Computational modeling of the effect of five mutations on the structure of the ACE2 receptor and their correlation with infectivity and virulence of some emerged variants of SARS-CoV-2 suggests mechanisms of binding affinity dysregulation.

Interactions between the human angiotensin-converting enzyme 2 (ACE2) and the RBD region of the SARS-CoV-2 Spike protein are critical for virus entry into the host cell. The objective of this work was to identify some of the most relevant SARS-CoV-2 Spike variants that emerged during the pandemic and evaluate their binding affinity with human variants of ACE2 since some ACE2 variants can enhance or reduce the affinity of the interaction between the ACE2 and S proteins. However, no information has been sought to extrapolate to different variants of SARS-CoV-2. Therefore, to understand the impact on the affinity of the interaction between ACE2 protein variants and SARS-CoV-2 protein S variants, molecular docking was used in this study to predict the effects of five mutations of ACE2 when they interact with Alpha, Beta, Delta, Omicron variants and a hypothetical variant, which present mutations in the RBD region of the SARS-CoV-2 Spike protein. Our results suggest that these variants could alter the interaction of the Spike and the human ACE2 protein, losing or creating new inter-protein contacts, enhancing viral fitness by improving binding affinity, and leading to an increase in infectivity, virulence, and transmission. This investigation highlighted that the S19P mutation of ACE2 decreases the binding affinity between the ACE2 and Spike proteins in the presence of the Beta variant and the wild-type variant of SARS-CoV-2 isolated in Wuhan-2019. The R115Q mutation of ACE2 lowers the binding affinity of these two proteins in the presence of the Beta and Delta variants. Similarly, the K26R mutation lowers the affinity of the interaction between the ACE2 and Spike proteins in the presence of the Alpha variant. This decrease in binding affinity is probably due to the lack of interaction between some of the key residues of the interaction complex between the ACE2 protein and the RBD region of the SARS-CoV-2 Spike protein. Therefore, ACE2 mutations appear in the presence of these variants, they could suggest an intrinsic resistance to COVID-19 disease. On the other hand, our results suggested that the K26R, M332L, and K341R mutations of ACE2 expressively showed the affinity between the ACE2 and Spike proteins in the Alpha, Beta, and Delta variants. Consequently, these ACE2 mutations in the presence of the Alpha, Beta, and delta variants of SARS-CoV-2 could be more infectious and virulent in human cells compared to the SARS-CoV-2 isolated in Wuhan-2019 and it could have a negative prognosis of the disease. Finally, the Omicron variant in interaction with ACE2 WT, S19P, R115Q, M332L, and K341R mutations of ACE2 showed a significant decrease in binding affinity. This could be consistent that the Omicron variant causes less severe symptoms than previous variants. On the other hand, our results suggested Omicron in the complex with K26R, the binding affinity is increased between ACE2/RBD, which could indicate a negative prognosis of the disease in people with these allelic conditions.

Sex differences in cardiac autonomic function of depressed young adults.

BACKGROUND: Cardiac autonomic dysfunction has been proposed as an important contributing factor to the increased cardiovascular risk observed in major depression (MDD). However, the evidence regarding alterations in heart rate variability (HRV) in otherwise healthy depressed subjects has been inconclusive. METHODS: A case-control study in 50 treatment-naïve young adults with a first MDD episode without comorbid psychiatric disorders and 50 healthy control subjects was conducted. Time- and frequency-domain indexes of HRV were determined at baseline supine and after 5-min of orthostatic stress at 60°. RESULTS: There were no significant differences in the time- or frequency-domain variables of HRV between depressed patients and controls. However, a random-effect ANOVA model showed that during orthostatic stress depressed men had a reduced HRV and decreased parasympathetic activity compared to control subjects, while no differences were found between depressed women and controls. CONCLUSION: These results suggest a sex-dependent relationship between major depression and cardiac autonomic dysfunction and provide one potential explanation for sex differences in the association of depressive symptoms with cardiovascular morbidity.

High prevalence of apical periodontitis amongst smokers in a sample of Spanish adults.

