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.

Breast cancer survivors suffering from lymphedema: What really do affect to corporeality/body image? A qualitative study.

Breast cancer-related lymphedema is currently one of the most serious complications that most affect the quality of life of women undergoing breast cancer. The aim of this study was to explore in-depth the experience of women who suffer from lymphoedema after breast cancer and how does this condition affect corporeality, with no judgements. For this purpose, a qualitative methodology was followed. In-depth interviews, interviewer's field notes and participants' letters were used for data collection. The participants were twenty Spanish women with lymphoedema after overcome a breast cancer in the past. Healthcare specialists with experience in the topic were also included. Results showed 2 main categories: "From cancer to lymphedema, another disease another disease" and "Potential for transition and transformation towards a new way of life". As a conclusion, the difficulty in accessing adequate treatment, the need for greater awareness of lymphedema and the importance of the emotional and psychological dimension of this chronic disease. Highlighting the attitudes that these women develop for self-care and the concept of new corporeality. After breast cancer, women with lymphedema experience a drastic change that affects all areas of their lives. The adaptation process, and the search for resources and aid, play a fundamental role in overcoming this process.

Next-generation sequencing-based gene panel tests for the detection of rare variants and hypomorphic alleles associated with primary open-angle glaucoma.

Primary open-angle glaucoma (POAG) is a complex disease with a strong hereditably component. Several genetic variants have recently been associated with POAG, partially due to technological improvements such as next-generation sequencing (NGS). The aim of this study was to genetically analyze patients with POAG to determine the contribution of rare variants and hypomorphic alleles associated with glaucoma as a future method of diagnosis and early treatment. Seventy-two genes potentially associated with adult glaucoma were studied in 61 patients with POAG. Additionally, we sequenced the coding sequence of CYP1B1 gene in 13 independent patients to deep analyze the potential association of hypomorphic CYP1B1 alleles in the pathogenesis of POAG. We detected nine rare variants in 16% of POAG patients studied by NGS. Those rare variants are located in CYP1B1, SIX6, CARD10, MFN1, OPTC, OPTN, and WDR36 glaucoma-related genes. Hypomorphic variants in CYP1B1 and SIX6 genes have been identified in 8% of the total POAG patient assessed. Our findings suggest that NGS could be a valuable tool to clarify the impact of genetic component on adult glaucoma. However, in order to demonstrate the contribution of these rare variants and hypomorphic alleles to glaucoma, segregation and functional studies would be necessary. The identification of new variants and hypomorphic alleles in glaucoma patients will help to configure the genetic identity of these patients, in order to make an early and precise molecular diagnosis.

Real-world study on microsatellite instability and mismatch repair deficiency testing patterns among patients with metastatic colorectal cancer in Spain.

PURPOSE: Clinical practice guidelines recommend that all patients with metastatic colorectal cancer (mCRC) should be tested for mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). We aimed to describe the dMMR/MSI-H testing practice in patients with mCRC in Spanish centers. METHODS: Multicenter, observational retrospective study that included patients newly diagnosed with mCRC or who progressed to a metastatic stage from early/localized stages. RESULTS: Three hundred patients were included in the study from May 2020 through May 2021, with a median age of 68 years, and two hundred twenty-five (75%) had stage IV disease at initial diagnosis; two hundred eighty-four patients received first-line treatment, and dMMR/MSI-H testing was performed in two hundred fifty-one (84%) patients. The results of the dMMR/MSI-H tests were available in 61 (24%) of 251 patients before the diagnosis of metastatic disease and in 191 (81%) of 236 evaluable patients for this outcome before the initiation of first-line treatment. Among the 244 patients who were tested for dMMR/MSI-H with IHC or PCR, 14 (6%) were MMR deficient. The most frequent type of first-line treatment was the combination of chemotherapy and biological agent, that was received by 71% and 50% of patients with MMR proficient and deficient tumors, respectively, followed by chemotherapy alone, received in over 20% of patients in each subgroup. Only 29% of dMMR/MSI-H tumors received first-line immunotherapy. CONCLUSION: Our study suggests that a high proportion of patients with mCRC are currently tested for dMMR/MSI-H in tertiary hospitals across Spain. However, there is still room for improvement until universal testing is achieved. TRIAL REGISTRATION: Not applicable.

