Involvement of the GABAA Receptor in the Antidepressant-Like Effects Produced by Low and High Doses of the Flavonoid Chrysin in the Rat: A Longitudinal Study.

BACKGROUND: The flavonoid chrysin produces rapid and long-lasting anxiolytic- and antidepressant-like effects in rats. However, it is not known whether low and high doses of chrysin produce differential anti-immobility effects through the Gamma-Aminobutyric Acid sub-type A (GABAA) receptor. The goal of this work was therefore to compare low and high doses of chrysin for their effects on depression-like behavior in a longitudinal study. Moreover, chrysin was compared with the serotonergic fluoxetine and Gamma-Aminobutyric Acid (GABA)ergic allopregnanolone, and its involvement with the GABAA receptor after chronic treatment was also investigated. METHODS: Male Wistar rats were assigned to five groups (n = 8 each): vehicle, 1 mg/kg chrysin, 5 mg/kg chrysin, 1 mg/kg fluoxetine, and 1 mg/kg allopregnanolone. In the first experiment, treatments were injected daily and the effects on locomotor activity and the forced swim test were evaluated at 0, 1, 14, and 28 days of treatment, and 48 h after the final treatment. In the second experiment, similar groups were treated for 28 days with injection of 1 mg/kg picrotoxin to investigate the role of the GABAA receptor. Depending on the experimental design, one- and two-way analysis of variance (ANOVA) tests were used for statistical analysis, with p < 0.05 set as the criteria for significance. RESULTS: In both experiments, the treatments did not alter locomotor activity. However, low and high doses of chrysin, allopregnanolone, and fluoxetine gradually produced antidepressant-like effects in the forced swim test, and maintained this effect for 48 h post-treatment, except with low dose chrysin. Picrotoxin blocked the antidepressant-like effects produced by low dose chrysin, but did not affect those produced by high dose chrysin, allopregnanolone, or fluoxetine. CONCLUSIONS: The differential antidepressant-like effects caused by low and high doses of chrysin are time-dependent. Low dose chrysin produces a rapid antidepressant-like effect, whereas high dose chrysin produces a delayed but sustained the effect, even 48 h after withdrawal. The effect with high dose chrysin was similar to that observed with allopregnanolone and fluoxetine. The mechanism for the antidepressant-like effect of low chrysin appears to be GABAergic, whereas the effect of high dose chrysin may involve other neurotransmission and neuromodulation systems related to the serotonergic system.

The Importance of Having a Single, Dedicated Medical Team to Treat Congenital Talipes Equinovarus Using the Ponseti Method: A Retrospective Analysis of Treatment Outcomes After 3 Years of Follow-up.

BACKGROUND: Congenital talipes equinovarus (CTEV) is a relatively common pediatric orthopaedic disorder and a frequent cause of disability in adult populations. The Ponseti method has emerged as the generally preferred for treating children with CTEV. Strict adherence to this technique's basic principles is critical to achieving favorable outcomes. In 2013, our institution decided that every case of pediatric CTEV would be treated by a single dedicated medical team. The present study aimed to compare the treatment outcomes of children with CTEV treated using the Ponseti method in period I (multiple surgeons) versus those in period II (single dedicated team). PATIENTS AND METHODS: We included respectively the children with CTEV treated using the Ponseti method in Geneva University Hospitals' pediatric units from 2007 to 2018. Data on patient demographics, clinical characteristics, and the treatment outcomes were collected. The primary outcome was the number of relapsed feet (treatment failure) after 3 years of follow-up. The 2 periods' outcomes were compared using χ 2 and independent Student t -tests. Run charts were used to report yearly rates of complications, minor and major recurrences, treatment failure, brace noncompliance, and feet that underwent tenotomy. RESULTS: A total of 48 feet (32 patients) and 42 feet (29 patients) in periods I and II were included. The periods showed similar rates for participants' characteristics. The run charts illustrated the overall improvements in treatment outcomes in period II. A total of 8 relapsed feet (5 patients) were reported, all during period I. CONCLUSIONS: Since all the pediatric CTEV patients at our institution began to be treated by a single dedicated medical team, we have observed a decrease in all recurrences and complications and an absence of treatment failure. These results highlight the importance of the continuity of care and strict adherence to the Ponseti method. LEVEL OF EVIDENCE: Level-III Retrospective comparative study.

