Do NPM1 and FLT3-ITD mutations modify prognosis in patients treated with non-intensive regimens?

FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.

A metabolic readout of the urine metabolome of COVID-19 patients.

Analysis of urine samples from COVID-19 patients by 1H NMR reveals important metabolic alterations due to SAR-CoV-2 infection. Previous studies have identified biomarkers in urine that reflect metabolic alterations in COVID-19 patients. We have used 1H NMR to better define these metabolic alterations since this technique allows us to obtain a broad profile of the metabolites present in urine. This technique offers the advantage that sample preparation is very simple and gives us very complete information on the metabolites present. To detect these alterations, we have compared urine samples from COVID-19 patients (n = 35) with healthy people (n = 18). We used unsupervised (Robust PCA) and supervised (PLS-LDA) multivariate analysis methods to evaluate the differences between the two groups: COVID-19 and healthy controls. The differences focus on a group of metabolites related to energy metabolism (glucose, ketone bodies, glycine, creatinine, and citrate) and other processes related to bacterial flora (TMAO and formic acid) and detoxification (hippuric acid). The alterations in the urinary metabolome shown in this work indicate that SARS-CoV-2 causes a metabolic change from a normal situation of glucose consumption towards a gluconeogenic situation and possible insulin resistance.

Asymptotic Self-Similar Blow-Up Profile for Three-Dimensional Axisymmetric Euler Equations Using Neural Networks.

Whether there exist finite-time blow-up solutions for the 2D Boussinesq and the 3D Euler equations are of fundamental importance to the field of fluid mechanics. We develop a new numerical framework, employing physics-informed neural networks, that discover, for the first time, a smooth self-similar blow-up profile for both equations. The solution itself could form the basis of a future computer-assisted proof of blow-up for both equations. In addition, we demonstrate physics-informed neural networks could be successfully applied to find unstable self-similar solutions to fluid equations by constructing the first example of an unstable self-similar solution to the Córdoba-Córdoba-Fontelos equation. We show that our numerical framework is both robust and adaptable to various other equations.

Diagnosis and treatment of primary thyroid lymphoma from a surgical perspective: a multi-institutional study.

PURPOSE: Surgery of primary thyroid lymphoma (PTL) has been mostly limited to diagnostic work-up. This study aimed to further study its potential role. METHODS: This was a retrospective study from a multi-institutional registry of PTL patients. Clinical, diagnostic work-up (fine needle aspiration, FNA; core needle biopsy, CoreNB), contribution of surgery (open surgical biopsy, OpenSB; thyroidectomy), histology subtype, and outcome data were evaluated. RESULTS: Some 54 patients were studied. Diagnostic work-up included FNA in 47 patients, CoreNB in 11, and OpenSB in 21. CoreNB yielded the best sensitivity (90.9%). Thyroidectomy was performed in 14 patients with other diagnosis (incidental PTL), in 4 for diagnosis and in 4 for elective treatment of PTL. Incidental PTL was associated with not performed FNA nor CoreNB (OR 52.5; P = 0.008), mucosa-associated lymphoid tissue (MALT) subtype (OR 24.3; P = 0.012), and Hashimoto's thyroiditis (OR 11.1; P = 0.032). Lymphoma-related death (10 cases) mostly occurred within the first year after diagnosis and was associated with diffuse large B-cell (DLBC) subtype (OR 10.3; P = 0.018) and older patients (OR 1.08 for every 1-year increase; P = 0.010). There was a trend towards lower mortality rate in patients receiving thyroidectomy (2/22 versus 8/32, P = 0.172). CONCLUSION: Incidental PTL accounts for most of thyroid surgery cases and are associated with incomplete diagnostic work-up, Hashimoto's thyroiditis and MALT subtype. CoreNB appears to be the best tool for diagnosis. Most of PTL deaths occurred during the first year after diagnosis and mostly related to systemic treatment. Age and DLBC subtype are poor prognostic factors.

Is There a Relationship Between the Functional Level of Juvenile and Adolescent Patients With Down Syndrome and Hip Dysplasia?

