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Plants have a sophisticated and multilayered immune system. However, plant pathogens, helped by effector proteins, have found several strategies to evade plant immunity. For instance, the clubroot pathogen Plasmodiophora brassicae is able to turn the roots of susceptible hosts into nutrient-sink galls suppressing pattern-triggered immunity (PTI) and effector-triggered immunity. Chitin, the main component of P. brassicae spore cell walls and a well-known pathogen-associated molecular pattern, can elicit PTI but is also the target of plant chitinases and chitin deacetylases. The fact that P. brassicae does not trigger PTI during infection of susceptible hosts motivated a genome-wide search of genes coding for secreted proteins with domains previously associated with chitin binding. We found that the P. brassicae genome encodes a repertoire of candidate-secreted effectors containing the chitin-binding domain carbohydrate-binding module family 18 (CBM18), chitinase, and chitin deacetylase domains. The role of these proteins in the pathogenicity of the clubroot pathogen is unknown. Here, we characterized two CBM18 proteins, PbChiB2 and PbChiB4, which are transcriptionally activated during infection. Through coprecipitation, we found that recombinant PbChiB2 and PbChiB4 bind to spores and to chitin oligomers. We also showed that both proteins suppress chitin-triggered activation of the map kinase proteins MPK3 and MPK6 in the host Brassica napus. These findings suggest that P. brassicae CBM18 proteins act as effectors for protecting the clubroot pathogen and for suppressing chitin-triggered immunity during infection. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Plant pathogen effector proteins are key to pathogen virulence. In susceptible host Brassicas, the clubroot pathogen, Plasmodiophora brassicae, induces the production of nutrient-sink root galls, at the site of infection. Among a list of 32 P. brassiae effector candidates previously reported by our group, we identified SSPbP53 as a putative apoplastic cystatin-like protein highly expressed during the secondary infection. Here we found that SSPbP53 encoding gene is conserved among several P. brassicae pathotypes and that SSPbP53 is an apoplastic protein able to directly interact with and inhibit cruciferous papain-like cysteine proteases (PLCPs), specifically Arabidopsis XYLEM CYSTEINE PEPTIDASE 1 (AtXCP1). The severity of clubroot disease is greatly reduced in the Arabidopsis xcp1 null mutant (AtΔxcp1) after infection with P. brassicae resting spores, indicating that the interaction of P. brassicae SSPbP53 with XCP1 is important to clubroot susceptibility. SSPbP53 is the first cystatin-like effector identified and characterized for a plant pathogenic protist.

Introduction and Objectives:Massive hemorrhage (MH) is a growing pathology in military settings and increasingly in civilian settings; it is now considered a public health problem in the United States with large-scale programs. Tourniquets are the fastest and most effective intervention in MH if direct pressure is not effective.The Liaison Committee on Resuscitation (ILCOR) recognizes a knowledge gap in optimal education techniques for first aid providers. This review aims to describe training and evaluation methods for teaching tourniquet use to both health care and military professionals.Methods:The MEDLINE, CINAHL, WEB of Science, and Scopus databases were reviewed (from 2010 through April 2020). The quality of the selected studies was assessed using the Consolidated Standards of Reporting Trials (CONSORT) scale. Studies that met at least 65% of the included items were included. Data were extracted independently by two reviewers.Results:Ten of the 172 articles found were selected, of which three were randomized clinical trials. Heterogeneity was observed in the design of the studies and in the training and evaluative methods that limit the comparison between studies.Conclusions:The results suggest that the training strategies studied are effective in improving knowledge, attitudes, and practical skills. There is no universal method, learning is meaningful but research should be directed to find out which ones work best.

Dengue is a single-stranded RNA virus belonging to the Flaviviridae family. It is an endemic virus in tropical countries. In Colombia, 4 serotypes are present, and the disease is a burden for public health, social programs, and the economic sectors. The main vector is Aedes aegypti, and most infections are asymptomatic or minimally symptomatic. The hemorrhagic appearances of severe dengue are due to plasma leakage as a result of increased vascular permeability, severe thrombopenia, and hemoconcentration. In 2020, 78,979 cases of dengue were reported in Colombia. 38,836 (49.2%) of them were warning-free signs, 39,246 (49.7%) with warning signs, and 897 (1.1%) of severe dengue. As it is well-known, viral diseases are immune system activators, triggering off a loss of tolerance in it. Dengue is not an exception, and it is able to explain different autoimmune phenomena including macrophage activation. Mechanisms have been described by which an exacerbated response of the disease is triggered through the increase of infected cells, formation of immune complexes, and complement pathway activation, which lead to a cross-reaction of viral antigens with epithelial cells with platelets with subsequent endothelial dysfunction and bleeds. The first description of Evans syndrome was made in 1951 by Robert Evans. This syndrome is characterized by the combination of autoimmune hemolytic anemia, immune thrombocytopenia, and, less common/usual, immune neutropenia. This disease’s etiology is unknown, and the dysregulation of the immune system is among its possibilities. Here, we present the case of an unusual hematological and immunological complication of a patient who developed Evans syndrome during severe dengue, taking into account the concomitantly limited literature available for these two diseases, the need for a broader diagnostic approach, multidisciplinary intervention, and a more complex therapeutic approach.

To examine the effects of a time-matched endurance vs. concurrent training on circulating IL-6, IL-13, IL-15, IL-15Ra, FGF21 levels in postmenopausal women with obesity, and to determine these myokines response to endurance training pre- and postmenopause. Thirty-five sedentary postmenopausal women with obesity were randomly divided into endurance training (EN1

Objective To develop a best practice document for the management of postmenopausal vulvovaginal atrophy (VVA). Method Literature review carried out using clinical terms, treatments or interventions and comorbidity related to VVA. Results There is a wide variety of interventions that may produce temporal benefits for VVA. However, there are significant limitations in scientific publications concerning VVA and related issues, including variable outcome evaluations, variability in population age range, and small, often underpowered sample sizes. Therapeutic management of VVA should follow a sequential order, considering women's age, symptoms, general health as well as treatment preference. Beneficial options include lubricants, moisturizers, vaginal estrogens (estradiol, estriol, promestriene, conjugated estrogens), androgens, prasterone, and laser application. In women with general menopausal symptoms who are candidates for systemic hormone therapy, the lowest effective dose should be used. Oral ospemifene is an effective selective estrogen receptor modulator to treat VVA. Systemic androgens have a limited role. Although laser procedures are commonly used, at this moment the International Society for the Study of Vulvovaginal Disease does not endorse its use out of the setting of clinical trials. Pelvic floor muscle training improves blood flow and elasticity of the vulvovaginal tissue. In breast cancer survivors, moisturizers and lubricants are first line therapy. However, limited absorption of low/ultra-low doses of estrogens suggests safety, especially in women under treatment with aromatase inhibitors. As clinical practice and available preparations vary between countries this text should be adapted to local circumstances. Conclusions There is a wide range of therapeutic options to individualize VVA treatments.

