Physical manifestations of stress in women. Correlations between temporomandibular and pelvic floor disorders.

INTRODUCTION: Stress is characterized as a challenging occurrence that triggers a physiological and/or behavioral allostatic response, alongside the demands typically encountered throughout the natural course of life. A sustained state of stress gives rise to secondary effects, including insomnia and neck pain. Also, the risk of musculoskeletal problems in the cervical and lumbar spine can be increased due to a sustained state of stress. The present study main objective is to study the association between orofacial and pelvic floor muscles in women in Spain. METHODOLOGY: An observational, cross-sectional, retrospective analytical study was designed and carried out in the laboratories of the European University of Madrid. Sixty-five participants were recruited with a mean age of 29.9 ± 7.69. Measurements were taken by myotonometry on natural oscillation frequency (Hz), dynamic stiffness (N/m), elasticity (N/m2), mechanical stress relaxation time (ms) and creep, for the following muscles: right and left masseter, right and left temporalis and central fibrous nucleus of the perineum (CFPF). On the other hand, the subjects completed the following questionnaires: perceived stress scale (PSS-14), anxiety scale (STAI), self-reported bruxism questionnaire (CBA), Fonseca Anamnestic Index and the Pittsburgh Sleep Quality Scale (PSQI). RESULTS: Significant correlations were found in several parameters between the right temporalis and CFPF (p<0.05). Highlighting the correlation between TMDs and lubrication r = -0.254 (p = 0.041) and bruxism with pain in sexual intercourse r = 0.261 (p = 0.036). CONCLUSION: The results support the proposed hypothesis. To the author's knowledge, this is the first study which relates both locations, and it is suggested to continue with the research and expand the knowledge of it.

Relationship between air pollution exposure and the progression of idiopathic pulmonary fibrosis in Madrid: Chronic respiratory failure, hospitalizations, and mortality. A retrospective study.

Introduction: Air pollution has a significant impact on the morbidity and mortality of various respiratory diseases. However, this has not been widely studied in diffuse interstitial lung diseases, specifically in idiopathic pulmonary fibrosis. Objective: In this study we aimed to assess the relationship between four major air pollutants individually [carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and nitrogen oxides (NOx)] and the development of chronic respiratory failure, hospitalization due to respiratory causes and mortality in patients with idiopathic pulmonary fibrosis. Methods: We conducted an exploratory retrospective panel study from 2011 to 2020 in 69 patients with idiopathic pulmonary fibrosis from the pulmonary medicine department of a tertiary hospital. Based on their geocoded residential address, levels of each pollutant were estimated 1, 3, 6, 12, and 36 months prior to each event (chronic respiratory failure, hospital admission and mortality). Data was collected from the air quality monitoring stations of the Community of Madrid located <3.5 km (2.2 miles) from each patient's home. Results: The increase in average values of CO [OR 1.62 (1.11-2.36) and OR 1.84 (1.1-3.06)], NO2 [OR 1.64 (1.01-2.66)], and NOx [OR 1.11 (1-1.23) and OR 1.19 (1.03-1.38)] were significantly associated with the probability of developing chronic respiratory failure in different periods. In addition, the averages of NO2, O3, and NOx were significantly associated with the probability of hospital admissions due to respiratory causes and mortality in these patients. Conclusion: Air pollution is associated with an increase in the probability of developing chronic respiratory failure, hospitalization due to respiratory causes and mortality in patients with idiopathic pulmonary fibrosis.

Air pollution exposure and its effects on idiopathic pulmonary fibrosis: clinical worsening, lung function decline, and radiological deterioration.