BACKGROUND: The prevalence of hip dysplasia among patients with Down syndrome (DS) is higher than in the general population. We hypothesize that a relationship may exist between functional level and hip dysplasia in DS, but this has not been studied to date. The aim of this study is to evaluate whether there is a relationship between functional level and radiographic parameters of hip dysplasia or other measures. METHODS: Retrospective cross-sectional comparative study of 652 patients with DS from a pediatric referral center database. Patients over 8 years of age with an anteroposterior pelvis radiograph and with no exclusion criteria were selected, totaling 132 patients (264 hips; 54.55% females; mean age 12.96 ± 2.87 y). Several radiographic parameters of the acetabulum [Sharp angle (SA), Tönnis angle (TA), Wiberg center-edge angle (W-CEA), extrusion index (EI), and acetabular retroversion signs], the proximal femur [neck shaft angle (NSA)], and joint congruence [Shenton line (SL)] were assessed. Patients were classified into 2 levels based on functional skills. A multivariate association analysis was performed between radiographic parameters and functional level. RESULTS: Sixty-one patients were compatible with a functional level I and 71 with a level II. Forty-six hips were dysplastic and 60 were borderline according to the W-CEA. A statistically significant relationship was found between the categorical distribution of certain radiographic measurements of hip dysplasia (EI, SA, TA, W-CEA, SL, and classification by functional level ( P < 0.0005). A significant receiver operating characteristic curve was obtained for W-CEA with a cutt-off point at 26.4 degrees for level I (area under the curve = 0.763; P < 0.005; sensitivity = 0.800 and specificity = 0.644). There was a fairly high correlation between EI and TA (0.749; P < 0.0005), EI and W-CEA (-0.817; P < 0.0005), and TA and W-CEA (-0.748; P < 0.0005). Numerous hips showed signs of acetabular retroversion, with no significant differences found between functional levels or association with hip dysplasia measures. CONCLUSIONS: The present study reveals a relationship between an increased risk of hip dysplasia and reduced functional levels in DS children older than 8 years. These findings may guide individualized clinical follow-up of hip development in DS children considering their functional level. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Long-term Impact of Planovalgus Foot on Activities of Daily Living in Patients With Down Syndrome.

INTRODUCTION: Planovalgus foot (PVF) is the most common orthopaedic abnormality in children with Down syndrome (DS), and as a result these patients rarely develop an adequate plantar arch in adulthood. The present study aims to evaluate the impact of PVF on activities of daily living and participation in sports among young adults with DS and determine whether this impact is related to the degree of foot deformity based on clinical and imaging studies. METHODS: Observational analytical study examining a database of 649 patients with DS from a pediatric referral center, identifying those individuals over age 20 years at the time of the study with a childhood diagnosis of PVF. Finally, 51 patients (102 feet) were evaluated based on clinical and imaging studies, and function was assessed using the The Foot and Ankle Outcome Score (FAOS) and the Visual Analogue Scale (VAS) pain scale. A correlation analysis was performed to determine the clinical and radiographic variables associated with functional outcomes. Linear regression models were obtained to quantify the impact of these variables on function. RESULTS: Patients had a mean age of 26.14±3.88 years and body mass index of 24.51±4.57. Clinically, 63.65% presented grade 3 or 4 PVF, and most were flexible. Radiographically, midfoot flattening was mild-moderate in 92.16%, 58.82% had medial talo-navicular uncoverage, and 30.39% had an increased hallux valgus (HV) angle. Mean scores for all FAOS subscales were between 65 and 71% and the mean VAS score was 1.45±1.96. An association analysis revealed a tendency toward lower scores on all FAOS subscales and greater pain according to the VAS scale in more severe PVF and in cases of moderate HV with asymmetry between feet. Linear regression models showed that major contributors to functional scores were radiographic evidence of hindfoot valgus, midfoot abduction, and flattening, and HV. CONCLUSIONS: Young adults with DS who are diagnosed with PVF in childhood have acceptable functional scores and low pain. Alteration of radiographic parameters toward flatter, more valgus and abducted feet and greater and asymmetric HV tend to be associated with worse long-term functional scores in activities of daily living and sports participation and increased pain. Therefore, non-operative management of these patients is justified, although individualized treatment is recommended. LEVEL OF EVIDENCE: Level IV, Case series.

Towards personalized dementia care through meaningful activities supported by technology: A multisite qualitative study with care professionals.

