Expected-value bias in mid-trimester preterm birth screening.

OBJECTIVES: Cervical length (CL) measurement ≤ 25 mm on mid-trimester ultrasound scan is a known risk factor for preterm birth, for which vaginal progesterone is recommended. The aims of this study were to evaluate whether CL measurement is affected by observer bias and to assess the impact on short cervix prevalence of masking CL measurement during routine mid-trimester ultrasound scan. METHODS: This was a flash study designed for a 2-month period (October and November 2018) at Cruces University Hospital (Bizkaia, Spain), in which all CL measurements from routine mid-trimester scans were masked. During the study period, there was no modification of the routine screening method, and women with a short cervix were prescribed 200 mg vaginal progesterone daily as per usual. The control group included women examined in a 2-month period (April and May 2018) prior to the study, in which CL measurements were taken as usual by a non-blinded operator. The primary outcome was the prevalence of short cervix in each group. RESULTS: A total of 983 CL measurements were analyzed, including 457 in the blinded group and 526 in the control group. The prevalence of short cervix was 2.7% in the non-blinded group and 5.5% in the blinded group (P = 0.024). We identified a statistically significant difference in the incidence of CL of 24-25 mm between the two groups, with a lower prevalence in the non-blinded vs blinded group (0.6% vs 2.4%; P < 0.005). Moreover, the distribution of CL values was normal in the blinded group, in contrast to the non-blinded group, which was characterized by skewed distribution of CL values. CONCLUSIONS: Expected-value bias exists and should be taken into account when measuring CL in mid-trimester preterm birth screening. Blinding has demonstrated to be an effective strategy to improve the performance of CL screening in clinical practice. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Self-assembly of iron oxide precursor micelles driven by magnetic stirring time in sol-gel coatings.

The purpose of this work is to fabricate self-assembled microstructures by the sol-gel method and study the morphological, structural and compositional dependence of ε-Fe2O3 nanoparticles embedded in silica when glycerol (GLY) and cetyl-trimethylammonium bromide (CTAB) are added as steric agents simultaneously. The combined action of a polyalcohol and a surfactant significantly modifies the morphology of the sample giving rise to a different microstructure in each of the studied cases (1, 3 and 7 days of magnetic stirring time). This is due to the fact that the addition of these two compounds leads to a considerable increase in gelation time as GLY can interact with the alkoxide group on the surface of the iron oxide precursor micelle and/or be incorporated into the hydrophilic chains of CTAB. This last effect causes the iron oxide precursor micelles to be interconnected forming aggregates whose size and structure depend on the magnetic stirring time of the sol-gel synthetic route. In this paper, crystalline structure, composition, purity and morphology of the sol-gel coatings densified at 960 °C are examined. Emphasis is placed on the nominal percentage of the different iron oxides found in the samples and on the morphological and structural differences. This work implies the possibility of patterning ε-Fe2O3 nanoparticles in coatings and controlling their purity by an easy one-pot sol-gel method.

Assessment of the extent of pituitary macroadenomas resection in immediate postoperative MRI. / Valoración del grado de resección de los macroadenomas hipofisarios en la resonancia magnética posquirúrgica inmediata.

OBJECTIVE: To evaluate if it is possible to determine the extent of pituitary macroadenomas resection in the immediate postoperative pituitary magnetic resonance imaging (MRI). MATERIAL AND METHODS: MRI of patient with pituitary macroadenomas from January 2010 until October 2014 were reviewed. Those patients who had diagnostic MRI, immediate post-surgical MRI and at least one MRI control were included. We evaluate if the findings between the immediate postsurgical MRI and the subsequent MRI were concordant. Cases which didn't have evolutionary controls and those who were reoperation for recurrence were excluded. The degree of tumor resection was divided into groups: total resection, partial resection and doubtful. All MRI studies were performed on a1.5T machine following the same protocol sequences for all cases. One morphological part, a dynamic contrast iv and late contrast part. RESULTS: Of the 73 cases included, immediate postoperative pituitary MRI was interpreted as total resection in 38 cases and tumoral rest in 28 cases, uncertainty among rest or inflammatory changes in 7 cases. Follow- up MRI identified 41 cases total resection and tumoral rest in 32. Sensitivity and specificity of 0.78 and 0.82 and positive and negative predictive value (PPV and NPV) 0.89 and 0.89 respectively were calculated. CONCLUSION: Immediate post-surgery pituitary MRI is useful for assessing the degree of tumor resection and is a good predictor of the final degree of real resection compared with the following MRI studies. It allows us to decide the most appropriate treatment at an early stage.