Introduction: Major urban pollutants have a considerable influence on the natural history of lung disease. However, this effect is not well known in idiopathic pulmonary fibrosis (IPF). Aim: This study aimed to investigate the effects of air pollution on clinical worsening, lung function, and radiological deterioration in patients with IPF. Methods: This exploratory retrospective cohort study included 69 patients with IPF, monitored from 2011 to 2020. Data on air pollution levels, including carbon monoxide (CO), nitrogen dioxide (NO2), particulate matter ≤ 2.5 µM (PM2.5), ozone (O3), and nitrogen oxides (NOx), were collected from the nearest air quality monitoring stations (<3.5 km from the patients' homes). Patient outcomes such as clinical worsening, lung function decline, and radiological deterioration were assessed over various exposure periods (1, 3, 6, 12, and 36 months). The statistical analyses were adjusted for various factors, including age, sex, smoking status, and treatment. Results: There was an association between higher O3 levels and an increased likelihood of clinical worsening over 6 and 36 months of exposure (odds ratio [OR] and 95% confidence interval [CI] = 1.16 [1.01-1.33] and OR and 95% CI = 1.80 [1.07-3.01], respectively). Increased CO levels were linked to lung function decline over 12-month exposure periods (OR and 95% CI 1.63 = [1.01-2.63]). Lastly, radiological deterioration was significantly associated with higher CO, NO2, and NOx levels over 6-month exposure periods (OR and 95% CI = 2.14 [1.33-3.44], OR and 95% CI = 1.76 [1.15-2.66] and OR and 95% CI = 1.16 [1.03-1.3], respectively). Conclusion: This study suggests that air pollution, specifically O3, CO, NO2, and NOx, could affect clinical worsening, lung function, and radiological outcomes in patients with IPF. These findings highlight the potential role of air pollution in the progression of IPF, emphasizing the need for further research and air quality control measures to mitigate its effects on respiratory health.

Association between RNAm-Based COVID-19 Vaccines and Permanency of Menstrual Cycle Alterations in Spanish Women: A Cross-Sectional Study.

Introduction: The purpose of this study was to delve more deeply into the medium and long-term relation between mRNA-based vaccines and changes in menstrual pain, cycle length, and amount of bleeding in Spanish women. Material and Methods: A total of 746 women (63% between 18−30 and 37% between 31−45 years old) participated in the study. A numerical rating scale was used for recording pain intensity, a pictorial chart for menstrual bleeding, and data from menstrual cycle duration, type of vaccine, number of doses and time from vaccination. Results: Sixty-five per cent of the women perceived changes in their menstrual cycle after receiving the vaccines, irrespective of type of vaccine or number of doses; all p values were >0.05. Most of them (n = 316 out of 484) reported more than one alteration in their menstrual cycle. Almost half of the participants had been vaccinated over 5 months (45%), 3−4 months (15%) 2−3 months (26%), and one month or less (13%) before. The percentage of women that reported alterations remained strongly constant across time, p > 0.05, ranging from 64 to 65%. Conclusions: Reported alterations in Spanish women after COVID vaccination remained more than 5 months after the last dose.

Clinical validation of a novel quantitative assay for the detection of MGMT methylation in glioblastoma patients.

BACKGROUND: The promoter hypermethylation of the methylguanine-DNA methyltransferase gene is a frequently used biomarker in daily clinical practice as it is associated with a favorable prognosis in glioblastoma patients treated with temozolamide. Due to the absence of adequately standardized techniques, international harmonization of the MGMT methylation biomarker is still an unmet clinical need for the diagnosis and treatment of glioblastoma patients. RESULTS: In this study we carried out a clinical validation of a quantitative assay for MGMT methylation detection by comparing a novel quantitative MSP using double-probe (dp_qMSP) with the conventional MSP in 100 FFPE glioblastoma samples. We performed both technologies and established the best cutoff for the identification of positive-methylated samples using the quantitative data obtained from dp_qMSP. Kaplan-Meier curves and ROC time dependent curves were employed for the comparison of both methodologies. CONCLUSIONS: We obtained similar results using both assays in the same cohort of patients, in terms of progression free survival and overall survival according to Kaplan-Meier curves. In addition, the results of ROC(t) curves showed that dp_qMSP increases the area under curve time-dependent in comparison with MSP for predicting progression free survival and overall survival over time. We concluded that dp_qMSP is an alternative methodology compatible with the results obtained with the conventional MSP. Our assay will improve the therapeutic management of glioblastoma patients, being a more sensitive and competitive alternative methodology that ensures the standardization of the MGMT-biomarker making it reliable and suitable for clinical use.