BACKGROUND: Person-centred care is widely recognised as important for helping people with dementia maintain a sense of self and purpose in life - especially for those living in care facilities. Despite this, most care practices still adopt a medical approach in which physical needs are prioritized over psychosocial well-being. Addressing the need to find ways of promoting person-centred approaches in care, this study explored care professionals' reflections on a novel, technological intervention (SENSE-GARDEN) that combines multisensory stimuli and digital media to create personalized environments for people with dementia. The aim of this study was to explore the experiences of care professionals who had used SENSE-GARDEN for approximately 1 year. METHODS: Three care homes in Norway, Belgium, and Portugal and 1 hospital in Romania used the SENSE-GARDEN with residents/patients with moderate to severe dementia over the course of 1 year. Qualitative data - including observations and interviews with 2 care professionals - were collected at the beginning of the study period from the Norwegian care home to explore initial impressions of the new SENSE-GARDEN room. At the end of the study period, 8 care professionals across the 4 facilities were interviewed for an in-depth exploration of their experiences. The two sets of data were analysed separately through reflexive thematic analysis. RESULTS: At the beginning of the study period, the staffs' focus was mainly on the novelty of the new SENSE-GARDEN room and how it provided opportunities for meaningful experiences. Post-intervention, the care professionals provided reflective accounts on how care could be delivered in alternative ways to standard practice. The themes generated from the post-intervention interviews were: "shifting focus onto personalized care", "building and fostering relationships", and "continuous discoveries". Through delivering person-centred care, the professionals reported a sense of purpose and achievement in their work. CONCLUSIONS: Professionals from care facilities across 4 different countries highlighted the value of interventions such as SENSE-GARDEN as a way of creating opportunities to better know people with dementia. Thus, they experienced improved relationships and greater job satisfaction. However, delivering person-centred interventions is time-consuming, and future research should evaluate the feasibility of sustaining them on a long-term basis.

Using Unsupervised Machine Learning to Identify Age- and Sex-Independent Severity Subgroups Among Patients with COVID-19: Observational Longitudinal Study.

BACKGROUND: Early detection and intervention are the key factors for improving outcomes in patients with COVID-19. OBJECTIVE: The objective of this observational longitudinal study was to identify nonoverlapping severity subgroups (ie, clusters) among patients with COVID-19, based exclusively on clinical data and standard laboratory tests obtained during patient assessment in the emergency department. METHODS: We applied unsupervised machine learning to a data set of 853 patients with COVID-19 from the HM group of hospitals (HM Hospitales) in Madrid, Spain. Age and sex were not considered while building the clusters, as these variables could introduce biases in machine learning algorithms and raise ethical implications or enable discrimination in triage protocols. RESULTS: From 850 clinical and laboratory variables, four tests-the serum levels of aspartate transaminase (AST), lactate dehydrogenase (LDH), C-reactive protein (CRP), and the number of neutrophils-were enough to segregate the entire patient pool into three separate clusters. Further, the percentage of monocytes and lymphocytes and the levels of alanine transaminase (ALT) distinguished cluster 3 patients from the other two clusters. The highest proportion of deceased patients; the highest levels of AST, ALT, LDH, and CRP; the highest number of neutrophils; and the lowest percentages of monocytes and lymphocytes characterized cluster 1. Cluster 2 included a lower proportion of deceased patients and intermediate levels of the previous laboratory tests. The lowest proportion of deceased patients; the lowest levels of AST, ALT, LDH, and CRP; the lowest number of neutrophils; and the highest percentages of monocytes and lymphocytes characterized cluster 3. CONCLUSIONS: A few standard laboratory tests, deemed available in all emergency departments, have shown good discriminative power for the characterization of severity subgroups among patients with COVID-19.

Application of propolis extract, nanovitamin C and nanovitamin E to prevent alveolar osteitis after impacted lower third molar surgery. A randomized, double-blind, split-mouth, pilot study.

BACKGROUND: Propolis has anti-inflammatory, analgesic and healing properties. The purpose of this study was to determine whether a gel containing 2% of propolis extract, 0.2% of ascorbic acid and 0.2% of tocopherol acetate is effective in preventing surgical complications related to impacted lower third molar extractions. MATERIAL AND METHODS: A randomized, double-blind, split-mouth study was performed. Fifteen patients were recruited who needed bilateral impacted lower third molar extractions with a similar surgical difficulty. A test or placebo gel was administered randomly inside post-extraction sockets. Each patient was instructed to apply the gel 3 times/day in the surgical wound for a week. After a month, the contralateral third molar was extracted, and the opposite gel applied. The following parameters were diagnosed/evaluated and then recorded: alveolar osteitis following Blum's criteria, swelling and trismus at day one, two, three and seven post-intervention, wound healing at day 7 post-intervention, and postoperative pain using a visual analog scale, as well as, the number of analgesic pill intake. RESULTS: A total of twenty-six surgical procedures were performed in 13 patients (mean age 20.67±2 years). Alveolar osteitis was reported in 3 patients from the placebo group (23.1%) and none in the test group (0%) (p=0.25). No statistically significant differences were reported in swelling, trismus, wound healing or analgesic pill consumption between two groups. But statistically lower postoperative pain during the 7 days after surgical extractions was found according to visual analog scale in test group compared to the placebo group (p=0.007). No side effects were reported. CONCLUSIONS: The application of this gel may be effective in preventing alveolitis and thus reducing postoperative pain after impacted third molar extractions. More randomized clinical trials with larger sample are needed to confirm these results.

