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Objective: To describe the clinical effects of a novel, combined ocular lubricant for treating patients with dry eye disease. Methods: A noncomparative, retrospective cohort of 67 eyes (67 patients) with a confirmed diagnosis of dry eye disease using the ocular surface disease index (>12), tear osmolarity, and ocular surface parameters (noninvasive break-up time, meniscus height, and meibography) evaluated using the Cornea550 were included. All patients were treated with a combination of 0.5% carboxymethylcellulose, glycerin 0.9%, and trehalose 3% with a dosing regimen of one drop four times a day for 1 month with a final evaluation of the same parameters. Results: We included 67 eyes (80.6% females) with a mean age of 48.3 ± 16.2 years (standard deviation [SD]). In total, 37% of the subjects had comorbidities such as hypothyroidism (9%), ocular rosacea (4%), Sjogren's syndrome (4%), and arterial hypertension (4%). Of these, 34% were taking systemic medications and 56.7% had previous ocular surgery. The mean ocular surface disease index score before treatment was 57.6 ± 17.2 (SD) and 22.2 ± 12.9 points (SD) after treatment ( P < 0.05). Other parameters such as noninvasive break-up time, meniscus height, and meibography improved without a statistically significant difference. Conclusion: Cristal Tears Plus is a novel, combined, and multipurpose treatment for dry eye disease.

This review aims to emphasize the important role that goats and dairy goats play for many small-scale rural families worldwide, as well as to introduce a proposal for categorizing the main dairy goat production systems (DGPSs), using a multifactorial approach but emphasizing rainfall and nutritional supplementation level, as the focal categorization factors. The main DGPSs were divided into two metasystems based on available resources, each consisting of three production subsystems. In the first metasystem, the three subsystems have limited water, biotic, and economic resources, whose main economic rationality is based on reducing risk rather than maximizing outputs. In contrast, the three subsystems of the second metasystem usually have increased biotic, economic, and water resources, whose main emphasis involves maximizing product yield rather than reducing risk. The first metasystem involves DGPSs with a very limited or null nutritional supplementation: (a) subsistence, (b) extensive, and (c) agro-silvopastoral. The second metasystem includes those DGPSs with different levels of nutritional supplementation: (d) semi-extensive, (e) semi-intensive, and (f) intensive. There are numerous significant global initiatives focused on scientific collaboration and sharing information regarding nutrition, reproductive, and genetic technologies related to the safety and nutraceutical quality of goat milk and products while contextualized in different DGPSs. Hence, such scenarios should create additional opportunities for researchers, producers, policymakers, and development workers to come together and align interests and needs and exchange knowledge on effective goat farmer support strategies, environmental management, and consumer education. Undoubtedly, it is essential to reevaluate the DGPSs in the world since millions of producers and their families-most of them poor and marginalized-need this species, society needs their products, most of the worldwide arid and semi-arid lands need their recovery, and all of us should encourage the fulfillment of the sustainable development goals.

Background: Discovering biological markers is essential for understanding and treating mental disorders. Despite the limitations of current non-invasive methods, neural progenitor cells from the olfactory epithelium (hNPCs-OE) have been emphasized as potential biomarker sources. This study measured soluble factors in these cells in Major Depressive Disorder (MDD), Borderline Personality Disorder (BPD), and healthy controls (HC)., Methods: We assessed thirty-five participants divided into MDD (n=14), BPD (n=14), and HC (n=7). MDD was assessed using the Hamilton Depression Rating Scale. BPD was evaluated using the DSM-5 criteria and the Structured Clinical Interview for Personality Disorders. We isolated hNPCs-OE, collected intracellular proteins and conditioned medium, and quantified markers and soluble factors, including Interleukin-6, interleukin-8, and others. Analysis was conducted using one-way ANOVA or Kruskal-Wallis test and linear regression., Results: We found that hNPCs-OE of MDD and BPD decreased Sox2 and laminin receptor-67 kDa levels. MASH-1 decreased in BPD, while tubulin beta-III decreased in MDD compared to controls and BPD. Also, we found significant differences in IL-6, IL-8, MCP-1, and thrombospondin-1 levels between controls and MDD, or BPD, but not between MDD and BPD., Conclusions: Altered protein markers are evident in the nhNPCs-OE in MDD and BPD patients. These cells also secrete higher concentrations of inflammatory cytokines than HC cells. The results suggest the potential utility of hNPCs-OE as an in vitro model for researching biological protein markers in psychiatric disorders. However, more extensive validation studies are needed to confirm their effectiveness and specificity in neuropsychiatric disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Davalos-Guzman, Vegas-Rodriguez, Ramirez-Rodriguez, Flores-Ramos, Romero-Luevano, Gonzalez-Olvera and Saracco-Alvarez.)

Competing Interests: Conflict of interest: None declared.

Recurrence of ovarian cancer (OvCa) following surgery and standard carboplatin/paclitaxel first-line therapy signifies poor median progression-free survival (<24 months) in the majority of patients with OvCa. The current study utilized unbiased high-throughput screening (HTS) to evaluate an FDA-approved compound library for drugs that could be repurposed to improve OvCa sensitivity to carboplatin. The initial screen revealed six compounds with agonistic activity for the adrenoceptor alpha-2a (ADRA2A). These findings were validated in multiple OvCa cell lines (TYKnu, CAOV3, OVCAR8) using three ADRA2A agonists (xylazine, dexmedetomidine, and clonidine) and two independent viability assays. In all the experiments, these compounds enhanced the cytotoxicity of carboplatin treatment. Genetic overexpression of ADRA2A was also sufficient to reduce cell viability and increase carboplatin sensitivity. Taken together, these data indicate that ADRA2A activation may promote chemosensitivity in OvCa, which could be targeted by widely used medications currently indicated for other disease states.

Introduction: Suspected preterm labor (SPL), defined as the presence of regular and painful uterine contractions and cervical shortening, represents a prenatal insult with potential long-term consequences. However, despite recent evidence demonstrating suboptimal neurodevelopment at 2 years in this population, it remains underestimated as a significant risk factor for neurodevelopmental disorders or other chronic diseases. The aim of this study is to assess the impact of suspected preterm labor during pregnancy on cardiometabolic profile and neurodevelopment during childhood (6-8 years)., Methods and Analysis: Prospective cohort study including children whose mothers suffered suspected preterm labour during pregnancy and paired controls. Neurodevelopmental, cardiovascular, and metabolic assessments will be performed at 6-8 years of age. A trained psychologist will carry out the neurodevelopment assessment including intelligence, visual perception, and behavioral assessment. Body composition and physical fitness assessment will be performed by one trained pediatrician and nurse. Finally, cardiovascular evaluation, including echocardiography and blood pressure, will be performed by two pediatric cardiologists. Data regarding perinatal and postnatal characteristics, diet, lifestyle, and weekly screen time of the child will be obtained from medical history and direct interviews with families. Primary outcome measures will include body mass index and adiposity, percentage of fat mass and total and regional lean mass, bone mineral content and density, cardiorespiratory resistance, isometric muscle strength, dynamic lower body strength, systolic and diastolic blood pressure, left ventricle (LV) systolic and diastolic function, general intelligence index, visuospatial working memory span, oculomotor control test, index of emotional, and behavioral problems.