AIM: To study the prevalence of apical periodontitis in smoker and nonsmoker patients. METHODOLOGY: In a cross-sectional study, the records of 180 subjects, 109 smokers and 71 nonsmokers, were examined. All participants underwent a full-mouth radiographic survey incorporating 14 periapical radiographs. The periapical region of all teeth, excluding third molars, was examined. Periapical status was assessed using the Periapical Index score. Statistical analyses were conducted using the Cohen's Kappa test, analysis of variance and logistic regression. RESULTS: Apical periodontitis in at least one tooth was found in 74% of smokers and in 41% of nonsmokers (P < 0.01; odds ratio = 4.2; 95% C. I. = 2.2-7.9). Amongst smoker patients 5% of the teeth had apical periodontitis, whereas in nonsmoker subjects 3% of teeth were affected (P = 0.008; odds ratio = 1.5; 95% C. I. = 1.1-2.1). The percentage of root filled teeth in smoker and nonsmoker patients was 2.5% and 1.5%, respectively (P < 0.05; odds ratio = 1.7; C. I. 95% = 1.0-2.6). CONCLUSIONS: In this study population, smoking was significantly associated with a greater frequency of root canal treatment and with an increased prevalence of apical periodontitis.

Spatial and temporal patterns of serotonin release in the rat's lumbar spinal cord following electrical stimulation of the nucleus raphe magnus.

The monoamine neurotransmitter serotonin is released from spinal terminals of nucleus raphe magnus (NRM) neurons and important in sensory and motor control, but its pattern of release has remained unclear. Serotonin was measured by the high-resolution method of fast cyclic voltammetry (2 Hz) with carbon-fiber microelectrodes in lumbar segments (L3-L6) of halothane-anesthetized rats during electrical stimulation of the NRM. Because sites of serotonin release are often histologically remote from membrane transporters and receptors, rapid emergence into aggregate extracellular space was expected. Increased monoamine oxidation currents were found in 94% of trials of 50-Hz, 20-s NRM stimulation across all laminae. The estimated peak serotonin concentration averaged 37.8 nM (maximum 287 nM), and was greater in dorsal and ventral laminae (I-III and VIII-IX) than in intermediate laminae (IV-VI). When measured near NRM-evoked changes, basal monoamine levels (relative to dorsal white matter) were highest in intermediate laminae, while changes in norepinephrine level produced by locus ceruleus (LC) stimulation were lowest in laminae II/III and VII. The NRM-evoked monoamine peak was linearly proportional to stimulus frequency (10-100 Hz). The peak often occurred before the stimulus ended (mean 15.6 s at 50 Hz, range 4-35 s) regardless of frequency, suggesting that release per impulse was constant during the rise but fell later. The latency from stimulus onset to electrochemical signal detection (mean 4.2 s, range 1-23 s) was inversely correlated with peak amplitude and directly correlated with time-to-peak. Quantitative modeling suggested that shorter latencies mostly reflected the time below detection threshold (5-10 nM), so that extrasynaptic serotonin was significantly elevated well within 1 s. Longer latencies (>5 s), which were confined to intermediate laminae, appeared mainly to be due to diffusion from distant sources. In conclusion, except possibly in intermediate laminae, serotonergic volume transmission is a significant mode of spinal control by the NRM.

High prevalence of apical periodontitis amongst type 2 diabetic patients.

AIM: To study the prevalence of AP in patients with and without type 2 diabetes mellitus. METHODOLOGY: In a retrospective cohort study, the records of 38 subjects with diabetes and 32 control subjects were examined. All participants underwent a full-mouth radiographic survey incorporating 14 periapical radiographs. The periapical region of all teeth, excluding third molars, was examined. Periapical status was assessed using the periapical index score. Statistical analyses were conducted using the Cohen's kappa test, analysis of variance and logistic regression. RESULTS: Apical periodontitis in at least one tooth was found in 81.3% of diabetic patients and in 58% of control subjects (P = 0.040; OR = 3.2; 95% CI = 1.1-9.4). Amongst diabetic patients 7% of the teeth had AP, whereas in the control subjects 4% of teeth were affected (P = 0.007; OR = 1.8; 95% CI = 1.2-2.8). CONCLUSIONS: Type 2 diabetes mellitus is significantly associated with an increased prevalence of AP.

Periapical status and quality of root fillings and coronal restorations in an adult Spanish population.