COVID-19 impact on nurses in Spain: a considered opinion survey.

AIM: To survey nurses' opinions about their work conditions at the onset of the COVID-19 pandemic in Spain. BACKGROUND: For the Spanish General Council of Nursing (the Consejo General de Enfermería de España), it was essential to have information on nursing workforce conditions and nurses' preparedness to wear protective measures at the pandemic's onset. The coronavirus outbreak was believed to have started in China and rapidly spread as a global pandemic requiring policies and actions for planning emergency healthcare delivery. METHODS: A cross-sectional survey was conducted online. Data were collected during April 2020 and covered social demography, working conditions, training, availability of personal protective equipment, and nurses' health conditions, including the impact of COVID-19. FINDINGS: From all national territories in Spain, 11 560 registered nurses from different services completed the questionnaire. Findings indicated that the lack of personal protective equipment was a crucial issue, as well as service planning and organization, and 80.2% reported high or very high psychological impact of COVID-19. Alarmingly, 29.5% of the nurses reported COVID-19 symptoms. Of these 23.3% had been tested, and 30.2% were confirmed as being positive to the virus. The nurses deemed proper preparedness for emergencies and disasters as a significant concern. CONCLUSION: Nurses' responses showed evidence of health services deficiencies as a source of damage to their capacity to provide safe patient care and protect themselves and their families' health. The working conditions of the nurses are at critical levels and are unacceptable. The study results provide evidence regarding the necessity of suitable planning and actions being taken to enable safe patient care and safety for nurses. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Our survey gathered nurses' views at the pandemic's onset. The evidence gathered is being used to advise policymakers and nursing organizations to take actions to control public health risks to populations. It is necessary that more investment in growing nursing workforce expertise and health infrastructure for pandemic and epidemic emergencies is provided.

Risk factors related to oral candidiasis in patients with primary Sjögren's syndrome.

BACKGROUND: Candidiasis is the most frequent mycotic infection of the oral cavity. The aim of this study was to investigate the presence of clinical oral candidiasis and Candida albicans yeast in a population diagnosed of primary Sjögren's syndrome (pSS) and to study the possible factors associated with this infection. MATERIAL AND METHODS: An observational cross-sectional study was conducted in 61 pSS patients (60 women, 1 man, mean age 57.64±13.52) where patient based information (demographic and medical, tobacco and alcohol consumption history), intraoral parameters (presence of dentures, clinical signs of candidiasis), salivary analytical information (number of Candida albicans as colony-forming units per millilitre (CFU/mL), salivary pH levels, unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) were collected. RESULTS: 13.1% of pSS patients presented oral signs of candidiasis. Denture stomatitis and angular cheilitis were the most common lesions. 87.5% of patients with clinical candidiasis presented reduced pH levels and salivary flow in both UWS and SWS. A significant statistical negative correlation was found between CFU/mL of Candida albicans and levels of UWS and SWS. A negative correlation was found between pH levels and CFU/mL, although not statistically significant. CONCLUSIONS: A reduced salivary flow may predispose pSS patients to Candida albicans overgrowth, which may show with clinical signs. Preventive measures are of great importance to avoid and to treat this condition promptly.

Oral lesions in patients with primary Sjögren's syndrome. A case-control cross-sectional study.