To investigate endocrine function changes after non-functioning pituitary adenomas (NFPA) transsphenoidal surgery and to search for predictors of hypopituitarism resolution and development. We included 117 patients with NFPA who underwent endoscopic transsphenoidal surgery from 2005 to 2019 by two neurosurgeons. Twenty-one patients were excluded because of previous pituitary surgery or radiotherapy. We assessed symptoms at diagnosis, tumour volume, tumour removal, hormonal status at diagnosis, hormonal outcomes at 2- and 12-month follow-up, and complications. Pituitary stalk and gland MRI status (visible or not) were included, and it theirs association to hormonal function was studied for the first time, to our knowledge. Pituitary gland visualization was more frequent in those patients who showed a smaller number of axes affected at 12 months (p = 0.011). Pituitary stalk status showed no association to hormonal function. The hormonal normalization rate at 12 months was 13%. The endocrine improvement rate at 12 months was 16.7%. Worsening of hormonal function occurred in 19.8% of patients. Younger age was associated to hormonal improvement (p = 0.004). Higher preoperative tumour volume (p = 0.015) and absence of gross total resection (GTR) (p = 0.049) were associated with worsening in at least one hormonal axis after surgery. Pituitary gland visibility was higher in those patients who showed better hormonal outcomes. Assessment of initial hormonal function and outcome after surgery regarding pituitary stalk status showed no significant association. Higher preoperative tumour volumes and absence of GTR were associated to postoperative endocrine function worsening, while younger age was associated to its improvement.

The saccharide chains of heparan sulfate appear to be involved in several aspects Alzheimer disease (AD) pathogenesis. Their structural complexity is due to the expression of different isoenzymes. We studied the differential transcription of heparan sulfate chain biosynthesis in AD brains, analyzing different brain regions in patients with different extents of AD pathology. The transcriptomic study was performed by RT-PCR using samples of amygdala, anterior hippocampus, posterior hippocampus, claustrum, calcarine fissure, globus pallidus and cerebellum from patients with mild, moderate, or severe AD, as well as healthy individuals. Certain heparan sulfate epitopes were also detected by immunohistochemistry. Several genes, across all stages of heparan sulfate synthesis, showed altered transcription in different brain regions of AD patients. The numbers of alterations were greater in in moderate versus mild AD patients. In severe patients, there were fewer alterations in genes related to early stages of biosynthesis, and overexpression of genes involved in late stages. The alterations correlated with progressive brain atrophy, although alterations were more common in the cerebellum. Detection of some heparan sulfate epitopes by immunohistochemistry was consistent with previous studies. In conclusion, transcriptional alterations in the biosynthetic genes of heparan sulfate depend on the brain region and the degree of AD pathology.

Objective Despite the efforts made to determine the achieved resection grade after pituitary adenoma surgery, there is a high level of disagreement among all the available classifications and measurement methods used. Our objective is to identify the factors that preoperatively could predict a gross total resection (GTR) of a clinically nonfunctioning pituitary adenoma through an endoscopic endonasal approach. Methods Across 100 surgeries, we analyzed epidemiologic and clinical data, radiologic relevant data, extent of resection (EOR), and postoperative outcomes. The EOR was measured objectively through an accurate volumetric analysis. Results The median presurgical volume was 8.58 cm3 (range, 0.5–58 cm3), the median maximum diameter was 27.3 mm (range, 7–67 mm), and the Knosp grade was 0 in 1 patient, 1 in 23%, 2 in 31%, 3 in 23% and 4 in 22% of patients. In the multivariate logistic regression analysis, we found 3 factors that significantly predicted the chances of a successful GTR: previous sellar surgery, Knosp grade, and tumor signal in the T2-weighted magnetic resonance imaging scan. Another 10 radiologic variables were analyzed and had no effect on the EOR. Conclusions Knosp grade (P

Keloids are a difficult-to-treat disease characterized by an imbalance in mechanisms of tissue reparation. We present the case of a middle-aged woman with spontaneous keloids which histologically and clinically improved after UVA-1 phototherapy treatment. There are few reported cases of keloids treated with high doses of UVA-1 phototherapy. We used a low-dosage regimen with a good response in only one cycle, which could diminish the risk of skin cancer development.

Introduction: We analysed the neurological complications of patients with severe SARS-CoV-2 infection who required intensive care unit (ICU) admission. Patients and methods: We conducted a retrospective, observational, descriptive study of consecutive patients admitted to the ICU due to severe respiratory symptoms secondary to SARS-CoV-2 infection between 1 April and 1 June 2020. Results: We included 30 patients with neurological symptoms; 21 were men (72.40%), and mean age (standard deviation [SD]) was 57.41 years (11.61). The mean duration of ICU stay was 18.83 days (14.33). The neurological conditions recorded were acute confusional syndrome in 28 patients (93.33%), neuromuscular disease in 15 (50%), headache in 5 (16.66%), cerebrovascular disease in 4 (13.33%), and encephalopathies/encephalitis in 4 (13.33%). CSF analysis results were normal in 6 patients (20%). Brain MRI or head CT showed alterations in 20 patients (66.6%). EEG was performed in all patients (100%), with 8 (26.66%) showing abnormal findings. In 5 of the 15 patients with clinical myopathy, diagnosis was confirmed with electroneuromyography. We found a correlation between older age and duration of ICU stay (P = 0.002; 95% CI, 4.032–6.022; OR). Conclusions: Severe COVID-19 mainly affects men, as observed in other series. Half of our patients presented acute myopathy, and almost all patients left the ICU with acute confusional syndrome, which fully resolved; no correlation was found with EEG or neuroimaging findings. Older age is associated with longer ICU stay. Resumen: Introducción: Nos proponemos analizar las complicaciones neurológicas de los pacientes con infección grave por SARS-CoV2, que han requerido ingreso en Unidad de Cuidados Intensivos (UCI). Pacientes y métodos: Estudio descriptivo retrospectivo, observacional, de pacientes consecutivos ingresado en UCI por infección respiratoria grave por SARS-CoV-2, desde el 1 de Abril hasta el 1 de Junio de 2020. Resultados: Registramos 30 pacientes con síntomas neurológicos, 21 hombres (72,40%), edad media: 57,41 años ± 11,61 desviación estándar (DE). Estancia media en UCI: 18,83 ± 14,33 DE. A nivel sindrómico: 28 pacientes (93,33%) con síndrome confusional agudo, 15 pacientes (50%) con patología neuromuscular, 5 (16,66%) cefalea, 4 (13,33%) con patología cerebrovascular, y 4 (13,33%) con encefalopatías/encefalitis. Punción lumbar normal en 6 pacientes (20%). La RMN craneal o TAC craneal mostró alteraciones en 20 casos (66,6%). Se realizó EEG en todos los pacientes (100%), alterado en 8 pacientes (26,66%). En 5 de los 15 pacientes con miopatía clínica se ha podido confirmar con ENMG. Hemos encontrado relación entre la mayor edad y los días de ingreso en UCI (P = 0,002, IC 95% 4,032-6,022; OR:). Conclusiones: La infección grave por COVID-19 afecta mayoritariamente a hombres, similar a lo descrito en otras series. La mitad de nuestros pacientes presentan una miopatía aguda, y casi la totalidad de los pacientes salen de la UCI con sindromes confusionales agudos, que evolucionan a la resolución completa, sin correlacionarse con los resultados del EEG o de pruebas de neuroimagen. La mayor edad sí se asocia con un mayor número de días de estancia en UCI.

