Genetic Variant of DNAM-1 rs763361 C>T Is Associated with Ankylosing Spondylitis in a Mexican Population.

DNAM-1 (CD226) is an activating receptor expressed in CD8+ T cells, NK cells, and monocytes. It has been reported that two SNPs in the DNAM-1 gene, rs763361 C>T and rs727088 G>A, have been associated with different autoimmune diseases; however, the role of DNAM-1 in ankylosing spondylitis has been less studied. For this reason, we focused on the study of these two SNPs in association with ankylosing spondylitis. For this, 34 patients and 70 controls were analyzed using endpoint PCR with allele-specific primers. Our results suggest that rs763361 C>T is involved as a possible protective factor under the CT co-dominant model (OR = 0.34, 95% CI = 0.13-0.88, p = 0.022) and the CT + TT dominant model (OR = 0.39, 95% CI = 0.17-0.90, p = 0.025), while rs727088 G>A did not show an association with the disease in any of the inheritance models. When analyzing the relationships of the haplotypes, we found that the T + A haplotype (OR = 0.31, 95% CI = 0.13-0.73, p = 0.0083) is a protective factor for developing the disease. In conclusion, the CT and CT + TT variants of rs763361 C>T and the T + A haplotype were considered as protective factors for developing ankylosing spondylitis.

Reactive astrocytes promote proteostasis in Huntington's disease through the JAK2-STAT3 pathway.

Huntington's disease is a fatal neurodegenerative disease characterized by striatal neurodegeneration, aggregation of mutant Huntingtin and the presence of reactive astrocytes. Astrocytes are important partners for neurons and engage in a specific reactive response in Huntington's disease that involves morphological, molecular and functional changes. How reactive astrocytes contribute to Huntington's disease is still an open question, especially because their reactive state is poorly reproduced in experimental mouse models. Here, we show that the JAK2-STAT3 pathway, a central cascade controlling astrocyte reactive response, is activated in the putamen of Huntington's disease patients. Selective activation of this cascade in astrocytes through viral gene transfer reduces the number and size of mutant Huntingtin aggregates in neurons and improves neuronal defects in two complementary mouse models of Huntington's disease. It also reduces striatal atrophy and increases glutamate levels, two central clinical outcomes measured by non-invasive magnetic resonance imaging. Moreover, astrocyte-specific transcriptomic analysis shows that activation of the JAK2-STAT3 pathway in astrocytes coordinates a transcriptional program that increases their intrinsic proteolytic capacity, through the lysosomal and ubiquitin-proteasome degradation systems. This pathway also enhances their production and exosomal release of the co-chaperone DNAJB1, which contributes to mutant Huntingtin clearance in neurons. Together, our results show that the JAK2-STAT3 pathway controls a beneficial proteostasis response in reactive astrocytes in Huntington's disease, which involves bi-directional signalling with neurons to reduce mutant Huntingtin aggregation, eventually improving disease outcomes.

Systematic review and meta-analysis of diagnostic test accuracy in chronic wound's microbiology.

PURPOSE: This study aims to assess the diagnostic accuracy of non-culture-based methodologies for detecting microorganisms in chronic wounds. METHODS: We systematically reviewed studies that evaluated the diagnostic accuracy of alternative tests in chronic wound samples, excluding studies focused on animal samples or unrelated conditions. The search encompassed PubMed, CINAHL, Scopus and Web of Science databases, employing the QUADAS-2 tool for risk of bias assessment. Our search included the PubMed, CINAHL, Scopus and Web of Science databases, and we assessed the risk of bias using the QUADAS-2 tool. A meta-analysis was conducted on polymerase chain reaction (PCR) and colorimetric methods to determine sensitivity, specificity, diagnostic odds ratio, and summary receiver-operating characteristic (sROC) curves using a random-effects model. For methods not suitable for quantitative synthesis, a narrative synthesis was performed. RESULTS: Nineteen studies involving various types of chronic wounds were analysed, revealing diverse diagnostic methods including fluorescence, PCR, colorimetry, voltammetry, electronic nose, biosensors, enzymatic methods, staining and microscopy. Combining fluorescence with clinical signs and symptoms (CSS) versus culture showed significant accuracy. Colorimetry demonstrated low sensitivity but high specificity, with a diagnostic odds ratio of 6.3. PCR generally exhibited good accuracy, although significant heterogeneity was noted, even in subgroup analyses. CONCLUSIONS: This study identified a broad spectrum of diagnostic approaches, highlighting the superior diagnostic accuracy achieved when microbiological analysis is combined with clinical assessments. However, the heterogeneity and methodological variations across studies present challenges in meta-analysis. Future research should aim for standardized and homogeneous study designs to enhance the assessment of diagnostic accuracy for alternative methods.

