Impact of COVID-19 on paracoccidioidomycosis. Which was the most influential: The pandemic or the virus?

The impact of COVID-19 on paracoccidioidomycosis (PCM) in Argentina and the consequences generated by the pandemic are discussed. From 2018 to 3 years after the pandemic declaration, 285 proven PCM patients were registered. No association between both diseases was documented. PCM frequency decreased to extremely low levels in 2020. Mandatory social isolation and the emotional and psychological effects generated under pandemic circumstances led to delays in diagnosis, severe disseminated cases, and other challenges for diagnosis in subsequent years. Probable underdiagnosis should be considered due to the overlap of clinical manifestations, the low index of suspicion and the lack of sensitive diagnostic tools.

Effects on Biochemical Parameters and Animal Welfare of Dusky Grouper (Epinephelus marginatus, Lowe 1834) by Feeding CTX Toxic Flesh.

Ciguatera is a foodborne disease caused by ciguatoxins (CTXs), produced by dinoflagellates (genera Gambierdiscus and Fukuyoa), which bioaccumulate in fish through the food web, causing poisoning in humans. Currently, the physiological mechanisms of the species with the highest amount of toxins in their adult stage of life that are capable of causing these poisonings are poorly understood. Dusky grouper (Epinephelus marginatus) is a relevant fishing species and is part of the CTX food chain in the Canary Islands. This study developed an experimental model of dietary exposure featuring adult dusky groupers with two diets of tissue naturally contaminated with CTXs (amberjack and moray eel flesh) with two different potential toxicities; both groups were studied at different stages of exposure (4, 6, 10, 12, and 18 weeks). The results showed that this species did not show changes in its behavior due to the provided feeding, but the changes were recorded in biochemical parameters (mainly lipid and hepatic metabolism) that may respond to liver damage and alterations in the homeostasis of the fish; more research is needed to understand histopathological and cytotoxic changes.

The effect of water in THF/water mixtures on CMC, aggregation sizes, and fluorescence quenching of a new calix[4]resorcinarene macrocycle.

This study explores how water content modulates the self-assembly and fluorescence behavior of a novel calixarene, C1. C1 forms large, flattened structures in pure THF, but water addition triggers a transition to smaller, unimodal clusters. A critical micellar concentration (CMC) is identified, decreasing with increasing water content. Fluorescence quenching is observed upon water addition, attributed to nonradiative deactivation. These findings highlight water as a key regulator of C1's assembly and fluorescence, paving the way for further development of water-responsive calixarene systems.

Differing Approaches to Pain Management for Intrauterine Device Insertion and Maintenance: A Scoping Review.

Intrauterine devices (IUDs) are considered a reliable contraceptive option for women, but they can come with side effects. There is a disconnect in standard guidelines for IUD insertion within and without the U.S. The objective of this review was to address a gap in the literature regarding official procedures for pain management during IUD implantation. This scoping review was initiated using keywords to extract relevant articles from multiple databases: U.S. National Library of Medicine National Institutes of Health (PubMed), MEDLINE (Ovid), and Excerpta Medica dataBASE (EMBASE, Ovid). Initially, 457 articles were identified and after a rigorous screening and selection process, 37 articles were chosen to be further assessed to ascertain if they met the study's inclusion criteria. Those 37 articles were further evaluated fully to check for relevancy. From that process, 19 articles were chosen for the review, and all passed quality assessment evaluations using the JB Appraisal Tools. To best address the research question, the data from the 19 articles were divided into three categories: 1) circumstantial factors, 2) non-pharmacological methods, and 3) pharmacological methods. Circumstantially, women with previous vaginal deliveries experienced the lowest pain during the procedure, and nulligravid (never pregnant) women experienced the most pain. Lower pain scores were reported by lactating women compared to non-lactating. Black women experienced the most anticipated pain compared to other races. Regarding non-pharmacological methods, different insertion techniques, tools, and the use of a cold compress were found to not affect the level of pain during IUD insertion. Lastly, it was shown that pharmacological methods such as lidocaine gel, lidocaine paracervical block, and lidocaine combined with either diclofenac or prilocaine decreased pain scores at different time stamps of the procedure. Also, oral ketorolac and a vaginal combination of misoprostol and dinoprostone helped reduce pain. Findings from this scoping review revealed a lack of uniformity across practices when performing IUD insertions, possibly due to differences in procedures across circumstantial factors, non-pharmacological methods, and pharmacological methods. More research is needed to investigate the intricacies of pain with IUD insertion. Moving forward, especially following a potential increase in the use of IUDs after the reversal of Roe v. Wade, establishing this gap may lead to a more refined standardized protocol to mitigate pain with IUD insertions.

