RESUMO

PURPOSE: Breast cancer (BC) is the most frequent neoplasm in women in Colombia and is associated with a higher mortality rate than in other countries and regions. Neoadjuvant chemotherapy (NACT) has become a standard treatment in locally advanced BC and provides an opportunity to improve clinical outcomes in BC. This study aims to describe characteristics, treatment patterns, and outcomes after NACT in a cohort of Colombian patients with BC. METHODS: We performed a retrospective cohort study. We included adult patients with BC treated with NACT. Clinical charts were retrospectively reviewed. Descriptive statistics and time to event for overall survival analyses were performed. Recursive partitioning was performed for survival curves to assess the complex relationship between survival times and other variables. RESULTS: Three hundred and fourteen patients were included for analysis. The pathologic complete response after neoadjuvant chemotherapy (ypCR) rate was 34.4%, with a higher ypCR in triple-negative BC (TNBC; 46.9%) and human epidermal growth factor receptor 2-positive BC (72.7%). Those who did not achieve ypCR had a higher percentage of death and relapse. The median follow-up was 4.9 years, with an 88.2% 5-year overall survival (OS). CONCLUSION: A total of 62.6% of the total patients identified were not treated with NACT, indicating a low utilization. Our global ypCR rate was higher when compared with similar studies in Colombia, likely because of differences in the NACT treatment regimens. ypCR was only associated with OS in the TNBC subgroup, emphasizing the importance of pursuing ypCR in these patients. We consider the use of NACT a valuable opportunity to implement innovative treatment approaches that improve outcomes in Colombian patients with BC.

Assuntos

RESUMO

The jalap roots, Operculina hamiltonii D.F. Austin & Staples (Convolvulaceae), are extensively commercialized as a depurative and laxative remedy in traditional medicine of the north and northeast regions of Brazil. The purification by recycling HPLC and structure elucidation of three new acyl sugars or resin glycosides are described here from a commercial product made of powdered roots. Three macrocyclic structures of a tetrasaccharide of (11S)-hydroxyhexadecanoic acid, operculinic acid C (1), the undescribed hamiltonins II and III (3 and 4), in addition to the known batatinoside III (5), presented a diastereoisomeric relationship as one residue of n-dodecanoic acid esterified the oligosaccharide core on a different position in each compound. Furthermore, hamiltonin IV (6) was characterized as an ester-type homodimer of acylated operculinic acid C with the same substitution pattern identified in hamiltonins II (3) and III (4) for each of the dimer subunits. All the isolated resin glycosides did not display any intrinsic cytotoxicity (IC50 > 25 µM). However, a combination of the individual isolated compounds 3-6 (1-50 µM) demonstrated an enhancement of cytotoxic effects with sublethal doses of vinblastine and podophyllotoxin (0.003 µM) in multidrug-resistant breast carcinoma epithelial cells (MCF-7/Vin).

Assuntos

RESUMO

We present an exhaustive exploration of the driving forces dominating the interaction between gold atoms in the trans-(AuX)2, where X is a halogen ligand. This work provides insights into the nature of the gold-gold contact in the trans-(AuX)2. The geometries and energies were calculated at the MP2, CCSD(T), and DFT-D3(BJ) (B3LYP, PBE, and TPSS) levels of theory. The results show a short Au-Au distance, typical of a covalent bond, but with a weak interaction energy associated with noncovalent interactions. It is established that the physical contributions from polarization and the electronic correlation forces are the most relevant at the post-Hartree-Fock level of theory. Also, the electrostatic term is attractive but with low contribution. Finally, the Wiberg indices and NBO analysis exposed a small covalent character between the gold atoms, revealing that this contribution is insufficient to explain the stability of the dimers. It is concluded that a sum of contributions makes it possible to establish an attraction between the gold atoms in the dimers studied beyond a classical aurophilic interaction.

