Willingness to vaccinate children against COVID-19 declined during the pandemic.

OBJECTIVES: To document the level of vaccine hesitancy in caregivers' of children younger than 12 years of age over the course of the pandemic in Pediatric Emergency Departments (ED). Study design Ongoing multicenter, cross-sectional survey of caregivers presenting to 19 pediatric EDs in the USA, Canada, Israel, and Switzerland during first months of the pandemic (phase1), when vaccines were approved for adults (phase2) and most recently when vaccines were approved for children (phase3). RESULTS: Willingness to vaccinate rate declined over the study period (59.7%, 56.1% and 52.1% in the three phases). Caregivers who are fully vaccinated, who have higher education, and those worried their child had COVID-19 upon arrival to the ED, were more likely to plan to vaccinate in all three phases. Mothers were less likely to vaccinate early in the pandemic, but this hesitancy attenuated in later phases. Older caregivers were more willing to vaccinate, and caregivers of older children were less likely to vaccinate their children in phase 3. During the last phase, willingness to vaccinate was lowest in those who had a primary care provider but did not rely on their advice for medical decisions (34%). Those with no primary care provider and those who do and rely on their medical advice, had similar rates of willingness to vaccinate (55.1% and 52.1%, respectively). CONCLUSIONS: COVID-19 vaccine hesitancy is widespread and growing over time, and public health measures should further try to leverage identified factors associated with hesitancy in order to enhance vaccination rates among children.

Hypermethylation of the tumor suppressor gene PRDM1/Blimp-1 supports a pathogenetic role in EBV-positive Burkitt lymphoma.

PRDM1/Blimp-1 is a tumor suppressor gene in the activated B-cell subtype of diffuse large B-cell lymphomas. Its inactivation contributes to pathogenesis in this setting by impairing terminal B-cell differentiation induced by constitutive nuclear factor-κB activation. The role of PRDM1 in Burkitt lymphoma (BL) lymphomagenesis is not known. Here we identified hypermethylation of the promoter region and exon 1 of PRDM1 in all six Epstein-Barr virus (EBV)-positive BL cell lines and 12 of 23 (52%) primary EBV-positive BL or BL-related cases examined, but in none of the EBV-negative BL cell lines or primary tumors that we assessed, implying a tumor suppressor role for PRDM1 specifically in EBV-associated BL. A direct induction of PRDM1 hypermethylation by EBV is unlikely, as PRDM1 hypermethylation was not observed in EBV-immortalized B lymphoblastoid cell lines. Treatment of EBV-positive BL cells with 5' azacytidine resulted in PRDM1 induction associated with PRDM1 demethylation, consistent with transcriptional silencing of PRDM1 as a result of DNA methylation. Overexpression of PRDM1 in EBV-positive BL cell lines resulted in cell cycle arrest. Our results expand the spectrum of lymphoid malignancies in which PRDM1 may have a tumor suppressor role and identify an epigenetic event that likely contributes to the pathogenesis of BL.

Room temperature strong coupling between a microwave oscillator and an ensemble of electron spins.

We demonstrate theoretically and experimentally the possibility to achieve the strong coupling regime at room temperature with a microwave electronic oscillator coupled with an ensemble of electron spins. The coupled system shows bistable behaviour, with a broad hysteresis and sharp transitions. The coupling strength and the hysteresis width can be adjusted through the number of spins in the ensemble, the temperature, and the microwave field strength.

Protein 3-nitrotyrosine formation during Trypanosoma cruzi infection in mice

Nitric oxide (ÀNO) is a diffusible messenger implicated in Trypanosoma cruzi resistance. Excess production of ÀNO and oxidants leads to the generation of nitrogen dioxide (ÀNO2), a strong nitrating agent. Tyrosine nitration is a post-translational modification resulting from the addition of a nitro (-NO2) group to the ortho-position of tyrosine residues. Detection of protein 3-nitrotyrosine is regarded as a marker of nitro-oxidative stress and is observed in inflammatory processes. The formation and role of nitrating species in the control and myocardiopathy of T. cruzi infection remain to be studied. We investigated the levels of ÀNO and protein 3-nitrotyrosine in the plasma of C3H and BALB/c mice and pharmacologically modulated their production during the acute phase of T. cruzi infection. We also looked for protein 3-nitrotyrosine in the hearts of infected animals. Our results demonstrated that C3H animals produced higher amounts of ÀNO than BALB/c mice, but their generation of peroxynitrite was not proportionally enhanced and they had higher parasitemias. While N G-nitro-arginine methyl ester treatment abolished ÀNO production and drastically augmented the parasitism, mercaptoethylguanidine and guanido-ethyl disulfide, at doses that moderately reduced the ÀNO and 3-nitrotyrosine levels, paradoxically diminished the parasitemia in both strains. Nitrated proteins were also demonstrated in myocardial cells of infected mice. These data suggest that the control of T. cruzi infection depends not only on the capacity to produce ÀNO, but also on its metabolic fate, including the generation of nitrating species that may constitute an important element in parasite resistance and collateral myocardial damage.