Advances in the Treatment of Gastroenteropancreatic Neuroendocrine Carcinomas: Are we Moving Forward?

Poorly differentiated gastroenteropancreatic neuroendocrine carcinomas are aggressive neoplasms of challenging clinical management. A small proportion of patients with early-stage disease may achieve long-term survival, but the majority of patients present with rapidly lethal metastatic disease. Current standard of care still follows the treatment paradigm of small cell lung cancer, a far more common G3 neuroendocrine neoplasm, although emerging molecular and clinical data increasingly question this approach. In this article, we will briefly summarize epidemiology and prognosis of gastroenteropancreatic neuroendocrine carcinomas to emphasize the very low incidence, aggressive nature, and orphan status of this tumor entity. We will also discuss the current pathological classification and its limitations, as well as recent data on their differential biological background compared with small cell lung cancer, and its potential implications for patients care. Then, we will review the standard of care of systemic therapy, basically focused on platinum-based cytotoxic chemotherapy, including some recent randomized trials providing evidence regarding efficacy of irinotecan vs etoposide platinum doublets. Finally, we will present a comprehensive overview of novel therapeutic strategies in current clinical development, including recently reported data on immunotherapy, tumor-agnostic therapies (microsatellite instability, high tumor mutational burden, NTRK and RET gene fusions, BRAF or KRAS inhibitors), and additional treatment strategies targeting other tumor vulnerabilities (ie, Notch pathway, novel targets for radioligand therapy), and provide some insights regarding unmet needs and future perspectives to improve patient's care and prognosis.

MicroRNA signature and integrative omics analyses define prognostic clusters and key pathways driving prognosis in patients with neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) are mutationally quiet (low number of mutations/Mb), and epigenetic mechanisms drive their development and progression. We aimed at comprehensively characterising the microRNA (miRNA) profile of NENs, and exploring downstream targets and their epigenetic modulation. In total, 84 cancer-related miRNAs were analysed in 85 NEN samples from lung and gastroenteropancreatic (GEP) origin, and their prognostic value was evaluated by univariate and multivariate models. Transcriptomics (N = 63) and methylomics (N = 30) were performed to predict miRNA target genes, signalling pathways and regulatory CpG sites. Findings were validated in The Cancer Genome Atlas cohorts and in NEN cell lines. We identified a signature of eight miRNAs that stratified patients in three prognostic groups (5-year survival of 80%, 66% and 36%). Expression of the eight-miRNA gene signature correlated with 71 target genes involved in PI3K-Akt and TNFα-NF-kB signalling. Of these, 28 were associated with survival and validated in silico and in vitro. Finally, we identified five CpG sites involved in the epigenetic regulation of these eight miRNAs. In brief, we identified an 8-miRNA signature able to predict survival of patients with GEP and lung NENs, and identified genes and regulatory mechanisms driving prognosis in NEN patients.

Autonomic stress response of physiotherapy student in the different scenarios of an objective structured clinical examination.

The aim of the present research was to analyse modifications in the autonomic stress response of Physiotherapy students undergoing a 12-scenario Objective Structured Clinical Evaluation (OSCE). A total of 86 last year students of the Physiotherapy bachelor's degree (27.29 years (SD = 6.66); 36 females and 50 males) randomly assigned were monitored during the complete OSCE to measure heart rate variability (HRV) in temporal, frequency, and non-linear domains. The HRV analysed showed a large anticipatory stress response of students maintained during the entire evaluation. The stress response varied regarding OSCE station complexity and demands and the highest sympathetic response was not found in higher emotional scenarios.The autonomic modulation monitoring allows teachers to design OSCE scenarios more adapted to the students, limiting the effect of the stress response to allow a better performance.

