Endothelial ILK induces cardioprotection by preventing coronary microvascular dysfunction and endothelial-to-mesenchymal transition.

Endothelial dysfunction is an early event in coronary microvascular disease. Integrin-linked kinase (ILK) prevents endothelial nitric oxide synthase (eNOS) uncoupling and, thus, endothelial dysfunction. However, the specific role of endothelial ILK in cardiac function remains to be fully elucidated. We hypothesised that endothelial ILK plays a crucial role in maintaining coronary microvascular function and contractile performance in the heart. We generated an endothelial cell-specific ILK conditional knock-out mouse (ecILK cKO) and investigated cardiovascular function. Coronary endothelial ILK deletion significantly impaired cardiac function: ejection fraction, fractional shortening and cardiac output decreased, whilst left ventricle diastolic internal diameter decreased and E/A and E/E' ratios increased, indicating not only systolic but also diastolic dysfunction. The functional data correlated with extensive extracellular matrix remodelling and perivascular fibrosis, indicative of adverse cardiac remodelling. Mice with endothelial ILK deletion suffered early ischaemic-like events with ST elevation and transient increases in cardiac troponins, which correlated with fibrotic remodelling. In addition, ecILK cKO mice exhibited many features of coronary microvascular disease: reduced cardiac perfusion, impaired coronary flow reserve and arterial remodelling with patent epicardial coronary arteries. Moreover, endothelial ILK deletion induced a moderate increase in blood pressure, but the antihypertensive drug Losartan did not affect microvascular remodelling whilst only partially ameliorated fibrotic remodelling. The plasma miRNA profile reveals endothelial-to-mesenchymal transition (endMT) as an upregulated pathway in endothelial ILK conditional KO mice. Our results show that endothelial cells in the microvasculature in endothelial ILK conditional KO mice underwent endMT. Moreover, endothelial cells isolated from these mice and ILK-silenced human microvascular endothelial cells underwent endMT, indicating that decreased endothelial ILK contributes directly to this endothelial phenotype shift. Our results identify ILK as a crucial regulator of microvascular endothelial homeostasis. Endothelial ILK prevents microvascular dysfunction and cardiac remodelling, contributing to the maintenance of the endothelial cell phenotype.

Description of Paravulvus zhongshanensis sp. nov. (Dorylaimida: Nygolaimidae) from Nanjing, China.

Paravulvus zhongshanensis sp. nov., isolated from soil in a location at Jiangsu Province, China, is described and illustrated based on morphological, morphometric and molecular characterizations. The new species is characterized by its body 1.17-1.53 mm long, lip region offset by marked constriction and 12.1-13.8 µm broad, mural tooth deltoid and 9.6-11.7 µm long, neck 278-360 µm long, pharyngeal expansion 164-208 µm long or occupying more than one-half (54-62%) of total neck length, uterus 32.5-35.3 µm long or 1.0-1.1 times the corresponding body diameter, V = 47.8-53.4, paravulvae absent, female tail subcylindrical conoid (30.5-39.5 µm, c = 36.0-45.5, c' = 1.7-2.2) with widely rounded end, and male unknown. The new species was compared with six known species of the genus including Paravulvus acuticaudatus, Paravulvus confusus, Paravulvus hartingii, Paravulvus iranicus, Paravulvus loofi and Paravulvus microdontus mainly by similarities in having conical tail and c' value larger than 1.3. The rRNA and mitochondrial cytochrome oxidase subunit 1 genes of the new species were obtained and were used for reconstructing the phylogenetic relationships of the new species.

Histopathological and virological features of lung, heart and liver percutaneous tissue core biopsy in patients with COVID-19: A clinicopathological case series.