RESUMO

Increased activity in the insula has been consistently reported to be associated with anxiety and anxiety-related disorders. However, little is known on how the insula regulates anxiety. The present study aims at determining the role of the insula on the effects of glucocorticoids in anxiety. A combination of pharmacological manipulations, including blockade of adrenal GC synthesis by metyrapone and intra-insular microinjections of corticosterone, corticosterone-BSA, mineralocorticoid receptor (MR) antagonist spironolactone and glucocorticoid receptor (GR) antagonist mifepristone, were used to assess the short-term (5 min) effects of intra-insular corticosterone in two anxiety-like behaviors in male Sprague-Dawley rats. The elevated plus maze (EPM) and Novelty Suppressed Feeding (hyponeophagia) were utilized. We found that corticosterone in the insula is sufficient to prevent the anxiolytic effects corticosterone synthesis blockade in anxiety, and that intra-insular corticosterone has anxiolytic or anxiogenic effects depending on the amount of corticosterone microinjected and the arousal associated to the test, without affecting the HPA axis. Glucocorticoid anxiolytic effects in the insula are mediated by MRs, while its anxiogenic effects are dependent on a mifepristone-sensitive membrane-bound mechanism. Anxiety appears to be modulated at the insula through a competition between fast MR-dependent anxiolytic and membrane-associated anxiogenic signaling pathways that orchestrate the behavioral response to stress and determines the resulting level of anxiety.

Assuntos

RESUMO

The biopharmaceutical classification system groups low-solubility drugs into two groups: II and IV, with high and low permeability, respectively. Most of the new drugs developed for common pathologies present solubility issues. This is the case of lurasidone hydrochloride-a drug used for the treatment of schizophrenia and bipolar depression. Likewise, the stability problems of some drugs limit the possibility of preparing them in liquid pharmaceutical forms where hydrolysis and oxidation reactions can be favored. Lurasidone hydrochloride presents the isoindole-1,3-dione ring, which is highly susceptible to alkaline hydrolysis, and the benzisothiazole ring, which is susceptible to a lesser extent to oxidation. Herein, we propose to study the increase in the solubility and stability of lurasidone hydrochloride by the formation of higher-order inclusion complexes with hydroxypropyl-ß-cyclodextrin. Several stoichiometric relationships were studied at between 0.5 and 3 hydroxypropyl-ß-cyclodextrin molecules per drug molecule. The obtained products were characterized, and their solubility and stability were assessed. According to the obtained results, the formation of inclusion complexes dramatically increased the solubility of the drug, and this increased with the increase in the inclusion ratio. This was associated with the loss of crystalline state of the drug, which was in an amorphous state according to infrared spectroscopy, calorimetry, and X-ray analysis. This was also correlated with the stabilization of lurasidone by the cyclodextrin inhibiting its recrystallization. Phase solubility,1H-NMR, and docking computational characterization suggested that the main stoichiometric ratio was 1:1; however, we cannot rule out a 1:2 ratio, where a second cyclodextrin molecule could bind through the isoindole-1,3-dione ring, improving its stability as well. Finally, we can conclude that the formation of higher-order inclusion complexes of lurasidone with hydroxypropyl-ß-cyclodextrin is a successful strategy to increase the solubility and stability of the drug.

RESUMO

Electronic absorption and emission spectra of [M25(MPA)18]- (M = Au, Ag; MPA = SCH2CH2COOH) clusters have been recorded for energies below 5 eV at the time-dependent density functional theory (TDDFT) level using B3LYP and TPSSh functionals and compared to the calculated ones using the computationally inexpensive simplified TDDFT (sTDDFT) approach. The results show a qualitative agreement between the TDDFT and sTDDFT approaches used here, which were also in line with the experimental and theoretical spectra previously reported. However, the sTDDFT calculations were several orders of magnitude faster than those obtained by TDDFT. Our results support that sTDDFT provides an excellent balance between accuracy and low computational cost, becoming a suitable approach for studying the absorption and emission spectra of noble-metal clusters of sizes that would be unaffordable by the traditional TDDFT methods. The main peaks of the experimental absorption spectrum of [Au25(MPA)18]- have been previously assigned, whereas [Ag25(MPA)18]- has not been synthesised. However, its absorption spectrum resulted in having similar features to the experimental spectrum of [Ag25(GSH)18]- (GSH = glutathione), used to validate our results. The emission spectra, which to date have not been reported either from experimental or theoretical means, were simulated by using the molecular structure of the first excited triplet state (T1). The emission spectra were obtained by comparing them to those of [M25(GSH)18]- since no experimental luminescence spectra have been reported for [M25(MPA)18]-. The calculations suggest that [Ag25(SR)18]- (SR = thiolate) clusters have a weak luminescence band in the NIR region. Finally, solvent shifts were found to be minor, whereas the absorption bands seem to be significantly redshifted in solid-state materials.

