LymPHOS 2.0: An update of a phosphosite database of primary human T cells

LymPHOS is a web-oriented database containing peptide and protein sequences and spectrometric information on the phosphoproteome of primary human T-Lymphocytes. Current release 2.0 contains 15 566 phosphorylation sites from 8273 unique phosphopeptides and 4937 proteins, which correspond to a 45-fold increase over the original database description. It now includes quantitative data on phosphorylation changes after time-dependent treatment with activators of the TCR-mediated signal transduction pathway. Sequence data quality has also been improved with the use of multiple search engines for database searching. LymPHOS can be publicly accessed at http://www.lymphos.org.This work was supported by project BIO2013-46492R from the Spanish Ministry of Economy and Competitiveness. T.D.N. was supported by a cooperation agreement between the Spanish National Research Council and the Vietnam Academy of Science and Technology (grant 2012VN0003). The CSIC/UAB Proteomics Facility belongs to ProteoRed and is partially funded by grants PT13/001 and PT13/008 from PRB2-ISCIII.Peer Reviewe

Vitamin d and leishmaniasis : Neither seasonal nor risk factor in canine host but potential adjuvant treatment through cbd103 expression

Red de Investigación Cooperativa en Enfermedades Tropicales RD12/0018/0010Vitamin D (VitD) deficiency has been shown to be a risk factor for a plethora of disorders. We have shown that dogs with clinical leishmaniasis presented lower VitD serum levels than non-infected dogs, and even lower than those with asymptomatic infection. However, if VitD deficiency is a risk factor to develop clinical leishmaniasis remains to be answered. It is also unknown if VitD participates in Leishmania control. First, we retrospectively analysed VitD concentration in serum samples from 36 healthy dogs collected in different periods of the year concluding that there isn't a seasonal variation of this vitamin in dogs. We also included 9 dogs with clinical leishmaniasis and 10 non-infected healthy dogs, in which we measured VitD levels at the beginning of the study, when all dogs were negative for serology and qPCR, and 1 year later. Whereas non-infected dogs showed no change in VitD levels along the study, those developing clinical leishmaniasis showed a significant VitD reduction at the end of the study (35%). When we compared VitD concentration between the two groups at the beginning of the study, no differences were detected (43.6 (38-59) ng/mL, P = 0.962). Furthermore, an in vitro model using a canine macrophage cell line proved that adding active VitD leads to a significant reduction in L. infantum load (31.4%). Analyzing expression of genes related to VitD pathway on primary canine monocytes, we showed that CBD103 expression was significantly enhanced after 1,25(OH)D addition. Our results show that VitD concentration is neither seasonal nor a risk factor for developing canine leishmaniasis, but it diminishes with the onset of clinical disease suggesting a role in parasitic control. Our in vitro results corroborate this hypothesis and point out that VitD regulates infection through CBD103 expression. These results open the possibility for studies testing VitD as an adjuvant in leishmaniasis therapy. Vitamin D (VitD), the precursor of the powerful steroid hormone calcitriol, has been widely known to regulate the calcium and phosphate homeostasis. Several studies have shown that VitD plays also an important role on innate immunity. The mechanisms by which VitD modulates the immune function have been studied within different contexts involving multiple pathogens, but not Leishmania sp. It is known that VitD strengthens the innate immune system by inducing the expression of anti-microbial peptides in Mycobacterium tuberculosis- infected human macrophages. Antimicrobial peptides act on the bacterial wall, increasing the formation of reactive oxygen species, modulating cytokine expression, and inducing autophagy. Immune system plays a key role in leishmaniasis disease control, thus VitD could have a relevant contribution in leishmaniasis. In a previous study, we shown that clinical leishmaniasis is associated with VitD deficiency. This research aims to determine whether vitamin D is seasonal and a risk factor for developing canine leishmaniasis and, also, to study the possible VitD anti-parasitic effect and the expression of genes related to VitD pathway. The results show that VitD in canine leishmaniasis is neither seasonal nor a risk factor for developing clinical disease. However, its role in reducing parasite load suggests that VitD could be an adjuvant in leishmaniasis therapy

An Observational Report of Intensive Robotic and Manual Gait Training in Sub-acute Stroke

Background: The use of automated electromechanical devices for gait training in neurological patients is increasing, yet the functional outcomes of well-defined training programs using these devices and the characteristics of patients that would most benefit are seldom reported in the literature. In an observational study of functional outcomes, we aimed to provide a benchmark for expected change in gait function in early stroke patients, from an intensive inpatient rehabilitation program including both robotic and manual gait training. Methods: We followed 103 sub-acute stroke patients who met the clinical inclusion criteria for Body Weight Supported Robotic Gait Training (BWSRGT). Patients completed an intensive 8-week gait-training program comprising robotic gait training (weeks 0-4) followed by manual gait training (weeks 4-8). A change in clinical function was determined by the following assessments taken at 0, 4 and 8 weeks (baseline, mid-point and end-point respectively): Functional Ambulatory Categories (FAC), 10 m Walking Test (10 MWT), and Tinetti Gait and Balance Scales. Results: Over half of the patients made a clinically meaningful improvement on the Tinetti Gait Scale (>3 points) and Tinetti Balance Scale (>5 points), while over 80% of the patients increased at least 1 point on the FAC scale (0-5) and improved walking speed by more than 0.2 m/s. Patients responded positively in gait function regardless of variables gender, age, aetiology (hemorrhagic/ischemic), and affected hemisphere. The most robust and significant change was observed for patients in the FAC categories two and three. The therapy was well tolerated and no patients withdrew for factors related to the type or intensity of training. Conclusions: Eight-weeks of intensive rehabilitation including robotic and manual gait training was well tolerated by early stroke patients, and was associated with significant gains in function. Patients with mid-level gait dysfunction showed the most robust improvement following robotic training