A comparative two-cohort study of pediatric patients with long term stay in ICUs.

During the last decades, the number of patients with long stay admissions (LSA) in PICU has increased. The purpose of this study was to identify factors associated with PICU LSA, assessing healthcare resources use and changes in the profile of these patients. A retrospective, observational, single-center study was carried out. Characteristics of LSA were compared between two periods (2006-2010 and 2011-2015). During the earlier period there were 2,118 admissions (3.9% of them LSA), whereas during the second period, there were 1,763 (5.4% of them LSA) (p = 0.025). LSA accounted for 33.7% PICU stay days during the first period and 46.7% during the second (p < 0.001). Higher use of non-invasive ventilation (80.2% vs. 37.8%, p = 0.001) and high-flow oxygen therapy (68.8% vs. 37.8%, p = 0.005) was observed in the 2011-2015 cohort, whereas the use of arterial catheter (77.1% vs. 92.6%, p = 0.005), continuous infusion of adrenaline (55.2% vs. 75.9%, p = 0.004), and hemoderivative transfusion (74% vs. 89.2%, p = 0.010) was less frequent. In the 2006-2010 cohort, hospital-acquired infections were more common (95.2% vs. 68.8%, p < 0.001) and mortality was higher (26.8% vs. 13.8%, p = 0.026). The number of long-stay PICU admissions have increased entailing an intensive use of healthcare resources. These patients have a high risk for complications and mortality.

Symptomatic heterozygous X-Linked myotubular myopathy female patient with a large deletion at Xq28 and decrease expression of normal allele.

X-linked myotubular myopathy (XLMTM; OMIM 310400) is a centronuclear congenital muscular disorder of X-linked recessive inheritance. Although female carriers are typically asymptomatic, affected heterozygous females have been described. Here, we describe the case of a sporadic female patient with suspicion of centronuclear myopathy and a heterozygous large deletion at Xq28 encompassing the MAMLD1, MTM1, MTMR1, CD99L2, and HMGB3 genes. The deletion was first detected using a custom next generation sequencing (NGS)-based multigene panel and finally characterized by comparative genomic hybridization array and multiplex ligation probe assay techniques. In this patient we have confirmed, by MTM1 mRNA quantification, a MTM1 gene expression less than the expected 50 percent in patient muscle. The significant 20% reduction in MTM1 mRNA expression in muscle, precludes low level of the normal myotubularin protein as the cause of the phenotype in this heterozygous female. We have also found that BIN1 expression in patient muscle biopsy was significantly increased, and postulate that BIN1 expression will be increased in XLMTM patient muscle as an attempt to maintain muscle function.

Transcription factor NRF2 uses the Hippo pathway effector TAZ to induce tumorigenesis in glioblastomas.

Transcription factor NRF2 orchestrates a cellular defense against oxidative stress and, so far, has been involved in tumor progression by providing a metabolic adaptation to tumorigenic demands and resistance to chemotherapeutics. In this study, we discover that NRF2 also propels tumorigenesis in gliomas and glioblastomas by inducing the expression of the transcriptional co-activator TAZ, a protein of the Hippo signaling pathway that promotes tumor growth. The expression of the genes encoding NRF2 (NFE2L2) and TAZ (WWTR1) showed a positive correlation in 721 gliomas from The Cancer Genome Atlas database. Moreover, NRF2 and TAZ protein levels also correlated in immunohistochemical tissue arrays of glioblastomas. Genetic knock-down of NRF2 decreased, while NRF2 overexpression or chemical activation with sulforaphane, increased TAZ transcript and protein levels. Mechanistically, we identified several NRF2-regulated functional enhancers in the regulatory region of WWTR1. The relevance of the new NRF2/TAZ axis in tumorigenesis was demonstrated in subcutaneous and intracranial grafts. Thus, intracranial inoculation of NRF2-depleted glioma stem cells did not develop tumors as determined by magnetic resonance imaging. Forced TAZ overexpression partly rescued both stem cell growth in neurospheres and tumorigenicity. Hence, NRF2 not only enables tumor cells to be competent to proliferate but it also propels tumorigenesis by activating the TAZ-mediated Hippo transcriptional program.