RESUMO

MLL3, also known as KMT2C, is a lysine mono-methyltransferase in charge of the writing of an epigenetic mark on lysine 4 from histone 3. The catalytic site of MLL3 is composed of four tyrosines, namely, Y44, Y69, Y128, and Y130. Tyrosine residues are highly conserved among lysine methyltransferases' catalytic sites, although their complete function is still unclear. The exploration of how modifications on these residues from the enzymatic machinery impact the enzymatic activity of MLL3 could shed light transversally into the inner functioning of enzymes with similar characteristics. Through the use of QMMM calculations, we focus on the effect of the mutation of each tyrosine from the catalytic site on the enzymatic activity and the product specificity in the current study. While we found that the mutations of Y44 and Y128 by phenylalanine inactivated the enzyme, the mutation of Y128 by alanine reactivated the enzymatic activity of MLL3. Moreover, according to our models, the Y128A mutant was even found to be capable of di- and tri-methylate lysine 4 from histone 3, what would represent a gain of function mutation, and could be responsible for the development of diseases. Finally, we were able to establish the inactivation mechanism, which involved the use of Y130 as a water occlusion structure, whose conformation, once perturbed by its mutation or Y128 mutant, allows the access of water molecules that sequester the electron pair from lysine 4 avoiding its methylation process and, thus, increasing the barrier height.

Assuntos

RESUMO

Peumus boldus is an endemic tree species from Chile whose leaves have been the focus of study for decades given that their infusions are reported to relieve rheumatic symptoms, headache, dyspepsia, urinary tract inflammation, and symptoms of other illnesses. These health properties have been studied mainly using leaves and bark, then it is relevant to know more about these properties in different parts of the plant. Considering the importance of P. boldus fruits in the diet of some rural populations, we analyzed their properties to explore its impact on the Chilean population health. Liquid chromatography and mass spectrometry analysis confirmed the presence of alkaloids such as boldine, although aporphine N-methyl-laurotetanine was the most abundant. In addition, flavonoids catechin, chrysin and quercetin were also found in the extract. Cytotoxicity and anti-inflammatory activities of the fruit extract were invitro tested by using a murine macrophage cell model, observing that a diluted fraction of the extract was not cytotoxic, but showed anti-inflammatory activity, which is likely attributed to antioxidants activities. By means of quantum chemical calculations, we calculated the redox potential of the respective alkaloids and flavonoids found in the extract. Results suggest a synergistic effect between alkaloids and flavonoids, where boldine and N-methyl-laurotetanine showed similar antioxidant properties. Finally, we present a description of the oxidation mechanisms for both groups of molecules which will sustain P. boldus fruit biological properties, in order to give this kind of fruits scientific value focusing on human health.

Assuntos

RESUMO

As most neotropical pipids, the four species of Pipa present in Colombia are poorly understood despite their particular biology. The tegument of these New-World pipids presents particular structures which variations have been hardly analyzed. Therefore, we aim to describe the morphological variations of the dermal flap, barbels, fingertips, and the lateral line pattern among these four species, focusing on changes during the ontogeny. The results of the study show that the dermal flap was exclusively found in P. pipa, while barbels are usually present in P. pipa but seldom in P. snethlageae. The lateral line pattern in the dorsum is shared by the four species, but P. pipa present more neuromast lines along the snout than P. snethlageae. These species were different from P. parva and P. myersi, which cannot be distinguished based on external morphology, as they were more similar in all lateral line elements and exhibited the same fingertip morphology. On the other hand, the fingertips of young individuals of P. pipa and P. snethlageae presented four simple distal lobes which bifurcate twice during the ontogeny, so that adults present sixteen lobes. The difference between species is observed in the fingertip morphology: P. pipa has all four lobes distally placed, but P. snethlageae has one pair more proximal. The tegument structures analyzed here have a taxonomic utility using external morphology for P. pipa and P. snethlageae, but for P. parva and P. myersi additional studies are necessary. For future research, evaluating the function and anatomy of these structures is important to the understanding these integumentary structures in Pipa.(AU)