The Effect of Studying a Double Degree in the Psychophysiological Stress Response in the Bachelor's Thesis Defense.

The aim of this research was to analyze the effect of studying a single or double degree in the psychophysiological stress response and academic performance of university students in their bachelor's thesis defense. We analyzed the autonomic stress response, cortical arousal, subjective distress perception, and the sense of objective and subjective academic fulfilment of 84 single-degree physiotherapy students and 26 double-degree sport sciences and physiotherapy students during their bachelor's thesis defense. The results showed that the bachelor's thesis defense was a stressful event for double-degree students, showing an activation of the sympathetic nervous system and presenting a higher autonomic habituation response for the double degree students compared to the single degree students. We found higher mean grades during the whole degree and higher grades in the written and oral bachelor's thesis academic achievements for single-degree students compared to double-degree students. No significant differences were found between single-degree and double-degree students in subjective distress perception and cortical arousal. No correlation was found between academic performance variables and subjective distress perception, cortical arousal, and autonomic modulation variables. We conclude that the bachelor's thesis defense produces a large anticipatory anxiety response in single-degree physiotherapy students and in double-degree sport sciences and physiotherapy students. Double-degree students showed higher levels of habituation and adaptability to the stressful event, with a better autonomic response. Academic achievements were significantly higher among single-degree students compared to the double-degree group.

Mutant PRPF8 Causes Widespread Splicing Changes in Spliceosome Components in Retinitis Pigmentosa Patient iPSC-Derived RPE Cells.

Retinitis pigmentosa (RP) is a rare, progressive disease that affects photoreceptors and retinal pigment epithelial (RPE) cells with blindness as a final outcome. Despite high medical and social impact, there is currently no therapeutic options to slow down the progression of or cure the disease. The development of effective therapies was largely hindered by high genetic heterogeneity, inaccessible disease tissue, and unfaithful model organisms. The fact that components of ubiquitously expressed splicing factors lead to the retina-specific disease is an additional intriguing question. Herein, we sought to correlate the retinal cell-type-specific disease phenotype with the splicing profile shown by a patient with autosomal recessive RP, caused by a mutation in pre-mRNA splicing factor 8 (PRPF8). In order to get insight into the role of PRPF8 in homeostasis and disease, we capitalize on the ability to generate patient-specific RPE cells and reveal differentially expressed genes unique to RPE cells. We found that spliceosomal complex and ribosomal functions are crucial in determining cell-type specificity through differential expression and alternative splicing (AS) and that PRPF8 mutation causes global changes in splice site selection and exon inclusion that particularly affect genes involved in these cellular functions. This finding corroborates the hypothesis that retinal tissue identity is conferred by a specific splicing program and identifies retinal AS events as a framework toward the design of novel therapeutic opportunities.

Chemotherapy in NEN: still has a role?

Neuroendocrine neoplasms (NENs) comprise a broad spectrum of tumors with widely variable biological and clinical behavior. Primary tumor site, extent of disease, tumor differentiation and expression of so matostatin receptors, proliferation and growth rates are the major prognostic factors that determine the therapeutic strategy. Treatment options for advanced disease have considerably expanded in recent years, particularly for well differentiated tumors (NETs). Novel drugs approved over the past decade in this context include somatostatin analogues and 177Lu-oxodotreotide for somatostatin-receptor-positive gastroenteropancreatic (GEP) NETs, sunitinib for pancreatic NETs (P-NETs), and everolimus for P-NETs and non-functioning lung or gastrointestinal NETs. Nevertheless, chemotherapy remains an essential component of the treatment armamentarium of patients with NENs, particularly of patients with P-NETs or those with bulky, symptomatic or rapidly progressive tumors (generally G3 or high-G2 NENs). In this manuscript we will comprehensively review available evidence related to the use of chemotherapy in lung and GEP NENs and will critically discuss its role in the treatment algorithm of this family of neoplasms.

Targeted Cancer Therapy: What's New in the Field of Neuroendocrine Neoplasms?