Purpose of Review: Approximately 370 million children and adolescents worldwide showed overweight or obesity in 2016. The risk of developing severe comorbidities depends on the age of onset and the duration of obesity. This review discusses available methodologies to detect excess body fat in children as well as the early life factors that predict excess body fat and its development., Recent Findings: Factors, such as parental nutritional status, maternal weight gain during pregnancy, maternal malnutrition, maternal smoking during pregnancy, low and high birth weight, rapid weight gain, and short infant sleep duration have been independently and positively associated with neonatal, infant, and children adiposity. Early detection of excess body fat in children through the use of various tools is the first step in preventing nutrition-related diseases in adulthood., Summary: The early detection of excess body fat and the implementation of efficient interventions to normalize the weight of children and adolescents at obesity risk are essential to prevent diseases in adult life., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background & Aims: There is a major unmet need to assess the prognostic impact of antifibrotics in clinical trials because of the slow rate of liver fibrosis progression. We aimed to develop a surrogate biomarker to predict future fibrosis progression., Methods: A fibrosis progression signature (FPS) was defined to predict fibrosis progression within 5 years in patients with hepatitis C virus and nonalcoholic fatty liver disease (NAFLD) with no to minimal fibrosis at baseline (n = 421) and was validated in an independent NAFLD cohort (n = 78). The FPS was used to assess response to 13 candidate antifibrotics in organotypic ex vivo cultures of clinical fibrotic liver tissues (n = 78) and cenicriviroc in patients with nonalcoholic steatohepatitis enrolled in a clinical trial (n = 19, NCT02217475). A serum protein-based surrogate FPS was developed and tested in a cohort of compensated cirrhosis patients (n = 122)., Results: A 20-gene FPS was defined and validated in an independent NAFLD cohort (adjusted odds ratio, 10.93; area under the receiver operating characteristic curve, 0.86). Among computationally inferred fibrosis-driving FPS genes, BCL2 was confirmed as a potential pharmacologic target using clinical liver tissues. Systematic ex vivo evaluation of 13 candidate antifibrotics identified rational combination therapies based on epigallocatechin gallate, which were validated for enhanced antifibrotic effect in ex vivo culture of clinical liver tissues. In patients with nonalcoholic steatohepatitis treated with cenicriviroc, FPS modulation was associated with 1-year fibrosis improvement accompanied by suppression of the E2F pathway. Induction of the PPARα pathway was absent in patients without fibrosis improvement, suggesting a benefit of combining PPARα agonism to improve the antifibrotic efficacy of cenicriviroc. A 7-protein serum protein-based surrogate FPS was associated with the development of decompensation in cirrhosis patients., Conclusion: The FPS predicts long-term fibrosis progression in an etiology-agnostic manner, which can inform antifibrotic drug development., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Acute respiratory failure from COVID-19 pneumonia is a major cause of death after SARS-CoV-2 infection. We investigated whether PaO 2 /FiO 2 , oxygenation index (OI), SpO 2 /FiO 2 , and oxygen saturation index (OSI), commonly used to assess the severity of acute respiratory distress syndrome (ARDS), can predict mortality in mechanically ventilated COVID-19 patients., Methods: In this single-centered retrospective pilot study, we enrolled 68 critically ill mechanically ventilated adult patients with confirmed COVID-19. Physiological variables were recorded on the day of intubation (day 0) and postintubation days 3 and 7. The association between physiological parameters, PaO 2 /FiO 2 , OI, SpO 2 /FiO 2 , and OSI with mortality was assessed using multiple variable logistic regression analysis. Receiver operating characteristic analysis was conducted to evaluate the performance of the predictive models., Results: The ARDS severity indices were not statistically different on the day of intubation, suggesting similar baseline conditions in nonsurviving and surviving patients. However, these indices were significantly worse in the nonsurviving as compared to surviving patients on postintubation days 3 and 7. On intubation day 3, PaO 2 /FiO 2 was 101.0 (61.4) in nonsurviving patients vs. 140.2 (109.6) in surviving patients, p =0.004, and on day 7 106.3 (94.2) vs. 178.0 (69.3), p < 0.001. OI was 135.0 (129.7) in nonsurviving vs. 84.8 (86.1) in surviving patients ( p =0.003) on day 3 and 150.0 (118.4) vs. 61.5 (46.7) ( p < 0.001) on day 7. OSI was 12.0 (11.7) vs. 8.0 (10.0) ( p =0.006) on day 3 and 14.7 (13.2) vs. 6.5 (5.4) ( p < 0.001) on day 7. Similarly, SpO 2 /FiO 2 was 130 (90) vs. 210 (90) ( p =0.003) on day 3 and 130 (90) vs. 230 (50) ( p < 0.001) on day 7, while OSI was 12.0 (11.7) vs. 8.0 (10.0) ( p =0.006) on day 3 and 14.7 (13.2) vs. 6.5 (5.4) ( p < 0.001) on day 7 in the nonsurviving and surviving patients, respectively. All measures were independently associated with hospital mortality, with significantly greater odds ratios observed on day 7. The area under the receiver operating characteristic curve (AUC) for mortality prediction was greatest on intubation day 7 (AUC = 0.775, 0.808, and 0.828 for PaO 2 /FiO 2 , OI, SpO 2 /FiO 2 , and OSI, respectively)., Conclusions: Decline in oxygenation indices after intubation is predictive of mortality in COVID-19 patients. This time window is critical to the outcome of these patients and a possible target for future interventions. Future large-scale studies to confirm the prognostic value of the indices in COVID-19 patients are warranted., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Ala Nozari et al.)

Introduction: The objective of this study was to compare airway management technique, performance, and peri-intubation complications during the novel coronavirus pandemic (COVID-19) using a single-center cohort of patients requiring emergent intubation., Methods: We retrospectively collected data on non-operating room (OR) intubations from February 1-April 23, 2020. All patients undergoing emergency intubation outside the OR were eligible for inclusion. Data were entered using an airway procedure note integrated within the electronic health record. Variables included level of training and specialty of the laryngoscopist, the patient's indication for intubation, methods of intubation, induction and paralytic agents, grade of view, use of video laryngoscopy, number of attempts, and adverse events. We performed a descriptive analysis comparing intubations with an available positive COVID-19 test result with cases that had either a negative or unavailable test result., Results: We obtained 406 independent procedure notes filed between February 1-April 23, 2020, and of these, 123 cases had a positive COVID-19 test result. Residents performed fewer tracheal intubations in COVID-19 cases when compared to nurse anesthetists (26.0% vs 37.4%). Video laryngoscopy was used significantly more in COVID-19 cases (91.1% vs 56.8%). No difference in first-pass success was observed between COVID-19 positive cases and controls (89.4% vs. 89.0%, p = 1.0). An increased rate of oxygen desaturation was observed in COVID-19 cases (20.3% vs. 9.9%) while there was no difference in the rate of other recorded complications and first-pass success., Discussion: An average twofold increase in the rate of tracheal intubation was observed after March 24, 2020, corresponding with an influx of COVID-19 positive cases. We observed adherence to society guidelines regarding performance of tracheal intubation by an expert laryngoscopist and the use of video laryngoscopy.

Objective. The auditory system is extremely efficient in extracting auditory information in the presence of background noise. However, people with auditory implants have a hard time understanding speech in noisy conditions. The neural mechanisms related to the processing of background noise, especially in the inferior colliculus (IC) where the auditory midbrain implant is located, are still not well understood. Understanding the mechanisms of perception in noise could lead to better stimulation or preprocessing strategies for such implants. We thus wish to investigate if there is a difference in the activity of neurons in the IC when presenting noisy vocalizations with different types of noise (stationary vs. non-stationary), input signal-to-noise ratios (SNR) and signal levels. Approach. We developed novel metrics based on a generalized linear model (GLM) to investigate the effect of a given input noise on neural activity. We used these metrics to analyze neural data recorded from the IC in ketamine-anesthetized female Hartley guinea pigs while presenting noisy vocalizations. Main results. We found that non-stationary noise clearly contributes to the multi-unit neural activity in the IC by causing excitation, regardless of the SNR, input level or vocalization type. However, when presenting white or natural stationary noises, a great diversity of responses was observed for the different conditions, where the multi-unit activity of some sites was affected by the presence of noise and the activity of others was not. Significance. The GLM-based metrics allowed the identification of a clear distinction between the effect of white or natural stationary noises and that of non-stationary noise on the multi-unit activity in the IC. This had not been observed before and indicates that the so-called noise invariance in the IC is dependent on the input noisy conditions. This could suggest different preprocessing or stimulation approaches for auditory midbrain implants depending on the noisy conditions., (© 2021 IOP Publishing Ltd.)