Comparative Study of the Efficacy of EHO-85, a Hydrogel Containing Olive Tree (Olea europaea) Leaf Extract, in Skin Wound Healing.

Olive tree (Olea europaea) leaf extract (OELE) has important antioxidant and anti-inflammatory properties, supporting its use in human clinical practice. We recently designed an amorphous hydrogel called EHO-85 (EHO indicates olive leaf extract in Spanish) containing OELE for skin ulcer treatments. Yet, its effectiveness has not been previously compared with other products used in routine clinical practice. This is necessary to evaluate its potential translation to the human clinic. Thus, in this study, the effect of EHO-85 on healing was evaluated in comparison with treatments containing Indian/Asiatic pennywort (Centella asiatica), hyaluronic acid, or dexpanthenol in a rat model. The speed of wound closure and histological parameters after seven and 14 days were analyzed. All treatments accelerated wound closure, but there were differences between them. Dexpanthenol after seven days produced the highest epithelialization and the lowest inflammation and vascularization. EHO-85 also promoted epithelialization and reduced vascularization. After 14 days, wounds treated with EHO-85 showed less inflammation and higher levels of collagen in the extracellular matrix. This indicates a higher degree of maturity in the regenerated tissue. In conclusion, the effect of EHO-85 on healing was equal to or superior to that of other treatments routinely used in human clinical practice. Therefore, these results, together with previous data on the effects of this hydrogel on ulcer healing in humans, indicate that EHO-85 is a suitable, low-cost, and efficient therapeutic option for wound healing.

Deleted genes associated with obesity in Mexican patients diagnosed with nonalcoholic fatty liver disease.

AIM: Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic condition in which both lifestyle and genetic factors have a pathogenic role. The LEP gene encodes leptin, which regulates appetite, body weight, and several metabolic functions. Proopiomelanocortin (POMC), regulates food intake and energy balance. The aim of the study was to determine partial or complete deletions of genes associated with obesity in patients diagnosed with NAFLD. MATERIAL AND METHODS: Blood samples and DNA from 43 individuals diagnosed with NAFLD by ultrasonographic technique (Fibroscan) were obtained. The partial or complete deletions of genes were determined by MLPA (Multiplex Ligation-dependent Probe Amplification) using the SALSA probemix P220-B2 Obesity only on 43 individuals. Fifty blood samples from healthy individuals were included. RESULTS: Eleven out of 43 individuals analyzed by MLPA presented some deletion of the genes analyzed: six were female and five were male. The partial or complete deletion of the LEPR and POMC genes was observed in eight patients (18.6%), SIM1 in six patients (13.9%), GRIK2 and SH2B1 in two patients (4.7%), SEZGL2 in four patients (9.3%), and MCR4 in one patient (2.3%). CONCLUSION: Partial deletion was observed in LEPR, POMC, SIM1, GRIK2, SH2B1, SEZGL2, and MCR4 genes in 26% of the cases, and we suggest that these alterations probably has a potential relationship for the development of NAFLD.

Antifouling Diterpenoids from the Sponge Dendrilla antarctica.

Two nor-diterpenes, 9,11-dihydrogracilin A (1) and the previously unreported 9,11-dihydrogracillinone A (2), were isolated from the sponge Dendrilla antarctica. The sponge was collected by trawling at a depth of 49 m, from the research vessel Puerto Deseado, near the coast of Tierra del Fuego, farther north than the reported habitat for this species. Since these compounds were particularly abundant and the sponge was free from epibionts, both 1 and 2 were included in soluble-matrix paints and tested for antifouling activity in the ocean. The results obtained from these experiments clearly indicated a potent antifouling activity for both compounds against a variety of colonizing organisms, and established a probable role as natural antifoulants for these abundant secondary metabolites and other structurally related compounds previously isolated from Dendrilla spp.

Adaptation to noise in normal and impaired hearing.

