Activation of G Protein-Coupled Estrogen Receptor (GPER) Negatively Modulates Cardiac Excitation-Contraction Coupling (ECC) through the PI3K/NOS/NO Pathway.

The G-protein-coupled estrogen receptor (GPER) has been described to exert several cardioprotective effects. However, the exact mechanism involved in cardiac protection remains unclear. The aim of this study is to investigate the role of GPER activation on excitation-contraction coupling (ECC) and the possibility that such effect participates in cardioprotection. The cardiac myocytes of male Wistar rats were isolated with a digestive buffer and loaded with Fura-2-AM for the measurement of intracellular calcium transient (CaT). Sarcomere shortening (SS) and L-type calcium current (ICaL) were also registered. The confocal technique was used to measure nitric oxide (NO) production in cells loaded with DAF-FM-diacetate. Cardiac myocytes exposed to 17-ß-estradiol (E2, 10 nM) or G-1 (1 µM) for fifteen minutes decreased CaT, SS, and ICaL. These effects were prevented using G-36 (antagonist of GPER, 1 µM), L-Name (NO synthase -NOS- inhibitor, 100 nM), or wortmannin (phosphoinositide-3-kinase -PI3K- inhibitor, 100 nM). Moreover, G1 increased NO production, and this effect was abolished in the presence of wortmannin. We concluded that the selective activation of GPER with E2 or G1 in the isolated cardiac myocytes of male rats induced a negative inotropic effect due to the reduction in ICaL and the decrease in CaT. Finally, the pathway that we proposed to be implicated in these effects is PI3K-NOS-NO.

Clinical and Radiological Differences between Patients Diagnosed with Acute Ischemic Stroke and Chameleons at the Emergency Room: Insights from a Single-Center Observational Study.

INTRODUCTION: Scarce data exist about clinical/radiological differences between acute ischemic strokes diagnosed in the emergency room (AISER) and stroke chameleons (SCs). We aimed at describing the differences observed in a comprehensive stroke center in Chile. METHODS: Prospective observational study of patients with ischemic stroke syndromes admitted to the emergency room (ER) of Clínica Alemana between December 2014 and October 2023. RESULTS: 1,197 patients were included; of these 63 (5.2%, 95% CI: 4.1-6.6) were SC; these were younger (p < 0.001), less frequently hypertensive (p = 0.03), and they also had lower systolic (SBP) (p < 0.001), diastolic blood pressures (DBP) (p = 0.011), and NIHSS (p < 0.001). Clinically, they presented less frequently gaze (p = 0.008) and campimetry alterations (p = 0.03), facial (p < 0.001) and limb weakness (left arm [p = 0.004], right arm (p = 0.041), left leg (p = 0.001), right leg p = 0.0029), sensory abnormalities (p < 0.001), and dysarthria (p < 0.001). Neuroradiological evaluations included less frequently large vessel occlusions (p = 0.01) and other stroke locations (p = 0.005); they also differed in their etiologies (p < 0.001). Brainstem strokes (p < 0.001) and extinction/inattention symptoms (p < 0.001) were only seen in AISER. In multivariate analysis, younger age (OR: 0.945; 95% CI: 0.93-0.96), DBP (OR: 0.97; 95% CI, 0.95-0.99), facial weakness (OR: 0.39; 95% CI: 0.19-0.78), sensory abnormities (OR: 0.16.18; 95% CI, 0.05-0.4), infratentorial location (OR: 0.36; 95% CI, 0.15-0.78), posterior circulation involvement (OR: 3.02; 95% CI, 1.45-6.3), cardioembolic (OR: 3.5; 95% CI, 1.56-7.99), and undetermined (OR: 2.42; 95% CI, 1.22-4.7; 95%) etiologies, remained statistically significant. A stepwise analysis including only clinical elements present on the patient's arrival to the ER, demonstrates that age (OR: 0.95; 95% CI: 0.94-0.97), DBP (OR: 0.97; 95% CI, 0.95-0.99), the presence of atrial fibrillation (OR: 2.22; 95% CI, 1.04-4.75, NIHSS (OR: 0.88; 95% CI, 0.71-0.89) and the presence in NIHSS of 1a level of consciousness (OR: 5.66; CI: 95% 1.8-16.9), 1b level of consciousness questions (OR: 3.023; 95% CI, 1.35-6.8), facial weakness (OR: 0.3; CI: 95% 0.17-0.8), and sensory abnormalities (OR: 0.27; 95% CI, 0.1-0.72) remained statistically significant. CONCLUSION: SC had clinical and radiological differences compared to AISER. An additional relevant finding is that neurological symptoms in a patient with atrial fibrillation, even with a negative diffusion-weighted imaging, should be carefully evaluated as a potential stroke until other causes are satisfactorily ruled out.

Cancer Prevalence in Children with Inborn Errors of Immunity: Report from a Single Institution.

