Search

Over the past century, age-related diseases, such as cancer, type-2 diabetes, obesity, and mental illness, have shown a significant increase, negatively impacting overall quality of life. Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels, including transcriptional, translational, and post-translational processes, resulting from cellular stress and circadian derangements. The circadian clock emerges as a key regulator, sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes, such as stem-cell function, cellular stress responses, and inter-tissue communication, which become disrupted during aging. Given the crucial role of hypothalamic circuits in regulating organismal physiology, metabolic control, sleep homeostasis, and circadian rhythms, and their dependence on these processes, strategies aimed at enhancing hypothalamic and circadian function, including pharmacological and non-pharmacological approaches, offer systemic benefits for healthy aging. Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions, like the hypothalamus, while reducing side effects associated with systemic drug delivery, thereby presenting new therapeutic possibilities for diverse age-related conditions., (Copyright © 2024 Copyright: © 2024 Neural Regeneration Research.)

Mannheimia haemolytica is the main bacterial pathogen isolated in bovine respiratory disease (BRD), a common disease affecting calves before weaning. Previous research has shown that experimental infection with bovine herpesvirus 1, a respiratory virus, decreases plasma zinc (Zn) levels. However, changes in plasma Zn concentrations in calves experimentally infected with M. haemolytica have not been studied thus far. The objective of this study was to evaluate the effect of experimental infection with M. haemolytica on plasma Zn concentration in calves. Total leukocyte count and bovine respiratory disease (BRD) clinical score were also evaluated. We conducted a 6-day trial in 14 male Holstein calves randomly assigned to one of two groups, experimental (EG, n = 8) and control (CG, n = 6). Animals in EG were intrabronchially inoculated with M. haemolytica (6.5 × 10 6  CFU/mL) on day 0 of the trial. Plasma Zn levels were affected by time, treatment, and time by treatment interaction, being lower in EG compared with CG on days 1, 2, and 3. Differences in total leukocyte count were significant on day 1, observing a tendency on day 3. BRD clinical score differed between groups, being higher in EG throughout the trial. We conclude that experimental M. haemolytica infection reduced plasma Zn concentration in clinically ill calves, suggesting that the clinical condition of animals (healthy/ill) should be considered to better interpret plasma Zn values.

Zinc (Zn) has important functions in mammalian reproductive processes. In cattle, Zn status can be classified as deficient, marginal, and adequate, depending on the plasma Zn concentration. In addition, Zn deficiency can lead to reproductive failure. The aim of this study was to investigate the effect of maternal Zn status at the beginning of a fixed-time artificial insemination (FTAI) treatment regimen on pregnancy rate in cattle, and evaluate the effect of supplementing in vitro fertilization (IVF) medium with Zn concentrations within the reference range for Zn status on sperm quality and IVF performance. Pregnancy rates of animals with marginal and adequate Zn status did not differ, and there were no Zn-deficient animals detected. Supplementation of 0.8 μg/mL Zn to IVF medium enhanced progressive motility, sperm viability, functional sperm membrane integrity (HOST), acrosomal integrity and sperm-zona binding, without modifying pronuclear formation, or development of embryos to the cleavage or blastocyst stage after IVF. In conclusion, the present results indicate pregnancy rates are not associated with maternal Zn status at the beginning of the FTAI treatment regimen if Zn status is marginal or adequate. Furthermore, supplementation of IVF medium with Zn at concentrations which is considered adequate for Zn status in cattle led to improved sperm quality, without having effects on embryo development in cattle., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Most patients with phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA)-related overgrowth spectrum become symptomatic early in life and need treatment before puberty. Recently, the specific inhibition of PIK3CA pathways has been proposed as a therapeutic option for these patients improving their surgical options and quality of life. Alpelisib, a specific alpha fraction inhibitor, has shown promising results., Case: A 17-year-old girl presented with severe involvement of her external genitalia with a combined vascular malformation in the context of congenital, lipomatous, overgrowth, vascular malformations, epidermal nevi and spinal/skeletal anomalies and/or scoliosis syndrome, needing frequent blood transfusions for anemia due to vaginal bleeding and use of a crutch for walking. After failure of treatment with rapamycin, compassionate treatment with alpelisib was started with excellent response., Summary and Conclusion: PIK3CA inhibitors might become a new option of treatment for PIK3CA-related overgrowth spectrum patients., (Copyright © 2019 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

The syndromes of wall-eyed monocular internuclear ophthalmoplegia and Millard-Gubler are very rare clinical complexes commonly caused by pontine infarction, hemorrhage, or tumors that compromise the paramedian tegmentum, medial longitudinal fascicle, and the basis pontis. We present the case of a 58-year-old female with an isolated pontine infarction characterized by acute vertigo, sudden horizontal diplopia due to ipsilateral internuclear ophthalmoplegia with exotropia, facial palsy and contralateral hemiparesis. This report analyzes, theorizes, and emphasizes the correlation between these atypical neurological findings, the pontine anatomy, and magnetic resonance imaging; encouraging the clinician to make expeditious diagnoses using the bedside skills and a high-quality oculomotor clinical examination. The phenotype and simultaneity of both syndromes makes this case a didactic exercise for the topo-diagnosis based on the neurology of eye movements, the intrinsic physiology of the pons, and the pathways that emerge or project towards it., Competing Interests: The authors have no conflicts of interest to declare.