As mammals evolved with exposure to particular diets, naturally abundant compounds may have become part of the set of environmental co-determinants that shaped brain structure and function. Here we investigated whether bioactive factors found in apples directly affect hippocampal neurogenesis in the adult mouse. We found that quercetin, the most abundant flavanol in apple peel, was anti-proliferative at high concentrations but pro-neurogenic at low concentrations. This was confirmed in vivo, with intraperitoneally delivered quercetin promoting survival and neuronal differentiation, without affecting proliferation. Using a bioassay-guided fractionation approach we also identified additional pro-neurogenic compounds in apple flesh that were not related to flavonoids. We found that 3,5-dihydroxybenzoic acid significantly increased neural precursor cell proliferation and neurogenesis. This work shows that both flavonoids and 3,5-dihydroxybenzoic acid are pro-neurogenic, not only by activating precursor cell proliferation but also by promoting cell-cycle exit, cellular survival, and neuronal differentiation., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Decompensated hemorrhagic shock (DHS) is the leading cause of preventable death in combat casualties. "Golden hour" resuscitation effects on cerebral blood flow and perfusion following DHS in prolonged field care (PFC) are not well investigated. Using an established non-human primate model of DHS, we hypothesized noninvasive regional tissue oxygenation (rSO2) and Transcranial Doppler (TCD) would correlate to the invasive measurement of partial pressure of oxygen (PtO2) and mean arterial pressure (MAP) in guiding hypotensive resuscitation in a PFC setting., Methods: Ten rhesus macaques underwent DHS followed by a 2 h PFC phase (T0-T120), and subsequent 4 h hospital resuscitation phase (T120-T360). Invasive monitoring (PtO2, MAP) was compared against noninvasive monitoring systems (rSO2, TCD). Results were analyzed using t tests and one-way repeated measures ANOVA. Linear correlation was determined via Pearson r. Significance = P < 0.05., Results: MAP, PtO2, rSO2, and mean flow velocity (MFV) significantly decreased from baseline at T0. MAP and PtO2 were restored to baseline by T15, while rSO2 was delayed through T30. At T120, MFV returned to baseline, while the Pulsatility Index significantly elevated by T120 (1.50 ± 0.31). PtO2 versus rSO2 (R2 = 0.2099) and MAP versus MFV (R2 = 0.2891) shared very weak effect sizes, MAP versus rSO2 (R2 = 0.4636) displayed a low effect size, and PtO2 versus MFV displayed a moderate effect size (R2 = 0.5540)., Conclusions: Though noninvasive monitoring methods assessed here did not correlate strongly enough against invasive methods to warrant a surrogate in the field, they do effectively augment and direct resuscitation, while potentially serving as a substitute in the absence of invasive capabilities., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by the Shock Society.)

The possible role of the social rank (R) (i.e., low-LSR, middle-MSR, or high-HSR) in anestrus goats exposed to a P4 + eCG (D) (i.e., 100 or 350 IU) estrus induction protocol (EIP) was evaluated. Goats (Alpine-Saanen-Nubian × Criollo; n = 70; 25° North) managed under stall-fed conditions were all ultrasound evaluated to confirm anestrous status, while the social rank was determined 30 d prior to the EIP. The response variables included estrus induction (EI, %), duration of estrus (DUR, h), ovulation rate (OR, n), live weight (LW, kg), thoracic perimeter (TP, cm), thoracic diameter (TD, cm), body length (BL, cm), height at withers (HW, cm), beard length (BEA, cm), compactness index (COM, cm), and anamorphosis index (ANA, cm), as affected by R, D, and the R × D interaction were evaluated, while the correlation coefficients among reproductive and morphometric variables were quantified. An R × D interaction ( p < 0.05) affected the response variables EI, DUR, and OR. While the largest ( p < 0.05) EI% occurred in the HSR goats, irrespective of eCG (i.e., 100 or 350 IU), both the shortest estrus duration (DUR, h) and the lowest ovulation rate (OR, n) occurred in the LSR + D100 combination, with no differences among HSR and MSR either with D100 or D350. Regarding the LW and morphometric response variables, (i.e., LW, TP, TD, BL, HW, BEA, COM, and ANA) all of them favored either the HSR and MSR groups, with the lowest phenotypic values occurring in the LSR-goats. The EI% was observed to be positively correlated ( p < 0.05) with DUR (0.71), LW (0.28), TP (0.31), TD (0.34), BL (0.33), HW (0.35), COM (0.23), and ANA (0.23). While DUR was correlated ( p < 0.05) with TP (0.26) and ANA (0.24), OR demonstrated no-correlation ( p > 0.05) with any response variable, either reproductive or morphometric. As expected, LW had high correlation coefficients ( p < 0.01) with TP (0.86), TD (0.88), BL (0.82), HW (0.75), BEA (0.51), COM (0.97), and ANA (0.75). In general, the morphometric variables as a whole demonstrated important correlation coefficients among them ( p < 0.01), ranging from 0.38 up to 0.84. To estimate the importance of the morphometric differences between social rank upon estrus induction, a principal component (PC) analysis was performed based on the correlation matrix derived from the corporal measurements. The PC1 and PC2 explained 70.3% and 17.6% of the morphometric variation, respectively. The PC1 was a measure of the goat size (i.e., small, medium, large) and its association with estrus occurrence was evaluated using a logistic regression model; the bigger the goat, the increased probability of being in estrus, by up to five times compared to small goats. Our results confirm that the higher social ranked, larger goats amalgamated some fundamental factors to be successful: aggressiveness, primacy to food access, augmented live weight, and corporal size; all of these were able to modulate out-of-season reproductive success in crossbred dairy goats subjected to an estrus induction protocol and managed under stall-fed conditions in Northern Mexico.

The coronavirus disease 2019 pandemic resulted in unprecedented numbers of patients with respiratory failure requiring ventilatory support. The number of patients who required critical care quickly outpaced the availability of intensive care unit (ICU) beds. Consequently, health care systems had to creatively expand critical care services into alternative hospital locations with repurposed staff and equipment. Deploying anesthesia workstations to the ICU to serve as mechanical ventilators requires equipment preparation, multidisciplinary planning, and targeted education. We aim to contextualize this process, highlighting major differences between anesthesia workstations and ICU ventilators, and to share the insights gained from our experiences creating an anesthesia provider-based ventilator management team.

The intraoperative anesthetic management for thoracic surgery can impact a patient's postoperative course, especially in patients with significant lung disease. One-lung ventilation poses an inherent risk to patients, including hypoxemia, acute lung injury, and right ventricular dysfunction. Patient-specific ventilator management strategies during one-lung ventilation can reduce postoperative morbidity., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Develop a model for quality improvement in tracheostomy care and decrease tracheostomy-related complications., Methods: This study was a prospective quality improvement project at an academic tertiary care hospital. A multidisciplinary team was assembled to create institutional guidelines for clinical care during the pre-operative, intra-operative, and post-operative periods. Baseline data was compiled by retrospective chart review of 160 patients, and prospective tracking of select points over 8 months in 73 patients allowed for analysis of complications and clinical parameters., Results: Implementation of a quality improvement team was successful in creating guidelines, setting baseline parameters, and tracking data with run charts. Comparison of pre- and post-guideline data showed a trend toward decreased rate of major complications from 4.38% to 2.74% (p = 0.096). Variables including time to tracheotomy for prolonged intubation, surgical technique, day of first tracheostomy tube change, and specialty performing surgery did not show increased risk of complications. There were increased tracheostomy-related complications in cold months (p = 0.04)., Conclusions: An interdisciplinary quality improvement team can improve tracheostomy care by identifying system factors, standardizing care among specialties, and providing continuous monitoring of select data points., Competing Interests: Declaration of competing interest None., (Copyright © 2019. Published by Elsevier Inc.)