BACKGROUND: Inborn Errors of Immunity (IEI) comprise several genetic anomalies that affect different components of the innate and adaptive responses, predisposing to infectious diseases, autoimmunity and malignancy. Different studies, mostly in adults, have reported a higher prevalence of cancer in IEI patients. However, in part due to the rarity of most of these IEI subtypes (classified in ten categories by the Primary Immunodeficiency Committee of the International Union of Immunological Societies), it is difficult to assess the risk in a large number of patients, especially during childhood. OBJECTIVE: To document the cancer prevalence in a pediatric cohort from a single referral institution, assessing their risk, together with the type of neoplasia within each IEI subgroup. METHOD: An extensive review of clinical records from 1989 to 2022 of IEI patients who at some point developed cancer before the age of sixteen. RESULTS: Of a total of 1642 patients with IEI diagnosis, 34 developed cancer before 16 years of age, showing a prevalence (2.1%) significantly higher than that of the general age matched population (0.22). Hematologic neoplasms (mostly lymphomas) were the most frequent malignancies. CONCLUSION: This study represents one of the few reports focused exclusively in pediatric IEI cases, describing not only the increased risk of developing malignancy compared with the age matched general population (a fact that must be taken into account by immunologists during follow-up) but also the association of the different neoplasms with particular IEI subtypes, thus disclosing the possible mechanisms involved.

Hysteroscopic subchorionic injection of methotrexate followed by laparoscopic excision of the gestational sac for the management of cesarean scar ectopic pregnancy: an innovative dual approach of a challenging pathology.

OBJECTIVE: To describe an effective two-step surgical approach for the management of cesarean scar ectopic pregnancies (CSEPs). CSEPs occur at an estimated frequency of 1 in 1,800 pregnancies, constituting approximately 6% of ectopic pregnancies in women with a history of prior cesarean delivery [1, 2]. Despite numerous recommended therapeutic approaches, the most effective treatment strategy remains uncertain [3]. DESIGN: We present an innovative double-step technique for the management of a patient with a CSEP involving hysteroscopic subchorionic injection of methotrexate (MTX), followed by laparoscopic resection of the residual gestational sac and simultaneous repair of the uterine defect. SETTING: Academic tertiary hospital. PATIENT: A 34-year-old G2P1001 with a history of prior cesarean section presented at 10 weeks of gestation. Ultrasound revealed a gestational sac within the niche of the previous cesarean scar, confirming the diagnosis of a CSEP. The patient included in this video gave consent for publication of the video and posting of the video online, including on social media, the journal website, scientific literature websites (such as PubMed, ScienceDirect, and Scopus, among others), and other applicable sites. INTERVENTION: The initial treatment involved hysteroscopic administration of MTX within the placental intervillous spaces, ensuring precise medication delivery. The administered dose of MTX was 1 mg/kg. Following the normalization of beta-human chorionic gonadotrophin (ß-hCG) levels, laparoscopic resection of the remaining gestational sac and reconstruction of the uterine wall defect were performed. MAIN OUTCOME MEASURES: We have implemented a management strategy focusing on ectopic pregnancy removal and addressing defect revision. The hysteroscopic approach allows for a clear assessment of the ectopic pregnancy and facilitates precise MTX administration, enhancing its effectiveness by increasing drug concentration within the placental intervillous space. Delaying surgical repair until after the ß-hCG levels have decreased reduces the risk of excessive bleeding during the procedure, as lower ß-hCG levels are associated with reduced vascularity at the ectopic site. Subsequent laparoscopic resection allows for complete removal of the remaining products of conception and repair of the defect, preserving the uterus and restoring normal anatomy. Compared to other surgical approaches, our two-step approach enables a more precise evaluation of placental implantation, making it a highly effective surgical method. RESULTS: We successfully managed a CSEP using a double-step technique. This involved hysteroscopic injection of subchorionic MTX, followed by laparoscopic resection of the residual gestational sac. Concurrently, we repaired the uterine defect. Both procedures were performed in an outpatient setting without complications detected during or after treatment. At the follow-up visit, the patient reported good health, and subsequent ultrasound confirmed an empty isthmocele. CONCLUSION: This sequential hysteroscopic and laparoscopic approach represents a definitive and effective minimally invasive surgical option for the treatment of CSEP.

Intravenous Thrombolysis in Patients 90 Years or Older with Moderate to Severe Acute Ischemic Stroke Increases Ambulation at Discharge and Is Safe: A Prospective Cohort Study from a Single Center in Santiago, Chile.