How much do we know about the metastatic process?

Cancer cells can leave their primary sites and travel through the circulation to distant sites, where they lodge as disseminated cancer cells (DCCs), even during the early and asymptomatic stages of tumor progression. In experimental models and clinical samples, DCCs can be detected in a non-proliferative state, defined as cellular dormancy. This state can persist for extended periods until DCCs reawaken, usually in response to niche-derived reactivation signals. Therefore, their clinical detection in sites like lymph nodes and bone marrow is linked to poor survival. Current cancer therapy designs are based on the biology of the primary tumor and do not target the biology of the dormant DCC population and thus fail to eradicate the initial or subsequent waves of metastasis. In this brief review, we discuss the current methods for detecting DCCs and highlight new strategies that aim to target DCCs that constitute minimal residual disease to reduce or prevent metastasis formation. Furthermore, we present current evidence on the relevance of DCCs derived from early stages of tumor progression in metastatic disease and describe the animal models available for their study. We also discuss our current understanding of the dissemination mechanisms utilized by genetically less- and more-advanced cancer cells, which include the functional analysis of intermediate or hybrid states of epithelial-mesenchymal transition (EMT). Finally, we raise some intriguing questions regarding the clinical impact of studying the crosstalk between evolutionary waves of DCCs and the initiation of metastatic disease.

Colorectal procedures with the novel Hugo™ RAS system: training process and case series report from a non-robotic surgical team.

BACKGROUND: The landscape of robotic surgery is evolving with the emergence of new platforms. However, reports on their applicability in different surgical fields are still limited and come from teams with robotics experience. This study aims to describe the training process for colorectal surgery with the Hugo™ RAS system of a robotics-inexperienced surgical team and present the initial patient series. METHODS: The training process is depicted, and data from the first 10 consecutive patients operated on for colorectal conditions with the Hugo™ RAS system by a surgical team with no prior experience in robotic surgery were prospectively recorded and analysed. RESULTS: The team received intensive training in robotic surgery and specifically in the Hugo™ RAS system previously to the first case. Between May 2023 and December 2023, 10 patients underwent colorectal procedures: 5 right colectomies, 3 sigmoid resections, 1 high rectal resection and 1 ventral mesh rectopexy. The first case was proctored by an expert. Median docking time was 14 min and median total operative time was 185 min. The only technical difficulty during the procedures was occasional clashing of robotic arms. None had to be converted, and no intraoperative or postoperative morbidity was recorded. Hospital stays ranged from 2 to 4 days. A median of 21 lymph nodes were yielded in the operations for malignant conditions. CONCLUSIONS: Common colorectal procedures can be safely performed using the Hugo™ RAS platform. Prior experience in robotic surgery is not a necessary requirement, but following a structured training program is essential.

Oncogenic enhancers prime quiescent metastatic cells to escape NK immune surveillance by eliciting transcriptional memory.

Metastasis arises from disseminated tumour cells (DTCs) that are characterized by intrinsic phenotypic plasticity and the capability of seeding to secondary organs. DTCs can remain latent for years before giving rise to symptomatic overt metastasis. In this context, DTCs fluctuate between a quiescent and proliferative state in response to systemic and microenvironmental signals including immune-mediated surveillance. Despite its relevance, how intrinsic mechanisms sustain DTCs plasticity has not been addressed. By interrogating the epigenetic state of metastatic cells, we find that tumour progression is coupled with the activation of oncogenic enhancers that are organized in variable interconnected chromatin domains. This spatial chromatin context leads to the activation of a robust transcriptional response upon repeated exposure to retinoic acid (RA). We show that this adaptive mechanism sustains the quiescence of DTCs through the activation of the master regulator SOX9. Finally, we determine that RA-stimulated transcriptional memory increases the fitness of metastatic cells by supporting the escape of quiescent DTCs from NK-mediated immune surveillance. Overall, these findings highlight the contribution of oncogenic enhancers in establishing transcriptional memories as an adaptive mechanism to reinforce cancer dormancy and immune escape, thus amenable for therapeutic intervention.