INTRODUCTION: Data on pathological changes in COVID-19 are scarce. The aim of this study was to describe the histopathological and virological findings of postmortem biopsies, and the existing clinical correlations, in people who died of COVID-19. MATERIALS AND METHODS: We performed postmortem needle core biopsies of the chest in 11 people who died of COVID-19 pneumonia. Tissue examination was done by light microscopy and real-time polymerase chain reaction (RTPCR). RESULTS: The age of the patients were between 61 to 94 years. Of the 11 postmortem chest biopsies, lung tissue was obtained in 8, myocardium tissue in 7, and liver tissue in 5. Histologically of lung, the main findings pertaining to the lung were diffuse alveolar damage in proliferative phase (n = 4, 50%), diffuse alveolar damage in exudative and proliferative phase (n = 3, 37.5%), diffuse alveolar damage in exudative (n=1; 12.5%) and acute pneumonia (n = 2, 25%). Necrotising pneumonia, acute fibrinous and organising pneumonia, and neutrophils were detected in one sample each (12.5%). Another case presented myocarditis. RT-PCR showed RNA of SARS-CoV-2 in 7 of the 8 lung samples (87.5%), 2 of the 7 myocardial tissue samples (28.6%), and 1 of the 5 liver tissue samples (20%). CONCLUSION: The postmortem examinations show diffuse alveolar damage, as well as acute or necrotising pneumonia. RT-PCR of SARS-CoV-2 was positive in most lung samples.

The silent variants of pituitary tumors: demographic, radiological and molecular characteristics.

INTRODUCTION: Tumors of the anterior pituitary gland (PTs) are mostly benign tumors with a low prevalence, which has nevertheless increased with advances in brain radiology techniques. Nearly half of PTs are not associated with a clinical endocrine syndrome. These tumors have been indistinctly named non-functioning pituitary adenomas (NFPAs) or silent pituitary tumors (SPTs) and the mechanisms of silencing are not fully known. AIM: To study the frequency and characterize the silent variant of PTs in a large local series, and to assess their pituitary adenohypophyseal gene expression. METHODS: This observational, cross-sectional study was performed in a Pituitary Tumor Center of Excellence and involved 268 PTs. After identifying the different subtypes according to the immunohistochemical (IHC) expression of adenohypophyseal hormones, we studied their gene expression by RT-qPCR. RESULTS: We found that silent tumors were larger and more invasive, but not more proliferative than their functional counterparts. The RT-qPCR complements the IHC typification of PTs, reducing the proportion of null-cell subtype. Finally, some silent PT subtype variants showed lower specific adenohypophyseal hormone gene expression than their functional counterparts, which may contribute to the absence of endocrine manifestations. CONCLUSIONS: This paper highlights the importance of identifying the silent variant of the PTs subtypes. As expected, silent tumors were larger and more invasive than their functioning counterparts. However, there was no difference in the proliferation activity between them. Finally, the lower specific gene expression in the silent than in the functioning counterparts of some PTs subtypes gives insights into the silencing mechanisms of PTs.

Molecular identification of Leishmania tropica and L. infantum isolated from cutaneous human leishmaniasis samples in central Morocco.

BACKGROUND & OBJECTIVES: Cutaneous leishmaniasis (CL) in Marrakesh-Safi region located in the central-south part of Morocco is a public health problem. This study assessed the efficiency of a microscopic examination method in establishing the diagnosis of CL and PCR for the characterization and identification of the circulating Leishmania strains in different CL foci of the study area. METHODS: A total of 297 smears obtained from cutaneous lesions of suspected patients with CL were stained with May-Grünwald Giemsa (MGG) for microscopic examination. For each positive smear, genomic DNA was extracted and PCR-analysed, targeting the small subunit ribosomal ribonucleic acid (ssu rRNA) gene to detect Leishmania DNA. Then, the internal transcribed spacer 1 (ITS1) was amplified and sequenced in order to identify the Leishmania species. The sensitivity and specificity of the conventional microscopy with ssu rRNA gene were compared by Leishmania nested PCR (LnPCR) and ITS1 gene by ITS-PCR. RESULTS: A total of 257 smears were positive in the microscopic examination, i.e. the detection rate of amastigotes by optical microscopy was 86.53% (257/297). The LnPCR was found to have a specificity and a sensitivity of 100%, each. Interestingly, the sequencing results showed that 99.61% (256/257) of the isolates had Leishmania tropica and 0.39% (1/257) had L. infantum infection. INTERPRETATION & CONCLUSION: Though, classical microscopic examination is useful and economical, it is not sensitive enough, especially in endemic regions where several Leishmania species coexist. In such situations, PCR constitutes a complementary method for the identification of the causal species. The results indicate that both the L. tropica (dominant) and L. infantum are the causative agents of CL in the Marrakesh-Safi region. The rate of CL infection is high in Imintanout, and Chichaoua provinces. Hence, early diagnosis and prompt treatment of CL patients is necessary to prevent its extension to neighboring localities.