INTRODUCTION: The World Health Organization predicts that the global population aged 60 years and older will double by 2050, leading to a significant rise in the public health impact of acute ischemic stroke (AIS). Existing stroke guidelines do not specify an upper age limit for the administration of intravenous thrombolysis (IVT), although some suggest a relative exclusion criterion in patients aged ≥80 in the 3-4.5-h window. Many physicians avoid treating these patients with IVT, argumenting high risk and little benefit. Our aim was to investigate the efficacy and safety of IVT treatment in patients with non-minor AIS aged ≥90, admitted to our institution. The primary efficacy endpoint was the ability to walk at discharge (mRS 0-3), and the primary safety endpoints were death and symptomatic intracranial hemorrhagic transformation (sIHT) at discharge. METHODS: Patients with AIS aged ≥90 admitted to our center from January 2003 to December 2022 were included. They were selected if had an NIHSS ≥5, were previously ambulatory (prestroke mRS score 3 or less), and arrived within 6 h from symptom onset. Those treated or not with IVT were compared with univariate analysis. RESULTS: The mean age was 93.2 (2.4) years, and 51 (73.9%) were female. The admission mRS and NIHSS were 1 (IQR 0-2) and 14 (IQR 7-22), respectively. Thrombolyzed patients had a shorter time from symptom onset to door and lower glycemia on admission. IVT was associated with a higher proportion of patients achieving mRS 0-3 at discharge (p = 0.03) and at 90 days (p = 0.04). There were no differences between groups in the risk of death (p = 0.55) or sIHT (p = 0.38). CONCLUSION: In this small sample, ambulatory patients aged ≥90 with moderate or severe AIS treated with IVT had increased odds of being able to walk independently at discharge than those not treated, without safety concerns.

A time-efficient workflow to purify a library of alanine mutants of surface-exposed residues of the domain III of the envelope protein of dengue virus serotype 1.

Dengue complex is formed by four viral serotypes that cause the disease of the same name. Dengue is the arthropod-borne disease with the highest incidence worldwide. The envelope glycoprotein comprises three structural domains. The domain III (DIII) induces neutralizing antibodies and is involved in the interactions with soluble plasma factors from human host. Recombinant DIII proteins have been used as analytical tools for the characterization of virus-host interactions and have been evaluated as sub-unit vaccines. Here, we report a purification procedure of recombinant DIII protein and seventy-four alanine mutants refolding by size exclusion chromatography that allows obtaining highly homogeneous protein preparations and suitable for efficient purification and folding check. Four positions are identified that significantly affect either the protein expression or folding of recombinant DIIIE1, K310, G304, D330 and P332.

Corrigendum: Home-based exercise program in the indeterminate form of Chagas disease (PEDI-CHAGAS study): a study protocol for a randomized clinical trial.

[This corrects the article DOI: 10.3389/fmed.2022.1087188.].

Activity of domain III-specific antibodies in early convalescence: A case study.

The Dengue virus complex (DENV), formed by four serotypes, constitutes the most important arbovirus affecting humans. The structural domain III of their envelope protein (DIII) elicits strongly neutralizing serotype-specific antibodies. Contrasting results have been obtained regarding their role in the serum neutralizing activity of infected patients. We used a DENV immune serum from a secondary infection to examine the impact of characterizing the anti-DIII antibody response after affinity purification with recombinant DIII proteins to eliminate potential interferences from the interactions with human plasma proteins and other anti-DENV antibodies. Total anti-DENV IgG repertoire and anti-DIIIE antibodies were compared in functionality. In early convalescence, reactivity of anti-DIII antibodies is serotype specific and exhibits the strongest reactivity with infecting serotypes. Purification of anti-DIII antibodies emphasizes the reactivity profile as compared to total IgG fraction and serum. Serotype-specificity of the virus neutralization activity correlated with the apparent kD of the binding to recombinant DIIIs.

Quantum Lyapunov exponent in dissipative systems.

The out-of-time order correlator (OTOC) has been widely studied in closed quantum systems. However, there are very few studies for open systems and they are mainly focused on isolating the effects of scrambling from those of decoherence. Adopting a different point of view, we study the interplay between these two processes. This proves crucial in order to explain the OTOC behavior when a phase space contracting dissipation is present, ubiquitous not only in real life quantum devices but in the dynamical systems area. The OTOC decay rate is closely related to the classical Lyapunov exponent-with some differences-and more sensitive in order to distinguish the chaotic from the regular behavior than other measures. On the other hand, it is revealed as a generally simple function of the longest lived eigenvalues of the quantum evolution operator. We find no simple connection with the Ruelle-Pollicott resonances, but by adding Gaussian noise of ℏ_{eff} size to the classical system we recover the OTOC decay rate, which is a consequence of the correspondence principle put forward in Phys. Rev. Lett. 108, 210605 (2012)10.1103/PhysRevLett.108.210605 and Phys. Rev. E 99, 042214 (2019)10.1103/PhysRevE.99.042214.

Conditional expression of NanoLuc luciferase through a multimodular system offers rapid detection of antimalarial drug activity.