miR-7 methylation as a biomarker to predict poor survival in early-stage non-small cell lung cancer patients.

Non-small-cell lung cancer (NSCLC) is the most common malignancy worldwide. Platinum-based chemotherapy is the standard of care for these patients. Recent research showed that miR-7 methylation status is a biomarker of cisplatin resistance in lung and ovarian cancer cells, which is one of the major limitations associated with their clinical management. The aim of the present study is to provide clinical insights associated with this novel potential biomarker in NSCLC patients by comparing the miR-7 methylation status with the cisplatin treatment response. Our results analyzed in 81 samples show that miR-7 methylation is a common event in tumor tissue and it is more frequent as the stage of the disease advances, remaining in 75% of metastatic patients. Tumor miR-7 unmethylation trend to a better PFS in early stages, and when our data was validated in an extended "in silico" cohort of 969 patients we obtained a significant increment in PFS and OS in those patients harboring miR-7 unmethylated (p = 0.010 and p = 0.007 respectively). When we select those early-stages patients harbouring miR-7 methylation, we observed that adenocarcinoma patients present a dramatic decrease in PFS compared with squamous cell carcinoma patients (median 18.9 versus 59.7 months, p = 0.002). In conclusion, our results show that presence of miR-7 methylation in early-stage NSCLC is suggestive of aggressive behavior, especially for adenocarcinoma patients. One major challenge in early diagnosis in NSCLC is identify the subgroup of patients that could benefit for adjuvant therapy, our data establish the basis for epigenetic classification on early-stage NSCLC that could influence treatment decisions in the future.

Autosomal dominant distal myopathy with nemaline rods due to p.Glu197Asp mutation in ACTA1.

In a previous report of a new phenotype with predominant scapulo-humeral-peroneal-distal myopathy associated with the Glu197Asp mutation in ACTA1, muscle biopsies did not show nemaline rods, nor could nemaline rods formation be demonstrated in an exhaustive functional in vivo or in vitro study. However, muscle biopsy in members of our family, carrying a similar clinical phenotype of some members of the original family and the same ACTA1 mutation, revealed the presence of numerous nemaline rods, suggesting that there must be other factors that explain the absence of nemaline rods.

Head and neck manifestations of an undiagnosed McCune-Albright syndrome: clinicopathological description and literature review.

Craniofacial fibrous dysplasia, characteristic of McCune-Albright syndrome (MAS), is usually present in patients with MAS-related acromegaly. We report here the first case of a patient with an undiagnosed MAS presenting with an acute hydrocephalus. A 21-year-old male with gigantism and craniofacial fibrous dysplasia consulted for rapidly progressive headache. An acute obstructive hydrocephalus due to a 39 × 35-mm cystic lesion in the third ventricle was discovered and operated, obtaining hydrocephalus resolution. Pathology described a colloid cyst material and a growth hormone-secreting pituitary adenoma. Genetic study revealed the mosaic GNAS R201H mutation in the pituitary tissue, confirming a MAS diagnosis. Adequate hormonal control was achieved postoperatively. Our results suggest that long-term untreated growth hormone excess in patients with MAS-related craniofacial fibrous dysplasia might end compromising cerebrospinal fluid flow. A prompt diagnosis and coordinated multidisciplinary treatment may help to avoid long-term deleterious impact of hyperfunctioning endocrinopathies in these patients.