Comparative study of weekly and three-weekly neoadjuvant carboplatin in triple-negative breast cancer: retrospective analysis in real-world settings.

PURPOSE: Tri-weekly carboplatin is an established neoadjuvant treatment for triple-negative breast cancer, enhancing pathological complete response (pCR) and overall survival. This study explores if weekly carboplatin provides lower toxicity and comparable pCR rates. METHODS/PATIENTS: A retrospective multicenter study (January 2021 to March 2023) compares outcomes of weekly and tri-weekly carboplatin. RESULTS: Among 104 participants, 60% received weekly and 40% tri-weekly treatments. Weekly administration had fewer discontinuations (56.5 vs. 70.7%, p = 0.154). Both schedules exhibited similar overall toxicity (p = 0.087), with slightly higher grade 3-4 toxicity in the tri-weekly group (56.1 vs. 48.4%, p = 0.126). Hematological toxicity was comparable, but the weekly group experienced more diarrhea (p = 0.432) and asthenia (p = 0.012). Weekly treatment correlated with more frequent breast-conserving surgeries (p = 0.004). pCR rates were 50% with weekly and 61% with tri-weekly regimens (p = 0.186). CONCLUSIONS: Weekly carboplatin exhibited comparable toxicity, a trend toward fewer interruptions, and similar pCR rates. Prospective studies are essential for validating these findings.

Impaired drainage through capillary-venous networks contributes to age-related white matter loss.

The gradual loss of cerebral white matter contributes to cognitive decline during aging. However, microvascular networks that support the metabolic demands of white matter remain poorly defined. We used in vivo deep multi-photon imaging to characterize microvascular networks that perfuse cortical layer 6 and corpus callosum, a highly studied region of white matter in the mouse brain. We show that these deep tissues are exclusively drained by sparse and wide-reaching venules, termed principal cortical venules, which mirror vascular architecture at the human cortical-U fiber interface. During aging, capillary networks draining into deep branches of principal cortical venules are selectively constricted, reduced in density, and diminished in pericyte numbers. This causes hypo-perfusion in deep tissues, and correlates with gliosis and demyelination, whereas superficial tissues become relatively hyper-perfused. Thus, age-related impairment of capillary-venular drainage is a key vascular deficit that contributes to the unique vulnerability of cerebral white matter during brain aging.

Clinical profiling of pediatric microtia patients: A cross-sectional analysis at a leading pediatric hospital in Ecuador (2015-2022).

BACKGROUND: Microtia is a frequent congenital deformity of the pinna, often with hearing loss. This study reviews the clinical profiles of microtia pediatric patients treated at a referral hospital in Quito, Ecuador, from 2015 to 2022. METHODS: A cross-sectional descriptive study was carried out based on the analysis of medical records of pediatric patients with microtia treated between January 2015 and December 2022 at the Hospital Pediátrico Baca Ortiz in Quito, Ecuador. Descriptive statistics were used, and the Chi-square test assessed associations between categorical variables. RESULTS: Of the 235 patients evaluated, 59.6% were male, 83.4% lived at high altitudes (2500-3500 m), and 19.1% had a family history of microtia. Grade III microtia was diagnosed in 63.8%, predominantly on the right side. Nearly all (99.1%) had hearing loss. Other anatomical alterations were observed in 27.7%, primarily the preauricular appendage. Bone vibrator implantation was a common treatment for 24.3%. Altitude did not show a significant correlation with microtia characteristics. CONCLUSIONS: Most patients had grade III microtia with associated hearing loss. Despite the high prevalence at elevated altitudes, no significant altitude-disease correlation was found. The study highlights the need for further research on microtia in regions like Ecuador.

The elusive brain perivascular fibroblast: a potential role in vascular stability and homeostasis.