Validation of the Mexican version of the EORTC QLQ-CR29 in patients with colorectal cancer.

BACKGROUND: The evaluation of the quality of life (QoL) of patients with colorectal cancer (CRC) is an essential measure to measure the impact of the disease and treatments on the lives of patients. However, in Latin America there is no validated and reliable instrument to assess this construct. OBJECTIVES: This study aims to validate the EORTC QLQ-CR29 instrument in the Mexican population with CRC. METHODS: This study aims to validate the EORTC QLQ-CR29 instrument in the Mexican population with CRC. The study used an instrumental design and a nonprobabilistic sample due to availability, made up of 251 patients with CRC, with an average age of 54.7 ± 12.28 years. Exploratory and confirmatory factor analyses were performed, as well as concurrent validity tests. RESULTS: The exploratory factorial analysis yielded 4 factors that explained 51.64% of the variance, with a Cronbach reliability coefficient of .766 and an Omega index of .725. The confirmatory factor analysis indicated that the proposed theoretical model fits the data almost perfectly, with an error close to 0, which shows that it is a balanced and parsimonious instrument to measure the QoL of the patients with CRC. SIGNIFICANCE OF RESULTS: The EORTC QLQ-CR29 instrument proved to be a valid and reliable instrument for use in clinical care and research directed at patients with CRC in Mexico. Its use is recommended by multidisciplinary health teams in oncology in Mexico, since it allows knowing the patient's perspective on the impact of CRC on their life, guiding therapeutic decision-making and being a primary outcome measure.

Cultural adaptation process of cancer-related interventions: A step-by-step guide.

INTRODUCTION: To contribute to the reduction and elimination of cancer-related local and global health disparities, interventions must be culturally adapted to reach diverse cultural groups and demonstrate success in improving clinical and psychosocial outcomes. We provide step-by-step information on the conceptual and methodological challenges involved in culturally adapting interventions and provide guidelines, suggestions, tools, and concrete steps for implementing the process. METHODS: This article provides information, guidelines, suggestions, tools, and concrete steps, based on three rigorous models of cultural adaptations, for implementing this process, followed with examples from the field, to illustrate the conceptual and methodological challenges involved in culturally adapting interventions. CONCLUSION: Our systematic step-by-step approach recommends (1) the guidance of well-established research models; (2) use of multiple data sources and input from various stakeholders (i.e., from patients and providers); (3) qualitative and quantitative data usage and integration; (4) a steering committee with multiple perspectives, stakeholders assessments, and qualitative analyses; (5) consensus meetings; and (6) diverse representation on the steering committee and/or research team.

Use of telehealth for psychosocial oncology: A mixed methods study about barriers to and opportunities with Latino patients from Latin America, Spain, and the United States.

OBJECTIVES: Telehealth for mental healthcare expanded rapidly with the COVID-19 pandemic's onset; however, global access disparities emerged. Telehealth challenges and opportunities for Latino cancer patients from different geographical regions must be explored. METHODS: A cross-sectional online survey (March-July 2021) of mental health providers, serving Latino cancer patients in Latin America, United States, and Spain, contained close-ended questions related to the use of telehealth during the pandemic and open-ended questions on recommending/not recommending telehealth. RESULTS: In a sample of 148 providers from 21 countries, 60.5% reported that at least some of their patients had difficulties with Internet speed and connectivity and lacked knowledge about using electronic devices (43.2%) or the Internet (45.4%). Lacking privacy at home (66.0%) and childcare (26.0%) were reported patient challenges. Internet connectivity or speed were issues for providers (43.2%) themselves. Improving patient reach was a reported telehealth benefit (64.2%). Geographical access (43.2%) and physical limitations (35.8%) were considerations in offering telehealth. Considerations for not recommending telehealth were patient age (24.3%) and lacking technological knowledge (29.1%). CONCLUSIONS: Telehealth for mental healthcare may improve patient access issues caused by geographical and transportation conditions and patient functionality. Findings provide insight into telehealth benefits and challenges in Latino patient populations. Future studies should examine patient access and use by region.