Neuroendocrine tumors (NETs) are a heterogeneous family of neoplasms of increasing incidence and high prevalence due to their relatively indolent nature. Their wide anatomic distribution and their characteristic ability to secrete hormonally active substances pose unique challenges for clinical management. They are also characterized by the common expression of somatostatin receptors, a target that has been extremely useful for diagnosis and treatment (i.e., somatostatin analogues (SSAs) and peptide-receptor radionuclide therapy (PRRT)). Chemotherapy is of limited use for NETs of non-pancreatic origin, and the only approved targeted agents for advanced progressive NETs are sunitinib for those of pancreatic origin, and everolimus for lung, gastrointestinal and pancreatic primaries. Despite recent therapeutic achievements, thus, systemic treatment options remain limited. In this review we will discuss the state-of-the-art targeted therapies in the field of NETs, and also future perspectives of novel therapeutic drugs or strategies in clinical development, including recently presented results from randomized trials of yet unapproved antiangiogenic agents (i.e., pazopanib, surufatinib and axitinib), PRRT including both approved radiopharmaceuticals (177Lu-Oxodotreotide) and others in development (177Lu-Edotreotide, 177Lu-Satoreotide Tetraxetan), immunotherapy and other innovative targeted strategies (antibody-drug conjugates, bites,…) that shall soon improve the landscape of personalized treatment options in NET patients.

The Impact of Nationality on the Psychophysiological Stress Response and Academic Fulfilment in the Final Degree Dissertation.

The aims of this study were: i. to analyze the effect of nationality on the psychophysiological stress response of physiotherapy last year students in their final degree dissertations; and ii. to analyze the relationship between the stress response and academic results according to nationality. We evaluated the autonomic stress response, cortical arousal, distress subjective perception, and objective and subjective academic fulfilment in Spanish, Italian, and French physiotherapy students during their final degree dissertation. Results showed a large anticipatory anxiety response before the dissertation in the three student groups. Only the Spanish group showed an increased tendency in the habituation process, reducing the psychophysiological stress response during the dissertation, while the Italian and French groups maintained a large sympathetic activation until the end of the dissertation. Cortical arousal and subjective perception of distress were similar in the three nationalities. In addition, no correlation between academic fulfilment and autonomic modulation was found. We concluded that there was no nationality effect in the psychophysiological stress response of physiotherapy last year students in their final degree dissertation, all of them showing a large anticipatory anxiety response.

Apert syndrome: Cranial procedures and brain malformations in a series of patients.

BACKGROUND: Apert syndrome is one of the most severe craniofacial disorders. This study aims to describe the craniofacial surgeries and central nervous system malformations of a cohort of children with Apert syndrome treated in the past 20 years and to compare these data with previously published data. METHODS: Retrospective analysis of a series of patients with Apert syndrome treated between 1999 and 2019 in our hospital. Information was analyzed regarding craniofacial procedures, hydrocephalus and presence of shunts, Chiari malformation Type 1, and other brain malformations such as corpus callosum and septum pellucidum anomalies. RESULTS: Thirty-seven patients were studied. Ventriculoperitoneal shunt prevalence was 24.3%, and 8.1% of patients required decompressive surgery for Chiari malformation. All of them needed at least one cranial vault remodeling procedure. The median age for this procedure was 8 months. In 69.7% of patients, the first cranial vault intervention was performed in the fronto-orbital region. In 36.4% of patients, a midface advancement had been performed at the time of this review, although this proportion was very dependent on the follow-up period and the age of the patients. The median age for the midface advancement procedure was 5.25 years. Anomalies of the corpus callosum and the septum pellucidum were reported in 43.2% and 59.5% of patients, respectively. CONCLUSION: Apert syndrome is a type of syndromic craniosynostosis, and patients usually require one or more cranial and facial surgeries. In comparison with other syndromic craniosynostosis types, Apert syndrome less frequently requires a VP shunt or treatment for a Chiari malformation.