In the brain, perivascular fibroblasts (PVFs) reside within the perivascular spaces (PVSs) of arterioles and large venules, however their physiological and pathophysiological roles remain largely unknown. PVFs express numerous extracellular matrix proteins that are found in the basement membrane and PVS surrounding large diameter vessels. PVFs are sandwiched between the mural cell layer and astrocytic endfeet, where they are poised to interact with mural cells, perivascular macrophages, and astrocytes. We draw connections between the more well-studied PVF pro-fibrotic response in ischemic injury and the less understood thickening of the vascular wall and enlargement of the PVS described in dementia and neurodegenerative diseases. We postulate that PVFs may be responsible for stability and homeostasis of the brain vasculature, and may also contribute to changes within the PVS during disease.

Aphasia improvement without logotherapy during motor neurorehabilitation of post-stroke hemiparesis using virtual reality or modified constraint-induced movement therapy: A retrospective cohort.

BACKGROUND: Some research suggests that post-stroke aphasia can recover "on its own", however, there is evidence of a common neural substrate for motor and language systems. We hypothesize, that motor neurorehabilitation of hemiparesis could be related to simultaneous improvement in aphasia. OBJECTIVE: To measure changes in post-stroke aphasia and its relation with hemiparesis treated with different therapies. METHODS: Database information (n = 32) on post-stroke hemiparesis (Fugl-Meyer Scale evaluated) managed with virtual reality (VR) versus modified constraint-induced movement therapy (mCIMT) or regular therapy (rPT/OT) was analyzed. None received logotherapy (LT) by appointment at four months. INCLUSION CRITERIA: < 3 months after the stroke, aphasia severe (Boston Aphasia Intensity Scale), and all three evaluations. RESULTS: Twenty-one patient records met inclusion criteria (71,4% women and mean age 66,67±3,13 years) who received VR, mCIMT, or rPT/OT (n = 6, 8, and 7, respectively). There was continuous intra-groups improvement in aphasia (p < 0.05), but inter-groups the greater aphasia recovery (p = 0.05) and hemiparesis (p = 0.02) were in VR, with a high correlation in evolution between them (r = 0.73; p = 0.047). CONCLUSION: High clinical correlation between aphasia, without LT, and hemiparesis evolution during motor neurorehabilitation would support common neural connections stimulation. We will conduct a clinical trial, with a larger sample size to contrast our hypothesis.

Capillary regression leads to sustained local hypoperfusion by inducing constriction of upstream transitional vessels.

In the brain, a microvascular sensory web coordinates oxygen delivery to regions of neuronal activity. This involves a dense network of capillaries that send conductive signals upstream to feeding arterioles to promote vasodilation and blood flow. Although this process is critical to the metabolic supply of healthy brain tissue, it may also be a point of vulnerability in disease. Deterioration of capillary networks is a hallmark of many neurological disorders and how this web is engaged during vascular damage remains unknown. We performed in vivo two-photon microscopy on young adult mural cell reporter mice and induced focal capillary injuries using precise two-photon laser irradiation of single capillaries. We found that ∼63% of the injuries resulted in regression of the capillary segment 7-14 days following injury, and the remaining repaired to re-establish blood flow within 7 days. Injuries that resulted in capillary regression induced sustained vasoconstriction in the upstream arteriole-capillary transition (ACT) zone at least 21 days post-injury in both awake and anesthetized mice. This abnormal vasoconstriction involved attenuation of vasomotor dynamics and uncoupling from mural cell calcium signaling following capillary regression. Consequently, blood flow was reduced in the ACT zone and in secondary, uninjured downstream capillaries. These findings demonstrate how capillary injury and regression, as often seen in age-related neurological disease, can impair the microvascular sensory web and contribute to cerebral hypoperfusion. SIGNIFICANCE: Deterioration of the capillary network is a characteristic of many neurological diseases and can exacerbate neuronal dysfunction and degeneration due to poor blood perfusion. Here we show that focal capillary injuries can induce vessel regression and elicit sustained vasoconstriction in upstream transitional vessels that branch from cortical penetrating arterioles. This reduces blood flow to broader, uninjured regions of the same microvascular network. These findings suggest that widespread and cumulative damage to brain capillaries in neurological disease may broadly affect blood supply and contribute to hypoperfusion through their remote actions.