Background: In the search for an effective closure without nasosinusal morbidity, we have studied the efficacy of free mucosal graft as a reconstructive technique of the sellar floor after the resection of nonfunctioning pituitary adenomas (NFPA). Methods: In 100 endonasal endoscopic surgeries, we analyzed the personal history, radiological and intraoperative aspects that could have an impact on the risk of postoperative cerebrospinal fluid (CSF) leak. They were divided into three groups: no mucosa flap/graft, mucosal free graft, and nasoseptal pedicled flap. Results: The characteristics of the patients and adenomas were the same in all three groups. Intraoperative CSF leak was observed in 1/13 cases of the group without graft/flap (7%), in 16/50 of the free mucosal graft (32%) and 12/37 (32%) of pedicle flap. The proportion of cases in which other means of reconstruction were used in addition (fat, collagen matrix, and sealant) was similar in the different groups. No CSF leaks were observed, except for a doubtful one in the free mucosal graft group, which resolved spontaneously within 24 h, without receiving any type of treatment. Conclusions: The middle turbinate free mucosal graft can be of great value in endonasal surgery: It achieves a hermetic closure in cases of low-flow CSF leaks, it can be useful as a rescue for cases where nasoseptal mucosa is not available to perform a pedicled nasoseptal flap, minimizes the nasosinusal complications of the pedicled flap by leaving a smaller surface area of the nasal cavity devoid of the mucosa, and achieves greater nasosinusal functionality because proper reepithelialization occurs in the area.

Avulsion fracture types II and III of flexor digitorum profundus (FPD), also called Jersey Finger, in flexor zone 1 are an uncommon pathology requiring surgical treatment. The aim of this study was to assess whether hook miniplates were an accessible and reliable option to repair FDP avulsion types II and III. Between July and August 2018, we treated 2 consecutive patients’ zone 1 Leddy-Packer type II and III FDP injuries with hook plates and 1.2 × 7 mm screws included in Medartis Aptus Hand fixation system set. Patients were aged 37 and 39 years, a man and a woman, respectively. At the end of the follow-up, we evaluated the Visual Analog Scale, range of motion, grip strength, and Quick Disabilities of the Arm, Shoulder, and Hand. Both patients completed 12 months of follow-up with excellent functional and radiological results. Neither presented complications or residual disability. This injury has been treated with a wide range of surgical techniques, including anchor suture, pullout button sutures, screws, and plates. However, due to the difficulty in surgical fixation of fragments around finger joints, limited access to ligaments and tendons, and the lack of cases, none of the techniques have turned out as a clear option above others. Hook plates placed in distal phalanx emerge as surgical treatment for FDP avulsion types II and III in flexor zone 1, with excellent clinical outcomes.

Doxycycline is a synthetic tetracycline that was approved in 1967. This wide-spectrum antibiotic has been shown to also have useful anti-inflammatory properties that make it suitable for the treatment of a number of noninfectious conditions. Tetracyclines are probably the most commonly prescribed antibiotics in dermatology, where they are usually used at doses lower than those effective against infections. They also have an excellent efficacy and safety profile. Because of doxycycline's ability to inhibit the molecular pathways associated with certain processes, this antibiotic can be used to treat hair follicle diseases, granulomatous diseases, and vascular proliferation, among other conditions. The main properties of doxycycline and its many applications in dermatology make this drug one that specialists should become familiar with.

AIM This study explored the association between the presence of uterine fibroids (UF), as determined by ultrasound, and preterm birth (PB) risk. METHODS Medline, Embase, Cochrane, Scopus and Web of Science databases. Studies reporting women with and without UF demonstrated by an ultrasound exam. The primary outcome was the risk of PB

Author(s): Arenas Bermejo, Carolina; Perez Alenza, Dolores; Garcia San Jose, Paula; Llauet, Lidia; Perez-Lopez, Laura; Melian, Carlos; C Feldman, Edward | Abstract: BackgroundResults of ACTH stimulation test (ACTHst), pre- and post-trilostane serum cortisol concentrations (SCCs), urine concentration (urine-specific gravity [USG]), and urine cortisol : creatinine ratios (UCCRs) are common variables used to monitor trilostane treatment of dogs with pituitary-dependent hyperadrenocorticism (PDH). However, none has consistently discriminated dogs receiving an adequate dose (A) from those overdosed (O) or underdosed (U).ObjectivesTo assess and compare recommended monitoring variables, including serial SCCs in a cohort of dogs with PDH treated with trilostane.AnimalsPrivately owned dogs with PDH (n = 22) and 3 healthy dogs (controls).MethodsProspective, multicenter, 2-day study. On day "a" (randomized): ACTHst was completed. Day "b" (g2 to l7 days later): SCCs were assessed -0.5 hours, immediately before, and 1, 2, 2.5, 3, 3.5, 4, 6, 8, and 12 hours after trilostane administration. On the first study day, urine collected at home was assessed for USG, UCCR and owner opinions regarding PDH were categorized as: A (clinical signs resolved), U (remains symptomatic), or ill (possible O).ResultsAt 27 pairs of evaluations, 7 dogs were categorized as A, 19 U, and 1 possible O (excluded from the study). There was overlap in SCC results from the A and U dogs at every time point. Results of USG, UCCR, and ACTHst did not discriminate A from U dogs. Trilostane suppresses SCC within 1 hour of administration and its duration of action in most PDH dogs is l8 hours.Conclusions and clinical importanceNo single variable or group of variables reliably discriminated A dogs from U dogs during trilostane treatment for PDH.

Purpose of review Examine recent evidence of randomized controlled trials and meta-analyses regarding the effect of maternal vitamin D status and supplementation over obstetrical and offspring outcomes. Recent findings Maternal serum 25-hydroxyvitamin [25(OH)D] progressively declines during pregnancy because of fetal physiological demands and adjustments. Vitamin D supplementation during pregnancy in women with low vitamin D status may improve fetal growth and reduce the risks for small-for-gestational-age, preeclampsia, preterm birth, and gestational diabetes. Mothers with sufficient vitamin D levels have offsprings with less enamel defects and less attention deficit and hyperactive disorders and autism. All pregnant women should be supplemented with 600 IU/day of vitamin D3. We discuss evidence indicating that higher vitamin D doses (1000-4000 IU/day) may be convenient to achieve better maternal and infant outcomes. Low maternal vitamin D status during pregnancy may be associated in infants with a higher risk for lower bone mineral content, enamel defects and attention deficit hyperactive disorder. Summary Recent evidence from vitamin D intervention studies and meta-analyses of a large number of studies support vitamin D supplementation during pregnancy to improve maternal, fetal and, immediate and later offspring health.