Conditional gene expression is a powerful tool to investigate putative vaccine and drug targets, especially in a haploid organism such as Plasmodium falciparum. Inducible systems based on regulation of either transcription, translation, protein or mRNA stability, among others, allow switching on an off the expression of any desired gene causing specific gain or loss of function phenotypes. However, those systems can be cumbersome involving the construction of large plasmids and generation of multiple transgenic parasite lines. In addition, the dynamic range of regulation achieved is not predictable for each individual gene and can be insufficient to generate detectable phenotypes when the genes of interest are silenced. Here, we combined up to three distinct inducible systems to regulate the expression of a single gene. Expression of the reporter NanoLuc luciferase was regulated over 40-fold, which correlates to the regulation achieved by each individual system multiplied by each other. We applied the conditionally expressed NanoLuc to evaluate the effect of fast-acting antimalarials such as chloroquine and artesunate as well as of slower-acting ones such as atovaquone. The conditionally expressed reporter allowed faster and more reliable detection of toxicity to the parasite, which correlated to the expected action of each compound. Bioluminescence achieved by the expression of this inducible highly sensitive reporter is therefore a promising tool to investigate the temporal effect of potential new antimalarials. This single plasmid combination system might also prove useful to achieve sufficient regulation of genes of interest to produce loss-of-function phenotypes.

Emergency laparoscopic intervention for fibrous band-induced intestinal obstruction and ischemia associated with Meckel's diverticulum: A case report.

INTRODUCTION AND IMPORTANCE: Meckel's diverticulum (MD) is a common congenital malformation of the digestive tract, often asymptomatic but occasionally leading to complications such as bowel obstruction and ischemia. Timely recognition and treatment of these complications are crucial. PRESENTATION OF CASE: We report the case of a 27-year-old male patient presenting with complete intestinal obstruction and ischemia of the ileum due to a fibrous band associated with MD. The patient presented with severe abdominal pain lasting for 10 h. Physical examination revealed a distended abdomen, antalgic position, and positive decompression. Laboratory tests showed leukocytosis and elevated lactic acid levels. Computed tomography revealed dilated small bowel loops with signs of intestinal ischemia. Emergency exploratory laparoscopy confirmed a complete ileum with ischemia and identified a fibrous band originating from the mesentery, strangulating the affected loop. The fibrous band was dissected and sectioned, confirming its association with the MD, which was resected with subsequent recovery of peristalsis and vascularization of the compromised segment. The patient had a favorable postoperative recovery without complications. DISCUSSION: MD is a rare cause of bowel obstruction, requiring a high index of suspicion for diagnosis. Despite the challenges in preoperative identification, early surgical intervention is crucial to prevent adverse outcomes. This case emphasizes the importance of promptly recognizing and managing MD-related complications to optimize patient outcomes. CONCLUSION: MD should be considered in cases of acute occlusive abdomen, despite its infrequent occurrence. Early diagnosis and timely surgical intervention are essential to minimize morbidity and mortality associated with MD-related complications.

Perillyl alcohol modulates activation, permeability and integrity of human brain endothelial cells induced by Plasmodium falciparum.

BACKGROUND: Cerebral malaria (CM) is a severe immunovasculopathy caused for Plasmodium falciparum infection, which is characterised by the sequestration of parasitised red blood cells (pRBCs) in brain microvessels. Previous studies have shown that some terpenes, such as perillyl alcohol (POH), exhibit a marked efficacy in preventing cerebrovascular inflammation, breakdown of the brain-blood barrier (BBB) and brain leucocyte accumulation in experimental CM models. OBJECTIVE: To analyse the effects of POH on the endothelium using human brain endothelial cell (HBEC) monolayers co-cultured with pRBCs. METHODOLOGY: The loss of tight junction proteins (TJPs) and features of endothelial activation, such as ICAM-1 and VCAM-1 expression were evaluated by quantitative immunofluorescence. Microvesicle (MV) release by HBEC upon stimulation by P. falciparum was evaluated by flow cytometry. Finally, the capacity of POH to revert P. falciparum-induced HBEC monolayer permeability was examined by monitoring trans-endothelial electrical resistance (TEER). FINDINGS: POH significantly prevented pRBCs-induced endothelial adhesion molecule (ICAM-1, VCAM-1) upregulation and MV release by HBEC, improved their trans-endothelial resistance, and restored their distribution of TJPs such as VE-cadherin, Occludin, and JAM-A. CONCLUSIONS: POH is a potent monoterpene that is efficient in preventing P. falciparum-pRBCs-induced changes in HBEC, namely their activation, increased permeability and alterations of integrity, all parameters of relevance to CM pathogenesis.

Who is in the emergency room matters when we talk about door-to-needle time: a single-center experience.