Data-Driven Approaches Used for Compound Library Design for the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease in older individuals worldwide. Pharmacological treatment for such a disease consists of drugs such as monoamine oxidase B (MAO-B) inhibitors to increase dopamine concentration in the brain. However, such drugs have adverse reactions that limit their use for extended periods; thus, the design of less toxic and more efficient compounds may be explored. In this context, cheminformatics and computational chemistry have recently contributed to developing new drugs and the search for new therapeutic targets. Therefore, through a data-driven approach, we used cheminformatic tools to find and optimize novel compounds with pharmacological activity against MAO-B for treating PD. First, we retrieved from the literature 3316 original articles published between 2015-2021 that experimentally tested 215 natural compounds against PD. From such compounds, we built a pharmacological network that showed rosmarinic acid, chrysin, naringenin, and cordycepin as the most connected nodes of the network. From such compounds, we performed fingerprinting analysis and developed evolutionary libraries to obtain novel derived structures. We filtered these compounds through a docking test against MAO-B and obtained five derived compounds with higher affinity and lead likeness potential. Then we evaluated its antioxidant and pharmacokinetic potential through a docking analysis (NADPH oxidase and CYP450) and physiologically-based pharmacokinetic (PBPK modeling). Interestingly, only one compound showed dual activity (antioxidant and MAO-B inhibitors) and pharmacokinetic potential to be considered a possible candidate for PD treatment and further experimental analysis.

The Hypotensive and Vasodilatory Effects Observed in Rats Exposed to Chiranthodendron pentadactylon Larreat Flowers Can Be Attributed to Cyanidin 3-O-Glucoside.

Chiranthodendron pentadactylon Larreat is a tree native to southeastern Mexico and Guatemala. Its flower is used in Mexican folk medicine to treat a variety of diseases, including conditions of blood pressure. However, scientific information on its usefulness in this pathology is lacking. The present study evaluates the effect of a methanolic extract (ME) from the flower and its active constituents on heart rate (HR) and mean arterial pressure (MAP) in anesthetized rats (MAPHR). The study also analyzed the effects on rat-isolated aortic rings (RIAR) and the rat mesenteric arterial bed (MABR). Active fractions were chromatographed, which led to the isolation of cyanidin 3-O-glucoside (C3G) identified through HPLC. The Chiranthodendron pentadactylon flowers produced hypotensive and vasorelaxant effects associated with C3G. The vasorelaxant effect is a mechanism underlying the synthesis and release of nitric oxide (NO). Neither cholinergic receptors nor prostaglandins are involved. ME and C3G cause cardiovascular depression in anesthetized rats via cholinergic and prostanoid mechanisms. Our research expands the scientific understanding of the flowers on the rat cardiovascular system. This amplifies the appreciation of the flower's ethnomedicine employed to control blood pressure. However, researchers need to conduct toxicity studies to determine the safety of this plant.

Discovering Potential Compounds for Venous Disease Treatment through Virtual Screening and Network Pharmacology Approach.

Peripheral venous hypertension has emerged as a prominent characteristic of venous disease (VD). This disease causes lower limb edema due to impaired blood transport in the veins. The phlebotonic drugs in use showed moderate evidence for reducing edema slightly in the lower legs and little or no difference in the quality of life. To enhance the probability of favorable experimental results, a virtual screening procedure was employed to identify molecules with potential therapeutic activity in VD. Compounds obtained from multiple databases, namely AC Discovery, NuBBE, BIOFACQUIM, and InflamNat, were compared with reference compounds. The examination of structural similarity, targets, and signaling pathways in venous diseases allows for the identification of compounds with potential usefulness in VD. The computational tools employed were rcdk and chemminer from R-Studio and Cytoscape. An extended fingerprint analysis allowed us to obtain 1846 from 41,655 compounds compiled. Only 229 compounds showed pharmacological targets in the PubChem server, of which 84 molecules interacted with the VD network. Because of their descriptors and multi-target capacity, only 18 molecules of 84 were identified as potential candidates for experimental evaluation. We opted to evaluate the berberine compound because of its affordability, and extensive literature support. The experiment showed the proposed activity in an acute venous hypertension model.

Behavioral Despair Is Blocked by the Flavonoid Chrysin (5,7-Dihydroxyflavone) in a Rat Model of Surgical Menopause.