Salvage I-125 brachytherapy for locally-recurrent prostate cancer after radiotherapy.

PURPOSE: Retrospective, single-institution analysis of clinical outcomes and treatment-related toxicity in patients treated with salvage I-125 low-dose rate (LDR) brachytherapy (BT) for locally-recurrent prostate cancer after radiotherapy. MATERIALS AND METHODS: Between 2008 and 2018, 30 patients with biopsy-confirmed prostate cancer recurrence underwent salvage treatment with I-125 LDR-BT. Of these 30 patients, 14 were previously treated with primary external beam radiotherapy (EBRT; median dose, 73 Gy) and 16 with primary I-125 LDR-BT (145 Gy and 160 Gy in 14 and 2 cases, respectively). At seed implantation, the mean age was 75.8 years, with a median Gleason score of 7 and pre-salvage PSA of <10 ng/mL. Six patients received androgen deprivation therapy for six months after relapse diagnosis. The prescribed salvage I-125 BT dose to the gland was 120-130 Gy, with dose restrictions of Dmax <135% (urethra) and <100% (rectum). Toxicity was evaluated according to the CTCAE scale (v4.0). RESULTS: At a median follow-up of 45 months, the biochemical recurrence-free survival rates at 1, 3 and 5 years were 86.7%, 56.7% and 53.3%, respectively. Overall survival at 5 years was 87%. On the multivariate analysis, two variables were significant predictors of recurrence: PSA at relapse and nadir PSA post-salvage. Grade 3 genitourinary toxicity was observed in 5 patients (radiation-induced cystitis in 3 cases and urethral stenosis in 2) and G3 gastrointestinal toxicity in 3 patients (rectal bleeding). CONCLUSION: Salvage therapy with I-125 brachytherapy is a safe and effective treatment option for locally-recurrent prostate cancer in previously-irradiated patients. High pre-salvage PSA and post-salvage nadir PSA values were significantly associated with a worse disease control after salvage I-125 LDR-BT. In well-selected patients, I-125 LDR-BT is comparable to other salvage therapies in terms of disease control and toxicity. However, more research is needed to determine the optimal management of locally-recurrent prostate cancer.

Impact of real-time, dose-escalated permanent seed implant brachytherapy in intermediate-risk prostate cancer.

PURPOSE: To retrospectively evaluate biochemical control and toxicity in patients who underwent 125I seed brachytherapy (BT) for intermediate-risk prostate cancer (PCa). MATERIALS AND METHODS: Between January 2004-December 2014, 395 patients with intermediate-risk PCa underwent 125I BT. Of these, 117 underwent preoperative planning (PP; 145 Gy) and 278 real-time intraoperative preplanning (IoP; 160 Gy). All patients were followed for ≥ 6 months (> 5 years in 48% of patients and > 7 years in 13%). Median follow-up was 59 months. RESULTS: Biochemical relapse-free survival (BRFS) rates at 5 and 8 years were, respectively, 91.7% and 82.1%. By treatment group, the corresponding BRFS rates were 93.5% and 90% for IoP and 89% and 76.8% for PP. The maximum dose to the urethra remained unchanged (217 Gy) despite the dose escalation (from 145 to 160 Gy), without any significant increase in treatment-related toxicity (p = 0.13). Overall toxicity outcomes in the series were excellent, with only 3 cases (0.76%) of grade 3 genitourinary toxicity. CONCLUSION: The real-time intraoperative planning technique at 160 Gy yields better biochemical controls than the preoperative planning technique at 145 Gy. Dose escalation did not increase urinary toxicity. The excellent results obtained with the IoP BT technique support its use as the first treatment option in this patient population.