Objectives The biochemical conditions in which patients arrive before renal transplantation (RT) are rarely evaluated; examples of them are found in the Dialysis Outcomes and Practice Patterns Study (DOPPS). The objective of our study was to ascertain the fulfillment of biochemical goals for patients on renal replacement therapy before RT. Material and Methods Observational, retrospective study of patients who were on a RT protocol between 2012 and 2017 in 2 RT centers in Mexico. The records of 1188 patients with a history of RT and their lab results before transplantation were analyzed. Anthropometric values including hemoglobin, iron levels, calcium, phosphorus, parathyroid hormone, urea, creatinine, uric acid, and left ventricular ejection fraction were studied. All values were categorized as low, optimal, or high levels. Results The fulfillment of pretransplant biochemical objectives for elimination of azotemia (urea and creatinine) was achieved in 60% of the patients. Optimal values for calcium were found in 715 (64%) patients and optimal values for albumin were found in 690 (61.8%) patients. In the case of phosphorus, hemoglobin, uric acid, and parathyroid hormone, the optimal values were below 50%. Conclusions It is essential to improve compliance with biochemical and clinical objectives for patients on renal replacement therapy (dialysis, hemodialysis) before RT. Only half of the variables were within the optimal range before surgical intervention took place.

Choroid plexus papilloma is an uncommon tumour of the central nervous system, accounting for less than 1% of all intracranial neoplasm. The usual locations are the lateral ventricle in infants and children and the fourth ventricle in adults. The third ventricle is a rare location, with few cases reported in the literature. We describe the case of a 3-month-old boy who was admitted to our centre with signs of raised intracranial pressure. Neuroimaging studies showed a third ventricular mass with associated hydrocephalus. The patient underwent complete tumour removal through a transfrontal approach and ventriculo-peritoneal shunt surgery. Postoperative course of the child was uneventful and follow-up magnetic resonance imaging revealed no residual tumour. Histopathology of the resected lesion confirmed the diagnosis of choroid plexus papilloma. We discuss the clinical, radiological and histological features of this infrequent type of tumours.

Background: Depressive symptoms may affect female mid-life sexuality, whereas sexual problems tend to aggravate depression. Despite this, data assessing this association drawn from mid-aged Paraguayan women are scarce. Objective: This study aimed to assess the association between depressed mood and the risk of sexual dysfunction during female mid-life. Methods: Sexually active urban-living women from Asuncion, Paraguay (n = 193, aged 40-60 years) were surveyed with the 6-item Female Sexual Function Index (FSFI-6), the 10-item Center for Epidemiological Studies Depression Scale (CESD-10), and a general questionnaire containing personal and partner information. Depressed mood was defined as a total CESD-10 score of 10 or more, and an increased risk for sexual dysfunction as an FSFI-6 total score of 19 or less. The association of depressed mood and an increased risk of sexual dysfunction was evaluated with multivariable Poisson regression. Results: The mean age (+/- standard deviation) of surveyed woman was 48.3 +/- 6.0 years and 61.1% (n = 118) were perimenopausal and postmenopausal. A total of 21.8% (n = 42) had depressed mood and 28.5% (n = 55) had an increased risk of sexual dysfunction. The final adjusted regression model determined that women with depressed mood were twice as likely to have an increased risk of sexual dysfunction, compared to women with normal mood (adjusted prevalence ratio = 2.14, 95% confidence interval 1.26-3.60). On the other hand, depressed mood was associated with a mean total FSFI-6 score that was 20% lower than that observed among women with normal mood (adjusted incidence rate ratio = 0.80, 95% confidence interval 0.68-0.93). Conclusion: In this mid-aged Paraguayan female sample there was a significant association between depressed mood and an increased risk of sexual dysfunction.

This review updates the knowledge regarding the association between the polycystic ovary syndrome (PCOS) and the risk of gynecological cancer. We performed a literature review of clinical and epidemiological studies concerning PCOS and the risk of breast, endometrial and ovarian cancer after selecting information by quality of scientific methodology. It was found that evidence does not support a link between PCOS and breast cancer risk. There is an increased risk of endometrial cancer, while data concerning ovarian cancer are contradictory. Regarding PCOS and its association to cervical, fallopian tube, and vulvar cancer, the quality of evidence is heterogeneous. In conclusion, women with PCOS should be screened for endometrial cancer and more research is warranted to determine in this population the true risk of developing other gynecological cancers such as breast and ovarian.

Plasmodiophora brassicae (Wor.) is an obligate intracellular plant pathogen affecting Brassicas worldwide. Identification of effector proteins is key to understanding the interaction between P. brassicae and its susceptible host plants. To date, there is very little information available on putative effector proteins secreted by P. brassicae during a secondary infection of susceptible host plants, resulting in root gall production. A bioinformatics pipeline approach to RNA‐Seq data from Arabidopsis thaliana (L.) Heynh. root tissues at 17, 20, and 24 d postinoculation (dpi) identified 32 small secreted P. brassicae proteins (SSPbPs) that were highly expressed over this secondary infection time frame. Functional signal peptides were confirmed for 31 of the SSPbPs, supporting the accuracy of the pipeline designed to identify secreted proteins. Expression profiles at 0, 2, 5, 7, 14, 21, and 28 dpi verified the involvement of some of the SSPbPs in secondary infection. For seven of the SSPbPs, a functional domain was identified using Blast2GO and 3D structure analysis and domain functionality was confirmed for SSPbP22, a kinase localized to the cytoplasm and nucleus.

Background: In people, obesity and prediabetes mellitus might predispose to chronic kidney disease (CKD). Aims: To assess the association of overweight [Body condition score (BCS) >5] and glucose metabolism alterations, with established or potential markers of CKD. In addition, fructosamine and fasted blood glucose were compared as predictors of early abnormal glucose metabolism. Methods: 54 clinically healthy cats were included in a cross-sectional study comprising 25 neutered males and 29 (28 neutered) females aged 7.2 (5.5–9.4) years. Two potential markers of CKD, namely urinary free active transforming growth factor-β1-creatinine ratio and urinary retinol binding protein-creatinine ratio were measured along with other parameters to assess CKD. A receiver operating curve was used to identify the best sensitivity and specificity of fructosamine to identify cats with fasting glucose >6.5 mmol/L. Results: No association was found between BCS and markers of CKD. Fructosamine was greater in cats with fasting glucose >6.5 mmol/L compared to those with fasting glucose ≤6.5 mmol/L. A fructosamine concentration ≥250 µmol/L was able to detect cats with hyperglycemia with a sensitivity of 77% and a specificity of 65%. Furthermore, fructosamine was more strongly correlated with fasting glucose than albumin-corrected fructosamine (r = 0.43, p = 0.002 vs r = 0.32, p = 0.026). Cats with higher fructosamine had lower serum symmetric dimethylarginine concentrations. Conclusion: The present study does not suggest an effect of obesity on renal function in domestic cats. Clinical relevance: Fructosamine might be of value for the diagnosis of prediabetes mellitus in cats.