The possible effect of glutamate supplementation upon ovarian reactivation and serum concentrations of insulin (INS) and triiodothyronine (T3) in anestrous yearling goats was evaluated. Goats (n = 32, 12 mo., 26° North, 1117 m) with a similar live weight (LW) and body condition score (BCS) were blood sampled twice per week for two weeks (2 × 1 week × 2 weeks) to confirm the anestrus status (<1 ng P4/mL; RIA). Thereafter, goats were randomly assigned to either 1) Glutamate (GLUT; n = 16, LW = 27.1 ± 1.09 kg, 3.5 ± 0.18 units, IV-supplemented with 7 mg of glutamate kg -1 LW), or 2) Control (CONT; n = 16; LW = 29.2 ± 1.09 kg; BCS = 3.5 ± 0.18, IV saline). During the treatment period, 16 goats (eight/group) were blood sampled twice per week for six weeks. Such serum samples (2 × 1 week × 6 weeks) were quantified by their P4 content to evaluate the ovarian-luteal activity, whereas a sample subset (1 × 1 week × 6 weeks) was used to quantify their INS & T3 content to evaluate their metabolic status. Neither LW (28.19 kg; p > 0.05) nor BCS (3.51 units; p > 0.05) differed between treatments. Goats depicting ovarian reactivation favored the GLUT group (50 vs. 12.5%; p < 0.05). Neither INS (1.72 ± 0.15 ng mL -1 ) nor T3 (2.32 ± 0.11 ng mL -1 ) differed between treatments, yet a treatment x time interaction regarding INS & T3 concentration across time favored ( p < 0.05) the GLUT group. The results unveil exogenous glutamate as an interesting modulator not only of ovarian reactivation, but of metabolic hormone synthesis.

Background: Tactical Combat Casualty Care guidelines for hemorrhage recommend resuscitation to systolic blood pressure (SBP) of 85±5 mm Hg during prehospital care. Success depends on transport to definitive care within the 'golden hour'. As future conflicts may demand longer prehospital/transport times, we sought to determine safety of prolonged permissive hypotension (PH)., Methods: Adult male swine were randomized into three experimental groups. Non-shock (NS)/normotensive underwent anesthesia only. NS/PH was bled to SBP of 85±5 mm Hg for 6 hours of prolonged field care (PFC) with SBP maintained via crystalloid, then recovered. Experimental group underwent controlled hemorrhage to mean arterial pressure 30 mm Hg until decompensation (Decomp/PH), followed by 6 hours of PFC. Hemorrhaged animals were then resuscitated with whole blood and observed for 24 hours. Physiologic variables, blood, tissue samples, and neurologic scores were collected., Results: Survival of all groups was 100%. Fluid volumes to maintain targeted SBP in PFC were significantly higher in the hemorrhage group than sham groups. After 24 hours' recovery, no significant differences were observed in neurologic scores or cerebrospinal fluid markers of brain injury. No significant changes in organ function related to treatment were observed during PFC through recovery, as assessed by serum chemistry and histological analysis., Conclusions: After 6 hours, a prolonged PH strategy showed no detrimental effect on survival or neurologic outcome despite the increased ischemic burden of hemorrhage. Significant fluid volume was required to maintain SBP-a potential logistic burden for prehospital care. Further work to define maximum allowable time of PH is needed., Study Type: Translational animal model., Level of Evidence: N/A., Competing Interests: Competing interests: SC, CGM, and LEN are civilian employees of the US Government. GJR and LJS are contract employees of the US Government. JJG and ENH are military service members and this work was prepared as part of their official duties. Title 17 USC §105 provides that ‘copyright protection under this title is not available for any work of the US Government.’ Title 17 USC §101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person’s official duties., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Sensory systems, such as the visual or auditory system, are highly non linear. It is therefore not easy to predict the effect of additive inputs on the spiking activity of related brain structures. Here, we propose two metrics to study the effect of additive covariates on the spiking activity of neurons. These metrics are directly obtained from a generalized linear model. We apply these metrics to the study of the effect of additive input audio noise on the spiking activity of neurons in the auditory system. To do so, we combine clean vocalisations with natural stationary or non-stationary noises and record activity in the auditory system while presenting the noisy vocalisations. We found that non-stationary noise has a greater effect on the neural activity than stationary noise. We observe that the results, obtained using the proposed metrics, is more consistent with current knowledge in auditory neuroscience than the results obtained when using a common metric from the literature, the extraction index.

A sugar solution measurement system was developed based on the dielectric properties of the sucrose molecule. An ac conductivity and tan δ study as a function of the frequency was performed to find the suitable frequency range for the measuring system. The results indicate that it is possible to obtain a better response of the sensor using the frequencies as the maxima peak in tan δ appears. Developed setup for sucrose solution was appropriate to measure in a 0.15 to 1 g/mL range with an experimental error of about 3%. The proposed system improves the measurement time over some other methods.