Genitourinary syndrome of menopause. Prevalence and quality of life in Spanish postmenopausal women. The GENISSE study.

OBJECTIVE: To determine the prevalence of genitourinary syndrome of menopause (GSM) and urogynecological conditions associated with menopause, and to evaluate the impact of GSM on quality of life in a cohort of Spanish postmenopausal women. METHODS: Multicenter, cross-sectional, and observational study involving 430 women. RESULTS: The prevalence of GSM was 70%. GSM was diagnosed in 60.2% of women with no known diagnosis of vulvovaginal atrophy or GSM. Most prevalent symptoms were vaginal dryness (93.3%) and reduced lubrication with sexual activity (90.0%). Most prevalent signs were decreased moisture (93.7%) and loss of vaginal rugae (78.4%). GSM was significantly associated with stress or mixed urinary incontinence, overactive bladder, and vaginal prolapse. Symptoms showed a low-moderate impact on quality of life, mainly in sexual functioning and self-concept and body image. CONCLUSIONS: The GSM is very prevalent in Spanish postmenopausal women, affecting up to 70% of those consulting the gynecologist. Despite the high prevalence of symptoms and signs and its impact on the women's well-being, GSM remains underdiagnosed and undertreated. Given its relationship with urogynecological conditions, it seems necessary to provide an adequate evaluation of postmenopausal women for identifying potential co-morbidities and providing most adequate treatments. An adequate management of GSM will contribute to an improvement in the quality of life of these women.

Asymptomatic carriers of Leishmania infantum in patients infected with human immunodeficiency virus (HIV) in Morocco.

In Morocco, visceral leishmaniasis (VL) is a parasitic disease caused by the flagellated protozoan parasite Leishmania infantum. L. infantum is transmitted by the bite of female phlebotomine sandflies, and its main reservoir hosts are domestic dogs. Asymptomatic infection with L. infantum is more frequent than clinically apparent disease. In HIV-infected patients, the risk of clinical VL is increased due to immunosuppression that may reactivate latent infections. However, coinfected subjects do not necessarily develop VL and may remain as asymptomatic carriers depending on their immune status. The present study investigates the asymptomatic carriers of L. infantum in HIV-infected patients in central Morocco, where human cases of visceral leishmaniasis by L. infantum have been reported. A total of 200 HIV-infected patients attending the Infectious Diseases Unit of the Ibn Zohar Hospital of Marrakech participated in the study. Parasitological and serological blood analyses included a direct microscopic examination (DME), culture in Novy-McNeal-Nicolle (NNN) medium, and serology by indirect immunofluorescence (IFI). We found prevalence rates of 5% (10/200) by IFI, 3% (6/200) by DME, and 2.5% (5/200) by culture. The parasite was identified as L. infantum by PCR from positive cultures.

Morphological and molecular characterization of two new species of the genus Aporcelinus Andrássy, 2009 (Nematoda, Dorylaimida, Aporcelaimidae) from the USA, with new insights on the phylogeny of the genus.

