48-5.09]). Antibiotic was optimized more frequently in group A (60.77% vs 47.03%, p 0.008). Mean in-hospital stay was 10.63 days (11.44 vs 8.53 days, p < 0.001). Complications during hospitalization appeared in 51.76% of patients, especially in group B (45.95% vs 56.58%, odds ratio 1.53 [1.12-2.09]). Hospital readmissions were higher in group A (40% vs 24.76%, p < 0.001). 28-day mortality was significantly lower in group A (20.95% vs 42.86%, odds ratio 0.33 [0.23-0.47]). CONCLUSIONS: Implementation of SC seems to be effective in improving short-term outcomes in IM patients, although therapy should be tailored in an individual basis.

The percentage of CD39+ monocytes is higher in pregnant COVID-19+ patients than in nonpregnant COVID-19+ patients.

Current medical guidelines consider pregnant women with COVID-19 to be a high-risk group. Since physiological gestation downregulates the immunological response to maintain "maternal-fetal tolerance", SARS-CoV-2 infection may constitute a potentially threatening condition to both the mother and the fetus. To establish the immune profile in pregnant COVID-19+ patients, a cross-sectional study was conducted. Pregnant women with COVID-19 (P-COVID-19+; n = 15) were analyzed and compared with nonpregnant women with COVID-19 (NP-COVID-19+; n = 15) or those with physiological pregnancy (P-COVID-19-; n = 13). Serological cytokine and chemokine concentrations, leucocyte immunophenotypes, and mononuclear leucocyte responses to polyclonal stimuli were analyzed in all groups. Higher concentrations of serological TNF-α, IL-6, MIP1b and IL-4 were observed within the P-COVID-19+ group, while cytokines and chemokines secreted by peripheral leucocytes in response to LPS, IL-6 or PMA-ionomicin were similar among the groups. Immunophenotype analysis showed a lower percentage of HLA-DR+ monocytes in P-COVID-19+ than in P-COVID-19- and a higher percentage of CD39+ monocytes in P-COVID-19+ than in NP-COVID-19+. After whole blood polyclonal stimulation, similar percentages of T cells and TNF+ monocytes between groups were observed. Our results suggest that P-COVID-19+ elicits a strong inflammatory response similar to NP-COVID19+ but also displays an anti-inflammatory response that controls the ATP/adenosine balance and prevents hyperinflammatory damage in COVID-19.

Anxiolytic-like effects of standardized extract of Justicia pectoralis (SEJP) in mice: Involvement of GABA/benzodiazepine in receptor.

Justicia pectoralis (Acanthaceae) is used as an antiinflammatory, antimicrobial and bronchodilator, and its extract exerts an anxiolytic-like effect profile in animal models. This work presents the behavioral effects of an aqueous standardized extract of Justicia pectoralis (SEJP) in animal models, such as the elevated plus maze (EPM), light/dark, open field, rota rod and pentobarbital sleep time. The extract was administered intragastrically to male mice at single doses of 50, 100 and 200 mg/kg, while diazepam 1 or 2 mg/kg was used as a standard drug and flumazenil 2.5 mg/kg was used to evaluate the participation of benzodiazepinic receptors. The results showed that, similar to diazepam (1 mg/kg), SEJP significantly modified all the observed parameters in the EPM test, without altering the general motor activity in the open field, rota rod and pentobarbital sleep time tests. Flumazenil reversed not only the diazepam effect but also the SEJP effect. In the same way, all doses of SEJP increased the time of permanence in the light box in the light/dark test. The results showed that SEJP presented an anxiolytic-like effect, disproving sedative effects.

UASB-polishing ponds design parameters: contributions from a pilot scale study in southeast Brazil.

This paper presents the results of five years monitoring of an experimental wastewater treatment plant in southeast Brazil, comprised of a UASB reactor followed by a submerged aerated biofilter (BF) (field scale) and shallow polishing ponds (pilot scale). Three ponds in series achieved high quality effluent standards in terms of ammonia and E.coli, but a fourth pond did not result in further efficiency. Well established models to predict ammonia and E.coli removal in facultative and/or maturation ponds were, in a way, validated for polishing ponds too. The paper also includes results of input design parameters, such as pH and E.coli die-off rate constants, and their variation along the pond series.

Database comparison of the adult-to-adult living donor liver transplantation cohort study (A2ALL) and the SRTR U.S. Transplant Registry.

Data submitted by transplant programs to the Organ Procurement and Transplantation Network (OPTN) are used by the Scientific Registry of Transplant Recipients (SRTR) for policy development, performance evaluation and research. This study compared OPTN/SRTR data with data extracted from medical records by research coordinators from the nine-center A2ALL study. A2ALL data were collected independently of OPTN data submission (48 data elements among 785 liver transplant candidates/recipients; 12 data elements among 386 donors). At least 90% agreement occurred between OPTN/SRTR and A2ALL for 11/29 baseline recipient elements, 4/19 recipient transplant or follow-up elements and 6/12 donor elements. For the remaining recipient and donor elements, >10% of values were missing in OPTN/SRTR but present in A2ALL, confirming that missing data were largely avoidable. Other than variables required for allocation, the percentage missing varied widely by center. These findings support an expanded focus on data quality control by OPTN/SRTR for a broader variable set than those used for allocation. Center-specific monitoring of missing values could substantially improve the data.