Salivary gland dysfunction markers in type 2 diabetes mellitus patients

Background: Diabetes mellitus (DM) is a chronic disease of the carbohydrate metabolism that, when not rigorously controlled, compromises systemic and organ integrity, thereby causing renal diseases, blindness, neuropathy, arteriosclerosis, infections, and glandular dysfunction, including the salivary glands. The aim of this study was to determine the relationship between the qualitative and quantitative parameters of salivary alteration, which are indicators of salivary gland dysfunction, and the level of metabolic control of type 2 diabetes patients. Material and Methods: A convenience sample of 74 voluntary patients with type 2 DM was selected, each of whom donated a sample of unstimulated saliva. Salivary parameters such as salivary flow rate, protein concentration, pH, and xerostomia were studied. Results: There is a positive relationship between the level of metabolic control measured with HbA1 and the protein concentration in saliva (Spearman rho = 0.329 and p = 0.004). The same assay showed an inverse correlation between HbA1 and pH (Spearman rho = -0.225 and p = 0.05). Conclusions: The protein concentration in saliva and, to a lesser extent, the pH may be useful as glandular dysfunction indicators in DM2 patients

Immunosuppression and Chagas disease: a management challenge

Immunosuppression, which has become an increasingly relevant clinical condition in the last 50 years, modifies the natural history of Trypanosoma cruzi infection in most patients with Chagas disease. The main goal in this setting is to prevent the consequences of reactivation of T. cruzi infection by close monitoring. We analyze the relationship between Chagas disease and three immunosuppressant conditions, including a description of clinical cases seen at our center, a brief review of the literature, and recommendations for the management of these patients based on our experience and on the data in the literature. T. cruzi infection is considered an opportunistic parasitic infection indicative of AIDS, and clinical manifestations of reactivation are more severe than in acute Chagas disease. Parasitemia is the most important defining feature of reactivation. Treatment with benznidazole and/or nifurtimox is strongly recommended in such cases. It seems reasonable to administer trypanocidal treatment only to asymptomatic immunosuppressed patients with detectable parasitemia, and/or patients with clinically defined reactivation. Specific treatment for Chagas disease does not appear to be related to a higher incidence of neoplasms, and a direct role of T. cruzi in the etiology of neoplastic disease has not been confirmed. Systemic immunosuppressive diseases or immunosuppressants can modify the natural course of T. cruzi infection. Immunosuppressive doses of corticosteroids have not been associated with higher rates of reactivation of Chagas disease. Despite a lack of evidence-based data, treatment with benznidazole or nifurtimox should be initiated before immunosuppression where possible to reduce the risk of reactivation. Timely antiparasitic treatment with benznidazole and nifurtimox (or with posaconazole in cases of therapeutic failure) has proven to be highly effective in preventing Chagas disease reactivation, even if such treatment has not been formally incorporated into management protocols for immunosuppressed patients. International consensus guidelines based on expert opinion would greatly contribute to standardizing the management of immunosuppressed patients with Chagas disease

Plasma-Derived Extracellular Vesicles as Potential Biomarkers in Heart Transplant Patient with Chronic Chagas Disease

Chagas disease is emerging in countries to which it is not endemic. Biomarkers for earlier therapeutic response assessment in patients with chronic Chagas disease are needed. We profiled plasma-derived extracellular vesicles from a heart transplant patient with chronic Chagas disease and showed the potential of this approach for discovering such biomarkers.Barcelona Institute for Global Health (ISGlobal) receives support from the Spanish Ministry of Science, Innovation and Universities through the Centro de Excelencia Severo Ochoa 2019–2023 Program (CEX2018-000806-S). ISGlobal and Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP) are members of the Centres de Recerca de Catalunya (CERCA Program), Generalitat de Catalunya. Work in the laboratory of C.F.B. is funded by Fundació La Marató de TV3 (reference 566/U/2018) and Fundación Mundo Sano. This project was co-financed by the European Union through the European Regional Development Fund with the support of Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya. N.C., M.G., J.G., and M.J.P. receive funds from the Redes temáticas de investigación cooperativa en salud (RETICS), Spanish Tropical Diseases Network “RD12/0018/0010” and from the Agencia de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya; grant “2017 SGR 00924.” M.G., C.B., J.G., M.J.P., and I.C.A. belong to the Ibero-American Nuevas Herramientas para el Diagnóstico y la Evaluación del Paciente con Enfermedad de Chagas network. I.C.A. is partially supported by grants no. 2G12MD007592 and 5U54MD007592 from the National Institute on Minority Health and Health Disparities of the US National Institutes of Health. We are grateful to the Biomolecule Analysis Core Facility at University of Texas at El Paso, Border Biomedical Research Center, funded by National Institute on Minority Health and Health Disparities grants 2G12MD007592 and 5U54MD007592. M.T.M. received a PhD fellowship from the Science Without Borders Program, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil.S