Protein 3-nitrotyrosine formation during Trypanosoma cruzi infection in mice.

Nitric oxide (.NO) is a diffusible messenger implicated in Trypanosoma cruzi resistance. Excess production of .NO and oxidants leads to the generation of nitrogen dioxide (.NO2), a strong nitrating agent. Tyrosine nitration is a post-translational modification resulting from the addition of a nitro (-NO2) group to the ortho-position of tyrosine residues. Detection of protein 3-nitrotyrosine is regarded as a marker of nitro-oxidative stress and is observed in inflammatory processes. The formation and role of nitrating species in the control and myocardiopathy of T. cruzi infection remain to be studied. We investigated the levels of .NO and protein 3-nitrotyrosine in the plasma of C3H and BALB/c mice and pharmacologically modulated their production during the acute phase of T. cruzi infection. We also looked for protein 3-nitrotyrosine in the hearts of infected animals. Our results demonstrated that C3H animals produced higher amounts of .NO than BALB/c mice, but their generation of peroxynitrite was not proportionally enhanced and they had higher parasitemias. While N G-nitro-arginine methyl ester treatment abolished .NO production and drastically augmented the parasitism, mercaptoethylguanidine and guanido-ethyl disulfide, at doses that moderately reduced the .NO and 3-nitrotyrosine levels, paradoxically diminished the parasitemia in both strains. Nitrated proteins were also demonstrated in myocardial cells of infected mice. These data suggest that the control of T. cruzi infection depends not only on the capacity to produce .NO, but also on its metabolic fate, including the generation of nitrating species that may constitute an important element in parasite resistance and collateral myocardial damage.

Relación entre la expresión de Glicoproteína P y los hallazgos de la centellografía con Tc-99m MIBI en pacientes con cáncer mamario avanzado / Relation between P-glycoprotein expression and scintigraphic findings with Tc-99m MIBI in advanced breast cancer patients

En un estudio previo encontramos que el grado de captación tumoral pre-tratamiento de Tc-99m MIBI, un sustrato de transporte de la Glicoproteína P (Pgp), se correlaciona con la respuesta clínica a la quimioterapia basada en antraciclinas en pacientes con cáncer mamario avanzado (CMA). El objetivo del presente estudio fue determinar la relación entre la expresión tumoral de Pgp, el grado de captación tumoral de MIBI y la respuesta clínica a la quimioterapia en pacientes con CMA. Se estudiaron 27 lesiones correspondientes a 26 pacientes. La expresión de Pgp fue investigada previamente a la quimioterapia mediante inmunocitoquímica. Las imágenes centellográficas fueron realizadas dentro de la semana previa a la quimioterapia, 10 minutos (fase temprana) y 60 minutos (fase tardía) después de la inyección de 740-1110 MBq de Tc-99m MIBI. La captación lesional fue cuantificada mediante tasa de conteo tumor/fondo en las fases precoz (T/Fp) y tardía (T/Ft) del estudio. Ambos índices fueron superiores (p< 0.05) en las lesiones Pgp negativas (n=21) que en las Pgp positivas (n=6). Además, fueron más elevados en las lesiones respondedoras que en las no respondedoras (T/Fp 2.2 vs 1.4; T/Ft 1.8 vs 1.4; p< 0.05). Todas las lesiones con un índice T/Fp mayor de 1.5 respondieron a la quimioterapia. No se encontró asociación significativa entre la expresión de Pgp y la respuesta a la quimioterapia. Concluimos que la centellografía con MIBI puede predecir el fenotipo MDR1 y la respuesta a la quimioterapia basada en adriamicina en pacientes con CMA. El nivel de expresión de Pgp no sería útil para predecir dicha respuesta.