Purpose: To compare OCT identified white thrombus decline, neointimal hyperplasia and clinical outcomes of patients treated with ticagrelor plus aspirin with those patients treated with clopidogrel plus aspirin after peripheral interventions., Background: Ticagrelor is a potent platelet inhibitor. In patients with coronary artery disease, ticagrelor and aspirin demonstrated reduced rates of stent thrombosis, compared to aspirin and clopidogrel. The clinical importance of potent antiplatelet inhibition after peripheral endovascular interventions is unknown., Methods: We enrolled 18 patients with superficial femoral artery disease and the presence of OCT-detected clot post-stent placement. Patients were randomized to 75 mg clopidogrel once daily for 1 month vs. 90 mg ticagrelor twice daily for 6 months, both in addition to 81 mg aspirin for 6 months. Clot volumes, ankle-brachial index (ABI), 6-minute walk test, and Rutherford classification were measured at baseline and 6-month follow-up. Neointimal hyperplasia and neovascularization were calculated at 6-month follow-up., Results: N = 11 patients were enrolled in the clopidogrel group and N = 7 in the ticagrelor group. There was a significantly greater decrease in white thrombus in the ticagrelor group (median volume/stent length (0.067 vs 0.014 mm 3 /mm, p = 0.05)). No differences were found in % neointima (0.412 vs 0.536 mm 3 /mm, p = 0.44) and neovascularization (28 vs 44, p = 0.16). ABI and Rutherford classification were improved significantly after 6 months in the clopidogrel group, with no difference between groups at 6 months in ABI or Rutherford., Conclusion: In symptomatic patients with PAD, ticagrelor showed significant improvement relative to clopidogrel with respect to white thrombus burden decline., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Management of left colonic perforation in emergency depends largely upon the attending surgeon. The primary endpoint of this observational, retrospective study analyses surgical technique chosen by the colorectal specialized (CS) or general surgeon (GS) and changes over time., Materials and Methods: Interventions for left colonic perforation from 2004 to 2015 are grouped for CS or GS. Type of operation (Hartmann (HP), primary anastomosis (RPA) ±covering ileostomy (IL)), year, Peritonitis Severity Score (PSS), morbidity, mortality, anastomotic dehiscence and stoma closure were recorded., Results: 190 patients were included. CS performed RPA ± IL in 83 pts (74.1%) and HP in 29 pts (25.9%) while GS performed RPA ± IL in 26 pts (33.3%) and HP in 52 pts (66.7%), (p < 0.001). CS performed over time more RPA with covering ileostomy to the detriment of HP. No differences were observed between the two surgeon-groups in terms of overall morbidity and mortality. Anastomotic dehiscence was higher among GS (20% vs 4.8%, p = 0.046). Mortality after HP overtrumped RPA (26.8% versus 11.0%, p = 0.009). Regression analysis showed that HP's probability increased 3.7 times by GS, 2.3 times by each PSS point and decreased 32.5% every forthcoming year (p < 0.001). A multinomial logistic model illustrates evolution of surgical management over time, CS leading towards extension of reconstructive techniques, subsequently adopted by GS., Conclusions: CS attempt bowel reconstruction in more patients than GS in left colonic perforation without differences in overall postoperative morbidity or mortality. CS introduced covering IL to further indicate primary anastomosis avoiding HP. GS stepwise adopted this management although results are improved by CS. These findings favor primary anastomosis with/without covering ileostomy in left colonic perforation in selected patients where PSS can be used as a tool to discriminate best candidates., (Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Multiple intestinal preparations have been used in children undergoing colonoscopy, with variable limitation due to acceptance, tolerance, and proper cleaning. The objective of this study was to compare the tolerability, safety and efficacy of the colonoscopy preparation with 1 day with PEG 3350 (poliethylenglycol) (4g/kg/day) + bisacodyl compared to 2 days of preparation with PEG 3350 (2g/kg/day) + bisacodyl in pediatric patients., Methods: A clinical, randomized, and blind trial was performed. Patients aged 2 to 18 years scheduled for colonoscopy were included. Patients were randomized into two groups: 1 day of preparation with PEG 3350 4g/kg/day + bisacodyl and 2 days of preparation with PEG 3350 2g/kg/day + bisacodyl. Through a questionnaire, physical examination and endoscopic evaluation (Boston scale), the tolerance, safety and efficacy of the 2 preparations to be evaluated were determined. Student's t test was performed for quantitative variables and χ 2 for qualitative variables., Results: There were no significant differences in compliance rates, adverse effects, and extent of colonoscopic evaluation., Conclusions: Tolerance and safety between the intestinal preparation for 1-day colonoscopy with PEG 3350 (4g/kg/day) + bisacodyl and the 2-day preparation with PEG 3350 (2g/kg/day) + bisacodyl were similar. The quality of cleanliness was good in both groups, being partially more effective in the 1-day group with PEG 3350 (4g/kg/day)., (Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.)

The head louse Pediculus humanus capitis (De Geer) is a hematophagous ectoparasite that inhabits the human scalp. Infestations by this insect are commonly known as pediculosis, which is more common in younger groups. These infestations are asymptomatic; however, skin irritation from scratching occasionally may cause secondary bacterial infections. In recent years, the prevalence of pediculosis has increased in children; this increase has been attributed to louse resistance to the insecticides used as a control measure for infestation. The aim of the present study was to determine the presence and frequency of the knockdown resistance mutation (kdr) T929I in 468 head lice collected from 32 elementary schools in the metropolitan area of Nuevo Leon (24) and Yucatan (8), Mexico. This is the first report of a knockdown resistance (kdr) mechanism in head lice from Mexico. The T929I mutation was present in all of the sampled schools, with variability observed in its allelic and genotypic frequencies., (© The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: To determine whether diabetes mellitus has an independent impact on major limb outcomes at 1 year after endovascular treatment of lower extremity peripheral artery disease (PAD)., Methods: The study involved 1906 consecutive patients (mean age 66 years; 1469 men) enrolled in the observational Excellence in Peripheral Artery Disease (XLPAD) registry ( ClinicalTrials.gov identifier NCT01904851) between January 2005 and October 2015 after undergoing index endovascular procedures in 2426 limbs for arterial occlusive disease. Patient outcomes included 12-month target limb amputation (above ankle) and target limb revascularization as well as all-cause death. Kaplan-Meier analysis and adjusted Cox proportional hazard models were used for time-to-event analysis of outcomes for the entire study sample as well as for the critical limb ischemia (CLI) and claudication subgroups. Results of the Cox regression models are reported as the hazard ratio (HR) and 95% confidence interval (CI)., Results: Diabetics undergoing endovascular procedures had higher rates of comorbid conditions (p<0.001), CLI (p<0.001), heavily calcified lesions (p=0.002), multivessel disease (p=0.030), and fewer infrapopliteal runoff vessels (p<0.001). Regression analysis after adjusting for confounders revealed significantly higher target limb major amputation in diabetics compared with nondiabetics (HR 5.02, 95% CI 1.44 to 17.56, p=0.011). However, repeat revascularization rates were similar. When considering CLI and claudication subgroups, diabetes was associated with a nonsignificant increased risk of 12-month major amputation only for patients presenting with CLI (HR 3.48, 95% CI 0.97 to 12.51, p=0.056). Diabetes was also associated with an increased risk of 12-month all-cause mortality in the overall study sample (HR 4.64, 95% CI 2.01 to 10.70, p<0.001) and in the CLI subgroup (HR 14.15, 95% CI 3.16 to 63.32, p<0.001) but not in the claudication subgroup (HR 1.42, 95% CI 0.45 to 4.54, p=0.552)., Conclusion: Diabetes increases the risk of major amputation and all-cause death at 12 months following endovascular revascularization in patients with symptomatic PAD. These risks are especially heightened in patients presenting with CLI.