For years, the presence of clubroot disease and its causal agent, Plasmodiophora brassicae, in Mexico has been given by granted. However, after a long search in the scientific literature in English and Spanish, as well as grey literature including thesis and government reports, we were not able to find any information regarding the actual detection of the pathogen, hosts affected, areas with the disease, or any real information about clubroot (‘hernia de la col’, in Mexico). To confirm if P. brassicae was indeed in Mexico, we started a true detective adventure. First, we identified agricultural communities in south-east Mexico known to grow cruciferous crops. Second, we asked to the growers if they have ever seen clubroot symptoms, showing them during the inquires pictures of the characteristic galls that might have been present in their crops. Third, we collected soil from two of the communities with positive response and grew an array of cruciferous in the soil as baits to “fish” the clubroot pathogen. We detected the presence of galls in the roots of 32 plants and observed the presence of resting spores. Through a P. brassicae specific PCR assay, we were able to confirm the presence of the clubroot pathogen in the samples and in Mexico for the very first time. This study is the first report and identification of P. brassicae in Mexico, opening the doors to understand the genetic diversity of this elusive and devastating plant pathogen.

BACKGROUND There are contradictory data concerning kisspeptin in gravids with preeclampsia and gestational hypertension (GH). OBJECTIVE To conduct a meta-analysis of studies comparing maternal kisspeptin levels in gravids with and without preeclampsia or GH. MATERIAL AND METHODS We searched PubMed, LILACS, and CNKI list of articles up to 20 August 2021, without language limitations, comparing circulating maternal kisspeptin levels, and maternal and neonatal outcomes in gravids with and without preeclampsia or GH. Meta-analyzed results are reported as standardized mean differences (SMD), and their 95% confidence interval (CI). RESULTS Seven studies with a low-to-moderate risk of bias were eligible for meta-analysis. Gravids with preeclampsia or GH displayed significantly lower circulating kisspeptin levels (SMD, -0.68, 95% CI, -1.04 to -0.32), lower gestational ages at delivery (SMD, -2.22, 95% CI, -3.25 to -1.18), and birth weight (SMD, -2.16, 95% CI, -3.15 to -1.17), and significantly higher body mass indices (MD, 0.56, 95% CI, 0.24-0.88), systolic (SMD, 2.87, 95% CI, 2.22-3.53), and diastolic blood pressures (SMD, 2.57, 95% CI, 2.19-2.95). CONCLUSION Gravids with preeclampsia or GH had lower kisspeptin levels as compared to normotensive controls.

OBJECTIVE This study aimed to evaluate the prevalence of dynapenia and factors related to low dominant handgrip strength (HGS) in postmenopausal women. METHODS A cross-sectional study was performed on 249 postmenopausal women aged 50 to 84 years. The following variables were recorded: age, age at menopause, smoking status, and the HGS measured with a digital dynamometer, body mass index, and adiposity assessed by bioelectric impedance. The physical activity level was evaluated by using the International Physical Activity Questionnaire. Bone mineral density was reported as T-scores, and blood biochemical parameters (calcium, phosphorus, vitamin D, and parathormone levels) were measured. RESULTS 31.3% of women had dynapenia, and those aged ≥65 years had lower HGS (P

Myocardial infarction (MI) is a leading cause of maladaptive cardiac remodeling and heart failure. In the damaged heart, loss of function is mainly due to cardiomyocyte death and remodeling of the cardiac tissue. The current study shows that A-kinase anchoring protein 2 (AKAP2) orchestrates cellular processes favoring cardioprotection in infarcted hearts. Induction of AKAP2 knockout (KO) in cardiomyocytes of adult mice increases infarct size and exacerbates cardiac dysfunction after MI, as visualized by increased left ventricular dilation and reduced fractional shortening and ejection fraction. In cardiomyocytes, AKAP2 forms a signaling complex with PKA and the steroid receptor co-activator 3 (Src3). Upon activation of cAMP signaling, the AKAP2/PKA/Src3 complex favors PKA-mediated phosphorylation and activation of estrogen receptor α (ERα). This results in the upregulation of ER-dependent genes involved in protection against apoptosis and angiogenesis, including Bcl2 and the vascular endothelial growth factor a (VEGFa). In line with these findings, cardiomyocyte-specific AKAP2 KO reduces Bcl2 and VEGFa expression, increases myocardial apoptosis and impairs the formation of new blood vessels in infarcted hearts. Collectively, our findings suggest that AKAP2 organizes a transcriptional complex that mediates pro-angiogenic and anti-apoptotic responses that protect infarcted hearts.

Informe de un caso; Enfermedad rara; Revisión sistemática Informe d'un cas; Malaltia rara; Revisió sistemàtica Case report; Rare disease; Systematic review Background: Case reports are usually excluded from systematic reviews. Patients with rare diseases are more dependent on novel individualized strategies than patients with common diseases. We reviewed and summarized the novelties reported by case reports in mucopolysaccharidosis type II (MPS-II) patients treated with enzyme replacement therapy (ERT). Methods: We selected the case reports included in a previous meta-analysis of patients with MPS-II treated with ERT. Later clinical studies evaluating the same topic of those case reports were reported. Our primary aim was to summarize novelties reported in previous case reports. Secondary objectives analyzed the number of novelties evaluated in subsequent clinical studies and the time elapsed between the publication of the case report to the publication of the clinical study. Results: We identified 11 innovative proposals in case reports that had not been previously considered in clinical studies. Only two (18.2%) were analyzed in subsequent nonrandomized cohort studies. The other nine novelties (81.8%) were analyzed in later case reports (five) or were not included in ulterior studies (four) after more than five years from their first publication. Conclusions: Case reports should be included in systematic reviews of rare disease to obtain a comprehensive summary of the state of research and offer valuable information for healthcare practitioners. This research received no external funding.

Clubroot is a devastating disease caused by the protist Plasmodiophora brassicae Woronin. After root hair colonization, the clubroot pathogen induces clubs that block water uptake, leading to dehydration and death. The study of the severity of plant diseases is very important. It allows us to characterize the level of resistance of plant germplasm and to classify the virulence of pathogen strains or isolates. Lately, the use of learning machines and automatization has expanded to plant pathology. Fast, reliable and unbiased methods are always necessary, and with clubroot disease indexing this is not different. From this perspective, we discuss why this is the case and how we could achieve this long overdue task for clubroot disease.