Adenovirus expressing ß2-microglobulin recovers HLA class I expression and antitumor immunity by increasing T-cell recognition.

Optimal tumor cell surface expression of human leukocyte antigen (HLA) class I molecules is essential for the presentation of tumor-associated peptides to T-lymphocytes. However, a hallmark of many types of tumor is the loss or downregulation of HLA class I expression associated with ineffective tumor antigen presentation to T cells. Frequently, HLA loss can be caused by structural alterations in genes coding for HLA class I complex, including the light chain of the complex, ß2-microglobulin (ß2m). Its best-characterized function is to interact with HLA heavy chain and stabilize the complex leading to a formation of antigen-binding cleft recognized by T-cell receptor on CD8+ T cells. Our previous study demonstrated that alterations in the ß2m gene are frequently associated with cancer immune escape leading to metastatic progression and resistance to immunotherapy. These types of defects require genetic transfer strategies to recover normal expression of HLA genes. Here we characterize a replication-deficient adenoviral vector carrying human ß2m gene, which is efficient in recovering proper tumor cell surface HLA class I expression in ß2m-negative tumor cells without compromising the antigen presentation machinery. Tumor cells transduced with ß2m induced strong activation of T cells in a peptide-specific HLA-restricted manner. Gene therapy using recombinant adenoviral vectors encoding HLA genes increases tumor antigen presentation and represents a powerful tool for modulation of tumor cell immunogenicity by restoration of missing or altered HLA genes. It should be considered as part of cancer treatment in combination with immunotherapy.

Study of survival in patients with malignant lung lesions treated with radiofrequency.

OBJECTIVE: To report on the survival of a series of patients with primary and metastatic lung tumours treated with radiofrequency (RF). Four years ago we published our preliminary experience with the use of this technique. MATERIALS AND METHODS: For a period of 8 years we have treated 59 patients (by means of a total of 70 procedures) with primary or metastatic pulmonary neoplastic lesions, which fulfilled inclusion criteria to perform the technique. They were in all cases non-surgical lesions that had been either previously treated or not. The technique was performed in the radiology suite, under conscious analgo-sedation. We treated primary pulmonary lesions, neoplastic recurrences, or metastases with curative or palliative intention (pain management). RESULTS: Current global survival rate is 19 patients (32 %) with a mean of 26.61 ± 3.17 months (range: 20.38 ± 32.83) and a median of 16.00 ± 3.57 (range: 8.99-23.00). If we establish the difference between primary and metastatic tumours, mean survival is 27.62 ± 4.12 months in primary tumours (median: 16.00) vs. 24.65 ± 4.47 months in metastatic tumours (median: 16.00). When we studied the survival in those cases with a curative intent, mean survival in primary tumours was 30.97 ± 4.57 months (median: 21.00) vs. 25.14 ± 4.68 (median: 16.00) months in metastatic tumours. CONCLUSIONS: RF ablation of lung lesions is a minimally invasive procedure that is useful in primary tumours (especially in stage I) and metastatic ones. RF has proven its usefulness in the multidisciplinary treatment of this pathology due to the low incidence of serious complications and survival obtained, considering that patients are elderly with significant comorbidity.

Targeting HLA class I expression to increase tumor immunogenicity.