We asked whether cell-cycle associated protein p27kip1 might be involved in the transition of precursor cells to postmitotic maturation in adult hippocampal neurogenesis. p27kip1 was expressed throughout the dentate gyrus with a strong nuclear expression in early postmitotic, calretinin-positive neurons and neuronally determined progenitor cells (type-3 and some type-2b), lower or absent expression in radial glia-like precursor cells (type-1) and type-2a cells and essentially no expression in granule cells. This suggested a transitory role in late proliferative and early postmitotic phases of neurogenesis. Inconsistent with a role limited to cell cycle arrest the acute stimuli, voluntary wheel running (RUN), environmental enrichment (ENR) and kainate-induced seizures increased p27kip1 expressing cells. Sequential short-term combination of RUN and ENR yielded more p27kip1 cells than either stimulus alone, indicating an additive effect. In vitro, p27kip1 was lowly expressed by proliferating precursor cells but increased upon differentiation. In p27kip1-/- mice neurogenesis was reduced in vivo, whereas the number of proliferating cells was increased. Accordingly, the microdissected dentate gyrus of p27kip1-/- mice generated more colonies in the neurosphere assay and an increased number of larger spheres with the differentiation potential unchanged. In p27kip1-/- monolayer cultures, proliferation was increased and cell cycle genes were upregulated. In the Morris water maze p27kip1-/- mice learned the task but were specifically impaired in the reversal phase explainable by the decrease in adult neurogenesis. We conclude that p27kip1 is involved in the decisive step around cell-cycle exit and plays an important role in activity-regulated and functionally relevant adult hippocampal neurogenesis. Stem Cells 2017;35:787-799., (© 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Objectives: The aim of this study was to assess actual procedural costs and outcomes comparing wire-catheter and dedicated chronic total occlusion (CTO) device strategies to cross peripheral artery CTOs., Background: Peripheral artery CTO interventions are frequently performed, but there are limited data on actual procedural costs and outcomes comparing wire-catheter and dedicated CTO devices., Methods: The XLPAD (Excellence in Peripheral Artery Disease Intervention) registry (NCT01904851) was accessed to retrospectively compare cost and 30-day and 12-month outcomes of wire-catheter and crossing device strategies for treatment of infrainguinal peripheral artery CTO., Results: Of all 3,234 treated lesions, 42% (n = 1,362) were CTOs in 1,006 unique patients. Wire-catheter approaches were used in 82% of CTOs, whereas dedicated CTO devices were used in 18% (p < 0.0001). CTO crossing device use was associated with significantly higher technical success (74% vs. 65%; p < 0.0001) and mean procedure cost ($7,800.09 vs. $4,973.24; p < 0.0001). Because 12-month repeat revascularization (11.3% vs. 17.2%; p = 0.02) and amputation rates (2.8% vs. 8.5%; p = 0.002) in the CTO crossing device arm were lower compared with the wire-catheter group, the net cost for an initial CTO crossing device strategy was $423.80 per procedure., Conclusions: An initial wire-catheter approach to cross a peripheral artery CTO is most frequently adopted. The use of dedicated CTO crossing devices provides significantly higher technical success and lower reintervention and amputation rates, at a net cost of $423.80 per procedure at 12 months., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Deep brain stimulation (DBS) is used as an alternative therapeutic procedure for pharmacoresistant psychiatric disorders. Recently the thalamic reticular nucleus (TRN) gained attention due to the description of a novel pathway from the amygdala to this nucleus suggesting that may be differentially disrupted in mood disorders. The limbic system is implicated in the regulation of these disorders that are accompanied by neuroplastic changes. The hippocampus is highly plastic and shows the generation of new neurons, process affected by stress but positively regulated by antidepressant drugs. We explored the impact of applying acute DBS to the TRN (DBS-TRN) in male Wistar rats exposed to acute stress caused by the forced-swim Porsolt's test (FST) and on initial events of hippocampal neurogenesis. After the first session of forced-swim, rats were randomly subdivided in a DBS-TRN and a Sham group. Stimulated rats received 10min of DBS, thus the depressant-like behavior reflected as immobility was evaluated in the second session of forced-swim. Locomotricity was evaluated in the open field test. Cell proliferation and doublecortin-associated cells were quantified in the hippocampus of other cohorts of rats. No effects of electrode implantation were found in locomotricity. Acute DBS-TRN reduced immobility in comparison to the Sham group (p<0.001). DBS-TRN increased cell proliferation (Ki67 or BrdU-positive cells; p=0.02, p=0.02) and the number of doublecortin-cells compared to the Sham group (p<0.02). Similar effects were found in rats previously exposed to the first session of forced-swim. Our data could suggest that TRN brain region may be a promising target for DBS to treat intractable depression., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Resveratrol (RVTL) is a flavonoid found in red wine and has been publicized heavily as an anti-aging compound. Indeed, basic research confirms that although there is much hype in the promotion of RVTL, flavonoids such as RVTL have a wide range of biological effects. We here investigated the effects of RVTL treatment on hippocampal plasticity and memory performance in female Balb/C mice, a strain with low baseline levels of adult neurogenesis. Two weeks of treatment with RVTL (40 mg/kg) induced the production of new neurons in vivo by increasing cell survival and possibly precursor cell proliferation. In addition, RVTL decreased the number of apoptotic cells. The number of doublecortin (DCX)-expressing intermediate cells was increased. RVTL stimulated neuronal differentiation in vitro without effects on proliferation. In the dentate gyrus, RVTL promoted the formation and maturation of spines on granule cell dendrites. RVTL also improved performance in the step down passive avoidance test. The RVTL-treated mice showed increase in the levels of two key signaling proteins, phospho-Akt and phospho-PKC, suggesting the involvement of these signaling pathways. Our results support the vision that flavonoids such as resveratrol deserve further examination as plasticity-inducing compounds in the context of successful cognitive aging.

The aim of this study was to examine whether breastfeeding may reduce the programming effect of birthweight on abdominal adiposity. Abdominal (in three regions: R1, R2 and R3) adiposity was measured by dual energy x-ray absorptiometry in 314 adolescents. Breastfeeding duration, birthweight, duration of gestation and maternal educational level were obtained from questionnaire. Physical activity was objectively measured. We detected significant interactions between breastfeeding and birthweight on abdominal adiposity (Ps = 0.02-0.07). We observed that birthweight was associated with abdominal adiposity in the group who had never been breastfed (β = -0.19 to -0.23; Ps < 0.05), while no association was found in adolescents who had breastfeeding for ≥3 months (β = -0.03 to -0.07). The results were independent of duration of gestation, age, sex, maternal educational level and physical activity. Breastfeeding may reduce the adverse influence conferred by low birthweight on abdominal adiposity in adolescents., (© 2014 John Wiley & Sons Ltd.)

Background: There are limited data regarding contemporary use of stent and non-stent based treatment strategies of infrainguinal peripheral artery disease (PAD)., Methods: We analyzed data from the ongoing multicenter XLPAD registry between July 2005 and October 2013 to report on the use of non-stent (atherectomy ± balloon angioplasty) and stent-based treatment of superficial femoral artery (SFA), popliteal, and below-the-knee (BTK) vessels in contemporary clinical practice., Results: A total of 584 interventions (SFA, 82.5%; popliteal, 7.2%; BTK, 9.9%) were performed in 372 patients (mean age, 63.2 years; diabetes mellitus, 57.7%; Rutherford category 1-3, 73.5%; Rutherford category 4-6, 20.1%). Stents were deployed in 389 lesions (66.6%; SFA, 90.5%; popliteal, 5.1%; BTK, 4.1%) and non-stent strategy (atherectomy, 49%) in 195 lesions (33.4%; SFA, 66.7%; popliteal, 11.3%; BTK, 21.5%). In the stent and non-stent groups, mean lesion lengths were 133.9 mm and 86.0 mm (P<.001), chronic total occlusions (CTOs) constituted 63.0% and 49.7% (P<.01), and restenotic lesions were 12.6% and 32.3% (P<.001), respectively. At a mean follow-up of 260 ± 130 days, in the stent and non-stent treated patients, all-cause mortality was 4.3% and 3.5% (P=.65), clinically indicated repeat revascularization was 17.5% and 14.9% (P=.42), and amputation was 4.6% and 9.2% (P<.01), respectively. SFA lesion location, long lesion length, and CTO were associated with the use of stents. Advanced Rutherford class was associated with a non-stent treatment strategy., Conclusion: The majority of endovascular peripheral arterial interventions are performed in the SFA; most include a CTO and in patients with diabetes mellitus. Operators use stents to primarily treat complex SFA lesions with overall similar outcomes, except for fewer amputations compared to a non-stent strategy.

The acute effects of short-term glutamate administration on the number of antral follicles and ovulation rate were examined in adult goats. Neither live weight (44.5±1.3 kg) nor body condition (3.3±0.8 units) differed between the control (untreated) and glutamate-treated (0.175 mg/kg) animals (p>0.05). However, the number of antral follicles (3.4 vs. 2.1, p=0.05) and ovulation rate (2.5 vs. 1.5, p=0.05) was higher in the glutamate-administered group than in the controls., (Copyright © 2014 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Background: To examine the association between physical activity (PA) and liver enzyme levels in adolescents from nine European countries., Methods: The study comprised 718 adolescents (397 girls). PA was measured by accelerometry and expressed as total PA (counts/min), and time (min/d) engaged in moderate to vigorous intensity PA (MVPA). Time spent sedentary was also objectively measured. We measured serum levels of alanine aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltransferase (GGT), and the AST/ALT ratio was computed., Results: There was an association between MVPA and AST and AST/ALT (age, sex, and center-adjusted β = 0.096, 95% confidence interval (CI): 0.016 to 0.118; and β = 0.090, 95% CI: 0.006 to 0.112, respectively). Meeting the PA recommendations (60 min/d of MVPA) was significantly associated with higher AST and AST/ALT, which persisted after further adjusting for sedentary time and waist circumference. Sedentary time was not associated with any of the studied liver enzyme levels., Conclusion: Meeting the current PA recommendations of 60 min/d of MVPA is associated with higher levels of AST and AST/ALT regardless of time spent sedentary as well as total and central body fat in European adolescents.