Women have a high susceptibility to the negative effects of stress. Hormonal changes experienced throughout their reproductive life partially contribute to a higher incidence of anxiety and depression symptoms, particularly, during natural or surgical menopause. In preclinical research, the flavonoid chrysin (5,7-dihydroxyflavone) exerts anxiolytic- and anti-despair-like effects; however, it is unknown whether chrysin exerts a protective effect against the behavioral changes produced by acute stress on locomotor activity and behavioral despair in rats at 12-weeks post-ovariectomy. Ovariectomized female Wistar rats were assigned to eight groups: vehicle group (10% DMSO), three groups with chrysin and three groups with the same dose of allopregnanolone (0.5, 1, and 2 mg/kg), and one group with diazepam (2 mg/kg). The treatments were administered for seven consecutive days and the effects were evaluated in the locomotor activity and swimming tests. Chrysin (2 mg/kg) increased the latency to first immobility and decreased the total immobility time in the swimming test as the reference drugs allopregnanolone and diazepam (2 mg/kg); while locomotor activity prevented the behavioral changes produced by swimming. In conclusion, chrysin exerts a protective effect against the behavioral changes induced by acute stress, similarly to the neurosteroid allopregnanolone and the benzodiazepine diazepam in rats subjected to a surgical menopause model.

Quality of life, anxiety, depression, and distress in patients with advanced and metastatic lung cancer.

OBJECTIVE: Lung cancer (LC) patients have shown a predisposition for developing emotional and physical symptoms, with detrimental effects on the quality of life (QoL). This study evaluates the bidirectional relationship between main psychological disorders and clinical/sociodemographic factors with the QoL. METHODS: In this observational cross-sectional study, patients with a confirmed LC diagnosis from February 2015 to March 2018 were eligible for this study. Each participant completed screening instruments of anxiety, depression, distress, and QoL assessment. Other relevant clinical data were extracted from electronic health records. Then comparisons, correlations, and logistic regression analyses were performed. RESULTS: Two hundred and four cases were eligible; of them, the median age was 61 (24-84) years, most had clinical stage IV (95%), and most were under first-line therapy (53%). Concerning psychological status, 46% had symptoms of emotional distress, 35% anxiety, and 31% depression. Patients with psychological disorders experienced a worse global QoL than those without psychological impairment (p < 0.001). Increased financial issues and physical symptoms, combined with lower functioning, were also significantly associated with anxiety, depression, and distress. In the multivariate analysis, female sex and emotional distress were positively associated with an increased risk of depression; likewise, female sex, low social functioning, insomnia, and emotional distress were associated with anxiety. CONCLUSIONS: Emotional symptoms and QoL had a significant bidirectional effect on this study; this underscores the necessity to identify and treat anxiety, depression, and distress to improve psychological well-being and the QoL in LC patients.

Validation of the Mexican version of the Schedule of Attitudes Toward Hastened Death in patients undergoing palliative care in Mexico.

OBJECTIVES: The Schedule of Attitudes Toward Hastened Death (SAHD) has emerged as a valid and reliable tool to assess the wish to hasten death (WTHD) among patients diagnosed with advanced cancer; however, the instrument has never been culturally adapted and validated for patients in Mexico. This study sought to validate and abbreviate the SAHD tool for use among patients attending the Palliative Care Service of the Instituto Nacional de Cancerología in Mexico. METHODS: The SAHD was culturally adapted from a previously published validation in patients from Spain. Eligible patients included Spanish literate subjects treated as outpatients in the Palliative Care Service, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3. Patients were asked to answer the Mexican version of SAHD (SAHD-Mx) instrument and the Brief Edinburgh Depression Scale (BEDS). RESULTS: A total of 225 patients were included in the study. Median positive response in the SAHD-Mx was 2 (range 0-18). Positive correlation was identified between the SAHD-Mx scale and ECOG performance status (r = 0.188, p = 0.005), as well as BEDS (r = 0.567, p < 0.001). SAHD-Mx displayed strong internal consistency (alpha = 0.85) and adequate reliability from test-retest phone interviews (r = 0.567, p < 0.001). Using the confirmatory factor analysis model, a factor was identified and the number of items was reduced to 6, including items 4, 5, 9, 10, 13, and 18. SIGNIFICANCE OF RESULTS: The SAHD-Mx emerges as an adequate tool, with appropriate psychometric characteristics, for assessing WTHD among patients diagnosed with cancer undergoing palliative care in Mexico. .

Detection of psychosocial distress in cancer patients: A survey of Mexican oncologists.