Many aspects of hearing function are negatively affected by background noise. Listeners, however, have some ability to adapt to background noise. For instance, the detection of pure tones and the recognition of isolated words embedded in noise can improve gradually as tones and words are delayed a few hundred milliseconds in the noise. While some evidence suggests that adaptation to noise could be mediated by the medial olivocochlear reflex, adaptation can occur for people who do not have a functional reflex. Since adaptation can facilitate hearing in noise, and hearing in noise is often harder for hearing-impaired than for normal-hearing listeners, it is conceivable that adaptation is impaired with hearing loss. It remains unclear, however, if and to what extent this is the case, or whether impaired adaptation contributes to the greater difficulties experienced by hearing-impaired listeners understanding speech in noise. Here, we review adaptation to noise, the mechanisms potentially contributing to this adaptation, and factors that might reduce the ability to adapt to background noise, including cochlear hearing loss, cochlear synaptopathy, aging, and noise exposure. The review highlights few knowns and many unknowns about adaptation to noise, and thus paves the way for further research on this topic.

Adaptation to Noise in Human Speech Recognition Depends on Noise-Level Statistics and Fast Dynamic-Range Compression.

Human hearing adapts to background noise, as evidenced by the fact that listeners recognize more isolated words when words are presented later rather than earlier in noise. This adaptation likely occurs because the leading noise shifts ("adapts") the dynamic range of auditory neurons, which can improve the neural encoding of speech spectral and temporal cues. Because neural dynamic range adaptation depends on stimulus-level statistics, here we investigated the importance of "statistical" adaptation for improving speech recognition in noisy backgrounds. We compared the recognition of noised-masked words in the presence and in the absence of adapting noise precursors whose level was either constant or was changing every 50 ms according to different statistical distributions. Adaptation was measured for 28 listeners (9 men) and was quantified as the recognition improvement in the precursor relative to the no-precursor condition. Adaptation was largest for constant-level precursors and did not occur for highly fluctuating precursors, even when the two types of precursors had the same mean level and both activated the medial olivocochlear reflex. Instantaneous amplitude compression of the highly fluctuating precursor produced as much adaptation as the constant-level precursor did without compression. Together, results suggest that noise adaptation in speech recognition is probably mediated by neural dynamic range adaptation to the most frequent sound level. Further, they suggest that auditory peripheral compression per se, rather than the medial olivocochlear reflex, could facilitate noise adaptation by reducing the level fluctuations in the noise.SIGNIFICANCE STATEMENT Recognizing speech in noise is challenging but can be facilitated by noise adaptation. The neural mechanisms underlying this adaptation remain unclear. Here, we report some benefits of adaptation for word-in-noise recognition and show that (1) adaptation occurs for stationary but not for highly fluctuating precursors with equal mean level; (2) both stationary and highly fluctuating noises activate the medial olivocochlear reflex; and (3) adaptation occurs even for highly fluctuating precursors when the stimuli are passed through a fast amplitude compressor. These findings suggest that noise adaptation reflects neural dynamic range adaptation to the most frequent noise level and that auditory peripheral compression, rather than the medial olivocochlear reflex, could facilitate noise adaptation.

Efficiency of Machine Learning Algorithms for the Determination of Macrovesicular Steatosis in Frozen Sections Stained with Sudan to Evaluate the Quality of the Graft in Liver Transplantation.

Liver transplantation is the only curative treatment option in patients diagnosed with end-stage liver disease. The low availability of organs demands an accurate selection procedure based on histological analysis, in order to evaluate the allograft. This assessment, traditionally carried out by a pathologist, is not exempt from subjectivity. In this sense, new tools based on machine learning and artificial vision are continuously being developed for the analysis of medical images of different typologies. Accordingly, in this work, we develop a computer vision-based application for the fast and automatic objective quantification of macrovesicular steatosis in histopathological liver section slides stained with Sudan stain. For this purpose, digital microscopy images were used to obtain thousands of feature vectors based on the RGB and CIE L*a*b* pixel values. These vectors, under a supervised process, were labelled as fat vacuole or non-fat vacuole, and a set of classifiers based on different algorithms were trained, accordingly. The results obtained showed an overall high accuracy for all classifiers (>0.99) with a sensitivity between 0.844 and 1, together with a specificity >0.99. In relation to their speed when classifying images, KNN and Naïve Bayes were substantially faster than other classification algorithms. Sudan stain is a convenient technique for evaluating ME in pre-transplant liver biopsies, providing reliable contrast and facilitating fast and accurate quantification through the machine learning algorithms tested.