Small-for-gestational-age (SGA) infants have been associated with increased risk of adverse perinatal outcomes (APOs). In this work, we assess the predictive ability of the ultrasound-estimated percentile weight (EPW) at 35 weeks of gestational age to predict late-onset SGA and APOs, according to six growth standards, and whether the ultrasound–delivery interval influences the detection rate. To this purpose, we analyze a retrospective cohort study of 9585 singleton pregnancies. EPWs at 35 weeks were calculated to the customized Miguel Servet University Hospital (MSUH) and Figueras standards and the non-customized MSUH, Fetal Medicine Foundation (FMF), INTERGROWTH-21st, and WHO standards. As results of our analysis, for a 10% false positive rate, the detection rates for SGA ranged between 48.9% with the customized Figueras standard (AUC 0.82) and 60.8% with the non-customized FMF standard (AUC 0.87). Detection rates to predict SGA by ultrasound–delivery interval (1–6 weeks) show higher detection rates as intervals decrease. APOs detection rates ranged from 27.0% with FMF to 7.9% with the Figueras standard. In conclusion, the ability of EPW to predict SGA at 35 weeks is good for all standards, and slightly better for non-customized standards. The APO detection rate is significantly greater for non-customized standards.

Among the millions of microorganisms inhabiting the soils, some can be plant pathogens, meaning they can become a disease to plants. Some diseases are more well-known than others. This is the case of clubroot, a very atypical microorganism that infects cruciferous plants, such as cabbage, kale, canola, and the common research plant thale cress. In this article, I will tell you more about clubroot and clubroot disease because there is still a lot to discover about the pathogen and the disease. Maybe you will be part of our lab in the future and investigate a fascinating soil-borne pathogen.

Purpose The aim of this study was to evaluate the associated factors of patients with LSS who undergo reoperation after a PLSF in a Hispanic-American population. Methods A retrospective single-center review was performed from all non-age-related Hispanic-Americans with LSS who underwent one or two-level PLSF from 2008 to 2018. Baseline characteristics were analyzed between the reoperation and no-reoperation group using a bivariate and multivariate analyses. Results Out of 425 patients who underwent PLSF, 38 patients underwent reoperation. At a two-year follow-up, the reoperation rate was 6.1% (26/425), mostly due to pseudoarthrosis (39.5%), recurrent stenosis (26.3%), new condition (15.8%), infection (10.5%), hematoma (5.3%), and dural tear (2.6%). Patients who underwent reoperation were more likely to have a preoperative history of epidural steroid injection (ESI) (OR 5.18, P = 0.009), four or more comorbidities (OR 2.69, P = 0.028), and operated only with a posterolateral fusion without intervertebral fusion (OR 2.15, P = 0.032). Finally, the multivariable analysis showed that ESI was the only independent associated factor in patients who underwent reoperation after a PLSF in our group. Conclusion Among this population who underwent surgery, a reoperation rate at two years of follow-up was less than ten percent. Our study did not find any associated factor inherent to Hispanic-Americans, as ethnic group, who were reoperated after LSS.

The severe acute respiratory syndrome due to coronavirus 2 (SARS-CoV-2) infection has affected millions of individuals worldwide, causing high mortality rates and severe physical sequelae, with a negative impact on society, economy, health care, lifestyle and personal relationships. Studies have confirmed this infection has sex and age differences in terms of disease severity and immune response, with a particular relationship with the anti-Müllerian hormone, a marker of aging, and estradiol, a marker of ovarian function. Postmenopausal women seem to present a more severe infection as compared to premenopausal ones. Estradiol protects the vascular system, mediating with the renin-angiotensin-aldosterone system, whereas testosterone enhances the levels of angiotensin-converting enzyme and the transmembrane protease serine-type 2, thus delaying viral clearance in men as compared to women. This new infection will stay among us, transforming our social, economic and daily lifestyle, and hence medical and health care as well as the use of menopause hormone therapy will need redefining, considering both preventive and curative perspectives.

Clubroot is a devastating disease affecting cruciferous crops worldwide. Clubroot was first described in the 13th century in Russia and from that moment has been affecting European, Asian, and American brassica production. Plasmodiophora brassicae is the clubroot causal agent, and it is an obligate intracellular parasite that, as soil-borne resting spores, can remain viable in soil for many years. This persistence in the soil is a major negative contributing factor to the management of clubroot disease and highlights the importance for brassica growers to have ready access to current information on the distribution of the pathogen. The interactive online tool ClubrootTracker ( http://clubroottracker.ca ) has been developed to enable users to view pathogen and disease presence in geographic locations across the world. ClubrootTracker, as described in this manuscript, has been developed to provide brassica farmers a tool that will contribute to clubroot management and aid in planning a clubroot-free farm. This tool is an open resource that has the main goal of acquisition of GPS information in reporting the pathogen or the disease by the researchers working with it around the world.

Menopause and aging are associated with changes in circulating gonadal steroid hormones, insulin sensitivity, body composition, and also lifestyle and social coordinates. Vitamin D status influences different metabolic adjustments, aside from calcium-phosphorus and bone metabolism. The main blood marker used to measure endogenous vitamin D status is 25-hydroxyvitamin D. Aging is associated with increases in serum parathyroid hormone and alkaline phosphatase, and a decrease of serum calcium, phosphorus, and vitamin D metabolites. 25-Hydroxyvitamin D status is also influenced by the circannual rhythm of sun irradiation. Results of clinical association studies have not correlated with intervention trials, experimental studies, and/or meta-analyses regarding the role of vitamin D on different outcomes in women during their second half of life and the vitamin D supplementation dose needed to improve clinical endpoints. Discordant results have been related to the method used to measure vitamin D, the studied population (i.e., sociodemographics and ethnicity), study designs, and biases of analyses. Vitamin D supplementation with cholecalciferol or calcifediol may improve some metabolic variables and clinical outcomes in young postmenopausal and older women. Studies seem to suggest that calcifediol may have some advantages over other forms of vitamin D supplementation. Further studies are needed to define interventions with supplements and effective food fortification.

