Early cadmium-induced effects on reactive oxygen species production, cell viability and membrane electrical potential in grapevine roots

Cadmium (Cd) is one of the most worldwide concerned metal pollutants. It is able to induce reactive oxygen species production through indirect mechanisms causing oxidative stress. Vitis vinifera roots were treated with 100 μM Cd for 0-180 min or 20-100 μM Cd for 24 h. Fluorescence confocal microscopy showed elevated hydrogen peroxide and superoxide levels in the apical root segments. Two phases (after 30 min and 24 h) of the superoxide raised levels were observed. This was accompanied by the decrease in root cell viability. Cd in concentrations between 0.005-10 mM induced significant, but different changes in membrane electrical potential (EM) of the root epidermal cells. The low concentrations of Cd (0.005-0.01 mM) caused transient EM hyperpolarization followed by depolarization, whereas by higher concentrations (0.05-5.0 mM) EM was depolarized. In any case, the depolarization or hyperpolarization were only transient up to 5 mM Cd concentration indicating that the plasma membrane function was not irreversibly destroyed. Hyperpolarization of EM induced by fusicoccin (FC) was completely suppressed only in the presence of 10 mM Cd pointing to the inhibition of H+-ATPase. The results suggest that the Cd interactions, depending on cellular development, result in activation of a complex of various mechanisms such as peroxide and hydrogen peroxide production, which in turn may be a more probable reason for the root cell responses to Cd toxicity than the transient EM changes

Dissimilar responses of membrane potential (EM), permeability properties and respiration to cadmium and nickel in maize root cells

The short-term treatment with Cd2+ and Ni2+ triggered transient depolarization of transplasma membrane potential (EM) in the outer cortical root cells of two maize cultivars (cv. Premia and cv. Blitz), however, both metals changed the EM in a quantitatively different way. The magnitude and duration of EM depolarization were concentration dependent and were greater in the metal susceptible cv. Blitz. The highest EM depolarization was recorded with simultaneous application of Cd2+ + Ni2+ in both maize cultivars. The EM depolarization induced by Cd2+ or Cd2+ + Ni2+ but not Ni2+ alone was accompanied with a tremendous increase of membrane conductivity, but it was not accompanied with the effect of heavy metals (HM) on respiration. Simultaneous application of fusiccocin (FC) with Cd2+ or Cd2+ + Ni2+ during the EM depolarization, inability of FC to stop the depolarization by FC-enhanced proton extrusion and rapid restoration of EM, suggested a transient inhibition of the plasma membrane H+-ATPase by these toxic metals. Our data support the opinion that differences in the effects of the studied ions were not the result of their direct action on PM, but rather of their different influence on intracellular processes within root cells

Cadmium uptake, localization and stress-induced morphogenic response in the fern Pteris vittata.

Cadmium uptake, tissue localization and structural changes induced at cellular level are essential to understand Cd tolerance in plants. In this study we have exposed plants of Pteris vittata to different concentrations of CdCl2 (0, 30, 60, 100 μM) to evaluate the tolerance of the fern to cadmium. Cadmium content determination and its histochemical localization showed that P. vittata not only takes up, but also transports and accumulates cadmium in the aboveground tissues, delocalizing it mainly in the less bioactive tissues of the frond, the trichomes and the scales. Cadmium tolerance in P. vittata was strictly related to morphogenic response induced by the metal itself in the root system. Adaptive response regarded changes of the root apex size, the developmental pattern of root hairs, the differentiation of xylem elements and endodermal suberin lamellae. All the considered parameters suggest that, in our experimental conditions, 60 μM of Cd may represent the highest concentration that P. vittata can tolerate; indeed this Cd level even improves the absorbance features of the root and allows good transport and accumulation of the metal in the fronds. The results of this study can provide useful information for phytoremediation strategies of soils contaminated by Cd, exploiting the established ability of P. vittata to transport, delocalize in the aboveground biomass and accumulate polluting metals

Prevalence of positivity for diabetes-associated autoantibodies in individuals with type 2 diabetes and their further characterisation: cross-sectional study from Slovakia

Background Individuals initially diagnosed with type 2 diabetes (T2D) might exhibit positivity for diabetes-associated autoantibodies (DAA +). We investigated the prevalence of DAA positivity in a group of individuals with T2D who were referred to a tertiary diabetes centre within a pre-specified period of time. We aimed to identify characteristics linked with DAA positivity by comparing DAA + individuals with their DAA-negative counterparts. Methods This was a cross-sectional study into which all T2D patients referred to the National Institute of Endocrinology and Diabetology, Ľubochňa, Slovakia, between 1 January and 30 June 2016 were included. Data on > 70 participants’ characteristics, including antibodies against glutamic acid decarboxylase (anti-GAD65), insulinoma-associated antigen IA-2 (IA-2A) and insulin (IAA), were collected. Results Six hundred and ninety-two individuals (387, 55.6% female) with a median (range) age of 62 (24–83) years, HbA1c of 8.9 (5.0–15.7)% [74 (31–148 mmol/mol)] and diabetes duration of 13.0 (0–42) years were analysed. One hundred and forty-five (145/692, 21.0%) tested positive for at least one DAA; 136/692 (19.7%) were positive for anti-GAD65, 21/692 (3.0%) were positive for IA-2A and 9/692 (1.3%) were positive for IAA. Only 84.9% of the DAA + individuals aged > 30 years at the time of diabetes diagnosis met the current diagnostic criteria for latent autoimmune diabetes of adults (LADA). DAA + differed from DAA − individuals in multiple characteristics, including the incidence of hypoglycaemia. Conclusion Several pathological processes linked with distinct types of diabetes can develop in parallel, including insulin resistance and autoimmune insulitis. In this single-centre cross-sectional study from Slovakia, we report a higher than previously published prevalence of DAA positivity in a group of individuals with a formal diagnosis of T2D