Prevalence and characteristics of older people with pressure ulcers and legs ulcers, in nursing homes in Barcelona.

BACKGROUND: Nursing home residents are vulnerable to chronic wounds. However, the prevalence data are scarce. AIM: The purpose of this study was to determine the prevalence of pressure ulcers and/or leg ulcers in nursing home residents, and describe the characteristics of the nursing homes, the residents and the wounds, as well as possible associations between these characteristics. METHODS: This was a cross-sectional survey of nursing home residents over the age of 65 in 168 facilities in Barcelona. Those presenting category II-IV pressure ulcers and/or leg ulcers were included. The data were collected by observation/examination. Descriptive, bivariate, and multivariate analyses were performed. RESULTS: The overall prevalence of pressure ulcers and leg ulcers combined was 4.4% (3.5% were pressure ulcers and 0.9% were leg ulcers). In small nursing homes with less nursing staff, the overall prevalence was greater than in large nursing homes (5.6% vs 3.8% [p = 0.01]). As expected, residents with pressure ulcers had higher pressure ulcer risk, worse dependence and cognitive status, urinary and faecal incontinence, and most were underweight. However, residents with leg ulcers had worse venous and arterial impairment and also were overweight. A multivariate analysis showed that pressure ulcers were statistically significantly associated with faecal incontinence (OR = 0.28, 95% CI = 0.09-0.81) and dyslipidaemia (OR = 0.21, 95% CI = 0.06-0.66), and leg ulcers were statistically significantly associated with venous insufficiency (OR = 4.93, 95% CI = 1.65-15.34). The characteristics of gluteal and ischial pressure ulcers, a high prevalence of infection, and a low reference to biofilm by nurses, in both types of wounds, suggest that these aspects are not adequately taken into account. CONCLUSIONS: Pressure ulcers and leg ulcers, mainly pressure ulcers, remain a public health problem in nursing homes. Further studies are required to confirm the associations found in this study.

Trends in mortality due to pressure ulcers in Spain, over the period 1999-2016.

AIM: to analyse trends in mortality by Pressure Ulcers (PU) in Spain, between 1999 and 2016. METHODS: Mortality due to PU in residents in Spain over 65, where a PU was underlying/basic cause of death, was analysed. Data for populations and deaths were gathered from the Spanish National Statistics Institute. Variables were age, sex, year of death and underlying/basic cause of death. Age-adjusted mortality rates were calculated (direct method), with 2013 European standard population. To analyse temporal trends and to detect significant changes, joinpoint regression models were adjusted to estimate average annual percentage change of Age-Adjusted mortality Rates for each segment detected. An analysis was performed for those over 65, and by the age groups 65-84, and over 84 years. RESULTS: A total of 11,238 deaths due to PU in people over 65, between 1999 and 2016, were analysed. There was a general decrease for both, women and men, over the period. From the Joinpoint analysis, for men, two changes were detected in those over 65, with a significant decrease observed until 2008. For those over 84, was a significant decrease of 4.4% on average per year. For women, a significant decrease is observed in all age groups, with a change of trend in 2007. CONCLUSION: This study provides a general overview of the epidemiology of PU mortality in Spain. It may serve as a confirmation of the good health policies carried out in the past on PU, given that we observe a generalised decrease in mortality from PUs over the period. Mortality was higher in women at the beginning of the period but without differences at the end, compared with men. Changes occurred over time could be explained by implementation of patient safety policies.

Matrix metalloproteinases 7, 8, 12, 13 gene haplotypes associated with colorectal cancer in a Mexican population.