Spinal adrenal cortical adenoma associated with Beckwith-Wiedemann syndrome: case report and review of the literature.

PURPOSE: Ectopic adrenal cortical adenoma in the spinal region is extremely rare. The majority of cases of ectopic adrenocortical tissue are found along the path of embryonic migration within the urogenital tract. Beckwith-Wiedemann syndrome (BWS) is a pediatric overgrowth disorder involving a predisposition to tumor development, including adrenal lesions. To date, only eight spinal cases have been reported. This is the third reported case in pediatric population, the first one associated with genetic syndrome and the first benign to recur. We review the current literature on this topic. CASE DESCRIPTION: We present a 2-year-old boy affected by Beckwith-Wiedemann syndrome who developed a tumor at L4-L5 level. He underwent a gross total resection with MRI post-surgery demonstrating non-residual tumor. Histology disclosed an ectopic adrenal cortical adenoma with oncocytic features. Immunohistochemically was positive for inhibin-alpha, synaptophysin, and melan-A. It was negative for chromogranin A, GFAP, S-100, and other markers. One year later, he developed a recurrence at the same level being necessary a second surgery leaving a small sheet of residual tumor. CONCLUSION: Spinal adrenocortical adenomas are exceptional, and its behavior could be related to other conditions such as BWS. Gross total resection can be curative but a tight follow-up is needed. Immunohistochemical studies that include inhibin-alpha, synaptophysin, and melan-A can be useful in differential diagnosis as ultrastructural study. The decision on how to treat these patients is difficult given the low number of cases.

Lung cancer and peritoneal carcinomatosis.

Lung cancer is currently one of the most common malignancies in the world and peritoneal involvement is rare in these types of tumors. Clinical manifestations of these metastases are also uncommon and include intestinal perforation and obstruction. The present study reviewed certain aspects of the complication of peritoneal involvement and illustrated it with four cases of patients that were diagnosed with primary lung carcinoma and secondary peritoneal carcinomatosis (PC). The outcome of these patients is poor and they rarely respond to chemotherapy. Surgery is successful in the majority of cases.

Squamous-cell carcinoma of the lungs: is it really so different?

BACKGROUND: Squamous cell carcinoma (SCC) is the predominant histological type in men, and adenocarcinoma is the most common subtype in women in the world. The incidence of SCC is decreasing in men, while the incidence of adenocarcinoma (AC) is stable or slightly increasing in western countries. There is active research on the AC subtype but SCC remains poorly studied. CONCLUSIONS: In this review, we have studied different aspects of the SCC subtype, including epidemiology, clinical features, pathology, molecular biology markers, and new therapeutic targets, treatments and prognosis implications.

Melanoma leptomeningeal dissemination following frontoparietal metastasis surgery: Case report and review of the literature.

We present the case of a patient with a solitary left frontoparietal brain metastasis of melanoma previously treated with surgery. Three months later, the patient was admitted to the emergency room in a confusional state with meningeal signs. A cerebrospinal fluid (CSF) test and magnetic resonance imaging findings suggested a subarachnoid haemorrhage (SAH) and/or meningeal carcinomatosis. The results of a cytological examination of the CSF showed neoplastic epithelial cells consistent with metastatic melanoma cells. Resection of metastatic posterior fossa lesions is often cited as a risk factor for leptomeningeal dissemination, however, when the resection is limited to the anterior fossa, this complication is relatively rare. In contrast, SAH may be a complication of leptomeningeal dissemination and responsible for acute meningeal syndrome. Treatment with high doses of corticoids did not show any improvement, and intrathecal chemotherapy was not possible due to the patient's poor functional status. She succumbed 1 week after admission.

Expression of matrix metalloproteinase-9 in high-grade salivary gland carcinomas is associated with their metastatic potential.