BACKGROUND: The efficacy of intravenous thrombolysis (IVT) is time-dependent. OBJECTIVE: To compare the door-to-needle (DTN) time of stroke neurologists (SNs) versus non-stroke neurologists (NSNs) and emergency room physicians (EPs). Additionally, we aimed to determine elements associated with DTN ≤ 20 minutes. METHODS: Prospective study of patients with IVT treated at Clínica Alemana between June 2016 and September 2021. RESULTS: A total of 301 patients underwent treatment for IVT. The mean DTN time was 43.3 ± 23.6 minutes. One hundred seventy-three (57.4%) patients were evaluated by SNs, 122 (40.5%) by NSNs, and 6 (2.1%) by EPs. The mean DTN times were 40.8 ± 23, 46 ± 24.7, and 58 ± 22.5 minutes, respectively. Door-to-needle time ≤ 20 minutes occurred more frequently when patients were treated by SNs compared to NSNs and EPs: 15%, 4%, and 0%, respectively (odds ratio [OR]: 4.3, 95% confidence interval [95%CI]: 1.66-11.5, p = 0.004). In univariate analysis DTN time ≤ 20 minutes was associated with treatment by a SN (p = 0.002), coronavirus disease 2019 pandemic period (p = 0.21), time to emergency room (ER) (p = 0.21), presence of diabetes (p = 0.142), hypercholesterolemia (p = 0.007), atrial fibrillation (p < 0.09), score on the National Institutes of Health Stroke Scale (NIHSS) (p = 0.001), lower systolic (p = 0.143) and diastolic (p = 0.21) blood pressures, the Alberta Stroke Program Early CT Score (ASPECTS; p = 0.09), vessel occlusion (p = 0.05), use of tenecteplase (p = 0.18), thrombectomy (p = 0.13), and years of experience of the physician (p < 0.001). After multivariate analysis, being treated by a SN (OR: 3.95; 95%CI: 1.44-10.8; p = 0.007), NIHSS (OR: 1.07; 95%CI: 1.02-1.12; p < 0.002) and lower systolic blood pressure (OR: 0.98; 95%CI: 0.96-0.99; p < 0.003) remained significant. CONCLUSION: Treatment by a SN resulted in a higher probability of treating the patient in a DTN time within 20 minutes.

ANTECEDENTES: La respuesta a la trombólisis intravenosa (TIV) es dependiente del tiempo. OBJECTIVO: Comparar los tiempo puerta-aguja (TPAs) de neurólogos vasculares (NVs) contra los de neurólogos no vasculares (NNVs) y médicos emergencistas (MEs), y determinar los elementos asociados a un PTA ≤ 20 minutos. MéTODOS: Análisis observacional prospectivo de pacientes con TIV tratados en Clínica Alemana entre junio de 2016 y septiembre de 2021. RESULTADOS: En total, 301 pacientes con TIV fueron tratados. El TPA promedio fue de 43,3 ± 23,6 minutos. Un total de 173 (57,4%) pacientes fueron evaluados por NVs, 122 (40,5%), por NNVs, y 6 (2,1%), por MEs; los TPAs promedios fueron de 40,8 ± 23; 46 ± 24,7 y 58 ± 22,5 minutos, respectivamente. Los TPAs ≤ 20 minutos fueron más frecuentes en pacientes tratados por NVs versus NNVs y MEs: 15%, 4% y 0%, respectivamente (odds ratio [OR]: 4,3; intervalo de confianza del 95% [IC95%]: 1,66­11,5; p = 0,004). El análisis univariado demostró que TPA ≤ 20 minutos se asoció con: tratamiento por NVs (p = 0,002), periodo de la pandemia de enfermedad por coronavirus 2019 (COVID-19; p = 0,21), tiempo a urgencia (p = 0,21), diabetes (p = 0,142), hipercolesterolemia (p = 0,007), fibrilación auricular (p < 0,09), puntaje en la National Institutes of Health Stroke Scale [NIHSS] (p = 0,001), presión arterial sistólica (p = 0,143) y diastólica menores (p = 0,21), Alberta Stroke Program Early CT Score (ASPECTS ; p = 0,09), oclusión de vasos cerebrales (p =0,05), uso de tecneteplase (p = 0,18), trombectomía (p = 0,13) y años de experiencia del médico (p < 0,001). El análisis multivariado demostró que ser tratado por NVs (OR: 3,95; IC95%: 1,44­10,8; p = 0,007), el puntaje en la NIHSS (OR: 1,07; IC95%: 1,02­1,12; p < 0,002) y la presión arterial sistólica (OR: 0,98; IC95%: 0,96­0,99; p < 0,003) se asociaron a TPA ≤ 20 minutos. CONCLUSIóN: El tratamiento por NVs resultó en un TPA menor y en una mayor probabilidad de tratamiento ≤ 20 minutos.

Thermodynamic and Kinetic Aspects of Gold Adsorption in Micrometric Activated Carbon and the Impact of Their Loss in Adsorption, Desorption, and Reactivation Plants.