Two new species of the genus Aporcelinus from the USA are described and illustrated. Aporcelinus floridensis sp. n. is characterized by its 1.12-1.52 mm long body, lip region offset by marked constriction and 14.5-17.0 µm broad with perioral liplets, odontostyle 16.5-20.0 µm at its ventral side and 1.1-1.2 times the lip region diameter, neck 316-395 µm long, pharyngeal expansion occupying 43-48% of total neck length, uterus simple and 33-56 µm long or 0.8-1.2 times the corresponding body diameter, V = 48-54, female tail conical (36-49 µm long, c = 27-41, c' = 1.2-2.0) with finely rounded terminus and no hyaline portion, and male absent. Aporcelinus paolae sp. n. is characterized by its 1.29-1.80 mm long body, lip region offset by marked constriction and 14-16 µm broad, odontostyle 15-17 µm at its ventral side and 1.0-1.1 times the lip region diameter, neck 314-397 µm long, pharyngeal expansion occupying 43-53% of total neck length, uterus tripartite and 128-164 µm long or 2.6-3.6 times the corresponding body diameter, V = 53-57, female tail conical (30-39 µm long, c = 40-51, c' = 1.1-1.3) with finely rounded terminus and variably re-curved dorsad, male tail conical (27-36 µm, c = 39-59, c' = 0.9-1.2), ventrally straight and dorsally convex, spicules 48-54 µm long, and 7-9 irregularly spaced ventromedian supplements lacking hiatus. The analyses of the D2-D3 expansion segments of 28S rRNA (LSU) gene sequences of the two new species confirmed the monophyly of the genus, based upon currently available data, showing a close relationship between the genera Aporcelinus and Makatinus, and justified the placement of Aporcelaimellus, Makatinus and Aporcelinus under the subfamily Aporcelaimellinae.

Changes in the Incidence of Skin and Lip Cancer Between 1978 and 2007. / Evolución de la incidencia del cáncer de piel y labio durante el periodo 1978-2007.

INTRODUCTION: The aim of this study was to analyze trends in the incidence of skin cancer worldwide, in Europe, and in Spain between 1978 and 2007. MATERIAL AND METHODS: Skin cancer incidence and trends for the period 1978 to 2007 were investigated using the age- and sex-standardized rates (per 100,000 population) published in the Cancer Incidence in Five Continents series. RESULTS: The incidence of cutaneous melanoma increased progressively from 1978 to 2002 but decreased in the last period analyzed (2003-2007). The highest rates were reported for Australia and the white population in Hawaii. In Spain, the incidence of melanoma tripled in both sexes over the study period. The incidence of nonmelanoma skin cancer also increased between 1978 and 2007, and higher rates were detected in men. The highest incidence rates were recorded in Australia, Brazil, and among the European inhabitants of Zimbabwe. In Spain, the incidence of nonmelanoma skin cancer had doubled or tripled in both sexes by the end of the study period. LIMITATIONS: We were unable to analyze data for the period 2008 to 2012 due to a 5-year delay in the publication of data by the International Agency for Research on Cancer. CONCLUSIONS: The rise in the incidence of skin cancer, assessed using age-standardized rates, suggests that primary prevention measures are insufficient or inappropriate. The reduction in the incidence of cutaneous melanoma in Australia between 2003 and 2007 suggests that the preventive strategies initiated several decades earlier in that country have been effective.

Antioxidant characteristics of extracts of Hibiscus sabdariffa calyces encapsulated with mesquite gum.

This study compared the stability of extracts of H. sabdariffa calyces microencapsulated with different concentrations of mesquite gum during storage. Dry Roselle calyces were mixed with 50:50 (v/v) ethanol:water solution to obtain 18°Bx concentrate. This Roselle extract concentrate was mixed with purified mesquite gum (100:1-100:5 v/w). The Roselle extract concentrate-gum (RECG) was spray dried at inlet and outlet temperatures of 180 ± 2 and 104 ± 2.3 °C, respectively, at an air flow rate of 38 m3/h. Encapsulated Roselle powders (ERP) were analyzed for moisture content, total monomeric anthocyanins (differential pH), phenolic compounds (Folin and Ciocalteu method), antioxidant capacity (ABTS), and color parameters ([Formula: see text], and [Formula: see text]) after 5 weeks and 1 year of storage. Sorption properties (isotherms) and micrographs of powders were also obtained. The average yield of RECG powders was 15.27 ± 0.81 g/100 mL. During storage, ERP showed average values of phenolic compounds, antioxidant capacity, and anthocyanins of 3.43 ± 0.25 g gallic acid equivalents/100 g, 9.34 ± 1.4 g Trolox equivalents/100 g, and 318.7 ± 20.6 mg cyanidin-O-glycoside/100 g, respectively. Color parameters remained constant along the storage time.