The effect of final dissertation defense language, native vs. non-native, in the psychophysiological stress response of university students.

The objective of this study was to analyze the effect of final dissertation defense language in the autonomic stress response and cortical arousal of Physiotherapy students. We analysed in 110 students divided in 2 groups: native language (83) and non-native language (27), the autonomic stress response in four different moments of the dissertation defense; the cortical arousal and subjective perception of distress before and after the dissertation; and academic performance perception of students and the real performance obtained. Results showed a high sympathetic modulation at the beginning of the evaluation, which was maintained until the end of the evaluation in both groups. In addition, no decrease in cortical activity was found, possibly due to the short time of exposure to the stressful event. The final dissertation defense of Physiotherapy students produces an anticipatory anxiety response and a maintained high sympathetic nervous system activation during the defense, not negatively affecting cortical arousal, regardless of defending in native or non-native language.

Effectiveness of manual lymphatic drainage vs. perineal massage in secundigravida women with gestational oedema: A randomised clinical trial.

Perineal trauma (PT) may be considered as a very common injury during the childbirth. The incidence of PT was estimated in 30% to 85%, with 60% to 70% requiring suture. The present study was a prospective, single-blinded, randomised, clinical trial carried out from January 2015 to January 2016. For this study, 49 secundigravida women diagnosed with gestational oedema were recruited and randomly divided into two groups (A and B). Group A (n = 30) received the conventional treatment plus perineal massage and group B (n = 19) the conventional treatment plus manual lymphatic drainage (MLD). Visual analogue scale (VAS) and King Health's Questionnaire (KHQ) were performed to assess pain intensity and quality of life-related with urinary incontinence (UI). Pain intensity measurements showed statistically significant differences for a decrease after 30-weeks (P = .037), after 36-weeks (P = .000), and at the end of puerperium (P = .014) for MLD with respect to perineal massage group. Moreover, inter-groups repeated measures ANOVA for the values related statistically significant differences to the interaction of each applied treatment (perineal massage and MLD group, separately) over the pain intensity variable. MLD treatment reduced pain intensity with respect to perineal massage in secundigravida women with gestational oedema from 25-weeks of gestation to the end of puerperium.

Psychophysiological stress response of physiotherapy last year students in his final degree dissertation.

Final dissertation is considered one of the most stressful situations in university studies, but the stress response and its incidence in academic achievement is poor knowledge. The aim of the present research was to analyze the effect of the psychophysiological stress response of physiotherapy last year students in his final degree dissertation performance. We analyzed the heart rate variability (HRV) of 110 volunteers during their final degree dissertation to evaluate the autonomic stress response. Results showed a large anticipatory anxiety response of students prior to the final degree dissertation and a no habituation response, since low HRV results were found before and during the final degree dissertation. Only after the dissertation, the HRV increased. No relationship between autonomic modulation and the dissertation academic achievement were found. Final degree dissertation in physiotherapy students, produce a large anticipatory anxiety response. Autonomic modulation parameters do not present relationship with the final degree dissertation performance.

Proprioceptive Stabilizer™ training of the abdominal wall muscles in healthy subjects: a quasi-experimental study.

OBJECTIVE: The present quasi-experimental study aimed to assess the transversus abdominis (TrA), internal oblique (IO) and external oblique (EO) thickness in healthy subjects with the proprioceptive Stabilizer™ training in abdominal wall muscles. METHODS: A sample of 41 healthy participants (age: 31.9 ± 4.5 y; height: 1.7 ± 0.1 m; weight: 68.3 ± 13.1 kg; body mass index, BMI: 22.9 ± 2.7 kg/m2) were recruited to participate in this study. Ultrasound images of the EO, IO, TrA, rectus anterior (RA) and interrecti distance (IRD) were measured and analyzed by the ImageJ software. Measurements were made at rest and during the abdominal drawing-maneuver (ADIM) developed by the patients with the Stabilizer™ located in the low back holding 40 mmHg for 10 seconds with a visual stimulus provided by a circular pressure marker. RESULTS: Ultrasound measurements for the abdominal wall muscles showed statistically significant differences (Π < .05) for a thickness decrease of the EO, IO and a thickness increase of TrA. A proprioceptive Stabilizer™ training produced a thickness increase in TrA muscle and a thickness decrease in EO and IO muscles in healthy subjects. CONCLUSIONS: These findings suggest that a proprioceptive Stabilizer™ training could be useful in individuals with low back pain and lumbopelvic pain.