The production and loss of fine particles of activated carbon (AC) loaded with gold in the adsorption processes is a worldwide problem, mainly due to the behavior of increasing its adsorption capacity with respect to the decrease in particle size, which becomes relevant to determine the thermodynamic and kinetic activity of the gold adsorption and the economic impact of its loss, with the escape towards the later stages of the system of adsorption, desorption, and reactivation (ADR) plants of AC. Through the adsorption of gold in a synthetic medium with sodium cyanide concentration, using different particle sizes, AC weights, and adsorption times, data were generated for analysis by three different isotherm models, resulting in a better tendency for the Freundlich isotherm, from which thermodynamic parameters of ΔG equal to -2.022 kcal/mol, ΔH equal to -16.710 kcal/mol, and ΔS equal to -0.049 kcal/molK were obtained, which shows that it is a spontaneous, exothermic process with a lower degree of disorder. The kinetic analysis was performed with two different models, from which the pseudo-second-order model was used due to a better tendency and displayed a behavior that leaves open the interpretation of the increase in adsorption with respect to the decrease in the AC particle size but demonstrated the importance of recovering these particles in relation to their gold concentration and the economic impact from their poor recovery, which, for this case study, amounted to ~0.3 million dollars per year.

Who is in the emergency room matters when we talk about door-to-needle time: a single-center experience / Quien está en el servicio de emergencia importa al hablar de tiempo puerta-aguja: experiencia de un centro clínico

Abstract Background The efficacy of intravenous thrombolysis (IVT) is time-dependent. Objective To compare the door-to-needle (DTN) time of stroke neurologists (SNs) versus non-stroke neurologists (NSNs) and emergency room physicians (EPs). Additionally, we aimed to determine elements associated with DTN ≤ 20 minutes. Methods Prospective study of patients with IVT treated at Clínica Alemana between June 2016 and September 2021. Results A total of 301 patients underwent treatment for IVT. The mean DTN time was 43.3 ± 23.6 minutes. One hundred seventy-three (57.4%) patients were evaluated by SNs, 122 (40.5%) by NSNs, and 6 (2.1%) by EPs. The mean DTN times were 40.8 ± 23, 46 ± 24.7, and 58 ± 22.5 minutes, respectively. Door-to-needle time ≤ 20 minutes occurred more frequently when patients were treated by SNs compared to NSNs and EPs: 15%, 4%, and 0%, respectively (odds ratio [OR]: 4.3, 95% confidence interval [95%CI]: 1.66-11.5, p = 0.004). In univariate analysis DTN time ≤ 20 minutes was associated with treatment by a SN (p = 0.002), coronavirus disease 2019 pandemic period (p = 0.21), time to emergency room (ER) (p = 0.21), presence of diabetes (p = 0.142), hypercholesterolemia (p = 0.007), atrial fibrillation (p < 0.09), score on the National Institutes of Health Stroke Scale (NIHSS) (p = 0.001), lower systolic (p = 0.143) and diastolic (p = 0.21) blood pressures, the Alberta Stroke Program Early CT Score (ASPECTS; p = 0.09), vessel occlusion (p = 0.05), use of tenecteplase (p = 0.18), thrombectomy (p = 0.13), and years of experience of the physician (p < 0.001). After multivariate analysis, being treated by a SN (OR: 3.95; 95%CI: 1.44-10.8; p = 0.007), NIHSS (OR: 1.07; 95%CI: 1.02-1.12; p < 0.002) and lower systolic blood pressure (OR: 0.98; 95%CI: 0.96-0.99; p < 0.003) remained significant. Conclusions Treatment by a SN resulted in a higher probability of treating the patient in a DTN time within 20 minutes.

Resumen Antecedentes La respuesta a la trombólisis intravenosa (TIV) es dependiente del tiempo. Objetivo Comparar los tiempo puerta-aguja (TPAs) de neurólogos vasculares (NVs) contra los de neurólogos no vasculares (NNVs) y médicos emergencistas (MEs), y determinar los elementos asociados a un PTA ≤ 20 minutos. Métodos Análisis observacional prospectivo de pacientes con TIV tratados en Clínica Alemana entre junio de 2016 y septiembre de 2021. Resultados En total, 301 pacientes con TIV fueron tratados. El TPA promedio fue de 43,3 ± 23,6 minutos. Un total de 173 (57,4%) pacientes fueron evaluados por NVs, 122 (40,5%), por NNVs, y 6 (2,1%), por MEs; los TPAs promedios fueron de 40,8 ± 23; 46 ± 24,7 y 58 ± 22,5 minutos, respectivamente. Los TPAs ≤ 20 minutos fueron más frecuentes en pacientes tratados por NVs versus NNVs y MEs: 15%, 4% y 0%, respectivamente (odds ratio [OR]: 4,3; intervalo de confianza del 95% [IC95%]: 1,66-11,5; p = 0,004). El análisis univariado demostró que TPA ≤ 20 minutos se asoció con: tratamiento por NVs (p = 0,002), periodo de la pandemia de enfermedad por coronavirus 2019 (COVID-19; p = 0,21), tiempo a urgencia (p = 0,21), diabetes (p = 0,142), hipercolesterolemia (p = 0,007), fibrilación auricular (p < 0,09), puntaje en la National Institutes of Health Stroke Scale [NIHSS] (p = 0,001), presión arterial sistólica (p = 0,143) y diastólica menores (p = 0,21), Alberta Stroke Program Early CT Score (ASPECTS ; p = 0,09), oclusión de vasos cerebrales (p =0,05), uso de tecneteplase (p = 0,18), trombectomía (p = 0,13) y años de experiencia del médico (p < 0,001). El análisis multivariado demostró que ser tratado por NVs (OR: 3,95; IC95%: 1,44-10,8; p = 0,007), el puntaje en la NIHSS (OR: 1,07; IC95%: 1,02-1,12; p < 0,002) y la presión arterial sistólica (OR: 0,98; IC95%: 0,96-0,99; p < 0,003) se asociaron a TPA ≤ 20 minutos. Conclusões El tratamiento por NVs resultó en un TPA menor y en una mayor probabilidad de tratamiento ≤ 20 minutos.