Endotracheal extubation should be performed without causing trauma, while maintaining adequate oxygenation and ventilation. The equipment needed to provide suction, ventilation, and reintubation should be readily available. If extubation is judged to be unsafe, the procedure should be postponed and the patient reevaluated. Most complications related to extubation are preventable. Before performing extubation, the clinician must carefully prepare the medical resources needed to address reasonably foreseeable complications. A failed extubation can lead to a precipitous deterioration in the patient's condition, and attempts to improvise solutions under these challenging circumstances are rarely satisfactory.

Toluene misuse is a health problem worldwide with broad effects at the level of the central nervous system; however, therapeutic alternatives for inhalant abusers are limited. Chronic use of volatile substances is associated with different neurological and cognitive alterations, being anxiety a psychiatric condition with high prevalence. At cellular level toluene reduces neurogenesis and induces neuronal death. On the other hand, environmental enrichment has demonstrated to produce positive effects at behavioral and neuronal levels. Thus, the aim of the present work was to model alterations occasioned after repeated exposure to toluene (anxiety, reduction in neurogenesis - measured as doublecortin-labeled cells - and neuronal death). Subsequently, the influence of environmental enrichment on these effects was evaluated. Adolescent mice were exposed to toluene vapors from 1 to 4 weeks. Effects on anxiety were evaluated with the burying behavior test, whereas neurogenesis and hippocampal cell death were analyzed with immunohistochemistry, using anti-doublecortin or anti-active-Caspase-3 antibodies, respectively. Results showed that chronic toluene exposure increased anxiety in the burying behavior test; additionally, toluene decreased neurogenesis and enhanced neuronal death. Environmental enrichment (EE) enhanced the anxiety like response in air-exposed mice but did not modify the toluene anxiety response. Additionally, EE enhanced neurogenesis in toluene-pretreated animals at the same level to that found in animals unexposed to toluene and decreased neuronal death. Overall, the present study showed that environmental enrichment positively impacts some effects produced by repeated exposure to toluene., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Williams syndrome (WS) is a neurodevelopmental genetic disorder, due to a 7q11.23 hemizygous deletion. WS has a characteristic neurocognitive profile that includes intellectual disability (ID). Haploinsufficiency of some of the deleted genes is partially associated with the cognitive phenotype. The aim of this paper is to determine the differences in the microRNA (miRNA) expression in WS patients, using a neural cell model from the patients olfactory neuroepithelium (ONE), and to establish the relationship with those genes involved in neurodevelopment and neural function. To assess these goals, we made a comparative analysis of the miRNAs expression profile between WS patients and controls. Through an in silico analysis, we established potential pathways and targets associated with neural tissue. The expression profile shows 14 dysregulated miRNAs, including nervous system (NS)-rich miRNAs such as miR-125b, let-7c and miR-200. Most of these miRNAs have potential targets associated with NS functions while others have been reported to have specific neuronal functions. These data suggest that miRNAs widely contribute to the regulation of neurodevelopmental intrinsic processes, and that specific miRNAs could participate in WS neurobiology.

This study aimed to evaluate the effects of betacarotene (BC) supplementation on ovulation rate (OR) and luteinizing hormone (LH) secretion in adult goats during the breeding season. Additionally, total ovarian activity (TOA) comprising the total number of ultrasonographically detectable antral follicles (AF) and corpora lutea (OR) was also assessed. In early October, adult goats [n=22, 3.5 years of age, 7/8 Sannen-Alpine; 26°N, 103°W at 1117m.a.s.l.] were randomly assigned to: (i) BC group (BCG), orally supplemented with 50mg of BC/goat/day [n=10; live weight (LW)=45.9±2.0kg, body condition score (BCS; range: 0-emaciated to 5-obese)=3.0±0.1], and (ii) control group (CONT) [n=12; LW=46.2±2.0kg, BCS=3.0±0.1]. All animals received a basal diet of alfalfa hay, corn silage and corn grain, with free access to water and mineral salts. The whole experimental period spanned 34 days before and 17 days after ovulation. On day 23 of the experiment, estrus was synchronized with progestin-releasing intravaginal sponges; 36h prior to estrus, an intensive blood sampling (every 15min for 6h) was performed to determine mean LH concentrations, pulsatility (LH-PULSE) and area under the curve (LH-AUC) for serial LH concentrations. Afterwards, by the end of the luteal phase (i.e., 17 days after the onset of estrus), an ultrasonographic scanning was performed to evaluate OR and TOA [AF+OR]. The average LW and BCS did not differ (p>0.05) during the experimental period. BC-supplemented goats showed an increase in OR (3.4±0.2 versus 2.8±0.2; p<0.05) and exhibited lower (p<0.05) serum LH concentrations, LH-AUC and LH-PULSE compared to CONT. A positive correlation was recorded between OR and LW (r(2)=0.42, p<0.05) and BCS (r(2)=0.47, p<0.05). In addition, AF (5.0±0.6 versus 3.4±0.6) and TOA (8.4±0.6 versus 6.2±0.6) were greater (p<0.05) in the BC-supplemented group than CONT. Supplementation with BC enhanced ovarian follicular development and ovulation rate in adult female goats under decreased photoperiods through LHRH-independant pathways or direct effects of BC on ovarian function., (Copyright © 2013 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

In the course of adult hippocampal neurogenesis, the postmitotic maturation and survival phase is associated with dendrite maturation. Melatonin modulates the survival of new neurons with relative specificity. During this phase, the new neurons express microtubule-associated protein doublecortin (DCX). Here, we show that the entire population of cells expressing DCX is increased after 14 days of treatment with melatonin. As melatonin also affects microtubule polymerization which is important for neuritogenesis and dendritogenesis, we studied the consequences of chronic melatonin administration on dendrite maturation of DCX-positive cells. Treatment with melatonin increased the number of DCX-positive immature neurons with more complex dendrites. Sholl analysis revealed that melatonin treatment lead to greater complexity of the dendritic tree. In addition, melatonin increased the total volume of the granular cell layer. Besides its survival-promoting effect, melatonin thus also increases dendritic maturation in adult neurogenesis. This might open the opportunity of using melatonin as an adjuvant in attempts to extrinsically stimulate adult hippocampal neurogenesis in neuropsychiatric disease, dementia or cognitive ageing., (© 2010 The Authors. Journal of Pineal Research © 2010 John Wiley & Sons A/S.)

Our aim in this study was to examine the association between breastfeeding duration and cardiorespiratory fitness, isometric strength, and explosive strength during adolescence. A total of 2567 adolescents (1426 girls) from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study aged 12.5-17.5 y were included. Information about duration of any and exclusive breastfeeding was obtained retrospectively by means of a parental questionnaire. The 20-m shuttle run, handgrip strength, and standing long jump tests were used to assess physical fitness. Significant differences among the categories of breastfeeding duration were tested using ANCOVA after adjusting for a set of potential confounders: gestational and current age, birth weight, sexual maturation, fat mass, fat-free mass, maternal education, parental weight status, country, smoking behavior, and days of vigorous physical activity. Longer breastfeeding (either any or exclusive) was associated with a higher performance in the standing long jump test in both boys and girls (P < 0.001), regardless of fat mass, fat-free mass, and the rest of potential confounders. In adolescents who were breastfed for 3-5 mo or ≥6 mo, the risk of having a standing long jump performance below the 5th percentile was reduced by half compared with those who were never breastfed [odds ratio (OR) = 0.54, 95% CI = 0.30-0.96, P < 0.05; and OR = 0.40, 95% CI = 0.22-0.74, P < 0.01, respectively). These findings suggest a role of breastfeeding in determining lower body explosive strength during adolescence.