BACKGROUND: Matrix metalloproteinases (MMPs) are involved in tumor invasion and progression in colorectal cancer (CRC). Variants rs11568818, rs11225395, rs2276109 and rs2252070 have been associated with this neoplasm. OBJECTIVE: To evaluate MMPs 7, 8, 12, and 13 haplotypes and their association with CRC. MATERIAL AND METHODS: One-hundred and four patients and 112 healthy individuals were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). For the association analysis, odds ratio and confidence interval values were calculated. Haplotype and linkage disequilibrium (LD) analysis was performed with Arlequin software, v3.5. RESULTS: LD was present between rs2276109 and rs2252070. Haplotypes rs11568818(A)-rs11225395(T)-rs2276109(A)-rs2252070(A) and rs11568818(A)-rs11225395(C)-rs2276109(A)-rs2252070(G) were associated with CRC risk, and haplotypes rs11568818(G)-rs11225395(C)-rs2276109(A)-rs2252070(A) and rs11568818(A)-rs11225395(T)-rs2276109(A)-rs2252070(G), with protection. CONCLUSION: Variants rs2276109 and rs2252070 showed genetic linkage. Two haplotypes were associated with the development of CRC (ATAA and ACAG) and two were associated with protection (GCAA and ATAG). This study represents the first report on variants rs11225395 and rs2276109 frequency in a Mexican population.

ANTECEDENTES: Las metaloproteinasas (MMP) se involucran en invasión y progresión tumoral en cáncer colorrectal (CCR). Las variantes rs11568818, rs11225395, rs2276109 y rs2252070 se han asociado con esta neoplasia. OBJETIVO: Evaluar haplotipos de las MMP 7, 8, 12, y 13 y su asociación con CCR. MATERIAL Y MÉTODOS: Se genotipificaron 104 pacientes y 112 individuos sanos mediante reacción en cadena de la polimerasa con análisis del polimorfismo de los fragmentos de restricción (PCR-RFLP). Para el análisis de asociación fueron calculados valores de odds ratio e intervalo de confianza. El análisis de haplotipos y desequilibrio de ligamiento (LD) se realizó con el software Arlequin v3.5. RESULTADOS: Se presentó LD entre rs2276109 y rs2252070. Los haplotipos rs11568818(A)-rs11225395(T)-rs2276109(A)-rs2252070(A) y rs11568818(A)-rs11225395(C)-rs2276109(A)-rs2252070(G) se asociaron con riesgo de CCR y los haplotipos rs11568818(G)-rs11225395(C)-rs2276109(A)-rs2252070(A) y rs11568818(A)-rs11225395(T)-rs2276109(A)-rs2252070(G) con protección. CONCLUSIÓN: Las variantes rs2276109 y rs2252070 mostraron ligamiento génico. Dos haplotipos fueron asociados con el desarrollo de CCR (ATAA y ACAG) y dos fueron asociados con protección (GCAA y ATAG). Este estudio representa el primer reporte de frecuencias de las variantes rs11225395 y rs2276109 en población mexicana.

Specialised wound care clinics in Spain: distribution and characteristics.

OBJECTIVE: To determine the number of specialised wound care units/clinics (SWCUs) in Spain, at present, and to describe their most important characteristics. METHOD: This was an observational study with a descriptive-analytical, cross-sectional, multicentre approach, where the studied population consisted of SWCUs in Spain. A specific data-collection questionnaire was designed using a modified Delphi method, consisting of four rounds, with the collaboration of 10 wound experts. The final questionnaire included 49 items distributed across four dimensions/areas with a content validity index (CVI-Total for pertinence=0.96 and CVI-Total for relevance=0.94. RESULTS: A total of 42 SWCUs were included in the study. Most SWCUs were based in hospitals (n=15, 35.7%) or healthcare centres, covering a specific healthcare area (n=17, 40.5%). SWCU coordinators were primarily nurses (n=33, 78.6%). Staff members' professions in SWCUs included registered nurses (n=38 units, 92.7%), nursing assistants (n=8 units, 19.5%), podiatrists (n=8 units, 19.5%), vascular surgeons (n=7 units, 17%), osteopaths (n=2 units, 4.8%) and medical doctors from different specialties (n=3 units, 7.2%). For wound aetiology, the most prevalent wounds managed were diabetic foot ulcers (n=38 units, 90.5%), followed by venous leg ulcers (n=36 units, 85.7%) and arterial ischaemic ulcers (n=36 units, 85.7%). A statistically significant association was found between the number of staff members in a SWCU and the existence of resistance/opposition barriers when developing a SWCU (Chi-square test, p=0.049; Cramér's V=0.34; 34%), as well as between resistance/opposition barriers when developing a SWCU and a nurse as coordinator of a SWCU (MacNemar test, p=0.007, Cramér's V=0.35; 35%). CONCLUSION: The typical SWCU implemented in Spain is located in a hospital or integrated in a healthcare structure that offers coverage to a whole health area and providing services for people with hard-to-heal wounds (wound management and prevention) and health professionals (advice, consultancy and training/education). Despite the growing number of SWCUs in Spain, the future of this new organisational model is uncertain, as there can be barriers to creating them and some deficiencies, such as low staff numbers, which need to be addressed.