Purpose: Identification of patients' distress is relevant for an on-time referral to psychosocial treatment. The objective was to assess the implementation of the guidelines for distress managing in Mexican oncologists based on the NCCN guidelines.Design: The study was non-experimental and cross-sectional.Sample: Two hundred thirty-one oncologists participated with an average age of 38 ± 11 years.Methods: The likelihood of distress assessment was quantitatively evaluated.Findings: A high percentage of oncologists knew and used procedures to assess psychosocial discomfort. However, a smaller percentage used a valid and reliable instrument. Factors associated with performing distress identification procedures were knowing the distress guidelines and lack of time. Factors for questionnaire usage are the availability of brief instruments and the percentage of patients suffering from stress.Implications for Psychosocial Providers: Psychosocial providers should develop strategies to educate and ensure that oncologists are familiar with guidelines on distress in oncology. More dissemination of screening procedures and referral to psychosocial programs in oncology is required. Integrating a distress screening program involving psychosocial providers and oncologists should be approached as a routine in high-quality cancer care, to reduce the stigma associated with mental health services.

Structural and Pharmacological Network Analysis of miRNAs Involved in Acute Ischemic Stroke: A Systematic Review.

Acute ischemic stroke (AIS) is among the main causes of mortality worldwide. A rapid and opportune diagnosis is crucial to improve a patient's outcomes; despite the current advanced image technologies for diagnosis, their implementation is challenging. MicroRNAs have been recognized as useful as biomarkers since they are specific and stable for characterization of AIS. However, there is still a lack of consensus over the primary miRNAs implicated in AIS. Here, we performed a systematic review of the literature covering from 2015-2021 regarding miRNAs expression during AIS and built structural networks to analyze and identify the most common miRNAs expressed during AIS and shared pathways, genes, and compounds that seem to influence their expression. We identified two sets of miRNAs: on one side, a set that was independent of geographical location and tissue (miR-124, miR-107, miR-221, miR-223, miR-140, miR-151a, miR-181a, miR-320b, and miR-484); and on the other side, a set that was connected (hubs) in biological networks (miR-27b-3p, miR-26b-5p, miR-124-3p, miR-570-3p, miR-19a-3p, miR-101-3p and miR-25-3p), which altered FOXO3, FOXO4, and EP300 genes. Interestingly, such genes are involved in cell death, FOXO-mediated transcription, and brain-derived neurotrophic factor signaling pathways. Finally, our pharmacological network analysis depicted a set of toxicants and drugs related to AIS for the first time.

Pharmacological, Neurochemical, and Behavioral Mechanisms Underlying the Anxiolytic- and Antidepressant-like Effects of Flavonoid Chrysin.

Chrysin (5,7-dihydroxyflavone) is a flavonoid isolated from plants, such as Passiflora coerulea, Passiflora incarnata, and Matricaria chamomilla. This natural molecule exerts diverse pharmacological effects, which includes antioxidant, anti-inflammatory, anti-cancer, neuroprotective, and anti-apoptotic effects. Additionally, in brain structures, such as the hippocampus, prefrontal cortex, raphe nucleus, and striatum, involved in the physiopathology of anxiety and depression disorders, several neuropharmacological activities, including the activation of neurotransmitter systems (GABAergic, serotonergic, dopaminergic, and noradrenergic), neurotrophic factors, such as brain-derived neurotrophic factor and the nerve growth factor, and some signaling pathways are affected. The results showed that the anxiolytic and antidepressant-like effects of chrysin occurs through its interaction with specific neurotransmitter systems, principally the GABAergic and the serotonergic, and activation of other neurotrophic factors. However, it is not possible to discard the antioxidant and anti-inflammatory activities of chrysin while producing its anxiolytic- and antidepressant-like effects. Although these results have been obtained principally from pre-clinical research, they consistently demonstrate the potential therapeutic use of flavonoid chrysin as an anxiolytic and antidepressant agent. Therefore, this flavonoid could be considered as a promising novel therapy for anxiety and depression disorders.

Dignity therapy in Mexican lung cancer patients with emotional distress: Impact on psychological symptoms and quality of life.