Sporotrichosis in Argentina: clinical and epidemiological analysis / Esporotricosis en Argentina: análisis clínico y epidemiológico

Introduction: Sporotrichosis is an implantation mycosis caused by Sporothrix spp. It is distributed worldwide and can be found in vegetation and soil. The most frequent route of infection is by trauma with elements contaminated with fungal propagules. Since domestic cats are the most affected animals and can transmit this infection to humans, sporotrichosis is considered a zoonosis. Clinical presentations include nodular lymphangitis, fixed cutaneous, pulmonary (rare), and disseminated (exceptional). Objectives: To analyze the epidemiology of sporotrichosis in Argentina during 2010 and 2022. To describe the clinical presentation, diagnostic methods, and treatment of cases diagnosed during this period. To know the circulating genotypes and to observe possible associations with the geographic location where the infection was acquired. Materials and methods: Analytical, retrospective, and observational study. We analyzed the medical records of patients with sporotrichosis from 12 health institutions in Argentina, between 2010 and 2022. Results: We present 54 cases in which the most frequent clinical form was nodular lymphangitis, and the treatment of choice was itraconazole. Conventional diagnosis was made in all cases. Culture of clinical samples was more sensitive than direct examination because it allowed the isolation of Sporothrix spp. in all 54 cases. Molecular identification was performed in 22 cases, with Sporothrix schenkii sensu stricto being the most frequently isolated species. Conclusions: This study allowed to know the epidemiology of this mycosis in Argentina, as well as the availability of diagnostic methods and the treatment of choice.

Introducción: La esporotricosis es una micosis de implantación causada por Sporothrix spp. Este se encuentra distribuido mundialmente y se puede encontrar en la vegetación y en el suelo. La ruta más frecuente de adquisición de la infección es por traumatismos con elementos contaminados con propágulos del hongo. Los gatos domésticos son los animales más afectados y pueden transmitirla a los humanos, por lo que es considerada una zoonosis. Las formas clínicas incluyen: la linfangítica nodular, la cutánea fija, la pulmonar (poco habitual) y la diseminada (excepcional). Objetivo: Analizar la epidemiología de la esporotricosis en Argentina entre los años 2010 y 2022. Describir la presentación clínica, los métodos de diagnóstico y el tratamiento de los casos diagnosticados en este período. Conocer los genotipos circulantes y observar su relación con el lugar geográfico de adquisición de la infección. Materiales y métodos. Se llevó a cabo un estudio analítico, retrospectivo y observacional, en el que se analizaron las historias clínicas de los pacientes con esporotricosis de 12 instituciones de salud de Argentina, entre los años 2010 y 2022. Resultados: Se presentan 54 casos en los que la forma clínica más frecuente fue la linfangítica nodular y el tratamiento de elección fue el itraconazol. En todos los casos se realizó diagnóstico convencional. El cultivo de las muestras clínicas resultó más sensible que el examen directo, ya que permitió el desarrollo de Sporothrix spp. en los 54 casos. En 22 casos se hizo identificación molecular y Sporothrix schenkii sensu stricto fue la especie más frecuentemente aislada. Conclusiones: Este estudio permitió conocer la epidemiología de esta micosis en Argentina, así como la disponibilidad de métodos diagnósticos y el tratamiento de elección.

The impact of sciatic nerve injury and social interactions testing on glucocorticoid receptor expression in catecholaminergic medullary cell populations.