Adrenergic innervation in reactive human lymph nodes.

Several experimental models have demonstrated that the central nervous system is functionally linked to the immune system by means of the autonomic nervous system. Samples of 36 lymph nodes of patients whose ages ranged from 16 to 69 y were studied. In order to demonstrate the existence and distribution of sympathetic nerve fibres, a polyclonal antibody antityrosine hydroxylase (TH), with the streptavidin-biotin system of detection, was used. TH-positive nerve fibres appeared in all reactive patterns of the lymph nodes studied. Thin nerve fascicles ramified at the hilar region and also in the connective tissue septae. Adventitial adrenergic nerve fibres were found following afferent, and to a lesser extent, efferent blood vessels. Another source of incoming nerve fibres was found at capsular level, accompanying blood vessels. On the arterial side, the innervation ceased before reaching the follicular arterioles. Our demonstration of innervation in postcapillary venules could support a regulatory role of adrenergic neurotransmitters in lymphocyte traffic. Occasional nerve fibres were also seen in T areas among parenchymatous cells. These findings confirm the existence of sympathetic innervation in human lymph nodes, and provide indirect evidence that the psychoneuroimmune axis could also exist in humans.

Peroxynitrite inhibits T lymphocyte activation and proliferation by promoting impairment of tyrosine phosphorylation and peroxynitrite-driven apoptotic death.

Peroxynitrite (ONOO-) is a potent oxidizing and nitrating agent produced by the reaction of nitric oxide with superoxide. It readily nitrates phenolic compounds such as tyrosine residues in proteins, and it has been demonstrated that nitration of tyrosine residues in proteins inhibits their phosphorylation. During immune responses, tyrosine phosphorylation of key substrates by protein tyrosine kinases is the earliest of the intracellular signaling pathways following activation through the TCR complex. This work was aimed to evaluate the effects of ONOO- on lymphocyte tyrosine phosphorylation, proliferation, and survival. Additionally, we studied the generation of nitrating species in vivo and in vitro during immune activation. Our results demonstrate that ONOO-, through nitration of tyrosine residues, is able to inhibit activation-induced protein tyrosine phosphorylation in purified lymphocytes and prime them to undergo apoptotic cell death after PHA- or CD3-mediated activation but not upon phorbol ester-mediated stimulation. We also provide evidence indicating that peroxynitrite is produced during in vitro immune activation, mainly by cells of the monocyte/macrophage lineage. Furthermore, immunohistochemical studies demonstrate the in vivo generation of nitrating species in human lymph nodes undergoing mild to strong immune activation. Our results point to a physiological role for ONOO- as a down-modulator of immune responses and also as key mediator in cellular and tissue injury associated with chronic activation of the immune system.

The interrelationship between tubular and papillary sectors of tubulo-villous colorectal adenomas: comparative morphometric analysis and evaluation of cell proliferation.

In a series of 100 colorectal adenomas, 23 tubulo-villous adenomas were individualized through the identification of papillae as structures persisting for more than 100 microm in serial sections with a connective axis lined with epithelial cells. In these adenomas, the tubular and villous areas with the highest dysplasia were selected, and a morphometric analysis was undertaken to assess the Index of Structural Atypia, the Nucleo-Glandular Index, and the Nuclear Stratification Index. The AgNor count and the proliferating cell nuclear antigen (PCNA) Label Index (LI) also were performed. The overall mean of each of these indexes was significantly higher in the villous sector than in the tubular one (P < .001). In 16 cases, the semi-objective method of dysplasia gradation showed a superior degree in the papillary sector, whereas it showed an equal degree in the remaining seven lesions. The AgNOR count was significantly different in all cases, with higher values in villous sectors (P < .05). With the exception of one case, this was confirmed by the PCNA LI. The Stratification Index showed significantly different values in 20 cases, whereas the other morphometric indexes showed a less discriminatory result. Our findings objectively show that the degree of dysplasia in tubulo-villous adenomas should be analyzed in the villous sector. The existence of heterogeneous cellular populations has been confirmed both in the structural organization of cells and in some basic parameters such as the cell proliferation rate in colorectal adenomas. Our findings suggest that the occurrence of villous architectural growth is a secondary event in a tubular adenoma. Enhanced cellular proliferation of the villous area allows the progressive substitution of tubular structures.