The dynamic interaction between the host immune system and growing cancer has been of central interest to the field of tumor immunology over the past years. Recognition of tumor-associated antigens (TAA) by self-HLA (human leukocyte antigen) class I-restricted CD8+ T cells is a main feature in the detection and destruction of malignant cells. The discovery and molecular characterization of TAA has changed the field of cancer treatment and introduced a new era of cancer immunotherapy aimed at increasing tumor immunogenicity and T-cell-mediated anti-tumor immunity. Unfortunately, while these new protocols of cancer immunotherapy are mediating induction of tumor-specific T lymphocytes in patients with certain malignancies, they have not yet delivered substantial clinical benefits, such as induction of tumor regression or increased disease-free survival. It has become apparent that lack of tumor rejection is the result of immune selection and escape by tumor cells that develop low immunogenic phenotypes. Substantial experimental data support the existence of a variety of different mechanisms involved in the tumor escape phase, including loss or downregulation of HLA class I antigens. These alterations could be caused by regulatory ('soft') or by structural/irreversible ('hard') defects. On the basis of the evidence obtained from experimental mouse cancer models and metastatic human tumors, the structural defects underlying HLA class I loss may have profound implications on T-cell-mediated tumor rejection and ultimately on the outcome of cancer immunotherapy. Strategies to overcome this obstacle, including gene therapy to recover normal expression of HLA class I genes, require consideration. In this review, we outline the importance of monitoring and correction of HLA class I alterations during cancer development and immunotherapy.

Efficient recovery of HLA class I expression in human tumor cells after beta2-microglobulin gene transfer using adenoviral vector: implications for cancer immunotherapy.

Here we report a successful use of a non-replicating adenovirus expressing the wild-type human beta2m gene in recovery of normal human leucocyte antigen (HLA) class I expression in beta2m-null cancer cells. Total loss of HLA class I expression in these cell lines is caused by a mutation in beta2m gene and a loss of heterozygosity in chromosome 15 carrying another copy of that gene. Normal HLA class I expression on the tumour cell surface is critical for the successful outcome of cancer immunotherapy as T cells can only recognize tumour-derived peptides in a complex with self-HLA class I molecules. In this report we characterize the newly generated adenoviral vector AdCMVbeta2m and demonstrate an efficient beta2m gene transfer in tumour cell lines of different histological origin, including melanoma, prostate and colorectal carcinoma. The beta2m re-expression lasted for an extended period of time both in vitro and in vivo in human tumour xenograft transplants. We propose that in a subset of cancer patients with structural defect in beta2m gene or chromosome 15, the adenoviral-mediated recovery (or even increase) of HLA class I expression on tumour cells in combination with vaccination or adoptive T-cell therapy can provide a complementary approach to improve the clinical efficacy of cancer immunotherapy.

Patterns of constitutive and IFN-gamma inducible expression of HLA class II molecules in human melanoma cell lines.

Major histocompatibility complex (MHC) class II proteins (HLA-DR, HLA-DP and HLA-DQ) play a fundamental role in the regulation of the immune response. The level of expression of human leukocyte antigen (HLA) class II antigens is regulated by interferon-gamma (IFN-gamma) and depends on the status of class II trans-activator protein (CIITA), a co-activator of the MHC class II gene promoter. In this study, we measured levels of constitutive and IFN-gamma-induced expression of MHC class II molecules, analysed the expression of CIITA and investigated the association between MHC class II transactivator polymorphism and expression of different MHC class II molecules in a large panel of melanoma cell lines obtained from the European Searchable Tumour Cell Line Database. Many cell lines showed no constitutive expression of HLA-DP, HLA-DQ and HLA-DR and no IFN-gamma-induced increase in HLA class II surface expression. However, in some cases, IFN-gamma treatment led to enhanced surface expression of HLA-DP and HLA-DR. HLA-DQ was less frequently expressed under basal conditions and was less frequently induced by IFN-gamma. In these melanoma cell lines, constitutive surface expression of HLA-DR and HLA-DP was higher than that of HLA-DQ. In addition, high constitutive level of cell surface expression of HLA-DR was correlated with lower inducibility of this expression by IFN-gamma. Finally, substitution A-->G in the 5' flanking region of CIITA promoter type III was associated with higher expression of constitutive HLA-DR (p<0.005). This study yielded a panel of melanoma cell lines with different patterns of constitutive and IFN-gamma-induced expression of HLA class II that can be used in future studies of the mechanisms of regulation of HLA class II expression.