Lung cancer (LC) is the most frequent and deadly neoplasm in the world, and patients have shown a tendency to have more emotional distress than other cancer populations. Dignity Therapy (DT) is a brief intervention aimed to improve emotional well-being in patients facing life-threatening illness. OBJECTIVE: To analyze the effect of DT on anxiety, depression, hopelessness, emotional distress, dignity-related distress, and quality of life (QoL) in a group of Mexican patients with stage IV LC undergoing active medical treatment with baseline emotional distress. METHOD: In this preliminary pretest-posttest study, patients received three sessions of DT and were evaluated with the HADS, Distress Thermometer, Patient Dignity Inventory, single-item questions, and QLQ-30. RESULTS: In total, 24 out of 29 patients completed the intervention. Statistically significant improvements were found in anxiety, depression, emotional distress, hopelessness, and dignity-related distress with large effect sizes. Patients reported that DT helped them, increased their meaning and purpose in life, their sense of dignity, and their will to live, while it decreased their suffering. No changes were found in QoL. SIGNIFICANCE OF RESULTS: DT was well accepted and effective in improving the emotional symptoms of LC patients with distress that were undergoing medical treatment. Although more research is warranted to confirm these results, this suggests that DT can be used in the context of Latin-American patients.

Low-Intensity Intradialytic Exercise Attenuates the Relative Blood Volume Drop Due to Intravascular Volume Loss during Hemodiafiltration.

INTRODUCTION: Patients in hemodiafiltration (HDF) eliminate volume overload by ultrafiltration. Vascular volume loss is among the main mechanisms contributing to adverse events such as intradialytic hypotension. Here, we hypothesize that the intradialytic exercise (IDEX) is an intervention that could improve the acute response of physiological mechanisms involved during vascular volume loss. To test this hypothesis, we evaluated the hemodynamic response to mild aerobic exercise during HDF. METHODS: Nineteen end-stage renal disease (ESRD) patients (11 women: 40 ± 10.8 years old, and 8 men: 42 ± 21 years old) receiving HDF thrice a week, with 6 months of previous physical conditioning, participated in this study. Three HDF sessions were scheduled for each patient: 1 resting in supine position, 1 resting in sitting position, and 1 doing aerobic exercise. The first 2 sessions were taken as control. The ultrafiltration rate was set to 800 mL/h in each session. The hemodynamic response was monitored through the relative blood volume (RBV), and cardiovascular variables measured noninvasively by photoplethysmography. Adequacy variables such as Kt/V and percentage reduction of urate, urea, creatinine (Cr), and phosphate were also monitored. FINDINGS: The decrease rate of the RBV was smaller in the session with IDEX compared to the sessions with no exercise. No differences were found neither in the cardiovascular variables nor in the adequacy variables among the 3 sessions. There were no hypotension events during the session with exercise, and 8 events during the sessions without exercise (p = 0.002). DISCUSSION: Mild exercise during HDF decreased the RBV drop and was associated with less hypotension events. The lack of differences in the hemodynamic variables suggests an adequate acute response of cardiovascular compensation variables to intradialytic hypovolemia.

Epigenetic variations due to nutritional status in early-life and its later impact on aging and disease.

Epigenetics refers to changes in gene function, not resulting from the primary DNA sequence, influenced by the environment. It provides a link between the molecular regulation of the genome and the environmental signals exposed during the life of individuals (including lifestyle, social behavior, development, and nutrition). Notably, early development (intrauterine or postnatal) is highly influenced by the adverse socioeconomic status that leads to malnutrition or obesity; these conditions induce changes over the fetal epigenetic programming and can be transferred by transgenerational inheritance, inducing alterations of the transcription of genes related to several metabolic and neurological processes. Moreover, obesity during pregnancy, and excessive gestational weight gain are associated with an increased risk of fatal pregnancy complications, and adverse cardio-metabolic, respiratory and cognitive-related outcomes of the future child. However, most of our knowledge in this field comes from experimental animal models, that partially resemble the nutritional effects of humans. In this context, nutritional effects implicated in historical famines represent valuable information about the transgenerational effects of undernutrition and stress. In the present review, we attempt to describe the most outstanding results from the most studied famines about the impact of malnutrition on the epigenome.

Infections after hematopoietic cell transplantation are not a burden for mortality at a limited-resource center in a developing country.