BACKGROUND: To evaluate the presence of oral lesions in a group of patients with primary Sjögren's syndrome (pSS) and compare these results with a matched control group (CG). MATERIAL AND METHODS: An observational cross-sectional study was conducted. 61 pSS patients (60 women, 1 man, mean age 57.64±13.52) diagnosed according to the American European Criteria (2002), and 122 matched control patients (120 women, 2 men, mean age 60.02±13.13) were included. Demographic and medical data, oral lesions and salivary flow rate were collected. RESULTS: Compared with the controls, pSS patients were 3.95 more likely to have oral lesions (OR 3.95; 95% CI 2.06-7.58; p=0.0001). 57.4% pSS patients presented oral lesions compared to 25.4% in CG. The most common were candidiasis (13.1% vs 2.5%), traumatic lesions (13.1% vs 4.1%), apthae (8.2% vs 0), and fissuration of the tongue (8.2% vs 0.8%). pSS patients with oral lesions had lower salivary flow levels (stimulated and unstimulated), although these differences were not significant. Significant associations were found between the presence of oral lesions and systemic manifestations and history of parotid gland enlargement in pSS patients. CONCLUSION: pSS patients suffer more oral lesions than general population and these lesions may aggravate the pSS disease.

Efficacy of a topical gel containing chitosan, chlorhexidine, allantoin and dexpanthenol for pain and inflammation control after third molar surgery: A randomized and placebo-controlled clinical trial.

BACKGROUND: The aim of this study was to evaluate and compare the postoperative effect of a topic gel containing chlorhexidine, chitosan, allantoine and dexpanthenol versus a placebo for pain and inflammation control after third molar surgery. MATERIAL AND METHODS: A gel combining 0.2% chlorhexdine, 0.5% chitosan, 5% dexpanthenol, 0.15% allantoin and 0.01% sodium saccharin was selected for this split mouth randomized controlled and double-blind trial including 36 patients with bilaterally and symmetrically impacted lower third molars. The teeth (n=72) were randomly divided into two groups before surgical removal: control group (CG; in which a placebo was given) and experimental group (EG). Swelling, trismus, postoperative pain, wound healing and complications were measured and recorded in order to evaluate differences between the placebo and experimental product. RESULTS: Five patients suffered from an alveolitis in the CG (13.9%), and none in the study group (0%), but no statistically significant difference was found (p=0.063). From day 0 to day 7, trismus and swelling were significantly less pronounced in the EG, and wound healing was considered 'good' in 22.2% for the CG and 97.2% for the EG (p<0.001). Mean VAS scores during the seven postoperative days were statistically lower in the study (2.56±1,19) compared to the placebo group (3.25±1.6) (p=0.002). The mean consumption of analgesic pills during the first 92 hours was also statistically lower in the EG (0.26±0.51) in comparison to the CG (0.56±0.67) (p=0.003). CONCLUSIONS: The use of an experimental gel containing chlorhexidine, chitosan, allantoine and dexpanthenol seems to significantly reduce postoperative pain, trismus and signs of inflammation. Future studies should further evaluate, if the gel is effective in dry socket preventing after third molar removal.

Using velocity-pressure loops in the operating room: a new approach of arterial mechanics for cardiac afterload monitoring under general anesthesia.

Cardiac afterload is usually assessed in the ascending aorta and can be defined by the association of peripheral vascular resistance (PVR), total arterial compliance (Ctot), and aortic wave reflection (WR). We recently proposed the global afterload angle (GALA) and ß-angle derived from the aortic velocity-pressure (VP) loop as continuous cardiac afterload monitoring in the descending thoracic aorta. The aim of this study was to 1) describe the arterial mechanic properties by studying the velocity-pressure relations according to cardiovascular risk (low-risk and high-risk patients) in the ascending and descending thoracic aorta and 2) analyze the association between the VP loop (GALA and ß-angle) and cardiac afterload parameters (PVR, Ctot, and WR). PVR, Ctot, WR, and VP loop parameters were measured in the ascending and descending thoracic aorta in 50 anesthetized patients. At each aortic level, the mean arterial pressure (MAP), cardiac output (CO), and PVR were similar between low-risk and high-risk patients. In contrast, Ctot, WR, GALA, and ß-angle were strongly influenced by cardiovascular risk factors regardless of the site of measurement along the aorta. The GALA angle was inversely related to aortic compliance, and the ß-angle reflected the magnitude of wave reflection in both the ascending and descending aortas (P < 0.001). Under general anesthesia, the VP loop can provide new visual insights into arterial mechanical properties compared with the traditional MAP and CO for the assessment of cardiac afterload. Further studies are necessary to demonstrate the clinical utility of the VP loop in the operating room.NEW & NOTEWORTHY Our team recently proposed the global afterload angle (GALA) and ß-angle derived from the aortic velocity-pressure (VP) loop as continuous cardiac afterload monitoring in the descending thoracic aorta under general anesthesia. However, the evaluation of cardiac afterload at this location is unusual. The present study shows that VP loop parameters can describe the components of cardiac afterload both in the ascending and descending thoracic aorta in the operating room. Aging and cardiovascular risk factors strongly influence VP loop parameters. The VP loop could provide continuous visual additional information on the arterial system than the traditional mean arterial pressure and cardiac output during the general anesthesia.