Assuntos

RESUMO

The mixed lineage leukemia 3 or MLL3 is the enzyme in charge of the writing of an epigenetic mark through the methylation of lysine 4 from the N-terminal domain of histone 3 and its deregulation has been related to several cancer lines. An interesting feature of this enzyme comes from its regulation mechanism, which involves its binding to an activating dimer before it can be catalytically functional. Once the trimer is formed, the reaction mechanism proceeds through the deprotonation of the lysine followed by the methyl-transfer reaction. Here we present a detailed exploration of the activation mechanism through a QM/MM approach focusing on both steps of the reaction, aiming to provide new insights into the deprotonation process and the role of the catalytic machinery in the methyl-transfer reaction. Our finding suggests that the source of the activation mechanism comes from conformational restriction mediated by the formation of a network of salt-bridges between MLL3 and one of the activating subunits, which restricts and stabilizes the positioning of several residues relevant for the catalysis. New insights into the deprotonation mechanism of lysine are provided, identifying a valine residue as crucial in the positioning of the water molecule in charge of the process. Finally, a tyrosine residue was found to assist the methyl transfer from SAM to the target lysine.

Assuntos

RESUMO

RESUMEN: Introducción: La rehabilitación cardíaca después de padecer un evento cardiovascular (CV) grave es un proceso en el cual el paciente establece una relación cercana con el equipo médico, brindando la oportunidad de conocer factores psicosociales que influyeron en el desenlace cardíaco y los eventuales aprendizajes de la experiencia. El objetivo de este estudio fue conocer la percepción sobre su propia salud de mujeres que participaron de un programa de rehabilitación cardíaca. Método: Se invitó a participar a 35 mujeres de 35 a 75 años con diverso nivel educativo, ingreso familiar y situación laboral. Los datos se recolectaron por medio de entrevistas presenciales semiestructuradas. Resultados: A pesar de haber pasado por un proceso de rehabilitación posterior a un evento CV las mujeres mencionaron en forma mayoritaria al cáncer de mama como la principal eventual causa de muerte. En relación con los factores de riesgo de CV, el más nombrado fue el estrés (57%), aunque solo el 29% de las entrevistadas realizó con posterioridad actividades orientadas a su manejo y control. En cuanto a las motivaciones más frecuentes para realizar cambios de hábitos, destacaron el cuidado de la familia (29%), el vivir más (26%) y el deseo de sentirse mejor (23%). Conclusión: Estos resultados sugieren la necesidad de una educación más integral en la mujer durante la rehabilitación, promoviendo no solo hábitos más saludables desde el punto de vista físico, sino también psicológico. Se sugiere integrar el manejo del estrés en los programas de prevención y rehabilitación CV.

ABSTRACT: Introduction: After suffering a serious cardiovascular event (CV), cardiac rehabilitation is a process in which the patient establishes a close relationship with the medical team, providing an opportunity to learn about psychosocial factors that influence cardiac outcome and eventual learnings from the experience. The objective of this study was to learn about women´s perception of their own health after participating in a cardiac rehabilitation program. Method: 35 women from 35 to 75 years of age with varying educational level, household income and employment status were invited to participate. Data was collected through semi-structured face-to-face interviews. Results: Women mentioned breast cancer as the leading cause of death (60%) despite having gone through a post-CV rehabilitation process. Stress was mentioned as the main CV risk factor (57%). Only 29% of responders subsequently carried out activities aimed at their management and control. The most common motivations for making changes in habits, were family care (29%), living longer (26%) and a desire to feel better (23%). Conclusion: These results suggest the need for a more comprehensive education in women during rehabilitation, promoting not only healthier habits from a physical but also from a psychological points of view. The introduction of stress management into CV prevention and rehabilitation programs is suggested.

Assuntos

RESUMO

The high mountain environment is a tough habitat that imposes many challenges to reptiles. As temperature decreases with altitude and has a dramatic variation throughout the day in the tropical mountains, ectotherms must cope with these harsh conditions. We studied the use of microhabitat and activity patterns of Stenocercus trachycephalus in the eastern Andes mountain range of Colombia. Three localities were sampled across the wide altitudinal distribution of this lizard species, in a range from 2,670 to 3,950 m a.s.l. The initial hypothesis was that these natural history traits would change with altitude but instead, we found that they remained roughly consistent, showing the great plasticity of this species. The results support that this lizard is a microhabitat-generalist using principally herb across the gradient, rarely shifting to specific plants or microhabitats such as rocks depending on availability. Regarding the activity pattern, this species was active throughout the day from 8:00 to 16:00 with a similar pattern along the gradient. Nevertheless, some differences were detected across localities. The activity pattern shifted from bimodal in the lower locality to unimodal in the higher ones. As expected, a correlation between temperature and activity patterns was found in one of the study sites. However, this was not the case for the lower and mid-elevation localities, where there was no correlation between these variables. The mid-elevation study site was the most interesting locality as the use of microhabitat relied virtually just on the herb stratum and the activity was constrained to the morning hours. These findings may be the result of the synergic effects of other ecological variables (weather variability, human impact, predation, population structure, or reproductive season). Our study gives the basis for a better understanding of how behavior (microhabitat choice and hours of activity) of ectotherms can help to counter thermal constraints in the neotropics when facing an altitudinal gradient. Further studies should focus on the thermal biology of this species, considering the influence of anthropic impact on these lizards populations.(AU)