Carcinoide de intestino delgado: una causa rara de infarto intestino mesentérico / Carcinoid tumor of small intestine, cause of mesenteric intestinal infarction

Las neoplasias del intestino delgado son poco frecuentes. Los carcinoides son el 20 por ciento de éstas. La mayoría son asintomáticos y son hallazgos incidentales, el resto se presenta por sus complicaciones, como cuadros agudos de abdomen, el más frecuente es la oclusión intestinal. El infarto intestino mesentérico y la isquemia intestinal han sido reconocidos como otra presentación muy rara, en estos casos la terapéutica quirúrgica agresiva, a pesar de la gravedad de la presentación, muestra beneficios en el pronóstico. Se presentan 2 casos y se discuten los eventos patogénicos

Carcinoide de intestino delgado: una causa rara de infarto intestino mesentérico / Carcinoid tumor of small intestine, cause of mesenteric intestinal infarction

Las neoplasias del intestino delgado son poco frecuentes. Los carcinoides son el 20 por ciento de éstas. La mayoría son asintomáticos y son hallazgos incidentales, el resto se presenta por sus complicaciones, como cuadros agudos de abdomen, el más frecuente es la oclusión intestinal. El infarto intestino mesentérico y la isquemia intestinal han sido reconocidos como otra presentación muy rara, en estos casos la terapéutica quirúrgica agresiva, a pesar de la gravedad de la presentación, muestra beneficios en el pronóstico. Se presentan 2 casos y se discuten los eventos patogénicos (AU)

[Quantitative evaluation of juxtatrabecular fibrosis in myelodysplastic syndromes]. / Valoración cuantitativa de la fibrosis yuxtatrabecular en los síndromes mielodisplásicos.

PURPOSE: Myelofibrosis is a common, poor-prognosis feature of myelodysplastic syndromes (MDS). The aim of this work was to evaluate quantitatively the extent of the juxtatrabecular fibrosis in primary MDS and in secondary myelodysplasias, along with the presence of immature precursor cells in anomalous position, that is, the displacement of granulopoiesis from the paratrabecular area to central positions. PATIENTS AND METHODS: Twenty-seven bone marrow samples were examined: 9 from primary MDS, 9 from secondary myelodysplasias, and 9 normal. The percentage of myeloblasts and promyelocytes with nucleoli located in the central areas was estimated, in an attempt to correlate such feature with the degree of juxtatrabecular fibrosis. The analysis of data was performed with the Kruskal-Wallis test, values of p < 0.01 being significant. RESULTS: Sectorial juxtatrabecular fibrosis was present in all the myelodysplastic samples, ranging from 6% to 55% of the trabecular surface; the highest values found in the controls were about 3.6% (p < 0.01). Although the juxtatrabecular fibrosis figures are higher in secondary MDS, the difference is not significant with regard to the primary MDS in the number of patients studied here. The count of myeloblasts and promyelocytes with nucleoli present in the MDS was significantly greater than that of the control group. The number of promyelocytes with nucleoli was significantly higher in the primary MDS with respect to the secondary ones, whereas no significant difference was seen between the two types of MDS regarding the myeloblast count. CONCLUSIONS: The increased number of central immature precursor cells in MDS was not directly correlated with the extent of the juxtatrabecular fibrosis. Although the number of cases is small, the fact that the juxtatrabecular fibrosis was higher in the two deceased patients in the series (49% and 56%, respectively) suggests a poor-risk prognosis for such finding.

[Primary small cell carcinoma of the esophagus]. / Carcinoma de células pequeñas primitivo de esófago.

Primary small cell carcinoma of the esophagus, morologically indistinguishable from its counterpart of the lung is a rare tumour with a frequency between 0.05 to 7.6% of all esophageal malignancies. Currently they are divided into oat cell and non oat cell, regarding the presence of neuroendocrine granules. We report 3 cases from our hospital. They were studied clinicopathologically and also examined by electron microscopy.

[Helicobacter pylori: comparative study of different diagnostic techniques]. / Helicobacter pylori: estudio comparativo de diferentes técnicas diagnósticas.

