Uncontrolled Diabetes as an Associated Factor with Dynapenia in Adults Aged 50 Years or Older: Sex Differences

BACKGROUND: Epidemiological studies demonstrate an association between diabetes and low neuromuscular strength (NMS). However, none have grouped participants into non-diabetics (ND), undiagnosed diabetics (UDD), controlled diabetics (CD) and uncontrolled diabetics (UCD) or investigated what glycated hemoglobin levels (HbA1c) are associated with low NMS (dynapenia) by sex. METHODS: We analyzed the association between UDD, CD and UCD and dynapenia, the extent to which the different groupings of these individuals modifies this association and the association between HbA1c levels and NMS, by sex, in a cross-sectional study involving 5,290 participants ≥ 50 years from the ELSA study. In the first two analyses, logistic regression models were used with dynapenia (grip strength < 26kg in men and < 16kg in women) as outcome and diabetes [ND, UDD, CD and UCD] as exposure. Next, linear regression was performed with grip strength as outcome and the participants classified based on HbA1c level as exposure. The models were adjusted by sociodemographic, behavioral and clinical characteristics. RESULTS: Compared to ND only UCD was associated with dynapenia (men OR=2.37 95% CI 1.36-4.14; women OR=1.67 95% CI 1.01-2.79). This association was less clear, particularly in women, when CD and UCD groups were merged. HbA1c ≥ 6.5% in men and ≥ 8.0% in women were associated with lower NMS. CONCLUSIONS: UCD increases the chance of dynapenia in both sexes. The different groupings based on diabetes status modify the association between UCD and dynapenia. The threshold of HbA1c associated with reduced NMS is lower in men compared to women

Engineering modular half-antibody conjugated nanoparticles for targeting CD44v6-expressing cancer cells

Gastric cancer (GC) remains a major cause of death worldwide mainly because of the late detection in advanced stage. Recently, we proposed CD44v6 as a relevant marker for early detection of GC, opening new avenues for GC-targeted theranostics. Here, we designed a modular nanoscale system that selectively targets CD44v6-expressing GC cells by the site-oriented conjugation of a new-engineered CD44v6 half-antibody fragment to maleimide-modified polystyrene nanoparticles (PNPs) via an efficient bioorthogonal thiol-Michael addition click chemistry. PNPs with optimal particle size (200 nm) for crossing a developed biomimetic CD44v6-associated GC stromal model were further modified with a heterobifunctional maleimide crosslinker and click conjugated to the novel CD44v6 half-antibody fragment, obtained by chemical reduction of full antibody, without affecting its bioactivity. Collectively, our results confirmed the specific targeting ability of CD44v6-PNPs to CD44v6-expressing cells (1.65-fold higher than controls), highlighting the potential of CD44v6 half-antibody conjugated nanoparticles as promising and clinically relevant tools for the early diagnosis and therapy of GC. Additionally, the rational design of our nanoscale system may be explored for the development of several other nanotechnology-based disease-targeted approaches.This work was supported by Norte Portugal Regional Operational Programme (NORTE2020) under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund (ERDF) projects Norte-01-0145-FEDER-000012 and NORTE-07-0124-FEDER-000029, through COMPETE 2020-Operational Programme for Competitiveness and Internationalization (POCI) Portugal 2020 and Portuguese Foundation for Science and Technology (FCT) in the framework of the projects POCI-01-0145-FEDER-007274, POCI-01-0145-FEDER-016390, and PTDC/CTMNAN/120958/2010, B.N.L. doctoral grant (SFRH/BD/87400/2012) and postdoctoral grant (PTDC/MEC-GIN/29232/2017). R.F.P. was supported by Institute of Network Bioengineering for Healthy Aging (0245_IBEROS_1_E)

The dynamics of apparent horizons in Robinson-Trautman spacetimes

We present an alternative scheme of finding apparent horizons based on spectral methods applied to Robinson-Trautman spacetimes. We have considered distinct initial data such as representing the spheroids of matter and the head-on collision of two non-rotating black holes. The evolution of the apparent horizon is presented. We have obtained in some cases a mass gap between the final Bondi and apparent horizon masses, whose implications were briefly commented in the light of the thermodynamics of black holes.Comment: 9 pages, 7 figure

airborne.cam: a risk calculator of SARS-CoV-2 aerosol transmission under well-mixed ventilation conditions

http://airborne.cam helps users understand how their surroundings and day-to-day behaviour can be adapted in order to minimise the risk of indoors transmission of the SARS-CoV-2 virus. The app is based on the well-mixed approach to calculate the individual risk of infection based on the exposure time of a healthy, susceptible individual to infectious long-suspended viral particles indoors. This approach considers that individuals are far apart from each other, that is, there is no risk of short-range transmission either by large or small droplets/aerosols, nor by contact with contaminated surfaces. The basic user can change inputs such as ventilation rate, type of face covering, number of occupants, and type of activity to assess their impact on risk of infection, while more advanced features are available for the user familiar with science concerning aerosol transmission