DNA injury induced by 5-aminouracil and caffeine in G2 checkpoints path of higher plant cells

This work evaluated the qualitative and quantitative cellular changes induced by treatment with 5-aminouracil (5-AU) and a combination of 5-AU and caffeine in plant cells in relation to DNA damage, repaired damage, and residual damage. As biological material, Allium cepa L. root tips were used, grown in filtered water, in darkness, with aeration at constant temperature of 25°C ± 0.5. Cell populations were synchronized using 5 mM caffeine in order to study the effects of 5-AU and caffeine/5-AU combined treatment on the DNA content and their incidence in the entrance to mitosis. The results showed a delay in the G2 period due to induced DNA damage by the 5-AU and caffeine/5-AU combined treatment, shown by aberrant metaphases, anaphases and telophases. The effect of caffeine in the combined treatment was heightened in spite of lengthening the checkpoints route that retains the cells in G2. The existence of G2 checkpoints was shown in the cell population studied, inducing lesions in the DNA, chromosomic aberrations and cellular instability

Expression and functional properties of group I metabotropic glutamate receptors in bovine chromaffin cells.

We demonstrate the presence and functional properties of Group I metabotropic glutamate receptors (mGluRs) expressed in chromaffin cells. Immunocytochemical techniques revealed that two mGluR subtypes (mGluR1alpha and mGluR5) are expressed in chromaffin cells, located in both the cytoplasmic membrane and the cytosol surrounding the nucleus. These mGluRs are functionally active on catecholamine (CA) secretion in chromaffin cells because both (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) and the specific agonist of Group I mGluRs, (S)-3,5-dihydroxyphenylglycine (DHPG), were able to stimulate the release of CAs (adrenaline and noradrenaline) in a dose-response manner. These effects were specifically reversed by L-(+)-2-amino-3-phosphonopropionic acid (L-AP3), a selective antagonist of the Group I metabotropic glutamate receptors. t-ACPD induced an increase in CA secretion in both the presence and absence of extracellular calcium, the former effect being accompanied by cell membrane depolarization. Noradrenaline (NA) release was higher in the presence of extracellular calcium than in its absence, whereas adrenaline release was of the same order under both conditions. These results indicate that different subtypes of Group I mGluRs are present in noradrenergic and adrenergic cells. Fluorescence imaging techniques in single cells showed different t-ACPD-induced increases in intracellular calcium in different chromaffin cells: in chromaffin cells, 67% expressed functional metabotropic glutamate receptors and with nicotinic receptors, whereas the remaining 33% expressed only nicotinic receptors. In the absence of external calcium, only about 25% of cells responded to t-ACPD-increased intracellular calcium by increasing inositol 1,4,5-trisphosphate (IP(3)) concentration and subsequent calcium mobilization from intracellular stores, whereas the remaining 75% increased intracellular calcium by promoting Ca(2+) influx from the extracellular medium through L- and N- but not P/Q voltage-dependent calcium channels.

[Complicated sinusitis and nasal endoscopic surgery]. / Sinusitis complicadas y cirugía endoscópica nasal.

BACKGROUND: Complicated sinusitis can result in a significant morbidity if not appropriately managed. Traditionally, surgical cases were treated by external approaches. Now a days, the introduction of endoscopic sinus surgery allows such complications to be endoscopically approached. AIM: This study was designed to evaluate our results in complicated sinusitis treated by endoscopic sinus surgery. METHODS: The study reviewed 18 patients with evidence of sinusitis complications treated with endoscopic sinus surgery between 1993 and March 2000. There were 12 orbital and 6 intracraneal complications. Six patients did need an additional surgical approach. RESULTS: Seventeen patients (94%) had a relief of their symptoms. One patient with a superior orbital fisura syndrome died a month later due to vascular and respiratory complications. Another patient with fronto-lateral sinusitis required frontal osteoplasty for persistent disease. Two patients had long-term neurological sequelae (seizure). None had ocular sequelae. There were no complications due to the surgery. CONCLUSION: The endoscopic sinus surgery is a safe procedure with a high success rate in the treatment of complicated sinusitis. At present, open approaches to the sinuses are rarely indicated.