OBJECTIVE: To compare the different diagnostic techniques of Helicobacter Pylori infection, confronting the bacteriological culture to other faster, less expensive and easier techniques, such as the urease test, methylen blue and Gram stained smears, the histopathologic examination of biopsies specimens, and the detection of IgG antibodies anti Helicobacter Pylori. MATERIAL AND METHODS: 43 patients with gastroduodenal symptoms who had not taken NSAIDs and who presented endoscopic signs of inlammation and/or gastroduodenal ulcer were prospectively studied. Biopsies specimens of antrum, gastric fundus and duodenal bulb were taken and processed in the following way: methylen blue and Gram stained smears and Hematoxylin and eosin stained section. Studies were performed in to all the 43 patients. Urease test was performed in the antrum specimens of 37 patients, and inmunologic test by inmunoenzimatic technique (ELISA) in 40 of them. RESULTS: Methylen blue and Gram stained smears: sensitivity (S): 100% and specificity (E): 76% Histopathologic examination (S): 86% (E): 61%, urease test (S) 100% (E) 62.5%, antibodies anti H.P. not possible to calculate. DISCUSSION: The authors have taken the microbiological culture as a reference technique because the isolation and identification of the bacteria are the most important signs of its presence and vitality. Stained smears, histopathologic examination and the urease test are fast, inexpensive techniques with high sensitivity for diagnosis. However, the inmunologic test is reveals better to the prevalence of the infection.

Carcinoma de células pequeñas primitivo de esófago. / [Primary small cell carcinoma of the esophagus]

Primary small cell carcinoma of the esophagus, morologically indistinguishable from its counterpart of the lung is a rare tumour with a frequency between 0.05 to 7.6

of all esophageal malignancies. Currently they are divided into oat cell and non oat cell, regarding the presence of neuroendocrine granules. We report 3 cases from our hospital. They were studied clinicopathologically and also examined by electron microscopy.

Helicobacter pylori: estudio comparativo de diferentes técnicas diagnósticas. / [Helicobacter pylori: comparative study of different diagnostic techniques]

OBJECTIVE: To compare the different diagnostic techniques of Helicobacter Pylori infection, confronting the bacteriological culture to other faster, less expensive and easier techniques, such as the urease test, methylen blue and Gram stained smears, the histopathologic examination of biopsies specimens, and the detection of IgG antibodies anti Helicobacter Pylori. MATERIAL AND METHODS: 43 patients with gastroduodenal symptoms who had not taken NSAIDs and who presented endoscopic signs of inlammation and/or gastroduodenal ulcer were prospectively studied. Biopsies specimens of antrum, gastric fundus and duodenal bulb were taken and processed in the following way: methylen blue and Gram stained smears and Hematoxylin and eosin stained section. Studies were performed in to all the 43 patients. Urease test was performed in the antrum specimens of 37 patients, and inmunologic test by inmunoenzimatic technique (ELISA) in 40 of them. RESULTS: Methylen blue and Gram stained smears: sensitivity (S): 100

and specificity (E): 76

Histopathologic examination (S): 86

(E): 61

, urease test (S) 100

(E) 62.5

, antibodies anti H.P. not possible to calculate. DISCUSSION: The authors have taken the microbiological culture as a reference technique because the isolation and identification of the bacteria are the most important signs of its presence and vitality. Stained smears, histopathologic examination and the urease test are fast, inexpensive techniques with high sensitivity for diagnosis. However, the inmunologic test is reveals better to the prevalence of the infection.

[Endoscopic-pathologic correlation of rectocolonic lesions less than 10 mm]. / Correlción endoscópico-patológica de lesiones rectocolónicas menores de 10 mm.

Ninety eight rectocolonic lesions up to 10 mm in diameter found in 50 patients were analyzed. The relationship between endoscopic and pathologic diagnosis was established. Emphasis was made on the detection of adenomas based in the following: Yamada III or IV lateral vision, Yamada I and II with smooth but erythematous surface, and in pale with irregular surface lesions. The sensitivity of the method was 92% and the specificity was 72% for adenomas. Six percent of adenomas were pale, with mucous hypersecretion on histopathology, and can be mistaken for hyperplastic polyps. This mucous hypersecretion correlates with low grade dysplasia, which supposedly indicates a lower evolutive risk.