Adaptation to Noise in Human Speech Recognition Unrelated to the Medial Olivocochlear Reflex.

Sensory systems constantly adapt their responses to the current environment. In hearing, adaptation may facilitate communication in noisy settings, a benefit frequently (but controversially) attributed to the medial olivocochlear reflex (MOCR) enhancing the neural representation of speech. Here, we show that human listeners (N = 14; five male) recognize more words presented monaurally in ipsilateral, contralateral, and bilateral noise when they are given some time to adapt to the noise. This finding challenges models and theories that claim that speech intelligibility in noise is invariant over time. In addition, we show that this adaptation to the noise occurs also for words processed to maintain the slow-amplitude modulations in speech (the envelope) disregarding the faster fluctuations (the temporal fine structure). This demonstrates that noise adaptation reflects an enhancement of amplitude modulation speech cues and is unaffected by temporal fine structure cues. Last, we show that cochlear implant users (N = 7; four male) show normal monaural adaptation to ipsilateral noise. Because the electrical stimulation delivered by cochlear implants is independent from the MOCR, this demonstrates that noise adaptation does not require the MOCR. We argue that noise adaptation probably reflects adaptation of the dynamic range of auditory neurons to the noise level statistics.SIGNIFICANCE STATEMENT People find it easier to understand speech in noisy environments when they are given some time to adapt to the noise. This benefit is frequently but controversially attributed to the medial olivocochlear efferent reflex enhancing the representation of speech cues in the auditory nerve. Here, we show that the adaptation to noise reflects an enhancement of the slow fluctuations in amplitude over time that are present in speech. In addition, we show that adaptation to noise for cochlear implant users is not statistically different from that for listeners with normal hearing. Because the electrical stimulation delivered by cochlear implants is independent from the medial olivocochlear efferent reflex, this demonstrates that adaptation to noise does not require this reflex.

IKZF1 Gene Deletion in Pediatric Patients Diagnosed with Acute Lymphoblastic Leukemia in Mexico.

The IKZF1 gene is formed by 8 exons and encodes IKAROS, a transcription factor that regulates the expression of genes that control cell cycle progression and cell survival. In general, 15-20% of the patients with preB acute lymphoblastic leukemia (preB ALL) harbor IKZF1 deletions, and the frequency of these deletions increases in BCR-ABL1 or Ph-like subgroups. These deletions have been associated with poor treatment response and the risk of relapse. The aim of this descriptive study was to determine the frequency of IKZF1 deletions and the success of an induction therapy response in Mexican pediatric patients diagnosed with preB ALL in 2 hospitals from 2017 to August 2018. Thirty-six bone marrow samples from patients at the Instituto Nacional de Pediatría in Mexico City and the Centro Estatal de Cancerología in Tepic were analyzed. The IKZF1 deletion was identified by MLPA using the SALSA MLPA P335 ALL-IKZF1 probemix. Deletions of at least 1 IKZF1 exon were observed in 7/34 samples (20.6%): 3 with 1 exon deleted; 1 with 2 exons, 1 with 5 exons, 1 with 6 exons, and 1 patient with a complete IKZF1 deletion. This study was descriptive in nature; we calculated the frequency of the IKZF1 gene deletion in a Mexican pediatric population with preB ALL as 20.6%.

IgA vasculitis (Henoch - Schönlein Purpura) as the first manifestation of juvenile Systemic Lupus Erythematosus: Case-control study and systematic review.