Paradoxically, while acute pain leads to transiently elevated corticosterone, chronic pain does not result in persistently elevated corticosterone. In the sciatic nerve chronic constriction injury (CCI) model of chronic pain, we have shown that the same nerve injury produces a range of behavioural outcomes, each associated with distinctive adaptations to the HPA-axis to achieve stable plasma corticosterone levels. We also demonstrated that CRF and GR expression in the paraventricular hypothalamus (PVH) was increased in rats that showed persistent changes to their social behaviours during Resident-Intruder testing ('Persistent Effect' rats) when compared to rats that showed no behavioural changes ('No Effect' rats). In this study, we investigated whether these changes were driven in part by altered sensitivity of the brainstem catecholaminergic pathways (known to regulate the PVH) to glucocorticoids. GR expression in adrenergic (C1,C2) and noradrenergic (A1,A2) cells was determined using immunohistochemistry in behaviourally tested CCI rats and in uninjured controls. We found no differences between Persistent Effect and No Effect rats in (1) the glucocorticoid sensitivity of these cells, or (2) the numbers of adrenergic and noradrenergic cells in each region. However, we discovered an overall reduction in GR expression in the non-catecholaminergic cells of these regions in both experimental groups when compared to uninjured controls, most likely attributable to the repeated Resident-Intruder testing. Taken together, these data suggest strongly that brainstem mechanisms are unlikely to play a key role in the rebalancing of the HPA-axis triggered by CCI, increasing the probability that these changes are driven by supra-hypothalamic regions.

Esporotricosis en Argentina: análisis clínico y epidemiológico / Sporotrichosis in Argentina: clinical and epidemiological analysis

Introducción. La esporotricosis es una micosis de implantación causada por Sporothrix spp. Este se encuentra distribuido mundialmente y se puede encontrar en la vegetación y en el suelo. La ruta más frecuente de adquisición de la infección es por traumatismos con elementos contaminados con propágulos del hongo. Los gatos domésticos son los animales más afectados y pueden transmitirla a los humanos, por lo que es considerada una zoonosis. Las formas clínicas incluyen: la linfangítica nodular, la cutánea fija, la pulmonar (poco habitual) y la diseminada (excepcional). Objetivo. Analizar la epidemiología de la esporotricosis en Argentina entre los años 2010 y 2022. Describir la presentación clínica, los métodos de diagnóstico y el tratamiento de los casos diagnosticados en este período. Conocer los genotipos circulantes y observar su relación con el lugar geográfico de adquisición de la infección. Materiales y métodos. Se llevó a cabo un estudio analítico, retrospectivo y observacional, en el que se analizaron las historias clínicas de los pacientes con esporotricosis de 12 instituciones de salud de Argentina, entre los años 2010 y 2022. Resultados. Se presentan 54 casos en los que la forma clínica más frecuente fue la linfangítica nodular y el tratamiento de elección fue el itraconazol. En todos los casos se realizó diagnóstico convencional. El cultivo de las muestras clínicas resultó más sensible que el examen directo, ya que permitió el desarrollo de Sporothrix spp. en los 54 casos. En 22 casos se hizo identificación molecular y Sporothrix schenkii sensu stricto fue la especie más frecuentemente aislada. Conclusiones. Este estudio permitió conocer la epidemiología de esta micosis en Argentina, así como la disponibilidad de métodos diagnósticos y el tratamiento de elección.

Introduction. Sporotrichosis is an implantation mycosis caused by Sporothrix spp. It is distributed worldwide and can be found in vegetation and soil. The most frequent route of infection is by trauma with elements contaminated with fungal propagules. Since domestic cats are the most affected animals and can transmit this infection to humans, sporotrichosis is considered a zoonosis. Clinical presentations include nodular lymphangitis, fixed cutaneous, pulmonary (rare), and disseminated (exceptional). Objective. To analyze the epidemiology of sporotrichosis in Argentina during 2010 and 2022. To describe the clinical presentation, diagnostic methods, and treatment of cases diagnosed during this period. To know the circulating genotypes and to observe possible associations with the geographic location where the infection was acquired. Materials and methods. Analytical, retrospective, and observational study. We analyzed the medical records of patients with sporotrichosis from 12 health institutions in Argentina, between 2010 and 2022. Results. We present 54 cases in which the most frequent clinical form was nodular lymphangitis, and the treatment of choice was itraconazole. Conventional diagnosis was made in all cases. Culture of clinical samples was more sensitive than direct examination because it allowed the isolation of Sporothrix spp. in all 54 cases. Molecular identification was performed in 22 cases, with Sporothrix schenkii sensu stricto being the most frequently isolated species. Conclusions. This study allowed to know the epidemiology of this mycosis in Argentina, as well as the availability of diagnostic methods and the treatment of choice.

5-Azacytidine- and retinoic-acid-induced reprogramming of DCCs into dormancy suppresses metastasis via restored TGF-ß-SMAD4 signaling.