Clinical characteristics, sepsis interventions and outcomes in the obese patients with septic shock: an international multicenter cohort study

La calidad educativa de los centros de hoy depende del nivel de competencias adquirido por sus educadores (Perrenoud, 2002). En este sentido, debemos apostar por un equipo humano formado por sujetos que sepan superarse permanentemente, aptos para ejercer tareas dinámicas y cambiantes y que compartan alternativas para crecer en todos los sentidos. Más todavía, debemos apostar por profesionales capaces de identificar y dominar los procesos que se deben realizar actuando con decisión y responsabilidad. La adquisición de competencias comporta aptitud y actitud para utilizar conocimientos, más concretamente, habilidades y valores, de manera interdisciplinaria, transversal e interactiva en contextos y situaciones que requieren la intervención de contenidos vinculados a las diferentes áreas del currículum (Lleixà, 2007), sin exclusividad, en este caso, del área de Educación Física. Presentamos una propuesta metodológica, el «Paradigma Estratégico para el desarrollo de habilidades competenciales», cuya ejecución implica comprensión, reflexión y discernimiento, teniendo en cuenta la dimensión social de cada situación. El estudio se ha llevado a cabo en la Universidad de Lleida con 40 alumnos de tercer curso de la asignatura «Educación Física y su didáctica». Se pretende valorar el impacto que provoca la implementación del programa «Paradigma estratégico para la adquisición de habilidades competenciales» sobre sus propias percepciones competenciales intrapersonales, antes y después de la aplicación de dicho programa

Thrive With Me: Protocol for a Randomized Controlled Trial to Test a Peer Support Intervention to Improve Antiretroviral Therapy Adherence Among Men Who Have Sex With Men

Background: The suboptimal rate of viral suppression among persons aged 13 years and older and residing in 37 states and the District of Columbia leaves considerable opportunities for onward transmission and contributes to poor health outcomes. Men who have sex with men (MSM) represent one of the most at-risk groups in the United States. There is a clear and continued need for innovative adherence support programs to optimize viral suppression. To address this gap, we designed and are implementing a randomized controlled trial (RCT) to test the efficacy of the Thrive with Me intervention for MSM living with HIV. Critical components of the protocol are presented. Objective: The aim of this study is to describe the protocol for rigorously testing the efficacy of Thrive with Me to improve antiretroviral therapy (ART) adherence among HIV-positive MSM residing in New York City. Methods: A community advisory board and beta testing were used to obtain feedback from HIV-positive MSM on the overall look and feel of Thrive with Me and problems with navigation to finalize intervention components and content. We will enroll 400 HIV-positive MSM residing in the New York City area into a two-arm prospective RCT and follow them for 17 months. Men in the Thrive with Me experimental intervention arm will have access to Thrive with Me for 5 months. Thrive with Me has three primary components: (1) a private social networking feature; (2) tailored HIV and ART adherence information; and (3) medication reminders, self-monitoring, and reflection. Gamification components include badges and leveling up to increase intrinsic motivation to engage with the intervention. Men randomized to the control condition will view a weekly newsletter for 5 months. The newsletter will be delivered via email and contains information on topics related to HIV with the exception of ART adherence. Study assessments will occur at enrollment and 5, 11, and 17 months post enrollment. The primary study outcome is HIV viral load, which is considered an objective indicator of ART adherence. Results: Participant recruitment for the RCT began in October 2016, and the data collection period is anticipated to end in the Fall of 2019. Conclusions: The efficacy trial of Thrive with Me will help to fill gaps in understanding about the utility of multicomponent, technology-based interventions to improve ART adherence among HIV-positive MSM. Of importance is the ability for the results of the Thrive with Me trial to inform best practices for conducting technology-based interventions that incorporate social media features

Umbilical endosalpingiosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Endosalpingiosis describes the ectopic growth of Fallopian tube epithelium. Pathology confirms the presence of a tube-like epithelium containing three types of cells: ciliated, columnar cells; non-ciliated, columnar secretory mucous cells; and intercalary cells.</p> <p>We report the case of a woman with umbilical endosalpingiosis and examine the nature and characteristics of cutaneous endosalpingiosis by reviewing and combining the other four cases existing in the international literature.</p> <p>Case presentation</p> <p>A 50-year-old Caucasian, Greek woman presented with a pale brown nodule in her umbilicus. The nodule was asymptomatic, with no cyclical discomfort or variation in size. Her personal medical, surgical and gynecologic history was uneventful. An excision within healthy margins was performed under local anesthesia. A cystic formation measuring 2.7×1.7×1 cm was removed. Histological examination confirmed umbilical endosalpingiosis.</p> <p>Conclusions</p> <p>Umbilical endosalpingiosis is a very rare manifestation of the non-neoplasmatic disorders of the Müllerian system. It appears with cyclic symptoms of pain and swelling of the umbilicus, but not always. The disease is diagnosed using pathologic findings and surgical excision is the definitive treatment.</p