Human SCGB1A1 protein has been shown to be significantly reduced in BAL, sputum, and serum from humans with asthma as compared with healthy individuals. However, the mechanism of this reduction and its functional impact have not been entirely elucidated. By mining online datasets, we found that the mRNA of SCGB1A1 was significantly repressed in brushed human airway epithelial cells from individuals with asthma, and this repression appeared to be associated with reduced expression of FOXA2. Consistently, both Scgb1A1 and FoxA2 were downregulated in an ovalbumin-induced mouse model of asthma. Furthermore, compared with wild-type mice, Scgb1a1 knockout mice had increased airway hyperreactivity and inflammation when they were exposed to ovalbumin, confirming the antiinflammatory role of Scgb1a1 in protection against asthma phenotypes. To search for potential asthma-related stimuli of SCGB1A1 repression, we tested T-helper cell type 2 cytokines. Both IL-4 and IL-13 repressed epithelial expression of SCGB1A1 and FOXA2. Importantly, infection of epithelial cells with human rhinovirus similarly reduced expression of these two genes, which suggests that FOXA2 may be the common regulator of SCGB1A1. To establish the causal role of reduced FOXA2 in SCGB1A1 repression, we demonstrated that FOXA2 was required for SCGB1A1 expression at baseline. FOXA2 overexpression was sufficient to drive promoter activity and expression of SCGB1A1 and was also able to restore the repressed SCGB1A1 expression in IL-13-treated or rhinovirus-infected cells. Taken together, these findings suggest that low levels of epithelial SCGB1A1 in asthma are caused by reduced FOXA2 expression.

Background: Because of its superior sensitivity and specificity, multianalyte high-performance liquid chromatography coupled with tandem mass spectrometry has become the gold standard in clinical toxicology. Although several qualitative and quantitative liquid chromatography coupled with tandem mass spectrometry assays on various mass spectrometry platforms have been described in the literature, most methods either analyze only a limited number of compounds and/or require tedious and time-consuming sample preparation., Methods: A major challenge in urine toxicology screening is the minimization of false-negative and false-positive results. This was addressed by screening for a comprehensive panel of 136 compounds of importance for pain and drug addiction clinics, using high-end, high-sensitivity, fast-scanning mass spectrometry in combination with simultaneous structural confirmation based on ion ratios. The assay was validated and successfully participated in proficiency challenges., Results: The assay met all predefined acceptance criteria. The lower limit of quantifications ranged from 10 to 100 ng/mL. Interday trueness and imprecisions ranged from 73.8% to 116.2% and 2.4%-20.0%, respectively. The total assay run time was 10 minutes., Conclusions: We developed and successfully validated a robust, sensitive, and specific liquid chromatography coupled with tandem mass spectrometry-based urine toxicology screening platform that allows for the addition of drugs to quickly adjust to new clinical needs. To date, more than 3000 clinical samples have successfully been analyzed. Our results also indicated that such a quantitative multianalyte assay is pushing against the limits of current fast-scanning MS/MS instrumentation and that the number of analytes and their internal standards must be balanced with acceptable sensitivity, reproducibility, structural confirmation, and the ability to reliably quantify, all of which was achieved.

Human rhinovirus (RV) is the major cause of common cold, and it also plays a significant role in asthma and asthma exacerbation. The airway epithelium is the primary site of RV infection and production. In contrast, monocytic cells (e.g., monocytes and macrophages) are believed to be nonpermissive for RV replication. Instead, RV has been shown to modulate inflammatory gene expressions in these cells via a replication-independent mechanism. In the study presented here, replication of RV16 (a major-group RV) was found to be significantly enhanced in monocytes when it was cocultivated with airway epithelial cells. This effect appeared to be mediated by secretory components from epithelial cells, which stimulated RV16 replication and significantly elevated the expression of a number of proinflammatory cytokines. The lack of such an effect on RV1A, a minor-group RV that enters the cell by a different receptor, suggests that intercellular adhesion molecule 1 (ICAM1), the receptor for major-group RVs, may be involved. Indeed, conditioned media from epithelial cells significantly increased ICAM1 expression in monocytes. Consistently, ICAM1 overexpression and ICAM1 knockdown enhanced and blocked RV production, respectively, confirming the role of ICAM1 in this process. Thus, this is the first report demonstrating that airway epithelial cells direct significant RV16 replication in monocytic cells via an ICAM1-dependent mechanism. This finding will open a new avenue for the study of RV infection in airway disease and its exacerbation.