Disseminated cancer cells (DCCs) in secondary organs can remain dormant for years to decades before reactivating into overt metastasis. Microenvironmental signals leading to cancer cell chromatin remodeling and transcriptional reprogramming appear to control onset and escape from dormancy. Here, we reveal that the therapeutic combination of the DNA methylation inhibitor 5-azacytidine (AZA) and the retinoic acid receptor ligands all-trans retinoic acid (atRA) or AM80, an RARα-specific agonist, promotes stable dormancy in cancer cells. Treatment of head and neck squamous cell carcinoma (HNSCC) or breast cancer cells with AZA+atRA induces a SMAD2/3/4-dependent transcriptional program that restores transforming growth factor ß (TGF-ß)-signaling and anti-proliferative function. Significantly, either combination, AZA+atRA or AZA+AM80, strongly suppresses HNSCC lung metastasis formation by inducing and maintaining solitary DCCs in a SMAD4+/NR2F1+ non-proliferative state. Notably, SMAD4 knockdown is sufficient to drive resistance to AZA+atRA-induced dormancy. We conclude that therapeutic doses of AZA and RAR agonists may induce and/or maintain dormancy and significantly limit metastasis development.

[Pain after panretinal photocoagulation: 50-millisecond pulse versus conventional pulse]. / Dolor posterior a panfotocoagulación retiniana: impulso de 50 milisegundos frente a impulso convencional.

Background: Diabetic retinopathy is a progressive disfunction of blood vessels of the retina secondary to chronic hyperglycemia. There are several treatments, out of which panretinal photocoagulation (PRP) stands out. Objective: To compare the level of pain in patients undergoing PRP with different impulse. Material and methods: Comparative, cross-sectional study that compared the level of pain in patients undergoing PRP with a 50-millisecond pulse (group A) versus conventional 200 milliseconds pulse (group B). Mann-Whitney U test was used. Results: There were 26 patients, 12 (46.16%) female and 14 (53.84%) males. The median age was 58.73 ± 7.31 (40-75) years. 40 eyes were studied, 18 (45%) right and 22 (55%) left. The mean level of glycated hemoglobin was 8.15 ± 1.08 (6.5-12) %. The mean laser power was 297 ± 53.61 (200-380) and 214.5 ± 41.73 (170-320) milliwatts; the mean fluence was 18.85 ± 5.28 (12-28) J/cm2 and 65.9 ± 12.87 (52-98) J/cm2; the mean level of pain was 3.1 ± 1.33 (1-5) and 7.5 ± 1.23 (6-10) points for group A and B, respectively, and there was statistically significant difference (p ˂ 0.001) in the level of pain. There were no complications in any group. Conclusion: The application of retinal 50-millisecond pulse PRP causes less pain and side effects than 200-millisecond pulse PRP.

Introducción: la retinopatía diabética es una disfunción progresiva del sistema vascular de la retina que es secundaria a una hiperglucemia crónica. Hay varias opciones de tratamiento, entre las que destaca la panfotocoagulación. Objetivo: comparar el nivel de dolor en pacientes sometidos a panfotocoagulación retiniana con diferente impulso. Material y métodos: estudio comparativo, transversal, que comparó el nivel de dolor en pacientes sometidos a panfotocoagulación con impulso de 50 milisegundos (grupo A) frente a impulso convencional de 200 milisegundos (grupo B). Se utilizó U de Mann Whitney. Resultados: fueron 26 pacientes, 12 (46.16%) mujeres y 14 (53.84%) hombres. La edad mediana fue 58.73 ± 7.31 (40-75) años. Se estudiaron 40 ojos, 18 (45%) derechos y 22 (55%) izquierdos. El nivel medio de hemoglobina glucosilada fue 8.15 ± 1.08 (6.5-12)%. La potencia láser media fue 297 ± 53.61 (200-380) y 214.5 ± 41.73 (170-320) miliwatts, la fluencia media fue 18.85 ± 5.28 (12-28) J/cm2 y 65.9 ± 12.87 (52-98) J/cm2, el nivel medio de dolor fue 3.1 ± 1.33 (1-5) y 7.5 ± 1.23 (6-10) puntos para el grupo A y B, respectivamente y hubo diferencia estadísticamente significativa (p ≤ 0.001) en el nivel de dolor. En ningún grupo hubo complicaciones. Conclusión: la aplicación de panfotocoagulación retiniana con impulso de 50 milisegundos provoca menos dolor y efectos secundarios que la panfotocoagulación con impulso de 200 milisegundos.