BACKGROUND: We have recognized 15 children with jSLE and the antecedent of IgA vasculitis (HSP). This association is not broadly present in the literature. AIM: To know the age and gender distribution of children with IgA vasculitis (HSP), compare it to our IgA vasculitis (HSP) + jSLE cases, and identify prognostic factors to develop jSLE within our case series, IgA vasculitis (HSP) vs. IgA vasculitis (HSP) + jSLE. METHODS: A systematic review was carried out to know the age and gender distribution of children with IgA vasculitis (HSP). The information obtained plus data from 110 children with IgA vasculitis (HSP) from the Instituto Nacional de Pediatría were used to compare groups and identify prognostic factors. We performed a case-control study in patients < 18 years, consisting of 15 cases retrospectively identified with IgA vasculitis (HSP) + jSLE, and 110 IgA vasculitis (HSP) control subjects. RESULTS: The information of 12,819 IgA vasculitis (HSP) subjects from the systematic review and 110 IgA vasculitis (HSP) controls was obtained and compared to our 15 IgA vasculitis (HSP) + jSLE cases. The mean age of IgA vasculitis (HSP) was 7.1-years vs. 10.4-years of IgA vasculitis (HSP) + jSLE at the HSP diagnosis. Female to male ratio of IgA vasculitis (HSP) was 1:1.33 vs. 1:0.25 of IgA vasculitis (HSP) + jSLE. Patients with IgA vasculitis (HSP) + jSLE had lower levels of Hemoglobin (Hb) compared to patients with IgA vasculitis (HSP) 109 g/L vs. 141 g/L. For the development of jSLE, we found older age and lower levels of Hb as prognostic factors with OR [95% CI]: 1.37 [1.06, 1.89] and 5.39 [2.69, 15.25], respectively. CONCLUSION: IgA vasculitis (HSP) + jSLE patients are older and have lower levels of Hb than patients with IgA vasculitis (HSP). It is necessary to confirm these findings through a prospective study.

Isolation and Antimacrofouling Activity of Indole and Furoquinoline Alkaloids from 'Guatambú' Trees (Aspidosperma australe and Balfourodendron riedelianum).

In this work, the antifouling activity of five alkaloids, isolated from trees of the Atlantic rainforest, was studied. The tested alkaloids were olivacine (1), uleine (2) and N-methyltetrahydroellipticine (3) from Aspidosperma australe ('yellow guatambú') and the furoquinoline alkaloids kokusaginine (4) and flindersiamine (5) from Balfourodendron riedelianum ('white guatambú'). All these compounds can be isolated from their natural sources in high yields in a sustainable way. The five compounds were subjected to laboratory tests (attachment test of the mussel Mytilus edulis platensis) and field trials, by incorporation into soluble matrix paints, and 45 days of exposure of the painted panels in the sea. The results show that compound 3 is a very potent antifoulant, and that compounds 4 and 5 are also very active, while compounds 1 and 2 did not show any significant antifouling activity. These results open the way for the development of environmentally friendly antifouling agents, based on abundant and easy-to-purify compounds that can be obtained in a sustainable way.

Epidemiology of venous leg ulcers in primary health care: Incidence and prevalence in a health centre-A time series study (2010-2014).

The aims of the study were to describe and analyse the temporal trend of the prevalence and incidence of venous leg ulcers (VLU) over the years 2010 to 2014, to determine healing times and temporal trends in the study period, and to evaluate related aspects such as the use of the Ankle-Brachial Pressure Index (ABPI) in a primary care health centre. This was a retrospective study based on a time series (years 2010-2014) of the prevalence and incidence of VLUs in people aged over 40 years in a primary care centre in Barcelona City. We reviewed 3920 electronic health records selecting patients, per year (2010-2014), with VLUs based on the ICD-10 diagnoses. For prevalence, we took into account any patient with an active VLU in the year of study. For incidence, we took into account patients with a new VLU in the year of study. A descriptive analysis was carried out based on each of the collected variables. The variables were examined according to the years of study (time series) by one-factor analysis of variance (anova) or Kruskal-Wallis non-parametric test, as appropriate. A survival analysis by Kaplan-Meier curves and log-rank test was also performed. A total of 139 patients met the VLU criteria. Among them, only 79.2% were classified as having a VLU and had a correct ICD diagnosis. The prevalence and incidence increased over the years, doubling in patients aged over 65 years. Incidence increased from 0.5 new cases per 1000 people/year in 2010 to 1 new case for every 1000 people/year in 2014. Moreover, the prevalence ranged between 0.8 and 2.2 patients with VLU for every 1000 people/year. During the study period, a total of 84.2% of the VLUs healed (117/139 VLU). Regarding average annual time to healing, the trend indicates that lesions took less time to heal (Kruskal-Wallis test, P = 0.004), ranging between 453,9 weeks in 2005 to 19 weeks in 2014. The use of ABPI also evolved and was found to be increasingly performed prior to the appearance of the lesion. The epidemiological profile of people affected by VLUs continues to be, mainly, that of women of an advanced age, over 70 years. The frequency of VLU occurrence rose continually over the years, but healing took less time, and use of ABPI improved. Assigning a reference nurse in the wounds unit and the organisational structure around this problem may have an influence on improving care and the approach to these types of lesions.