Relationship between intact HIV-1 proviruses in circulating CD4+ T cells and rebound viruses emerging during treatment interruption.

Combination antiretroviral therapy controls but does not cure HIV-1 infection because a small fraction of cells harbor latent viruses that can produce rebound viremia when therapy is interrupted. The circulating latent virus reservoir has been documented by a variety of methods, most prominently by viral outgrowth assays (VOAs) in which CD4+ T cells are activated to produce virus in vitro, or more recently by amplifying proviral near full-length (NFL) sequences from DNA. Analysis of samples obtained in clinical studies in which individuals underwent analytical treatment interruption (ATI), showed little if any overlap between circulating latent viruses obtained from outgrowth cultures and rebound viruses from plasma. To determine whether intact proviruses amplified from DNA are more closely related to rebound viruses than those obtained from VOAs, we assayed 12 individuals who underwent ATI after infusion of a combination of two monoclonal anti-HIV-1 antibodies. A total of 435 intact proviruses obtained by NFL sequencing were compared with 650 latent viruses from VOAs and 246 plasma rebound viruses. Although, intact NFL and outgrowth culture sequences showed similar levels of stability and diversity with 39% overlap, the size of the reservoir estimated from NFL sequencing was larger than and did not correlate with VOAs. Finally, intact proviruses documented by NFL sequencing showed no sequence overlap with rebound viruses; however, they appear to contribute to recombinant viruses found in plasma during rebound

Estimates of the stochasticity of droplet dispersion by a cough.

In this paper, the statistical distributions of the position and the size of the evaporating droplets after a cough are evaluated, thus characterizing the inherent stochasticity of respiratory releases due to turbulence. For that, ten independent realizations of a cough with realistic initial conditions and in a room at 20 °C and 40% relative humidity were performed with large eddy simulations and Lagrangian tracking of the liquid phase. It was found that although turbulence decreases far from the emitter, it results in large variations in the spatial distribution of the droplets. The total suspended liquid mass after 60 s from the cough is in good agreement with that estimated by a one-dimensional model accounting for settling and evaporation under quiescent conditions, while deposition times of droplets in the 10-100 μm range are found to vary significantly, reflected in the mass of liquid, and hence the virus content, potentially inhaled by a receptor. The high variability between events is due to the local fluctuations of temperature, humidity, and velocity on droplet evaporation and motion. The droplet distribution suggests that, in the absence of face coverings, an unprotected cough is not safe at 2 m away from the emitter even outdoors. The results indicate that mitigation measures, such as ventilation to address long-range transmission, can be based on the total suspended liquid content evaluated from reduced-order models. However, the large variability of viral content in the near field produces wide variations in estimates of risk; therefore, a stochastic approach is needed for evaluating short-range transmission risk

Dopamine-induced ascorbate release from retinal neurons involves glutamate release, activation of AMPA/Kainate receptors and downstream signaling pathways