Association between self-reported evidence-based medicine competencies and prescribing of drugs without scientific evidence against mild COVID-19 among recently graduated physicians in Peru.

Objective: To evaluate the association between self-rated evidence-based medicine (EBM) competencies and the prescription of drugs without scientific evidence against mild COVID-19 (present with any of the signs and symptoms of COVID-19 but who do not have shortness of breath, dyspnea, or abnormal chest imaging) among recently graduated physicians in Peru. Methods: We conducted an analytical cross-sectional study where we evaluated a non-probability sample of recently graduated physicians during June and July 2021 (end of second wave of COVID-19 in Peru). Self-rated EBM competencies were assessed by four domains (formulation of a clinical question, search, analysis, and application) using a Likert scale with scores from zero to four ("Very inadequate" = 0, to "Very Adequate" = 4), it was considered as "Adequate" if the score was three or four. In addition, the variable "General competence on EBM" was rated as "Adequate" if in all domains evaluated it presented an adequate self-rating. For the outcome, drug prescription, we considered the use of ivermectin, azithromycin, other antibiotics, hydroxychloroquine, dexamethasone, and anticoagulants (drugs with no efficacy demonstrated for patients with mild COVID-19). To assess the association, we used Poisson regression models with robust variances and obtaining crude (cPR) and adjusted (aPR) prevalence ratios with their 95% confidence intervals (95%CI). Results: Of a total of 239 physicians included 70.7% prescribed at least one drug without scientific evidence. A total of 51.1% reported adequate ratings in all evaluated domains of EBM. Self-rating the "Clinical Question Formulation" competency as adequate was associated with a lower frequency of prescribing medications for mild COVID-19 (aPR: 0.93; 95% CI: 0.91-0.95). While self-rating as adequate the competency of "Identify possible implications of investigations" was associated with an increase in the prescription of such drugs (aPR: 1.14; 95% CI: 1.09-1.20). Additionally, self-rating all domains as adequate were associated with less prescription (aPR: 0.93; 95% CI: 0.90-0.96). Conclusion: Seven out of ten recently graduated physicians prescribed some type of medication without scientific evidence to treat patients with mild COVID-19. Having adequate self-perceived EBM competencies was associated with a lower frequency of prescribing medications without scientific evidence to manage patients with mild COVID-19.

Clinical and Demographic Features of Paracoccidioidomycosis in Argentina: A Multicenter Study Analysis of 466 Cases.

Information on paracoccidioidomycosis (PCM) in Argentina is fragmented and has historically been based on estimates, supported only by a series of a few reported cases. Considering the lack of global information, a national multicentric study in order to carry out a more comprehensive analysis was warranted. We present a data analysis including demographic and clinical aspects of a historical series of 466 cases recorded over 10 years (2012-2021). Patients were aged from 1 to 89 years. The general male: female (M:F) ratio was 9.5:1 with significant variation according to the age group. Interestingly, the age range 21-30 shows an M:F ratio of 2:1. Most of the cases (86%) were registered in northeast Argentina (NEA), showing hyperendemic areas in Chaco province with more than 2 cases per 10,000 inhabitants. The chronic clinical form occurred in 85.6% of cases and the acute/subacute form occurred in 14.4% of cases, but most of these juvenile type cases occurred in northwestern Argentina (NWA). In NEA, the incidence of the chronic form was 90.6%; in NWA, the acute/subacute form exceeded 37%. Diagnosis by microscopy showed 96% positivity but antibody detection displays 17% of false negatives. Tuberculosis was the most frequent comorbidity, but a diverse spectrum of bacterial, fungal, viral, parasitic, and other non-infectious comorbidities was recorded. This national multicenter registry was launched in order to better understand the current status of PCM in Argentina and shows the two endemic zones with a highly diverse epidemiology.