BACKGROUND: Hematopoietic cell transplantation (HCT) outcomes, including infectious complications, change between centers and countries. Thus, the aim of this study was to report the incidence of infections and isolated pathogens among recipients of HCT and the association with mortality at a tertiary referral center in Mexico. METHODS: Two hundred and eighty-two patients undergoing autologous or allogeneic HCT between January 2005 and December 2018 at the National Institute of Medical Sciences and Nutricion Salvador Zubiran were included. RESULTS: In autologous HCT (n = 176), within the preengraftment and the early postengraftment, 130 (74%) and 31 (18%) recipients presented infections, respectively. Within the preengraftment, the early postengraftment, and the late postengraftment, 81 (76%), 34 (33%), and 58 (60%) allogeneic HCT recipients presented infections, respectively. Non-relapse mortality (NRM) as a result of infections occurred in 1 (0.6%) and 5 (5%) autologous and allogeneic HCT recipients, respectively. CONCLUSIONS: Our results demonstrated that despite our limited resources, infections were not a significant burden for NRM among HCT recipients. More importantly, the isolation rates were higher than international studies, which could be explained by the existence of a specialized infectious diseases department and laboratory, which we consider key elements for the establishment of an HCT program worldwide.

Blocking properties of terguride at the 5-HT2 receptor subtypes mediating cardiovascular responses in the rat.

In vitro studies have suggested that terguride blocks the contractile and relaxant responses produced by 5-hydroxytryptamine (5-HT) via 5-HT2A/2B receptors. This study has now investigated terguride's blocking properties on central/peripheral 5-HT2 receptors in anaesthetized or pithed rats. Male Wistar anaesthetized/pithed rats were cannulated for recording blood pressure and heart rate and for i.v. administration of several compounds. In both groups of rats, i.v. bolus injections of 5-HT or (±)-DOI (a 5-HT2 receptor agonist; 1-1000 µg/kg) produced dose-dependent increases in diastolic blood pressure and heart rate. These responses were dose-dependently antagonized by terguride (10-3000 µg/kg). In anaesthetized rats, i.v. bolus injections of BW723C86 (a 5-HT2B receptor agonist; 1-1000 µg/kg) produced dose-dependent increases in diastolic blood pressure and not dose-dependent increases in heart rate, while in pithed rats, these responses were attenuated. The vasopressor responses elicited by BW723C86 in anaesthetized rats were dose-dependently blocked by terguride (10-300 µg/kg), whereas its the tachycardic responses were dose-independently blocked. These results, taken together, suggest that terguride behaved as an antagonist at the 5-HT2 receptors located in the central nervous system and (or) the systemic vasculature. This is the first evidence demonstrating that terguride can block central/peripheral 5-HT2 receptors mediating cardiovascular responses in anaesthetized or pithed rats.

Comparison of Subacromial Injection and Interscalene Block for Immediate Pain Management After Arthroscopic Rotator Cuff Repair.

PURPOSE: To compare the efficacy of a subacromial injection (SAI) with a single-shot interscalene block (ISB) for immediate postoperative pain relief after outpatient arthroscopic rotator cuff repair (ARCR). METHODS: We performed a retrospective chart review of consecutive patients who underwent ARCR. Patients received either an ISB before the procedure or an SAI after the procedure. Preoperative baseline patient characteristics were collected and compared. Visual analog scale (VAS) pain scores were recorded preoperatively, at 15-minute intervals over a 120-minute period in the postanesthesia care unit (PACU), and at discharge. Differences in VAS scores between groups were compared with known values of the minimal clinically important difference, and the percentage of patients with VAS scores below the patient acceptable symptom state was tabulated. Differences between preoperative characteristics were assessed using the Mann-Whitney U, Fisher exact, or χ2 test. The Mann-Whitney U test was also used to evaluate VAS scores and total time spent in the PACU between groups. RESULTS: The median VAS score was significantly lower in the ISB group at PACU admission, at all intervals throughout the PACU stay, and at discharge (P < .0001). The median total time in the PACU was 107 minutes (25th percentile-75th percentile, 90-120 minutes) and 210 minutes (25th percentile-75th percentile, 175-274 minutes) in the ISB and SAI groups, respectively (P < .0001). Between-group differences in VAS scores were greater than the values of the minimal clinically important difference at each measured interval. A total of 98% and 67% of patients in the ISB and SAI groups, respectively, were discharged with VAS scores below the patient acceptable symptom state of 3. CONCLUSIONS: Patients receiving an ISB experience significantly less pain than those receiving an SAI. In addition, they are discharged home from the PACU in half the time as patients receiving an SAI. On the basis of the comparative efficacy, an SAI cannot replace an ISB after ARCR. The ISB should therefore remain the standard of care as an adjunct to postoperative analgesia for patients who undergo outpatient ARCR. LEVEL OF EVIDENCE: Level III, retrospective, comparative therapeutic trial.