Assuntos

RESUMO

Abstract The high mountain environment is a tough habitat that imposes many challenges to reptiles. As temperature decreases with altitude and has a dramatic variation throughout the day in the tropical mountains, ectotherms must cope with these harsh conditions. We studied the use of microhabitat and activity patterns of Stenocercus trachycephalus in the eastern Andes mountain range of Colombia. Three localities were sampled across the wide altitudinal distribution of this lizard species, in a range from 2,670 to 3,950 m a.s.l. The initial hypothesis was that these natural history traits would change with altitude but instead, we found that they remained roughly consistent, showing the great plasticity of this species. The results support that this lizard is a microhabitat-generalist using principally herb across the gradient, rarely shifting to specific plants or microhabitats such as rocks depending on availability. Regarding the activity pattern, this species was active throughout the day from 8:00 to 16:00 with a similar pattern along the gradient. Nevertheless, some differences were detected across localities. The activity pattern shifted from bimodal in the lower locality to unimodal in the higher ones. As expected, a correlation between temperature and activity patterns was found in one of the study sites. However, this was not the case for the lower and mid-elevation localities, where there was no correlation between these variables. The mid-elevation study site was the most interesting locality as the use of microhabitat relied virtually just on the herb stratum and the activity was constrained to the morning hours. These findings may be the result of the synergic effects of other ecological variables (weather variability, human impact, predation, population structure, or reproductive season). Our study gives the basis for a better understanding of how behavior (microhabitat choice and hours of activity) of ectotherms can help to counter thermal constraints in the neotropics when facing an altitudinal gradient. Further studies should focus on the thermal biology of this species, considering the influence of anthropic impact on these lizards populations.

RESUMO

Abstract The high mountain environment is a tough habitat that imposes many challenges to reptiles. As temperature decreases with altitude and has a dramatic variation throughout the day in the tropical mountains, ectotherms must cope with these harsh conditions. We studied the use of microhabitat and activity patterns of Stenocercus trachycephalus in the eastern Andes mountain range of Colombia. Three localities were sampled across the wide altitudinal distribution of this lizard species, in a range from 2,670 to 3,950 m a.s.l. The initial hypothesis was that these natural history traits would change with altitude but instead, we found that they remained roughly consistent, showing the great plasticity of this species. The results support that this lizard is a microhabitat-generalist using principally herb across the gradient, rarely shifting to specific plants or microhabitats such as rocks depending on availability. Regarding the activity pattern, this species was active throughout the day from 8:00 to 16:00 with a similar pattern along the gradient. Nevertheless, some differences were detected across localities. The activity pattern shifted from bimodal in the lower locality to unimodal in the higher ones. As expected, a correlation between temperature and activity patterns was found in one of the study sites. However, this was not the case for the lower and mid-elevation localities, where there was no correlation between these variables. The mid-elevation study site was the most interesting locality as the use of microhabitat relied virtually just on the herb stratum and the activity was constrained to the morning hours. These findings may be the result of the synergic effects of other ecological variables (weather variability, human impact, predation, population structure, or reproductive season). Our study gives the basis for a better understanding of how behavior (microhabitat choice and hours of activity) of ectotherms can help to counter thermal constraints in the neotropics when facing an altitudinal gradient. Further studies should focus on the thermal biology of this species, considering the influence of anthropic impact on these lizards' populations.