Reduced Apaf-1 expression in human cutaneous melanomas

Malignant melanoma is a life-threatening skin cancer due to its highly metastatic character and resistance to radio- and chemotherapy. It is believed that the ability to evade apoptosis is the key mechanism for the rapid growth of cancer cells. However, the exact mechanism for failure in the apoptotic pathway in melanoma cells is unclear. p53, the most frequently mutated tumour suppressor gene in human cancers, is a key apoptosis inducer. However, p53 mutation is only found in 15–20% of melanoma biopsies. Recently, it was found that Apaf-1, a downstream target of p53, is inactivated in metastatic melanoma. Specifically, loss of heterozygosity (LOH) of the Apaf-1 gene was found in 40% of metastatic melanoma. To determine if loss of Apaf-1 expression is indeed involved in melanoma progression, we employed the tissue microarray technology and examined Apaf-1 expression in 70 human primary malignant melanoma biopsies by immunohistochemistry. Our data showed that Apaf-1 expression is significantly reduced in melanoma cells compared with normal nevi (χ2=6.02, P=0.014). Our results also revealed that loss of Apaf-1 was not associated with the tumour thickness, ulceration or subtype, patient's gender, age and 5-year survival. In addition, our in vitro apoptosis assay revealed that overexpression of Apaf-1 can sensitise melanoma cells to anticancer drug treatment. Taken together, our data indicate that Apaf-1 expression is significantly reduced in human melanoma and that Apaf-1 may serve as a therapeutic target in melanoma

Prion Shedding from Olfactory Neurons into Nasal Secretions

This study investigated the role of prion infection of the olfactory mucosa in the shedding of prion infectivity into nasal secretions. Prion infection with the HY strain of the transmissible mink encephalopathy (TME) agent resulted in a prominent infection of the olfactory bulb and the olfactory sensory epithelium including the olfactory receptor neurons (ORNs) and vomeronasal receptor neurons (VRNs), whose axons comprise the two olfactory cranial nerves. A distinct glycoform of the disease-specific isoform of the prion protein, PrPSc, was found in the olfactory mucosa compared to the olfactory bulb, but the total amount of HY TME infectivity in the nasal turbinates was within 100-fold of the titer in the olfactory bulb. PrPSc co-localized with olfactory marker protein in the soma and dendrites of ORNs and VRNs and also with adenylyl cyclase III, which is present in the sensory cilia of ORNs that project into the lumen of the nasal airway. Nasal lavages from HY TME-infected hamsters contained prion titers as high as 103.9 median lethal doses per ml, which would be up to 500-fold more infectious in undiluted nasal fluids. These findings were confirmed using the rapid PrPSc amplification QuIC assay, indicating that nasal swabs have the potential to be used for prion diagnostics. These studies demonstrate that prion infection in the olfactory epithelium is likely due to retrograde spread from the olfactory bulb along the olfactory and vomeronasal axons to the soma, dendrites, and cilia of these peripheral neurons. Since prions can replicate to high levels in neurons, we propose that ORNs can release prion infectivity into nasal fluids. The continual turnover and replacement of mature ORNs throughout the adult lifespan may also contribute to prion shedding from the nasal passage and could play a role in transmission of natural prion diseases in domestic and free-ranging ruminants

Nuclear ING2 expression is reduced in human cutaneous melanomas

Cutaneous malignant melanoma is a severe and sometimes life-threatening cancer. The molecular mechanism of melanomagenesis is incompletely understood. Deregulation of apoptosis is probably one of the key factors contributing to the progression of melanoma. The inhibitor of growth (ING) family proteins are candidate tumour suppressors which play important roles in apoptosis. Downregulated expression of ING proteins have been reported in several tumour types, including the loss of nuclear expression of p33ING1b in melanoma. As ING2 exhibits 58.9% homology with p33ING1b, we hypothesized that the aberrant expression of ING2 may be involved in melanomagenesis. Here, we used tissue microarray technology and immunohistochemistry to examine ING2 expression in human nevi and melanoma biopsies. Our data showed that nuclear ING2 expression was significantly reduced in radial growth phase (RGP), vertical growth phase (VGP), and metastatic melanomas compared with dysplastic nevi (P<0.05). Our data also revealed that nuclear ING2 expression was not associated with patient's gender, age or tumour thickness, ulceration, American Joint Committee on Cancer (AJCC) stage, tumour subtype, location and 5-year survival (P>0.05). Taken together, our results suggest that nuclear ING2 expression is significantly reduced in human melanomas and that reduced ING2 may be an important molecular event in the initiation of melanoma development