AIM: To investigate the quality of root fillings and coronal restorations and their association with periapical status in an adult Spanish population. METHODOLOGY: A total of 180 subjects, aged 37.1 +/- 15.7 years, who presented as new patients at the Faculty of Dentistry, Seville, Spain, were examined. All participants underwent a full-mouth radiographic survey incorporating 14 periapical radiographs. The periapical region of all root filled teeth, excluding third molars, were examined. The technical quality of root fillings was evaluated in terms of length in relation to the root apex and lateral adaptation to the canal wall. Radiographic signs of overhang or open margins associated with coronal restorations were also evaluated. Periapical status was assessed using the Periapical Index score. Statistical analyses were conducted using the Cohen's kappa test and logistic regression. RESULTS: The total number of root filled teeth was 93, and 60 (64.5%) had apical periodontitis (AP). Presence of AP in root filled teeth was associated with inadequate adaptation of the filling (OR = 2.29; P = 0.06), inadequate length of the root filling (OR = 2.44; P = 0.048), and with poor radiographic quality of the coronal restoration (OR = 2.38; P = 0.054). Only 34.4% of the root fillings were adequate from a technical perspective. When both root fillings and coronal restorations were adequate the incidence of AP decreased to 31.3% (OR = 5.50; P < 0.01). CONCLUSIONS: The incidence of AP in root filled teeth was high. Many root fillings were technically unsatisfactory. Adequate root fillings and coronal restorations were associated with a lower incidence of AP; an adequate root filling had a more substantial impact on the outcome of treatment than the quality of the coronal restoration.

Prevalence of apical periodontitis and frequency of root-filled teeth in an adult Spanish population.

AIM: To estimate the prevalence of teeth with apical periodontitis (AP) and root-filled teeth in an adult Spanish population. METHODOLOGY: A total of 180 subjects, aged 37.1 +/- 15.7 years, presenting as new patients to the Faculty of Dentistry, Seville, Spain, were examined. All participants underwent a full-mouth radiographic survey (14 periapical radiographs). The frequency of root canal treatment and the periapical status of all teeth, using the periapical index (PAI) score, were assessed. An intraobserver agreement test on PAI scores produced a Cohen's kappa of 0.77 (substantial agreement). Results were analysed statistically using the Chi-square test. RESULTS: Apical periodontitis in one or several teeth was found in 110 subjects (61.1% prevalence), and 73 (40.6% prevalence) had at least one root-filled tooth. Among subjects with root-filled teeth, 48 (65.8%) had AP affecting at least one root-filled tooth. A total of 4453 teeth were examined, of these 186 (4.2%) had AP. The total number of root-filled teeth was 93 (2.1%), of which 60 (64.5%) had AP. Among non-root filled teeth, only 2.9% had AP. The prevalence of AP in connection with molar teeth was higher (5.5%) than for premolar (4.5%) and anterior teeth (3.2%; P < 0.01). More premolar and molar teeth were root-filled (2.8 and 2.7%, respectively) than anterior teeth (1.3%; P < 0.01). The prevalence of AP increased with age. CONCLUSIONS: The prevalence of AP in root-filled and untreated teeth, and the frequency of root-filled teeth were comparable to those reported in previous similar studies carried out in European countries. The prevalence of root-filled teeth with AP was found to be higher compared to that demonstrated in other epidemiological studies.

Enfermedad por reflujo gastroesofágico: visión actual de su manejo / Gastroesophageal reflux disease: current management

El reflujo gastroesofagico (RGE) es una de las entidades patologicas más frecuentes en la consulta medica general. Por lo tanto, el conocimiento de la entidad corresponde a todo aquel que tenga que ver con la profesion medica. Clinicamente pueden distinguirse dos tipos de RGE: fisiologico y patologico. La presente revision pretende analizar el manejo que actualmente se propone para el RGE de tipo patologico, haciendo enfasis en los metodos diagnosticos principales y en las alternativas quirurgicas de manejo.

Conduction of impulses by axons regenerated in a Schwann cell graft in the transected adult rat thoracic spinal cord.