The feeding apparatus of Rhea americana (Aves, Palaeognathae): Jaw myology and ontogenetic allometry.

In birds, the jaw musculature is a crucial adaptive feature involved in feeding. The morphological traits and postnatal growth patterns of jaw muscles constitute a useful proxy to interpret feeding function and ecology. This study aims to describe the jaw muscles of Rhea americana and explore their postnatal growth pattern. A total of 20 specimens of R. americana representing four ontogenetic stages were studied. Jaw muscles were described, weighed and their proportions with respect to body mass were calculated. Linear regression analysis was used to characterize ontogenetic scaling patterns. The morphological patterns of jaw muscles were characterized by their simplicity: bellies with few or no subdivisions and similar to those described for other flightless paleognathous birds. In all stages, the muscles pterygoideus lateralis, depressor mandibulae, and pseudotemporalis had the greatest mass values. The proportion of total jaw muscle mass decreased with age from 0.22% in 1-month-old chicks to 0.05% in adults. Linear regression analysis showed that all muscles scaled with negative allometry with respect to body mass. The progressive decrease of jaw muscle mass relative to body mass in adults could be related to the generation of less force, which is in accordance with the herbivorous diet of adults. In contrast, the diet of rhea chicks includes a large proportion of insects thus, this greater muscle proportion could be associated with the ability to generate more force, thus providing better abilities to grasp and hold more mobile prey.

1D Supramolecular Assemblies That Crystallize and Form Gels in Response to the Shape-Complementarity of Alcohols.

N-9-Fluorenylmethyloxycarbonyl (Fmoc)- and C-tertiary butyl (t-Bu)-protected glutamate (L-2), bearing a phenanthroline moiety at the side residue, forms 1D supramolecular assemblies via H-bonding as well as undergoing π-stacking interactions to afford crystals or gels that depend on the shape-complementarity of coexisting alcohols, as demonstrated by structural analyses on these assemblies by means of single-crystal X-ray diffractometry and supplemented with small- and wide-angle X-ray scattering data. Moreover, the rheological measurements on the gels help to define a model for when gels and crystals are expected and found. These observations and conclusions highlight an important, but not very appreciated, aspect of solute-solvent interactions within supramolecular assemblies that can allow the constituent-aggregating molecules in some systems to exhibit high selectivity toward the structures of their solvents. The consequences of this selectivity, as demonstrated here by single-crystal and powder X-ray diffraction data, can lead to self-assembled structures which alter completely the bulk phase properties and morphology of the materials. In that regard, rheological measurements have helped to develop a model to explain when gels and phase-separated mixtures of crystals and solvents are expected.

Epidemiología, resistencia antimicrobiana y tratamiento antibiótico empírico en peritonitis secundarias de la comunidad en un centro de la prov. de Buenos Aires / Epidemiology and review of antibiotic treatment in secondary community peritonitis in a province Buenos Aires's center

Las peritonitis secundarias constituyen una causa frecuente de internación y de uso de antibioticoterapia dentro de las infecciones intraabdominales. Realizamos un estudio retrospectivo, descriptivo y observacional de centro único desde enero a diciembre de 2021. El objetivo del estudio fue conocer la epidemiología local y adecuar el tratamiento empírico de las peritonitis secundarias de la comunidad. Se incluyeron pacientes mayores a 16 años con peritonitis secundaria, intervención quirúrgica, envío de material a cultivo y desarrollo microbiano de bacterias aerobias a través de la revisión de historias clínicas. Se analizaron cultivos de 36 pacientes, 64% de sexo masculino con una media de edad de 48,8 años. El 22% requirió internación en unidad de cuidados intensivos. La principal causa fue apendicitis aguda en el 61%, seguido por perforación secundaria a tumores. Se aislaron 43 bacterias aerobias (1,2 bacterias por episodio) siendo E. coli el microorganismo más frecuente. En la institución se utiliza piperacilina-tazobactam como tratamiento empírico. De acuerdo a las recomendaciones de la Sociedad Argentina de Infectología de 2018, en infecciones no complicadas podría utilizarse aminoglucósidos + metronidazol, optando por piperacilina-tazobactam en casos graves. No es recomendado como tratamiento empírico el uso de ampicilina-sulbactam y ciprofloxacina para infecciones graves o con difícil control del foco por la alta tasa de resistencia. En base a nuestro estudio podemos concluir que la epidemiología de los pacientes coincide con lo descrito en publicaciones nacionales, lo que nos lleva a reconsiderar el tratamiento empírico en casos leves, pudiendo optar por aminoglucósidos + metronidazol.