RESUMO

In medicinal chemistry, it is extremely important to evaluate, as accurately as possible, the molecular interactions involved in the formation of different ligand-receptor (L-R) complexes. Evaluating the different molecular interactions by quantum mechanics calculations is not a simple task, since formation of an L-R complex is a dynamic process. In this case, the use of combined techniques of molecular dynamics (MD) and quantum calculations is one the best possible approaches. In this work we report a comparative study using combined MD and QTAIM (Quantum Theory of Atoms In Molecules) calculations for five biological systems with different levels of structural complexity. We have studied Acetylcholinesterase (AChE), D2 Dopamine Receptor (D2DR), beta Secretase (BACE1), Dihydrofolate Reductase (DHFR) and Sphingosine Kinase 1 (SphK1). In these molecular targets, we have analyzed different ligands with diverse structural characteristics. The inhibitory activities of most of them have been previously measured in our laboratory. Our results indicate that QTAIM calculations can be extremely useful for in silico studies. It is possible to obtain very accurate information about the strength of the molecular interactions that stabilize the formation of the different L-R complexes. Better correlations can be obtained between theoretical and experimental data by using QTAIM calculations, allowing us to discriminate among ligands with similar affinities. QTAIM analysis gives fairly accurate information for weak interactions which are not well described by MD simulations. QTAIM study also allowed us to evaluate and determine which parts of the ligand need to be modified in order to increase its interactions with the molecular target. In this study we have discussed the importance of combined MD/QTAIM calculations for this type of simulations, showing their scopes and limitations.

Assuntos

RESUMO

Nowadays, the use of sulfur-based ligands to modify gold-based materials has become a common trend. Here, we present a theoretical exploration of the modulation of the chalcogenides-gold interaction strength, using sulfur, selenium, and tellurium as anchor atoms. To characterize the chalcogenide-gold interaction, we designed a nanocluster of 42 gold atoms (Au42) to model a gold surface (111) and a series of 60 functionalized phenyl-chalcogenolate ligands to determine the ability of electron-donor and -withdrawing groups to modulate the interaction. The analysis of the interaction was performed by using energy decomposition analysis (EDA), non-covalent interactions index (NCI), and natural population analysis (NPA) to describe the charge transfer processes and to determine data correlation analyses. The results revealed that the magnitudes of the interaction energies increase following the order S < Se < Te, where this interaction strength can be augmented by electron-donor groups, under the donor-acceptor character the chalcogen-gold interaction. We also found that the functionalization in meta position leads to better control of the interaction strength than the ortho substitution due to the steric and inductive effects involved when functionalized in this position.

RESUMO

Dear Director: Reading your article "The pandemic due to the new covid-19 coronavirus", I would like to deepen the contributions of the symptoms of this disease. What has started as a pathology manifested by a respiratory syndrome such as atypical pneumonia, is currently associated with several non-respiratory manifestations (1). Guillain-Barré syndrome in a female traveler from Wuhan is one of the first reported neurological manifestations (2). The literature is rich in terms of headaches, seizures and strokes in seriously ill patients, although the first and last of these may be due to systemic complications of this novel coronavirus, a higher incidence of events has been reported in patients with a history of neurological manifestations. (3.4). One of the most recent manifestations reported is neuromuscular diseases. Guidon et al. criticize the lack of rigor in the reports on neuromuscular manifestations (4). If anything is certain, one manifestation of this pandemic is the large amount of information available in the scientific field, many of these without the same methodological rigor as before the pandemic, accentuating the responsibility of the reader to critically analyze all the information.

Estimado Director: Leyendo su artículo "La pandemia por el nuevo coronavirus covid-19", me gustaría profundizar los aportes de la sintomatología de esta enfermedad. Lo que ha comenzado como una patología manifestada por un síndrome respiratorio como neumonías atípicas, actualmente está asociada a varias manifestaciones no respiratorias(1). De las primeras manifestaciones neurológicas reportadas está el síndrome de Guillain-Barré en una viajera proveniente de Wuhan(2). La literatura es rica en cuanto a cefaleas, convulsiones e ictus en los pacientes graves, si bien la primera y última de estas pueden deberse a complicaciones sistémicas de este novel coronavirus, se ha reportado una mayor incidencia de eventos en pacientes con antecedentes de manifestaciones neurológicas(3,4). Una de las más recientes manifestaciones reportadas, son las enfermedades neuromusculares. Guidon et al. critican la falta de rigurosidad en los reportes sobre manifestaciones neuromusculares(4). Si algo es seguro, una manifestación de esta pandemia es la gran cantidad de información disponible en el ámbito científico, muchas veces de estas sin la misma rigurosidad metodológica anterior a la pandemia, acentuando la responsabilidad del lector de analizar críticamente toda la información.

Assuntos

Assuntos

Assuntos