Ascorbate, the reduced form of Vitamin C, is one of the most abundant and important low-molecular weight antioxidants in living tissues. Most animals synthesize Vitamin C, but some primates, including humans, have lost this capacity due to disruption in L-gulono-gamma-lactone oxidase gene. Because of this incapacity, those animals must obtain Vitamin C from the diet. Ascorbate is highly concentrated in the central nervous system (CNS), including the retina, and plays essential roles in neuronal physiology. Ascorbate transport into cells is controlled by Sodium Vitamin C Co-Transporters (SVCTs). There are four SVCT isoforms and SVCT2 is the major isoform controlling ascorbate transport in the CNS. Regarding ascorbate release from retinal neurons, Glutamate, by activating its ionotropic receptors leads to ascorbate release via the reversion of SVCT2. Moreover, dopamine, via activation of D1 receptor/cyclic AMP/EPAC2 pathway, also induces ascorbate release via SVCT2 reversion. Because the dopaminergic and glutamatergic systems are interconnected in the CNS, we hypothesized that dopamine could regulate ascorbate release indirectly, via the glutamatergic system. Here we reveal that dopamine increases the release of D-Aspartate from retinal neurons in a way independent on calcium ions and dependent on excitatory amino acid transporters. In addition, dopamine-dependent SVCT2 reversion leading to ascorbate release occurs by activation of AMPA/Kainate receptors and downstream ERK/AKT pathways. Overall, our data reveal a dopamine-to-glutamate signaling that regulates the bioavailability of ascorbate in neuronal cells.This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), and Pró-Reitoria de Pesquisa, Pós-Graduação e Inovação da Universidade Federal Fluminense (PROPPI/UFF). TGE, ID, and NAO were recipients of graduate student fellowships from CAPES. RPC is a research fellow from CNPq and FAPERJ. CCP and RS hold employment contracts financed by national funds through FCT – Fundação para a Ciência e a Tecnologia, I.P., in the context of the program-contract described in paragraphs 4, 5 and 6 of art. 23 of Law no. 57/2016, of August 29, as amended by Law no. 57/2017 of July 19

Indeterminate thyroid cytology: Detecting malignancy using analysis of nuclear images

Background: Thyroid nodules diagnosed as 'atypia of undetermined significance/ follicular lesion of undetermined significance' (AUS/FLUS) or 'follicular neoplasm/ suspected follicular neoplasm' (FN/SFN), according to Bethesda’s classification, represena challenge in clinical practice. Computerized analysis of nuclear images (CANI) could be a useful tool for these cases. Our aim was to evaluate the ability of CANI to correctly classify AUS/FLUS and FN/SFN thyroid nodules for malignancy. Methods: We studied 101 nodules cytologically classified as AUS/FLUS (n = 68) or FN/SFN (n = 33) from 97 thyroidectomy patients. Slides with cytological material were submitted for manual selection and analysis of the follicular cell nuclei for morphometric and texture parameters using ImageJ software. The histologically benign and malignant lesions were compared for such parameters which were then evaluated for the capacity to predict malignancy using the classification and regression trees gini model. The intraclass coefficient of correlation was used to evaluate method reproducibility. Results: In AUS/FLUS nodule analysis, the benign and malignant nodules differed for entropy (P < 0.05), while the FN/SFN nodules differed for fractal analysis, coefficient of variation (CV) of roughness, and CV-entropy (P < 0.05). Considering the AUS/FLUS and FN/SFN nodules separately, it correctly classified 90.0 and 100.0% malignant nodules, with a correct global classification of 94.1 and 97%, respectively. We observed that reproducibility was substantially or nearly complete (0.61–0.93) in 10 of the 12 nuclear parameters evaluated. Conclusion: CANI demonstrated a high capacity for correctly classifying AUS/FLUS and FN/SFN thyroid nodules for malignancy. This could be a useful method to help increase diagnostic accuracy in the indeterminate thyroid cytology.This study received financial support from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; processes number 2016/14987-0 and number 2016/14988-6). Further funding through 'Fundação para a Ciência e Tecnologi' – FCT and FEDER 'Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020'; by Operacional Programme for Competitiveness and Internationalization 'POCI' (Grant no. POCI-01-0145-FEDER-007274); by the 'Advancing cancer research: from basic knowledge to application' (grant no. NORTE-01-0145-FEDER-000029); and by the 'Projetos Estruturados de I & D & I', funded by Norte 2020 – Programa Operacional Regional do Norte

Stroke in patients with sickle cell disease - Clinical and neurological aspects

The aim of this study was to characterize a group of patients (n=8) with sickle cell disease (SCD) and ischemic stroke concerning the clinical, neurological, imaging and progressive aspects. Data were collected from records and completed with an interview of patients and their parents. In this study there were 8 patients with ages ranging from 10 to 23 years old; SCD diagnosis was given between one and two years of age with clinical features of fatigue and anemia. The stroke was ischemic in all individuals and the first cerebrovascular event occurred before 6 years of age; 3 patients had recurrence of stroke despite prophylactic blood transfusion therapy and both cerebral hemispheres were affected in 4 patients. Clinical and neurological current features observed were: acute pain crises, sialorrhea, mouth breathing, motor, and neuropsychological impairments resulting from cortical-subcortical structure lesions.661303