Secondary peritonitis is a frequent cause of hospital admission and an usual cause of use of antibiotic therapy in abdominal infections. We did a retrospective and observational study in one health center between January 2021 and December 2021. The aim of the study was to analyze the local epidemiology and adapt antibiotic empirical therapy of secondary community peritonitis. Patients aged 16 years and older with secondary peritonitis were included in this study. These patients needed surgical intervention and they had a positive culture with aerobic microorganism. We analyzed abdominal cultures from 36 patients, 64% men with a median age of 48.8 years. Twenty- two percent of these patients were admitted to intensive care unit. Acute appendicitis was the principal cause of secondary peritonitis in 61% of cases, followed by tumors. We found 43 aerobic bacterias (1.2 bacteria/episode), E.coli was the most frequent microorganism. In our hospital we use piperacillin- tazobactam for empirical treatment. According to the 2018 recommendations from the Argentine Society of Infectious Diseases, aminoglycosides + metronidazole can be used for uncomplicated intra-abdominal infections, and piperacillin-tazobactam should be used only in severe cases. However, ampicillin-sulbactam or ciprofloxacin is not recommended for severe cases or complicated infections due to the high resistance rates. Based on the finding of the study, it could be said that the epidemiology of the patients coincides with what was described in other national medical journals. Therefore, we should reconsider the use of aminoglycosides + metronidazole as empirical treatment for mild cases.

Laparoscopic right adrenalectomy in a patient with Carney syndrome: A case report.

INTRODUCTION AND IMPORTANCE: Carney complex (CNC) is an extremely infrequent multiple endocrine neoplasia syndrome characterized by distinctive pigmented skin and mucosal lesions, cardiac and noncardiac myxomatous tumors, and multiple endocrine tumors. We herein report a case of CNC and surgical and history of laparoscopic left adrenalectomy complicated with a primary pigmented nodular adrenocortical disease (PPNAD). PRESENTATION OF CASE: We present the case of a 38-year-old woman with a previous diagnosis of CNC and history of laparoscopic left adrenalectomy who consulted for severe depression refractory to medical treatment. In the laboratory tests performed, altered ACTH, prolactin, Somatomedin C-IGF-1 and estradiol. An abdomen and pelvis C/T scan was requested, where an 8 mm lesion was found at the level of the right adrenal gland. Laparoscopic right adrenalectomy was performed. Histopathology of the surgical resection specimen revealed PPNAD. DISCUSSION: CNC is an infrequent syndrome with autosomal dominant inheritance and genetically heterogeneous. PPNAD is a consistent feature in CNC patients, however, reports of Cushing's syndrome in the literature indicate that only 25-45 % of CNC patients have PPNAD. CONCLUSION: PPNAD can be present in patients with Carney complex, with surgical adrenalectomy history. With an adequate selection of patients, laparoscopic adrenalectomy with subsequent hormone replacement therapy should be performed.

Muscle architecture of the hindlimb of Tyto furcata (Aves Strigiformes): Highlights in owl morphology.

The American barn owl is a nocturnal bird of prey in which hind limb movements are a key factor in obtaining food; however, the architectural properties of its hind limb muscles have not been studied. This study sought to identify functional trends in the Tyto furcata hindlimb muscles by studying muscular architecture. The architectural parameters of the selected hip, knee, ankle, and digit muscles were studied in three specimens of the Tyto furcata and joint muscular proportions with an additional dataset were calculated. Previously published information on Asio otus was used for comparison. The flexor muscles of the digits had the highest muscle mass. Regarding architectural parameters, the main flexor of the digits (flexor digitorum longus) and the muscles that extend the knee and ankle joints (femorotibialis and gastrocnemius) showed a high physiological cross-sectional area (PCSA) and short fibers, allowing powerful digit flexion and knee and ankle extension. These mentioned features are in accordance with hunting behavior, in which prey capture is not only closely linked to the flexion of the digits but also to the movements of the ankle. During hunting, the distal hind limb is flexed and then fully extended at the moment of contact with the prey, whereas the digits are close to grasping the prey. The hip muscles showed a predominance of extensors over flexors, which were more massive, with parallel fibers and without tendons or short fibers. These features lead to a higher capacity to generate velocity to the detriment of forces, as indicated by the high values of the architectural index, their relatively low PCSA, and short or intermediate fiber length, which enhance the control of the joint positions and muscle length. Compared to Asio otus, Tyto furcata showed longer fibers; however, the relationship between fiber length and PCSA was similar for both species.