Introducción: El debut de la Enfermedad Renal Crónica (ERC) se ha relacionado en parte con los escasos conocimientos de los pacientes acerca de la fisiopatología renal y los factores de riesgo relacionados, lo que a su vez predice un peor diagnóstico y pronóstico. En este sentido, una correcta alfabetización en salud desde edades tempranas puede prevenir el desarrollo de hábitos de vida perniciosos. Objetivo principal: Evaluar los conocimientos de la población universitaria de Málaga sobre los conceptos básicos asociados a la ERC. Material y Método: Se llevó a cabo un estudio transversal-descriptivo con estudiantes de Grado en la Universidad de Málaga durante el curso 2016-2017, a través de un cuestionario autoadministrado elaborado Ad Hoc para determinar sus conocimientos sobre fisiopatología renal y su prevención. El cuestionario constó de 28 preguntas, divididas en 5 categorías temáticas y fue revisado previa administración, por 10 expertos en nefrología (médicos y enfermeras) y pilotado con 38 personas. Resultados: El nivel de conocimientos resultó ser bajo en general, con 14,3±4,7 respuestas correctas de 28. Se encontraron diferencias estadísticamente significativas según rama de conocimiento, donde los estudiantes de Ciencias de la Salud obtuvieron los mejores resultados con 18,25 (IC 17,18-19,32) respuestas correctas (p

Low doses of sulpiride have been used off-label to treat menopausal hot slashes in Southern Brazil despite limited scientific evidence. This randomized controlled trial aimed at assessing the effects of sulpiride as compared to placebo on the frequency and severity of hot flashes. Postmenopausal women, aged 47-62, were recruited from the Menopause Clinic at Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil, between March 2016 and January 2017. After a baseline assessment of 4 weeks, women were included if they had at least a mean of five moderate to severe hot flashes per day and then randomized to receive for 8 weeks either placebo (

Background Diabetes mellitus is the main cause of chronic kidney disease (CKD) in humans. The relationship between the 2 diseases in cats is unclear. Objective To assess the association between diabetes and CKD in a population of adult cats. Animals Five hundred sixty‐one cats that attended 2 veterinary centers in Gran Canaria, Spain, between 2014 and 2016. Methods Medical records were retrospectively reviewed. Cats aged 3 years or older, with sufficient data to define whether or not they had diabetes and CKD, were selected. Cats in critical condition, with dehydration or potential causes of prerenal azotemia and those treated with nephrotoxic drugs were excluded. Diagnosis of CKD was established when creatinine concentrations were >2 mg/dL, or serum creatinine 1.6‐2 mg/dL and urine specific gravity 0.4. Factors associated with CKD were identified through multivariate logistic regression analyses. Results Sixty‐seven (11.9%) cats had CKD and 16 (2.9%) cats had diabetes. Sixty cats without diabetes (11%) and 7 with diabetes (44%) had CKD. Among the latter, both conditions were diagnosed simultaneously in 6 cases, whereas diabetes preceded CKD in the other. Multivariate analysis showed that diabetes was significantly associated with CKD (odds ratio = 4.47; 95% confidence interval, 1.51‐13.28; P = .007). Other variables associated with CKD were age and mixed breed. Conclusions and Clinical Importance After adjusting for age, this study showed an association between diabetes and CKD in adult cats.

Background We review 2 previously published cases of epidural lipomatosis associated with syringomyelia. We also present the case of a 42-year-old woman with a medullary syrinx from C1 to T3, initially only with upper limb paresthesias that presented after 10 years of follow-up for left hemiparesis and paresthesias in the tongue. Chiari malformation and cerebral or spinal space-occupying lesions were ruled out, as were other causes of syrinx except the presence of epidural lipomatosis extending from T1 to T12. Case Description Right laminotomies were performed from T1 to T12, removing excessive epidural fat tissue. After surgery the symptoms remained stable. At discharge the patient progressively recovered from the hemiparesis, and in follow-up magnetic resonance imaging the resolution of the syrinx was confirmed. Conclusions This is the third case of a patient with a spinal syrinx and no other related causes except from spinal lipomatosis, although with only 3 cases it is not possible to completely state that lipomatosis caused the syrinx. Our case supports the trend established by the 2 previous cases. For treatment, initially patients should be managed conservatively, trying to correct the underlying etiologies of spinal lipomatosis. In case of failed conservative treatment, removal of adipose epidural excess in the most appropriate way is preferred.

Our research team previously developed an accelerometry-based device, which can be worn on the waist during daily life activities and detects the occurrence of dyskinesia in patients with Parkinson’s disease. The goal of this study was to analyze the magnitude of correlation between the numeric output of the device algorithm and the results of the Unified Dyskinesia Rating Scale (UDysRS), administered by a physician. In this study, 13 Parkinson’s patients, who were symptomatic with dyskinesias, were monitored with the device at home, for an average period of 30 minutes, while performing normal daily life activities. Each patient’s activity was simultaneously video-recorded. A physician was in charge of reviewing the recorded videos and determining the severity of dyskinesia through the UDysRS for every patient. The sensor device yielded only one value for dyskinesia severity, which was calculated by averaging the recorded device readings. Correlation between the results of physician’s assessment and the sensor output was analyzed with the Spearman’s correlation coefficient. The correlation coefficient between the sensor output and UDysRS result was 0.70 (CI 95%: 0.33–0.88; p = 0.01). Since the sensor was located on the waist, the correlation between the sensor output and the results of the trunk and legs scale sub-items was calculated: 0.91 (CI 95% 0.76–0.97: p

Introduction: Much has been published on syringomyelia related to Chiari malformation. In contrast, little is known about the condition when it is not associated with this malformation, but this presentation of syringomyelia constitutes a different entity and therefore requires specific management. We conducted a literature review to summarise the most accepted and widespread ideas about the pathophysiology, management and other aspects of syringomyelia unrelated to Chiari malformation. Development: We reviewed the most relevant literature on this condition, focusing on the pathophysiology, clinical presentation, diagnosis, and treatment. Conclusions: Syringomyelia unrelated to Chiari malformation is a distinct entity that must be well understood to guarantee correct diagnosis, monitoring, and management. When the disease is suspected, a thorough study should be conducted to identify its aetiology. Treatment must aim to eliminate the cause of the disease; symptomatic treatment should remain a second-line option. Resumen: Introducción: Son muchos los conocimientos y publicaciones existentes sobre la siringomielia relacionada con la malformación de Chiari, pero existe poca difusión de este cuadro cuando no se presenta en relación con dicha malformación. Ello es importante ya que es una entidad propia que precisa de un conocimiento y manejo específico. Presentamos esta revisión con el objetivo de dar a conocer las ideas más aceptadas y difundidas a día de hoy al respecto de la fisiopatología, manejo y otros aspectos de la siringomielia no secundaria a malformación de Chiari. Desarrollo: Se ha realizado una revisión de la literatura más relevante en torno a esta patología, centrándose en su fisiopatología, presentación clínica, estudio diagnóstico y manejo. Conclusiones: La siringomielia no relacionada con malformación de Chiari es una entidad propia que precisa de un conocimiento adecuado en su profundidad para su sospecha, seguimiento y manejo adecuado. Ante el hallazgo de este cuadro debe realizarse un estudio detallado encaminado a intentar identificar la causa, quedando el tratamiento sintomático como opción de rescate. Keywords: Arachnolysis, Chiari malformation, CINE-MRI, Syringopleural shunting, Syringosubarachnoid shunting, Syringomyelia, Palabras clave: Aracnólisis, Chiari, Cine-RM, Derivación cistopleural, Derivación cisto-subaracnoidea, Siringomielia

The metabolic syndrome (METS) is an entity diagnosed by three or more of the following factors: abdominal obesity, low high-density lipoprotein cholesterol, and high serum triglycerides, fasting glucose, and/or blood pressure levels. Abdominal obesity is the most prevalent component of the syndrome that favors insulin resistance and a proinflammatory and prothrombotic status, and the risk of developing diabetes, hypertension, and other chronic conditions. During the menopausal transition, women tend to gain weight and this has been related to an increase in the prevalence of the METS. Rates have also been linked to hormonal status (perimenopausal vs. postmenopausal), changes in lifestyle, and endocrine adjustments. Abnormal cytokine secretion subsequently produces endothelial dysfunction, which will consequently increase cardiovascular risk and related morbidity and mortality. This document will review the various risks that arise as a consequence of the METS during female midlife.