OBJECTIVE: The aim of this study was to investigate the role of matrix metalloproteinase (MMP)-9 protein in high-grade malignant tumors of salivary gland origin as well as its utility as a prognostic marker. METHODS: Four micrometer sections from 27 malignant salivary neoplasms were immunostained using a specific antibody against MMP-9. The staining results (proportion of the stained tumor cells and intensity of tumor stainings) were correlated with the clinical data and with patient outcomes. RESULTS: Immunostaining for MMP-9 was observed in 17 cases, predominantly localized in the tumor cells and occasionally in the inflammatory stroma cells. MMP-9 protein expression correlated with N (P = .04), M (P = .02), and TNM stages (P = .03). MMP-9 expression was prognostic for shortened survival (P = .01). Our results show that the invasiveness and prognosis of high-grade salivary gland cancers may depend on their MMP-9 expression profile.

[Pulmonary atresia with intact ventricular septum associated with severe aortic stenosis]. / Atresia pulmonar con septo integro asociada a estenosis aórtica severa.

Pulmonary atresia with intact ventricular septum is the complete obstruction of the right ventricular outflow tract due to pulmonary valve atresia in the absence of ventricular septal defect. Pulmonary flow is dependent on the ductus arteriosus. Other morphological anomalies are also present. Aortic stenosis in association with pulmonary atresia with intact ventricular septum is extremely infrequent, and very few cases have been described. We report a 19-year-old primiparous woman in whom the fetal echocardiogram showed pulmonary atresia with intact ventricular septum. The neonate had low oxygen saturation and a systolic murmur originating in the aorta. An echocardiogram showed pulmonary atresia with intact ventricular septum and a bicuspid, thickened, stenotic aortic valve. Low cardiac output ensued and could not be controlled, and the infant died.

Atresia pulmonar con septo íntegro asociada a estenosis aórtica severa / Pulmonary atresia with intact ventricular septum associated with severe aortic stenosis

La atresia pulmonar con septo íntegro es la obstrucción completa del tracto de salida del ventrículo derecho por la válvula pulmonar atrésica, sin defecto septal interventricular y con un flujo pulmonar dependiente de un ductus. Se acompaña de otras anomalías morfológicas. La asociación a estenosis aórtica es extremadamente infrecuente y los casos publicados son excepcionales. Presentamos el caso de una primípara de 19 años en la que un ecocardiograma fetal evidenció atresia pulmonar con septo íntegro. La recién nacida presentó desaturación y soplo sistólico en el foco aórtico. Un ecocardiograma mostró una atresia pulmonar con el septo íntegro y una válvula aórtica bicúspide engrosada y estenótica. Evolucionó hacia el bajo gasto sistémico, incontrolable y mortal (AU)

Expression of ErbB-3 and ErbB-4 protooncogene proteins in oral squamous cell carcinoma: a pilot study.

BACKGROUND: To examine the occurrence of ErbB-3 and ErbB- 4 in oral squamous cell carcinoma, as well as investigate statistical correlations between the expression of these protooncogene proteins and clinical and pathological tumor characteristics. STUDY DESIGN: Nineteen oral squamous cell carcinomas (SCC) were analyzed using immunohistochemistry. RESULTS: Positive immunostaining for ErbB-3 was found in 13/19 (68%) cases and for ErbB-4 in 10/19 (52%). The intensity of immunostaining for ErbB-3 positive cases was low in 8 (42.1%) and high in 5 (26.3%) cases, and for ErbB-4 ones was low in 6 (31.6%) and high in 4 (21%) of the 19 cases. ErbB-4 overexpression and TNM stage showed a significant correlation (Spearman correlation coefficient=0.467; P=0.04). The Kaplan-Meier analysis showed that the overexpression of ErbB-3 and ErbB-4 had no an influence on survival (P>0.05), but TNM stage was inversely related to survival (P=0.04). There was a significant association between the expression of ErbB-3 and ErbB-4 (chi2=6.193, P=0.037). CONCLUSION: The results of the present study suggest that c-erbB-4 may contribute to tumor growth and progression.