The immune response to Hymenolepis nana in mice decreases tumorigenesis induced by 7,12 dimethylbenz-anthracene.

BACKGROUND: Cancer is a high-impact disease throughout the world. A negative correlation has been established between the development of cancer and the Th2 immune response. Infection by helminth parasites is characterized by the induction of a strong and long-lasting Th2 response. The aim of this work was to evaluate the effect of the immune response induced by the infection with the helminth Hymenolepis nana, on the tumorigenesis induced by dimethylbenz-anthracene (DMBA) in mice. METHODOLOGY: Four different groups of 14 female BALB/c mice were formed; Group A, dimethyl sulfoxide (DMSO) (vehicle) was administered cutaneously, Group B infected with H. nana, group C, cutaneously DMBA and finally Group D infected with H. nana and cutaneous DMBA. The tumor load was determined in those animals that developed cancerous lesions. In all groups were determined: serum concentration of IgE, IFNγ, IL-10, IL-5 and malondialdehyde (MDA). The inflammatory infiltrate was analyzed from skin samples and the expression of the main eosinophilic protein and myeloperoxidase was determined. RESULTS: The group previously infected with H. nana had a reduced amount of tumors with smaller size, in comparison to the group that received only DMBA; this reduction was associated with lower levels of IFNγ and IL-10, while levels of IgE, IL-5 and MDA were higher. Further, the number of eosinophils and neutrophils was statistically higher in the animals that were previously infected with the helminth and developed less tumors. CONCLUSION: The immune response induced by H. nana infection is associated with the reduction of tumors probably due to the activity of eosinophils and neutrophils.

Synthesis and in vitro activity of new biguanide-containing dendrimers on pathogenic isolates of Acanthamoeba polyphaga and Acanthamoeba griffini.

The genus Acanthamoeba can cause Acanthamoeba keratitis (AK) and granulomatous amoebic encephalitis (GAE). The treatment of these illnesses is hampered by the existence of a resistance stage that many times causes infection relapses. In an attempt to add new agents to our chemotherapeutic arsenal against acanthamebiasis, two Acanthamoeba isolates were treated in vitro with newly synthesized biguanide dendrimers. Trophozoite viability analysis and ultrastructural studies showed that dendrimers prevent encystment by lysing the cellular membrane of the amoeba. Moreover, one of the dendrimers showed low toxicity when tested on mammalian cell cultures, which suggest that it might be eventually used as an amoebicidal drug or as a disinfection compound in contact lens solutions.

Tremor severity in Parkinson's disease and cortical changes of areas controlling movement sequencing: A preliminary study.

There remains much to learn about the changes in cortical anatomy that are associated with tremor severity in Parkinson's disease (PD). For this reason, we used a combination of structural neuroimaging to measure cortical thickness and neurophysiological studies to analyze whether PD tremor was associated with cortex integrity. Magnetic resonance imaging and neurophysiological assessment were performed in 13 nondemented PD patients (9 women, 69.2%) with a clearly tremor-dominant phenotype. Cortical reconstruction and volumetric segmentation were performed with the Freesurfer image analysis software. Assessment of tremor was performed by means of high-density surface electromyography (hdEMG) and inertial measurement units (IMUs). Individual motor unit discharge patterns were identified from surface hdEMG and tremor metrics quantifying motor unit synchronization from IMUs. Increased motor unit synchronization (i.e., more severe tremor) was associated with cortical changes (i.e., atrophy) in wide-spread cortical areas, including caudal middle frontal regions bilaterally (dorsal premotor cortices), left inferior parietal lobe (posterior parietal cortex), left lateral orbitofrontal cortex, cingulate cortex bilaterally, left posterior and transverse temporal cortex, and left occipital lobe, as well as reduced left middle temporal volume. Given that the majority of these areas are involved in controlling movement sequencing, our results support Albert's classic hypothesis that PD tremor may be the result of an involuntary activation of a program of motor behavior used in the genesis of rapid voluntary alternating movements.