Proprioceptive Stabilizer™ training of the abdominal wall muscles in healthy subjects: a quasi-experimental study

SUMMARY The present quasi-experimental study aimed to assess the transversus abdominis (TrA), internal oblique (IO) and external oblique (EO) thickness in healthy subjects with the proprioceptive Stabilizer™ training in abdominal wall muscles. A sample of 41 healthy participants (age: 31.9 ± 4.5 y; height: 1.7 ± 0.1 m; weight: 68.3 ± 13.1 kg; body mass index, BMI: 22.9 ± 2.7 kg/m2) were recruited to participate in this study. Ultrasound images of the EO, IO, TrA, rectus anterior (RA) and interrecti distance (IRD) were measured and analyzed by the ImageJ software. Measurements were made at rest and during the abdominal drawing-maneuver (ADIM) developed by the patients with the Stabilizer™ located in the low back holding 40 mmHg for 10 seconds with a visual stimulus provided by a circular pressure marker. Ultrasound measurements for the abdominal wall muscles showed statistically significant differences (Π < .05) for a thickness decrease of the EO, IO and a thickness increase of TrA. A proprioceptive Stabilizer™ training produced a thickness increase in TrA muscle and a thickness decrease in EO and IO muscles in healthy subjects. These findings suggest that a proprioceptive Stabilizer™ training could be useful in individuals with low back pain and lumbopelvic pain.

RESUMO O objetivo do presente estudo foi avaliar o transverso abdominal (TrA), o oblíquo interno (OI) e a espessura oblíqua externa (EO) em indivíduos saudáveis com o treinamento proprioceptivo Stabilizer™ nos músculos da parede abdominal. Uma amostra de 41 participantes saudáveis (idade: 31,9±4,5 y, altura: 1,7±0,1 m; peso: 68,3±13,1 kg; índice de massa corporal, IMC: 22,9±2,7 kg / m2) foram recrutados para participar deste estudo. As imagens de ultrassom do EO, IO, TrA, reto anterior (RA) e distância interrecti (IRD) foram medidas e analisadas pelo software ImageJ. As medidas foram feitas em repouso e durante a manobra de desenho abdominal (Adim) desenvolvida pelos pacientes com o StabilizerTM localizado na parte inferior das costas segurando 40 mmHg por 10 segundos com um estímulo visual fornecido por um marcador de pressão circular. As medidas de ultrassom para os músculos da parede abdominal apresentaram diferenças estatisticamente significativas (P<0,05) para uma diminuição da espessura do EO, IO e um aumento de espessura do TrA. Um treinamento proprioceptivo Stabilizer™ produziu um aumento de espessura no músculo TrA e uma diminuição da espessura nos músculos EO e IO em indivíduos saudáveis. Esses achados sugerem que um treinamento de Stabilizer™ proprioceptivo poderia ser útil em indivíduos com dor lombar e dor lombo-pélvica.

Relationship between attention and balance: a dual-task condition study in children.

This study explored the relationship between motor functions and attention in children aged 4-5 years. A sample of 85 children was collected from a primary school (44 boys and 41 girls). We applied a standardized continuous attention performance test, the Kiddie Continuous Performance Test, under two conditions (sitting and balancing). Data were collected from two standardized balance tests, the Battelle and Pediatric Balance Scale. There was a significant relationship between attention and balance and gender differences that may condition the way to address balance issues in boys and girls. Gender should be considered when addressing balance problems to get efficient interventions. Balance skill may be a contributing factor in attention-deficit/hyperactivity disorder.