Assessing Viral Abundance and Community Composition in Four Contrasting Regions of the Southern Ocean

We explored how changes of viral abundance and community composition among four contrasting regions in the Southern Ocean relied on physicochemical and microbiological traits. During January–February 2015, we visited areas north and south of the South Orkney Islands (NSO and SSO) characterized by low temperature and salinity and high inorganic nutrient concentration, north of South Georgia Island (NSG) and west of Anvers Island (WA), which have relatively higher temperatures and lower inorganic nutrient concentrations. Surface viral abundance (VA) was highest in NSG (21.50 ± 10.70 × 106 viruses mL−1) and lowest in SSO (2.96 ± 1.48 × 106 viruses mL−1). VA was positively correlated with temperature, prokaryote abundance and prokaryotic heterotrophic production, chlorophyll a, diatoms, haptophytes, fluorescent organic matter, and isoprene concentration, and was negatively correlated with inorganic nutrients (NO3−, SiO42−, PO43−), and dimethyl sulfide (DMS) concentrations. Viral communities determined by randomly amplified polymorphic DNA–polymerase chain reaction (RAPD-PCR) were grouped according to the sampling location, being more similar within them than among regions. The first two axes of a canonical correspondence analysis, including physicochemical (temperature, salinity, inorganic nutrients—NO3−, SiO42−, and dimethyl sulfoniopropionate -DMSP- and isoprene concentrations) and microbiological (chlorophyll a, haptophytes and diatom, and prokaryote abundance and prokaryotic heterotrophic production) factors accounted for 62.9% of the variance. The first axis, temperature-related, accounted for 33.8%; the second one, salinity-related, accounted for 29.1%. Thus, different environmental situations likely select different hosts for viruses, leading to distinct viral communities.En prens

Health Problems Encountered by Short-Term European Volunteers in a Nongovernmental Organization in Cambodia

Short-term volunteers are susceptible to a wide spectrum of morbidities, mostly infectious diseases preventable with general hygiene and preventive measures. This study aimed to identify the health problems encountered by European short-term volunteers collaborating for 1 month with a nongovernmental organization (NGO) in Cambodia and to describe their characteristics. A prospective, descriptive observational study was conducted on short-term volunteers who collaborated with an NGO in Cambodia during August 2018. Informed consent and sociodemographic, clinical, and preventative health-related questionnaire data were provided by 198 volunteers. The health problems encountered were confirmed in a primary care consultation with healthcare professionals. Univariate and bivariate analyses were performed. The median age of the volunteers was 22 years (interquartile range = 21-24), and 64% were women. Some (18.2%) had allergies, 8.6% had preexisting health conditions, and 10.6% were under regular treatment. A total of 77.3% visited a pretravel consultation clinic, 39.9% completed a specific pretravel health course, 21.7% took malaria prophylaxis, 92.4% received hepatitis A vaccination, and 82.3% received typhoid fever vaccination. Medical assistance was sought by 112 (57.3%) of the volunteers. The average number of health problems was 2.5 (standard deviation = 1.5), and the total number of health problems attended by the medical team was 279. The most common health problems were upper respiratory infections (12.2 per 1,000 person/days), wounds (10.8 per 1,000 person/days), and diarrhea (6.3 per 1,000 person/days). Short-term volunteers experienced a high rate of health problems during their stay in Cambodia, but most of the problems were mild and preventable and resolved quickly. Pretravel consultation and specific pretravel health training seemed to increase disease awareness

Mycobacterium manresensis induces trained immunity in vitro

The COVID-19 pandemic posed a global health crisis, with new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants weakening vaccine-driven protection. Trained immunity could help tackle COVID-19 disease. Our objective was to analyze whether heat-killed Mycobacterium manresensis (hkMm), an environmental mycobacterium, induces trained immunity and confers protection against SARS-CoV-2 infection. To this end, THP-1 cells and primary monocytes were trained with hkMm. The increased secretion of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, and IL-10, metabolic activity, and changes in epigenetic marks suggested hkMm-induced trained immunity in vitro. Healthcare workers at risk of SARS-CoV-2 infection were enrolled into the MANRECOVID19 clinical trial (NCT04452773) and were administered Nyaditum resae (NR, containing hkMm) or placebo. No significant differences in monocyte inflammatory responses or the incidence of SARS-CoV-2 infection were found between the groups, although NR modified the profile of circulating immune cell populations. Our results show that M. manresensis induces trained immunity in vitro but not in vivo when orally administered as NR daily for 14 days. Biological sciences; Molecular biology; Immunology; Microbiolog