Effect of cadmium on the nucleoli of meristematic cells of onion Allium cepa L: an ultrastructural study.

This study of the effect of cadmium on nucleolar ultrastructure was carried out with meristematic cell populations of Allium cepa L. Meristems, grown at 25 degrees C, were treated with 10 ppm cadmium chloride. Conventional and silver staining techniques were carried out, and the ultrastructure was analyzed using electron microscopy. Observation showed alterations in the nucleoli of the cells that had been treated with cadmium and this effect varied according to the time of exposure to the metal. After 4h of treatment, nucleolar segregation was observed in interphase, probably because of the effect of cadmium on the synthesis of ribosomal RNA precursors. A decrease in the fibrillar to granular component ratio also occurred in the cells exposed to Cd2+ for 8 h. Some changes were observed in the G1 cells; their chromatin still remained very condensed, and prenucleolus bodies remained scattered within the nucleus. At the same time, there was a large amount of interchromatin granules. These changes produced by cadmium resembled those produced during inhibition of RNA synthesis. The fibrillar bodies, another morphologic feature, resulting from a blocked transcription, were also evidenced. All these observations suggest that one of the ways that cadmium exercises its toxicity is by altering the biosynthesis of the preribosomal RNA precursor.

Centrofacial lifting, up to date.

The centrofacial lifting is a procedure that has proved its benefits and advantages for treating the aging effects on the centrofacial area. The author presents the procedure that he is using currently, with technical details and maneuvers developed to get better results. With the experience of 664 cases in 10 years, indications, complications, and long-term results are presented.

Procedure for successful interspecific embryo transfer from mouflon (Ovis gmelini musimon) to Spanish Merino sheep (Ovis aries).

Embryos from five anesthetized mouflons (Ovis gmelini musimon), superovulated with FSH-o (Ovagen) were transferred into preselected Spanish Merino sheep (Ovis aries). Myorelaxation was complete in four of five donor mouflons. The status of the uterus of potential recipients was evaluated by transrectal ultrasonography, and those ewes with fluid in the uterine horn were rejected. The corpus luteum in each ewe was assessed ultrasonographically the day before surgery. Plasma progesterone levels and the quality of the corpora lutea were the criteria for selection of recipients. Ten embryos were transferred to the five selected Spanish Merino recipients, resulting in four pregnancies and seven live-born lambs, including three sets of twins. This study shows that determination of plasma progesterone levels combined with ultrasonographic assessment of the corpus luteum provides information useful for screening of potential recipients.

[New bone distraction device for induced osteogenesis of the mandible. Experience with 126 clinical cases]. / Nuevo distractor oseo simplificado, para la osteogénesis inducida en la mandíbula. Experiencia en 126 casos clínicos.

In this paper, the author describes the distraction devise designed and developed by the author to perform the procedure of inducted bone generation or "bone distraction". The characteristics, principles, and advantages of this device are also described in comparison with other more expensive devices. The author's clinic experience using this device: 126 patients with a maximum follow-up of 54/12 years and an average bone distraction of 31 mm. The procedure was done on patients from 8/12 to 38 years of age. Bone distraction is a good option for early reconstruction of craniofacial skeletal defects, eliminating the need for bone grafts, maxillo-mandibular fixation, and other more aggressive and complex procedures. The results obtained with this distractor show that it is a stable, precise, and useful device. Its low cost and the simplicity of the technique make it very accessible to every surgeon with some experience in bone surgery and craniofacial or othognatic surgery.

Umbilical transposition in TRAM flap: a simple horizontal translocation.

A simple method of umbilical repositioning by incising the anterior rectus sheath and rectus abdominis muscle is reported for cases of unilateral abdominal wall plication during the TRAM flap operation. This method keeps the umbilicus stable and nonstenotic, and it avoids hypertrophic scars, which result from other techniques such as direct suturing of the stalk to the skin. Although this method might weaken contralateral muscle activity, the patients we operated on maintained their ability to perform sit-ups, and no periumbilical weakening was noticed.