Background: Adult neurogenesis is a particular example of brain plasticity that is partially modulated by the endocannabinoid system. Whereas the impact of synthetic cannabinoids on the neuronal progenitor cells has been described, there has been lack of information about the action of plant-derived extracts on neurogenesis. Therefore we here focused on the effects of Delta9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) fed to female C57Bl/6 and Nestin-GFP-reporter mice on proliferation and maturation of neuronal progenitor cells and spatial learning performance. In addition we used cannabinoid receptor 1 (CB1) deficient mice and treatment with CB1 antagonist AM251 in Nestin-GFP-reporter mice to investigate the role of the CB1 receptor in adult neurogenesis in detail., Results: THC and CBD differed in their effects on spatial learning and adult neurogenesis. CBD did not impair learning but increased adult neurogenesis, whereas THC reduced learning without affecting adult neurogenesis. We found the neurogenic effect of CBD to be dependent on the CB1 receptor, which is expressed over the whole dentate gyrus. Similarly, the neurogenic effect of environmental enrichment and voluntary wheel running depends on the presence of the CB1 receptor. We found that in the absence of CB1 receptors, cell proliferation was increased and neuronal differentiation reduced, which could be related to CB1 receptor mediated signaling in Doublecortin (DCX)-expressing intermediate progenitor cells., Conclusion: CB1 affected the stages of adult neurogenesis that involve intermediate highly proliferative progenitor cells and the survival and maturation of new neurons. The pro-neurogenic effects of CBD might explain some of the positive therapeutic features of CBD-based compounds.

Lifestyle plays an important role in the development of obesity during childhood and adolescence. We provide up-to-date information about the relationship between obesity and food intake and dietary patterns in adolescents. Scientific evidence is increasing about the dietary factors associated with this relationship, specifically a low meal frequency, skipping breakfast, and a high consumption of sugar sweetened beverages. Maybe some of the reviewed dietary factors could cluster in the same population of adolescents, increasing the individual risk. There is little information about dietary patterns and current time trends in adolescents; however, the available data seem to show that the tendency in the adolescent population worldwide is to increase those dietary factors related with obesity development. Public health efforts should be emphasized in order to decrease the current tendency. Regular family meals could serve as role models for healthy eating behaviors. Educational intervention programs for parents, aiming to modify the healthfulness of the diet, seems to be one of the most adequate tools to deal with the worldwide obesity epidemic.

Adult hippocampal neurogenesis is regulated by activity. But how do neural precursor cells in the hippocampus respond to surrounding network activity and translate increased neural activity into a developmental program? Here we show that long-term potentiation (LTP)-like synaptic activity within a cellular network of mature hippocampal neurons promotes neuronal differentiation of newly generated cells. In co-cultures of precursor cells with primary hippocampal neurons, LTP-like synaptic plasticity induced by addition of glycine in Mg(2+)-free media for 5 min, produced synchronous network activity and subsequently increased synaptic strength between neurons. Furthermore, this synchronous network activity led to a significant increase in neuronal differentiation from the co-cultured neural precursor cells. When applied directly to precursor cells, glycine- and Mg(2+)-free solution did not induce neuronal differentiation. Synaptic plasticity-induced neuronal differentiation of precursor cells was observed in the presence of GABAergic neurotransmission blockers but was dependent on NMDA-mediated Ca(2+) influx. Most importantly, neuronal differentiation required the release of brain-derived neurotrophic factor (BDNF) from the underlying substrate hippocampal neurons as well as TrkB receptor phosphorylation in precursor cells. This suggests that activity-dependent stem cell differentiation within the hippocampal network is mediated via synaptically evoked BDNF signaling.

Objectives: To describe a surgical and anesthetic technique for chondrolaryngoplasty ("tracheal shaving") involving external translaryngeal needle insertion under general anesthesia, using a flexible fiberoptic bronchoscope and laryngeal mask airway., Design: Retrospective review of 31 patients who underwent chondrolaryngoplasty performed by a single surgeon., Setting: Academic medical center., Patients: Thirty-one consecutive patients presenting for aesthetic treatment of their thyroid cartilage., Results: The procedures were all successful, with no voice complications and only 1 transient anesthetic complication., Conclusion: Chondrolaryngoplasty with translaryngeal needle placement to identify the level of the anterior commissure is a safe, effective surgical technique that minimizes the most significant risks of the surgical procedure.

The authors investigated correlations between retrospective dream characteristics, food preferences, and eating attitudes. Graduate students (7 men, 42 women) at Santa Clara University were administered the MEGA food scale and the KJP Dream Inventory. High intake of organic food was positively correlated with reports of multiple dream factors. Conversely, high scores on preferences for fast food, potato chips, and carbohydrates were negatively correlated with several factors. Findings are discussed in terms of the hypothesis that certain foods may influence dreaming.

Background: In the course of adult hippocampal neurogenesis most regulation takes place during the phase of doublecortin (DCX) expression, either as pro-proliferative effect on precursor cells or as survival-promoting effect on postmitotic cells. We here obtained quantitative data about the proliferative population and the dynamics of postmitotic dendrite development during the period of DCX expression. The question was, whether any indication could be obtained that the initiation of dendrite development is timely bound to the exit from the cell cycle. Alternatively, the temporal course of morphological maturation might be subject to additional regulatory events., Results: We found that (1) 20% of the DCX population were precursor cells in cell cycle, whereas more than 70% were postmitotic, (2) the time span until newborn cells had reached the most mature stage associated with DCX expression varied between 3 days and several weeks, (3) positive or negative regulation of precursor cell proliferation did not alter the pattern and dynamics of dendrite development. Dendrite maturation was largely independent of close contacts to astrocytes., Conclusion: These data imply that dendrite maturation of immature neurons is initiated at varying times after cell cycle exit, is variable in duration, and is controlled independently of the regulation of precursor cell proliferation. We conclude that in addition to the major regulatory events in cell proliferation and selective survival, additional micro-regulatory events influence the course of adult hippocampal neurogenesis.

Minimal access surgical techniques have been described for diskectomy and laminectomy procedures performed through tubular exposures. Tubular exposures, however, restrain visibility to a fixed diameter and require co-axial instrument manipulation. An independent blade retractor system has been developed to overcome the obstacles of working through a tube. Decompression and circumferential fusion can be accomplished through this minimal access exposure via a combination of laminectomy and transforaminal lumbar interbody fusion (TLIF) coupled with minimally invasive pedicle screw fixation. Herein, we describe a minimally-invasive technique for TLIF exposure. Illustrations, intraoperative photographs, and fluoroscopic images supplement this technique. We found that the described minimally-invasive system provides comparable exposure to the traditional-open techniques with the benefits of minimally-invasive techniques. Additionally, it does not have the added constraints of a tubular system. We were able to perform TLIFs without any additional complications. Minimal access decompression and TLIF can be performed safely and effectively using this minimally-invasive system. Besides the retractor system, no additional specialized instruments are required. An operative microscope is not required, in fact, all our cases were performed using operative loupes. The light attachment provides superb visbility without the discomfort of having to wear a headlight. Thus far we have found no added risks or complications using this system. We are currently working on long-term analysis and follow-up to further evaluate this system's efficacy.