Central nervous system axons regenerate into a Schwann cell implant placed in the transected thoracic spinal cord of an adult rat. The present study was designed to test whether these regenerated axons are capable of conducting action potentials. Following the transection and removal of a 4- to 5-mm segment of the thoracic spinal cord (T8-T9), a polymer guidance channel filled with a mixture of adult rat Schwann cells and Matrigel was grafted into a 4- to 5-mm-long gap in the transected thoracic spinal cord. The two cut ends of the spinal cord were eased into the guidance channel openings. Transected control animals received a channel containing Matrigel only. Three months after implantation, electrophysiological studies were performed. Tungsten microelectrodes were used for monopolar stimulation of regenerated axons within the Schwann cell graft. Glass microelectrodes were used to record responses in the spinal cord rostral to the stimulation site. Evoked responses to electrical stimulation of the axon cable were found in two out of nine Schwann cell-grafted animals. These responses had approximate latencies in the range of those of myelinated axons. No responses were seen in any of the Matrigel-grafted animals. Histological analysis revealed that the two cases that showed evoked potentials had the largest number of myelinated axons present in the cable. This study demonstrates that axons regenerating through Schwann cell grafts in the complete transected spinal cord can produce measurable evoked responses following electrical stimulation.

Inmunoregulacion mediada por Calcitriol / Inmunoregulatory role of Calcitiol

El papel clásico endocrino del calcitrol (la,25-dihidroxivitamina D3) en la homeostasis del calcio es bien conocido. Los hallazgos relativamente recientes de la presencia del receptor de calcitrol en monocitos, linfocitos y diversas líneas celulares, y el hallazgo de la producción ectópica y localizada del calcitrol por los macrófagos, sugiere un papel importante de esta vitamina/hormona en eventos de inmunoregulación. A partir de la nueva evidencia experimental, es claro, a diferencia de los planteamientos iniciales que consideraban al calcitrol como un agente inmunosupresor, que esta hormona es capaz de estimular y de suprimir la función inmune, dependiendo de las condiciones de activación y del microambiente inmunológico. La información clínica disponible y la experimentación in vivo e in vitro apoyan un efecto inmunomodulador del calcitrol; éste debe ser considerado, por lo tanto, como uno mas de la larga y creciente lista de moduladores

Gastrostomía por endoscopia: presentación de 22 pacientes / Endoscopic gastrostomy: report on 22 patients

Desde enero de 1997 hasta enero de 1999, hemos realizado 22 gastrostomias endoscopicas, como parte de nuestra práctica en el Hospital de Caldas, Clinica de la Presentacion, Clinica Aman, Clinica de la Policia y Clinica Manizales. Para dicho procedimiento utilizamos el sistema de videoendoscopia, y en 77 casos un kit de gastrostomia de Abbott, realizandola en los otros 5 pacientes con un equipo fabricado en el mismo hospital con aditamentos tornados de sondas y pipetas de laboratorio. La principal indicacion para realizar el procedimiento fue la enfermedad neurologica con afeccion secundaria de la deglucion (14 pacientes), carcinoma del esofago en tratamiento con radioterapia (3 pacientes); trauma maxilofacial severo (3 pacientes); y cancer laringeo con criterios de irresecabilidad (2 pacientes). Tuvimos 13 pacientes de sexo femenino y 9 de sexo masculino. Las edades oscilaron entre 23 y 75 años. La duracion del procedimiento fue entre 20 y 30 minutos, y siempre fue realizado fuera del quirofano, sin requerir de instrumental especial. No tuvimos complicaciones en el acto quirurgico, el cual fue realizado solo con anestesia local. En ningun paciente se utilizó sedacion. La complicacion temprana posprocedimiento más frecuente, fue la infeccion de la herida alrededor de la gastrostomia, que se presento en 2 pacientes (9,09 por ciento), no teniendo, al parecer relacion con el tipo de equipo utilizado. En los 7 primeros casos iniciamos la nutricion 24 horas despues del procedimiento, pero en los 15 ultimas se hizo casi inmediatamente despues de terminado el mismo, sin complicaciones derivadas de esta conducta. Concluimos que el procedimiento es fácil de ejecutar, con muy pocas complicaciones, y que en hospitales de bajos recursos pueden fabricarse y usarse sondas que, cumpliendo con las especificaciones tecnicas, reemplazan las de marca, obteniendo los mismos resultados.

Endometriosis en cicatríz post-cesarea: report de un caso / Endometriosis in post-cesarean scar report of a case

Se comenta un nuevo caso de endometriosis en la cicatriz de cesárea; es el tercer caso en la literatura nacional