Introduction and Objective: This work presents deeper studies of comorbidity between anxiety and vestibular pathology. The aim of this work was to comprehend the reasons why patients do not feel «fully recovered» even though the treating professionals discharge them. We studied the features of personality that can favour the continuity of the condition., Methods: The questionnaire for measuring the emotional impact of vertigo makes it possible to determine if the patient has a psychological style with a tendency to develop pathological anxiety levels. Anxiety is a subjective characteristic determinant in difficulties with medical treatment. The questionnaire was applied to 198 patients in Argentina and Mexico in parallel. Each pathology was treated by standard medical procedures. The study focused on determining the correlation between «feeling fully recovered or not at the end of treatment» and the questionnaire scores obtained before the approach., Results: In more than 80% of cases, high scores (>15 points) on the questionnaire were correlated with the difficulty presented by the patients for full recovery from the pathology after medical treatment., Conclusions: The objective assessments (duration and intensity of symptoms, time of onset of the disease, etc.) do not exactly predict possible difficulties during treatment of vertigo. Consequently, we consider the patient's subjective assessment of how the vestibular pathology affects him or her to be determinant. That key information allows us to predict the course of the illness and the probability of a full recovery., (Copyright © 2013 Elsevier España, S.L. All rights reserved.)

The choice of a venous access system to provide safe blood collection and reliable analytical results for that sample is of paramount importance in any accident and emergency department. The objective of this study was to identify the factors associated with haemolysis in venous blood samples, where the variables studied were: type of venipuncture (needle and catheter), type of catheter (3 catheters of 3 different materials) and diameter of the catheter. The sample was obtained from all patients who required a blood test in the accident and emergencies department of the Virgen del Camino Hospital over 34 days, collected in 3 different periods (September-November), involving a total of 1.933 procedures. Positive haemolysis determined by laboratory technicians was found in 2% (7/348) of samples obtained by needle compared to 14% (222/1585) obtained by catheter. We observe an 8% (39/475) of haemolysis in the samples taken by protective Teflon catheter, 18% (77/426) by Protectiv plus polyurethane and 15% (106/684) by BD-Nexiva Vialone. The haemolysis index fell with an increase in the size of the catheter, those of 18G showing 13% (115/867) and those of 20G showing 15% (107/708). The combination of catheter type and size maintains the smallest percentages of haemolysis in Teflon catheters and high diameters of 18G with 6% (19/301), less than half the haemolysis of the polyurethane catheters and a third of that for Vialone catheters respectively.

1. Chronic respiratory disease (CRD) caused by Mycoplasma synoviae in association with Escherichia coli is the disease most frequently encountered in poultry in Mexico. 2. Differences of antimycoplasmal activity, pharmacokinetics and cost among fluoroquinolones were the impetus for this clinical evaluation of efficacy of enrofloxacin and norfloxacin-nicotinate in broilers with CRD. 3. A total of 99,600 broilers, naturally infected with M. synoviae and E. coli, were treated with enrofloxacin (10 mg/kg/d for 3 d) (n = 49,800) or norfloxacin-nicotinate (20 mg/kg/d for 3 d) (n = 49,800). 4. Based on survivor analysis, there were no significant differences of efficacy of the 2 drugs. Survivor probabilities were above 0.99. 5. These results indicate that enrofloxacin and norfloxacin-nicotinate are efficacious for treatment of CRD. Questions remaining to be answered by other studies include: public health concern about the use of fluoroquinolones for the treatment of CRD; clinical superiority of one of these drugs on the basis of an attribute other than antimicrobial activity, such as cost:benefit ratio or ability to prevent bacterial resistance. 6. Clinical efficacy is not a relevant variable in assessing whether norfloxacin-nicotinate or enrofloxacin should be used for the treatment of CRD associated with E. coli in broilers.

We studied clinical and EEG features of 36 cases with congenital malformations of the CNS. Patients were followed at the outpatient clinic of Hospital Cayetano Heredia and of Hogar Clinica San Juan de Dios in Lima-Peru, from January 1984 to June 1992. Eighty percent of the patients had convulsive syndromes and mental retardation. The most frequent malformation was agenesis of corpus callosum, and it was not possible to find a "typical" EEG pattern. The second were porencephalic cysts, with a good clinical-EEG correlation. There were two typical cases of schizencephaly, one of hemimegalencephaly with good prognosis, and one of holoprosencephaly. The results are compared to those obtained for a series we previously reported. Data discussed take into account reports on the subject registered in the literature. It is concluded that EEG is an useful method to evaluate possible CNS malformations in developing countries.