The aims of this study were to determine the prevalence of severe mental illness (SMI) in patients in contact with mental health services and to determine the factors associated with SMI. A total of 260 patients who met diagnostic criteria for SMI were assessed using the Global Assessment of Functioning (GAF) scale and Health of the Nation Outcome Scales. The overall prevalence of SMI was 6.08 per thousand. According to the three different cutoff points with GAF, the prevalence of SMI ranged from 5.38 per thousand under the weak criterion (GAF < 70) to 1.01 per thousand under the strict criterion (GAF < 50). In the regression model, the dependent variable (presence of SMI) was defined using a GAF < 60, and the variables independently associated with the dependent variable were years of disease duration since diagnose, mental health service use, alcohol or other substance abuse, and depressive anxiety and other psychological symptoms.

The aim of the study was to validate the Portuguese language version of the 10-item Cervantes Scale (CS-10), a self-reporting instrument that assesses menopausal symptoms, and to compare the results (both symptom severity and multigroup invariance) of middle-aged women who completed the questionnaire in paper-and-pencil format (PPF) or in the online format (OF).A total of 292 women, aged 45 to 65 years, completed the questionnaires (PPF = 66; OF = 226). Construct (factorial and convergent) and external validity, as well as reliability and psychometric sensitivity were studied. Multigroup confirmatory factor analysis was performed to compare PPF with OF, regarding the measure's invariance.The CS-10 showed good psychometric properties (ie, factor and external validity), as well as good sensitivity and reliability. The association with the Utian Quality of Life Scale (UQoLS) was significant and positive, though weak. The measured structure was invariant when comparing both subsamples (PPF and OF), evidencing an equivalent structure in both. No differences in reported symptoms were observed between the two subgroups.The Portuguese language version of the CS-10 rendered data with good psychometric properties in a sample of middle-aged Portuguese women. Therefore, it can be used in both clinical and community settings. The weak association between both instruments (UQoLS and CS-10) might be due to the different conceptualization of the quality of life construct: the CS-10 focuses on symptom severity, whereas the UQoLS assesses domains such as work-related or health-related behaviors.

BackgroundGasdermin-B gene (GSDMB) is frequently over-expressed in tumors, and its shortest translated variant (isoform 2; GSDMB2) increases aggressive behavior in breast cancer cells. Paradoxically, GSDMB could have either pro-tumor or tumor suppressor properties depending on the biological context. Since GSDMB gene is not present in the mouse genome, deciphering fully the functional roles of GSDMB in cancer requires novel in vivo models.MethodsWe first generated by gene targeting a conditional knock-in mouse model (R26-STOP-GB2) harboring human GSDMB2 transcript within the ROSA26 locus. We next derived the R26-GB2 model ubiquitously expressing GSDMB2 in multiple tissues (confirmed by western blot and immunohistochemistry) and performed a comprehensive histopathological analysis in multiple tissues from 75 male and female mice up to 18 months of age. Additionally, we produced the double transgenic model R26-GB2/MMTV-PyMT, co-expressing GSDMB2 and the Polyoma-Middle-T oncogene, and assessed breast cancer generation and progression in GSDMB2-homozygous (n=10) and control (n=17) female mice up to 15 weeks of age.ResultsIn the R26-GB2 model, which showed different GSDMB2 cytoplasmic and/or nuclear localization among tissues, we investigated if GSDMB2 expression had intrinsic tumorigenic activity. 41% of mice developed spontaneous lung tumors, but neither the frequency nor the histology of these neoplasias was significantly different from wildtype animals. Strikingly, while 17% control mice developed gastric carcinomas, no GSDMB2-positive mice did. No other tumor types or additional histological alterations were frequently seen in these mice. In the R26-GB2/MMTV-PyMT model, the strong nucleus-cytoplasmic GSDMB2 expression in breast cancer cells did not significantly affect cancer formation (number of tumors, latency, tumor weight, histology or proliferation) or lung metastasis potential compared to controls.ConclusionsGSDMB2 expression alone does not have an overall tumorigenic potential in mice, but it might reduce gastric carcinogenesis. Contrary to human cancers, GSDMB2 upregulation does not significantly affect breast cancer generation and progression in mouse models. However, to evidence the GSDMB functions in cancer and other pathologies in vivo may require the presence of specific stimulus or cellular contexts. Our novel mouse strains will serve as the basis for the future development of more precise tissue-specific and context-dependent cancer models.

It is estimated that 50% of women will suffer a severe form of vulvovaginal atrophy (VVA) related to menopause. Equally, young women may temporarily present this clinical problem while receiving various pharmacological or endocrine treatments or radiotherapy.To determine clinical and diagnostic exams required to confirm the presence of VVA (also referred to as atrophic vaginitis, urogenital atrophy, or genitourinary syndrome of menopause) and rule out other genital or pelvic clinical conditions.Literature review searches were carried out on the main scientific article search engines (PubMed, SciELO, Cochrane) using different clinical terms, treatments or interventions and comorbidity related to VVA.The development and severity of VVA depend mainly on the duration of hypoestrogenism. Hypoestrogenism causes changes in the urogenital tissue, generating signs and symptoms, such as dryness, burning, soreness, itching, and irritation of the genital skin. The diagnosis can be made through anamnesis (patient history), questionnaires, physical exam, and, sometimes, complementary exams. Objective vaginal assessment is essential and can be completed with the Vaginal Health Index, the Vaginal Maturation Index, or vaginal pH in the absence of infection or semen. The exclusion of other vulvovaginal organic pathology is essential to reach an accurate diagnosis and provide adequate treatment.The specialist should be able to identify VVA, rule out other pathologies that make a differential diagnosis and conduct proper management.

Chordoma is a rare, slow-growing malignant bone tumor originating from the remains of the notochord and predominantly affecting the axial skeleton (especially the sacrum and occipital region). Clival chordomas represent 1-4% of intracranial neoplasms and only 0.2% of central nervous system tumors, so their prevalence is very low (1 case per 2 million inhabitants). The mean age of onset is in the 4th decade of life and its usual symptoms are diplopia due to involvement of the ocular pairs, dysphagia and headache (1,2). More rarely, it affects phonetics in isolation due to the involvement of the lower cranial nerves (hypoglossal or glossopharyngeal) (3-5).