Modelling and experimental checking of the influence of substrate concentration on the first order kinetic constant in photo-processes.

Most photoprocesses follow a pseudo first order kinetic law and, commonly, the kinetic parameter depends on the initial concentration of the substrate. In this work, a kinetic model, which explains this dependence on the substrate concentration and on the other operational variables, has been developed. In the model, mass transfer of substrate from the bulk solution to the wall of the photoreactor was assumed as the step determining the rate of the process. To check the model, methylene blue (MB) has been used as model substrate and photodegradation experiments have been carried out in an exciplex KrCl flow-through photoreactor, It was observed that the methylene blue conversion improved with a decrease in its initial concentration, in good agreement with the model. Also, by fitting the experimental data to the model, high correlation coefficients and a high degree of agreement between experimental and calculated conversion was obtained, which validates the model.

Different patterns of A*80:01:01:01 allele generation based on exon or intron sequences.

Generation of the HLA-A*80:01:01:01 allele has been analysed using its complete sequence. Direct comparison of the sequences and phylogenetic trees using the human leukocyte antigen (HLA)-A representative alleles and the major histocompatibility complex (MHC)-A sequences of non-human primates has been made. Results based on exon sequences confirm previously published, but considering only the sequences of the introns, two distinct regions can be differentiated. The first one comprises from the 5' untranslated region region to the first part of intron 3 sequence (shared with A2 family), and the second one includes the sequence from the end of intron 3 to intron 7 (shared with A1/A3/A11/A36/A30 family). Each of them clusters with Gorilla and Chimpanzee MHC-A sequences, respectively, suggesting an origin coming from a common ancestor to Gorilla and Chimpanzee.

Identification of the novel HLA-DQB1*03:03:02:04 allele in a Spanish individual.

HLA-DQB1*03:03:02:04 and DQB1*03:03:02:02 alleles differ by a single point mutation in intron 2.

The Tinea Hospital in Granada, 1679-1923: an institution with a long history.

The Tinea hospital in Granada, Spain, was a charitable health facility founded in the 17th century and still treating patients well into the 20th century. The hospital accepted patients from anywhere, not only those residing in the surrounding area. We describe the hospital's founding and the characteristics of the patients and caregivers. We also discuss how tinea was considered at the time, including the typology and treatment protocols applied as well as diet and hygiene measures used. It is striking that a hospital so focused on treating a single disease did not produce studies on the condition or on the application of contemporary knowledge to guide treatment.

Donor-transmitted malaria after heart transplant managed successfully with artesunate.

Donor-transmitted malaria is a rare complication in solid organ transplantation, which causes high mortality. Data concerning the use of artesunate in solid organ transplant recipients are lacking. We report a heart transplant patient who developed donor-derived severe Plasmodium falciparum malaria, successfully treated with artesunate. Transmission of malaria to 2 of the other transplant recipients from the same donor was also documented.

Polyamide nanofiltration membranes to remove aniline in aqueous solutions.

Aniline is commonly used in a number of industrial processes. It is known to be a harmful and persistent pollutant and its presence in wastewater requires treatment before disposal. In this paper, the effectiveness of nanofiltration (NF) to remove aniline from aqueous solutions is studied in a flat membrane test module using two thin-layer composite membranes of polyamide (NF97 and NF99HF). The influence of different operational variables (applied pressure, feed concentration and pH) on the removal of aniline from synthetic aqueous solutions was analysed. The experimental NF results are compared with results previously obtained by reverse osmosis. Based on this comparative study, the effective order for aniline rejection is: HR98PP > NF97 > DESAL3B > SEPA-MS05 > NF99HF.