Facial nerve stimulation in normal pigs and healthy human volunteers: transitional development of a medical device for the emergency treatment of ischemic stroke.

BACKGROUND: Magnetic stimulation of the facial nerve has been tested in preclinical studies as a new, non-invasive emergency treatment of ischemic stroke that acts by increasing cerebral blood flow (CBF). The objective of the studies reported herein was to identify minimal stimulation parameters that increase CBF in large animals and then test those stimulation parameters in healthy volunteers for safety, tolerability, and effectiveness at increasing CBF. This translational research is necessary preparation for clinical studies in ischemic stroke patients. METHODS: Initial experiments in anesthetized Yorkshire pigs were undertaken in order to identify the lowest stimulus power and duration that increase CBF. A full 3 × 3 factorial design was used to evaluate magnetic stimulation of the facial nerve at various stimulation powers (1.3, 1.6, and 1.9 Tesla field strength at coil surface) and for various durations (2, 3.5, and 5 min). CBF was measured with contrast MRI perfusion imaging and the internal carotid arteries were assessed with MR angiography. Magnetic facial nerve stimulation with parameters identified in the pig study was then applied to 35 healthy volunteers. Safety was assessed with adverse event reports and by medical examination. Tolerability was defined as each volunteer's ability to withstand at least 2 min of stimulation. Volunteers could determine the maximum power of stimulation they received during a ramp-up period. RESULTS: In pigs, unilateral facial nerve stimulation increased CBF by as much as 77% over pre-stimulation baseline when administered across a range of 1.3-1.9 Tesla power and for 2- to 5-min duration. No clear dose-response relationship could be observed across this range, but lower powers and durations than these were markedly less effective. The effect of a single stimulation lasted 90 min. A second stimulation delivered 100 min after the first stimulation sustained the increased CBF without evidence of tachyphylaxis. In human, bilateral facial nerve stimulation caused only non-serious adverse events that were limited to the 2-min stimulation period. Tolerability was greatly improved by gentle encouragement from the study staff, which enabled most volunteers to tolerate 1.6-1.8 Tesla of stimulation power. CBF measures taken approximately 10 min after stimulation demonstrated on average a 32 ± 6% increase in CBF, with ≥ 25% increases in CBF occurring in 10 of the 31 volunteers who had adequate CBF measurements. CONCLUSIONS: The minimal effective stimulation parameters defined by increased CBF, as identified in the pig study, translated into safe, tolerable, and effective stimulation of healthy volunteers. These results support the future development and evaluation of non-invasive facial nerve stimulation for the emergency treatment of ischemic stroke. Trial Registration retrospectively registered with clinicaltrials.gov NRV_P1_01_15 on June 6, 2017.

pirA- and pirB-like gene identification in Micrococcus luteus strains in Mexico.

Acute hepatopancreatic necrosis disease (AHPND) was first reported in China in 2009 and afterwards in Mexico in 2013. AHPND is caused by Vibrio parahaemolyticus and affects Penaeus monodon and Litopenaeus vannamei shrimp cultures. The bacterium contains the pirA- and pirB-like genes in 69- to 70-Kb plasmids, which encode the toxins that produce the disease. The aim of this study was to determine whether pirA- and pirB-like genes existed in bacterial genera distinct from Vibrio before the first cases of AHPND were documented in Mexico. Two bacterial isolates were selected from shrimp farms in Nayarit in 2006 and analysed by nested-PCR to determine the presence of pirA- and pirB-like genes. The two isolates chosen did indeed show the presence of these genes, and those findings were confirmed by sequencing. Both strains matched to the bacterial species Micrococcus luteus. Results revealed two important situations: (a) the pirA- and pirB-like genes were present in a bacterial species that has not been reported previously (Micrococcus luteus); and (b) pirA- and pirB-like bacterial genes were present in Mexico before the first AHPND outbreak was reported in China.