Reduction of respiratory infections in asthma patients supplemented with vitamin D is related to increased serum IL-10 and IFNγ levels and cathelicidin expression.

BACKGROUND: Vitamin D is a molecule that modulates the immune response and shows anti-inflammatory effects that are beneficial for the control of chronic diseases such as asthma. The trial aim was to explore the effect of vitamin D supplementation on the colonization of pathogenic bacteria in the upper respiratory tract of allergic asthmatic patients. METHODS: This study was conducted in 86 patients between 18 and 50 years of age who were randomly divided into two groups. Both groups received the treatment recommended by the Global Initiative for Asthma (GINA). One group also received calcitriol (1,25-(OH)2D3), and the other group received a placebo. At baseline and 6 months, skin prick tests were conducted, pharyngeal bacterial cultures were performed, and cathelicidin LL-37 was measured in sputum. Serum levels of IgE, eosinophils, IL-5, IL-9, IL-10, IL-13, and IFNγ were quantified at the beginning and the end of the study. RESULTS: Serum levels of IL-10 and IFNγ increased significantly in the group of patients with vitamin D supplementation, while IL-5, IL-9, and IL-13 decreased significantly. At the end of the trial, IgE and eosinophil levels significantly decreased but allergen sensitivity did not show any changes from baseline. Respiratory infections were drastically reduced, and this decrease was related to the number of patients who had high serum levels of IL-10 and IFNγ and expressed LL-37 in their sputum. CONCLUSION: Treatment of asthma patients with vitamin D reduced respiratory infections, and this effect was related to the increase of cathelicidin LL-37.

Maternal mortality in Spain and its association with country of origin: cross-sectional study during the period 1999-2015.

BACKGROUND: The available literature suggests that there are significant differences in maternal mortality according to maternal origin in high income countries. The objective of this study was to quantify the risk of maternal death by maternal origin and region of Spain where the birth occurred and to identify the most important causes of maternal death in our country. METHODS: An ecological cross-sectional study was conducted that included all deliveries that resulted in maternal survival and cases of maternal death during 1999-2015 in Spain. A descriptive analysis of the maternal mortality rate by maternal origin, region and year of birth was performed. The risk of maternal death was calculated using univariate and multivariate logistic regression analysis, with adjustment for the variables included in the descriptive analysis. RESULTS: There were 272 maternal deaths during this period, most of which were due to haemorrhage (63 cases, 23.16%).Women whose continent of origin was South America had the highest adjusted risk of maternal death, with an OR of 3.92 (95% CI 2.75-5.58). The region of Spain with the highest risk of maternal death was Ceuta, with an OR of 12.11 (95% CI 2.02-72.68). CONCLUSIONS: This study shows that there are inequalities in maternal mortality according to maternal origin and region where labour occurred. These findings highlight the need to establish strategies at the national and European levels to analyse the most relevant causes and risk factors associated with maternal mortality in order to reduce it and pay closer attention in identifying and carefully managing pregnant women from this at risk groups.

Cognitive performance of people with traumatic spinal cord injury: a cross-sectional study comparing people with subacute and chronic injuries.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To assess the impact of spinal cord injury (SCI) on cognitive function in individuals with subacute and chronic SCI. SETTING: National Hospital for SCI patients (Spain). METHODS: The present investigation was designed to determine the nature, pattern, and extent of cognitive deficits in a group of participants with subacute (n = 32) and chronic (n = 34) SCI, using a comprehensive battery of reliable and validated neuropsychological assessments to study a broad range of cognitive functions. Twenty-seven able-bodied subjects matched to the groups with SCI for age and educational level formed the control group. RESULTS: The neuropsychological assessment showed alterations in the domain of attention, processing speed, memory and learning, executive functions, and in recognition in participants with SCI. The prevalence of cognitive dysfunction in the chronic stage was also confirmed at the individual level. The comparison of the neuropsychological assessment between the groups with subacute and chronic SCI showed a worsening of cognitive functions in those with chronic SCI compared to the group with subacute SCI. CONCLUSIONS: In participants with SCI, cognitive dysfunctions are present in the subacute stage and worsen over time. From a clinical point of view, we confirmed the presence of cognitive dysfunction that may interfere with the first stage of rehabilitation which is the most intense and important. Moreover, cognitive dysfunction may be important beyond the end of the first stage of rehabilitation as it can affect an individual's quality of life and possible integration to society.